Sample records for acids survival mechanisms

  1. Survival mechanism of Escherichia coli O157:H7 against combined treatment with acetic acid and sodium chloride. (United States)

    Lee, Sun-Young; Kang, Dong-Hyun


    The combination of salt and acid is commonly used in the production of many foods, including pickles and fermented foods. However, in our previous studies, the addition of salt significantly reduced the inhibitory effect of acetic acid on Escherichia coli O157:H7 in laboratory media and pickled cucumbers. Therefore, this study was conducted to determine the mechanism by which salt confers resistance against acetic acid in E. coli O157:H7. The addition of high concentrations (up to 9% or 15% [w/v]) of salt increased the resistance of E. coli O157:H7 to acetic acid treatment. Combined treatment with acetic acid and salt showed varying results among different bacterial strains (an antagonistic effect for E. coli O157:H7 and Shigella and a synergistic effect for Listeria monocytogenes and Staphylococcus aureus). The addition of salt increased the cytoplasmic pH of E. coli O157:H7, but decreased the cytoplasmic pH of L. monocytogenes and S. aureus on treatment with acetic acid. Therefore, the addition of salt increases the acid resistance of E. coli O157:H7 possibly by increasing its acid resistance response and consequently preventing the acidification of its cytoplasm by organic acids.

  2. Molecular mechanisms of (-)-epicatechin and chlorogenic acid on the regulation of the apoptotic and survival/proliferation pathways in a human hepatoma cell line. (United States)

    Granado-Serrano, Ana Belén; Martín, María Angeles; Izquierdo-Pulido, María; Goya, Luis; Bravo, Laura; Ramos, Sonia


    Dietary polyphenols have been associated with reduced risk of chronic diseases, but the precise molecular mechanisms of protection remain unclear. This work was aimed at studying the effect of (-)-epicatechin (EC) and chlorogenic acid (CGA) on the regulation of apoptotic and survival/proliferation pathways in a human hepatoma cell line (HepG2). EC or CGA treatment for 18 h had a slight effect on cell viability and decreased reactive oxygen species formation, and EC alone promoted cell proliferation, whereas CGA increased glutathione levels. Phenols neither induced the caspase cascade for apoptosis nor affected expression levels of Bcl-xL or Bax. A sustained activation of the major survival signals AKT/PI-3-kinase and ERK was shown in EC-treated cells, rather than in CGA-exposed cells. These data suggest that EC and CGA have no effect on apoptosis and enhance the intrinsic cellular tolerance against oxidative insults either by activating survival/proliferation pathways or by increasing antioxidant potential in HepG2.

  3. Dinosaur Peptides Suggest Mechanisms of Protein Survival

    Energy Technology Data Exchange (ETDEWEB)

    San Antonio, James D.; Schweitzer, Mary H.; Jensen, Shane T.; Kalluri, Raghu; Buckley, Michael; Orgel, Joseph P.R.O. (Harvard-Med); (IIT); (NCSU); (UPENN); (Manchester); (Orthovita)


    Eleven collagen peptide sequences recovered from chemical extracts of dinosaur bones were mapped onto molecular models of the vertebrate collagen fibril derived from extant taxa. The dinosaur peptides localized to fibril regions protected by the close packing of collagen molecules, and contained few acidic amino acids. Four peptides mapped to collagen regions crucial for cell-collagen interactions and tissue development. Dinosaur peptides were not represented in more exposed parts of the collagen fibril or regions mediating intermolecular cross-linking. Thus functionally significant regions of collagen fibrils that are physically shielded within the fibril may be preferentially preserved in fossils. These results show empirically that structure-function relationships at the molecular level could contribute to selective preservation in fossilized vertebrate remains across geological time, suggest a 'preservation motif', and bolster current concepts linking collagen structure to biological function. This non-random distribution supports the hypothesis that the peptides are produced by the extinct organisms and suggests a chemical mechanism for survival.

  4. Amino acid survival in large cometary impacts (United States)

    Pierazzo, E.; Chyba, C. F.


    A significant fraction of the Earth's prebiotic volatile inventory may have been delivered by asteroidal and cometary impacts during the period of heavy bombardment. The realization that comets are particularly rich in organic material seemed to strengthen this suggestion. Previous modeling studies, however, indicated that most organics would be entirely destroyed in large comet and asteroid impacts. The availability of new kinetic parameters for the thermal degradation of amino acids in the solid phase made it possible to readdress this question. We present the results of new high-resolution hydrocode simulations of asteroid and comet impact coupled with recent experimental data for amino acid pyrolysis in the solid phase. Differences due to impact velocity as well as projectile material have been investigated. Effects of angle of impacts were also addressed. The results suggest that some amino acids would survive the shock heating of large (kilometer-radius) cometary impacts. At the time of the origins of life on Earth, the steady-state oceanic concentration of certain amino acids (like aspartic and glutamic acid) delivered by comets could have equaled or substantially exceeded that due to Miller-Urey synthesis in a carbon dioxide-rich atmosphere. Furthermore, in the unlikely case of a grazing impact (impact angle around 5 degrees from the horizontal) an amount of some amino acids comparable to that due to the background steady-state production or delivery would be delivered to the early Earth.

  5. Fatty acids as modulators of neutrophil recruitment, function and survival. (United States)

    Rodrigues, Hosana G; Takeo Sato, Fabio; Curi, Rui; Vinolo, Marco A R


    Neutrophils are well-known to act in the destruction of invading microorganisms. They have also been implicated in the activation of other immune cells including B- and T-lymphocytes and in the resolution of inflammation and tissue regeneration. Neutrophils are produced in the bone marrow and released into the circulation from where they migrate to tissues to perform their effector functions. Neutrophils are in constant contact with fatty acids that can modulate their function, activation and fate (survival or cell death) through different mechanisms. In this review, the effects of fatty acids pertaining to five classes, namely, long-chain saturated fatty acids (LCSFAs), short-chain fatty acids (SCFAs), and omega-3 (n-3), omega-6 (n-6) and omega-9 (n-9) unsaturated fatty acids, on neutrophils and the relevance of these effects for disease development are discussed.

  6. Docosahexaenoic acid-derived neuroprotectin D1 induces neuronal survival via secretase- and PPARγ-mediated mechanisms in Alzheimer's disease models.

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    Yuhai Zhao

    Full Text Available Neuroprotectin D1 (NPD1 is a stereoselective mediator derived from the omega-3 essential fatty acid docosahexaenoic acid (DHA with potent inflammatory resolving and neuroprotective bioactivity. NPD1 reduces Aβ42 peptide release from aging human brain cells and is severely depleted in Alzheimer's disease (AD brain. Here we further characterize the mechanism of NPD1's neurogenic actions using 3xTg-AD mouse models and human neuronal-glial (HNG cells in primary culture, either challenged with Aβ42 oligomeric peptide, or transfected with beta amyloid precursor protein (βAPP(sw (Swedish double mutation APP695(sw, K595N-M596L. We also show that NPD1 downregulates Aβ42-triggered expression of the pro-inflammatory enzyme cyclooxygenase-2 (COX-2 and of B-94 (a TNF-α-inducible pro-inflammatory element and apoptosis in HNG cells. Moreover, NPD1 suppresses Aβ42 peptide shedding by down-regulating β-secretase-1 (BACE1 while activating the α-secretase ADAM10 and up-regulating sAPPα, thus shifting the cleavage of βAPP holoenzyme from an amyloidogenic into the non-amyloidogenic pathway. Use of the thiazolidinedione peroxisome proliferator-activated receptor gamma (PPARγ agonist rosiglitazone, the irreversible PPARγ antagonist GW9662, and overexpressing PPARγ suggests that the NPD1-mediated down-regulation of BACE1 and Aβ42 peptide release is PPARγ-dependent. In conclusion, NPD1 bioactivity potently down regulates inflammatory signaling, amyloidogenic APP cleavage and apoptosis, underscoring the potential of this lipid mediator to rescue human brain cells in early stages of neurodegenerations.

  7. The Survival Advantage: Underlying Mechanisms and Extant Limitations

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    Stephanie A. Kazanas


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

  8. Neuronal survival in the brain: neuron type-specific mechanisms. (United States)

    Pfisterer, Ulrich; Khodosevich, Konstantin


    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation. Furthermore, pro-survival factors and intracellular responses depend on the type of neuron and region of the brain. Thus, in addition to some common neuronal pro-survival signaling, different types of neurons possess a variety of 'neuron type-specific' pro-survival constituents that might help them to adapt for survival in a certain brain region. This review focuses on how immature neurons survive during normal and impaired brain development, both in the embryonic/neonatal brain and in brain regions associated with adult neurogenesis, and emphasizes neuron type-specific mechanisms that help to survive for various types of immature neurons. Importantly, we mainly focus on in vivo data to describe neuronal survival specifically in the brain, without extrapolating data obtained in the PNS or spinal cord, and thus emphasize the influence of the complex brain environment on neuronal survival during development.

  9. Stress-Survival Gene Identification From an Acid Mine Drainage Algal Mat Community (United States)

    Urbina-Navarrete, J.; Fujishima, K.; Paulino-Lima, I. G.; Rothschild-Mancinelli, B.; Rothschild, L. J.


    Microbial communities from acid mine drainage environments are exposed to multiple stressors to include low pH, high dissolved metal loads, seasonal freezing, and desiccation. The microbial and algal communities that inhabit these niche environments have evolved strategies that allow for their ecological success. Metagenomic analyses are useful in identifying species diversity, however they do not elucidate the mechanisms that allow for the resilience of a community under these extreme conditions. Many known or predicted genes encode for protein products that are unknown, or similarly, many proteins cannot be traced to their gene of origin. This investigation seeks to identify genes that are active in an algal consortium during stress from living in an acid mine drainage environment. Our approach involves using the entire community transcriptome for a functional screen in an Escherichia coli host. This approach directly targets the genes involved in survival, without need for characterizing the members of the consortium.The consortium was harvested and stressed with conditions similar to the native environment it was collected from. Exposure to low pH (DNA (cDNA) libraries in E. coli. The transformed E. coli were exposed to the same stressors as the original algal consortium to select for surviving cells. Successful cells incorporated the transcripts that encode survival mechanisms, thus allowing for selection and identification of the gene(s) involved. Initial selection screens for freeze and desiccation tolerance have yielded E. coli that are 1 order of magnitude more resistant to freezing (0.01% survival of control with no transcript, 0.2% survival of E. coli with transcript) and 3 orders of magnitude more resistant to desiccation (0.005% survival of control cells with no transcripts, 5% survival of cells with transcript).This work is transformative because genetic functions can be selected without having prior knowledge of the genes or of the organisms involved

  10. Harvest Survive : Game Mechanics of Unity 2D Game



    The purpose of this project was to learn how to create Games in Unity 2D, to see the work-flow and to test if the new Unity 2D feature of the Unity engine was a good alternative for developing 2D games. A further aspect was to learn the different steps and mechanics of the Unity environment. The goal was to create a survival game, in which the player would have to grow plants in order to get food and money to stay alive in a hostile environment. The player has to survive in six different...

  11. A New SDH-Based ATM Network Survivability Escalation Mechanism

    Institute of Scientific and Technical Information of China (English)


    This paper investigates survivability escalation strategies in multi-layers transport networks such as ATM/SDH/WDM networks, and presents oriented-failures and oriented-traffic escalation mechanisms. Furthermore, We present a new survivability Escalation strategy for SDH-Based ATM transport networks, which addresses difficult problem for resources sharing pool(RSP) among different layers restoration mechanisms. In this paper, we also present integer programming (IP) model for the resources sharing pool (RSP) design problem and the node simulation model for escalation Node. The simulation results show that the proposed ESP is very efficient. The proposed model can be easily extended for other types of multi-layer networks, such as WDM-based ATM networks or WDM-based SDH networks.

  12. Cell survival signalling through PPARδ and arachidonic acid metabolites in neuroblastoma.

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    Emma Bell

    Full Text Available Retinoic acid (RA has paradoxical effects on cancer cells: promoting cell death, differentiation and cell cycle arrest, or cell survival and proliferation. Arachidonic acid (AA release occurs in response to RA treatment and, therefore, AA and its downstream metabolites may be involved in cell survival signalling. To test this, we inhibited phospholipase A2-mediated AA release, cyclooxygenases and lipoxygenases with small-molecule inhibitors to determine if this would sensitise cells to cell death after RA treatment. The data suggest that, in response to RA, phospholipase A2-mediated release of AA and subsequent metabolism by lipoxygenases is important for cell survival. Evidence from gene expression reporter assays and PPARδ knockdown suggests that lipoxygenase metabolites activate PPARδ. The involvement of PPARδ in cell survival is supported by results of experiments with the PPARδ inhibitor GSK0660 and siRNA-mediated knockdown. Quantitative reverse transcriptase PCR studies demonstrated that inhibition of 5-lipoxygenase after RA treatment resulted in a strong up-regulation of mRNA for PPARδ2, a putative inhibitory PPARδ isoform. Over-expression of PPARδ2 using a tetracycline-inducible system in neuroblastoma cells reduced proliferation and induced cell death. These data provide evidence linking lipoxygenases and PPARδ in a cell survival-signalling mechanism and suggest new drug-development targets for malignant and hyper-proliferative diseases.

  13. Interactive effects involving different classes of excitatory amino acid receptors and the survival of cerebellar granule cells in culture

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen


    Differentiating granule cells develop survival requirements in culture which can be met by treatment with high K+ or N-methyl-D-aspartate (NMDA) and, according to our recent findings, also with low concentrations of kainic acid (KA, 50 microM). We have now attempted to elucidate the mechanism(s) ...

  14. Survival Predictions of Ceramic Crowns Using Statistical Fracture Mechanics. (United States)

    Nasrin, S; Katsube, N; Seghi, R R; Rokhlin, S I


    This work establishes a survival probability methodology for interface-initiated fatigue failures of monolithic ceramic crowns under simulated masticatory loading. A complete 3-dimensional (3D) finite element analysis model of a minimally reduced molar crown was developed using commercially available hardware and software. Estimates of material surface flaw distributions and fatigue parameters for 3 reinforced glass-ceramics (fluormica [FM], leucite [LR], and lithium disilicate [LD]) and a dense sintered yttrium-stabilized zirconia (YZ) were obtained from the literature and incorporated into the model. Utilizing the proposed fracture mechanics-based model, crown survival probability as a function of loading cycles was obtained from simulations performed on the 4 ceramic materials utilizing identical crown geometries and loading conditions. The weaker ceramic materials (FM and LR) resulted in lower survival rates than the more recently developed higher-strength ceramic materials (LD and YZ). The simulated 10-y survival rate of crowns fabricated from YZ was only slightly better than those fabricated from LD. In addition, 2 of the model crown systems (FM and LD) were expanded to determine regional-dependent failure probabilities. This analysis predicted that the LD-based crowns were more likely to fail from fractures initiating from margin areas, whereas the FM-based crowns showed a slightly higher probability of failure from fractures initiating from the occlusal table below the contact areas. These 2 predicted fracture initiation locations have some agreement with reported fractographic analyses of failed crowns. In this model, we considered the maximum tensile stress tangential to the interfacial surface, as opposed to the more universally reported maximum principal stress, because it more directly impacts crack propagation. While the accuracy of these predictions needs to be experimentally verified, the model can provide a fundamental understanding of the

  15. Mitotic death: a mechanism of survival? A review

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    Cragg M S


    Full Text Available Abstract Mitotic death is a delayed response of p53 mutant tumours that are resistant to genotoxic damage. Questions surround why this response is so delayed and how its mechanisms serve a survival function. After uncoupling apoptosis from G1 and S phase arrests and adapting these checkpoints, p53 mutated tumour cells arrive at the G2 compartment where decisions regarding survival and death are made. Missed or insufficient DNA repair in G1 and S phases after severe genotoxic damage results in cells arriving in G2 with an accumulation of point mutations and chromosome breaks. Double strand breaks can be repaired by homologous recombination during G2 arrest. However, cells with excessive chromosome lesions either directly bypass the G2/M checkpoint, starting endocycles from G2 arrest, or are subsequently detected by the spindle checkpoint and present with the features of mitotic death. These complex features include apoptosis from metaphase and mitosis restitution, the latter of which can also facilitate transient endocycles, producing endopolyploid cells. The ability of cells to initiate endocycles during G2 arrest and mitosis restitution most likely reflects their similar molecular environments, with down-regulated mitosis promoting factor activity. Resulting endocycling cells have the ability to repair damaged DNA, and although mostly reproductively dead, in some cases give rise to mitotic progeny. We conclude that the features of mitotic death do not simply represent aberrations of dying cells but are indicative of a switch to amitotic modes of cell survival that may provide additional mechanisms of genotoxic resistance.

  16. A Mycobacterium avium subsp. paratuberculosis predicted serine protease is associated with acid stress and intraphagosomal survival

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    Abirami Kugadas


    Full Text Available AbstractThe ability to maintain intra-cellular pH is crucial for bacteria and other microbes to survive in diverse environments, particularly those that undergo fluctuations in pH. Mechanisms of acid resistance remain poorly understood in mycobacteria. Although studies investigating acid stress in M. tuberculosis are gaining traction, few center on Mycobacterium avium subsp. paratuberculosis (MAP, the etiological agent of chronic enteritis in ruminants. We identified a MAP acid stress response network involved in macrophage infection. The central node of this network was MAP0403, a predicted serine protease that shared an 86% amino acid identity with MarP in M. tuberculosis. Previous studies confirmed MarP as a serine protease integral to maintaining intra-bacterial pH and survival in acid in vitro and in vivo. We show that MAP0403 is upregulated in infected macrophage and MAC-T cells and coincided with phagosome acidification. Treatment of mammalian cells with bafilomcyin A1, a potent inhibitor of phagosomal vATPases, diminished MAP0403 transcription. MAP0403 expression was also noted in acidic medium. A surrogate host, M. smegmatis mc2 155, was designed to express MAP0403 and when exposed to either macrophages or in vitro acid stress had increase bacterial cell viability, which corresponds to maintenance of intra-bacterial pH in acidic (pH = 5 conditions. These data suggest that MAP0403 may be the equivalent of MarP in MAP. Future studies confirming MAP0403 as a serine protease and exploring its structure and possible substrates are warranted.

  17. Quorum sensing mechanism in lactic acid bacteria

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    Hatice Yılmaz - Yıldıran


    and detection occurs as a consecution it is hard to understand their QS mechanism. In this review, connection between QS mechanism and some characteristics of lactic acid bacteria are evaluated such as concordance with its host, inhibition of pathogen development and colonization in gastrointestinal system, bacteriocin production, acid and bile resistance, adhesion to epithelium cells. Understanding QS mechanism of lactic acid bacteria will be useful to design metabiotics which is defined as novel probiotics.

  18. Mechanism of histone survival during transcription by RNA polymerase II. (United States)

    Kulaeva, Olga I; Studitsky, Vasily M


    This work is related to and stems from our recent NSMB paper, "Mechanism of chromatin remodeling and recovery during passage of RNA polymerase II" (December 2009). Synopsis. Recent genomic studies from many laboratories have suggested that nucleosomes are not displaced from moderately transcribed genes. Furthermore, histones H3/H4 carrying the primary epigenetic marks are not displaced or exchanged (in contrast to H2A/H2B histones) during moderate transcription by RNA polymerase II (Pol II) in vivo. These exciting observations suggest that the large molecule of Pol II passes through chromatin structure without even transient displacement of H3/H4 histones. The most recent analysis of the RNA polymerase II (Pol II)-type mechanism of chromatin remodeling in vitro (described in our NSMB 2009 paper) suggests that nucleosome survival is tightly coupled with formation of a novel intermediate: a very small intranucleosomal DNA loop (Ø-loop) containing transcribing Pol II. In the submitted manuscript we critically evaluate one of the key predictions of this model: the lack of even transient displacement of histones H3/H4 during Pol II transcription in vitro. The data suggest that, indeed, histones H3/H4 are not displaced during Pol II transcription in vitro. These studies are directly connected with the observation in vivo on the lack of exchange of histones H3/H4 during Pol II transcription.

  19. The Role of Amino Acid Permeases and Tryptophan Biosynthesis in Cryptococcus neoformans Survival.

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    João Daniel Santos Fernandes

    Full Text Available Metabolic diversity is an important factor during microbial adaptation to different environments. Among metabolic processes, amino acid biosynthesis has been demonstrated to be relevant for survival for many microbial pathogens, whereas the association between pathogenesis and amino acid uptake and recycling are less well-established. Cryptococcus neoformans is an opportunistic fungal pathogen with many habitats. As a result, it faces frequent metabolic shifts and challenges during its life cycle. Here we studied the C. neoformans tryptophan biosynthetic pathway and found that the pathway is essential. RNAi indicated that interruptions in the biosynthetic pathway render strains inviable. However, auxotroph complementation can be partially achieved by tryptophan uptake when a non preferred nitrogen source and lower growth temperature are applied, suggesting that amino acid permeases may be the target of nitrogen catabolism repression (NCR. We used bioinformatics to search for amino acid permeases in the C. neoformans and found eight potential global permeases (AAP1 to AAP8. The transcriptional profile of them revealed that they are subjected to regulatory mechanisms which are known to respond to nutritional status in other fungi, such as (i quality of nitrogen (Nitrogen Catabolism Repression, NCR and carbon sources (Carbon Catabolism Repression, CCR, (ii amino acid availability in the extracellular environment (SPS-sensing and (iii nutritional deprivation (Global Amino Acid Control, GAAC. This study shows that C. neoformans has fewer amino acid permeases than other model yeasts, and that these proteins may be subjected to complex regulatory mechanisms. Our data suggest that the C. neoformans tryptophan biosynthetic pathway is an excellent pharmacological target. Furthermore, inhibitors of this pathway cause Cryptococcus growth arrest in vitro.

  20. Nucleic acids and survival of excised anthers in vitro. (United States)

    VASIL, I K


    Excised anthers of Allium cepa and Rhoeo discolor have been successfully cultured in modified White's medium supplemented with various concentrations of ribonucleic acid and deoxyribonucleic acid. Ribonucleic acid proved to be much more useful than deoxyribonucleic acid and reduced the time required for the completion of meiosis from 48 hours to 24 hours. The role of nucleic acids in the control of nuclear divisions has been indicated.

  1. Overview on mechanisms of acetic acid resistance in acetic acid bacteria. (United States)

    Wang, Bin; Shao, Yanchun; Chen, Fusheng


    Acetic acid bacteria (AAB) are a group of gram-negative or gram-variable bacteria which possess an obligate aerobic property with oxygen as the terminal electron acceptor, meanwhile transform ethanol and sugar to corresponding aldehydes, ketones and organic acids. Since the first genus Acetobacter of AAB was established in 1898, 16 AAB genera have been recorded so far. As the main producer of a world-wide condiment, vinegar, AAB have evolved an elegant adaptive system that enables them to survive and produce a high concentration of acetic acid. Some researches and reviews focused on mechanisms of acid resistance in enteric bacteria and made the mechanisms thoroughly understood, while a few investigations did in AAB. As the related technologies with proteome, transcriptome and genome were rapidly developed and applied to AAB research, some plausible mechanisms conferring acetic acid resistance in some AAB strains have been published. In this review, the related mechanisms of AAB against acetic acid with acetic acid assimilation, transportation systems, cell morphology and membrane compositions, adaptation response, and fermentation conditions will be described. Finally, a framework for future research for anti-acid AAB will be provided.

  2. Survival and resuscitation of ten strains of Campylobacter jejuni and Campylobacter coli under acid conditions

    NARCIS (Netherlands)

    Chaveerach, P.; Huurne, ter A.A.H.M.; Lipman, L.J.A.; Knapen, van F.


    The culturability of 10 strains of Campylobacter jejuni and Campylobacter coli was studied after the bacteria were exposed to acid conditions for various periods of time. Campylobacter cells could not survive 2 h under acid conditions (formic acid at pH 4). The 10 Campylobacter strains could not be

  3. Mechanisms of gene regulation by fatty acids

    NARCIS (Netherlands)

    Georgiadi, A.; Kersten, A.H.


    Consumption of specific dietary fatty acids has been shown to influence risk and progression of several chronic diseases, such as cardiovascular disease, obesity, cancer, and arthritis. In recent years, insights into the mechanisms underlying the biological effects of fatty acids have improved consi

  4. Analysis of the mechanism of nucleosome survival during transcription. (United States)

    Chang, Han-Wen; Kulaeva, Olga I; Shaytan, Alexey K; Kibanov, Mikhail; Kuznedelov, Konstantin; Severinov, Konstantin V; Kirpichnikov, Mikhail P; Clark, David J; Studitsky, Vasily M


    Maintenance of nucleosomal structure in the cell nuclei is essential for cell viability, regulation of gene expression and normal aging. Our previous data identified a key intermediate (a small intranucleosomal DNA loop, Ø-loop) that is likely required for nucleosome survival during transcription by RNA polymerase II (Pol II) through chromatin, and suggested that strong nucleosomal pausing guarantees efficient nucleosome survival. To evaluate these predictions, we analysed transcription through a nucleosome by different, structurally related RNA polymerases and mutant yeast Pol II having different histone-interacting surfaces that presumably stabilize the Ø-loop. The height of the nucleosomal barrier to transcription and efficiency of nucleosome survival correlate with the net negative charges of the histone-interacting surfaces. Molecular modeling and analysis of Pol II-nucleosome intermediates by DNase I footprinting suggest that efficient Ø-loop formation and nucleosome survival are mediated by electrostatic interactions between the largest subunit of Pol II and core histones.

  5. The proximate memory mechanism underlying the survival-processing effect: richness of encoding or interactive imagery? (United States)

    Kroneisen, Meike; Erdfelder, Edgar; Buchner, Axel


    Nairne and collaborators showed that assessing the relevance of words in the context of an imagined survival scenario boosts memory for these words. Although this survival-processing advantage has attracted a considerable amount of research, little is known about the proximate memory mechanism mediating this effect. Recently, Kroneisen and Erdfelder (2011) argued that it is not survival processing itself that facilitates recall but rather the richness and distinctiveness of encoding that is triggered by the survival-processing task. Alternatively, however, it is also conceivable that survival processing fosters interactive imagery, a process known to improve associative learning. To test these explanations we compared relevance-rating and interactive imagery tasks for survival and control scenarios. Results show that the survival advantage replicates in the relevance-rating condition but vanishes in the interactive imagery condition. This refutes the interactive imagery explanation and corroborates the richness-of-encoding hypothesis of the survival-processing effect.

  6. Neuronal survival in the brain: neuron type-specific mechanisms

    DEFF Research Database (Denmark)

    Pfisterer, Ulrich Gottfried; Khodosevich, Konstantin


    Neurogenic regions of mammalian brain produce many more neurons that will eventually survive and reach a mature stage. Developmental cell death affects both embryonically produced immature neurons and those immature neurons that are generated in regions of adult neurogenesis. Removal of substantial...... a particular neuron will die. To accommodate this signaling, immature neurons in the brain express a number of transmembrane factors as well as intracellular signaling molecules that will regulate the cell survival/death decision, and many of these factors cease being expressed upon neuronal maturation...... numbers of neurons that are not yet completely integrated into the local circuits helps to ensure that maturation and homeostatic function of neuronal networks in the brain proceed correctly. External signals from brain microenvironment together with intrinsic signaling pathways determine whether...

  7. The Molecular Mechanisms of Glucocorticoids-Mediated Neutrophil Survival



    Neutrophil-dominated inflammation plays an important role in many airway diseases including asthma, chronic obstructive pulmonary disease (COPD), bronchiolitis and cystic fibrosis. In cases of asthma where neutrophil-dominated inflammation is a major contributing factor to the disease, treatment with corticosteroids can be problematic as corticosteroids have been shown to promote neutrophil survival which, in turn, accentuates neutrophilic inflammation. In light of such cases, novel targeted ...

  8. Dietary proteins extend the survival of salmonella dublin in a gastric Acid environment

    DEFF Research Database (Denmark)

    Birk, Tina; Kristensen, Kim; Harboe, Anne;


    The pH of the human stomach is dynamic and changes over time, depending on the composition of the food ingested and a number of host-related factors such as age. To evaluate the number of bacteria surviving the gastric acid barrier, we have developed a simple gastric acid model, in which we...... mimicked the dynamic pH changes in the human stomach. In the present study, model gastric fluid was set up to imitate pH dynamics in the stomachs of young and elderly people after ingestion of a standard meal. To model a serious foodborne pathogen, we followed the survival of Salmonella enterica serotype...

  9. Branched-chain amino acid supplementation reduces oxidative stress and prolongs survival in rats with advanced liver cirrhosis.

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    Motoh Iwasa

    Full Text Available Long-term supplementation with branched-chain amino acids (BCAA is associated with prolonged survival and decreased frequency of development of hepatocellular carcinoma (HCC in patients with liver cirrhosis. However, the pharmaceutical mechanism underlying this association is still unclear. We investigated whether continuous BCAA supplementation increases survival rate of rats exposed to a fibrogenic agent and influences the iron accumulation, oxidative stress, fibrosis, and gluconeogenesis in the liver. Further, the effects of BCAA on gluconeogenesis in cultured cells were also investigated. A significant improvement in cumulative survival was observed in BCAA-supplemented rats with advanced cirrhosis compared to untreated rats with cirrhosis (P<0.05. The prolonged survival due to BCAA supplementation was associated with reduction of iron contents, reactive oxygen species production and attenuated fibrosis in the liver. In addition, BCAA ameliorated glucose metabolism by forkhead box protein O1 pathway in the liver. BCAA prolongs survival in cirrhotic rats and this was likely the consequences of reduced iron accumulation, oxidative stress and fibrosis and improved glucose metabolism in the liver.

  10. Surviving the acid barrier: responses of pathogenic Vibrio cholerae to simulated gastric fluid. (United States)

    Singh, Atheesha; Barnard, Tobias G


    When bacteria are subjected to low acidic pHs of the gastric environment, they may enter the viable but nonculturable (VBNC) state of survival. In this state, bacteria cannot be cultured on solid media, still exhibit signs of metabolic activity (viability). In this study, the response of pathogenic Vibrio cholerae O1 and O139 to low pH-simulated environments of the human stomach was evaluated for their survival by culturability (plate count) and viability (flow cytometry-FC) assays. Bacteria were acid challenged with simulated gastric fluid (SGF) at pH 1.5, 2.5, 3.5 and 4.5 over a period of 180 min. Exposure to SGF up to 120 min increased acid tolerance of the Vibrios up to pH 3.5 with acid challenge occurring at pH 4.5. Bacteria were culturable from pH 2.5 to 4.5 up to 60 min SGF exposure. The stationary-phase cultures of Vibrio were able to survive SGF at all pHs in an 'injured' state with FC. This could possibly mean that the bacteria have entered the VBNC stage of survival. This is a worrying public health concern due to the fact that once favourable conditions arise (intestines), these Vibrios can change back to an infectious state and cause disease.

  11. Survival and growth of probiotic lactic acid bacteria in refrigerated pickle products (United States)

    We examined 10 lactic acid bacteria that have been previously characterized for commercial use as probiotic cultures, mostly for dairy products, including 1 Pediococcus and 9 Lactobacilli. Our objectives were to develop a rapid procedure for determining the long-term survivability of these cultures ...

  12. Survival of Salmonella serovars on beef carcasses and molecular mechanisms to survive low temperature stress and desiccation

    DEFF Research Database (Denmark)

    Knudsen, Gitte Maegaard; Thomsen, Line Elnif; Aabo, Søren


    . Infantis and S. Newport. This experiment indicates that storage at low temperature of beef carcasses can be used as a reduction strategy for Salmonella spp. in beef. In addition molecular mechanisms to resist low temperature stress and desiccation have been investigated. Mutants in the otsA, rpoS and clp......We have investigated survival of Salmonella serotypes on beef cuts over a 14-days period at 3°C. A reduction in the colony forming (CFU) units were found for all the tested serotypes. The reductions varied from a 30-fold reduction for S. Typhimurium DT104 to a more than 1000-fold reduction for S...

  13. Influences of acid mine drainage and thermal enrichment on stream fish reproduction and larval survival (United States)

    Hafs, Andrew W.; Horn, C.D.; Mazik, P.M.; Hartman, K.J.


    Potential effects of acid mine drainage (AMD) and thermal enrichment on the reproduction of fishes were investigated through a larval-trapping survey in the Stony River watershed, Grant County, WV. Trapping was conducted at seven sites from 26 March to 2 July 2004. Overall larval catch was low (379 individuals in 220 hours of trapping). More larval White Suckers were captured than all other species. Vectors fitted to nonparametric multidimensional scaling ordinations suggested that temperature was highly correlated to fish communities captured at our sites. Survival of larval Fathead Minnows was examined in situ at six sites from 13 May to 11 June 2004 in the same system. Larval survival was lower, but not significantly different between sites directly downstream of AMD-impacted tributaries (40% survival) and non-AMD sites (52% survival). The lower survival was caused by a significant mortality event at one site that coincided with acute pH depression in an AMD tributary immediately upstream of the site. Results from a Cox proportional hazard test suggests that low pH is having a significant negative influence on larval fish survival in this system. The results from this research indicate that the combination of low pH events and elevated temperature are negatively influencing the larval fish populations of the Stony River watershed. Management actions that address these problems would have the potential to substantially increase both reproduction rates and larval survival, therefore greatly enhancing the fishery.

  14. Effect of alpha lipoic acid on retinal ganglion cell survival in an optic nerve crush model (United States)

    Liu, Ruixing; Wang, Yanling; Pu, Mingliang


    Purpose This study was conducted to determine whether alpha lipoic acid (ALA) promotes the survival of retinal ganglion cells (RGCs) in a rat model of optic nerve crush (ONC) injury and to investigate the neuroprotective mechanisms of ALA in the retina in this ONC injury model. Methods Adult male Sprague-Dawley rats (180–220 g) were subjected to ONC injury surgery. ALA (63 mg/kg) was injected intravenously 1 day before or after the ONC injury. Animals were euthanized after 10 days, and the number of ganglion cells positive for RNA-binding protein with multiple splicing (Rbpms), which is an RGC marker, were counted on the whole mount retinas. In addition, immunofluorescence and immunoblotting were performed to examine the localization and levels of erythropoietin receptor (EPOR) and neurotrophin-4/5 (NT4/5) in the retinas in all experimental groups. To determine whether the EPO/EPOR signaling pathway was involved in the ALA antioxidant pathway, the rats were subjected to ruxolitinib (INCB018424, 0.25 mg/kg, bid, intraperitoneal, i.p.) treatment after the animals were injected intravenously with ALA 1 day before ONC injury. Results The average number of Rbpms-positive cells/mm2 in the control group (sham-operated group), the ONC group, the ALA-ONC group, and the ONC-ALA group retinas was 2219±28, 418±8, 848±22, and 613±18/mm2, respectively. The ALA-ONC and ONC-ALA groups showed a statistically significantly increased RGC survival rate compared to the ONC group. There were statistical differences in the RGC survival rates between the ALA-ONC (39%) and ONC-ALA groups (28%; p<0.05). Immunofluorescent labeling showed that EPOR and NT4/5 expression was significant in the retinal ganglion cell layer (GCL). At the same time, western blot analysis revealed that ALA induced upregulation of EPOR protein and NT4/5 protein expression in the retina after ONC injury. However, INCB018424 reversed the protective effects of ALA on the ONC retinas. Conclusions ALA has

  15. An astrophysically-relevant mechanism for amino acid enantiomer enrichment

    NARCIS (Netherlands)

    P. Fletcher, S.; B. C. Jagt, R.; Feringa, B.L.


    The sublimation of low ee amino acids was examined while exploring simple mechanisms by which high ee amino acids can be generated under conditions that exist in space; significant enantioenrichment of a variety of amino acids by sublimation was achieved.

  16. Mechanisms of acid tolerance in bacteria and prospects in biotechnology and bioremediation. (United States)

    Liu, Yuping; Tang, Hongzhi; Lin, Zhanglin; Xu, Ping


    Acidogenic and aciduric bacteria have developed several survival systems in various acidic environments to prevent cell damage due to acid stress such as that on the human gastric surface and in the fermentation medium used for industrial production of acidic products. Common mechanisms for acid resistance in bacteria are proton pumping by F1-F0-ATPase, the glutamate decarboxylase system, formation of a protective cloud of ammonia, high cytoplasmic urease activity, repair or protection of macromolecules, and biofilm formation. The field of synthetic biology has rapidly advanced and generated an ever-increasing assortment of genetic devices and biological modules for applications in biofuel and novel biomaterial productions. Better understanding of aspects such as overproduction of general shock proteins, molecular mechanisms, and responses to cell density adopted by microorganisms for survival in low pH conditions will prove useful in synthetic biology for potential industrial and environmental applications.

  17. Effect of fatty acids on human bone marrow mesenchymal stem cell energy metabolism and survival. (United States)

    Fillmore, Natasha; Huqi, Alda; Jaswal, Jagdip S; Mori, Jun; Paulin, Roxane; Haromy, Alois; Onay-Besikci, Arzu; Ionescu, Lavinia; Thébaud, Bernard; Michelakis, Evangelos; Lopaschuk, Gary D


    Successful stem cell therapy requires the optimal proliferation, engraftment, and differentiation of stem cells into the desired cell lineage of tissues. However, stem cell therapy clinical trials to date have had limited success, suggesting that a better understanding of stem cell biology is needed. This includes a better understanding of stem cell energy metabolism because of the importance of energy metabolism in stem cell proliferation and differentiation. We report here the first direct evidence that human bone marrow mesenchymal stem cell (BMMSC) energy metabolism is highly glycolytic with low rates of mitochondrial oxidative metabolism. The contribution of glycolysis to ATP production is greater than 97% in undifferentiated BMMSCs, while glucose and fatty acid oxidation combined only contribute 3% of ATP production. We also assessed the effect of physiological levels of fatty acids on human BMMSC survival and energy metabolism. We found that the saturated fatty acid palmitate induces BMMSC apoptosis and decreases proliferation, an effect prevented by the unsaturated fatty acid oleate. Interestingly, chronic exposure of human BMMSCs to physiological levels of palmitate (for 24 hr) reduces palmitate oxidation rates. This decrease in palmitate oxidation is prevented by chronic exposure of the BMMSCs to oleate. These results suggest that reducing saturated fatty acid oxidation can decrease human BMMSC proliferation and cause cell death. These results also suggest that saturated fatty acids may be involved in the long-term impairment of BMMSC survival in vivo.

  18. Retinoic acid as a survival factor in neuronal development of the grasshopper, Locusta migratoria. (United States)

    Sukiban, Jeyathevy; Bräunig, Peter; Mey, Jörg; Bui-Göbbels, Katrin


    Based on experience with cell cultures of adult insect neurons, we develop a serum-free culture system for embryonic locust neurons. Influences of trophic substances on survival and neurite outgrowth of developing neurons are investigated. For the first time, a positive trophic effect of 9-cis retinoic acid (9-cis RA) was shown in vitro on embryonic neurons of an insect. We observed longer cell survival of 50 % developmental stage neurons in cultures supplemented with 0.3 nM 9-cis RA. Furthermore, an influence on neuron morphology was revealed, as the addition of 9-cis RA to cell culture medium led to an increase in the number of neurites per cell. Although an RA receptor gene, LmRXR (Locusta migratoria retinoid X receptor), was expressed in the central nervous system throughout development, the influence of 9-cis RA on neuronal survival and outgrowth was restricted to 50 % stage embryonic cells.

  19. Survival of gas phase amino acids and nucleobases in space radiation conditions (United States)

    Pilling, S.; Andrade, D. P. P.; de Castilho, R. B.; Cavasso-Filho, R. L.; Lago, A. F.; Coutinho, L. H.; de Souza, G. G. B.; Boechat-Roberty, H. M.; de Brito, A. Naves


    We present experimental studies on the photoionization and photodissociation processes (photodestruction) of gaseous amino acids and nucleobases in interstellar and interpla-netary radiation analogs conditions. The measurements have been undertaken at the Brazilian Synchrotron Light Laboratory (LNLS), employing vacuum ultraviolet (VUV) and soft X-ray photons. The experimental set up basically consists of a time-of-flight mass spectrometer kept under high vacuum conditions. Mass spectra were obtained using a photoelectron photoion coincidence technique. We have shown that the amino acids are effectively more destroyed (up to 70 80%) by the stellar radiation than the nucleobases, mainly in the VUV. Since polycyclic aromatic hydrocarbons have the same survival capability and seem to be ubiquitous in the ISM, it is not unreasonable to predict that nucleobases could survive in the interstellar medium and/or in comets, even as a stable cation.

  20. Survival of gas phase amino acids and nucleobases in space radiation conditions

    CERN Document Server

    Pilling, S; de Castilho, R B; Cavasso-Filho, R L; Lago, A F; Coutinho, L H; de Souza, G G B; Boechat-Roberty, H M; de Brito, A Naves


    We present experimental studies on the photoionization and photodissociation processes (photodestruction) of gaseous amino acids and nucleobases in interstellar and interplanetary radiation conditions analogs. The measurements have been undertaken at the Brazilian Synchrotron Light Laboratory (LNLS), employing vacuum ultraviolet (VUV) and soft X-ray photons. The experimental set up basically consists of a time-of-flight mass spectrometer kept under high vacuum conditions. Mass spectra were obtained using photoelectron photoion coincidence technique. We have shown that the amino acids are effectively more destroyed (up to 70-80%) by the stellar radiation than the nucleobases, mainly in the VUV. Since polycyclic aromatic hydrocarbons have the same survival capability and seem to be ubiquitous in the ISM, it is not unreasonable to predict that nucleobases could survive in the interstellar medium and/or in comets, even as a stable cation.

  1. Asiatic Acid Prevents the Deleterious Effects of Valproic Acid on Cognition and Hippocampal Cell Proliferation and Survival

    Directory of Open Access Journals (Sweden)

    Jariya Umka Welbat


    Full Text Available Valproic acid (VPA is commonly prescribed as an anticonvulsant and mood stabilizer used in the treatment of epilepsy and bipolar disorder. A recent study has demonstrated that VPA reduces histone deacetylase (HDAC activity, an action which is believed to contribute to the effects of VPA on neural stem cell proliferation and differentiation which may explain the cognitive impairments produced in rodents and patients. Asiatic acid is a triterpenoid derived from the medicinal plant Centella asiatica. Our previous study has shown that Asiatic acid improves working spatial memory and increases cell proliferation in the sub granular zone of the hippocampal dentate gyrus. In the present study we investigate the effects of Asiatic acid in preventing the memory and cellular effects of VPA. Male Spraque-Dawley rats were orally administered Asiatic acid (30 mg/kg/day for 28 days, while VPA-treated animals received injections of VPA (300 mg/kg twice a day from Day 15 to Day 28 for 14 days. Spatial memory was determined using the novel object location (NOL test and hippocampal cell proliferation and survival was quantified by immuostaining for Ki-67 and Bromodeoxyuridine (BrdU, respectively. The results showed that VPA-treated animals were unable to discriminate between objects in familiar and novel locations. Moreover, VPA significantly reduced numbers of Ki-67 and BrdU positive cells. These results indicate that VPA treatment caused impairments of spatial working memory, cell proliferation and survival in the subgranular zone (SGZ of the hippocampal dentate gyrus (DG. However, these abnormalities were restored to control levels by co-treatment with Asiatic acid. These data demonstrate that Asiatic acid could prevent the spatial memory and neurogenesis impairments caused by VPA.

  2. Bile components and amino acids affect survival of the newly excysted juvenile Clonorchis sinensis in maintaining media. (United States)

    Li, Shunyu; Kim, Tae Im; Yoo, Won Gi; Cho, Pyo Yun; Kim, Tong-Soo; Hong, Sung-Jong


    Clonorchis sinensis thrives on bile juice. The effects of bile and bile acids on newly excysted juvenile C. sinensis (CsNEJ) were studied in terms of survival. Survival of CsNEJs maintained in 1x Locke's solution, Dulbecco's modified Eagle's medium, NCTC 109, Eagle's, RPMI 1640, and 0.1% glucose was high, but dropped rapidly in 2x Locke's, 0.85% NaCl, and phosphate-buffered saline. Most amino acids in the media favored CsNEJ survival; however, aspartic and glutamic acids and adenine reduced survival. Survival was also significantly lower in media containing more than 0.1% bile. CsNEJs preconditioned in low bile media survived longer in higher bile media. All bile acids and conjugated bile salts were found to favor CsNEJ survival, except for lithocholic acid (LCA) which was toxic. NCTC 109 medium was found to be optimal for the in vitro maintenance of CsNEJs and 1x Locke's solution to be suitable for analyzing the biological effects of bioactive compounds and molecules. Based on these results, we propose that bile acids enhance activity of CsNEJs, but LCA deteriorate CsNEJs.

  3. Burkholderia cepacia complex isolates survive intracellularly without replication within acidic vacuoles of Acanthamoeba polyphaga. (United States)

    Lamothe, Julie; Thyssen, Sandra; Valvano, Miguel A


    We have previously demonstrated that isolates of the Burkholderia cepacia complex can survive intracellularly in murine macrophages and in free-living Acanthamoeba. In this work, we show that the clinical isolates B. vietnamiensis strain CEP040 and B. cenocepacia H111 survived but did not replicate within vacuoles of A. polyphaga. B. cepacia-containing vacuoles accumulated the fluid phase marker Lysosensor Blue and displayed strong blue fluorescence, indicating that they had low pH. In contrast, the majority of intracellular bacteria within amoebae treated with the V-ATPse inhibitor bafilomycin A1 localized in vacuoles that did not fluoresce with Lysosensor Blue. Experiments using bacteria fluorescently labelled with chloromethylfluorescein diacetate demonstrated that intracellular bacteria remained viable for at least 24 h. In contrast, Escherichia coli did not survive within amoebae after 2 h post infection. Furthermore, intracellular B. vietnamiensis CEP040 retained green fluorescent protein within the bacterial cytoplasm, while this protein rapidly escaped from the cytosol of phagocytized heat-killed bacteria into the vacuolar lumen. Transmission electron microscopy analysis confirmed that intracellular Burkholderia cells were structurally intact. In addition, both Legionella pneumophila- and B. vietnamiensis-containing vacuoles did not accumulate cationized ferritin, a compound that localizes within the lysosome. Thus, our observations support the notion that B. cepacia complex isolates can use amoebae as a reservoir in the environment by surviving without intracellular replication within an acidic vacuole that is distinct from the lysosomal compartment.

  4. Programmed cell death in trypanosomatids: is it an altruistic mechanism for survival of the fittest? (United States)

    Debrabant, Alain; Nakhasi, Hira


    The protozoan parasites Leishmania, Trypanosoma cruzi and Trypanosoma brucei show multiple features consistent with a form of programmed cell death (PCD). Despite some similarities with apoptosis of mammalian cells, PCD in trypanosomatid protozoans appears to be significantly different. In these unicellular organisms, PCD could represent an altruistic mechanism for the selection of cells, from the parasite population, that are fit to be transmitted to the next host. Alternatively, PCD could help in controlling the population of parasites in the host, thereby increasing host survival and favoring parasite transmission, as proposed by Seed and Wenk. Therefore, PCD in trypanosomatid parasites may represent a pathway involved both in survival and propagation of the species.

  5. The Francisella intracellular life cycle: towards molecular mechanisms of intracellular survival and proliferation

    Directory of Open Access Journals (Sweden)

    Audrey eChong


    Full Text Available The tularemia-causing bacterium Francisella tularensis is a facultative intracellular organism with a complex intracellular lifecycle that ensures its survival and proliferation in a variety of mammalian cell types, including professional phagocytes. Because this cycle is essential to Francisella pathogenesis and virulence, much research has focused on deciphering the mechanisms of its intracellular survival and replication and characterizing both bacterial and host determinants of the bacterium’s intracellular cycle. Studies of various strains and host cell models have led to the consensual paradigm of Francisella as a cytosolic pathogen, but also to some controversy about its intracellular cycle. In this review, we will detail major findings that have advanced our knowledge of Francisella intracellular survival strategies and also attempt to reconcile discrepancies that exist in our molecular understanding of the Francisella-phagocyte interaction.

  6. Dietary Omega-3 Fatty Acids Increase Survival and Decrease Bacterial Load in Mice Subjected to Staphylococcus aureus-Induced Sepsis. (United States)

    Svahn, Sara L; Ulleryd, Marcus A; Grahnemo, Louise; Ståhlman, Marcus; Borén, Jan; Nilsson, Staffan; Jansson, John-Olov; Johansson, Maria E


    Sepsis caused by Staphylococcus aureus is increasing in incidence. With the alarming use of antibiotics,S. aureus is prone to become methicillin resistant. Antibiotics are the only widely used pharmacological treatment for sepsis. Interestingly, mice fed high-fat diet (HFD) rich in polyunsaturated fatty acids have better survival of S. aureus-induced sepsis than mice fed HFD rich in saturated fatty acids (HFD-S). To investigate what component of polyunsaturated fatty acids, i.e., omega-3 or omega-6 fatty acids, exerts beneficial effects on the survival of S. aureus-induced sepsis, mice were fed HFD rich in omega-3 or omega-6 fatty acids for 8 weeks prior to inoculation with S. aureus Further, mice fed HFD-S were treated with omega-3 fatty acid metabolites known as resolvins. Mice fed HFD rich in omega-3 fatty acids had increased survival and decreased bacterial loads compared to those for mice fed HFD-S after S. aureus-induced sepsis. Furthermore, the bacterial load was decreased in resolvin-treated mice fed HFD-S after S. aureus-induced sepsis compared with that in mice treated with vehicle. Dietary omega-3 fatty acids increase the survival of S. aureus-induced sepsis by reversing the deleterious effect of HFD-S on mouse survival.

  7. Survival of the functional yeast Kluyveromyces marxianus B0399 in fermented milk with added sorbic acid. (United States)

    Tabanelli, G; Verardo, V; Pasini, F; Cavina, P; Lanciotti, R; Caboni, M F; Gardini, F; Montanari, C


    In this study, the survival of the functional yeast Kluyveromyces marxianus B0399 in an industrially produced fermented milk was evaluated. In particular, the yeast viability was assessed throughout the entire shelf-life of the product (30 d) to ensure the presence of the effective yeast dose (20 million viable cells for each serving of 125 g) while avoiding, by sorbic acid addition, yeast growth, which could affect product quality and stability. To find the best combination of yeast and sorbic acid concentration, 13 different combinations were tested, and then 2 of them were chosen for industrial production. In production at lower concentrations (30 million viable cells, 150 mg/kg of sorbic acid) the effective dose was maintained only at 4 and 6°C, whereas at higher dosages (70 million viable cells, 250 mg/kg of sorbic acid) the effect of temperature was less evident. In all the trials, the concentration of sorbic acid was not affected by microbial metabolism and remained stable throughout the entire shelf-life.

  8. Kinetics and Mechanism of Oxidation of Phenyl Acetic Acid and Dl-Mandelic Acid by Permanganate in Acid Medium

    Directory of Open Access Journals (Sweden)

    B.Syama Sundar


    Full Text Available Kinetics of oxidation of phenyl acetic acid and DL- Mandelic acid by potassium permanganate in aqueous acetic acid and perchloric acid mixture reveals that the kinetic orders are first order in oxidant, first order in H+ and zero order in substrate for phenyl acetic acid. DL-Mandelic acid exhibits first order in oxidant and zero order in substrate. The results are rationalised by a mechanism involving intermediate formation of mandelic acid in case of Phenyl acetic acid and ester formation with Mn (VII in case of DL-Mandelic acid. The following order of reactivity is observed: DL-Mandelic acid > Phenyl acetic acid. The high reactivity of DL-Mandelic acid over phenyl acetic acid may be due to different mechanisms operating with the two substrates and benzaldehyde is the final product in both the cases.

  9. Mechanisms of Sensorineural Cell Damage, Death and Survival in the Cochlea

    Directory of Open Access Journals (Sweden)

    Allen Frederic Ryan


    Full Text Available The majority of acquired hearing loss, including presbycusis, is caused by irreversible damage to the sensorineural tissues of the cochlea. This article reviews the intracellular mechanisms that contribute to sensorineural damage in the cochlea, as well as the survival signaling pathways that can provide endogenous protection and tissue rescue. These data have primarily been generated in hearing loss not directly related to age. However, there is evidence that similar mechanisms operate in presbycusis. Moreover, accumulation of damage from other causes can contribute to age-related hearing loss. Potential therapeutic interventions to balance opposing but interconnected cell damage and survival pathways, such as antioxidants, anti-apoptotics, and pro-inflammatory cytokine inhibitors, are also discussed.

  10. Resilient Voting Mechanisms for Mission Survivability in Cyberspace: Combining Replication and Diversity

    Directory of Open Access Journals (Sweden)

    Charles A. Kamhoua


    Full Text Available While information systems became ever more complex and the interdependence of these systems increased, mission-critical services should be survivable even in the presence of cyber attacks or internal failures. Node replication can be used to protect a mission-critical system against faults that may occur naturally or be caused by malicious attackers. The overall reliability increases by the number of replicas. However, when the replicas are a perfect copy of each other, a successful attack or failure in any node can be instantaneously repeated in all the other nodes. Eventually, the service of those nodes will discontinue, which may affect the system’s mission. Therefore, it becomes evident that there must be more survivable approach with diversity among the replicas in mission-critical systems. In particular, thisresearch investigates the best binary voting mechanism among replicas. Furthermore, with experimental results, we compare the simple majority mechanism with hierarchical decision process and discuss theirtrade-offs.

  11. Polysialic acid sustains cancer cell survival and migratory capacity in a hypoxic environment (United States)

    Elkashef, Sara M.; Allison, Simon J.; Sadiq, Maria; Basheer, Haneen A.; Ribeiro Morais, Goreti; Loadman, Paul M.; Pors, Klaus; Falconer, Robert A.


    Polysialic acid (polySia) is a unique carbohydrate polymer expressed on the surface of NCAM (neuronal cell adhesion molecule) in a number of cancers where it modulates cell-cell and cell-matrix adhesion, migration, invasion and metastasis and is strongly associated with poor clinical prognosis. We have carried out the first investigation into the effect of polySia expression on the behaviour of cancer cells in hypoxia, a key source of chemoresistance in tumours. The role of polysialylation and associated tumour cell migration and cell adhesion were studied in hypoxia, along with effects on cell survival and the potential role of HIF-1. Our findings provide the first evidence that polySia expression sustains migratory capacity and is associated with tumour cell survival in hypoxia. Initial mechanistic studies indicate a potential role for HIF-1 in sustaining polySia-mediated migratory capacity, but not cell survival. These data add to the growing body of evidence pointing to a crucial role for the polysialyltransferases (polySTs) in neuroendocrine tumour progression and provide the first evidence to suggest that polySia is associated with an aggressive phenotype in tumour hypoxia. These results have significant potential implications for polyST inhibition as an anti-metastatic therapeutic strategy and for targeting hypoxic cancer cells. PMID:27611649

  12. Survival of acid adapted and non-acid adapted Salmonella Typhimurium in pasteurized orange juice and yogurt under different storage temperatures. (United States)

    Álvarez-Ordóñez, Avelino; Valdés, Lorena; Bernardo, Ana; Prieto, Miguel; López, Mercedes


    The survival capacity of Salmonella enterica serovar Typhimurium acid adapted and non-acid adapted cells was monitored in pasteurized yogurt (pH 4.1) and orange juice (pH 3.6) during storage at different temperatures (4, 10, 25 and 37 ). Acid adapted and non-acid adapted cells were obtained by means of their growth for 36 h in Brain Heart Infusion broth acidified at pH 4.8 with citric acid and buffered (pH 7.0) Brain Heart Infusion broth, respectively. S. typhimurium showed a great ability to survive in both foodstuffs and, especially, in yogurt, where both acid adapted and non-acid adapted populations suffered only a reduction of about 1.3-1.9 log10 cycles after 43 days of storage in the range of temperatures 4-25 . At 37  a higher bacterial inactivation was observed (4.0-4.4 log10 cycles). In orange juice, a different behaviour was observed for acid-adapted and non-acid adapted cells. Whereas non-acid adapted cells survived better than acid adapted cells at 4 and 10 , acid adapted cells showed enhanced survival abilities at higher temperatures (25 and 37 ). Thus, the times required to achieve a 5 log10 cycles reduction for non-acid adapted and acid adapted cells were 10.2 and 6.0 (4 ), 6.3 and 4.2 (10 ), 0.6 and 1.0 (25 ) and 0.10 and 0.15 (37 ) days, respectively. Evidence found in this study demonstrates that refrigeration temperatures protect S. typhimurium from inactivation in acid foods and indicates that S. typhimurium acid tolerance response (ATR) is determined by storage temperature and food composition.

  13. Effects of food resources on the fatty acid composition, growth and survival of freshwater mussels (United States)

    Richardson, William B.; Vallazza, Jon M.; Moraska Lafrancois, Brenda


    Increased nutrient and sediment loading in rivers have caused observable changes in algal community composition, and thereby, altered the quality and quantity of food resources available to native freshwater mussels. Our objective was to characterize the relationship between nutrient conditions and mussel food quality and examine the effects on fatty acid composition, growth and survival of juvenile mussels. Juvenile Lampsilis cardium and L. siliquoidea were deployed in cages for 28 d at four riverine and four lacustrine sites in the lower St. Croix River, Minnesota/Wisconsin, USA. Mussel foot tissue and food resources (four seston fractions and surficial sediment) were analyzed for quantitative fatty acid (FA) composition. Green algae were abundant in riverine sites, whereas cyanobacteria were most abundant in the lacustrine sites. Mussel survival was high (95%) for both species. Lampsilis cardium exhibited lower growth relative to L. siliquoidea (p 63 μm) of seston, including the bacterial FAs, and several of the FAs associated with sediments. Reduced mussel growth was observed in L. siliquoidea when the abundance of cyanobacteria exceeded 9% of the total phytoplankton biovolume. Areas dominated by cyanobacteria may not provide sufficient food quality to promote or sustain mussel growth. PMID:28267810

  14. Effects of food resources on the fatty acid composition, growth and survival of freshwater mussels (United States)

    Bartsch, Michelle; Bartsch, Lynn; Richardson, William B.; Vallazza, Jon; Moraska Lafrancois, Brenda


    Increased nutrient and sediment loading in rivers have caused observable changes in algal community composition, and thereby, altered the quality and quantity of food resources available to native freshwater mussels. Our objective was to characterize the relationship between nutrient conditions and mussel food quality and examine the effects on fatty acid composition, growth and survival of juvenile mussels. Juvenile Lampsilis cardium and L. siliquoidea were deployed in cages for 28 d at four riverine and four lacustrine sites in the lower St. Croix River, Minnesota/Wisconsin, USA. Mussel foot tissue and food resources (four seston fractions and surficial sediment) were analyzed for quantitative fatty acid (FA) composition. Green algae were abundant in riverine sites, whereas cyanobacteria were most abundant in the lacustrine sites. Mussel survival was high (95%) for both species. Lampsilis cardium exhibited lower growth relative to L. siliquoidea (p 63 μm) of seston, including the bacterial FAs, and several of the FAs associated with sediments. Reduced mussel growth was observed in L. siliquoidea when the abundance of cyanobacteria exceeded 9% of the total phytoplankton biovolume. Areas dominated by cyanobacteria may not provide sufficient food quality to promote or sustain mussel growth.

  15. Association Mechanism Between Propionic Acid and Trioctylamine

    Institute of Scientific and Technical Information of China (English)

    李振宇; 秦炜; 戴猷元


    Tertiary amines dissolved in diluents are attractive extractants for recovery of carboxylic acids from dilute aqueous solutions. Quantitative Fourier transform infrared (FTIR) analysis of organic solutions containing various concentrations of trioctylamine (TOA), n-octanol, and propionic acid was carried out, and liquid-liquid equilibrium was investigated using TOA in n-octanol as the solvent. The fraction of ion-pair association between TOA and propionic acid in the organic phase was quantitatively determined by FTIR. The apparent reactive extraction equilibrium constant, K11, was calculated using the quantitative FTIR spectrum and the equilibrium data. The results show that the fraction of ion-pair association depends on diluent concentration, complex dissolution for propionic acid, and association between TOA and propionic acid. The K11 based on quantitative FTIR has the same loading trend as that from the equilibrium data.

  16. Acid mine pollution: effects on survival, reproduction and aging of stream bottom microinvertebrates. Completion report

    Energy Technology Data Exchange (ETDEWEB)

    Hummon, W.D.


    Warbug manometry was used to assess the effect of acid mine water on respiratory processes in three species of aquatic insect larvae. Field collections and laboratory toxicity tests indicated short longevity under strong acid mine conditions. Mixed results were found with respect to weight-dependent respiratory rates. Sequential respiration determinations, under control-control or control-treatment fluids, indicated that acid mine water did not consistently alter rates. Animals maintained in mine water until death showed gradual decreases in respiratory rates over time, rather than stepwise drops that would accompany ionic interference. For these species the toxic mode of action of acid mine water does not appear to operate through mechanisms that are detectable by respirometry.

  17. Explorative multifactor approach for investigating global survival mechanisms of Campylobacter jejuni under environmental conditions. (United States)

    Moen, Birgitte; Oust, Astrid; Langsrud, Øyvind; Dorrell, Nick; Marsden, Gemma L; Hinds, Jason; Kohler, Achim; Wren, Brendan W; Rudi, Knut


    Explorative approaches such as DNA microarray experiments are becoming increasingly important in microbial research. Despite these major technical advancements, approaches to study multifactor experiments are still lacking. We have addressed this problem by using rotation testing and a novel multivariate analysis of variance (MANOVA) approach (50-50 MANOVA) to investigate interacting experimental factors in a complex experimental design. Furthermore, a new rotation testing based method was introduced to calculate false-discovery rates for each response. This novel analytical concept was used to investigate global survival mechanisms in the environment of the major food-borne pathogen C. jejuni. We simulated nongrowth environmental conditions by investigating combinations of the factors temperature (5 and 25 degrees C) and oxygen tension (anaerobic, microaerobic, and aerobic). Data were generated with DNA microarrays for information about gene expression patterns and Fourier transform infrared (FT-IR) spectroscopy to study global macromolecular changes in the cell. Microarray analyses showed that most genes were either unchanged or down regulated compared to the reference (day 0) for the conditions tested and that the 25 degrees C anaerobic condition gave the most distinct expression pattern with the fewest genes expressed. The few up-regulated genes were generally stress related and/or related to the cell envelope. We found, using FT-IR spectroscopy, that the amount of polysaccharides and oligosaccharides increased under the nongrowth survival conditions. Potential mechanisms for survival could be to down regulate most functions to save energy and to produce polysaccharides and oligosaccharides for protection against harsh environments. Basic knowledge about the survival mechanisms is of fundamental importance in preventing transmission of this bacterium through the food chain.

  18. Bone Marrow Adipocytes Facilitate Fatty Acid Oxidation Activating AMPK and a Transcriptional Network Supporting Survival of Acute Monocytic Leukemia Cells. (United States)

    Tabe, Yoko; Yamamoto, Shinichi; Saitoh, Kaori; Sekihara, Kazumasa; Monma, Norikazu; Ikeo, Kazuho; Mogushi, Kaoru; Shikami, Masato; Ruvolo, Vivian; Ishizawa, Jo; Hail, Numsen; Kazuno, Saiko; Igarashi, Mamoru; Matsushita, Hiromichi; Yamanaka, Yasunari; Arai, Hajime; Nagaoka, Isao; Miida, Takashi; Hayashizaki, Yoshihide; Konopleva, Marina; Andreeff, Michael


    Leukemia cells in the bone marrow must meet the biochemical demands of increased cell proliferation and also survive by continually adapting to fluctuations in nutrient and oxygen availability. Thus, targeting metabolic abnormalities in leukemia cells located in the bone marrow is a novel therapeutic approach. In this study, we investigated the metabolic role of bone marrow adipocytes in supporting the growth of leukemic blasts. Prevention of nutrient starvation-induced apoptosis of leukemic cells by bone marrow adipocytes, as well as the metabolic and molecular mechanisms involved in this process, was investigated using various analytic techniques. In acute monocytic leukemia (AMoL) cells, the prevention of spontaneous apoptosis by bone marrow adipocytes was associated with an increase in fatty acid β-oxidation (FAO) along with the upregulation of PPARγ, FABP4, CD36, and BCL2 genes. In AMoL cells, bone marrow adipocyte coculture increased adiponectin receptor gene expression and its downstream target stress response kinase AMPK, p38 MAPK with autophagy activation, and upregulated antiapoptotic chaperone HSPs. Inhibition of FAO disrupted metabolic homeostasis, increased reactive oxygen species production, and induced the integrated stress response mediator ATF4 and apoptosis in AMoL cells cocultured with bone marrow adipocytes. Our results suggest that bone marrow adipocytes support AMoL cell survival by regulating their metabolic energy balance and that the disruption of FAO in bone marrow adipocytes may be an alternative, novel therapeutic strategy for AMoL therapy. Cancer Res; 77(6); 1453-64. ©2017 AACR.

  19. Sialic acid transporter NanT participates in Tannerella forsythia biofilm formation and survival on epithelial cells. (United States)

    Honma, Kiyonobu; Ruscitto, Angela; Frey, Andrew M; Stafford, Graham P; Sharma, Ashu


    Tannerella forsythia is a periodontal pathogen implicated in periodontitis. This gram-negative pathogen depends on exogenous peptidoglycan amino sugar N-acetylmuramic acid (NAM) for growth. In the biofilm state the bacterium can utilize sialic acid (Neu5Ac) instead of NAM to sustain its growth. Thus, the sialic acid utilization system of the bacterium plays a critical role in the growth and survival of the organism in the absence of NAM. We sought the function of a T. forsythia gene annotated as nanT coding for an inner-membrane sugar transporter located on a sialic acid utilization genetic cluster. To determine the function of this putative sialic acid transporter, an isogenic nanT-deletion mutant generated by allelic replacement strategy was evaluated for biofilm formation on NAM or Neu5Ac, and survival on KB epithelial cells. Moreover, since T. forsythia forms synergistic biofilms with Fusobacterium nucleatum, co-biofilm formation activity in mixed culture and sialic acid uptake in culture were also assessed. The data showed that the nanT-inactivated mutant of T. forsythia was attenuated in its ability to uptake sialic acid. The mutant formed weaker biofilms compared to the wild-type strain in the presence of sialic acid and as co-biofilms with F. nucleatum. Moreover, compared to the wild-type T. forsythia nanT-inactivated mutant showed reduced survival when incubated on KB epithelial cells. Taken together, the data presented here demonstrate that NanT-mediated sialic transportation is essential for sialic acid utilization during biofilm growth and survival of the organism on epithelial cells and implies sialic acid might be key for its survival both in subgingival biofilms and during infection of human epithelial cells in vivo.

  20. Mechanisms Regulating Acid-Base Transporter Expression in Breast- and Pancreatic Cancer

    DEFF Research Database (Denmark)

    Gorbatenko, Andrej

    , characteristics of which are a shift towards glycolytic metabolism and increased acid production. HER2 receptor overexpression in breast cancer leads to further increased glycolysis, invasion and metastasis, drug resistance and poor prognosis. Increased tumor glycolysis requires acquisition of mechanisms...... for dealing with excess acid production. In this light, evidence accumulates on the importance of pH regulatory proteins to cancer cell survival and motility. Our group previously demonstrated upregulation of the Na+/HCO3 - co-transporter NBCn1 (SLC4A7) by a constitutively active form of HER2 receptor (p95HER...

  1. A reexamination of amino acids in lunar soils: Implications for the survival of exogenous organic material during impact delivery (United States)

    Brinton, Karen L. F.; Bada, Jeffrey L.


    Using a sensitive high performance liquid chromatography technique, we have analyzed both the hot water extract and the acid hydrolyzed hot water extract of lunar soil collected during the Apollo 17 mission. Both free amino acids and those derived from acid labile precursors are present at a level of roughly 15 ppb. Based on the D/L amino acid ratios, the free alanine and aspartic acid observed in the hot water extract can be entirely attributed to terrestrial biogenic contamination. However, in the acid labile fraction, precursors which yield amino acids are apparently present in the lunar soil. The amino acid distribution suggests that the precursor is probably solar wind implanted HCN. We have evaluated our results with regard to the meteoritic input of intact organic compounds to the moon based on an upper limit of ≤ 0.3 ppb for α-aminoisobutyric acid, a non-protein amino acid which does not generally occur in terrestrial organisms and which is not a major amino acid produced from HCN, but which is a predominant amino acid in many carbonaceous chondrites. We find that the survival of exogenous organic compounds during lunar impact is ≤ 0.8%. This result represents an example of minimum organic impact survivability. This is an important first step toward a better understanding of similar processes on Earth and on Mars, and their possible contribution to the budget of prebiotic organic compounds on the primitive Earth.

  2. Study of network survivability based on multi-path routing mechanism

    Institute of Scientific and Technical Information of China (English)

    HUANG Song; XU Yong; ZHANG Ling


    As an important secure routing mechanism, multi-path routing is one of the major ways to improve network efficiency and to guarantee the network security, which ensures the reliability of data transmission by using backup paths when the pri mary one is unavailable due to local node or link failures. Most current studies on multi-path routing mechanism are based on experiments or simulations. The re sults are usually specific application scenarios oriented heuristic algorithms, lacking universal significance. In this paper, a theoretic analysis is performed on the relationship between the multi-path routing policy, the network efficiency and its survivability. Starting with point-to-point communication network, an impact oriented analysis is made on the network interference under multi-path routing mechanism. Based on the analysis, the upper-limit of network performance under interference impact is also discussed.

  3. Sulfuric acid leaching of mechanically activated manganese carbonate ore

    Directory of Open Access Journals (Sweden)

    Kenan Yıldız


    Full Text Available Acidic leaching of mechanically activated manganese ore from Denizli – Tavas was investigated. The ore was activated mechanically in a planetary mill and the amorphisation in manganese structure was analyzed with X-ray diffraction. The parameters in acidic leaching of the ore were milling time, acid concentration and time. All experiments were performed at 25°C with solid to liquid ratio: 1/10. The activation procedure led to amorphization and structural disordering in manganese ore and accelerated the dissolution of manganese in acidic media.

  4. The mechanism and properties of acid-coagulated milk gels

    Directory of Open Access Journals (Sweden)

    Chanokphat Phadungath


    Full Text Available Acid-coagulated milk products such as fresh acid-coagulated cheese varieties and yogurt areimportant dairy food products. However, little is known regarding the mechanisms involved in gel formation, physical properties of acid gels, and the effects of processing variables such as heat treatment and gelation temperature on the important physical properties of acid milk gels. This paper reviews the modern concepts of possible mechanisms involved in the formation of particle milk gel aggregation, along with recent developments including the use of techniques such as dynamic low amplitude oscillatory rheology to observe the gel formation process, and confocal laser scanning microscopy to monitor gel microstructure.

  5. Mechanisms of survival, responses and sources of Salmonella in low-moisture environments

    Directory of Open Access Journals (Sweden)

    Sarah eFinn


    Full Text Available Some Enterobacteriaceae possess the ability to survive in low-moisture environments for extended periods of time. Many of the reported food-borne outbreaks associated with low-moisture foods involve Salmonella contamination. The control of Salmonella in low-moisture foods and their production environments represents a significant challenge for all food manufacturers. This review summarises the current state of knowledge with respect to Salmonella survival in intermediate- and low-moisture food matrices and their production environments. The mechanisms utilised by this bacterium to ensure their survival in these dry conditions remain to be fully elucidated, however in depth transcriptiomic data is now beginning to emerge regarding this observation. Earlier research work described the effect(s that low-moisture can exert on the long-term persistence and heat tolerance of Salmonella, however, data are also now available highlighting the potential cross-tolerance to other stressors including commonly used microbicidal agents. Sources and potential control measures to reduce the risk of contamination will be explored. By extending our understanding of these geno- and phenotypes, we may be able to exploit them to improve food safety and protect public health.

  6. Molecular mechanisms of Saccharomyces cerevisiae stress adaptation and programmed cell death in response to acetic acid

    Directory of Open Access Journals (Sweden)

    Sergio eGiannattasio


    Full Text Available Beyond its classical biotechnological applications such as food and beverage production or as a cell factory, the yeast Saccharomyces cerevisiae is a valuable model organism to study fundamental mechanisms of cell response to stressful environmental changes. Acetic acid is a physiological product of yeast fermentation and it is a well-known food preservative due to its antimicrobial action. Acetic acid has recently been shown to cause yeast cell death and aging. Here we shall focus on the molecular mechanisms of S. cerevisiae stress adaptation and programmed cell death in response to acetic acid. We shall elaborate on the intracellular signaling pathways involved in the cross-talk of pro-survival and pro-death pathways underlying the importance of understanding fundamental aspects of yeast cell homeostasis to improve the performance of a given yeast strain in biotechnological applications.

  7. Salvianolic acid B promotes survival of transplanted mesenchymal stem cells in spinal cord-injured rats

    Institute of Scientific and Technical Information of China (English)

    Xiao-bin BI; Yu-bin DENG; Dan-hui GAN; Ya-zhu WANG


    Aim: Stem cells hold great promise for brain and spinal cord injuries (SCI), but cell survival following transplantation to adult central nervous system has been poor. Salvianolic acid B (Sal B) has been shown to improve functional recovery in brain-injured rats. The present study was designed to determine whether Sal B could improve transplanted mesenchymal stem cell (MSC) survival in SCI rats. Methods: SCI rats were treated with Sal B. The Basso-Beatie-Bresnahan (BBB) scale was used to test the functional recovery. Sal B was used to protect MSC from being damaged by TNF-α in vitro. Bromodeoxyuridine-labeled MSC were transplanted into SCI rats with Sal B intraperitoneal injection, simul-taneously. MSC were examined, and the functional recovery of the SCI rats was tested. Results: Sal B treatment significantly reduced the lesion area from 0.26±0.05 mm2 to 0.15±0.03 mm2 (P<0.01) and remarkably raised the BBB scores on d 28, post-injury, from 7.3±0.9 to 10.5±1.3 (P<0.05), compared with the phosphate-buffered saline (PBS) control group. MSC were protected from the damage of TNF-α by Sal B. The number of surviving MSC in the MSC plus Sal B groups were 1143.3± 195.6 and 764.0±81.3 on d 7 and 28, post-transplantation, more than those in the MSC group, which was 569.3±72.3 and 237.0±61.3, respectively (P<0.05). Rats with MSC trans-planted and Sal B injected obtained higher BBB scores than those with MSC transplanted alone (P<0.05) and PBS (P<0.01). Conclusion: Sal B provides neuroprotection to SCI and promotes the survival of MSC in vitro and after cell transplantation to the injured spinal cord in vivo.

  8. In-Situ Survival Mechanisms of U and Tc Reducing Bacteria in Contaminated Sediments

    Energy Technology Data Exchange (ETDEWEB)

    Krumholz, Lee R.


    Desulfovibrio desulfuricans G20 and Shewanella oneidensis MR-1 are model subsurface organisms for studying genes involving in situ radionuclide transformation and sediment survival. Our research objective for this project has been to develop a signature-tagged mutagenesis (STM) procedure and use it to identify mutants in genes of these subsurface bacteria involved in sediment survival and radionuclide reduction. The mutant genes identified in these studies allow us for the first time to describe at the genetic level microbial processes that are actually being used by environmental bacteria while growing in their natural ecosystems. Identification of these genes revealed facets of microbial physiology and ecology that are not accessible through laboratory studies. Ultimately, this information may be used to optimize bioremediation or other engineered microbial processes. Furthermore, the identification of a mutant in a gene conferring multidrug resistance in strain MR-1 shows that this widespread mechanism of antibiotic resistance, likely has its origins as a mechanism of bacterial defense against naturally occurring toxins. Studies with D. desulfuricans G20: The STM procedure first involved generating a library of 5760 G20 mutants and screening for potential non-survivors in subsurface sediment microcosms. After two rounds of screening, a total of 117 mutants were confirmed to be true non-survivors. 97 transposon insertion regions have been sequenced to date. Upon further analysis of these mutants, we classified the sediment survival genes into COG functional categories. STM mutant insertions were located in genes encoding proteins related to metabolism (33%), cellular processes (42%), and information storage and processing (17%). We also noted 8% of STM mutants identified had insertions in genes for hypothetical proteins or unknown functions. Interestingly, at least 64 of these genes encode cytoplasmic proteins, 46 encode inner membrane proteins, and only 7 encode

  9. Pathway analysis reveals common pro-survival mechanisms of metyrapone and carbenoxolone after traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Helen L Hellmich

    Full Text Available Developing new pharmacotherapies for traumatic brain injury (TBI requires elucidation of the neuroprotective mechanisms of many structurally and functionally diverse compounds. To test our hypothesis that diverse neuroprotective drugs similarly affect common gene targets after TBI, we compared the effects of two drugs, metyrapone (MT and carbenoxolone (CB, which, though used clinically for noncognitive conditions, improved learning and memory in rats and humans. Although structurally different, both MT and CB inhibit a common molecular target, 11β hydroxysteroid dehydrogenase type 1, which converts inactive cortisone to cortisol, thereby effectively reducing glucocorticoid levels. We examined injury-induced signaling pathways to determine how the effects of these two compounds correlate with pro-survival effects in surviving neurons of the injured rat hippocampus. We found that treatment of TBI rats with MT or CB acutely induced in hippocampal neurons transcriptional profiles that were remarkably similar (i.e., a coordinated attenuation of gene expression across multiple injury-induced cell signaling networks. We also found, to a lesser extent, a coordinated increase in cell survival signals. Analysis of injury-induced gene expression altered by MT and CB provided additional insight into the protective effects of each. Both drugs attenuated expression of genes in the apoptosis, death receptor and stress signaling pathways, as well as multiple genes in the oxidative phosphorylation pathway such as subunits of NADH dehydrogenase (Complex1, cytochrome c oxidase (Complex IV and ATP synthase (Complex V. This suggests an overall inhibition of mitochondrial function. Complex 1 is the primary source of reactive oxygen species in the mitochondrial oxidative phosphorylation pathway, thus linking the protective effects of these drugs to a reduction in oxidative stress. The net effect of the drug-induced transcriptional changes observed here indicates that

  10. Interaction Mechanism of Anthracene with Benzoic Acid and Its Derivatives

    Institute of Scientific and Technical Information of China (English)

    HE Ying-Ying; WANG Xiao-Chang; FAN Xiao-Yuan; ZHAO Bo; JIN Peng-Kang


    Interaction mechanism of anthracene, one of the typical polycyclic aromatic hydrocarbons, with benzoic acid and its hydroxyl-substituted derivatives, o-hydroxylbenzoic acid and p-hydroxylbenzoic acid, were studied using FFIR, UV and fluorescence spectra. The experiments confirmed that there was a specific and oriented interaction between anthracene and the aromatic carboxylic acids, and the bonding mode depended on both the chemical struc- ture of reactants and acidity of solution. The π-H hydrogen bond played a main role in the interaction between an-thracene and the aromatic carboxylic proton of benzoic acid or o-hydroxylbenzoic acid when pH≤pK, and the π-π electron donor-acceptor (EDA) interaction increasingly became the main binding mode when pH>pK. The de-crease of interaction intensity of benzoic acid was observed by introducing hydroxyl at its ortho position. The spe-cial D-π-A structure of p-hydroxylbenzoic acid made it easy to form the planar multi-molecule congeries that could interact with anthracene, so the interaction between anthracene and p-hydroxylbenzoic acid always followed the π-π EDA model no matter the solution acidity. For p-hydroxylbenzoic acid, the π-π interaction mode remained un-changed when pH increased from 2.0 to 10.0, and the binding intensity was higher than that between benzoic acid and anthracene because of the formation of the multi-molecule congeries.

  11. Analysis of proteins responsive to acetic acid in Acetobacter: molecular mechanisms conferring acetic acid resistance in acetic acid bacteria. (United States)

    Nakano, Shigeru; Fukaya, Masahiro


    Acetic acid bacteria are used for industrial vinegar production because of their remarkable ability to oxidize ethanol and high resistance to acetic acid. Although several molecular machineries responsible for acetic acid resistance in acetic acid bacteria have been reported, the entire mechanism that confers acetic acid resistance has not been completely understood. One of the promising methods to elucidate the entire mechanism is global analysis of proteins responsive to acetic acid by two-dimensional gel electrophoresis. Recently, two proteins whose production was greatly enhanced by acetic acid in Acetobacter aceti were identified to be aconitase and a putative ABC-transporter, respectively; furthermore, overexpression or disruption of the genes encoding these proteins affected acetic acid resistance in A. aceti, indicating that these proteins are involved in acetic acid resistance. Overexpression of each gene increased acetic acid resistance in Acetobacter, which resulted in an improvement in the productivity of acetic acid fermentation. Taken together, the results of the proteomic analysis and those of previous studies indicate that acetic acid resistance in acetic acid bacteria is conferred by several mechanisms. These findings also provide a clue to breed a strain having high resistance to acetic acid for vinegar fermentation.

  12. Endotoxin-stimulated Rat Hepatic Stellate Cells Induce Autophagy in Hepatocytes as a Survival Mechanism. (United States)

    Dangi, Anil; Huang, Chao; Tandon, Ashish; Stolz, Donna; Wu, Tong; Gandhi, Chandrashekhar R


    Bacterial lipopolysaccharide (LPS)-stimulated hepatic stellate cells (HSCs) produce many cytokines including IFNβ, TNFα, and IL6, strongly inhibit DNA synthesis, but induce apoptosis of a small number of hepatocytes. In vivo administration of LPS (up to 10 mg/mL) causes modest inflammation and weight loss in rats but not mortality. We determined whether LPS-stimulated HSCs instigate mechanisms of hepatocyte survival. Rats received 10 mg/kg LPS (i.p.) and determinations were made at 6 h. In vitro, HSCs were treated with 100 ng/mL LPS till 24 h. The medium was transferred to hepatocytes, and determinations were made at 0-12 h. Controls were HSC-conditioned medium or medium-containing LPS. LPS treatment of rats caused autophagy in hepatocytes, a physiological process for clearance of undesirable material including injured or damaged organelles. This was accompanied by activation of c-Jun NH2 terminal kinase (JNK) and apoptosis of ~4-5% of hepatocytes. In vitro, LPS-conditioned HSC medium (LPS/HSC) induced autophagy in hepatocytes but apoptosis of only ~10% of hepatocytes. While LPS/HSC stimulated activation of JNK (associated with cell death), it also activated NFkB and ERK1/2 (associated with cell survival). LPS-stimulated HSCs produced IFNβ, and LPS/HSC-induced autophagy in hepatocytes and their apoptosis were significantly inhibited by anti-IFNβ antibody. Blockade of autophagy, on the other hand, strongly augmented hepatocyte apoptosis. While LPS-stimulated HSCs cause apoptosis of a subpopulation of hepatocytes by producing IFNβ, they also induce cell survival mechanisms, which may be of critical importance in resistance to liver injury during endotoxemia.

  13. Cisplatin Resistant Spheroids Model Clinically Relevant Survival Mechanisms in Ovarian Tumors.

    Directory of Open Access Journals (Sweden)

    Winyoo Chowanadisai

    Full Text Available The majority of ovarian tumors eventually recur in a drug resistant form. Using cisplatin sensitive and resistant cell lines assembled into 3D spheroids we profiled gene expression and identified candidate mechanisms and biological pathways associated with cisplatin resistance. OVCAR-8 human ovarian carcinoma cells were exposed to sub-lethal concentrations of cisplatin to create a matched cisplatin-resistant cell line, OVCAR-8R. Genome-wide gene expression profiling of sensitive and resistant ovarian cancer spheroids identified 3,331 significantly differentially expressed probesets coding for 3,139 distinct protein-coding genes (Fc >2, FDR < 0.05 (S2 Table. Despite significant expression changes in some transporters including MDR1, cisplatin resistance was not associated with differences in intracellular cisplatin concentration. Cisplatin resistant cells were significantly enriched for a mesenchymal gene expression signature. OVCAR-8R resistance derived gene sets were significantly more biased to patients with shorter survival. From the most differentially expressed genes, we derived a 17-gene expression signature that identifies ovarian cancer patients with shorter overall survival in three independent datasets. We propose that the use of cisplatin resistant cell lines in 3D spheroid models is a viable approach to gain insight into resistance mechanisms relevant to ovarian tumors in patients. Our data support the emerging concept that ovarian cancers can acquire drug resistance through an epithelial-to-mesenchymal transition.

  14. Substitued (E-b-(benzoylacrylic acids suppressed survival of neoplastic human HeLa cells

    Directory of Open Access Journals (Sweden)



    Full Text Available The bacteriostatic activity of some of alkyl substituted (E-b-(benzoylacrylic acids was shown earlier. The aim of this study was to investigate the antiproliferative action of 19 alkyl-, or halogeno-, or methoxy-, or acetamido- substituted (E-b-(benzoylacrylic acids, against human cervix carcinoma, HeLa, cells. Target HeLa cells were continuously treated with increasing concentrations of substituted (E-b-(benzoylacrylic acids during two days. The MTT test was used for assessment of the antiproliferative action of this group of compounds. Treatment of HeLa cells with 4-methyl-, 4-fluoro-, 4-chloro-, 4-bromo- and 4-methoxy- derivatives of (E-b-(benzoyl acrylic acid leads to the expression of cytostatic activity against HeLa cells (IC50 were in the range from 31-40 µM. Their antiproliferative action was less than that of the basic compound (E-b-(benzoylacrylic acid whose IC50 was 28.5 µM. The 3,4-dimethyl-, 2,4-dimethyl- and 2,5-dimethyl- derivatives as well as the 4-ethyl- and 3,4-dichloro- and 2,4-dichloro-derivatives, have stronger cytostatic activity than the correspoding monosubstituted and parent compound. Their IC50 were 18.5 µM; 17.5 µM; 17.0 mM; 17.5 µM; 22.0 µM and 18 µM, respectively. The 4-iso-propyl- and 4-n-butyl-derivatives exerted higher cytostatic activity than the compounds with a lower number of methylene -CH2- groups in the substitutent. Their IC50 were 14.5 µM and 6.5 µM respectively. The 2,5-di-iso-propyl- and 4-tert-butyl-derivatives expressed the most strong antiproliferative action against the investigated HeLa cells, IC50 being 4.5 µM and 5.5 µM, respectively. The investigated compounds affected the survival of HeLa cells, expressing a strong structure-activity relationship of the Hansch type.

  15. The prebiotic synthesis of amino acids - interstellar vs. atmospheric mechanisms (United States)

    Meierhenrich, U. J.; Muñoz Caro, G. M.; Schutte, W. A.; Barbier, B.; Arcones Segovia, A.; Rosenbauer, H.; Thiemann, W. H.-P.; Brack, A.


    Until very recently, prebiotic amino acids were believed to have been generated in the atmosphere of the early Earth, as successfully simulated by the Urey-Miller experiments. Two independent studies now identified ice photochemistry in the interstellar medium as a possible source of prebiotic amino acids. Ultraviolet irradiation of ice mixtures containing identified interstellar molecules (such as H2O, CO2, CO, CH3OH, and NH3) in the conditions of vacuum and low temperature found in the interstellar medium generated amino acid structures including glycine, alanine, serine, valine, proline, and aspartic acid. After warmup, hydrolysis and derivatization, our team was able to identify 16 amino acids as well as furans and pyrroles. Enantioselective analyses of the amino acids showed racemic mixtures. A prebiotic interstellar origin of amino acid structures is now discussed to be a plausible alternative to the Urey-Miller mechanism.

  16. Identification of organic acids in wine that stimulate mechanisms of gastric acid secretion. (United States)

    Liszt, Kathrin Ingrid; Walker, Jessica; Somoza, Veronika


    Wine may cause stomach irritation due to its stimulatory effect on gastric acid secretion, although the mechanisms by which wine or components thereof activate pathways of gastric acid secretion are poorly understood. Gastric pH was measured with a noninvasive intragastric probe, demonstrating that administration of 125 mL of white or red wine to healthy volunteers stimulated gastric acid secretion more potently than the administration of equivalent amounts of ethanol. Between both beverages, red wine showed a clear trend for being more active in stimulating gastric acid secretion than white wine (p = 0.054). Quantification of the intracellular proton concentration in human gastric tumor cells (HGT-1), a well-established indicator of proton secretion and, in turn, stomach acid formation in vivo, confirmed the stronger effect of red wine as compared to white wine. RT-qPCR experiments on cells exposed to red wine also revealed a more pronounced effect than white wine on the fold change expression of genes associated with gastric acid secretion. Of the quantitatively abundant organic acids in wine, malic acid and succinic acid most actively stimulated proton secretion in vitro. However, addition of ethanol to individual organic acids attenuated the secretory effect of tartaric acid, but not that of the other organic acids. It was concluded that malic acid for white wine and succinic acid for red wine are key organic acids that contribute to gastric acid stimulation.

  17. Single sample expression-anchored mechanisms predict survival in head and neck cancer.

    Directory of Open Access Journals (Sweden)

    Xinan Yang


    Full Text Available Gene expression signatures that are predictive of therapeutic response or prognosis are increasingly useful in clinical care; however, mechanistic (and intuitive interpretation of expression arrays remains an unmet challenge. Additionally, there is surprisingly little gene overlap among distinct clinically validated expression signatures. These "causality challenges" hinder the adoption of signatures as compared to functionally well-characterized single gene biomarkers. To increase the utility of multi-gene signatures in survival studies, we developed a novel approach to generate "personal mechanism signatures" of molecular pathways and functions from gene expression arrays. FAIME, the Functional Analysis of Individual Microarray Expression, computes mechanism scores using rank-weighted gene expression of an individual sample. By comparing head and neck squamous cell carcinoma (HNSCC samples with non-tumor control tissues, the precision and recall of deregulated FAIME-derived mechanisms of pathways and molecular functions are comparable to those produced by conventional cohort-wide methods (e.g. GSEA. The overlap of "Oncogenic FAIME Features of HNSCC" (statistically significant and differentially regulated FAIME-derived genesets representing GO functions or KEGG pathways derived from HNSCC tissue among three distinct HNSCC datasets (pathways:46%, p<0.001 is more significant than the gene overlap (genes:4%. These Oncogenic FAIME Features of HNSCC can accurately discriminate tumors from control tissues in two additional HNSCC datasets (n = 35 and 91, F-accuracy = 100% and 97%, empirical p<0.001, area under the receiver operating characteristic curves = 99% and 92%, and stratify recurrence-free survival in patients from two independent studies (p = 0.0018 and p = 0.032, log-rank. Previous approaches depending on group assignment of individual samples before selecting features or learning a classifier are limited by design to

  18. Identification of beer bitter acids regulating mechanisms of gastric acid secretion. (United States)

    Walker, Jessica; Hell, Johannes; Liszt, Kathrin I; Dresel, Michael; Pignitter, Marc; Hofmann, Thomas; Somoza, Veronika


    Beer, one of the most consumed beverages worldwide, has been shown to stimulate gastric acid secretion. Although organic acids, formed by fermentation of glucose, are known to be stimulants of gastric acid secretion, very little is known about the effects of different types of beer or the active constituents thereof. In the present study, we compared the effects of different beers on mechanisms of gastric acid secretion. To investigate compound-specific effects on mechanisms of gastric acid secretion, organic acids and bitter compounds were quantified by HPLC-DAD and UPLC-MS/MS and tested in human gastric cancer cells (HGT-1) by means of a pH-sensitive fluorescent dye which determines the intracellular pH as an indicator of proton secretion. The expression of relevant genes, coding the H(+)/K(+)-ATPase, ATP4A, the histamine receptor, HRH2, the acetylcholine receptor, CHRM3, and the somatostatin receptor, SSTR2, was determined by qPCR. Ethanol and the organic acids succinic acid, malic acid, and citric acid were demonstrated to contribute to some extent to the effect of beer. The bitter acids comprising α-, β-, and iso-α-acids were identified as potential key components promoting gastric acid secretion and up-regulation of CHRM3 gene expression by a maximum factor of 2.01 compared to that of untreated control cells with a correlation to their respective bitterness.

  19. Queen survival and oxalic acid residues in sugar stores after summer application against Varroa destructor in honey bees (Apis mellifera)

    NARCIS (Netherlands)

    Cornelissen, B.; Donders, J.N.L.C.; Stratum, van P.; Blacquière, T.; Dooremalen, van C.


    Methods using oxalic acid (OA) to control Varroa destructor in honey bee (Apis mellifera) colonies are widely applied. In this study, the effects of an OA spray application in early summer on the survival of young and old queens, and on OA residues in sugar stores were investigated. A questionnaire

  20. Survival and SOS response induction in ultraviolet B irradiated Escherichia coli cells with defective repair mechanisms. (United States)

    Prada Medina, Cesar Augusto; Aristizabal Tessmer, Elke Tatjana; Quintero Ruiz, Nathalia; Serment-Guerrero, Jorge; Fuentes, Jorge Luis


    Purpose In this paper, the contribution of different genes involved in DNA repair for both survival and SOS induction in Escherichia coli mutants exposed to ultraviolet B radiation (UVB, [wavelength range 280-315 nm]) was evaluated. Materials and methods E. coli strains defective in uvrA, oxyR, recO, recN, recJ, exoX, recB, recD or xonA genes were used to determine cell survival. All strains also had the genetic sulA::lacZ fusion, which allowed for the quantification of SOS induction through the SOS Chromotest. Results Five gene products were particularly important for survival, as follows: UvrA > RecB > RecO > RecJ > XonA. Strains defective in uvrA and recJ genes showed elevated SOS induction compared with the wild type, which remained stable for up to 240 min after UVB-irradiation. In addition, E. coli strains carrying the recO or recN mutation showed no SOS induction. Conclusions The nucleotide excision and DNA recombination pathways were equally used to repair UVB-induced DNA damage in E. coli cells. The sulA gene was not turned off in strains defective in UvrA and RecJ. RecO protein was essential for processing DNA damage prior to SOS induction. In this study, the roles of DNA repair proteins and their contributions to the mechanisms that induce SOS genes in E. coli are proposed.

  1. Survival and acid resistance of Listeria innocua in Feta cheese and yogurt, in the presence or absence of fungi. (United States)

    Belessi, Charalambia-Irini A; Papanikolaou, Seraphim; Drosinos, Eleftherios H; Skandamis, Panagiotis N


    The objective of the study was to assess the survival of Listeria innocua, alone or coinoculated with fungal isolates, during storage of Feta cheese (pH 4.43 to 4.56) and yogurt (pH 4.01 to 4.27) at 3 to 15 degrees C. The acid resistance of the bacterium during subsequent exposure to pH 2.5 for 3 h was also evaluated in samples stored at 3 and 10 degrees C. In Feta cheese, L. innocua survived better than it did in yogurt at all temperatures. At 5, 10, and 15 degrees C, the pH of cheese increased due to fungal growth, and this enhanced the survival of L. innocua more than during storage at 3 degrees C. Moreover, during storage of Feta cheese, L. innocua was capable of surviving the subsequent exposure for 3 h in broth of pH 2.5, in contrast to cultures not inoculated in the product (control cultures; 24 h at 30 degrees C in broth). In yogurt, L. innocua reduced more than 5 log within 15 days of storage at 5, 10, and 15 degrees C, whereas extended survival was observed at 3 degrees C until day 22, with total reduction of approximately 4.5 log. In contrast to what was observed in Feta cheese, surviving populations of L. innocua in yogurt were eliminated after subsequent exposure for 3 h to pH 2.5. The findings indicate that growth of fungi on the surface of Feta cheese and yogurt may compromise the safety of these products by enhancing survival of the bacterium. Particularly, when fungi increase the pH of Feta cheese, L. innocua demonstrates better survival and prolonged storage may raise concerns for the development of acid-resistant Listeria populations.

  2. Mechanism of arylboronic acid-catalyzed amidation reaction between carboxylic acids and amines. (United States)

    Wang, Chen; Yu, Hai-Zhu; Fu, Yao; Guo, Qing-Xiang


    Arylboronic acids were found to be efficient catalysts for the amidation reactions between carboxylic acids and amines. Theoretical calculations have been carried out to investigate the mechanism of this catalytic process. It is found that the formation of the acyloxyboronic acid intermediates from the carboxylic acid and the arylboronic acid is kinetically facile but thermodynamically unfavorable. Removal of water (as experimentally accomplished by using molecular sieves) is therefore essential for overall transformation. Subsequently C-N bond formation between the acyloxyboronic acid intermediates and the amine occurs readily to generate the desired amide product. The cleavage of the C-O bond of the tetracoordinate acyl boronate intermediates is the rate-determining step in this process. Our analysis indicates that the mono(acyloxy)boronic acid is the key intermediate. The high catalytic activity of ortho-iodophenylboronic acid is attributed to the steric effect as well as the orbital interaction between the iodine atom and the boron atom.

  3. Inhibition mechanism of aspartic acid on crystal growth of hydroxyapatite

    Institute of Scientific and Technical Information of China (English)

    HUANG Su-ping; ZHOU Ke-chao; LI Zhi-you


    The effects of aspartic acid on the crystal growth, morphology of hydroxyapatite(HAP) crystal were investigated, and the inhibition mechanism of aspartic acid on the crystal growth of hydroxyapatite was studied. The results show that the crystal growth rate of HAP decreases with the increase of the aspartic acid concentration, and the HAP crystal is thinner significantly compared with that without amino acid, which is mainly due to the (10(-)10) surface of HAP crystal being inhibited by the aspartic acids. The calculation analysis indicates that the crystal growth mechanism of HAP, following surface diffusion controlled mechanism, is not changed due to the presence of aspartic acid. AFM result shows that the front of terrace on vicinal growth hillocks is pinned, which suggests that the aspartic acid is adsorbed onto the (10(-)10) surface of HAP and interacts with the Ca2+ ions of HAP surface, so as to block the growth active sites and result in retarding of the growth of HAP crystal.

  4. Selective stimulation of excitatory amino acid receptor subtypes and the survival of cerebellar granule cells in culture: effect of kainic acid

    DEFF Research Database (Denmark)

    Balázs, R; Hack, N; Jørgensen, Ole Steen


    Our previous studies showed that the survival of cerebellar granule cells in culture is promoted by treatment with N-methyl-D-aspartate. Here we report on the influence of another glutamate analogue, kainic acid, which, in contrast to N-methyl-D-aspartate, is believed to stimulate transmitter rec...

  5. Kinetic studies of Candida parapsilosis phagocytosis by macrophages and detection of intracellular survival mechanisms

    Directory of Open Access Journals (Sweden)

    Renata eToth


    Full Text Available Even though the number of Candida infections due to non-albicans species like C. parapsilosis has been increasing, little is known about their pathomechanisms. Certain aspects of C. parapsilosis and host interactions have already been investigated; however we lack information about the innate cellular responses towards this species. The aim of our project was to dissect and compare the phagocytosis of C. parapsilosis to C. albicans and to another Candida species C. glabrata by murine and human macrophages by live cell video microscopy. We broke down the phagocytic process into three stages: macrophage migration, engulfment of fungal cells and host cell killing after the uptake. Our results showed increased macrophage migration towards C. parapsilosis and we observed differences during the engulfment processes when comparing the three species. The engulfment time of C. parapsilosis was comparable to that of C. albicans regardless of the pseudohypha length and spatial orientation relative to phagocytes, while the rate of host cell killing and the overall uptake regarding C. parapsilosis showed similarities mainly with C. glabrata. Furthermore, we observed difference between human and murine phagocytes in the uptake of C. parapsilosis. UV-treatment of fungal cells had varied effects on phagocytosis dependent upon which Candida strain was used. Besides statistical analysis, live cell imaging videos showed that this species similarly to the other two also has the ability to survive in host cells via the following mechanisms: yeast replication, and pseudohypha growth inside of phagocytes, exocytosis of fungal cells and also abortion of host cell mitosis following the uptake. According to our knowledge this is the first study that provides a thorough examination of C. parapsilosis phagocytosis and reports intracellular survival mechanisms associated with this species.

  6. Promoting extracellular matrix remodeling via ascorbic acid enhances the survival of primary ovarian follicles encapsulated in alginate hydrogels. (United States)

    Tagler, David; Makanji, Yogeshwar; Tu, Tao; Bernabé, Beatriz Peñalver; Lee, Raymond; Zhu, Jie; Kniazeva, Ekaterina; Hornick, Jessica E; Woodruff, Teresa K; Shea, Lonnie D


    The in vitro growth of ovarian follicles is an emerging technology for fertility preservation. Various strategies support the culture of secondary and multilayer follicles from various species including mice, non-human primate, and human; however, the culture of early stage (primary and primordial) follicles, which are more abundant in the ovary and survive cryopreservation, has been limited. Hydrogel-encapsulating follicle culture systems that employed feeder cells, such as mouse embryonic fibroblasts (MEFs), stimulated the growth of primary follicles (70-80 µm); yet, survival was low and smaller follicles (ascorbic acid based on its role in extracellular matrix (ECM) deposition/remodeling for other applications. The selection of ascorbic acid was further supported by a microarray analysis that suggested a decrease in mRNA levels of enzymes within the ascorbate pathway between primordial, primary, and secondary follicles. The supplementation of ascorbic acid (50 µg/mL) significantly enhanced the survival of primary follicles (<80 µm) cultured in alginate hydrogels, which coincided with improved structural integrity. Follicles developed antral cavities and increased to diameters exceeding 250 µm. Consistent with improved structural integrity, the gene/protein expression of ECM and cell adhesion molecules was significantly changed. This research supports the notion that modifying the culture environment (medium components) can substantially enhance the survival and growth of early stage follicles.

  7. Effect of dietary arachidonic acid, eicosapentaenoic acid and docosahexaenoic acid on survival, growth and pigmentation in larvae of common sole ( Solea solea L.)

    DEFF Research Database (Denmark)

    Lund, Ivar; Steenfeldt, Svend Jørgen; Hansen, B.W.


    reflected dietary composition, neither standard growth nor larval survival were significantly related to the absolute concentrations of ARA, EPA and DHA or their ratios. This suggests low requirements for essential polyunsaturated fatty acids (PUFAs) in common sole. Malpigmentation was significantly related...... to increased dietary ARA content. However, pigmentation was not affected by inclusion levels of EPA or DHA when ARA was high. This, and no relation between DHA: EPA or ARA: EPA ratios and pigmentation and only a weak relation to ARA: DHA ratio, advocate for that it is the absolute concentration of ARA...... resulted in a lower growth rate, which suggests that visual aberrations affected prey capture. (C) 2007 Elsevier B.V. All rights reserved....

  8. Interaction of sulfuric acid corrosion and mechanical wear of iron (United States)

    Rengstorff, G. W. P.; Miyoshi, K.; Buckley, D. H.


    Friction and wear experiment were conducted with elemental iron sliding on aluminum oxide in aerated sulfuric acid at concentrations ranging from very dilute (0.00007 N; i.e., 4 ppm) to very concentrated (96 percent acid). Load and reciprocating sliding speed were kept constant. With the most dilute acid concentration of 0.00007 to 0.0002 N, a complex corrosion product formed that was friable and often increased friction and wear. At slightly higher concentrations of 0.001 N, metal losses were essentially by wear alone. Because no buildup of corrosion products occurred, this acid concentration became the standard from which to separate metal loss from direct corrosion and mechanical wear losses. When the acid concentration was increased to 5 percent (1 N), the well-established high corrosion rate of iron in sulfuric acid strongly dominated the total wear loss. This strong corrosion increased to 30 percent acid and decreased somewhat to 50 percent acid in accordance with expectations. However, the low corrosion of iron expected at acid concentrations of 65 to 96 percent was not observed in the wear area. It was apparent that the normal passivating film was being worn away and a galvanic cell established that rapidly attacked the wear area. Under the conditions where direct corrosion losses were highest, the coefficient of friction was the lowest.

  9. Specific Monoclonal Antibody Overcomes the Salmonella enterica Serovar Typhimurium's Adaptive Mechanisms of Intramacrophage Survival and Replication.

    Directory of Open Access Journals (Sweden)

    Swarmistha Devi Aribam

    Full Text Available Salmonella-specific antibodies play an important role in host immunity; however, the mechanisms of Salmonella clearance by pathogen-specific antibodies remain to be completely elucidated since previous studies on antibody-mediated protection have yielded inconsistent results. These inconsistencies are at least partially attributable to the use of polyclonal antibodies against Salmonella antigens. Here, we developed a new monoclonal antibody (mAb-449 and identified its related immunogen that protected BALB/c mice from infection with Salmonella enterica serovar Typhimurium. In addition, these data indicate that the mAb-449 immunogen is likely a major protective antigen. Using in vitro infection studies, we also analyzed the mechanism by which mAb-449 conferred host protection. Notably, macrophages infected with mAb-449-treated S. Typhimurium showed enhanced pathogen uptake compared to counterparts infected with control IgG-treated bacteria. Moreover, these macrophages produced elevated levels of pro-inflammatory cytokine TNFα and nitric oxide, indicating that mAb-449 enhanced macrophage activation. Finally, the number of intracellular bacteria in mAb-449-activated macrophages decreased considerably, while the opposite was found in IgG-treated controls. Based on these findings, we suggest that, although S. Typhimurium has the potential to survive and replicate within macrophages, host production of a specific antibody can effectively mediate macrophage activation for clearance of intracellular bacteria.

  10. Fatty Acid Synthase Polymorphisms, Tumor Expression, Body Mass Index, Prostate Cancer Risk, and Survival (United States)

    Nguyen, Paul L.; Ma, Jing; Chavarro, Jorge E.; Freedman, Matthew L.; Lis, Rosina; Fedele, Giuseppe; Fiore, Christopher; Qiu, Weiliang; Fiorentino, Michelangelo; Finn, Stephen; Penney, Kathryn L.; Eisenstein, Anna; Schumacher, Fredrick R.; Mucci, Lorelei A.; Stampfer, Meir J.; Giovannucci, Edward; Loda, Massimo


    Purpose Fatty acid synthase (FASN) regulates de novo lipogenesis, body weight, and tumor growth. We examined whether common germline single nucleotide polymorphisms (SNPs) in the FASN gene affect prostate cancer (PCa) risk or PCa-specific mortality and whether these effects vary by body mass index (BMI). Methods In a prospective nested case-control study of 1,331 white patients with PCa and 1,267 age-matched controls, we examined associations of five common SNPs within FASN (and 5 kb upstream/downstream, R2 > 0.8) with PCa incidence and, among patients, PCa-specific death and tested for an interaction with BMI. Survival analyses were repeated for tumor FASN expression (n = 909). Results Four of the five SNPs were associated with lethal PCa. SNP rs1127678 was significantly related to higher BMI and interacted with BMI for both PCa risk (Pinteraction = .004) and PCa mortality (Pinteraction = .056). Among overweight men (BMI ≥ 25 kg/m2), but not leaner men, the homozygous variant allele carried a relative risk of advanced PCa of 2.49 (95% CI, 1.00 to 6.23) compared with lean men with the wild type. Overweight patients carrying the variant allele had a 2.04 (95% CI, 1.31 to 3.17) times higher risk of PCa mortality. Similarly, overweight patients with elevated tumor FASN expression had a 2.73 (95% CI, 1.05 to 7.08) times higher risk of lethal PCa (Pinteraction = .02). Conclusion FASN germline polymorphisms were significantly associated with risk of lethal PCa. Significant interactions of BMI with FASN polymorphisms and FASN tumor expression suggest FASN as a potential link between obesity and poor PCa outcome and raise the possibility that FASN inhibition could reduce PCa-specific mortality, particularly in overweight men. PMID:20679621

  11. Valproic Acid Use During Radiation Therapy for Glioblastoma Associated With Improved Survival

    Energy Technology Data Exchange (ETDEWEB)

    Barker, Christopher A., E-mail: [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Bishop, Andrew J.; Chang, Maria; Beal, Kathryn; Chan, Timothy A. [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, New York (United States)


    Purpose: Valproic acid (VA) is an antiepileptic drug (AED) and histone deacetylase (HDAC) inhibitor taken by patients with glioblastoma (GB) to manage seizures, and it can modulate the biologic effects of radiation therapy (RT). We investigated whether VA use during RT for GB was associated with overall survival (OS). Methods and Materials: Medical records of 544 adults with GB were retrospectively reviewed. Analyses were performed to determine the association of Radiation Therapy Oncology Group recursive partitioning analysis (RTOG RPA) class, seizure history, and concurrent temozolomide (TMZ) and AED use during RT with OS. Results: Seizures before the end of RT were noted in 217 (40%) patients, and 403 (74%) were taking an AED during RT; 29 (7%) were taking VA. Median OS in patients taking VA was 16.9 months (vs 13.6 months taking another AED, P=.16). Among patients taking an AED during RT, OS was associated with VA (P=.047; hazard ratio [HR], 0.67; 95% confidence interval [CI], 0.27-1.07), and RTOG RPA class (P<.0001; HR, 1.49; 95% CI, 1.37-1.61). Of the 5 most common AEDs, only VA was associated with OS. Median OS of patients receiving VA and TMZ during RT was 23.9 months (vs 15.2 months for patients taking another AED, P=.26). When the analysis was restricted to patients who received concurrent TMZ, VA use was marginally associated with OS (P=.057; HR, 0.54; 95% CI, −0.09 to 1.17), independently of RTOG RPA class and seizure history. Conclusions: VA use during RT for GB was associated with improved OS, independently of RTOG RPA, seizure history, and concurrent TMZ use. Further studies of treatment that combines HDAC inhibitors and RT are warranted.

  12. VILIP-1 downregulation in non-small cell lung carcinomas: mechanisms and prediction of survival.

    Directory of Open Access Journals (Sweden)

    Jian Fu

    Full Text Available VILIP-1, a member of the neuronal Ca++ sensor protein family, acts as a tumor suppressor gene in an experimental animal model by inhibiting cell proliferation, adhesion and invasiveness of squamous cell carcinoma cells. Western Blot analysis of human tumor cells showed that VILIP-1 expression was undetectable in several types of human tumor cells, including 11 out of 12 non-small cell lung carcinoma (NSCLC cell lines. The down-regulation of VILIP-1 was due to loss of VILIP-1 mRNA transcripts. Rearrangements, large gene deletions or mutations were not found. Hypermethylation of the VILIP-1 promoter played an important role in gene silencing. In most VILIP-1-silent cells the VILIP-1 promoter was methylated. In vitro methylation of the VILIP-1 promoter reduced its activity in a promoter-reporter assay. Transcriptional activity of endogenous VILIP-1 promoter was recovered by treatment with 5'-aza-2'-deoxycytidine (5'-Aza-dC. Trichostatin A (TSA, a histone deacetylase inhibitor, potently induced VILIP-1 expression, indicating that histone deacetylation is an additional mechanism of VILIP-1 silencing. TSA increased histone H3 and H4 acetylation in the region of the VILIP-1 promoter. Furthermore, statistical analysis of expression and promoter methylation (n = 150 primary NSCLC samples showed a significant relationship between promoter methylation and protein expression downregulation as well as between survival and decreased or absent VILIP-1 expression in lung cancer tissues (p<0.0001. VILIP-1 expression is silenced by promoter hypermethylation and histone deacetylation in aggressive NSCLC cell lines and primary tumors and its clinical evaluation could have a role as a predictor of short-term survival in lung cancer patients.

  13. Applications of hydroxy acids: classification, mechanisms, and photoactivity

    Directory of Open Access Journals (Sweden)

    Andrija Kornhauser


    Full Text Available Andrija Kornhauser1, Sergio G Coelho2, Vincent J Hearing21US Food and Drug Administration [retired], Annandale, VA, USA; 2Laboratory of Cell Biology, National Cancer Institute, National Institutes of Health, Bethesda, MD, USAAbstract: Hydroxy acids (HAs represent a class of compounds which have been widely used in a number of cosmetic and therapeutic formulations in order to achieve a variety of beneficial effects for the skin. We review and discuss the most frequently used classes of these compounds, such as a-hydroxy acids, β-hydroxy acids, polyhydroxy acids, and bionic acids, and describe their applications as cosmetic and therapeutic agents. Special emphasis is devoted to the safety evaluation of these formulations, in particular on the effects of their prolonged use on sun-exposed skin. Furthermore, we summarize the very limited number of studies dealing with the modifications evoked by topical application of products containing HAs on photocarcinogenesis. In spite of the large number of reports on the cosmetic and clinical effects of HAs, their biological mechanism(s of action still require more clarification. Some of these mechanisms are discussed in this article along with important findings on the effect of HAs on melanogenesis and on tanning. We also emphasize the important contribution of cosmetic vehicles in these types of studies. Thus, HAs play an important role in cosmetic formulations, as well as in many dermatologic applications, such as in treating photoaging, acne, ichthyosis, rosacea, pigmentation disorders, and psoriasis.Keywords: hydroxy acids, glycolic acid, salicylic acid, UV, erythema, cosmetics

  14. Formation mechanism of coamorphous drug−amino acid mixtures

    DEFF Research Database (Denmark)

    Jensen, Katrine Birgitte Tarp; Larsen, Flemming Hofmann; Cornett, Claus


    Two coamorphous drug−amino acid systems, indomethacin−tryptophan (Ind−Trp) and furosemide−tryptophan Fur−Trp), were analyzed toward their ease of amorphization and mechanism of coamorphization during ball milling. The two mixtures were compared to the corresponding amorphization of the pure drug...

  15. Temperature dependence of poly(lactic acid) mechanical properties

    DEFF Research Database (Denmark)

    Zhou, Chengbo; Guo, Huilong; Li, Jingqing


    The mechanical properties of polymers are not only determined by their structures, but also related to the temperature field in which they are located. The yield behaviors, Young's modulus and structures of injection-molded poly(lactic acid) (PLA) samples after annealing at different temperatures...

  16. Drying of micro-encapsulated lactic acid bacteria — Effects of trehalose and immobilization on cell survival and release properties (United States)

    Li, Xiaoyan; Chen, Xiguang


    Lactic acid bacteria (LAB) were encapsulated with alginate, gelatin and trehalose additives by the extrusion method and dried at 4 °C. The microcapsules were generally spherical and had a wrinkled surface with a size of 1.7 mm ± 0.2 mm. Trehalose as a carbohydrate source in the culture medium could reduce acid production and performed no function in the positive proliferation of LAB. Using trehalose as a carbohydrate source and protective medium simultaneously had a benefit in the protection of LAB cells during the storage at 4 °C. The density of live LAB cells could be 107 CFU g-1 after 8 weeks of storage. Cells of LAB could be continuously released from the capsules from the acidic (pH 1.2) to neutral conditions (pH 6.8). The release amounts and proliferation speeds of LAB cells in neutral medium were much larger and faster than those in acidic conditions. Additionally, immobilization of LAB could improve the survival of cells when they were exposed to acidic medium (pH 1.2) with a survival rate of 76 %.

  17. Drying of Micro-Encapsulated Lactic Acid Bacteria-Effects of Trehalose and Immobilization on Cell Survival and Release Properties

    Institute of Scientific and Technical Information of China (English)

    LI Xiaoyan; CHEN Xiguang


    Lactic acid bacteria (LAB) were encapsulated with alginate, gelatin and trehalose additives by the extrusion method and dried at 4℃. The microcapsules were generally spherical and had a wrinkled surface with a size of 1.7mm±0.2mm. Trehalose as a carbohydrate source in the culture medium could reduce acid production and performed no function in the positive proliferation of LAB. Using trehalose as a carbohydrate source and protective medium simultaneously had a benefit in the protection of LAB cells during the storage at 4℃. The density of hve LAB cells could be 10- CFU g-1 after 8 weeks of storage. Cells of LAB could be con-tinuously released from the capsules from the acidic (pH 1.2) to neutral conditions (plt 6.8). The release amounts and proliferation speeds of LAB cells in neutral medium were much larger and faster than those m acidic conditions. Additionally, immobilization of LAB could improve the survival of cells when they, were exposed to acidic medium (pH 1.2) with a survival rate of 76 %.

  18. Plurality of anxiety and depression alteration mechanism by oleanolic acid. (United States)

    Fajemiroye, James O; Galdino, Pablinny M; Florentino, Iziara F; Da Rocha, Fabio F; Ghedini, Paulo C; Polepally, Prabhakar R; Zjawiony, Jordan K; Costa, Elson A


    Our study sought to evaluate the anxiolytic and antidepressant activities of oleanolic acid as well as the neural mechanisms involved. Animal models such as barbiturate sleep-induction, light-dark box, elevated plus maze, forced swimming test, tail suspension test and open field test were conducted. Male Albino Swiss mice were treated orally with vehicle 10 mL/kg, fluoxetine 20 mg/kg, imipramine 15 mg/kg, diazepam 1 mg/kg or oleanolic acid 5-40 mg/kg. Pretreatment (intraperitoneal) of animals with pentylenetetrazole (PTZ) 20 mg/kg, 1-(2-methoxyphenyl)-4-[4- (2-phthalimido) butyl]piperazine hydrobromide (NAN-190) 0.5 mg/kg, p-chlorophenylalanine methyl ester (PCPA) 100 mg/kg or α-methyl-p-tyrosine (AMPT) 100 mg/kg, WAY100635 (WAY) 0.3 mg/kg, prazosin (PRAZ) 1 mg/kg, yohimbine 2 mg/kg as well as monoamine oxidase assay and hippocampal brain-derived neurotrophic factor (BDNF) quantification were carried out. Oleanolic acid potentiated the hypnotic effect of barbiturate and demonstrated an anxiolytic effect in both the light-dark box and elevated plus maze. This effect was not reversed by PTZ. Acute and/or chronic oral treatment of mice with oleanolic acid (5-20 mg/kg) elicited an antidepressant effect in the forced swimming test and the tail suspension test without interfering with the locomotor activity. The antidepressant effect of oleanolic acid was attenuated by NAN-190, AMPT, PCPA, WAY and PRAZ. Although monoamine oxidase activity remained unaltered by oleanolic acid, chronic administration of oleanolic acid augmented hippocampal BDNF level. These findings demonstrate multiple mechanisms of the anxiolytic and antidepressant effect of oleanolic acid.

  19. The role and mechanism of fatty acids in gallstones

    Institute of Scientific and Technical Information of China (English)

    Shuo-Dong Wu; Kazuhisa Uchiyama; Ying Fan


    BACKGROUND: Cholelithiasis is a common entity in China, but its etiology and pathogenesis have not been fully elucidated. Pigment stones of the intrahepatic and extrahepatic bile duct still form a high proportion in China, while they are rare in Europeans. To date, reports on fatty acids in stones remain few. We analyzed the quantity of fatty acids in different stones from Chinese and Japanese cases and discussed the role and mechanism of fatty acids in the formation of pigment stones. METHODS: Clinical data from 18 Chinese and 37 Japanese patients with different types of stones were analyzed using the procedure for extracting fatty acids from gallstones and high performance liquid chromatography. RESULTS: The total fatty acid and free fatty acid contents of pigment stones were markedly higher than those in black or cholesterol stones. The ratio of free saturated to free unsaturated fatty acids was highest in intrahepatic and less in extrahepatic pigment stones, which were signiifcantly different from the other two kinds of stones. CONCLUSIONS: This indicates that phospholipase participates in the course of pigment stone formation. The action of phospholipase A1 is more important than phospholipase A2.

  20. Glycolic acid modulates the mechanical property and degradation of poly(glycerol, sebacate, glycolic acid). (United States)

    Sun, Zhi-Jie; Wu, Lan; Huang, Wei; Chen, Chang; Chen, Yan; Lu, Xi-Li; Zhang, Xiao-Lan; Yang, Bao-Feng; Dong, De-Li


    The development of biodegradable materials with controllable degradation properties is beneficial for a variety of applications. Poly(glycerol-sebacate) (PGS) is a promising candidate of biomaterials; so we synthesize a series of poly(glycerol, sebacate, glycolic acid) (PGSG) with 1:2:0, 1:2:0.2, 1:2:0.4, 1:2:0.6, 1:2:1 mole ratio of glycerol, sebacate, and glycolic acid to elucidate the relation of doped glycolic acid to the degradation rate and mechanical properties. The microstructures of the polymers with different doping of glycolic acid were dissimilar. PGSG with glycolic acid in the ratio of 0.2 displayed an integral degree of ordering, different to those with glycolic acid in the ratio of 0, 0.4, 0.6, and 1, which showed mild phase separation structure. The number, DeltaH(m), and temperature of the PGSG melting peaks tended to decrease with the increasing ratio of doped glycolic acid. In vitro and in vivo degradation tests showed that the degradation rate of PGSG with glycolic acid in the ratio of 0.2 was slowest, but in the ratio range of 0, 0.4, and 0.6, the degradation rate increased with the increase of glycolic acid. All PGSG samples displayed good tissue response and anticoagulant effects. Our data suggest that doping glycolic acid can modulate the microstructure and degree of crosslinking of PGS, thereby control the degradation rate of PGS.

  1. Metabolic mechanisms for anoxia tolerance and freezing survival in the intertidal gastropod, Littorina littorea. (United States)

    Storey, Kenneth B; Lant, Benjamin; Anozie, Obiajulu O; Storey, Janet M


    The gastropod mollusk, Littorina littorea L., is a common inhabitant of the intertidal zone along rocky coastlines of the north Atlantic. This species has well-developed anoxia tolerance and freeze tolerance and is extensively used as a model for exploring the biochemical adaptations that support these tolerances as well as for toxicological studies aimed at identifying effective biomarkers of aquatic pollution. This article highlights our current understanding of the molecular mechanisms involved in anaerobiosis and freezing survival of periwinkles, particularly with respect to anoxia-induced metabolic rate depression. Analysis of foot muscle and hepatopancreas metabolism includes anoxia-responsive changes in enzyme regulation, signal transduction, gene expression, post-transcriptional regulation of mRNA, control of translation, and cytoprotective strategies including chaperones and antioxidant defenses. New studies describe the regulation of glucose-6-phosphate dehydrogenase by reversible protein phosphorylation, the role of microRNAs in suppressing mRNA translation in the hypometabolic state, modulation of glutathione S-transferase isozyme patterns, and the regulation of the unfolded protein response.

  2. Autophagy as a Survival Mechanism for Squamous Cell Carcinoma Cells in Endonuclease G-Mediated Apoptosis (United States)

    Masui, Atsushi; Hamada, Masakazu; Kameyama, Hiroyasu; Wakabayashi, Ken; Takasu, Ayako; Imai, Tomoaki; Iwai, Soichi; Yura, Yoshiaki


    Safingol, L- threo-dihydrosphingosine, induces cell death in human oral squamous cell carcinoma (SCC) cells through an endonuclease G (endoG) -mediated pathway. We herein determined whether safingol induced apoptosis and autophagy in oral SCC cells. Safingol induced apoptotic cell death in oral SCC cells in a dose-dependent manner. In safingol-treated cells, microtubule-associated protein 1 light chain 3 (LC3)-I was changed to LC3-II and the cytoplasmic expression of LC3, amount of acidic vesicular organelles (AVOs) stained by acridine orange and autophagic vacuoles were increased, indicating the occurrence of autophagy. An inhibitor of autophagy, 3-methyladenine (3-MA), enhanced the suppressive effects of safingol on cell viability, and this was accompanied by an increase in the number of apoptotic cells and extent of nuclear fragmentation. The nuclear translocation of endoG was minimal at a low concentration of safingol, but markedly increased when combined with 3-MA. The suppressive effects of safingol and 3-MA on cell viability were reduced in endoG siRNA- transfected cells. The scavenging of reactive oxygen species (ROS) prevented cell death induced by the combinational treatment, whereas a pretreatment with a pan-caspase inhibitor z-VAD-fmk did not. These results indicated that safingol induced apoptosis and autophagy in SCC cells and that the suppression of autophagy by 3-MA enhanced apoptosis. Autophagy supports cell survival, but not cell death in the SCC cell system in which apoptosis occurs in an endoG-mediated manner. PMID:27658240

  3. Acid and low temperature treatments on Salmonella Enteritidis inoculated in pork and its subsequent survival in simulated gastric fluid

    Directory of Open Access Journals (Sweden)

    Simone Quintão Silva


    Full Text Available ABSTRACT: The objective of this study was to evaluate the acid resistance of Salmonella enterica serovar Enteritidis (S. Enteritidis in stored pork and in simulated gastric fluid (SGF. A culture of S. Enteritidis was subjected to acid treatment prior to inoculation into pork, stored under refrigeration at frozen temperatures and exposed to SGF. The S. Enteritidis CCS3 and ATCC 13076 strains previously subjected to acid treatment (at pH 4.0-5.0 were inoculated in pork and stored at 4°C and -18°C. Storage at 4ºC did not affect the populations of both S. Enteritidis strains. After 84 days at -18°C, the mean population of both CCS3 and ATCC strains were reduced by 0.8 and 1.5 log cycles, respectively. Prior acid treatment did not enhance the survival of both strains at low temperatures. After acid treatment and low temperature storage, S. Enteritidis ATCC 13076 lost culturability after being exposed to SGF for 10 minutes. In contrast, S. Enteritidis CCS3 was tolerant until three hours of SGF exposure. S. Enteritidis CCS3 submitted to pH 4.0 was more tolerant to SGF exposure than when submitted to pH 4.5, 5.0 and without acid treatment. Therefore, this study indicates that exposure to an acidic and cold environment during processing enhanced the ability of S. Enteritidis to survive in the gastric environment of the human stomach, possibly increasing the risk of a Salmonella infection after consumption of pork.

  4. Nodulation of cowpeas and survival of cowpeas Rhizobia in acid, aluminum-rich soils. [Vigna unguiculata; Rhizobium

    Energy Technology Data Exchange (ETDEWEB)

    Hartel, P.G.; Whelan, A.M.; Alexander, M.


    A study was undertaken to determine whether the reduced nodulation of cowpeas (Vigna unguiculata (L.) Walp) grown in certain acid, Alrich soils resulted from the poor survival of the potentially infective rhizobia. Two strains of Rhizobium capable of nodulating cowpeas were used. The lowest pH for growth in defined liquid medium was 4.2 for one strain and 3.9 for the other. Only the latter was Al tolerant and could grow in a defined liquid medium containing 50 KAl(SO/sub 4/)/sub 2/. The survival of the bacteria and their ability to nodulate cowpeas in three soils were measured after the soils were amended with Ca or Al salts to give pH values ranging from 5.7 to 4.1 and extractable-Al concentrations from < 0.1 to 3.7 cmol(p/sup +/)/kg of soil. Only small differences in survival in 7 or 8 weeks were noted between the two strains. Plants inoculated with the Al-sensitive strain bore significantly fewer nodules in the more acid, Al-rich soils than in the same soils with higher pH values and less extractable Al. No significant reduction in nodule number was evident for plants inoculated with the Al-tolerant strain and grown in the more acid, Al-rich soils compared to cowpeas grown in the same soils with higher pH values and less extractable Al. It is suggested that the Al content of soil is not a major factor in the survival of cowpea rhizobia but that it does have a significant effect on nodulation. 24 references, 3 figures, 2 tables.

  5. Molecular Simulation of Naphthenic Acid Removal on Acidic Catalyst (Ⅰ) Mechanism of Catalytic Decarboxylation

    Institute of Scientific and Technical Information of China (English)

    Fu Xiaoqin; Dai Zhenyu; Tian Songbai; Hou Suandi; Wang Xieqing


    In this paper, the charge distribution, the chemical bond order and the reactive performance of carboxylic acid model compounds on acidic catalyst were investigated by using molecular simulation technology. The simulation results showed that the bond order of C-O was higher than that of C-C,and C-C bond connected to the carbon atom in the carboxyl radical had the lowest bond order. The charge distributions of model naphthenic acids were similar in characteristics that the negative charges were concentrated on carboxyls. According to the simulation results, the mechanisms of catalytic decarboxylation over acidic solid catalyst were proposed, and a new route was put forward regarding removal of the naphthenic acid from crude oil through catalytic decarboxylation.

  6. Thermal tolerance and survival of Cronobacter sakazakii in powdered infant formula supplemented with vanillin, ethyl vanillin, and vanillic acid. (United States)

    Yemiş, Gökçe Polat; Pagotto, Franco; Bach, Susan; Delaquis, Pascal


    The thermal tolerance Cronobacter sakazakii was examined in sterile powdered infant formula (PIF) rehydrated at 58 °C in water or apple juice supplemented with vanillin, ethyl vanillin, or vanillic acid. All three compounds decreased thermal tolerance during-rehydration and the lowest decimal reduction time (D-value, 0.19 ± 0.01 min) was measured in PIF rehydrated in apple juice supplemented with 20 mM vanillic acid. At this level of supplementation no C. sakazakii were detected in PIF stored for 48 h at 10 and 24 h at 21 °C subsequent to a sublethal heat treatment. Thermal tolerance during rehydration and survival in reconstituted PIF were influenced by compound type, concentration, and temperature. Supplementation of PIF with vanillin, ethyl vanillin, or vanillic acid could enhance the safety of PIF or other dehydrated foods contaminated with C. sakazakii.

  7. Quinic Acid Could Be a Potential Rejuvenating Natural Compound by Improving Survival of Caenorhabditis elegans under Deleterious Conditions (United States)

    Zhang, Longze; Zhang, Junjing


    Abstract Quinic acid (QA) is an active ingredient of Cat's Claw (Uncaria tomentosa), which is found to be active in enhancing DNA repair and immunity in model systems and able to generate neuroprotective effects in neurons. However, QA's role in improving survival is not well studied. Here we report that QA can provide protection in Caenorhabidits elegans and improve worm survival under stress. Under heat stress and oxidative stress, QA-treated wild-type C. elegans N2 (N2) survived 17.8% and 29.7% longer, respectively, than the control worms. Our data suggest that under heat stress, QA can upregulate the expression of the small heat shock protein hsp-16.2 gene, which could help the worms survive a longer time. We also found that QA extended the C. elegans mutant VC475 [hsp-16.2 (gk249)] life span by 15.7% under normal culture conditions. However, under normal culture conditions, QA did not affect hsp-16.2 expression, but upregulated the expression of daf-16 and sod-3 in a DAF-16–dependent manner, and downregulated the level of reactive oxygen species (ROS), suggesting that under normal conditions QA acts in different pathways. As a natural product, QA demonstrates great potential as a rejuvenating compound. PMID:22950425

  8. Antiatherogenic effects of n-3 fatty acids - evidence and mechanisms

    Directory of Open Access Journals (Sweden)

    Antonella Zampolli


    Full Text Available N-3 (omega-3 (polyunsaturated fatty acids are thought to display a variety of beneficial effects for human health. Clues to the occurrence of cardiovascular protective effects have been, however, the spur for the first biomedical interest in these compounds, and are the best documented. Historically, the epidemiologic association between dietary consumption of n-3 fatty acids and cardiovascular protection was first suggested by Bang and Dyerberg, who identified the high consumption of fish, and therefore, of fish oil-derived n-3 fatty acids, as the likely explanation for the strikingly low rate of coronary heart disease events reported in the Inuit population. Since their initial reports, research has proceeded in parallel to provide further evidence for their cardioprotection and to understand underlying mechanisms. Decreased atherogenesis is currently thought to be a part of the cardiovascular protection by n-3 fatty acids. This article summarizes the evidence for such a claim and the mechanisms putatively involved. (Heart International 2006; 3-4: 141-54

  9. Mechanism of arachidonic acid action on syntaxin-Munc18. (United States)

    Connell, Emma; Darios, Frédéric; Broersen, Kerensa; Gatsby, Naomi; Peak-Chew, Sew-Yeu; Rickman, Colin; Davletov, Bazbek


    Syntaxin and Munc18 are, in tandem, essential for exocytosis in all eukaryotes. Recently, it was shown that Munc18 inhibition of neuronal syntaxin 1 can be overcome by arachidonic acid, indicating that this common second messenger acts to disrupt the syntaxin-Munc18 interaction. Here, we show that arachidonic acid can stimulate syntaxin 1 alone, indicating that it is syntaxin 1 that undergoes a structural change in the syntaxin 1-Munc18 complex. Arachidonic acid is incapable of dissociating Munc18 from syntaxin 1 and, crucially, Munc18 remains associated with syntaxin 1 after arachidonic-acid-induced syntaxin 1 binding to synaptosomal-associated protein 25 kDa (SNAP25). We also show that the same principle operates in the case of the ubiquitous syntaxin 3 isoform, highlighting the conserved nature of the mechanism of arachidonic acid action. Neuronal soluble N-ethyl maleimide sensitive factor attachment protein receptors (SNAREs) can be isolated from brain membranes in a complex with endogenous Munc18, consistent with a proposed function of Munc18 in vesicle docking and fusion.

  10. Decreased Polyunsaturated Fatty Acid Content Contributes to Increased Survival in Human Colon Cancer

    Directory of Open Access Journals (Sweden)

    Manuela Oraldi


    Full Text Available Among diet components, some fatty acids are known to affect several stages of colon carcinogenesis, whereas others are probably helpful in preventing tumors. In light of this, our aim was to determine the composition of fatty acids and the possible correlation with apoptosis in human colon carcinoma specimens at different Duke's stages and to evaluate the effect of enriching human colon cancer cell line with the possible reduced fatty acid(s. Specimens of carcinoma were compared with the corresponding non-neoplastic mucosa: a significant decrease of arachidonic acid, PPARα, Bad, and Bax and a significant increase of COX-2, Bcl-2, and pBad were found. The importance of arachidonic acid in apoptosis was demonstrated by enriching a Caco-2 cell line with this fatty acid. It induced apoptosis in a dose- and time-dependent manner via induction of PPARα that, in turn, decreased COX-2. In conclusion, the reduced content of arachidonic acid is likely related to carcinogenic process decreasing the susceptibility of cancer cells to apoptosis.

  11. Survival of Salmonella in home-style mayonnaise and acid solutions as affected by acidulant type and preservatives. (United States)

    Zhu, Junli; Li, Jianrong; Chen, Jinru


    Mayonnaise made from contaminated eggs has been linked to outbreaks of Salmonella infections. This study was undertaken to determine the fate of salmonellae in home-style mayonnaise and acid solutions with or without chemical preservatives. Egg yolks were inoculated with different levels of a three-serotype (Typhimurium, Heidelberg, and Enteritidis [untypeable phage type]) mixture of Salmonella or a three-phage-type (4, 8, and 13) mixture of Salmonella Enteritidis. The inoculated yolks were used to make mayonnaise with 2, 3, or 4 teaspoons of a commercial wine vinegar or lemon juice. The mayonnaise was sampled for salmonellae over a 15-day period at 4°C, and negative samples were tested further by a three-tube most-probable-number assay. The same Salmonella mixtures were respectively inoculated into six acid solutions including wine vinegar, lemon juice, and acetic or citric solutions with or without chemical preservatives. The Salmonella populations of the Salmonella Enteritidis mixture were more persistent than those of the other Salmonella mixture in mayonnaise. Both Salmonella mixtures survived longer in mayonnaise made with vinegar than with lemon juice during storage at 4°C. In the acid solutions, however, the populations of the two Salmonella mixtures were not significantly different. The numbers of the two Salmonella mixtures in acetic or citric acid solutions with the preservatives were significantly lower than those in vinegar, lemon juice, and the solutions without the preservatives. Results suggest that Salmonella in contaminated egg yolks could survive the mayonnaise-making process. The inhibition of Salmonella by vinegar and lemon juice is due to the hurdle effect of organic acids and chemical preservatives.

  12. Putrescine production via the ornithine decarboxylation pathway improves the acid stress survival of Lactobacillus brevis and is part of a horizontally transferred acid resistance locus. (United States)

    Romano, Andrea; Ladero, Victor; Alvarez, Miguel A; Lucas, Patrick M


    Decarboxylation pathways are widespread among lactic acid bacteria; their physiological role is related to acid resistance through the regulation of the intracellular pH and to the production of metabolic energy via the generation of a proton motive force and its conversion into ATP. These pathways include, among others, biogenic amine (BA) production pathways. BA accumulation in foodstuffs is a health risk; thus, the study of the factors involved in their production is of major concern. The analysis of several lactic acid bacterial strains isolated from different environments, including fermented foods and beverages, revealed that the genes encoding these pathways are clustered on the chromosome, which suggests that these genes are part of a genetic hotspot related to acid stress resistance. Further attention was devoted to the ornithine decarboxylase pathway, which affords putrescine from ornithine. Studies were performed on three lactic acid bacteria belonging to different species. The ODC pathway was always shown to be involved in cytosolic pH alkalinisation and acid shock survival, which were observed to occur with a concomitant increase in putrescine production.

  13. Vascular endothelial growth factor regulates osteoblast survival – evidence for an autocrine feedback mechanism

    Directory of Open Access Journals (Sweden)

    Street John


    Full Text Available Abstract Background Apoptosis of osteoblasts and osteoclasts regulates bone homeostasis. Skeletal injury in humans results in 'angiogenic' responses primarily mediated by vascular endothelial growth factor(VEGF, a protein essential for bone repair in animal models. Osteoblasts release VEGF in response to a number of stimuli and express receptors for VEGF in a differentiation dependent manner. This study investigates the putative role of VEGF in regulating the lifespan of primary human osteoblasts(PHOB in vitro. Methods PHOB were examined for VEGF receptors. Cultures were supplemented with VEGF(0–50 ng/mL, a neutralising antibody to VEGF, mAB VEGF(0.3 ug/mL and Placental Growth Factor (PlGF, an Flt-1 receptor-specific VEGF ligand(0–100 ng/mL to examine their effects on mineralised nodule assay, alkaline phosphatase assay and apoptosis.. The role of the VEGF specific antiapoptotic gene target BCl2 in apoptosis was determined. Results PHOB expressed functional VEGF receptors. VEGF 10 and 25 ng/mL increased nodule formation 2.3- and 3.16-fold and alkaline phosphatase release 2.6 and 4.1-fold respectively while 0.3 ug/mL of mAB VEGF resulted in approx 40% reductions in both. PlGF 50 ng/mL had greater effects on alkaline phosphatase release (103% increase than on nodule formation (57% increase. 10 ng/mL of VEGF inhibited spontaneous and pathological apoptosis by 83.6% and 71% respectively, while PlGF had no significant effect. Pretreatment with mAB VEGF, in the absence of exogenous VEGF resulted in a significant increase in apoptosis (14 vs 3%. VEGF 10 ng/mL increased BCl2 expression 4 fold while mAB VEGF decreased it by over 50%. Conclusion VEGF is a potent regulator of osteoblast life-span in vitro. This autocrine feedback regulates survival of these cells, mediated via a non flt-1 receptor mechanism and expression of BCl2 antiapoptotic gene.

  14. Molecular mechanisms of acid-base sensing by the kidney. (United States)

    Brown, Dennis; Wagner, Carsten A


    A major function of the kidney is to collaborate with the respiratory system to maintain systemic acid-base status within limits compatible with normal cell and organ function. It achieves this by regulating the excretion and recovery of bicarbonate (mainly in the proximal tubule) and the secretion of buffered protons (mainly in the distal tubule and collecting duct). How proximal tubular cells and distal professional proton transporting (intercalated) cells sense and respond to changes in pH, bicarbonate, and CO(2) status is a question that has intrigued many generations of renal physiologists. Over the past few years, however, some candidate molecular pH sensors have been identified, including acid/alkali-sensing receptors (GPR4, InsR-RR), kinases (Pyk2, ErbB1/2), pH-sensitive ion channels (ASICs, TASK, ROMK), and the bicarbonate-stimulated adenylyl cyclase (sAC). Some acid-sensing mechanisms in other tissues, such as CAII-PDK2L1 in taste buds, might also have similar roles to play in the kidney. Finally, the function of a variety of additional membrane channels and transporters is altered by pH variations both within and outside the cell, and the expression of several metabolic enzymes are altered by acid-base status in parts of the nephron. Thus, it is possible that a master pH sensor will never be identified. Rather, the kidney seems equipped with a battery of molecules that scan the epithelial cell environment to mount a coordinated physiologic response that maintains acid-base homeostasis. This review collates current knowledge on renal acid-base sensing in the context of a whole organ sensing and response process.

  15. Cardioprotective mechanism of omega-3 polyunsaturated fatty acids. (United States)

    Endo, Jin; Arita, Makoto


    Omega-3 polyunsaturated fatty acids (PUFAs), such as eicosapentaenoic acid and docosahexaenoic acid, are widely regarded as cardioprotective. Several large-scale, randomized clinical trials have shown that dietary intake of omega-3 PUFAs improves the prognosis of patients with symptomatic heart failure or recent myocardial infarction. Therefore, dietary consumption of omega-3 PUFA is recommended in international guidelines for the general population to prevent the occurrence of cardiovascular diseases (CVDs). However, the precise mechanisms underlying the cardioprotective effects of omega-3 PUFAs are not fully understood. Omega-3 PUFAs can be incorporated into the phospholipid bilayer of cell membranes and can affect membrane fluidity, lipid microdomain formation, and signaling across membranes. Omega-3 PUFAs also modulate the function of membrane ion channels, such as Na and L-type Ca channels, to prevent lethal arrhythmias. Moreover, omega-3 PUFAs also prevent the conversion of arachidonic acid into pro-inflammatory eicosanoids by serving as an alternative substrate for cyclooxygenase or lipoxygenase, resulting in the production of less potent products. In addition, a number of enzymatically oxygenated metabolites derived from omega-3 PUFAs were recently identified as anti-inflammatory mediators. These omega-3 metabolites may contribute to the beneficial effects against CVDs that are attributed to omega-3 PUFAs.

  16. Reactive oxygen species and autophagy associated apoptosis and limitation of clonogenic survival induced by zoledronic acid in salivary adenoid cystic carcinoma cell line SACC-83.

    Directory of Open Access Journals (Sweden)

    Xi-Yuan Ge

    Full Text Available Salivary adenoid cystic carcinoma is an epithelial tumor in the head and neck region. Despite its slow growth, patients with salivary adenoid cystic carcinoma exhibit poor long term survival because of a high rate of distant metastasis. Lung and bone are common distant metastasis sites. Zoledronic acid, a third generation bisphosphonate, has been used for tumor-induced osteolysis due to bone metastasis and has direct antitumor activity in several human neoplasms. Here, we observed that zoledronic acid inhibited salivary adenoid cystic carcinoma cell line SACC-83 xenograft tumor growth in nude mice. In vitro, zoledronic acid induced apoptosis and reduced clonogenic survival in SACC-83. Flow cytometry and western blotting indicated that the cell cycle was arrested at G0/G1. Zoledronic acid treatment upregulated reactive oxygen species as well as the autophagy marker protein LC-3B. Reactive oxygen species scavenger N-acetylcysteine and autophagy antagonist 3-methyladenine decreased zoledronic acid-induced apoptosis and increased clonogenic survival. Silencing of the autophagy related gene Beclin-1 also decreased zoledronic acid-induced apoptosis and inhibition of clonogenic formation. In addition, isobolographic analysis revealed synergistic effects on apoptosis when zoledronic acid and paclitaxel/cisplatin were combined. Taken together, our results suggest that zoledronic acid induced apoptosis and reduced clonogenic survival via upregulation of reactive oxygen species and autophagy in the SACC-83 cell line. Thus, zoledronic acid should be considered a promising drug for the treatment of salivary adenoid cystic carcinoma.

  17. Molecular mechanisms mediating contrasting flooding survival strategies in two Rumex species

    NARCIS (Netherlands)

    van Veen, H.


    Flooding is a major recurring event for many ecosystems and is important in shaping vegetation composition. It negatively affects plant survival because in water gas diffusion is approximately 10,000 times slower than in air. This has major repercussions for photosynthesis that requires carbon dioxi

  18. Aging mechanisms and service life of lead-acid batteries (United States)

    Ruetschi, Paul

    In lead-acid batteries, major aging processes, leading to gradual loss of performance, and eventually to the end of service life, are: Anodic corrosion (of grids, plate-lugs, straps or posts). Positive active mass degradation and loss of adherence to the grid (shedding, sludging). Irreversible formation of lead sulfate in the active mass (crystallization, sulfation). Short-circuits. Loss of water. Aging mechanisms are often inter-dependent. For example, corrosion of the grids will lead to increased resistance to current flow, which will in turn impede proper charge of certain parts of the active mass, resulting in sulfation. Active mass degradation may lead to short-circuits. Sulfation may be the result of a loss of water, and so forth. The rates of the different aging processes strongly depend on the type of use (or misuse) of the battery. Over-charge will lead to accelerated corrosion and also to accelerated loss of water. With increasing depth-of-discharge during cycling, positive active mass degradation is accelerated. Some aging mechanisms are occurring only upon misuse. Short-circuits across the separators, due to the formation of metallic lead dendrites, for example, are usually formed only after (excessively) deep discharge. Stationary batteries, operated under float-charge conditions, will age typically by corrosion of the positive grids. On the other hand, service life of batteries subject to cycling regimes, will typically age by degradation of the structure of the positive active mass. Starter batteries are usually aging by grid corrosion, for instance in normal passenger car use. However, starter batteries of city buses, making frequent stops, may age (prematurely) by positive active mass degradation, because the batteries are subject to numerous shallow discharge cycles. Valve-regulated batteries often fail as a result of negative active mass sulfation, or water loss. For each battery design, and type of use, there is usually a characteristic

  19. Potential mechanisms for low uric acid in Parkinson disease. (United States)

    Sampat, Radhika; Young, Sarah; Rosen, Ami; Bernhard, Douglas; Millington, David; Factor, Stewart; Jinnah, H A


    Several epidemiologic studies have described an association between low serum uric acid (UA) and Parkinson disease (PD). Uric acid is a known antioxidant, and one proposed mechanism of neurodegeneration in PD is oxidative damage of dopamine neurons. However, other complex metabolic pathways may contribute. The purpose of this study is to elucidate potential mechanisms of low serum UA in PD. Subjects who met diagnostic criteria for definite or probable PD (n = 20) and controls (n = 20) aged 55-80 years were recruited. Twenty-four hour urine samples were collected from all participants, and both uric acid and allantoin were measured and corrected for body mass index (BMI). Urinary metabolites were compared using a twoway ANOVA with diagnosis and sex as the explanatory variables. There were no significant differences between PD and controls for total UA (p = 0.60), UA corrected for BMI (p = 0.37), or in the interaction of diagnosis and sex on UA (p = 0.24). Similarly, there were no significant differences between PD and controls for allantoin (p = 0.47), allantoin corrected for BMI (p = 0.57), or in the interaction of diagnosis and sex on allantoin (p = 0.78). Allantoin/UA ratios also did not significantly differ by diagnosis (p = 0.99). Our results imply that low serum UA in PD may be due to an intrinsic mechanism that alters the homeostatic set point for serum UA in PD, and may contribute to relatively lower protection against oxidative damage. These findings provide indirect support for neuroprotection trials aimed at raising serum UA.

  20. Mechanisms and mediation in survival analysis: towards an integrated analytical framework

    Directory of Open Access Journals (Sweden)

    Jonathan Pratschke


    Full Text Available Abstract Background A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare. Methods The authors begin by summarising debates on causal inference, mediated effects and statistical models, showing that these three strands of research have powerful synergies. They review a range of approaches which seek to extend existing survival models to obtain valid estimates of mediation effects. They then argue for an alternative strategy, which involves integrating survival outcomes within Structural Equation Models via the discrete-time survival model. This approach can provide an integrated framework for studying mediation effects in relation to survival outcomes, an issue of great relevance in applied health research. The authors provide an example of how these techniques can be used to explore whether the social class position of patients has a significant indirect effect on the hazard of death from colon cancer. Results The results suggest that the indirect effects of social class on survival are substantial and negative (-0.23 overall. In addition to the substantial direct effect of this variable (-0.60, its indirect effects account for more than one quarter of the total effect. The two main pathways for this indirect effect, via emergency admission (-0.12, on the one hand, and hospital caseload, on the other, (-0.10 are of similar size. Conclusions The discrete-time survival model provides an attractive way of integrating time-to-event data within the field of

  1. Salmonella Enteritidis strains from poultry exhibit differential responses to acid stress, oxidative stress, and survival in the egg albumen. (United States)

    Shah, Devendra H; Casavant, Carol; Hawley, Quincy; Addwebi, Tarek; Call, Douglas R; Guard, Jean


    Salmonella Enteritidis is the major foodborne pathogen that is primarily transmitted by contaminated chicken meat and eggs. We recently demonstrated that Salmonella Enteritidis strains from poultry differ in their ability to invade human intestinal cells and cause disease in orally challenged mice. Here we hypothesized that the differential virulence of Salmonella Enteritidis strains is due to the differential fitness in the adverse environments that may be encountered during infection in the host. The responses of a panel of six Salmonella Enteritidis strains to acid stress, oxidative stress, survival in egg albumen, and the ability to cause infection in chickens were analyzed. This analysis allowed classification of strains into two categories, stress-sensitive and stress-resistant, with the former showing significantly (p<0.05) reduced survival in acidic (gastric phase of infection) and oxidative (intestinal and systemic phase of infection) stress. Stress-sensitive strains also showed impaired intestinal colonization and systemic dissemination in orally inoculated chickens and failed to survive/grow in egg albumen. Comparative genomic hybridization microarray analysis revealed no differences at the discriminatory level of the whole gene content between stress-sensitive and stress-resistant strains. However, sequencing of rpoS, a stress-regulatory gene, revealed that one of the three stress-sensitive strains carried an insertion mutation in the rpoS resulting in truncation of σ(S). Finding that one of the stress-sensitive strains carried an easily identifiable small polymorphism within a stress-response gene suggests that the other strains may also have small polymorphisms elsewhere in the genome, which likely impact regulation of stress or virulence associated genes in some manner.

  2. Kinetics and mechanism of the oxidation of some neutral and acidic -amino acids by tetrabutylammonium tribromide

    Indian Academy of Sciences (India)

    Raghvendra Shukla; Pradeep K Sharma; Kalyan K Banerji


    The oxidation of eleven amino acids by tetrabutylammonium tribromide (TBATB) in aqueous acetic acid results in the formation of the corresponding carbonyl compounds and ammonia. The reaction is first order with respect to TBATB. Michaelis-Menten type kinetics is observed with some of the amino acids while others exhibit second-order dependence. It failed to induce polymerization of acrylonitrile. The effect of solvent composition indicate that the rate of reaction increases with increase in the polarity of the medium. Addition of tetrabutylammonium chloride has no effect on the rate of oxidation. Addition of bromide ion causes decrease in the oxidation rate but only to a limiting value. The reaction is susceptible to both polar and steric effects of the substituents. A suitable mechanism has been proposed.

  3. Comparative Transcriptomics Reveals Discrete Survival Responses of S. aureus and S. epidermidis to Sapienic Acid (United States)

    Moran, Josephine C.; Alorabi, Jamal A.; Horsburgh, Malcolm J.


    Staphylococcal colonization of human skin is ubiquitous, with particular species more frequent at different body sites. Whereas Staphylococcus epidermidis can be isolated from the skin of every individual tested, Staphylococcus aureus is isolated from arginine deiminase, the oxygen-responsive NreABC nitrogen regulation system and the nitrate and nitrite reduction pathways. The role of S. aureus ACME and chromosomal arginine deiminase pathways in sapienic acid resistance was determined through mutational studies. We speculate that ammonia production could contribute to sapienic acid resistance in staphylococci. PMID:28179897

  4. Research progress on the anticarcinogenic actions and mechanisms of ellagic acid

    Institute of Scientific and Technical Information of China (English)

    Hong-Mei Zhang; Lei Zhao; Hao Li; Hao Xu; Wen-Wen Chen; Lin Tao


    Cancer is a leading cause of death worldwide. Cancer treatments by chemotherapeutic agents, surgery, and radiation have not been highly effective in reducing the incidence of cancers and increasing the survival rate of cancer patients. In recent years, plant-derived compounds have attracted considerable attention as alternative cancer remedies for enhancing cancer prevention and treatment because of their low toxicities, low costs, and low side effects. Ellagic acid (EA) is a natural phenolic constituent. Recentin vitro and in vivo experiments have revealed that EA elicits anticarcinogenic effects by inhibiting tumor cell proliferation, inducing apoptosis, breaking DNA binding to carcinogens, blocking virus infection, and disturbing inlfammation, angiogenesis, and drug-resistance processes required for tumor growth and metastasis. hTis review enumerates the anticarcinogenic actions and mechanisms of EA. It also discusses future directions on the applications of EA.

  5. Studies on the mechanism of long term survival of Taenia taeniaeformis in rats. (United States)

    Kwa, B H; Liew, F Y


    An attempt was made to determine if blocking antibody is involved in protecting cysticerci of Taenia taeniaeformis against a host immune response. Immunoflourescence microscopy confirmed that host antibody is presnet on the parasite surface within the capsule. To test if the larvae can still survive after such a coat of blocking antibody is removed, the larvae were trysinised and then implanted into recipients. The results indicate that blocking antibody could be involved in the survival of 1 year old established larvae. Untrypsinised larvae were normal 14 days after implantation into control or immunised rats. Trypsinised larvae implanted in control rats were alive but showed on intense cell adherence on their surface. On the other hand, trypsinised larvae implanted into immunised rats were dead and completely encapsulated. However, experiments with 1 month old larvae were inconclusive.

  6. Prebiotically plausible mechanisms increase compositional diversity of nucleic acid sequences. (United States)

    Derr, Julien; Manapat, Michael L; Rajamani, Sudha; Leu, Kevin; Xulvi-Brunet, Ramon; Joseph, Isaac; Nowak, Martin A; Chen, Irene A


    During the origin of life, the biological information of nucleic acid polymers must have increased to encode functional molecules (the RNA world). Ribozymes tend to be compositionally unbiased, as is the vast majority of possible sequence space. However, ribonucleotides vary greatly in synthetic yield, reactivity and degradation rate, and their non-enzymatic polymerization results in compositionally biased sequences. While natural selection could lead to complex sequences, molecules with some activity are required to begin this process. Was the emergence of compositionally diverse sequences a matter of chance, or could prebiotically plausible reactions counter chemical biases to increase the probability of finding a ribozyme? Our in silico simulations using a two-letter alphabet show that template-directed ligation and high concatenation rates counter compositional bias and shift the pool toward longer sequences, permitting greater exploration of sequence space and stable folding. We verified experimentally that unbiased DNA sequences are more efficient templates for ligation, thus increasing the compositional diversity of the pool. Our work suggests that prebiotically plausible chemical mechanisms of nucleic acid polymerization and ligation could predispose toward a diverse pool of longer, potentially structured molecules. Such mechanisms could have set the stage for the appearance of functional activity very early in the emergence of life.

  7. Mechanisms and mediation in survival analysis: towards an integrated analytical framework.

    LENUS (Irish Health Repository)

    Haase, Trutz


    A wide-ranging debate has taken place in recent years on mediation analysis and causal modelling, raising profound theoretical, philosophical and methodological questions. The authors build on the results of these discussions to work towards an integrated approach to the analysis of research questions that situate survival outcomes in relation to complex causal pathways with multiple mediators. The background to this contribution is the increasingly urgent need for policy-relevant research on the nature of inequalities in health and healthcare.

  8. Survivability and condensation of amino acids in simulated submarine hydrothermal environments


    Chandru, Balasanthiran Kuhan


    The discovery of hydrothermal systems in the late 70’s brought a new hypothesis to the origin of life. Previously, the Urey-Miller experiment had made waves in this new field, indicating that a reducing atmosphere could form amino acids from basic chemicals. The further discovery of hydrothermal systems with earth’s prebiotic conditions added another notion to the field. Since then, different kinds of simulation were conducted to test the hypothesis. Initially and autoclave was extensively us...

  9. Survival of gas phase amino acids and nucleobases in space radiation conditions


    Pilling, S.; Andrade, D. P. P.; de Castilho, R. B.; Cavasso-Filho, R L; Lago, A. F.; de Coutinho, L. H.; de Souza, G. G. B.; Boechat-Roberty, H. M.; de Brito, A. Naves


    We present experimental studies on the photoionization and photodissociation processes (photodestruction) of gaseous amino acids and nucleobases in interstellar and interplanetary radiation conditions analogs. The measurements have been undertaken at the Brazilian Synchrotron Light Laboratory (LNLS), employing vacuum ultraviolet (VUV) and soft X-ray photons. The experimental set up basically consists of a time-of-flight mass spectrometer kept under high vacuum conditions. Mass spectra were ob...

  10. 4-Hydroxy-3-Methoxybenzoic Acid Methyl Ester: A Curcumin Derivative Targets Akt/NFκB Cell Survival Signaling Pathway: Potential for Prostate Cancer Management

    Directory of Open Access Journals (Sweden)

    Addanki P. Kumar


    Full Text Available Transcription factor NFKB and the serine/threonine kinase Akt play critical roles in mammalian cell survival signaling and have been shown to be activated in various malignancies including prostate cancer (PCA. We have developed an analogue of curcumin called 4hydroxy-3-methoxybenzoic acid methyl ester (HMBME that targets the Akt/NFκB signaling pathway. Here, we demonstrate the ability of this novel compound to inhibit the proliferation of human and mouse PCA cells. HMBME-induced apoptosis in these cells was tested by using multiple biochemical approaches, in addition to morphological analysis. Overexpression of constitutively active Akt reversed the HMBME-induced growth inhibition and apoptosis, illustrating the direct role of Akt signaling in HMBME-mediated growth inhibition and apoptosis. Further, investigation of the molecular events associated with its action in LNCaP cells shows that: 1 HMBME reduces the level of activated form of Akt (phosphorylated Akt; and 2 inhibits the Akt kinase activity. Further, the transcriptional activity of NFκB, the DNA-binding activity of NFκB, and levels of p65 were all significantly reduced following treatment with HMBME. Overexpression of constitutively active Akt, but not the kinase dead mutant of Akt, activated the basal NFκB transcriptional activity. HMBME treatment had no influence on this constitutively active Aktaugmented NFκB transcriptional activity. These data indicate that HMBME-mediated inhibition of Akt kinase activity may have a potential in suppressing/decreasing the activity of major survival/antiapoptotic pathways. The potential use of HMBME as an agent that targets survival mechanisms in PCA cells is discussed.

  11. 15-lipoxygenase metabolites of docosahexaenoic acid inhibit prostate cancer cell proliferation and survival.

    Directory of Open Access Journals (Sweden)

    Joseph T O'Flaherty

    Full Text Available A 15-LOX, it is proposed, suppresses the growth of prostate cancer in part by converting arachidonic, eicosatrienoic, and/or eicosapentaenoic acids to n-6 hydroxy metabolites. These metabolites inhibit the proliferation of PC3, LNCaP, and DU145 prostate cancer cells but only at ≥1-10 µM. We show here that the 15-LOX metabolites of docosahexaenoic acid (DHA, 17-hydroperoxy-, 17-hydroxy-, 10,17-dihydroxy-, and 7,17-dihydroxy-DHA inhibit the proliferation of these cells at ≥0.001, 0.01, 1, and 1 µM, respectively. By comparison, the corresponding 15-hydroperoxy, 15-hydroxy, 8,15-dihydroxy, and 5,15-dihydroxy metabolites of arachidonic acid as well as DHA itself require ≥10-100 µM to do this. Like DHA, the DHA metabolites a induce PC3 cells to activate a peroxisome proliferator-activated receptor-γ (PPARγ reporter, express syndecan-1, and become apoptotic and b are blocked from slowing cell proliferation by pharmacological inhibition or knockdown of PPARγ or syndecan-1. The DHA metabolites thus slow prostate cancer cell proliferation by engaging the PPARγ/syndecan-1 pathway of apoptosis and thereby may contribute to the prostate cancer-suppressing effects of not only 15-LOX but also dietary DHA.

  12. Cell survival during complete nutrient deprivation depends on lipid droplet-fueled β-oxidation of fatty acids. (United States)

    Cabodevilla, Ainara G; Sánchez-Caballero, Laura; Nintou, Eleni; Boiadjieva, Violeta G; Picatoste, Fernando; Gubern, Albert; Claro, Enrique


    Cells exposed to stress of different origins synthesize triacylglycerols and generate lipid droplets (LD), but the physiological relevance of this response is uncertain. Using complete nutrient deprivation of cells in culture as a simple model of stress, we have addressed whether LD biogenesis has a protective role in cells committed to die. Complete nutrient deprivation induced the biogenesis of LD in human LN18 glioblastoma and HeLa cells and also in CHO and rat primary astrocytes. In all cell types, death was associated with LD depletion and was accelerated by blocking LD biogenesis after pharmacological inhibition of Group IVA phospholipase A2 (cPLA2α) or down-regulation of ceramide kinase. Nutrient deprivation also induced β-oxidation of fatty acids that was sensitive to cPLA2α inhibition, and cell survival in these conditions became strictly dependent on fatty acid catabolism. These results show that, during nutrient deprivation, cell viability is sustained by β-oxidation of fatty acids that requires biogenesis and mobilization of LD.

  13. Molecular Mechanism of Isocupressic Acid Supresses MA-10 Cell Steroidogenesis

    Directory of Open Access Journals (Sweden)

    Kuan-Hao Tsui


    Full Text Available Consumption of ponderosa pine needles causes late-term abortions in cattle and is a serious poisonous plant problem in foothill and mountain rangelands. Isocupressic acid (IA is the component of pine needles responsible for the abortifacient effect, its abortifacient effect may be due to inhibition of steroidogenesis. To investigate the more detail molecular mechanism, we used MA-10 cell, which is wild used to investigate molecular mechanism of steroidogenesis, to characterize the molecular mechanisms underlying the actions of IA in more detail. In this report, we focus on the function of IA on important steroidogenic genes, including steroidogenic acute regulatory protein (StAR, cytochrome P450 cholesterol side-chain cleavage (P450scc, and 3β-hydroxysteroid dehydrogenase (3β-HSD. We found that IA does not affect enzyme activities of these genes but inhibits transcription of P450scc and translation of StAR and P450scc through attenuating cAMP-PKA signaling. Thus, steroid productions of cells were suppressed.

  14. Influence of sub-lethal stresses on the survival of lactic acid bacteria after spray-drying in orange juice. (United States)

    Barbosa, J; Borges, S; Teixeira, P


    The demand for new functional non-dairy based products makes the production of a probiotic orange juice powder an encouraging challenge. However, during drying process and storage, loss of viability of the dried probiotic cultures can occur, since the cells are exposed to various stresses. The influence of sub-lethal conditions of temperature, acidic pH and hydrogen peroxide on the viability of Pediococcus acidilactici HA-6111-2 and Lactobacillus plantarum 299v during spray drying in orange juice and subsequent storage under different conditions was investigated. At the end of storage, the survival of both microorganisms through simulated gastro-intestinal tract (GIT) conditions was also determined. The viability of cells previously exposed to each stress was not affected by the drying process. However, during 180 days of storage at room temperature, unlike P. acidilactici HA-6111-2, survival of L. plantarum 299v was enhanced by prior exposure to sub-lethal conditions. Previous exposure to sub-lethal stresses of each microorganism did not improve their viability after passage through simulated GIT. Nevertheless, as cellular inactivation during 180 days of storage was low, both microorganisms were present in numbers of ca. 10(7) cfu/mL at the end of GIT. This is an indication that both bacteria are good candidates for use in the development of an orange juice powder with functional characteristics.

  15. Degradation mechanism and stability of 5-aminolevulinic acid. (United States)

    Bunke, A; Zerbe, O; Schmid, H; Burmeister, G; Merkle, H P; Gander, B


    The physiological substance and precursor of the heme synthesis 5-aminolevulinic acid (ALA) is a promising prodrug for photodiagnosis and photodynamic therapy of epithelial tumors, particularly in urological and gynecological tissues. For the clinical use of this substance, a chemically stable and sterile drug formulation is required. In the present study, degradation mechanism of ALA in aqueous solution and possibilities to improve its stability were examined. A capillary electrophoretic method was developed that was suitable for the quantification of ALA and of two degradation products. The intermediate degradation product was 2, 5-dicarboxyethyl-3,6-dihydropyrazine, which was further oxidized to 2,5-dicarboxyethylpyrazine. The structures of the degradation products were proven by (1)H and (13)C nuclear magnetic resonance spectroscopy. ALA degradation was very efficiently inhibited by adjusting the pH of the aqueous solution to a value market introduction.

  16. Deciphering Molecular Mechanism Underlying Hypolipidemic Activity of Echinocystic Acid

    Directory of Open Access Journals (Sweden)

    Li Han


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

  17. Development, survival and reproduction of Podisus nigrispinus (Dallas, 1851 (Heteroptera: Pentatomidae with salt and amino acids solutions supplementary diet

    Directory of Open Access Journals (Sweden)

    Simone Patrícia Carneiro Freitas


    Full Text Available This study presents the effect of a supplementary diet with amino acids and sodium chloride solutions in addition to prey on the development, survival and reproduction of the predator Podisus nigrispinus (Heteroptera, Pentatomidae. Both solutions showed deleterious effects on nymph survival, adult weight, female longevity, number of egg masses, eggs per female, eggs per egg mass and nymphs per female besides egg viability of P. nigrispinus when compared with diet with water and prey. When compared with plant supplements in the diet the use of amino acids and salt solutions for mass rearing of P. nigrispinus was inferior.O presente estudo mostra o efeito da suplementação alimentar com soluções de aminoácidos e salina (NaCl no desenvolvimento, sobrevivência e reprodução de Podisus nigrispinus (Dallas (Heteroptera: Pentatomidae. Ambas soluções causaram efeito deletério na sobrevivência ninfal, peso dos adultos, longevidade das fêmeas e nos números de posturas, de ovos/fêmea, de ovos/postura e de ninfas, bem como na viabilidade dos ovos de P. nigrispinus quando comparado com estes insetos que além de presa receberam água. Estes resultados são discutidos em comparação com o efeito positivo que a suplementação alimentar com plantas tem sido relatada para esses predadores e sugerem que o uso de plantas é melhor que a substituição por solução de aminoácidos em sistemas de criação em laboratório desses predadores.

  18. Expression of lipases and lipid receptors in sperm storage tubules and possible role of fatty acids in sperm survival in the hen oviduct. (United States)

    Huang, A; Isobe, N; Obitsu, T; Yoshimura, Y


    The aim of this study was to determine the role of fatty acids for sperm survival in the sperm storage tubules (SSTs) of the hen oviduct. The mucosa tissues of uterovaginal junction (UVJ) of White Leghorn laying hens with or without artificial insemination using semen from Barred Plymouth Rock roosters were collected. The lipid density in the epithelium of UVJ and SST was analyzed by Sudan black B staining. The expressions of genes encoding lipid receptors and lipases were assayed by polymerase chain reaction in UVJ mucosa and SST cells isolated by laser microdissection. Fatty acid composition was analyzed by gas chromatography, and sperm were cultured with or without the identified predominant fatty acids for 24 hours to examine their effect on sperm viability. The lipid droplets were localized in the epithelium of UVJ mucosa and SSTs. The expression of genes encoding very low-density lipoprotein receptor(VLDLR), low-density lipoprotein receptor (LDLR), and fatty acid translocase (FAT/CD36) were found in SST cells. Expression of genes encoding endothelial lipase (EL), lipase H (LIPH), adipose triglyceride lipase (ATGL), and lipoprotein lipase (LPL) were found in UVJ. In contrast, only ATGL was found in SST cells, and its expression was significantly upregulated after artificial insemination. In UVJ mucosal tissues, five fatty acids, namely myristic acid (C14), palmitic acid (C16), stearic acid (C18), oleic acid (C18:1n9), and linoleic acid (C18:2n6), were identified as predominant fatty acids. The viability of sperm cultured with 1 mM oleic acid or linoleic acid was significantly higher than the sperm in the control culture without fatty acids. These results suggest that lipids in the SST cells may be degraded by ATGL, and fatty acids including oleic acid and linoleic acid may be released into the SST lumen to support sperm survival.

  19. Survival comparison of the ross procedure and mechanical valve replacement with optimal self-management anticoagulation therapy: Propensity-matched cohort study

    NARCIS (Netherlands)

    M.M. Mokhles (Mostafa); H. Körtke (Heinrich); U. Stierle (Ulrich); O. Wagner (Otto); E.I. Charitos (Efstratios); A.J.J.C. Bogers (Ad); J. Gummert (Jan Fritz); H. Sievers (Hans Hinrich); J.J.M. Takkenberg (Hanneke)


    textabstractBackground-: It is suggested that in young adults the Ross procedure results in better late patient survival compared with mechanical prosthesis implantation. We performed a propensity score-matched study that assessed late survival in young adult patients after a Ross procedure versus t

  20. Electrochemical mechanism of thioglycolic acid depressing sulphide minerals

    Institute of Scientific and Technical Information of China (English)


    The effects of thioglycolic acid (TGA) on the rest potential and zeta potential of sulphide minerals were studied and the electrochemical mechanism of TGA depressing sulphide minerals was put forward. Results of flotation test show that galena, pyrite and chalcopyrite can be well depressed by TGA, but sphalerite and arsenopyrite can not be depressed. Tests also show that TGA has a little influence on zeta potential of sulfide minerals covered by xanthate coatings and TGA can lower the rest potential of sulphide minerals. The electrochemical mechanism of TGA depressing sulphide minerals is that the dixanthogen adsorbing on the mineral surface will be unstable and reduced when rest potential value of sulphide mineral (φMS) is less than the reversible potential of reduction of dixanthogen to xanthate φX-|X2 in the presence of TGA, flotability of sulphide mineral becomes weak; inversely, the coatings of dixanthogen on mineral surface will keep stable when φMS>φX-|X2, sulphide mineral keeps flotability. In the system of mixed minerals, the electrochemical condition of separation of two sulphide minerals by TGA is φMS1<φX-|X2(φX-|PbX2)<φMS2.

  1. New mitochandrial mechanisms of asiatic acid against hepatotoxicity

    Institute of Scientific and Technical Information of China (English)

    JingGAO; Xin-huiTANG; JinCHEN


    AIM Terminalia Catappa L. is a combretaceous plant broadly distributed on tropical and subtropical areas. The leaves of this plant have been used as a folk medicine for treating hepatitis in Indian, the Philippines et al. Our previous studies showed that the extract of Terminalia Catappa L. leaves (TCCE) exerted antioxidative, anti - inflammatory and hepatoprotective activities, but the active substitutes and mechanisms remain unknown. The present research focused on investigating the antihepatotoxic activity and the new mitochondrial mechanisms of asiatic acid (AA), an important active component of TCCE,on acute liver injury. METHODS LPS+D-GaIN induced-hepatic injury models was adopted to study the antihepatotoxic role of AA. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were detected, and the morphological change was observed. At the same time, the level of mRNA and protein of voltage dependent anion channel (VDAC), the most important componentprotein of mitochondrial permeability transition pore (PTP) in insulted liver was analyzed using RT-PCR and Western blot. Furthermore,

  2. Effect of Gallic acid on mechanical and water barrier properties of zein-oleic acid composite films. (United States)

    Masamba, Kingsley; Li, Yue; Hategekimana, Joseph; Liu, Fei; Ma, Jianguo; Zhong, Fang


    In this study, the effect of gallic acid on mechanical and water barrier properties of zein-oleic acid 0-4 % composite films was investigated. Molecular weight distribution analysis was carried out to confirm gallic acid induced cross linking through change in molecular weight in fraction containing zein proteins. Results revealed that gallic acid treatment increased tensile strength from 17.9 MPa to 26.0 MPa, decreased water vapour permeability from 0.60 (g mm m(-2) h(-1) kPa(-1)) to 0.41 (g mm m(-2) h(-1) kPa(-1)), increased solubility from 6.3 % to 10.2 % and marginally increased elongation at break from 3.7 % to 4.2 % in zein films only. However, gallic acid treatment in zein-oleic composite films did not significantly influence mechanical and water barrier properties and in most instances irrespective of oleic acid concentration, the properties were negatively affected. Results from scanning electron microscopy showed that both gallic acid treated and untreated zein films and composite films containing 3 % oleic acid had a compact and homogeneous structure while those containing 4 % oleic acid had inhomogeneous structure. The findings have demonstrated that gallic acid treatment can significantly improve mechanical and water barrier properties especially in zein films only as opposed to when used in composite films using zein and oleic acid.

  3. Identification by random forest method of HLA class I amino acid substitutions associated with lower survival at day 100 in unrelated donor hematopoietic cell transplantation. (United States)

    Marino, S R; Lin, S; Maiers, M; Haagenson, M; Spellman, S; Klein, J P; Binkowski, T A; Lee, S J; van Besien, K


    The identification of important amino acid substitutions associated with low survival in hematopoietic cell transplantation (HCT) is hampered by the large number of observed substitutions compared with the small number of patients available for analysis. Random forest analysis is designed to address these limitations. We studied 2107 HCT recipients with good or intermediate risk hematological malignancies to identify HLA class I amino acid substitutions associated with reduced survival at day 100 post transplant. Random forest analysis and traditional univariate and multivariate analyses were used. Random forest analysis identified amino acid substitutions in 33 positions that were associated with reduced 100 day survival, including HLA-A 9, 43, 62, 63, 76, 77, 95, 97, 114, 116, 152, 156, 166 and 167; HLA-B 97, 109, 116 and 156; and HLA-C 6, 9, 11, 14, 21, 66, 77, 80, 95, 97, 99, 116, 156, 163 and 173. In all 13 had been previously reported by other investigators using classical biostatistical approaches. Using the same data set, traditional multivariate logistic regression identified only five amino acid substitutions associated with lower day 100 survival. Random forest analysis is a novel statistical methodology for analysis of HLA mismatching and outcome studies, capable of identifying important amino acid substitutions missed by other methods.

  4. Comparative Molecular Mechanics and Quantum Mechanics Study of Microhydration of Nucleic Acid Bases

    CERN Document Server

    Lino, J; Deriabina, A; Velasco, M; Poltev, V


    DNA is the most important biological molecule, and its hydration contributes essentially to the structure and functions of the double helix. We analyze the microhydration of the individual bases of nucleic acids and their methyl derivatives using methods of molecular mechanics (MM) with the Poltev-Malenkov (PM), AMBER and OPLS force fields, as well as ab initio Quantum Mechanics (QM) calculations at MP2/6-31G(d,p) level of theory. A comparison is made between the calculated interaction energies and the experimental enthalpies of microhydration of bases, obtained from mass spectrometry at low temperatures. Each local water-base interaction energy minimum obtained with MM corresponds to the minimum obtained with QM. General qualitative agreement was observed in the geometrical characteristics of the local minima obtained via the two groups of methods. MM minima correspond to slightly more coplanar structures than those obtained via QM methods, and the absolute MM energy values overestimate corresponding values ...

  5. Salvianolic acid B enhances in vitro angiogenesis and improves skin flap survival in Sprague-Dawley rats. (United States)

    Lay, Ing-Shiow; Hsieh, Cheng-Chu; Chiu, Jen-Hwey; Shiao, Ming-Shi; Lui, Wing-Yiu; Wu, Chew-Wun


    Insufficient angiogenesis and microcirculatory intravascular clotting have been implicated in the pathophysiology of skin flap failure. Salvianolic acid B (Sal B), isolated from Salvia miltiorrhiza, has been reported to enhance angiogenesis in vitro. This study was aimed to determine the efficacy of Sal B on ischemia-reperfusion injury of the skin flap in Sprague-Dawley rats. Sal B was administered intraperitoneally 2 h before operation, and on the 2nd and 4th days after surgical elevation of an extended epigastric adipocutaneous flap (5 x 7 cm) in ketamine-anesthetized rats. Flap ischemia was achieved by ligating the right superficial epigastric artery and vein and clamping the left superficial epigastric artery and vein for 3 h and then released. Percentage of flap necrosis area (FNA) and plasma levels of aspartate aminotransferase, alanine aminotransferase, creatinine, and malondialdehyde were measured at 7 days after the operation. Animals were divided into six groups, including: vehicle, Sal B low dose (5 mg/kg), Sal B high dose (50 mg/kg) and each with [mesh(+)] or without mesh [mesh(-)] placement. In the three groups with mesh(+), FNA in control flaps was 53.7 +/- 6.9%, whereas low-dose and high-dose Sal B significantly improved flap survival with FNA 27.4 +/- 3.8% and 25.3 +/- 4.3%, respectively (P mesh(-), control flaps were 35.9 +/- 4.5%, whereas high-dose Sal B also significantly improved flap survival with FNA 17.9 +/- 4.7% (P < 0.05, one-way ANOVA). There were no differences in aspartate aminotransferase, alanine aminotransferase, creatinine, or malondialdehyde between groups. We conclude that Sal B attenuates ischemia-reperfusion injury of skin flap, and provides therapeutic potential in reconstructive plastic surgery.

  6. Retinoic acid-loaded polymeric nanoparticles enhance vascular regulation of neural stem cell survival and differentiation after ischaemia (United States)

    Ferreira, R.; Fonseca, M. C.; Santos, T.; Sargento-Freitas, J.; Tjeng, R.; Paiva, F.; Castelo-Branco, M.; Ferreira, L. S.; Bernardino, L.


    Stroke is one of the leading causes of death and disability worldwide. However, current therapies only reach a small percentage of patients and may cause serious side effects. We propose the therapeutic use of retinoic acid-loaded nanoparticles (RA-NP) to safely and efficiently repair the ischaemic brain by creating a favourable pro-angiogenic environment that enhances neurogenesis and neuronal restitution. Our data showed that RA-NP enhanced endothelial cell proliferation and tubule network formation and protected against ischaemia-induced death. To evaluate the effect of RA-NP on vascular regulation of neural stem cell (NSC) survival and differentiation, endothelial cell-conditioned media (EC-CM) were collected. EC-CM from healthy RA-NP-treated cells reduced NSC death and promoted proliferation while EC-CM from ischaemic RA-NP-treated cells decreased cell death, increased proliferation and neuronal differentiation. In parallel, human endothelial progenitor cells (hEPC), which are part of the endogenous repair response to vascular injury, were collected from ischaemic stroke patients. hEPC treated with RA-NP had significantly higher proliferation, which further highlights the therapeutic potential of this formulation. To conclude, RA-NP protected endothelial cells from ischaemic death and stimulated the release of pro-survival, proliferation-stimulating factors and differentiation cues for NSC. RA-NP were shown to be up to 83-fold more efficient than free RA and to enhance hEPC proliferation. These data serve as a stepping stone to use RA-NP as vasculotrophic and neurogenic agents for vascular disorders and neurodegenerative diseases with compromised vasculature.

  7. Under Stress: Social Coping Mechanisms for Survival among the Working Professionals

    Directory of Open Access Journals (Sweden)

    Ms. Coral Barboza


    Full Text Available The nature of work of professionals and their family life may very often expose them to high level of stress which has the potential of affecting their productive and earning capacity. Coping strategies have been the subject of many studies and various suggestions have been made regarding the most appropriate way to categorise them in terms of function and efficacy (Amble, 2006; Buys et al., 2010. The goal of the current study was to examine how social coping mechanisms are helpful to employees in reducing stress and the stressful situations for their behavioural and emotional well-being. In achieving this goal, the researcher collected the data from the field through a structured questionnaire consisting of three phases- the demographic details, the stressors at workplace, social coping mechanisms adopted by them. Findings from the study show the existence of high level of stress among the working professionals. The sources of stress among the working professionals range from their nature of their work to work-family imbalance. In terms of coping strategies of stress, it was revealed that the respondents indulge in setting their goals, relaxing, exercising, diet, using sedatives and various others strategies suiting their needs. The need for appropriate mechanisms to be put in place by the managements of these organisations to address the stress needs of employees is essential to help reduce their stress levels

  8. Mechanism of microglia neuroprotection: Involvement of P2X7, TNFα, and valproic acid. (United States)

    Masuch, Annette; Shieh, Chu-Hsin; van Rooijen, Nico; van Calker, Dietrich; Biber, Knut


    Recently, we have demonstrated that ramified microglia are neuroprotective in N-methyl-D-aspartate (NMDA)-induced excitotoxicity in organotypic hippocampal slice cultures (OHSCs). The present study aimed to elucidate the underlying neuron-glia communication mechanism. It is shown here that pretreatment of OHSC with high concentrations of adenosine 5'-triphosphate (ATP) reduced NMDA-induced neuronal death only in presence of microglia. Specific agonists and antagonists identified the P2X7 receptor as neuroprotective receptor which was confirmed by absence of ATP-dependent neuroprotection in P2X7-deficient OHSC. Microglia replenished chimeric OHSC consisting of wild-type tissue replenished with P2X7-deficient microglia confirmed the involvement of microglial P2X7 receptor in neuroprotection. Stimulation of P2X7 in primary microglia induced tumor necrosis factor α (TNFα) release and blocking TNFα by a neutralizing antibody in OHSC abolished neuroprotection by ATP. OHSC from TNFα-deficient mice show increased exicitoxicity and activation of P2X7 did not rescue neuronal survival in the absence of TNFα. The neuroprotective effect of valproic acid (VPA) was strictly dependent on the presence of microglia and was mediated by upregulation of P2X7 in the cells. The present study demonstrates that microglia-mediated neuroprotection depends on ATP-activated purine receptor P2X7 and induction of TNFα release. This neuroprotective pathway was strengthened by VPA elucidating a novel mechanism for the neuroprotective function of VPA.

  9. Structural evidence for solvent-stabilisation by aspartic acid as a mechanism for halophilic protein stability in high salt concentrations. (United States)

    Lenton, Samuel; Walsh, Danielle L; Rhys, Natasha H; Soper, Alan K; Dougan, Lorna


    Halophilic organisms have adapted to survive in high salt environments, where mesophilic organisms would perish. One of the biggest challenges faced by halophilic proteins is the ability to maintain both the structure and function at molar concentrations of salt. A distinct adaptation of halophilic proteins, compared to mesophilic homologues, is the abundance of aspartic acid on the protein surface. Mutagenesis and crystallographic studies of halophilic proteins suggest an important role for solvent interactions with the surface aspartic acid residues. This interaction, between the regions of the acidic protein surface and the solvent, is thought to maintain a hydration layer around the protein at molar salt concentrations thereby allowing halophilic proteins to retain their functional state. Here we present neutron diffraction data of the monomeric zwitterionic form of aspartic acid solutions at physiological pH in 0.25 M and 2.5 M concentration of potassium chloride, to mimic mesophilic and halophilic-like environmental conditions. We have used isotopic substitution in combination with empirical potential structure refinement to extract atomic-scale information from the data. Our study provides structural insights that support the hypothesis that carboxyl groups on acidic residues bind water more tightly under high salt conditions, in support of the residue-ion interaction model of halophilic protein stabilisation. Furthermore our data show that in the presence of high salt the self-association between the zwitterionic form of aspartic acid molecules is reduced, suggesting a possible mechanism through which protein aggregation is prevented.

  10. Feeding ω-3 PUFA enriched rotifers to Galaxias maculatus (Jenyns, 1842 larvae reared at different salinity conditions: effects on growth parameters, survival and fatty acids profile

    Directory of Open Access Journals (Sweden)

    Patricio Dantagnan


    Full Text Available Despite the well known importance of ω-3 polyunsaturated fatty acids (PUFA in marine and freshwater fish larvae, there are few studies on how essential fatty acid requirements and composition on whole body can be altered by changes in water salinity. The present study aimed to determine the effect of salinity on ω-3 PUFA requirements, larval growth survival and fatty acid composition of Galaxias maculatus larvae cultured at two different salinities (0 and 15 g L-1 for 20 days while fed rotifers containing two different levels of ω-3 PUFA (1.87 and 3.16%. The results denoted a marked difference in ω-3 PUFA requirements and in the pattern of fatty acid deposition in the whole body of larvae reared at different salinities, depending of ω-3 PUFA in diets. Thus, to improve growth and survival larvae of G. maculatus reared at 0 g L-1 require higher levels of ω-3 PUFA, principally 18:3 ω-3. Larvae reared at salinities of 15 g L-1 require low levels of ω-3 PUFA for optimal survival, especially 18:3 ω-3. Eicosapentaenoic acid and docosahexaenoic acid content in the whole body of larvae was also affected by water salinity.

  11. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

    Energy Technology Data Exchange (ETDEWEB)

    Latham, Antony M.; Odell, Adam F. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Mughal, Nadeem A. [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Issitt, Theo; Ulyatt, Clare; Walker, John H. [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom); Homer-Vanniasinkam, Shervanthi [Leeds Vascular Institute, Leeds General Infirmary, Great George Street, Leeds LS1 3EX (United Kingdom); Ponnambalam, Sreenivasan, E-mail: [Endothelial Cell Biology Unit, School of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT (United Kingdom)


    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a high VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black

  12. Mechanisms of attenuation of abdominal sepsis induced acute lung injury by ascorbic acid. (United States)

    Fisher, Bernard J; Kraskauskas, Donatas; Martin, Erika J; Farkas, Daniela; Wegelin, Jacob A; Brophy, Donald; Ward, Kevin R; Voelkel, Norbert F; Fowler, Alpha A; Natarajan, Ramesh


    Bacterial infections of the lungs and abdomen are among the most common causes of sepsis. Abdominal peritonitis often results in acute lung injury (ALI). Recent reports demonstrate a potential benefit of parenteral vitamin C [ascorbic acid (AscA)] in the pathogenesis of sepsis. Therefore we examined the mechanisms of vitamin C supplementation in the setting of abdominal peritonitis-mediated ALI. We hypothesized that vitamin C supplementation would protect lungs by restoring alveolar epithelial barrier integrity and preventing sepsis-associated coagulopathy. Male C57BL/6 mice were intraperitoneally injected with a fecal stem solution to induce abdominal peritonitis (FIP) 30 min prior to receiving either AscA (200 mg/kg) or dehydroascorbic acid (200 mg/kg). Variables examined included survival, extent of ALI, pulmonary inflammatory markers (myeloperoxidase, chemokines), bronchoalveolar epithelial permeability, alveolar fluid clearance, epithelial ion channel, and pump expression (aquaporin 5, cystic fibrosis transmembrane conductance regulator, epithelial sodium channel, and Na(+)-K(+)-ATPase), tight junction protein expression (claudins, occludins, zona occludens), cytoskeletal rearrangements (F-actin polymerization), and coagulation parameters (thromboelastography, pro- and anticoagulants, fibrinolysis mediators) of septic blood. FIP-mediated ALI was characterized by compromised lung epithelial permeability, reduced alveolar fluid clearance, pulmonary inflammation and neutrophil sequestration, coagulation abnormalities, and increased mortality. Parenteral vitamin C infusion protected mice from the deleterious consequences of sepsis by multiple mechanisms, including attenuation of the proinflammatory response, enhancement of epithelial barrier function, increasing alveolar fluid clearance, and prevention of sepsis-associated coagulation abnormalities. Parenteral vitamin C may potentially have a role in the management of sepsis and ALI associated with sepsis.

  13. Genome-Wide Transposon Mutagenesis Indicates that Mycobacterium marinum Customizes Its Virulence Mechanisms for Survival and Replication in Different Hosts

    KAUST Repository

    Weerdenburg, Eveline M.


    The interaction of environmental bacteria with unicellular eukaryotes is generally considered a major driving force for the evolution of intracellular pathogens, allowing them to survive and replicate in phagocytic cells of vertebrate hosts. To test this hypothesis on a genome-wide level, we determined for the intracellular pathogen Mycobacterium marinum whether it uses conserved strategies to exploit host cells from both protozoan and vertebrate origin. Using transposon-directed insertion site sequencing (TraDIS), we determined differences in genetic requirements for survival and replication in phagocytic cells of organisms from different kingdoms. In line with the general hypothesis, we identified a number of general virulence mechanisms, including the type VII protein secretion system ESX-1, biosynthesis of polyketide lipids, and utilization of sterols. However, we were also able to show that M. marinum contains an even larger set of host-specific virulence determinants, including proteins involved in the modification of surface glycolipids and, surprisingly, the auxiliary proteins of the ESX-1 system. Several of these factors were in fact counterproductive in other hosts. Therefore, M. marinum contains different sets of virulence factors that are tailored for specific hosts. Our data imply that although amoebae could function as a training ground for intracellular pathogens, they do not fully prepare pathogens for crossing species barriers.

  14. Omega-3 fatty acids improve psychomotor performance via mechanism not related to nitric acid production

    Directory of Open Access Journals (Sweden)

    Marwan S. M. Al-Nimer


    Full Text Available Omega-3 fatty acids (ω-3FAs are essential polyunsaturated fats that protect the brain from cognitive impairment. It increases the activity of endothelial nitric oxide synthetase (eNOS and thereby increases the nitric acid (NO production. This study aimed to explore the effect of ω-3FAs on psychomotor performance and to relate this effect to the reactive nitrogen species. This study was conducted in Department of Pharmacology, College of Medicine, Al-Mustansiriya University in Baghdad, Iraq. Twenty healthy subjects, allocated randomly from medical college students, were participated in the single blind clinical trial. Participants were divided into two groups, each of ten subjects to receive either placebo or (ω-3FAs (750 mg single oral dose daily for 5 days. They were asked to perform psychomotor performance before and after 5 days of treatment, and venous blood was obtained for determination of serum nitric oxide (NO and peroxynitrite (ONOO. ω-3FAs treated group was significantly different from placebo-treated group in reducing choice and motor reaction times as well as the critical flicker frequency threshold. The serum levels of NO and ONOO in ω-3FAs-treated group did not significantly differ from placebo-treated group. Short term supplementation of ω-3FAs improves the psychomotor performance in young healthy subjects via a mechanism not related to the production of nitric oxide production. Inflorescence is a panicle few flowered and fruit is a capsule. The data of the results obtained were presented and discussed.

  15. Blood-brain barrier permeability and brain uptake mechanism of kainic acid and dihydrokainic acid. (United States)

    Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen H; Bunch, Lennart; Pickering, Darryl S


    The glutamatergic neurotransmitter system is involved in important neurophysiological processes and thus constitutes a promising target for the treatment of neurological diseases. The two ionotropic glutamate receptor agonists kainic acid (KA) and dihydrokainic acid (DHK) have been used as research tools in various in vivo central nervous system disease models in rodents, as well as being templates in the design of novel ligands affecting the glutamatergic system. Both molecules are highly polar but yet capable of crossing the blood-brain barrier (BBB). We used an in situ rat brain perfusion technique to determine the brain uptake mechanism and permeability across the BBB. To determine KA and DHK concentrations in the rat brain, simple and rapid sample preparation and liquid chromatography mass spectrometer methods were developed. According to our results the BBB permeability of KA and DHK is low, 0.25 × 10(-6) and 0.28 × 10(-6) cm/s for KA and DHK, respectively. In addition, the brain uptake is mediated by passive diffusion, and not by active transport. Furthermore, the non-specific plasma and brain protein binding of KA and DHK was determined to be low, which means that the unbound drug volume of distribution in brain is also low. Therefore, even though the total KA and DHK concentrations in the brain are low after systemic dosing, the concentrations in the vicinity of the glutamate receptors are sufficient for their activation and thus the observed efficacy.

  16. Quality attributes and microbial survival on whole cantaloupes with antimicrobial coatings containing chitosan, lauric arginate, cinnamon oil and ethylenediaminetetraacetic acid. (United States)

    Ma, Qiumin; Zhang, Yue; Critzer, Faith; Davidson, P Michael; Zhong, Qixin


    Cantaloupes are susceptible to microbiological contamination in pre- or postharvest environments. Novel intervention strategies, such as antimicrobial coatings, are needed to improve the microbiological safety of cantaloupes. The objective of this study was to prepare whole cantaloupes coated with mixtures containing chitosan, lauric arginate (LAE), cinnamon oil (CO), and ethylenediaminetetraacetic acid (EDTA) and determine survival characteristics of inoculated foodborne pathogens during storage as well as cantaloupe quality attributes. Chitosan coating with 0.1% LAE, 0.1% EDTA, and 1% CO was the most effective for inactivating foodborne pathogens inoculated on cantaloupes. This coating caused a >3logCFU/cm(2) reduction of Escherichia coli O157:H7 and Listeria monocytogenes immediately after coating and reduced Salmonella enterica to below the detection limit during a 14-day storage. Total molds and yeasts also were reduced to the detection limit by the coating. The redness and yellowness of uncoated cantaloupes were significantly higher than coated ones from day 6. The firmness of uncoated cantaloupes and those coated with chitosan only was significantly lower than other treatments from day 10. No significant differences were found in total soluble solids content or weight loss between coated and uncoated cantaloupes. Results showed the potential benefits of applying the coating mixtures to improve the quality and microbiological safety of cantaloupes.

  17. 高生存性乳酸菌的筛选%Screening of lactic acid bacteria strains with high survivability

    Institute of Scientific and Technical Information of China (English)

    朱宏; 陆淳; 冯丽莉; 卢晓丽; 王世杰


    There were 80 straim of bacterias isolated from traditional fermented milk in Inner Mongolia of China with anaerobic cultured in MRSA. Among 80 strains, 43 strains of Lactobacilli were proved with G+, H2O2 test with positive, using ribose, growing at 15 ℃ and 37 ℃.And 43 strains of Lactobacilli were assessed for for their survivability, 14 strains turned out to be acid resistance and bile salt tolerance. LAB spcies of 2 strains were identified and named Lactobacillus paracase N1115 and Lactobadllus plantarum.%对MRS培养基进行了厌氧培养,从内蒙古传统发酵乳制品中分离了80株菌,通过镜检、过氧化氢实验、发酵核糖、15℃和37℃发酵试验,获得了43株乳杆菌.结果表明,14株菌具有一定的耐酸和耐胆盐特性;其中2株鉴定为副干酪乳杆菌和植物乳杆菌,分别命名为Lactobacillus paracasei N1115和Lactobacillus plantarum N3114.


    Directory of Open Access Journals (Sweden)

    N. F. Puchinyan


    Full Text Available Aim. To evaluate risk of repeated atherothrombotic events in patients survived acute coronary syndrome (ACS and having poorly reduced platelet aggregation (proven by optical aggregometry in response to acetylsalicylic acid (ASA therapy.Material and methods. 200 patients with ACS (aged 56,6±9,2 y.o. were included in the study. Platelet functional activity during ASA therapy was evaluated with laser aggregometer. ASA resistance was defined if the summarizing index of platelet aggregation (induced with ADP, 5 mμml/l was 50% or higher during ASA therapy. Observation period was 18±6 months. Atherothrombotic events (unstable angina, myocardial infarction, stroke, cardiovascular death were considered.Results. Lack ASA response rate was about 12%. Totally 22 repeated atherothrombotic events were registered: 5,6% among ASA sensitive patients and 50% - among ASA resistant patients. Repeated atherothrombotic events were registered in ASA resistance patients during first 14 days. ASA sensitive patients showed repeated atherothrombotic events in some months after ACS. The relative risk of cardiovascular event in ASA resistance patients was 8,92 (CI 95% 4,39; 17,84 р=0,05.Conclusion. The high level of the induced platelet aggregation (proven by laser aggregometry points to high risk of repeated atherothrombotic events in patients with ACS.

  19. Naturally occurring and stress induced tubular structures from mammalian cells, a survival mechanism

    Directory of Open Access Journals (Sweden)

    He Jian


    Full Text Available Abstract Background Tubular shaped mammalian cells in response to dehydration have not been previously reported. This may be due to the invisibility of these cells in aqueous solution, and because sugars and salts added to the cell culture for manipulation of the osmotic conditions inhibit transformation of normal cells into tubular shaped structures. Results We report the transformation of normal spherical mammalian cells into tubular shaped structures in response to stress. We have termed these transformed structures 'straw cells' which we have associated with a variety of human tissue types, including fresh, post mortem and frozen lung, liver, skin, and heart. We have also documented the presence of straw cells in bovine brain and prostate tissues of mice. The number of straw cells in heart, lung tissues, and collapsed straw cells in urine increases with the age of the mammal. Straw cells were also reproduced in vitro from human cancer cells (THP1, CACO2, and MCF7 and mouse stem cells (D1 and adipose D1 by dehydrating cultured cells. The tubular center of the straw cells is much smaller than the original cell; houses condensed organelles and have filamentous extensions that are covered with microscopic hair-like structures and circular openings. When rehydrated, the filaments uptake water rapidly. The straw cell walls, have a range of 120 nm to 200 nm and are composed of sulfated-glucose polymers and glycosylated acidic proteins. The transformation from normal cell to straw cells takes 5 to 8 hr in open-air. This process is characterized by an increase in metabolic activity. When rehydrated, the straw cells regain their normal spherical shape and begin to divide in 10 to 15 days. Like various types of microbial spores, straw cells are resistant to harsh environmental conditions such as UV-C radiation. Conclusion Straw cells are specialized cellular structures and not artifacts from spontaneous polymerization, which are generated in response

  20. Effects of inhaled acid aerosols on lung mechanics: an analysis of human exposure studies. (United States)

    Utell, M J


    There exist significant gaps in our understanding of human health effects from inhalation of pollutants associated with acid precipitation. Controlled clinical studies examine effects of criteria pollutants almost exclusively by assessing changes in lung mechanics. One constituent of acid precipitation, sulfuric acid aerosols, has been shown to induce bronchoconstriction in exercising extrinsic asthmatics at near ambient levels. These asthmatics may be an order of magnitude more sensitive to sulfuric acid aerosols than normal adults. More recently, a second component nitrogen dioxide has been observed to provoke changes in lung mechanics at progressively lower concentrations. To date, virtually no data exist from clinical exposures to acidic aerosols for subjects with chronic obstructive pulmonary disease.

  1. Influence of redox conditions and mechanical action on change in peat humic acid composition



    Mechanical action on humic acids is shown to result in change of their composition accompanying decrease in aromaticity degree and increase in oxygen-containing fragments. Mechanical treatment of peat in oxidizing conditions increases the efficiency of extracting water-soluble components and humic acids to the maximum. Structural parameters and functional composition of humic acid molecules change at peat treatment in the redox conditions depending on the conditions.

  2. Molecular mechanism of recombinant liver fatty acid binding protein's antioxidant activity


    YAN, JING; Gong, Yuewen; She, Yi-Min; Wang, Guqi; Roberts, Michael S; Burczynski, Frank J.


    Hepatocytes expressing liver fatty acid binding protein (L-FABP) are known to be more resistant to oxidative stress than those devoid of this protein. The mechanism for the observed antioxidant activity is not known. We examined the antioxidant mechanism of a recombinant rat L-FABP in the presence of a hydrophilic (AAPH) or lipophilic (AMVN) free radical generator. Recombinant L-FABP amino acid sequence and its amino acid oxidative products following oxidation were identified by MALDI quadrup...

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

    Energy Technology Data Exchange (ETDEWEB)

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


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

  4. Long-term survival in elderly patients with a do-not-intubate order treated with noninvasive mechanical ventilation

    Directory of Open Access Journals (Sweden)

    Riario-Sforza GG


    Full Text Available Paolo Scarpazza1, Cristoforo Incorvaia2, Paolo Amboni3, Giuseppe di Franco1, Stefania Raschi1, Pierfranco Usai1, Monica Bernareggi1, Cristiano Bonacina1, Chiara Melacini1, Roberta Cattaneo1, Serena Bencini1, Chiara Pravettoni2, Gian Galeazzo Riario-Sforza2, Gianni Passalacqua4, Walter Casali11Divisione di Broncopneumotisiologia, Ospedale Civile, Vimercate, Italy; 2Pulmonary Rehabilitation, Istituti Clinici di Perfezionamento, Milan, Italy; 3Clinical Chemistry Laboratory, Ospedali Riuniti, Bergamo, Italy; 4Allergy and Respiratory Diseases, University Of Genoa, Genoa, ItalyBackground: Noninvasive mechanical ventilation (NIMV is an effective tool in treating patients with acute respiratory failure (ARF, since it reduces both the need for endotracheal intubation and the mortality in comparison with nonventilated patients. A particular issue is represented by the outcome of NIMV in patients referred to the emergency department for ARF and with a do-not-intubate (DNI status because of advanced age or excessively critical conditions. This study evaluated long-term survival in a group of elderly patients with acute hypercapnic ARF who had a DNI order and who were successfully treated by NIMV.Methods: The population consisted of 54 patients with a favorable outcome after NIMV for ARF. They were followed up for 3 years by regular control visits, with at least one visit every 4 months, or as needed according to the patient’s condition. Of these, 31 continued NIMV at home and 23 were on long-term oxygen therapy (LTOT alone.Results: A total of 16 of the 52 patients had not survived at the 1-year follow-up, and another eight patients died during the 3-year observation, with an overall mortality rate of 30.8% after 1 year and 46.2% after 3 years. Comparing patients who continued NIMV at home with those who were on LTOT alone, 9 of the 29 patients on home NIMV died (6 after 1 year and 3 after 3 years and 15 of the 23 patients on LTOT alone died (10 after 1

  5. Dietary fatty acids affecting hepatic metabolism and atherosclerosis - mechanisms unravelled using a proteomics approach

    Energy Technology Data Exchange (ETDEWEB)

    Rodriguez Gutierrez, G.; Roos, B. de


    Dietary fatty acids play an important role in the aetiology of coronary heart disease. The effects of dietary fatty acids on lipoprotein metabolism are well described, but additional or alternative mechanisms relating to potential influence on coronary heart disease are not known. This review describes how proteomics techniques have been used to identify proteins that are differentially regulated by dietary fatty acids. Such proteins may reveal pathways by which dietary fatty acids influence disease risk. (Author) 40 refs.

  6. Retinoic acid signaling controls the formation, proliferation and survival of the blastema during adult zebrafish fin regeneration. (United States)

    Blum, Nicola; Begemann, Gerrit


    Adult teleosts rebuild amputated fins through a proliferation-dependent process called epimorphic regeneration, in which a blastema of cycling progenitor cells replaces the lost fin tissue. The genetic networks that control formation of blastema cells from formerly quiescent stump tissue and subsequent blastema function are still poorly understood. Here, we investigated the cellular and molecular consequences of genetically interfering with retinoic acid (RA) signaling for the formation of the zebrafish blastema. We show that RA signaling is upregulated within the first few hours after fin amputation in the stump mesenchyme, where it controls Fgf, Wnt/β-catenin and Igf signaling. Genetic inhibition of the RA pathway at this stage blocks blastema formation by inhibiting cell cycle entry of stump cells and impairs the formation of the basal epidermal layer, a signaling center in the wound epidermis. In the established blastema, RA signaling remains active to ensure the survival of the highly proliferative blastemal population by controlling expression of the anti-apoptotic factor bcl2. In addition, RA signaling maintains blastema proliferation through the activation of growth-stimulatory signals mediated by Fgf and Wnt/β-catenin signaling, as well as by reducing signaling through the growth-inhibitory non-canonical Wnt pathway. The endogenous roles of RA in adult vertebrate appendage regeneration are uncovered here for the first time. They provide a mechanistic framework to understand previous observations in salamanders that link endogenous sources of RA to the regeneration process itself and support the hypothesis that the RA signaling pathway is an essential component of vertebrate tissue regeneration.

  7. Effect of Initial Population Density of Criconemella xenoplax on Reducing Sugars, Free Amino Acids, and Survival of Peach Seedlings over Time. (United States)

    Nyczepir, A P; Reilly, C C; Okie, W R


    Percentage of mortality, growth suppression, and changes in free amino acid and reducing sugar content in root and (or) stem tissue of Nemaguard peach seedlings were studied in the greenhouse in relation to time and eight different initial population densities (Pi) of Criconemella xenoplax. After 90 and 180 days, free amino acid content in root tissue significantly increased with increasing nematode numbers. Suppression of root volume, dry root and stem weight, height increase, plant survival, and content of reducing sugars in root tissue were detected at 180 and 270 days and following pruning. All criteria were negatively correlated with nematode Pi. Changes in growth, metabolic parameters, and survival percentage were attributed to Pi density of C. xenoplax, duration of the experiment, and nematode reproduction rate.

  8. Lysophosphatidic acid is a major serum noncytokine survival factor for murine macrophages which acts via the phosphatidylinositol 3-kinase signaling pathway.


    Koh, J. S.; Lieberthal, W; Heydrick, S; Levine, J. S.


    Lysophosphatidic acid (LPA) is the smallest and structurally simplest of all the glycerophospholipids. It occurs normally in serum and binds with high affinity to albumin, while retaining its biological activity. The effects of LPA are pleiotropic and range from mitogenesis to stress fiber formation. We show a novel role for LPA: as a macrophage survival factor with potency equivalent to serum. Administration of LPA protects macrophages from apoptosis induced by serum deprivation, and protect...

  9. Non-enzymatic depurination of nucleic acids: factors and mechanisms.

    Directory of Open Access Journals (Sweden)

    Ran An

    Full Text Available Depurination has attracted considerable attention since a long time for it is closely related to the damage and repair of nucleic acids. In the present study, depurination using a pool of 30-nt short DNA pieces with various sequences at diverse pH values was analyzed by High Performance Liquid Chromatography (HPLC. Kinetic analysis results showed that non-enzymatic depurination of oligodeoxynucleotides exhibited typical first-order kinetics, and its temperature dependence obeyed Arrhenius' law very well. Our results also clearly showed that the linear relationship between the logarithms of rate constants and pH values had a salient point around pH 2.5. Interestingly and unexpectedly, depurination depended greatly on the DNA sequences. The depurination of poly (dA was found to be extremely slow, and thymine rich sequences depurinated faster than other sequences. These results could be explained to some extent by the protonation of nucleotide bases. Moreover, two equations were obtained based on our data for predicting the rate of depurination under various conditions. These results provide basic data for gene mutagenesis and nucleic acids metabolism in acidic gastric juice and some acidic organelles, and may also help to rectify some misconceptions about depurination.

  10. CSF Amino Acids, Pterins and Mechanism of the Ketogenic Diet

    Directory of Open Access Journals (Sweden)

    J. Gordon Millichap


    Full Text Available Investigators from Hospital Sant Joan de Deu, Barcelona, Spain, studied the relationship between the etiology of refractory childhood epilepsy, CSF neurotransmitters, pterins, and amino acids, and response to a ketogenic diet in 60 patients with refractory epilepsy, 83% focal and 52% idiopathic.

  11. Cisplatin-induced apoptosis inhibits autophagy, which acts as a pro-survival mechanism in human melanoma cells.

    Directory of Open Access Journals (Sweden)

    Barbara Del Bello

    Full Text Available The interplay between a non-lethal autophagic response and apoptotic cell death is still a matter of debate in cancer cell biology. In the present study performed on human melanoma cells, we investigate the role of basal or stimulated autophagy in cisplatin-induced cytotoxicity, as well as the contribution of cisplatin-induced activation of caspases 3/7 and conventional calpains. The results show that, while down-regulating Beclin-1, Atg14 and LC3-II, cisplatin treatment inhibits the basal autophagic response, impairing a physiological pro-survival response. Consistently, exogenously stimulated autophagy, obtained with trehalose or calpains inhibitors (MDL-28170 and calpeptin, protects from cisplatin-induced apoptosis, and such a protection is reverted by inhibiting autophagy with 3-methyladenine or ATG5 silencing. In addition, during trehalose-stimulated autophagy, the cisplatin-induced activation of calpains is abrogated, suggesting the existence of a feedback loop between the autophagic process and calpains. On the whole, our results demonstrate that in human melanoma cells autophagy may function as a beneficial stress response, hindered by cisplatin-induced death mechanisms. In a therapeutic perspective, these findings suggest that the efficacy of cisplatin-based polychemotherapies for melanoma could be potentiated by inhibitors of autophagy.

  12. Surviving the crisis: Adaptive wisdom, coping mechanisms and local responses to avian influenza threats in Haining, China. (United States)

    Zhang, Letian; Pan, Tianshu


    Based on ethnographic research conducted in the summer of 2006, this paper examines local responses to the imminent threat of avian flu in Haining County of Zhejiang Province. During our field investigation, we conducted interviews with officials from local medical institutions (including the hospitals, the animal husbandry and veterinary station, and health clinics), to bureaus of public health and agro-economy. We also visited chicken farms, restaurants and farming households. We address the following factors that commonly structured the perceptions and actions of different social actors in the area of study: The changing mode of information-sharing and communication practices in the local communities; the official drive to professionalize the emergency response management system in the county; and the coping mechanisms that helped the villagers and town residents to weather the storm of avian flu. Our field research suggests that collective survival consciousness was translated into a spirit of voluntarism during the crisis. One important practical lesson we have learned from this study is that the adaptive wisdom embedded in local memories demonstrated its operational worth as a resourceful knowledge base for ordinary farmers to deal with food shortage, famine, plague and future pandemics.

  13. From nature to bedside: pro-survival and cell death mechanisms as therapeutic targets in cancer treatment. (United States)

    Cerella, Claudia; Teiten, Marie-Hélène; Radogna, Flavia; Dicato, Mario; Diederich, Marc


    Cell death is an important physiological regulator during development, tissue homeostasis and stress response but it is also a protective tumor suppressive mechanism. Tumor cells almost universally acquire the ability to evade cell death pathways that in normal cells act as a protective mechanism to remove damaged cells. As a result, a population of death-resistant cells with accumulating genetic and epigenetic abnormalities contributes to malignant transformation. Any alteration of the homeostatic balance between survival and death is therefore a critical factor in carcinogenesis. Several forms of cell death exist and cross talk among them is emerging; however, we still miss many molecular details. It becomes essential to revisit the role of each type of cell death to understand interconnections existing between different cell death pathways as well as the network of their mediators to eventually develop new effective strategies to kill cancer cells. More specifically, new therapies based on compounds selectively triggering apoptosis, necrosis or autophagy recently became both appealing and challenging. Despite the rather clear classification of the different cell death modalities according to morphological criteria and the attempt to describe them with distinct signaling pathways, the reality reveals a complex interplay between apoptosis, regulated necrosis and autophagy involving a heterogeneous mix of molecular mediators. Nature, presenting an almost endless plenitude of bioactive scaffolds, can efficiently contribute compounds that allow deciphering the intricate pathways of cell death pathways and thus eventually contribute to selectively target cancer-type specific pathways in an attempt to personalize cancer patient treatment depending on cancer death pathway specificities. The aim of this review is to provide first an overview of molecular cell death specificities and to highlight how compounds of natural origins, with or without hemisynthetic

  14. Lowering GTP level increases survival of amino acid starvation but slows growth rate for Bacillus subtilis cells lacking (p)ppGpp. (United States)

    Bittner, Alycia N; Kriel, Allison; Wang, Jue D


    Bacterial cells sense external nutrient availability to regulate macromolecular synthesis and consequently their growth. In the Gram-positive bacterium Bacillus subtilis, the starvation-inducible nucleotide (p)ppGpp negatively regulates GTP levels, both to resist nutritional stress and to maintain GTP homeostasis during growth. Here, we quantitatively investigated the relationship between GTP level, survival of amino acid starvation, and growth rate when GTP synthesis is uncoupled from its major homeostatic regulator, (p)ppGpp. We analyzed growth and nucleotide levels in cells that lack (p)ppGpp and found that their survival of treatment with a nonfunctional amino acid analog negatively correlates with both growth rate and GTP level. Manipulation of GTP levels modulates the exponential growth rate of these cells in a positive dose-dependent manner, such that increasing the GTP level increases growth rate. However, accumulation of GTP levels above a threshold inhibits growth, suggesting a toxic effect. Strikingly, adenine counteracts GTP stress by preventing GTP accumulation in cells lacking (p)ppGpp. Our results emphasize the importance of maintaining appropriate levels of GTP to maximize growth: cells can survive amino acid starvation by decreasing GTP level, which comes at a cost to growth, while (p)ppGpp enables rapid adjustment to nutritional stress by adjusting GTP level, thus maximizing fitness.

  15. Molecular mechanisms behind the antimicrobial activity of hop iso-α-acids in Lactobacillus brevis. (United States)

    Schurr, Benjamin C; Hahne, Hannes; Kuster, Bernhard; Behr, Jürgen; Vogel, Rudi F


    The main bittering component in beer, hop iso-α-acids, have been characterised as weak acids, which act as ionophores impairing microbial cells' function under acidic conditions as present in beer. Besides medium pH, divalent cations play a central role regarding the efficacy of the antimicrobial effect. The iso-α-acids' non-bitter derivatives humulinic acids can be found in isomerised hop extracts and can be generated during hop storage. Therefore, they have been under investigation concerning their influence on beer sensory properties. This study sketches the molecular mechanism behind iso-α-acids' antimicrobial activity in Lactobacillus (L.) brevis regarding their ionophore activity versus the dependence of the inhibitory potential on manganese binding, and suggests humulinic acids as novel tasteless food preservatives. We designed and synthesised chemically modified iso-α-acids to enhance the basic understanding of the molecular mechanism of antimicrobial iso-α-acids. It could be observed that a manganese-binding dependent transmembrane redox reaction (oxidative stress) plays a crucial role in inhibition. Privation of an acidic hydroxyl group neither erased ionophore activity, nor did it entirely abolish antimicrobial activity. Humulinic acids proved to be highly inhibitory, even outperforming iso-α-acids.

  16. Kinetics and mechanism of the oxidation of some -hydroxy acids by hexamethylenetetramine-bromine

    Indian Academy of Sciences (India)

    Dimple Garg; Seema Kothari


    The oxidation of lactic acid, mandelic acid and ten monosubstituted mandelic acids by hexamethylenetetramine-bromine (HABR) in glacial acetic acid, leads to the formation of the corresponding oxoacid. The reaction is first order with respect to each of the hydroxy acids and HABR. It is proposed that HABR itself is the reactive oxidizing species. The oxidation of -deuteriomandelic acid exhibits the presence of a substantial kinetic isotope effect (/ = 5.91 at 298 K). The rates of oxidation of the substituted mandelic acids show excellent correlation with Brown’s + values. The reaction constants are negative. The oxidation exhibits an extensive cross conjugation between the electron-donating substituent and the reaction centre in the transition state. A mechanism involving transfer of a hydride ion from the acid to the oxidant is postulated.

  17. Mechanisms for lowering of interfacial tension in alkali/acidic oil systems; Effect of added surfactant

    Energy Technology Data Exchange (ETDEWEB)

    Rudin, J. Wasan, D.T. (Illinois Inst. of Tech., Chicago, IL (United States). Dept. of Chemical Engineering)


    This paper reports that experimental studies are conducted in order to determine the physicochemical mechanism responsible for lowering of interfacial tension in alkali, surfactant, and surfactant-enhanced alkali/acidic oil systems. A well-defined model oil is chosen to examine the influence of various surfactants and surfactant mixtures, such as oleic acid and its ionic counterpart, sodium dodecyl sulfate, petroleum sulfonate, and isobutanol, on equilibrium interfacial tension. With added surfactant alone, the interfacial tension goes through an ultralow minimum with increasing acid concentration. This proves for the first time that the un-ionized acid species plays a major role in affecting interfacial tension, and the ionized acid species.

  18. Ursolic acid inhibits the initiation, progression of prostate cancer and prolongs the survival of TRAMP mice by modulating pro-inflammatory pathways.

    Directory of Open Access Journals (Sweden)

    Muthu K Shanmugam

    Full Text Available Prostate cancer is one of the leading causes of cancer death among men worldwide. In this study, using transgenic adenocarcinoma of mouse prostate (TRAMP mice, the effect of diet enriched with 1% w/w ursolic acid (UA was investigated to evaluate the stage specific chemopreventive activity against prostate cancer. We found that TRAMP mice fed with UA diet for 8 weeks (weeks 4 to 12 delayed formation of prostate intraepithelial neoplasia (PIN. Similarly, mice fed with UA diet for 6 weeks (weeks 12 to 18 inhibited progression of PIN to adenocarcinoma as determined by hematoxylin and eosin staining. Finally, TRAMP mice fed with UA diet for 12 weeks (weeks 24 to 36 demonstrated markedly reduced tumor growth without any significant effects on total body weight and prolonged overall survival. With respect to the molecular mechanism, we found that UA down-regulated activation of various pro-inflammatory mediators including, NF-κB, STAT3, AKT and IKKα/β phosphorylation in the dorsolateral prostate (DLP tissues that correlated with the reduction in serum levels of TNF-α and IL-6. In addition, UA significantly down-regulated the expression levels of cyclin D1 and COX-2 but up-regulated the levels of caspase-3 as revealed by immunohistochemical analysis of tumor tissue sections. Finally, UA was detected in serum samples obtained from various mice groups fed with enriched diet in nanogram quantity indicating that it is well absorbed in the GI tract. Overall, our findings provide strong evidence that UA can be an excellent agent for both the prevention and treatment of prostate cancer.

  19. Tranexamic Acid Mechanisms and Pharmacokinetics in Traumatic Injury (United States)


    patients with severe traumatic injury will determine if the use of tranexamic acid within 2 hours of injury is associated with less immune suppression...forms”, contact information for the study team, links to our Facebook and Twitter pages, feedback forms, our community power point presentation, and...4308 Nearest person month worked 1 Contribution to Project: Dr. Fuchs has developed and validated laboratory techniques associated with the

  20. Acetic acid-catalyzed formation of N-phenylphthalimide from phthalanilic acid: a computational study of the mechanism. (United States)

    Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi


    In glacial acetic acid, phthalanilic acid and its monosubstituents are known to be converted to the corresponding phthalimides in relatively good yields. In this study, we computationally investigated the experimentally proposed two-step (addition-elimination or cyclization-dehydration) mechanism at the second-order Møller-Plesset perturbation (MP2) level of theory for the unsubstituted phthalanilic acid, with an explicit acetic acid molecule included in the calculations. In the first step, a gem-diol tetrahedral intermediate is formed by the nucleophilic attack of the amide nitrogen. The second step is dehydration of the intermediate to give N-phenylphthalimide. In agreement with experimental findings, the second step has been shown to be rate-determining. Most importantly, both of the steps are catalyzed by an acetic acid molecule, which acts both as proton donor and acceptor. The present findings, along with those from our previous studies, suggest that acetic acid and other carboxylic acids (in their undissociated forms) can catalyze intramolecular nucleophilic attacks by amide nitrogens and breakdown of the resulting tetrahedral intermediates, acting simultaneously as proton donor and acceptor. In other words, double proton transfers involving a carboxylic acid molecule can be part of an extensive bond reorganization process from cyclic hydrogen-bonded complexes.

  1. Mechanical dyssynchrony evaluated by tissue Doppler cross-correlation analysis is associated with long-term survival in patients after cardiac resynchronization therapy

    DEFF Research Database (Denmark)

    Risum, Niels; Williams, Eric S; Khouri, Michel G;


    Aims Pre-implant assessment of longitudinal mechanical dyssynchrony using cross-correlation analysis (XCA) was tested for association with long-term survival and compared with other tissue Doppler imaging (TDI)-derived indices. Methods and results In 131 patients referred for cardiac resynchroniz...

  2. Three- to nine-year survival estimates and fracture mechanisms of zirconia- and alumina-based restorations using standardized criteria to distinguish the severity of ceramic fractures


    Moraguez, Osvaldo; Wiskott, Anselm; Scherrer, Susanne


    The aims of this study were set as follows: 1. To provide verifiable criteria to categorize the ceramic fractures into non-critical (i.e., amenable to polishing) or critical (i.e., in need of replacement) 2. To establish the corresponding survival rates for alumina and zirconia restorations 3. To establish the mechanism of fracture using fractography

  3. Effects of Two Dietary Lipid Sources at Two Levels on the Survival, Growth and Fatty Acid Composition of the Giant Freshwater Prawn, Macrobrachium rosenbergii

    Directory of Open Access Journals (Sweden)

    Young Chul kim


    Full Text Available A 10 week feeding trial was conducted to investigate dietary crude palm oil (CPO or squid liver oil (SLO, at 3.5% (low or 9.5% (high as a 2 × 2 factorial design on survival, growth and whole body fatty acid composition of the giant freshwater prawn, Macrobrachium rosenbergii.  Growth performance was lowest and highest for prawns fed the CPO-low and SLO-high diets, respectively.  While prawns fed the CPO-high diet had lower growth than those fed the SLO-low diet, no significant differences were detected.  Significant interactions were found for oleic acid, arachidonic acid, n-6 polyunsaturated fatty acids (PUFA and n-3/n-6 PUFA, while long chain PUFA, eicosapentaenoic acid and docosahexaenoic acid of the prawns were significantly lower when fed the CPO-based diets.  Lower growth of M. rosenbergii fed the CPO-based diets may be related to less favorable fatty acid ratios and/ or lowered digestibility but higher dietary CPO can help mitigate this. 

  4. Short communication: Latin-style fresh cheese enhances lactic acid bacteria survival but not Listeria monocytogenes resistance under in vitro simulated gastrointestinal conditions. (United States)

    Silva, C C G; Domingos-Lopes, M F P; Magalhães, V A F; Freitas, D A S R; Coelho, M C; Rosa, H J D; Dapkevicius, M L N E


    Different studies in humans have provided evidence about the health benefits of probiotics. However, most probiotic strains do not maintain good viability in the harsh conditions of the gastrointestinal tract (GIT). In the present study, Latin-style fresh cheese produced with potential probiotic bacteria was tested to evaluate this cheese type as a food carrier for the delivery of viable microorganisms after exposure to simulated GIT conditions. The resistance of 28 lactic acid bacteria (LAB) strains and Listeria monocytogenes upon exposure to acidic conditions (pH 2.5) and bile and pancreatic enzymes (0.3% of bile salts and 0.1% of pancreatin) was evaluated in vitro. When compared with fresh cultures, fresh cheese greatly improved LAB survival to simulated GIT conditions, as no loss of viability was observed in either acidic conditions (pH 2.5) or bile salts and pancreatin environment over a 3-h period. In opposition, L. monocytogenes did not survive after 1h under acidic conditions. These data demonstrated that Latin-style fresh cheese could play an important role in probiotic protection against gastrointestinal juices, enhancing delivery within the gut and thereby maximizing potential health benefits of LAB.

  5. Effects of inhaled acid aerosols on lung mechanics: an analysis of human exposure studies.


    Utell, M J


    There exist significant gaps in our understanding of human health effects from inhalation of pollutants associated with acid precipitation. Controlled clinical studies examine effects of criteria pollutants almost exclusively by assessing changes in lung mechanics. One constituent of acid precipitation, sulfuric acid aerosols, has been shown to induce bronchoconstriction in exercising extrinsic asthmatics at near ambient levels. These asthmatics may be an order of magnitude more sensitive to ...

  6. Setting mechanisms of an acidic premixed calcium phosphate cement



    Premixed calcium phosphate cements (pCPC), where glycerol is used instead of water as mixing liquid, present better handling characteristics than water-based cements. However, the setting mechanisms of pCPC have not been described thoroughly. The aim of this paper is to increase the understanding of the setting mechanism of pCPC. The investigated cement starts to set when glycerol is exchanged with water via diffusion of glycerol out to the surrounding body fluid and water into the material. ...

  7. Kinetics and Mechanism of Oxidation of Glutamic Acid by N-Bromophthalimide in Aqueous Acidic Medium



    The kinetics of oxidation of glutamic acid (Glu) with N-bromophthalimide (NBP) was studied in perchloric acid medium at 30 °C by potentiometric method. The reaction is first order each in NBP and glutamic acid and is negative fractional order in [H+]. Addition of KBr or the reaction product, phthalimide had no effect on the rate. Similarly variation of ionic strength of the medium did not affect the rate of the reaction. Also the rate increased with decrease in dielectric constant of the reac...

  8. A TRPA1-dependent mechanism for the pungent sensation of weak acids. (United States)

    Wang, Yuanyuan Y; Chang, Rui B; Allgood, Sallie D; Silver, Wayne L; Liman, Emily R


    Acetic acid produces an irritating sensation that can be attributed to activation of nociceptors within the trigeminal ganglion that innervate the nasal or oral cavities. These sensory neurons sense a diverse array of noxious agents in the environment, allowing animals to actively avoid tissue damage. Although receptor mechanisms have been identified for many noxious chemicals, the mechanisms by which animals detect weak acids, such as acetic acid, are less well understood. Weak acids are only partially dissociated at neutral pH and, as such, some can cross the cell membrane, acidifying the cell cytosol. The nociceptor ion channel TRPA1 is activated by CO(2), through gating of the channel by intracellular protons, making it a candidate to more generally mediate sensory responses to weak acids. To test this possibility, we measured responses to weak acids from heterologously expressed TRPA1 channels and trigeminal neurons with patch clamp recording and Ca(2+) microfluorometry. Our results show that heterologously expressed TRPA1 currents can be induced by a series of weak organic acids, including acetic, propionic, formic, and lactic acid, but not by strong acids. Notably, the degree of channel activation was predicted by the degree of intracellular acidification produced by each acid, suggesting that intracellular protons are the proximate stimulus that gates the channel. Responses to weak acids produced a Ca(2+)-independent inactivation that precluded further activation by weak acids or reactive chemicals, whereas preactivation by reactive electrophiles sensitized TRPA1 channels to weak acids. Importantly, responses of trigeminal neurons to weak acids were highly overrepresented in the subpopulation of TRPA1-expressing neurons and were severely reduced in neurons from TRPA1 knockout mice. We conclude that TRPA1 is a general sensor for weak acids that produce intracellular acidification and suggest that it functions within the pain pathway to mediate sensitivity to

  9. Understanding the 3-hydroxypropionic acid tolerance mechanism in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Kildegaard, Kanchana Rueksomtawin; Juncker, Agnieszka; Hallstrom, Bjorn;


    a sustainable alternative for production of acrylic acid from renewable feedstocks. We are establishing Saccharomyces cerevisiae as an alternative host for 3HP production. However, 3HP also inhibits yeast grow th at level well below what is desired for commercial applications. Therefore, we are aiming...... to improve 3HP tolerance in S. cerevisiae by applying adaptive evolution approach. We have generated yeast strains with sign ificantly improved capacity for tolerating 3HP when compared to the wild-type. We will present physiolo gical characterization, genome re-sequencing, and transcriptome analysis...

  10. Mechanism of acid corrosion inhibition using magnetic nanofluid (United States)

    Parekh, Kinnari; Jauhari, Smita; Upadhyay, R. V.


    The inhibition effect of magnetic nanofluid on carbon steel in acid solutions was investigated using gravimetric, potentiodynamic and SEM measurement. The inhibition efficiency increases up to 95% and 75% for 51.7 mM concentration, respectively, in 1 M HCl and 1 M H2SO4 medium. The adsorption of nanoparticles to the steel surface forms a barrier between the metal and the aggressive environment, which is responsible for observed inhibition action. The adsorption of nanoparticles on steel surface is supported by the Langmuir and Freundlich adsorption isotherm and surface morphology scanned through SEM.

  11. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking (United States)

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B


    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression. PMID:21964384

  12. Clavulanic acid increases dopamine release in neuronal cells through a mechanism involving enhanced vesicle trafficking. (United States)

    Kost, Gina Chun; Selvaraj, Senthil; Lee, Young Bok; Kim, Deog Joong; Ahn, Chang-Ho; Singh, Brij B


    Clavulanic acid is a CNS-modulating compound with exceptional blood-brain barrier permeability and safety profile. Clavulanic acid has been proposed to have anti-depressant activity and is currently entering Phase IIb clinical trials for the treatment of Major Depressive Disorder (MDD). Studies have also shown that clavulanic acid suppresses anxiety and enhances sexual functions in rodent and primate models by a mechanism involving central nervous system (CNS) modulation, although its detailed mechanism of action has yet to be elucidated. To further examine its potential as a CNS modulating agent as well as its mechanism of action, we investigated the effects of clavulanic acid in neuronal cells. Our results indicate that clavulanic acid enhances dopamine release in PC12 and SH-SY5Y cells without affecting dopamine synthesis. Furthermore, using affinity chromatography we were able to identify two proteins, Munc18-1 and Rab4 that potentially bind to clavulanic acid and play a critical role in neurosecretion and the vesicle trafficking process. Consistent with this result, an increase in the translocation of Munc18-1 and Rab4 from the cytoplasm to the plasma membrane was observed in clavulanic acid treated cells. Overall, these data suggest that clavulanic acid enhances dopamine release in a mechanism involving Munc18-1 and Rab4 modulation and warrants further investigation of its therapeutic use in CNS disorders, such as depression.

  13. The use of citric acid as attractant in diet of grand sturgeon Huso huso fry and its effects on growing factors and survival rate

    Directory of Open Access Journals (Sweden)

    Abbas Hosseini


    Full Text Available In an 8-weeks feeding trial, attractant (citric acid was added to juvenile beluga (Huso husodiets at different levels in order to increase growth and survival. In this trial that was carried out inShahid Marjani complex of sturgeon propagation and cultivation, three different dietary of attractants(0.5%, 1% and 1.5% were taken into account. The trial was carried out in 500 liter PVC tanks whichwere filled with about 350 liter of water. 50 juvenile beluga (mean initial weight 26.04±0.43g werestocked in tanks and were fed up four meals a day. Growth and survival factors were analyzed at theend of trial period. After 54 days, weight gain, feed intake, feed conversion ratio (FCR, Daily GrowthIndex (DGI, Daily Growth Rate (DGR, Specific Growth Rate (SGR, Condition Factor (CF, were higherin beluga fed the three citric acid–added diets compared with control feed. Among the citric acid–addeddiets, juvenile beluga fed citric acid of 5, 10, 15 g Kg-1 level showed highest weight gain (134 g byregistering 136.6 % increase in growth over control and higher feed intake (7.34 and good FCR (2.20.There was highly significant differences (P0.05 in survival among treatment.

  14. Omega-3 fatty acids and metabolic syndrome: effects and emerging mechanisms of action. (United States)

    Poudyal, Hemant; Panchal, Sunil K; Diwan, Vishal; Brown, Lindsay


    Epidemiological, human, animal, and cell culture studies show that n-3 fatty acids, especially α-linolenic acid (ALA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA), reduce the risk factors of cardiovascular diseases. EPA and DHA, rather than ALA, have been the focus of research on the n-3 fatty acids, probably due to the relatively inefficient conversion of ALA to EPA and DHA in rodents and humans. This review will assess our current understanding of the effects and potential mechanisms of actions of individual n-3 fatty acids on multiple risk factors of metabolic syndrome. Evidence for pharmacological responses and the mechanism of action of each of the n-3 fatty acid trio will be discussed for the major risk factors of metabolic syndrome, especially adiposity, dyslipidemia, insulin resistance and diabetes, hypertension, oxidative stress, and inflammation. Metabolism of n-3 and n-6 fatty acids as well as the interactions of n-3 fatty acids with nutrients, gene expression, and disease states will be addressed to provide a rationale for the use of n-3 fatty acids to reduce the risk factors of metabolic syndrome.

  15. Mechanism-based pharmacokinetic-pharmacodynamic modeling of salvianolic acid A effects on plasma xanthine oxidase activity and uric acid levels in acute myocardial infarction rats. (United States)

    Wang, Haidong; Li, Xi; Zhang, Wenting; Liu, Yao; Wang, Shijun; Liu, Xiaoquan; He, Hua


    1. Salvianolic acid A (SalA) was found to attenuate plasma uric acid (UA) concentration and xanthine oxidase (XO) activity in acute myocardial infraction (AMI) rats, which was characterized with developed mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) model. 2. AMI was induced in rats by coronary artery ligation. Surviving AMI rats received a single intravenous dose of 5 mg/kg of SalA and normal saline. The plasma SalA concentrations were determined by HPLC-MS/MS method. The plasma UA concentrations were determined by HPLC method and plasma XO activity were measured spectrophotometrically. An integrated mathematical model characterized the relationship between plasma UA and SalA. 3. Pharmacokinetics was described using two-compartment model for SalA with linear metabolic process. In post-AMI rats, XO activity and UA concentrations were increased, while SalA dosing palliated this increase. These effects were well captured by using two series of transduction models, simulating the delay of inhibition on XO driven by SalA and UA elevation resulted from the multiple factors, respectively. 4. The effect was well described by the developed PK-PD model, indicating that SalA can exert cardiovascular protective effects by decreasing elevated plasma UA levels induced by AMI.

  16. Chemistry enters nucleic acids biology: enzymatic mechanisms of RNA modification. (United States)

    Boschi-Muller, S; Motorin, Y


    Modified nucleotides are universally conserved in all living kingdoms and are present in almost all types of cellular RNAs, including tRNA, rRNA, sn(sno)RNA, and mRNA and in recently discovered regulatory RNAs. Altogether, over 110 chemically distinct RNA modifications have been characterized and localized in RNA by various analytical methods. However, this impressive list of known modified nucleotides is certainly incomplete, mainly due to difficulties in identification and characterization of these particular residues in low abundance cellular RNAs. In DNA, modified residues are formed by both enzymatic reactions (like DNA methylations, for example) and by spontaneous chemical reactions resulting from oxidative damage. In contrast, all modified residues characterized in cellular RNA molecules are formed by specific action of dedicated RNA-modification enzymes, which recognize their RNA substrate with high specificity. These RNA-modification enzymes display a great diversity in terms of the chemical reaction and use various low molecular weight cofactors (or co-substrates) in enzymatic catalysis. Depending on the nature of the target base and of the co-substrate, precise chemical mechanisms are used for appropriate activation of the base and the co-substrate in the enzyme active site. In this review, we give an extended summary of the enzymatic mechanisms involved in formation of different methylated nucleotides in RNA, as well as pseudouridine residues, which are almost universally conserved in all living organisms. Other interesting mechanisms include thiolation of uridine residues by ThiI and the reaction of guanine exchange catalyzed by TGT. The latter implies the reversible cleavage of the N-glycosidic bond in order to replace the initially encoded guanine by an aza-guanosine base. Despite the extensive studies of RNA modification and RNA-modification machinery during the last 20 years, our knowledge on the exact chemical steps involved in catalysis of RNA

  17. New mechanisms that regulate Saccharomyces cerevisiae short peptide transporter achieve balanced intracellular amino acid concentrations. (United States)

    Melnykov, Artem V


    The budding yeast Saccharomyces cerevisiae is able to take up large quantities of amino acids in the form of di- and tripeptides via a short peptide transporter, Ptr2p. It is known that PTR2 can be induced by certain peptides and amino acids, and the mechanisms governing this upregulation are understood at the molecular level. We describe two new opposing mechanisms of regulation that emphasize potential toxicity of amino acids: the first is upregulation of PTR2 in a population of cells, caused by amino acid secretion that accompanies peptide uptake; the second is loss of Ptr2p activity, due to transporter internalization following peptide uptake. Our findings emphasize the importance of proper amino acid balance in the cell and extend understanding of peptide import regulation in yeast.

  18. Blood-brain barrier permeability and brain uptake mechanism of kainic Acid and dihydrokainic Acid

    DEFF Research Database (Denmark)

    Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen Honoré;


    The glutamatergic neurotransmitter system is involved in important neurophysiological processes and thus constitutes a promising target for the treatment of neurological diseases. The two ionotropic glutamate receptor agonists kainic acid (KA) and dihydrokainic acid (DHK) have been used as research...... volume of distribution in brain is also low. Therefore, even though the total KA and DHK concentrations in the brain are low after systemic dosing, the concentrations in the vicinity of the glutamate receptors are sufficient for their activation and thus the observed efficacy....

  19. Dynamic mechanical and swelling properties of maleated hyaluronic acid hydrogels. (United States)

    Lin, Hai; Liu, Jun; Zhang, Kai; Fan, Yujiang; Zhang, Xingdong


    A series of maleated hyaluronan (MaHA) are developed by modification with maleic anhydride. The degrees of substitution (DS) of MaHA vary between 7% and 75%. The DS of MaHA is both higher and wider than methacrylated HA derivatives (MeHA) reported in the literature. MaHA hydrogels are then prepared by photopolymerization and their dynamic mechanical and swelling properties of the hydrogels are investigated. The results showed that MaHA hydrogels with moderate DS (25%, 50% and 65%) have higher storage modulus and lower equilibrium swelling ratios than those with either low or high DS (7%, 15% and 75%). Theoretical analyses also suggest a similar pattern among hydrogels with different DS. The results confirm that the increased cross-linking density enhances the strength of hydrogels. Meanwhile, the hydrophilicity of introduced groups during modification and the degree of incomplete crosslinking reaction might have negative impact on the mechanical and swelling properties of MaHA hydrogels.

  20. Effects of Calanoid Copepod Schmackeria poplesia as a Live Food on the Growth, Survival and Fatty Acid Composition of Larvae and Juveniles of Japanese Flounder, Paralichthys olivaceus

    Institute of Scientific and Technical Information of China (English)

    LIU Guangxing; XU Donghui


    Zooplankton constitutes a major part of the diet for fish larvae in the marine food web, and it is generally believed that copepods can meet the nutritional requirements of fish larvae. In this study, calanoid copepod Schmackeria poplesia, rotifer Brachionus plicatilis and anostraca crustacean Artemia sp. were analyzed for fatty acid contents, and were used as live food for culturing larval Japanese flounder, Paralichthys olivaceus. The total content of three types of HUFAs (DHA, EPA and ARA) in S. poplesia was significantly higher than that in the other two live foods (P<0.01). Three live organisms were used for raising larvae and juveniles ofParalichthys olivaceus respectively for 15 and 10 d. Then the growth, survival and fatty acid composition of the larvae and juveniles were investigated. The results showed that the larvae and juveniles fed with copepods (S. poplesia) had significantly higher growth rate than thosc fed with the other two organisms (P<0.01). The survival of the flounder larvae fed with copepods was significantly higher than that of the others (P<0.01), and the survival of the juvenile fish fed with copepods was higher than that fed with Artemia (P<0.05). The contents of three types of HUFAs (DHA, EPA and ARA) and the ratio of DHA/EPA in larval and juvenile flounder P. olivaceus were analyzed. The results showed that the contents of DHA, EPA and ARA in the larvae and juveniles fed with S. poplesia were higher than those fed with a mixed diet or Artemia only, and the ratio of EPA/ARA in larvae and juveniles of P. olivaceus fed with S. poplesia was lower than that in the case of feeding with a mixed diet or Artemia only. The present data showed that copepod is the best choice for feeding the larvae and juveniles of fish considering its effects on the survival, growth and nutrition composition of the fish.

  1. Effect of dietary (n-3 highly unsaturated fatty acids on growth and survival of fat snook (Centropomus parallelus, Pisces: Centropomidae larvae during first feeding

    Directory of Open Access Journals (Sweden)

    M.E.B. Seiffert


    Full Text Available The effect of rotifers, Brachionus rotundiformis (S-type, fed three different diets: A (rotifer fed Nannochloropsis oculata, B (rotifer fed N. oculata and baker's yeast, 1:1, and C (rotifer fed N. oculata and baker's yeast, 1:1, and enriched with Selcoâ, was evaluated based on the survival, growth and swim bladder inflation rate of fat snook larvae. Rotifers of treatment A had higher levels (4.58 mg/g dry weight of eicosapentaenoic acid (EPA than B (1.81 mg/g dry weight, and similar levels (0.04 and 0.06 mg/g dry weight, respectively of docosahexaenoic acid (DHA. Rotifers of treatment C had the highest levels of EPA (13.2 mg/g dry weight and DHA (6.08 mg/g dry weight. Fat snook eggs were obtained by spawning induction with human chorionic gonadotropin. Thirty hours after hatching, 30 larvae/liter were stocked in black cylindric-conical tanks (36-liter capacity. After 14 days of culture, there were no significant differences among treatments. Mean standard length was 3.13 mm for treatment A, 3.17 mm for B, and 3.39 mm for C. Mean survival rates were very low (2.7% for treatment A, 2.3% for B, and 1.8% for C. Swim bladder inflation rates were 34.7% for treatment A, 27.1% for B, and 11.9% for C. The lack of differences in growth and survival among treatments showed that the improvement of the dietary value of rotifer may not have been sufficient to solve the problem of larval rearing. Some other factor, probably pertaining to the quality of the larvae, may have negatively influenced survival.

  2. Cyclobutyl methyl ketone as a model compound for pinonic acid to elucidate oxidation mechanisms

    Directory of Open Access Journals (Sweden)

    A. P. Praplan


    Full Text Available 3-Methyl-1,2,3-tricarboxylic acid (MBTCA, terpenylic acid and diaterpenylic acid acetate were identified in secondary organic aerosol (SOA from α-pinene photooxidation or ozonolysis. These compounds display interesting structural features: MBTCA has a high oxygen to carbon ratio, terpenylic acid contains a lactone ring in its structure and diaterpenylic acid acetate possesses an ester functional group. The reaction mechanisms leading to these products are still unknown, but it was demonstrated experimentally in earlier studies that MBTCA is formed from pinonic acid, a primary ozonolysis product of α-pinene. Because the direct observation of pinonic acid oxidation in a smog chamber would be difficult due to its relatively low volatility, a model compound possessing the substructure of interest was used instead: cyclobutyl methyl ketone (CMK. From its oxidation, several organic acids could be measured with ion chromatography (IC coupled to a mass spectrometer (MS. Succinic acid, the analogous product of MBTCA is formed at molar yields of 2 to 5%. Butyrolactone is detected as butanoic acid, due to hydrolysis in the sampling device. A monocarboxylic acid with nominal mass 146 was detected in the absence of nitrogen oxides (NOx and could be the analogous product of diaterpenylic acid acetate. However, due to a lack of available standards, the exact structure of this compound remains unelucidated. Finally, 4-oxobutanoic acid could also be measured and two structures of its expected analogous compound from pinonic acid oxidation are proposed. Because these compounds are primary products of the CMK oxidation, reaction mechanisms capable of adding one or two carboxylic functional groups without formation of stable intermediate products needs to be formulated. Such a formation mechanism of MBTCA from pinonic acid was found in the literature; however, it includes a hydrogen atom migration to an acyloxy radical, which is expected to loose

  3. Study on Mechanism for Formation of Carbon Oxides During Catalytic Cracking of High Acidic Crude

    Institute of Scientific and Technical Information of China (English)

    Wei Xiaoli; Mao Anguo; Xie Chaogang


    Based on the basis of analysis and interpretation of the products distribution of catalytic cracking of high acidic crude,the mechanism for decarboxylation of petroleum acids during FCC process was discussed.The protons originated from the Br(o)nsted acid sites can combine with oxygen of the carbonyl groups with more negative charges to form reaction intermediates that Call be subjected to cleavage at the weak bonds,leading to breaking of carboxylic groups from the carboxylic acids followed by its decomposition to form alkyl three-coordinated carbenium ions,CO and H2O.The Lewis acid as an electrophilic reagent can abstract carboxylic groups from carboxylic acids to subsequently release CO2.

  4. Survival in acidic and alcoholic medium of Shiga toxin-producing Escherichia coli O157:H7 and non-O157:H7 isolated in Argentina

    Directory of Open Access Journals (Sweden)

    Sanz Marcelo E


    Full Text Available Abstract Background In spite of Argentina having one of the highest frequencies of haemolytic uraemic syndrome (HUS, the incidence of Escherichia coli O157:H7 is low in comparison to rates registered in the US. Isolation of several non-O157 shiga toxin-producing Escherichia coli (STEC strains from cattle and foods suggests that E. coli O157:H7 is an uncommon serotype in Argentina. The present study was undertaken to compare the survival rates of selected non-O157 STEC strains under acidic and alcoholic stress conditions, using an E. coli O157:H7 strain as reference. Results Growth at 37°C of E. coli O26:H11, O88:H21, O91:H21, O111:H-, O113:H21, O116:H21, O117:H7, O157:H7, O171:H2 and OX3:H21, was found to occur at pH higher than 4.0. When the strains were challenged to acid tolerance at pH as low as 2.5, viability extended beyond 8 h, but none of the bacteria, except E. coli O91:H21, could survive longer than 24 h, the autochthonous E. coli O91:H21 being the more resistant serotype. No survival was found after 24 h in Luria Bertani broth supplemented with 12% ethanol, but all these serotypes were shown to be very resistant to 6% ethanol. E. coli O91:H21 showed the highest resistance among serotypes tested. Conclusions This information is relevant in food industry, which strongly relies on the acid or alcoholic conditions to inactivate pathogens. This study revealed that stress resistance of some STEC serotypes isolated in Argentina is higher than that for E. coli O157:H7.

  5. Induction of Bladder Lesion by Terephthalic Acid and Its Mechanism

    Institute of Scientific and Technical Information of China (English)


    Objective To provide more information for rational evaluation of potential risks of terephthalic acid (TPA), we studied the effects of TPA on rats' bladders in 90 days after TPA exposure. Methods Sprague Dawley rats were subdivided into five groups, ingesting 0 %, 0.04 %, 0.2 %, 1 %, and 5 % TPA respectively for a sub-chronic feeding study lasting for 90 days. Urine, serum and samples of brain, liver, lung, kidney, bladder, etc. Were collected and analyzed. Results TPA ingesting decreased the value of urinary pH, and increased the contents of Ca2+, Zn2+, Mg2+, Na+, K+ in urine. The volume of 24 h urine was significantly increased in male rats in the 1 % and 5 % TPA groups. Urinary white sediment was found in both sexes, and its formation in male rats seemed more susceptible than that in female rats. Alpha 2u-globulin (AUG) in serum and urine of male rats was markedly increased in a dose-dependent manner. Fifteen cases of hyperplasia (simple or atypical) were determined in the 5 % TPA ingesting group, 14/52 in male rats and1/23 in female rats. Among them 3 male rats had no stone or calculus. Those with either bladder stones or hyperplasia were accompanied with urinary white sediments. Conclusion White sediment accompanied with elevated urine AUG is the basis of TPA induced urolith formation, and is also associated with TPA induced bladder epithelialcell proliferation. It can act as an early biomarker for the potential toxic effect of TPA.

  6. Acetic Acid Can Catalyze Succinimide Formation from Aspartic Acid Residues by a Concerted Bond Reorganization Mechanism: A Computational Study (United States)

    Takahashi, Ohgi; Kirikoshi, Ryota; Manabe, Noriyoshi


    Succinimide formation from aspartic acid (Asp) residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe) as a model compound, we propose the possibility that acetic acid (AA), which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition) to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds) occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism. PMID:25588215

  7. Acetic Acid Can Catalyze Succinimide Formation from Aspartic Acid Residues by a Concerted Bond Reorganization Mechanism: A Computational Study

    Directory of Open Access Journals (Sweden)

    Ohgi Takahashi


    Full Text Available Succinimide formation from aspartic acid (Asp residues is a concern in the formulation of protein drugs. Based on density functional theory calculations using Ace-Asp-Nme (Ace = acetyl, Nme = NHMe as a model compound, we propose the possibility that acetic acid (AA, which is often used in protein drug formulation for mildly acidic buffer solutions, catalyzes the succinimide formation from Asp residues by acting as a proton-transfer mediator. The proposed mechanism comprises two steps: cyclization (intramolecular addition to form a gem-diol tetrahedral intermediate and dehydration of the intermediate. Both steps are catalyzed by an AA molecule, and the first step was predicted to be rate-determining. The cyclization results from a bond formation between the amide nitrogen on the C-terminal side and the side-chain carboxyl carbon, which is part of an extensive bond reorganization (formation and breaking of single bonds and the interchange of single and double bonds occurring concertedly in a cyclic structure formed by the amide NH bond, the AA molecule and the side-chain C=O group and involving a double proton transfer. The second step also involves an AA-mediated bond reorganization. Carboxylic acids other than AA are also expected to catalyze the succinimide formation by a similar mechanism.

  8. Molecular Mechanisms of Ursodeoxycholic Acid Toxicity & Side Effects: Ursodeoxycholic Acid Freezes Regeneration & Induces Hibernation Mode

    Directory of Open Access Journals (Sweden)

    Magd A. Kotb


    Full Text Available Ursodeoxycholic acid (UDCA is a steroid bile acid approved for primary biliary cirrhosis (PBC. UDCA is reported to have “hepato-protective properties”. Yet, UDCA has “unanticipated” toxicity, pronounced by more than double number of deaths, and eligibility for liver transplantation compared to the control group in 28 mg/kg/day in primary sclerosing cholangitis, necessitating trial halt in North America. UDCA is associated with increase in hepatocellular carcinoma in PBC especially when it fails to achieve biochemical response (10 and 15 years incidence of 9% and 20% respectively. “Unanticipated” UDCA toxicity includes hepatitis, pruritus, cholangitis, ascites, vanishing bile duct syndrome, liver cell failure, death, severe watery diarrhea, pneumonia, dysuria, immune-suppression, mutagenic effects and withdrawal syndrome upon sudden halt. UDCA inhibits DNA repair, co-enzyme A, cyclic AMP, p53, phagocytosis, and inhibits induction of nitric oxide synthatase. It is genotoxic, exerts aneugenic activity, and arrests apoptosis even after cellular phosphatidylserine externalization. UDCA toxicity is related to its interference with drug detoxification, being hydrophilic and anti-apoptotic, has a long half-life, has transcriptional mutational abilities, down-regulates cellular functions, has a very narrow difference between the recommended (13 mg/kg/day and toxic dose (28 mg/kg/day, and it typically transforms into lithocholic acid that induces DNA strand breakage, it is uniquely co-mutagenic, and promotes cell transformation. UDCA beyond PBC is unjustified.

  9. Kinetics and mechanism of the oxidation of formic and oxalic acids by quinolinium fluorochromate

    Indian Academy of Sciences (India)

    Madhu Khurana; Pradeep K Sharma; Kalyan K Banerji


    Kinetics and mechanism of oxidation of formic and oxalic acids by quinolinium fluorochromate (QFC) have been studied in dimethylsulphoxide. The main product of oxidation is carbon dioxide. The reaction is first-order with respect to QFC. Michaelis-Menten type of kinetics were observed with respect to the reductants. The reaction is acid-catalysed and the acid dependence has the form: obs = + [H+]. The oxidation of -deuterioformic acid exhibits a substantial primary kinetic isotope effect (H/D = 6.01 at 303 K). The reaction has been studied in nineteen different organic solvents and the solvent effect has been analysed using Taft’s and Swain’s multiparametric equations. The temperature dependence of the kinetic isotope effect indicates the presence of a symmetrical cyclic transition state in the rate-determining step. Suitable mechanisms have been proposed

  10. Non-specific SIRT inhibition as a mechanism for the cytotoxicity of ginkgolic acids and urushiols. (United States)

    Ryckewaert, Lucie; Sacconnay, Lionel; Carrupt, Pierre-Alain; Nurisso, Alessandra; Simões-Pires, Claudia


    Ginkgolic acids and urushiols are natural alkylphenols known for their mutagenic, carcinogenic and genotoxic potential. However, the mechanism of toxicity of these compounds has not been thoroughly elucidated so far. Considering that the SIRT inhibitory potential of anacardic acids has been hypothesized by in silico techniques, we herein demonstrated through both in vitro and computational methods that structurally related compounds such as ginkgolic acids and urushiols are able to modulate SIRT activity. Moreover, their SIRT inhibitory profile and cytotoxicity were comparable to sirtinol, a non-specific SIRT inhibitor (SIRT1 and SIRT2), and different from EX-527, a SIRT1 specific inhibitor. This is the first report on the SIRT inhibition of ginkgolic acids and urushiols. The results reported here are in line with previously observed effects on the induction of apoptosis by this class of compounds, and the non-specific SIRT inhibition is suggested as a new mechanism for their in vitro cytotoxicity.

  11. [Regulating acid stress resistance of lactic acid bacteria--a review]. (United States)

    Wu, Chongde; Huang, Jun; Zhou, Rongqing


    As cell factories, lactic acid bacteria are widely used in food, agriculture, pharmaceutical and other industries. Acid stress is one the important survival challenges encountered by lactic acid bacteria both in fermentation process and in the gastrointestinal tract. Recently, the development of systems biology and metabolic engineering brings unprecedented opportunity for further elucidating the acid tolerance mechanisms and improving the acid stress resistance of lactic acid bacteria. This review addresses physiological mechanisms of lactic acid bacteria during acid stress. Moreover, strategies to improve the acid stress resistance of lactic acid were proposed.

  12. Decrease of intracellular pH as possible mechanism of embryotoxicity of glycol ether alkoxyacetic acid metabolites.

    NARCIS (Netherlands)

    Louisse, J.; Bai, Y.; Verwei, M.; van de Sandt, J.J.M.; Blaauboer, B.J.; Rietjens, I.M.C.M.


    Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabol

  13. Decrease of intracellular pH as possible mechanism of embryotoxicity of glycol ether alkoxyacetic acid metabolites

    NARCIS (Netherlands)

    Louisse, J.; Bai, Y.; Verwei, M.; Sandt, J.J.M. van de; Blaauboer, B.J.; Rietjens, I.M.C.M.


    Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabol

  14. Decrease of intercellular pH as possible mechanism of action of embryotoxicity of glycol ether alkoxyacetic acid metabolites

    NARCIS (Netherlands)

    Louisse, J.; Yanquin Bai,; Verwei, M.; Sandt, van de J.J.M.; Blaauboer, B.J.; Rietjens, I.


    Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabol

  15. Effect and mechanism of diphosphonic acid on flotation characteristic of fersmite and intergrowth gangue

    Institute of Scientific and Technical Information of China (English)

    任暤; 纪绯绯; 张书香


    The effect of several collectors and their dosage on the flotation characteristics of the synthetical fersmite at different pH values, the collecting strength and selectivity of several representative collectors were investigated. The experimental results indicate that diphosphonic acid is a good collector for fersmite and recovery of fersmite ranges from 83.27% to 85.10% when the pulp pH value is at 2.5-5.0 and the dosage is 20 mg/L. The rank sequence of selectivity for several collectors is as follows: diphosphonic acid > benzyl arsonic acid >α-styrolphosphonic acid>alkyl hydroximic acid (C7-9) > cyclic alkyl hydroximic acid. At the same time, Infrared Absorption Spectrum (IAS) and X-ray Photoelectron Spectroscopy (XPS) were used to detect and analyze the action mechanism of diphosphonic acid on fersmite. IAS results show that the characteristic absorption peak relating to PO as well as P-O vibration occurs between wave number 1 178 cm-1, 1 142 cm-1, 1 087 cm-1 and 934 cm-1, and diphosphonic acid is adsorbed on the surface of fersmite. XPS results indicate that the binding energy of P 2p peak of fersmite treated by diphosphonic acid is increased by 3.85 eV. It is proved that the adsorption is mainly chemical adsorption.

  16. Effects of diphosphonic acid on ilmenorutile collecting property and research of action mechanism

    Institute of Scientific and Technical Information of China (English)


    The effects of several collectors and their dosage on pure ilmenorutile at different pH values were studied and the collecting strength of several representative collectors was investigated. The experimental results indicate that diphosphonic acid is a good collector for ilmenorutile and the recovery of ilmenorutile ranges from 90.87% to 91.70% when the pulp pH value is 2.0-4.0 and the dosage is 75mg/L. Thesequence of collecting ability for several collectors is as follows: diphosphonic acid > TF279 > cyclic alkyl hydroximic acid > benzyl arsenic acid > salicylic hydroximic acid > alkyl hydroximic acid. Meanwhile, IAS (infrared absorption spectrum) and XPS (X-ray photoelectron spectroscopy) were used to detect and analyze the action mechanism of diphosphonic acid on ilmenorutile. IAS results showed that the characterid between wave numeber and cm, and diphosphonic acid had adsorbed on the surface of ilmenorutile. XPS results indicated that the binding energy of P2P peak of ilmenorutile had changed 0.45eV after treated by diphosphonic acid. This proves that the adsorption is mainly chemical adsorption.

  17. Expression and Subcellular Localization of Retinoic Acid Receptor-α (RARα) in Healthy and Varicocele Human Spermatozoa: Its Possible Regulatory Role in Capacitation and Survival. (United States)

    Perrotta, Ida; Perri, Mariarita; Santoro, Marta; Panza, Salvatore; Caroleo, Maria C; Guido, Carmela; Mete, Annamaria; Cione, Erika; Aquila, Saveria


    Varicocele, an abnormal tortuosity and dilation of veins of the pampiniform plexus, is the most common identifiable and correctable cause of male infertility. It is now becoming apparent that signaling through vitamin A metabolites, such as all-trans retinoic acid (ATRA), is indispensable for spermatogenesis and disruption of retinoic acid receptor-α (RARα) function may result in male sterility and aberrant spermatogenesis. Herein, we investigated by Western blot and immunogold electron microscopy the expression profiles and subcellular localization of RARα in healthy and varicocele human sperm; in addition, we analyzed the effects of ATRA on cholesterol efflux and sperm survival utilizing enzymatic colorimetric CHOD-PAP method and Eosin Y technique, respectively. In varicocele samples, a strong reduction of RARα expression was observed. Immunogold labeling evidenced cellular location of RARα also confirming its reduced expression in "varicocele" samples. Sperm responsiveness to ATRA treatment was reduced in varicocele sperm. Our study showed that RARα is expressed in human sperm probably with a dual role in promoting both cholesterol efflux and survival. RARα might be involved in the pathogenesis of varicocele as its expression is reduced in pathologic samples. Thus, ATRA administration in procedures for artificial insemination or dietary vitamin A supplementation might represent a promising therapeutic approach for the management of male infertility.

  18. Mechanisms of amino acid-stimulated insulin secretion in congenital hyperinsulinism

    Institute of Scientific and Technical Information of China (English)

    Tingting Zhang; Changhong Li


    The role of amino acids in the regulation of insulin secretion in pancreatic beta-cells is highlighted in three forms of congenital hyperinsulinism (HI),namely gain-of-function mutations of glutamate dehydrogenase (GDH),loss-of-function mutations of ATP-dependent potassium channels,and a deficiency of short-chain 3-hydroxyacyl-CoA dehydrogenase.Studies on disease mouse models of HI suggest that amino acid oxidation and signaling effects are the major mechanisms of amino acid-stimulated insulin secretion.Amino acid oxidation via GDH produces ATP and triggers insulin secretion.The signaling effect of amino acids amplifies insulin release after beta-cell depolarization and elevation of cytosolic calcium.

  19. Mechanism and controlling strategy of the production and accumulation of propionic acid for anaerobic wastewater treatment

    Institute of Scientific and Technical Information of China (English)

    任南琪; 李建政; 赵丹; 陈晓蕾


    The production and accumulation of propionic acid affect significantly anaerobic wastewater treatment system, but the reasons are not approached until now. Based on the results of continuous-flow tests and the analysis of biochemistry and ecology, two mechanisms of producing propionic acid have been put forward. It is demonstrated that the reasons of propionic acid production and accumulation are not caused by higher hydrogen partial pressure. The combination of specific pH value and ORP is the ecological factor affecting propionic acid production, and the equilibrium regulation of NADH/NAD+ ratio in cells is the physiological factor. Meanwhile, it is put forward that using the two-phase anaerobic treatment process and the ethanol type fermentation in anaerobic reactor to avoid propionic acid accumulation are efficient methods.

  20. Receptor for advanced glycation end products plays a more important role in cellular survival than in neurite outgrowth during retinoic acid-induced differentiation of neuroblastoma cells. (United States)

    Sajithlal, Gangadharan; Huttunen, Henri; Rauvala, Heikki; Munch, Gerald


    The receptor for advanced glycation end products (RAGE), a member of the immunoglobulin superfamily, is known to interact with amphoterin. This interaction has been proposed to play a role in neurite outgrowth and process elongation during neurodifferentiation. However, there is as yet no direct evidence of the relevance of this pathway to neurodifferentiation under physiological conditions. In this study we have investigated a possible role of RAGE and amphoterin in the retinoic acid-induced differentiation of neuroblastoma cells. The functional inactivation of RAGE by dominant negative and antisense strategies showed that RAGE is not required for process outgrowth or differentiation, although overexpression of RAGE accelerates the elongation of neuritic processes. Using the antisense strategy, amphoterin was shown to be essential for process outgrowth and differentiation, suggesting that amphoterin may interact with other molecules to exert its effect in this context. Interestingly, the survival of the neuroblastoma cells treated with retinoic acid was partly dependent on the expression of RAGE, and inhibition of RAGE function partially blocked the increase in anti-apoptotic protein Bcl-2 following retinoic acid treatment. Based on these results we propose that a combination therapy using RAGE blockers and retinoic acid may prove as a useful approach for chemotherapy for the treatment of neuroblastoma.

  1. Biochemical mechanism of Caffeic Acid Phenylethyl Ester (CAPE) selective toxicity towards melanoma cell lines


    Kudugunti, Shashi K.; Vad, Nikhil M.; Whiteside, Amanda J.; Naik, Bhakti U.; Yusuf, Mohd. A.; Srivenugopal, Kalkunte S.; Moridani, Majid Y.


    In the current work, we investigated the in-vitro biochemical mechanism of caffeic acid phenylethyl ester (CAPE) toxicity and eight hydroxycinnamic/caffeic acid derivatives in-vitro, using tyrosinase enzyme as a molecular target in human SK-MEL-28 melanoma cells. Enzymatic reaction models using tyrosinase/O2 and HRP/H2O2 were used to delineate the role of one- and two-electron oxidation. Ascorbic acid (AA), NADH and GSH depletion were used as markers of quinone formation and oxidative stress ...

  2. New Perspectives on Mechanisms of Decarboxylation in Hydrothermal Fluids from Studies of Substituted Phenylacetic Acids (United States)

    Glein, C. R.; Gould, I. R.; Lorance, E. D.; Shock, E. L.


    Decarboxylation reactions are thought to play a crucial role in transforming organic compounds in the deep carbon cycle [1]. Simple decarboxylation, defined as conversion of a carboxylic acid into an alkane and carbon dioxide, can turn substances of little economic value into ones of great value. Rates of decarboxylation of acetic acid and acetate at hydrothermal conditions have been reported [2], but no theory exists to rationalize those data. Without a theoretical model for how decarboxylations occur, it is risky to extrapolate available information to diverse geochemical conditions and molecular structures found in natural systems. We have been studying kinetics of decarboxylation of substituted phenylacetic acids and phenylacetates to gain insights into mechanisms of decarboxylation in water at high temperatures and pressures. These model compounds represent powerful tools for deciphering said mechanisms, as their patterns of reactivity reflect mechanistic details. Results from experiments performed at 300°C and 103 MPa suggest that simple decarboxylation of phenylacetic acids to toluenes follows an electrophilic substitution mechanism, featuring a benzyl anion as the key intermediate. This mechanism is consistent with the observed reactivity order of fluorophenylacetic acids: para (1) JACS 86, 404-409.

  3. Review: Mechanisms of How the Intestinal Microbiota Alters the Effects of Drugs and Bile Acids. (United States)

    Klaassen, Curtis D; Cui, Julia Yue


    Information on the intestinal microbiota has increased exponentially this century because of technical advancements in genomics and metabolomics. Although information on the synthesis of bile acids by the liver and their transformation to secondary bile acids by the intestinal microbiota was the first example of the importance of the intestinal microbiota in biotransforming chemicals, this review will discuss numerous examples of the mechanisms by which the intestinal microbiota alters the pharmacology and toxicology of drugs and other chemicals. More specifically, the altered pharmacology and toxicology of salicylazosulfapridine, digoxin, l-dopa, acetaminophen, caffeic acid, phosphatidyl choline, carnitine, sorivudine, irinotecan, nonsteroidal anti-inflammatory drugs, heterocyclic amines, melamine, nitrazepam, and lovastatin will be reviewed. In addition, recent data that the intestinal microbiota alters drug metabolism of the host, especially Cyp3a, as well as the significance and potential mechanisms of this phenomenon are summarized. The review will conclude with an update of bile acid research, emphasizing the bile acid receptors (FXR and TGR5) that regulate not only bile acid synthesis and transport but also energy metabolism. Recent data indicate that by altering the intestinal microbiota, either by diet or drugs, one may be able to minimize the adverse effects of the Western diet by altering the composition of bile acids in the intestine that are agonists or antagonists of FXR and TGR5. Therefore, it may be possible to consider the intestinal microbiota as another drug target.

  4. Identification of lactic acid bacteria in the rumen and feces of dairy cows fed total mixed ration silage to assess the survival of silage bacteria in the gut. (United States)

    Han, H; Ogata, Y; Yamamoto, Y; Nagao, S; Nishino, N


    The survival of silage lactic acid bacteria (LAB) in the gut of dairy cows was evaluated by examining the LAB communities of silage and gut contents. Samples were collected at 2 different research institutes (Mie and Okayama) that offered total mixed ration (TMR) silage throughout the year. Silage and feces were sampled in August, October, and November at the Mie institute, whereas silage, rumen fluid, and feces were sampled in June and August at the Okayama institute. Denaturing gradient gel electrophoresis using Lactobacillus-specific primers was performed to detect LAB species in the samples. The selected bands were purified for species identification and the band patterns were used for principal component analysis. Lactic acid was the predominant fermentation product in all the TMR silages analyzed, and the lactic acid level tended to be constant regardless of the sampling time and region. A total of 14 LAB species were detected in the TMR silage samples, of which 5 (Lactobacillus acetotolerans, Lactobacillus pontis, Lactobacillus casei, Lactobacillus suebicus, and Lactobacillus plantarum) were detected in the dairy cow feces. Most of the denaturing gradient gel electrophoresis bands for the feces samples were also detected in the rumen fluid, suggesting that any elimination of silage LAB occurred in the rumen and not in the postruminal gut segments. The principal component analysis indicated that the LAB communities in the silage, rumen fluid, and feces were separately grouped; hence, the survival of silage LAB in the cow rumen and lower gut was deemed difficult. It was concluded that, although the gut LAB community is robust and not easily affected by the silage conditions, several LAB species can inhabit both silage and feces, which suggests the potential of using silage as a vehicle for conveying probiotics.

  5. Plant resistance mechanisms to air pollutants: rhythms in ascorbic acid production during growth under ozone stress

    Energy Technology Data Exchange (ETDEWEB)

    Lee, E.H. (Climate Stress Laboratory, USDA, ARS, Beltsville, MD (United States))


    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.

  6. Effects and mechanism of acid rain on plant chloroplast ATP synthase. (United States)

    Sun, Jingwen; Hu, Huiqing; Li, Yueli; Wang, Lihong; Zhou, Qing; Huang, Xiaohua


    Acid rain can directly or indirectly affect plant physiological functions, especially photosynthesis. The enzyme ATP synthase is the key in photosynthetic energy conversion, and thus, it affects plant photosynthesis. To clarify the mechanism by which acid rain affects photosynthesis, we studied the effects of acid rain on plant growth, photosynthesis, chloroplast ATP synthase activity and gene expression, chloroplast ultrastructure, intracellular H(+) level, and water content of rice seedlings. Acid rain at pH 4.5 remained the chloroplast structure unchanged but increased the expression of six chloroplast ATP synthase subunits, promoted chloroplast ATP synthase activity, and increased photosynthesis and plant growth. Acid rain at pH 4.0 or less decreased leaf water content, destroyed chloroplast structure, inhibited the expression of six chloroplast ATP synthase subunits, decreased chloroplast ATP synthase activity, and reduced photosynthesis and plant growth. In conclusion, acid rain affected the chloroplast ultrastructure, chloroplast ATPase transcription and activity, and P n by changing the acidity in the cells, and thus influencing the plant growth and development. Finally, the effects of simulated acid rain on the test indices were found to be dose-dependent.

  7. Mechanical, thermal, and biodegradable properties of polylactic acid (PLA)/coir fibre biocomposites (United States)

    Dong, Y.; Ghataura, A.; Haroosh, H. J.


    Polylactic acid (PLA)/coir fibre biocomposites were fabricated using a compression moulding technique. The effects of fibre content (5-30 wt%) and fibre treatment on mechanical, thermal and biodegradable properties of biocomposites were holistically investigated via mechanical testing, scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and soil burial method to understand the applicability of manufacturing eco-efficient and sustainable "green composites".

  8. Self-assembled polyhydroxy fatty acids vesicles: a mechanism for plant cutin synthesis. (United States)

    Heredia-Guerrero, José A; Benítez, José J; Heredia, Antonio


    Despite its biological importance, the mechanism of formation of cutin, the polymeric matrix of plant cuticles, has not yet been fully clarified. Here, for the first time, we show the participation in the process of lipid vesicles formed by the self-assembly of endogenous polyhydroxy fatty acids. The accumulation and fusion of these vesicles (cutinsomes) at the outer part of epidermal cell wall is proposed as the mechanism for early cuticle formation.

  9. Structural basis of the alternating-access mechanism in a bile acid transporter (United States)

    Zhou, Xiaoming; Levin, Elena J.; Pan, Yaping; McCoy, Jason G.; Sharma, Ruchika; Kloss, Brian; Bruni, Renato; Quick, Matthias; Zhou, Ming


    Bile acids are synthesized from cholesterol in hepatocytes and secreted through the biliary tract into the small intestine, where they aid in absorption of lipids and fat-soluble vitamins. Through a process known as enterohepatic recirculation, more than 90% of secreted bile acids are then retrieved from the intestine and returned to the liver for resecretion. In humans, there are two Na+-dependent bile acid transporters involved in enterohepatic recirculation, the Na+-taurocholate co-transporting polypeptide (NTCP; also known as SLC10A1) expressed in hepatocytes, and the apical sodium-dependent bile acid transporter (ASBT; also known as SLC10A2) expressed on enterocytes in the terminal ileum. In recent years, ASBT has attracted much interest as a potential drug target for treatment of hypercholesterolaemia, because inhibition of ASBT reduces reabsorption of bile acids, thus increasing bile acid synthesis and consequently cholesterol consumption. However, a lack of three-dimensional structures of bile acid transporters hampers our ability to understand the molecular mechanisms of substrate selectivity and transport, and to interpret the wealth of existing functional data. The crystal structure of an ASBT homologue from Neisseria meningitidis (ASBTNM) in detergent was reported recently, showing the protein in an inward-open conformation bound to two Na+ and a taurocholic acid. However, the structural changes that bring bile acid and Na+ across the membrane are difficult to infer from a single structure. To understand the structural changes associated with the coupled transport of Na+ and bile acids, here we solved two structures of an ASBT homologue from Yersinia frederiksenii (ASBTYf) in a lipid environment, which reveal that a large rigid-body rotation of a substrate-binding domain gives the conserved `crossover' region, where two discontinuous helices cross each other, alternating accessibility from either side of the cell membrane. This result has implications

  10. Antimicrobial Activity of Ferulic Acid Against Cronobacter sakazakii and Possible Mechanism of Action. (United States)

    Shi, Chao; Zhang, Xiaorong; Sun, Yi; Yang, Miaochun; Song, Kaikuo; Zheng, Zhiwei; Chen, Yifei; Liu, Xin; Jia, Zhenyu; Dong, Rui; Cui, Lu; Xia, Xiaodong


    Cronobacter sakazakii is an opportunistic pathogen transmitted by food that affects mainly newborns, infants, and immune-compromised adults. In this study, the antibacterial activity of ferulic acid was tested against C. sakazakii strains. Minimum inhibitory concentration of ferulic acid against C. sakazakii strains was determined using the agar dilution method. Changes in intracellular pH, membrane potential and intracellular ATP concentration were measured to elucidate the possible antibacterial mechanism. Moreover, SYTO 9 nucleic acid staining was used to assess the effect of ferulic acid on bacterial membrane integrity. Cell morphology changes were observed under a field emission scanning electron microscope. The minimum inhibitory concentrations of ferulic acid against C. sakazakii strains ranged from 2.5 to 5.0 mg/mL. Addition of ferulic acid exerted an immediate and sustained inhibition of C. sakazakii proliferation. Ferulic acid affected the membrane integrity of C. sakazakii, as evidenced by intracellular ATP concentration decrease. Moreover, reduction of intracellular pH and cell membrane hyperpolarization were detected in C. sakazakii after exposure to ferulic acid. Reduction of green fluorescence indicated the injury of cell membrane. Electronic microscopy confirmed that cell membrane of C. sakazakii was damaged by ferulic acid. Our results demonstrate that ferulic acid has moderate antimicrobial activity against C. sakazakii. It exerts its antimicrobial action partly through causing cell membrane dysfunction and changes in cellular morphology. Considering its antimicrobial properties, together with its well-known nutritional functions, ferulic acid has potential to be developed as a supplement in infant formula or other foods to control C. sakazakii.

  11. Cinnamic Acid and Its Derivatives: Mechanisms for Prevention and Management of Diabetes and Its Complications (United States)

    Adisakwattana, Sirichai


    With recent insight into the development of dietary supplements and functional foods, search of effective phytochemical compounds and their mechanisms involved in prevention and management of diabetes and its complications are now being assessed. Cinnamic acid and its derivatives occur naturally in high levels of plant-based foods. Among various biological activities, cinnamic acid and its derivatives are associated with a beneficial influence on diabetes and its complications. The aim of the review is to summarize the potential mechanisms of these compounds for prevention and management of diabetes and its complications. Based on several in vitro studies and animal models, cinnamic acid and its derivatives act on different mechanism of actions, including stimulation of insulin secretion, improvement of pancreatic β-cell functionality, inhibition of hepatic gluconeogenesis, enhanced glucose uptake, increased insulin signaling pathway, delay of carbohydrate digestion and glucose absorption, and inhibition of protein glycation and insulin fibrillation. However, due to the limited intestinal absorption being a result of low bioavailability of cinnamic acid and its derivatives, current improvement efforts with entrapping into solid and liquid particles are highlighted. Further human clinical studies are needed to clarify the effects of cinnamic acid and its derivatives in diabetic patients. PMID:28230764

  12. Structure-dependent effects of pyridine derivatives on mechanisms of intestinal fatty acid uptake: regulation of nicotinic acid receptor and fatty acid transporter expression. (United States)

    Riedel, Annett; Lang, Roman; Rohm, Barbara; Rubach, Malte; Hofmann, Thomas; Somoza, Veronika


    Pyridines are widely distributed in foods. Nicotinic acid (NA), a carboxylated pyridine derivative, inhibits lipolysis in adipocytes by activation of the orphan NA receptor (HM74A) and is applied to treat hyperlipidemia. However, knowledge on the impact of pyridine derivatives on intestinal lipid metabolism is scarce. This study was performed to identify the structural determinants of pyridines for their effects on fatty acid uptake in enterocyte-like Caco-2 cells and to elucidate the mechanisms of action. The impact of 17 pyridine derivatives on fatty acid uptake was tested. Multiple regression analysis revealed the presence of a methyl group to be the structural determinant at 0.1 mM, whereas at 1 mM, the presence of a carboxylic group and the N-methylation presented further structural characteristics to affect the fatty acid uptake. NA, showing a stimulating effect on FA uptake, and N-methyl-4-phenylpyridinium (MPP), inhibiting FA uptake, were selected for mechanistic studies. Gene expression of the fatty acid transporters CD36, FATP2 and FATP4, and the lipid metabolism regulating transcription factors peroxisome proliferator-activated receptor (PPAR) α and PPARγ was up-regulated upon NA treatment. Caco-2 cells were demonstrated to express the low-affinity NA receptor HM74 of which the gene expression was up-regulated upon NA treatment. We hypothesize that the NA-induced fatty acid uptake might result from NA receptor activation and related intracellular signaling cascades. In contrast, MPP increased transepithelial electrical resistance. We therefore conclude that NA and MPP, both sharing the pyridine motif core, exhibit their contrary effects on intestinal FA uptake by activation of different mechanisms.

  13. Branched-Chain Amino Acids Are Required for the Survival and Virulence of Actinobacillus pleuropneumoniae in Swine▿


    Subashchandrabose, Sargurunathan; LeVeque, Rhiannon M.; Wagner, Trevor K.; Kirkwood, Roy N; Kiupel, Matti; Mulks, Martha H.


    In Actinobacillus pleuropneumoniae, which causes porcine pleuropneumonia, ilvI was identified as an in vivo-induced (ivi) gene and encodes the enzyme acetohydroxyacid synthase (AHAS) required for branched-chain amino acid (BCAA) biosynthesis. ilvI and 7 of 32 additional ivi promoters were upregulated in vitro when grown in chemically defined medium (CDM) lacking BCAA. Based on these observations, we hypothesized that BCAA would be found at limiting concentrations in pulmonary secretions and t...

  14. Effect of steam and lactic acid treatments on the survival of Salmonella Enteritidis and Campylobacter jejuni inoculated on chicken skin. (United States)

    Chaine, Aline; Arnaud, Elodie; Kondjoyan, Alain; Collignan, Antoine; Sarter, Samira


    Campylobacteriosis and salmonellosis are the most frequently reported zoonotic infectious diseases. The present work evaluated the effectiveness of steam treatment at 100 °C for 8s, a 5% lactic acid treatment for 1 min and their combination for inactivating Salmonella Enteritidis and Campylobacter jejuni inoculated on chicken skin. The impact of each treatment on the total aerobic mesophilic bacteria and the effect of rinsing after contact with lactic acid were also evaluated. Residual bacteria were counted immediately after treatment or after seven days of storage at 4 °C. Results demonstrated the immediate efficiency of the steam and the combined treatments with reductions of approximately 6 and 5 log cfu/cm2 respectively for S. Enteritidis and C. jejuni. They also showed significant reductions (equal to or >3.2 log cfu/cm2) in the total aerobic mesophilic plate count. Lactic acid had a persistent effect on pathogen growth during storage which was significantly higher when the skin was not rinsed, reaching reductions of 3.8 log cfu/cm2 for both S. Enteritidis and C. jejuni. Only the combined treatments significantly reduced the recovery of the total aerobic mesophilic bacteria during storage. The significant reductions in both pathogens and total aerobic mesophilic bacteria on treated chicken skins are possible ways to improve the safety and shelf life of the product although high levels of indigenous non-pathogenic bacteria may be beneficial due to their protective effect against potential re-contamination of chicken skin.

  15. Physical and mechanical properties of extruded poly(lactic acid)-based Paulownia elongata biocomposites (United States)

    Paulownia wood flour (PWF), a byproduct of milling lumber, was tested as bio-filler with polylactic acid (PLA). Paulownia wood (PW) shavings were milled and separated into particle fractions and then blended with PLA with a single screw extruder. Mechanical and thermal properties were tested. Dif...


    Institute of Scientific and Technical Information of China (English)

    WANGYu-Feng; CHENGJiun; CHENGZhi-Ping


    The etTects of 23 amino acids on the membrane potential of toad ( Bufo bufo gargarizans ) oocytes and the mechanisms involved were investigated in vitro by means of microelectrode. At a concentration of I mmol/L-alanine, leucine and lyaine induced signfiant depolarization, and tryptophan provoked a marked hyperpolarization during

  17. Mechanisms underlying the anti-aging and anti-tumor effects of lithocholic bile acid. (United States)

    Arlia-Ciommo, Anthony; Piano, Amanda; Svistkova, Veronika; Mohtashami, Sadaf; Titorenko, Vladimir I


    Bile acids are cholesterol-derived bioactive lipids that play essential roles in the maintenance of a heathy lifespan. These amphipathic molecules with detergent-like properties display numerous beneficial effects on various longevity- and healthspan-promoting processes in evolutionarily distant organisms. Recent studies revealed that lithocholic bile acid not only causes a considerable lifespan extension in yeast, but also exhibits a substantial cytotoxic effect in cultured cancer cells derived from different tissues and organisms. The molecular and cellular mechanisms underlying the robust anti-aging and anti-tumor effects of lithocholic acid have emerged. This review summarizes the current knowledge of these mechanisms, outlines the most important unanswered questions and suggests directions for future research.

  18. CEC mechanism in electrochemical oxidation of nitrocatechol-boric acid complexes

    Energy Technology Data Exchange (ETDEWEB)

    Rafiee, Mohammad, E-mail: [Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Zanjan (Iran, Islamic Republic of); Nematollahi, Davood; Salehzadeh, Hamid [Faculty of Chemistry, Bu-Ali Sina University, Hamedan (Iran, Islamic Republic of)


    Graphical abstract: Display Omitted Highlights: > Nitrochetechol and its anionic form undergo complex reaction with boric acid. > The electron transfer of complex is coupled with both proceeding and following chemical reactions. > Electrochemical behavior of complex is resolved by diagnostic criteria and digital simulation. - Abstract: The electrochemical behavior of nitrocatechols-boric acid complexes in aqueous solution has been studied using cyclic voltammetry. The results indicate that nitrocatechol-boric acid complex derivatives are involved in the CEC mechanism. In this work, the impact of empirical parameters on the shape of the voltammograms is examined based on a CEC mechanism. In addition, homogeneous rate constants of both the preceding and the following reactions were estimated by comparing the experimental cyclic voltammograms with the digitally simulated results. The calculated dissociation constants for the complexes (K{sub d}) and for ring cleavage of nitroquinone (k{sub f2}) were found to vary in the following order: 4-nitrocatechol > 3-methylnitrocatechol > 3-metoxynitrocatechol.

  19. Theoretical Structures of Triflic Acid-Water Clusters and the Molecular Mechanism of Proton Dissociation

    Energy Technology Data Exchange (ETDEWEB)

    Paddison, S.J.; Pratt, L.R.; Zawodzinski, T.A.


    Structural and energetic information required for recently proposed quasi-chemical theories of solution chemistry have been obtained for clusters of water with triflic acid, CF{sub 3}SO{sub 3}H(H{sub 2}O){sub n} for n=1-6. Quantum mechanical calculations on the clusters indicate that the acid proton does not dissociate with n=1 or 2 hydrating water molecules, but does dissociate for n>=3 water molecule partners. The computed minimum energy structures indicate that both ''Eigen'' (H{sub 9}O{sub 4}{sup +}) (n=3,4,6) and ''Zundel'' (H{sub 5}O{sub 2}{sup +}) (n=5) structures are likely to play a role in the molecular mechanism of acid dissociation in Nafion{reg_sign}.

  20. Elastoviscous Transitions of Articular Cartilage Reveal a Mechanism of Synergy between Lubricin and Hyaluronic Acid.

    Directory of Open Access Journals (Sweden)

    Edward D Bonnevie

    Full Text Available When lubricated by synovial fluid, articular cartilage provides some of the lowest friction coefficients found in nature. While it is known that macromolecular constituents of synovial fluid provide it with its lubricating ability, it is not fully understood how two of the main molecules, lubricin and hyaluronic acid, lubricate and interact with one another. Here, we develop a novel framework for cartilage lubrication based on the elastoviscous transition to show that lubricin and hyaluronic acid lubricate by distinct mechanisms. Such analysis revealed nonspecific interactions between these molecules in which lubricin acts to concentrate hyaluronic acid near the tissue surface and promotes a transition to a low friction regime consistent with the theory of viscous boundary lubrication. Understanding the mechanics of synovial fluid not only provides insight into the progression of diseases such as arthritis, but also may be applicable to the development of new biomimetic lubricants.

  1. Elastoviscous Transitions of Articular Cartilage Reveal a Mechanism of Synergy between Lubricin and Hyaluronic Acid. (United States)

    Bonnevie, Edward D; Galesso, Devis; Secchieri, Cynthia; Cohen, Itai; Bonassar, Lawrence J


    When lubricated by synovial fluid, articular cartilage provides some of the lowest friction coefficients found in nature. While it is known that macromolecular constituents of synovial fluid provide it with its lubricating ability, it is not fully understood how two of the main molecules, lubricin and hyaluronic acid, lubricate and interact with one another. Here, we develop a novel framework for cartilage lubrication based on the elastoviscous transition to show that lubricin and hyaluronic acid lubricate by distinct mechanisms. Such analysis revealed nonspecific interactions between these molecules in which lubricin acts to concentrate hyaluronic acid near the tissue surface and promotes a transition to a low friction regime consistent with the theory of viscous boundary lubrication. Understanding the mechanics of synovial fluid not only provides insight into the progression of diseases such as arthritis, but also may be applicable to the development of new biomimetic lubricants.

  2. Survival of Escherichia coli O157:H7 in set yogurt as influenced by the production of an exopolysaccharide, colanic acid. (United States)

    Lee, Shiao Mei; Chen, Jinru


    Previous studies conducted in our laboratory revealed that Escherichia coli O157:H7 cells capable of producing colanic acid (CA), the acidic polysaccharide of mucoid slime, had increased tolerance to sublethal heat and the extreme pH of microbiological culture media. This study was undertaken to determine the effect of CA on the fate of E. coli O157:H7 during the processing and storage of an acid food: yogurt. Pasteurized and homogenized whole milk was inoculated with a wild-type E. coli O157:H7, its CA-deficient mutant, or a mixture (1:1) of the two strains. Set yogurt was processed from the contaminated milk and stored at 4 degrees and 15 degrees C for 3 weeks. Samples of milk and yogurt were withdrawn during processing and storage and analyzed for total plate counts and populations of E. coli O157:H7 and starter cultures. The results showed that E. coli O157:H7 survived longer in yogurt stored at 15 degrees C than at 4 degrees C. Cells of E. coli O157:H7 deficient in CA production died off more rapidly than those of the parent strain. This suggests that CA plays a role in protecting cells of E. coli O157:H7 from stress during the processing and storage of set yogurt.

  3. Atmospheric sulphuric acid and aerosol formation: implications from atmospheric measurements for nucleation and early growth mechanisms

    Directory of Open Access Journals (Sweden)

    S.-L. Sihto


    Full Text Available We have investigated the formation and early growth of atmospheric secondary aerosol particles building on atmospheric measurements. The measurements were part of the QUEST 2 campaign which took place in spring 2003 in Hyytiälä (Finland. During the campaign numerous aerosol particle formation events occurred of which 15 were accompanied by gaseous sulphuric acid measurements. Our detailed analysis of these 15 events is focussed on nucleation and early growth (to a diameter of 3 nm of fresh particles. It revealed that new particle formation seems to be a function of the gaseous sulphuric acid concentration to the power from one to two when the time delay between the sulphuric acid and particle number concentration is taken into account. From the time delay the growth rates of freshly nucleated particles from 1 nm to 3 nm were determined. The mean growth rate was 1.2 nm/h and it was clearly correlated with the gaseous sulphuric acid concentration. We tested two nucleation mechanisms – recently proposed cluster activation and kinetic type nucleation – as possible candidates to explain the observed dependences, and determined experimental nucleation coefficients. We found that some events are dominated by the activation mechanism and some by the kinetic mechanism. Inferred coefficients for the two nucleation mechanisms are the same order of magnitude as chemical reaction coefficients in the gas phase and they correlate with the product of gaseous sulphuric acid and ammonia concentrations. This indicates that besides gaseous sulphuric acid also ammonia has a role in nucleation.

  4. Electronic properties of amino acid side chains: quantum mechanics calculation of substituent effects

    Directory of Open Access Journals (Sweden)

    Dwyer Donard S


    Full Text Available Abstract Background Electronic properties of amino acid side chains such as inductive and field effects have not been characterized in any detail. Quantum mechanics (QM calculations and fundamental equations that account for substituent effects may provide insight into these important properties. PM3 analysis of electron distribution and polarizability was used to derive quantitative scales that describe steric factors, inductive effects, resonance effects, and field effects of amino acid side chains. Results These studies revealed that: (1 different semiempirical QM methods yield similar results for the electronic effects of side chain groups, (2 polarizability, which reflects molecular deformability, represents steric factors in electronic terms, and (3 inductive effects contribute to the propensity of an amino acid for α-helices. Conclusion The data provide initial characterization of the substituent effects of amino acid side chains and suggest that these properties affect electron density along the peptide backbone.

  5. Study on the preparation and formation mechanism of barium sulphate nanoparticles modified by different organic acids

    Indian Academy of Sciences (India)

    Yuhua Shen; Chuanhao Li; Xuemei Zhu; Anjian Xie; Lingguang Qiu; Jinmiao Zhu


    This paper reports a simple method to prepare barium sulphate nanoparticles by use of tetradecanoic acid, hexadecanoic acid and stearic acid as modifier. The barium sulphate nanoparticles obtained are characterized by using Fourier transform infra-red spectroscopy (FT-IR), powder X-ray diffraction (XRD), transmission electron microscopy (TEM), dynamic laser light scatter (DLLS) and thermogravimetric analysis (TGA), respectively. The results show that the BaSO4 particles are all spherical and in the nano-scale. Our method has a better dispersion and controllable diameter dependent on the length of the chain of organic acid and the pH value of the system. A possible mechanism is also discussed.

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

    Directory of Open Access Journals (Sweden)

    Alfonso eGil-Sánchez


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

  7. Modulation of membrane currents and mechanical activity by niflumic acid in rat vascular smooth muscle. (United States)

    Kirkup, A J; Edwards, G; Green, M E; Miller, M; Walker, S D; Weston, A H


    The effects of niflumic acid on whole-cell membrane currents and mechanical activity were examined in the rat portal vein. In freshly dispersed portal vein cells clamped at -60 mV in caesium (Cs+)-containing solutions, niflumic acid (1-100 microM) inhibited calcium (Ca2+)-activated chloride currents (IC1(Ca)) induced by caffeine (10 mM) and by noradrenaline (10 microM). In a potassium (K+)-containing solution and at a holding potential of - 10 mV, niflumic acid (10-100 microM) induced an outward K+ current (IK(ATP)) which was sensitive to glibenclamide (10-30 microM). At concentrations < 30 microM and at a holding potential of -2 mV, niflumic acid had no effect on the magnitude of the caffeine- or noradrenaline-stimulated current (IBK(Ca)) carried by the large conductance, Ca(2+)-sensitive K+ channel (BKCa). However, at a concentration of 100 microM, niflumic acid significantly inhibited IBK(Ca)) evoked by caffeine (10 mM) but not by NS1619 (1-(2'-hydroxy-5'-trifluoromethylphenyl)-5-trifluoromethyl-2(3 H) benzimidazolone; 20 microM). In Cs(+)-containing solutions, niflumic acid (10-100 microM) did not inhibit voltage-sensitive Ca2+ currents. In intact portal veins, niflumic acid (1-300 microM) inhibited spontaneous mechanical activity, an action which was partially antagonised by glibenclamide (1-10 microM), and contractions produced by noradrenaline (10 microM), an effect which was glibenclamide-insensitive. It is concluded that inhibition of ICl(Ca) and stimulation of IK(ATP) both contribute to the mechano-inhibitory actions of niflumic acid in the rat portal vein.

  8. The mechanism of the dehydration of alcohols and the hydration of alkenes in acid solution (United States)

    Vinnik, M. I.; Obraztsov, P. A.


    Kinetic data for the hydration of unsaturated compounds, the dehydration of alcohols, and the isotope exchange of the oxygen atom in alcohols and aqueous solutions of strong acids are analysed to establish the detailed mechanisms of these reactions. The catalytic action of the acid is caused not only by its ability to protonate the reactant but also by the possibility of the formation of reactive complexes of the reactant with the acid hydrates or the molecules of the undissociated acids. Equations are presented whereby the influence of the ionising capacity of the medium on the effective rate constants for the reactions indicated can be taken into account quantitatively. The question of the involvement of carbonium ions as reactive intermediates in reactions involving the dehydration of alcohols, the hydration of unsaturated compounds, and the isotope exchange of the oxygen atom in alcohols is examined. Complexes of the reactant with a solvated proton, the acid molecules, and the acid hydrates are the intermediates in these reactions. The relative contributions of the complexes to the effective rate constant depend on the acid concentration in the aqueous solution. The bibliography includes 65 references

  9. Could gut microbiota serve as prognostic biomarker associated with colorectal cancer patients' survival? A pilot study on relevant mechanism (United States)

    Wei, Zhiliang; Cao, Shougen; Liu, Shanglong; Yao, Zengwu; Sun, Teng; Li, Yi; Li, Jiante; Zhang, Dongfeng; Zhou, Yanbing


    Evidences have shown that dysbiosis could promote the progression of colorectal cancer (CRC). However, the association of dysbiosis and prognosis of CRC is barely investigated. Therefore, we used 16S rRNA gene sequencing approach to determine differences in microbiota among tumor tissues of different prognosis and found that Fusobacterium nucleatum and Bacteroides fragilis were more abundant in worse prognosis groups, while Faecalibacterium prausnitzii displayed higher abundance in survival group. To further explore the prognostic value of the found bacteria, Kaplan–Meier and Cox proportional regression analyses were used and the results exhibited that high abundance of F. nucleatum and B. fragilis were independent indicators of poor patient's survival. Besides, the expression of major inflammatory mediator were analyzed using PCR and western blot methods, and it turned out that high abundance of F. nucleatum was associated with increased expression of TNF-α, β-catenin and NF-κB, while COX-2, MMP-9 and NF-κB were positively related with high B. fragilis level, and high level of F. prausnitzii showed lower expression of β-catenin, MMP-9 and NF-κB. Moreover, immunohistochemical analysis indicated that KRAS and BRAF expression were prominent in F. nucleatum and B. fragilis high abundance group, while MLH1 showed lower expression. In conclusion, F. nucleatum, B. fragilis and F. prausnitzii can be identified as useful prognostic biomarkers for CRC, and dysbiosis might worsen the patients' prognosis by up-regulating gut inflammation level. PMID:27323816

  10. Molecular approaches unravel the mechanism of acid soil tolerance in plants

    Institute of Scientific and Technical Information of China (English)

    Miao; Bian; Meixue; Zhou; Dongfa; Sun; Chengdao; Li


    Acid soil is a worldwide problem to plant production. Acid toxicity is mainly caused by a lack of essential nutrients in the soil and excessive toxic metals in the plant root zone. Of the toxic metals, aluminum(Al) is the most prevalent and most toxic. Plant species have evolved to variable levels of tolerance to aluminum enabling breeding of high Al-tolerant cultivars.Physiological and molecular approaches have revealed some mechanisms of Al toxicity in higher plants. Mechanisms of plant tolerance to Al stress include: 1) exclusion of Al from the root tips, and 2) absorbance, but tolerance of Al in root cells. Organic acid exudation to chelate Al is a feature shared by many higher plants. The future challenge for Al tolerance studies is the identification of novel tolerance mechanisms and the combination of different mechanisms to achieve higher tolerance. Molecular approaches have led to significant progress in explaining mechanisms and detection of genes responsible for Al tolerance.Gene-specific molecular markers offer better options for marker-assisted selection in breeding programs than linked marker strategies. This paper mainly focuses on recent progress in the use of molecular approaches in Al tolerance research.

  11. Aristoxazole analogues. Conversion of 8-nitro-1-naphthoic acid to 2-methylnaphtho[1,2-d]oxazole-9-carboxylic acid: comments on the chemical mechanism of formation of DNA adducts by the aristolochic acids. (United States)

    Priestap, Horacio A; Barbieri, Manuel A; Johnson, Francis


    2-Methylnaphtho[1,2-d]oxazole-9-carboxylic acid was obtained by reduction of 8-nitro-1-naphthoic acid with zinc-acetic acid. This naphthoxazole is a condensation product between an 8-nitro-1-naphthoic acid reduction intermediate and acetic acid and is a lower homologue of aristoxazole, a similar condensation product of aristolochic acid I with acetic acid that was previously reported. Both oxazoles are believed to arise via a common nitrenium/carbocation ion mechanism that is likely related to that which leads to aristolochic acid-DNA-adducts.

  12. Effect of milk fermentation by kefir grains and selected single strains of lactic acid bacteria on the survival of Mycobacterium bovis BCG. (United States)

    Macuamule, C L S; Wiid, I J; van Helden, P D; Tanner, M; Witthuhn, R C


    Mycobacterium bovis that causes Bovine tuberculosis (BTB) can be transmitted to humans thought consumption of raw and raw fermented milk products from diseased animals. Lactic acid bacteria (LAB) used in popular traditional milk products in Africa produce anti-microbial compounds that inhibit some pathogenic and spoilage bacteria. M. bovis BCG is an attenuated non-pathogenic vaccine strain of M. bovis and the aim of the study was to determine the effect of the fermentation process on the survival of M. bovis BCG in milk. M. bovis BCG at concentrations of 6 log CFU/ml was added to products of kefir fermentation. The survival of M. bovis BCG was monitored at 12-h intervals for 72 h by enumerating viable cells on Middlebrook 7H10 agar plates enriched with 2% BD BACTEC PANTA™. M. bovis BCG was increasingly reduced in sterile kefir that was fermented for a period of 24h and longer. In the milk fermented with kefir grains, Lactobacillus paracasei subsp. paracasei or Lactobacillus casei, the viability of M. bovis BCG was reduced by 0.4 logs after 24h and by 2 logs after 48 h of fermentation. No viable M. bovis BCG was detected after 60 h of fermentation. Results from this study show that long term fermentation under certain conditions may have the potential to inactivate M. bovis BCG present in the milk. However, to ensure safety of fermented milk in Africa, fermentation should be combined with other hurdle technologies such as boiling and milk pasteurisation.


    Institute of Scientific and Technical Information of China (English)

    ZHANGHui; SHAOTong; 等


    The adsorption isotherms of glycine,alanine and oxidized glutathion on strong acid cation and strong base anion exchange resins from aqueous solutions were measured and the superequivalent adsorptions of glycine and alanine observed.The infrared spectra of glycine adsorbed on the cation and the anion exchange resins,001×7 and 201×7,were measured.From these results,it is concluded that the amino acid adsorption on the ion exchange resin proceeds not only through ion exchange and proton transfer mechanisms,but also through aminecarboxylate interaction between the adsorbed amino acid molecules,and the formation of second layer of amino acid molecules is the mechanism of superequivalent adsorption of amino acid,the carboxylate or amine groups of the first layer of amino acid molecules on the ion exchange resin act as the exchange sites for the second layer of amino acid molecules.

  14. Effects of mechanical stress or abscisic acid on growth, water status and leaf abscisic acid content of eggplant seedlings (United States)

    Latimer, J. G.; Mitchell, C. A.


    Container-grown eggplant (Solanum melongena L. var esculentum Nees. 'Burpee's Black Beauty') seedlings were conditioned with brief, periodic mechanical stress or abscisic acid (ABA) in a greenhouse prior to outdoor exposure. Mechanical stress consisted of seismic (shaking) or thigmic (stem flexing) treatment. Exogenous ABA (10(-3) or 10(-4)M) was applied as a soil drench 3 days prior to outdoor transfer. During conditioning, only thigmic stress reduced stem elongation and only 10(-3) M ABA reduced relative growth rate (RGR). Both conditioning treatments increased leaf specific chlorophyll content, but mechanical stress did not affect leaf ABA content. Outdoor exposure of unconditioned eggplant seedlings decreased RGR and leaf-specific chlorophyll content, but tended to increase leaf ABA content relative to that of plants maintained in the greenhouse. Conditioning did not affect RGR of plants subsequently transferred outdoors, but did reduce stem growth. Seismic stress applied in the greenhouse reduced dry weight gain by plants subsequently transferred outdoors. Mechanical stress treatments increased leaf water potential by 18-25% relative to that of untreated plants.

  15. Docosahexaenoic acid signaling modulates cell survival in experimental ischemic stroke penumbra and initiates long-term repair in young and aged rats.

    Directory of Open Access Journals (Sweden)

    Tiffany N Eady

    Full Text Available BACKGROUND: Docosahexaenoic acid, a major omega-3 essential fatty acid family member, improves behavioral deficit and reduces infarct volume and edema after experimental focal cerebral ischemia. We hypothesize that DHA elicits neuroprotection by inducing AKT/p70S6K phosphorylation, which in turn leads to cell survival and protects against ischemic stroke in young and aged rats. METHODS AND RESULTS: Rats underwent 2 h of middle cerebral artery occlusion (MCAo. DHA, neuroprotectin D1 (NPD1 or vehicle (saline was administered 3 h after onset of stroke. Neurological function was evaluated on days 1, 2, 3, and 7. DHA treatment improved functional recovery and reduced cortical, subcortical and total infarct volumes 7 days after stroke. DHA also reduced microglia infiltration and increased the number of astrocytes and neurons when compared to vehicle on days 1 and 7. Increases in p473 AKT and p308 AKT phosphorylation/activation were observed in animals treated with DHA 4 h after MCAo. Activation of other members of the AKT signaling pathway were also observed in DHA treated animals including increases in pS6 at 4 h and pGSK at 24 h. DHA or NPD1 remarkably reduced total and cortical infarct in aged rats. Moreover, we show that in young and aged rats DHA treatment after MCAo potentiates NPD1 biosynthesis. The phosphorylation of p308 AKT or pGSK was not different between groups in aged rats. However, pS6 expression was increased with DHA or NPD1 treatment when compared to vehicle. CONCLUSIONS: We suggest that DHA induces cell survival, modulates the neuroinflammatory response and triggers long term restoration of synaptic circuits. Both DHA and NPD1 elicited remarkable protection in aged animals. Accordingly, activation of DHA signaling might provide benefits in the management of ischemic stroke both acutely as well as long term to limit ensuing disabilities.

  16. Investigation of mechanism of fade of gastrin-stimulated gastric acid secretion in the cat. (United States)

    Hirst, B H


    1. In conscious cats prepared with gastric fistulae gastric acid secretion in response to pentagastrin was found to reach a maximum after 45 min of stimulation, and to fade thereafter. Over the period 45-150 min of stimulation the fade was 5.4-7.8% of the maximum response per 15 min. 2. Once the response to pentagastrin had declined, acid secretion could not be restored by doubling the dose of pentagastrin, although an equisecretory dose of histamine could restore it. 3. Low doses of histamine were additive to the pentagastrin acid secretory response; they tended to prolong the peak response, but did not alter the subsequent fade of acid secretion. The histamine H1-receptor antagonist mepyramine did not affect maximal acid secretion or the fade of the pentagastrin response. 4. The beta-adrenoreceptor antagonist propranolol increased the secretory response to pentagastrin, whilst the alpha-adrenoreceptor antagonist phentolamine was without effect. Neither agent altered the fade of the pentagastrin response. Isoprenaline tended to inhibit pentagastrin-stimulated acid secretion and increase the rate of fade of the response. 5. The 5-hydroxytryptamine (5-HT) receptor antagonist methylsergide slightly enhanced the acid secretory response to pentagastrin, but did not alter the fade of the response. A low dose of 5-HT did not alter pentagastrin-stimulated acid secretion, whilst a higher dose of 5-HT inhibited it. 6. Tetra-, penta- and pentadecagastrin demonstrated tachyphylaxis, i.e. progressively reduced responses upon repeated stimulation, whilst histamine did not. A low dose of histamine did not prevent tachyphylaxis of the pentagastrin response. 7. It is concluded that fade of pentagastrin-stimulated acid secretion in the conscious cat cannot be satisfactorily explained by the failure of the acid secretory mechanism, depletion of histamine, release of 5-HT, or activation of histamine H1-, alpha- or beta-adreno-, or 5-HT-receptors. The similar characteristics of fade

  17. Passivation Mechanism of 316L Stainless Steel in Oxidizing Acid Solution

    Institute of Scientific and Technical Information of China (English)


    The compositions and the chemical valence states of elements of 316L stainless steel passive film formed in the oxidizing acid solution were studied by X-ray Photoelectron Spectroscopic (XPS) analysis. The electrochemical polarization curve was measured. The passivation process in the oxidizing acid solution was studied by AC impedance technology. The results indicated that the stable compounds layer was formed on the surface of the sample and the adsorption was the main step in the nitrite solution during passivation process. The catalysis passivation mechanism was put forward according to the experimental results. During passivation process, the water molecule was adsorbed on the surface of the sample at first in the oxidizing acid solution. The oxidizer in the solution played a role as catalyst. The oxide and hydroxide, which could be changed each other and finally formed stable passive film, were generated from adsorbing intermediate under the catalytic action. The mathematical models for predicting the steady polarization curve and the AC impedance spectra at certain conditions have been obtained. The passivation mechanism of 316L stainless steel in the oxidizing acid solution can be interpreted by the catalysis passivation mechanism.

  18. Solid lipid nanoparticles as nucleic acid delivery system: properties and molecular mechanisms. (United States)

    de Jesus, Marcelo B; Zuhorn, Inge S


    Solid lipid nanoparticles (SLNs) have been proposed in the 1990s as appropriate drug delivery systems, and ever since they have been applied in a wide variety of cosmetic and pharmaceutical applications. In addition, SLNs are considered suitable alternatives as carriers in gene delivery. Although important advances have been made in this particular field, fundamental knowledge of the underlying mechanisms of SLN-mediated gene delivery is conspicuously lacking, an imperative requirement in efforts aimed at further improving their efficiency. Here, we address recent advances in the use of SLNs as platform for delivery of nucleic acids as therapeutic agents. In addition, we will discuss available technology for conveniently producing SLNs. In particular, we will focus on underlying molecular mechanisms by which SLNs and nucleic acids assemble into complexes and how the nucleic acid cargo may be released intracellularly. In discussing underlying mechanisms, we will, when appropriate, refer to analogous studies carried out with systems based on cationic lipids and polymers, that have proven useful in the assessment of structure-function relationships. Finally, we will give suggestions for improving SLN-based gene delivery systems, by pointing to alternative methods for SLNplex assembly, focusing on the realization of a sustained nucleic acid release.

  19. Sprouty2 and -4 hypomorphism promotes neuronal survival and astrocytosis in a mouse model of kainic acid induced neuronal damage. (United States)

    Thongrong, Sitthisak; Hausott, Barbara; Marvaldi, Letizia; Agostinho, Alexandra S; Zangrandi, Luca; Burtscher, Johannes; Fogli, Barbara; Schwarzer, Christoph; Klimaschewski, Lars


    Sprouty (Spry) proteins play a key role as negative feedback inhibitors of the Ras/Raf/MAPK/ERK pathway downstream of various receptor tyrosine kinases. Among the four Sprouty isoforms, Spry2 and Spry4 are expressed in the hippocampus. In this study, possible effects of Spry2 and Spry4 hypomorphism on neurodegeneration and seizure thresholds in a mouse model of epileptogenesis was analyzed. The Spry2/4 hypomorphs exhibited stronger ERK activation which was limited to the CA3 pyramidal cell layer and to the hilar region. The seizure threshold of Spry2/4(+/-) mice was significantly reduced at naive state but no difference to wildtype mice was observed 1 month following KA treatment. Histomorphological analysis revealed that dentate granule cell dispersion (GCD) was diminished in Spry2/4(+/-) mice in the subchronic phase after KA injection. Neuronal degeneration was reduced in CA1 and CA3 principal neuron layers as well as in scattered neurons of the contralateral CA1 and hilar regions. Moreover, Spry2/4 reduction resulted in enhanced survival of somatostatin and neuropeptide Y expressing interneurons. GFAP staining intensity and number of reactive astrocytes markedly increased in lesioned areas of Spry2/4(+/-) mice as compared with wildtype mice. Taken together, although the seizure threshold is reduced in naive Spry2/4(+/-) mice, neurodegeneration and GCD is mitigated following KA induced hippocampal lesions, identifying Spry proteins as possible pharmacological targets in brain injuries resulting in neurodegeneration. The present data are consistent with the established functions of the ERK pathway in astrocyte proliferation as well as protection from neuronal cell death and suggest a novel role of Spry proteins in the migration of differentiated neurons.

  20. Mechanisms of all-trans retinoic acid-induced differentiation of acute promyelocytic leukemia cells

    Indian Academy of Sciences (India)

    Ji-Wang Zhang; Jian Gu; Zhen-Yi Wang; Sai-Juan Chen; Zhu Chen


    Retinoic acids (RA) play a key role in myeloid differentiation through their agonistic nuclear receptors (RAR/RXR) to modulate the expression of target genes. In acute promyelocytic leukemia (APL) cells with rearrangement of retinoic acid receptor (RAR) (including: PML-RAR, PLZF-RAR, NPM-RAR, NuMA-RAR or STAT5b-RAR) as a result of chromosomal translocations, the RA signal pathway is disrupted and myeloid differentiation is arrested at the promyelocytic stage. Pharmacologic dosage of all-trans retinoic acid (ATRA) directly modulates PML-RAR and its interaction with the nuclear receptor co-repressor complex, which restores the wild-type RAR/RXR regulatory pathway and induces the transcriptional expression of downstream genes. Analysing gene expression profiles in APL cells before and after ATRA treatment represents a useful approach to identify genes whose functions are involved in this new cancer treatment. A chronologically well coordinated modulation of ATRA-regulated genes has thus been revealed which seems to constitute a balanced functional network underlying decreased cellular proliferation, initiation and progression of maturation, and maintenance of cell survival before terminal differentiation.

  1. Examination of 12-lipoxygenase (12-LOX) as a therapeutic target in non-small cell lung cancer (NSCLC): Mechanisms controlling survival and induction of apoptosis following selective inhibition

    LENUS (Irish Health Repository)

    Cathcart, Mary Clare


    Background: Platelet-type 12-LOX is an arachidonic acid metabolising enzyme resulting in the formation of 12(S)-HETE, which stimulates tumour cell adhesion, invasion and metastasis. This study aimed to examine the expression profile and role of this enzyme in NSCLC, and determine if it is a potential target for intervention. Methods: A panel of retrospective resected lung tumours was stained for 12-LOX expression by IHC. Levels of the 12-LOX metabolite, 12(S)-HETE, were examined in 50 NSCLC serum samples, and correlated with serum VEGF. A panel of NSCLC cell lines were treated with baicalein (10 uM), a selective inhibitor of 12-LOX, or 12(S)-HETE (100 ng\\/ml) and cell survival\\/proliferation examined by BrdU. Apoptosis following 12-LOX inhibition was examined by HCS and validated by FACS and DNA laddering. The effect of 12-LOX inhibition on NSCLC tumour growth and survival was examined in-vivo using an athymic nude mouse model. Gene alterations following 12-LOX inhibition in NSCLC cell lines were assessed by qPCR arrays and validated by RT-PCR. Transient transfection methods were used to examine the effects of 12-LOX overexpression in NSCLC cells. Results: 12-LOX expression was observed to a varying degree in human lung cancers of varying histological subtypes. 12(S)-HETE levels were correlated (p<0.05) with those of VEGF. Baicalein inhibited proliferation\\/survival in all cell lines, while 12(S)-HETE increased proliferation. 12-LOX inhibition increased apoptosis, indicated by a reduction in f-actin content and mitochondrial mass potential. Treatment with baicalein significantly reduced the growth of NSCLC tumours and increased overall survival in athymic nude mice. qPCR array data implicated a number of apoptosis\\/angiogenesis genes regulating these effects, including bcl-2, VEGF, integrin A2 and A4. 12-LOX overexpression resulted in an increase in VEGF secretion, confirming qPCR observations. Conclusions: 12-LOX is a survival factor\\/potential target in

  2. Mechanism of cAMP-induced H+ -efflux of Dictyostelium cells: a role for fatty acids

    Indian Academy of Sciences (India)

    H Flaadt; R Schaloske; D Malchow


    Aggregating Dictyostelium cells release protons when stimulated with cAMP. To find out whether the protons are generated by acidic vesicles or in the cytosol, we permeabilized the cells and found that this did not alter the cAMP-response. Proton efflux in intact cells was inhibited by preincubation with the V-type H+ ATPase inhibitor concanamycin A and with the plasma membrane H+ ATPase blocker miconazole. Surprisingly, miconazole also inhibited efflux in permeabilized cells, indicating that this type of H+ ATPase is present on intracellular vesicles as well. Vesicular acidification was inhibited by miconazole and by concanamycin A, suggesting that the acidic vesicles contain both V-type and P-type H+ ATPases. Moreover, concanamycin A and miconazole acted in concert, both in intact cells and in vesicles. The mechanism of cAMP-induced Ca2+-fluxes involves phospholipase A2 activity. Fatty acids circumvent the plasma membrane and stimulate vesicular Ca2+-efflux. Here we show that arachidonic acid elicited H+-efflux not only from intact cells but also from acidic vesicles. The target of regulation by arachidonic acid seemed to be the vesicular Ca2+-relase channel.

  3. To break a coralline: mechanical constraints on the size and survival of a wave-swept seaweed. (United States)

    Martone, Patrick T; Denny, Mark W


    Previous studies have hypothesized that wave-induced drag forces may constrain the size of intertidal organisms by dislodging or breaking organisms that exceed some critical dimension. In this study, we explored constraints on the size of the articulated coralline alga Calliarthron, which thrives in wave-exposed intertidal habitats. Its ability to survive depends critically upon its segmented morphology (calcified segments separated by flexible joints or ;genicula'), which allows otherwise rigid fronds to bend and thereby reduce drag. However, bending also amplifies stress within genicula near the base of fronds. We quantified breakage of genicula in bending by applying known forces to fronds until they broke. Using a mathematical model, we demonstrate the mitigating effect of neighboring fronds on breakage and show that fronds growing within dense populations are no more likely to break in bending than in tension, suggesting that genicular morphology approaches an engineering optimum, possibly reflecting adaptation to hydrodynamic stress. We measured drag in a re-circulating water flume (0.23-3.6 m s(-1)) and a gravity-accelerated water flume, which generates jets of water that mimic the impact of breaking waves (6-10 m s(-1)). We used frond Reynolds number to extrapolate drag coefficients in the field and to predict water velocities necessary to break fronds of given sizes. Laboratory data successfully predicted frond sizes found in the field, suggesting that, although Calliarthron is well adapted to resist breakage, wave forces may ultimately limit the size of intertidal fronds.

  4. Sensory-motor responses to mechanical stimulation of the esophagus after sensitization with acid

    Institute of Scientific and Technical Information of China (English)

    Asbj(ф)rn Mlohr Drewes; Hariprasad Reddy; Camilla Staahl; Jan Pedersen; Peter Funch-Jensen; Lars Arendt-Nielsen; Hans Gregersen


    AIM: Sensitization most likely plays an important role in chronic pain disorders, and such sensitization can be mimicked by experimental acid perfusion of the esophagus.The current study systematically investigated the sensory and motor responses of the esophagus to controlled mechanical stimuli before and after sensitization.METHODS: Thirty healthy subjects were included.Distension of the distal esophagus with a balloon was performed before and after perfusion with 0.1 mol/L hydrochloric acid for 30 min. An impedance planimetry system was used to measure cross-sectional area,volume, pressure, and tension during the distensions. A new model allowed evaluation of the phasic contractions by the tension during contractions as a function of the initial muscle length before the contraction (comparable to the Frank-Starling law for the heart). Length-tension diagrams were used to evaluate the muscle tone before and after relaxation of the smooth muscle with butylscopolamine.RESULTS: The sensitization resulted in allodynia and hyperalgesia to the distension volumes, and the degree of sensitization was related to the infused volume of acid. Furthermore, a nearly 50% increase in the evoked referred pain was seen after sensitization. The mechanical analysis demonstrated hyper-reactivity of the esophagus following acid perfusion, with an increased number and force of the phasic contractions, but the muscle tone did not change.CONCLUSION: Acid perfusion of the esophagus sensitizes the sensory pathways and facilitates secondary contractions.The new model can be used to study abnormal sensorymotor mechanisms in visceral organs.

  5. Mechanism of intracellular detection of glucose through nonenzymatic and boronic acid functionalized carbon dots. (United States)

    Kiran, S; Misra, R D K


    The objective of the research described here is to elucidate the fundamental mechanism by which the new class of "inert" non-enzymatic and boronic acid functionalized carbon dots-based sensors facilitate intracellular detection of glucose. The study suggests that the mechanism of detection of glucose involved selective assembly and fluorescence quenching of the carbon dots with excellent dynamic response to varying concentration of glucose within the biological range (1-100 mM). The strong dynamic response was related to high selectivity to biomolecules and inertness of carbon dots. Furthermore, the functionalization of carbon dots with boronic acid was the governing factor response for the passive character of the carbon dots. The study lays the foundation for the new field of carbon-based nanochemosensors.

  6. Kinetics and Mechanism of Oxidation of Lactic Acid by Dihydroxyditelluratoargentate(Ⅲ) in Alkaline Medium

    Institute of Scientific and Technical Information of China (English)


    The kinetics of the oxidation of lactic acid(Lac) by dihydroxyditelluratoargentate(Ⅲ)[abbreviated as DDA of Ag(Ⅲ)] anions was studied in an aqueous alkaline medium by conventional spectrophotometry in a temperature range of 25—40 ℃. The order of the redox reaction of lactic acid and DDA was found to be first-order. The rates increased with the increase in [OH-] and decreased with the increase in [tellurate]. No free radical was detected. In the view of this the dihydroxymonotelluratoargentate(Ⅲ) species(DMA) is assumed to be the active species. A plausible mechanism involving a two-electron transfer is proposed, and the rate equation derived from the mechanism can be used to explain all the experimental results. The activation parameters(25 ℃) and the rate constants of the rate-determining step along with the preequilibrium constants at different temperatures were evaluated.

  7. Kinetics and Mechanism of Oxidation of Lactic Acid by Dihydroxyditelluratoargentate(Ⅲ)in Alkaline Medium

    Institute of Scientific and Technical Information of China (English)

    SHANJin-huan; WANGLi; LIUBao-sheng; SHENShi-gang


    The kinetics of the oxidation of lactic acid(Lac) by dihydroxyditelluratoargentate(Ⅲ)[abbreviated as DDA of Ag(Ⅲ)]anions was studied in an aqueous alkaline medium by conventional spectrophotometry in a temperature range of 25-40℃.The order of the redox reaction of lactic acid and DDA was found to be first-order.The rates increased with the increase in [OH-]and decreased with the increase in [tellurate].No free radical was detected.In the view of this the dihydroxymonotelluratoargentate(Ⅲ)species(DMA) is assumed to be the active species.A plausible mechanism involving a two-electron transfer is proposed,and the rate equation derived from the mechanism can be used to explain all the experimenttal results.The activation parameters(25℃)and the rate constants of the rate-determining step along with the preequilibrium constants at different temperatures were evaluated.

  8. Green tea catechins: Proposed mechanisms of action in breast cancer focusing on the interplay between survival and apoptosis. (United States)

    Yiannakopoulou, Eugenia Ch


    Recent data have shown strong chemopreventive and possibly cancer chemotherapeutic effects of green tea polyphenols against cancer. Despite advances in breast cancer treatment, mortality from breast cancer is still high. Undoubtedly novel treatment strategies are needed for chemoprevention of high risk women and for the treatment of receptor negative breast cancer. Green tea catechins have been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. This review attempts a critical presentation of the mechanisms of action of green tea catechins in breast cancer. Several mechanisms of action of green tea catechins in breast cancer have been proposed including modulation of extracellular signalling, induction of apoptosis through redox regulation, or through modulation of epigenetic alterations. A number of molecular targets of green tea catechins have been suggested i.e molecular chaperones, telomerase, apoptotic cascade. Although the molecular links among the proposed mechanisms of action of green tea catechins are often missing, it must be emphasized that all the proposed mechanisms indicate that green tea catechins inhibit growth and /or promote apoptosis. It would be interesting if future experimental trials could take into account that green tea catechins are multi-target agents and attempt to link every novel proposed target with the other already proposed targets of green tea catechins.

  9. Identifying the receptor subtype selectivity of retinoid X and retinoic acid receptors via quantum mechanics. (United States)

    Tsuji, Motonori; Shudo, Koichi; Kagechika, Hiroyuki


    Understanding and identifying the receptor subtype selectivity of a ligand is an important issue in the field of drug discovery. Using a combination of classical molecular mechanics and quantum mechanical calculations, this report assesses the receptor subtype selectivity for the human retinoid X receptor (hRXR) and retinoic acid receptor (hRAR) ligand-binding domains (LBDs) complexed with retinoid ligands. The calculated energies show good correlation with the experimentally reported binding affinities. The technique proposed here is a promising method as it reveals the origin of the receptor subtype selectivity of selective ligands.

  10. Mechanical and Thermal Properties of Compression Molded Poly (acrylic acid) Salts with Multivalent Metal Ions


    Gotoh, Y.; Ohkoshi, Y; Nagura, M


    Films of zinc, calcium and aluminum salts of poly (acrylic acid) (PAA) were prepared from their powdery salts by compression molding at 190_??_200°C, 600MPa for 0.5hr and their mechanical and thermal properties were investigated. From the results of the dynamic mechanical thermal analysis the storage modulus of each PAA salts exhibited about 20GPa at room temperature because of highly intermolecular crosslinking of PAA by metal ions. Modulus of PAA calcium salt was 7GPa even at 400°C, while m...

  11. Mechanism of Calcium Lactate Facilitating Phytic Acid Degradation in Soybean during Germination. (United States)

    Hui, Qianru; Yang, Runqiang; Shen, Chang; Zhou, Yulin; Gu, Zhenxin


    Calcium lactate facilitates the growth and phytic acid degradation of soybean sprouts, but the mechanism is unclear. In this study, calcium lactate (Ca) and calcium lactate with lanthanum chloride (Ca+La) were used to treat soybean sprouts to reveal the relevant mechanism. Results showed that the phytic acid content decreased and the availability of phosphorus increased under Ca treatment. This must be due to the enhancement of enzyme activity related to phytic acid degradation. In addition, the energy metabolism was accelerated by Ca treatment. The energy status and energy metabolism-associated enzyme activity also increased. However, the transmembrane transport of calcium was inhibited by La(3+) and concentrated in intercellular space or between the cell wall and cell membrane; thus, Ca+La treatment showed reverse results compared with those of Ca treatment. Interestingly, gene expression did not vary in accordance with their enzyme activity. These results demonstrated that calcium lactate increased the rate of phytic acid degradation by enhancing growth, phosphorus metabolism, and energy metabolism.

  12. Lignin hydrolysis and phosphorylation mechanism during phosphoric acid-acetone pretreatment: a DFT study. (United States)

    Qin, Wu; Wu, Lingnan; Zheng, Zongming; Dong, Changqing; Yang, Yongping


    The study focused on the structural sensitivity of lignin during the phosphoric acid-acetone pretreatment process and the resulting hydrolysis and phosphorylation reaction mechanisms using density functional theory calculations. The chemical stabilities of the seven most common linkages (β-O-4, β-β, 4-O-5, β-1, 5-5, α-O-4, and β-5) of lignin in H3PO4, CH3COCH3, and H2O solutions were detected, which shows that α-O-4 linkage and β-O-4 linkage tend to break during the phosphoric acid-acetone pretreatment process. Then α-O-4 phosphorylation and β-O-4 phosphorylation follow a two-step reaction mechanism in the acid treatment step, respectively. However, since phosphorylation of α-O-4 is more energetically accessible than phosphorylation of β-O-4 in phosphoric acid, the phosphorylation of α-O-4 could be controllably realized under certain operational conditions, which could tune the electron and hole transfer on the right side of β-O-4 in the H2PO4- functionalized lignin. The results provide a fundamental understanding for process-controlled modification of lignin and the potential novel applications in lignin-based imprinted polymers, sensors, and molecular devices.

  13. Processing of poly(lactic acid): characterization of chemical structure, thermal stability and mechanical properties


    Carrasco Alonso, Félix Ángel; Pagès Figueras, Pere; Gamez Pérez, José; Santana Pérez, Orlando Onofre; Maspoch Rulduà, Mª Lluïsa


    The processing of poly(lactic acid) (injection and extrusion/injection) as well as annealing of processed materials were studied in order to analyze the variation of its chemical structure, thermal degradation and mechanical properties. Processing of PLA was responsible for a decrease in molecular weight, as determined by GPC, due to chain scission. The degree of crystallinity was evaluated by means of differential scanning calorimetry and X-ray diffraction. It was found that mech...

  14. DDQ-promoted dehydrogenation from natural rigid polycyclic acids or flexible alkyl acids to generate lactones by a radical ion mechanism. (United States)

    Ding, Ye; Huang, Zhangjian; Yin, Jian; Lai, Yisheng; Zhang, Shibo; Zhang, Zhiguo; Fang, Lei; Peng, Sixun; Zhang, Yihua


    A novel and facile DDQ-mediated dehydrogenation from natural rigid polycyclic acids or flexible alkyl acids to generate lactones is described. The formation of lactones proceeds by a radical ion mechanism, which has been established by DPPH˙-mediated chemical identification, ESR spectroscopy and an enol intermediate trapping.

  15. Browning inhibition mechanisms by cysteine, ascorbic acid and citric acid, and identifying PPO-catechol-cysteine reaction products. (United States)

    Ali, Hussein M; El-Gizawy, Ahmed M; El-Bassiouny, Rawia E I; Saleh, Mahmoud A


    The titled compounds were examined as PPO inhibitors and antibrowning agents; their various mechanisms were investigated and discussed. All compounds reduced significantly both the browning process and PPO activity. Browning index gave strong correlation with PPO activity (r(2) = 0.96, n = 19) indicating that the browning process is mainly enzymatic. Ascorbic acid could reduce the formed quinone instantly to the original substrate (catechol) at high concentration (>1.5 %) while at lower concentrations acted as competitive inhibitor (KI = 0.256 ± 0.067 mM). Cysteine, at higher concentrations (≥1.0 %), reacted with the resulted quinone to give a colorless products while at the low concentrations, cysteine worked as competitive inhibitor (KI = 1.113 ± 0.176 mM). Citric acid acted only as PPO non-competitive inhibitor with KI = 2.074 ± 0.363 mM. The products of PPO-catechole-cysteine reaction could be separation and identification by LC-ESI-MS. Results indicated that the product of the enzymatic oxidation of catechol, quinone, undergoes two successive nucleophilic attacks by cysteine thiol group. Cysteine was condensed with the resulted mono and dithiocatechols to form peptide side chains.

  16. Boron stress activates the general amino acid control mechanism and inhibits protein synthesis.

    Directory of Open Access Journals (Sweden)

    Irem Uluisik

    Full Text Available Boron is an essential micronutrient for plants, and it is beneficial for animals. However, at high concentrations boron is toxic to cells although the mechanism of this toxicity is not known. Atr1 has recently been identified as a boron efflux pump whose expression is upregulated in response to boron treatment. Here, we found that the expression of ATR1 is associated with expression of genes involved in amino acid biosynthesis. These mechanisms are strictly controlled by the transcription factor Gcn4 in response to boron treatment. Further analyses have shown that boron impaired protein synthesis by promoting phosphorylation of eIF2α in a Gcn2 kinase dependent manner. The uncharged tRNA binding domain (HisRS of Gcn2 is necessary for the phosphorylation of eIF2α in the presence of boron. We postulate that boron exerts its toxic effect through activation of the general amino acid control system and inhibition of protein synthesis. Since the general amino acid control pathway is conserved among eukaryotes, this mechanism of boron toxicity may be of general importance.

  17. Static and Dynamic Mechanical Behavior of Hydroxyapatite-Polyacrylic Acid Composites Under Simulated Body Fluid

    Directory of Open Access Journals (Sweden)

    Kalpana S. Katti


    Full Text Available In this work, we have investigated mechanical response of hydroxyapatite/polyacrylic composites under dry, wet and simulated body fluid conditions. Hydroxyapatite (HAP is mineralized under two conditions; one, in presence of polyacrylic acid (in situ HAP, second, in absence of polyacrylic acid (ex situ HAP. Further, in situ and ex situ HAP are mixed with polyacrylic acid to make HAP/PAAc composites. Interfacial interactions between PAAc and HAP have been studied using photoacoustic Fourier transform infrared spectroscopy (PAS-FTIR. The mechanical response of the composites under wet condition is studied by soaking composite samples in simulated body fluid (SBF. Under wet conditions, SBF and water weaken the HAP-HAP interface significantly. PAS-FTIR data suggests that PAAc attaches to HAP through the dissociated carboxylate groups. The water and SBF soaked samples showed creep-like behavior and exhibit large residual strain after unloading. Loading under different strain rates has significant effect on mechanical properties of these composites. Both in situ and ex situ 70:30 composites exhibit highest elastic modulus at strain rate of 0.01 sec-1. XRD study indicates formation of Ca2P2O7 phase in ex situ composite after soaking in SBF and water for 3 hours, whereas in situ composites showed presence of only hydroxyapatite phase after soaking in SBF and water for same duration of time.

  18. Mechanism analysis of acid tolerance response of bifidobacterium longum subsp. longum BBMN 68 by gene expression profile using RNA-sequencing.

    Directory of Open Access Journals (Sweden)

    Junhua Jin

    Full Text Available To analyze the mechanism of the acid tolerance response (ATR in Bifidobacterium longum subsp. longum BBMN68, we optimized the acid-adaptation condition to stimulate ATR effectively and analyzed the change of gene expression profile after acid-adaptation using high-throughput RNA-Seq. After acid-adaptation at pH 4.5 for 2 hours, the survival rate of BBMN68 at lethal pH 3.5 for 120 min was increased by 70 fold and the expression of 293 genes were upregulated by more than 2 fold, and 245 genes were downregulated by more than 2 fold. Gene expression profiling of ATR in BBMN68 suggested that, when the bacteria faced acid stress, the cells strengthened the integrity of cell wall and changed the permeability of membrane to keep the H(+ from entering. Once the H(+ entered the cytoplasm, the cells showed four main responses: First, the F(0F(1-ATPase system was initiated to discharge H(+. Second, the ability to produce NH(3 by cysteine-cystathionine-cycle was strengthened to neutralize excess H(+. Third, the cells started NER-UVR and NER-VSR systems to minimize the damage to DNA and upregulated HtpX, IbpA, and γ-glutamylcysteine production to protect proteins against damage. Fourth, the cells initiated global response signals ((pppGpp, polyP, and Sec-SRP to bring the whole cell into a state of response to the stress. The cells also secreted the quorum sensing signal (AI-2 to communicate between intraspecies cells by the cellular signal system, such as two-component systems, to improve the overall survival rate. Besides, the cells varied the pathways of producing energy by shifting to BCAA metabolism and enhanced the ability to utilize sugar to supply sufficient energy for the operation of the mechanism mentioned above. Based on these reults, it was inferred that, during industrial applications, the acid resistance of bifidobacteria could be improved by adding BCAA, γ-glutamylcysteine, cysteine, and cystathionine into the acid-stress environment.

  19. Mechanisms increasing n-3 highly unsaturated fatty acids in the heart. (United States)

    Glück, Tobias; Rupp, Heinz; Alter, Peter


    Due to ambiguous findings on cardiovascular benefits of systemic omega-3 fatty acid therapy, endogenous mechanisms contributing to local organ-specific concentrations of highly unsaturated fatty acids (HUFA) were examined. Using gas chromatography, 43 fatty acids were analyzed in atrial and ventricular myocardium and in pericardial fluid of male Wistar rats. To examine the endogenous fatty acid metabolism, precursors were administered into the pericardial sac. Pro- and anti-inflammatory actions were induced by talc or fenofibrate, respectively. Physical exercise and a sedentary obese state were used for increased beta-oxidation. DHA (22:6n-3) was increased in ventricular when compared with atrial myocardium (9.0 ± 2.1% vs. 4.7 ± 1.0%, p acid (24:5n-3) in atrial myocardium, which is a key precursor of DHA. In contrast, proinflammatory stimulation of the n-6 HUFA pathway did not influence the n-3 metabolism. Exercise- and obesity-induced increased beta-oxidation, the finalizing step of DHA synthesis, was associated with increased ventricular DHA concentrations (6.7 ± 1.0% vs. 8.4 ± 1.2%, p < 0.01). It is concluded that the endogenous metabolism contributes markedly to myocardial HUFA concentrations. The findings are supposed to influence the efficacy of oral HUFA treatment and provide a rationale for divergent findings of previous trials on omega-3 therapy.

  20. Iron-catalyzed photochemical transformation of benzoic acid in atmospheric liquids: Product identification and reaction mechanisms (United States)

    Deng, Yiwei; Zhang, Kai; Chen, Hao; Wu, Taixing; Krzyaniak, Metthew; Wellons, Amina; Bolla, Dawn; Douglas, Kenneth; Zuo, Yuegang

    This study investigated iron-catalyzed photochemical oxidation of benzoic acid (BA), one of the major photodegradation products of petroleum hydrocarbons, under sunlight or monochromatic light irradiation in a wavelength range of 254-419 nm. The photochemical degradation of BA in the absence of iron (III) occurred at irradiation wavelengths below 300 nm. The photochemical transformation of BA in the presence Fe(III) was observed at both 254, 350, 419 nm and under solar irradiation. The half-life for the photodegradation of BA (100 μM) was 160±20 min in the presence of 20 μM Fe(III) at pH 3.20 on sunny August days at noon time. The degradation rate increased with increasing concentration of Fe(III). The reaction products were separated and identified using capillary electrophoresis (CE), gas chromatography/mass spectrometry (GC/MS) and UV-Visible spectrophotometry. The major reaction products were 2-hydroxybenzoic, 3-hydroxybenzoic and 4-hydroxybenzoic acids. Hydrogen peroxide (H 2O 2) and Fe(II) species were also formed during the photochemical reactions. The proposed reaction mechanisms include the photoexcitation of Fe(III) hydroxide complexes to form Fe(II) ions and hydroxyl radicals (OH rad ) that attack ortho, meta and para positions of BA to form corresponding monohydroxybenzoic acids and H 2O 2. The monohydroxybenzoic acids formed further react with hydroxyl and surperoxide radicals (HO 2- rad /O 2- rad ) to yield dihydroxybenzoic acids in atmospheric water droplets.

  1. Loss of N-glycolylneuraminic acid in humans: Mechanisms, consequences, and implications for hominid evolution. (United States)

    Varki, A


    The surface of all mammalian cells is covered with a dense and complex array of sugar chains, which are frequently terminated by members of a family of molecules called sialic acids. One particular sialic acid called N-glycolylneuraminic acid (Neu5Gc) is widely expressed on most mammalian tissues, but is not easily detectable on human cells. In fact, it provokes an immune response in adult humans. The human deficiency of Neu5Gc is explained by an inactivating mutation in the gene encoding CMP-N-acetylneuraminic acid hydroxylase, the rate-limiting enzyme in generating Neu5Gc in cells of other mammals. This deficiency also results in an excess of the precursor sialic acid N-acetylneuraminic acid (Neu5Ac) in humans. This mutation appears universal to modern humans, occurred sometime after our last common ancestor with the great apes, and happens to be one of the first known human-great ape genetic differences with an obvious biochemical readout. While the original selection mechanisms and major biological consequences of this human-specific mutation remain uncertain, several interesting clues are currently being pursued. First, there is evidence that the human condition can explain differences in susceptibility or resistance to certain microbial pathogens. Second, the functions of some endogenous receptors for sialic acids in the immune system may be altered by this difference. Third, despite the lack of any obvious alternate pathway for synthesis, Neu5Gc has been reported in human tumors and possibly in human fetal tissues, and traces have even been detected in normal human tissues. One possible explanation is that this represents accumulation of Neu5Gc from dietary sources of animal origin. Finally, a markedly reduced expression of hydroxylase in the brains of other mammals raises the possibility that the human-specific mutation of this enzyme could have played a role in human brain evolution.

  2. The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms

    DEFF Research Database (Denmark)

    Chiang, Wen-Chi; Pamp, Sünje Johanna; Nilsson, Martin


    Biofilms are reported to be inherently refractory toward antimicrobial attack and, therefore, cause problems in industrial and medical settings. Pseudomonas aeruginosa biofilms contain subpopulations that exhibit high metabolic activity and subpopulations that exhibit low metabolic activity. We......-targeting compounds colistin, EDTA, SDS, and chlorhexidine resulted in the same spatial distribution of live and dead bacteria, we investigated whether tolerance to these compounds originated from the same molecular mechanisms. Development of colistin-tolerant subpopulations was found to depend on the pmr genes...

  3. Depletion of retinoic acid receptors initiates a novel positive feedback mechanism that promotes teratogenic increases in retinoic acid.

    Directory of Open Access Journals (Sweden)

    Enrico D'Aniello

    Full Text Available Normal embryonic development and tissue homeostasis require precise levels of retinoic acid (RA signaling. Despite the importance of appropriate embryonic RA signaling levels, the mechanisms underlying congenital defects due to perturbations of RA signaling are not completely understood. Here, we report that zebrafish embryos deficient for RA receptor αb1 (RARαb1, a conserved RAR splice variant, have enlarged hearts with increased cardiomyocyte (CM specification, which are surprisingly the consequence of increased RA signaling. Importantly, depletion of RARαb2 or concurrent depletion of RARαb1 and RARαb2 also results in increased RA signaling, suggesting this effect is a broader consequence of RAR depletion. Concurrent depletion of RARαb1 and Cyp26a1, an enzyme that facilitates degradation of RA, and employment of a novel transgenic RA sensor line support the hypothesis that the increases in RA signaling in RAR deficient embryos are the result of increased embryonic RA coupled with compensatory RAR expression. Our results support an intriguing novel mechanism by which depletion of RARs elicits a previously unrecognized positive feedback loop that can result in developmental defects due to teratogenic increases in embryonic RA.

  4. Microbial production of amino acid-modified spider dragline silk protein with intensively improved mechanical properties. (United States)

    Zhang, Haibo; Zhou, Fengli; Jiang, Xinglin; Cao, Mingle; Wang, Shilu; Zou, Huibin; Cao, Yujin; Xian, Mo; Liu, Huizhou


    Spider dragline silk is a remarkably strong fiber with impressive mechanical properties, which were thought to result from the specific structures of the underlying proteins and their molecular size. In this study, silk protein 11R26 from the dragline silk protein of Nephila clavipes was used to analyze the potential effects of the special amino acids on the function of 11R26. Three protein derivatives, ZF4, ZF5, and ZF6, were obtained by site-directed mutagenesis, based on the sequence of 11R26, and among these derivatives, serine was replaced with cysteine, isoleucine, and arginine, respectively. After these were expressed and purified, the mechanical performance of the fibers derived from the four proteins was tested. Both hardness and average elastic modulus of ZF4 fiber increased 2.2 times compared with those of 11R26. The number of disulfide bonds in ZF4 protein was 4.67 times that of 11R26, which implied that disulfide bonds outside the poly-Ala region affect the mechanical properties of spider silk more efficiently. The results indicated that the mechanical performances of spider silk proteins with small molecular size can be enhanced by modification of the amino acids residues. Our research not only has shown the feasibility of large-scale production of spider silk proteins but also provides valuable information for protein rational design.

  5. Gastroprotective Mechanisms of Action of Semisynthetic Carnosic Acid Derivatives in Human Cells

    Directory of Open Access Journals (Sweden)

    Cristina Theoduloz


    Full Text Available Carnosic acid (CA and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS and lung fibroblasts (MRC-5 were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT-induced damage, and to increase the cellular reduced glutathione (GSH and prostaglandin E2 (PGE2 content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10–18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16–18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.

  6. Mechanism of toxicity of the branched-chain fatty acid phytanic acid, a marker of Refsum disease, in astrocytes involves mitochondrial impairment. (United States)

    Reiser, Georg; Schönfeld, Peter; Kahlert, Stefan


    Phytanic acid is a saturated branched-chain fatty acid, which is formed by bacterial degradation of chlorophyll in the intestinal tract of ruminants. The methyl group in beta-position prevents degradation of phytanic acid by the beta-oxidation pathway. Therefore, degradation of phytanic acid is initiated by alpha-oxidation in peroxisomes. The inherited peroxisomal disorder Refsum disease is characterised by accumulation of phytanic acid. Unusually high concentrations of phytanic acid can be found in the plasma of Refsum disease patients, who suffer from neurodegeneration and muscle dystrophy. Phytanic acid has been suggested to be causally involved in the clinical symptoms. To elucidate the pathogenic mechanism, we investigated the influence of phytanic acid in rat hippocampal astrocytes by monitoring the cytosolic Ca(2+) concentration, the mitochondrial membrane potential (Deltapsi(m)), the generation of reactive oxygen species as well as the cellular ATP level. In response to phytanic acid (100 microM) cytosolic Ca(2+) was quickly increased. The phytanic acid-evoked Ca(2+) response was transient and involved activation of intracellular Ca(2+) stores. In isolated rat brain mitochondria, phytanic acid dissipated Deltapsi(m) in a reversible and dose-dependent manner. Moreover, phytanic acid released cytochrome c from mitochondria. Depending on the mitochondrial activity state, phytanic acid either stimulated or inhibited the electron flux within the respiratory chain. In addition, phytanic acid induced substantial generation of reactive oxygen species in isolated mitochondria as well as in intact cells. Phytanic acid caused cell death of astrocytes within a few hours of exposure. In conclusion, we suggest that phytanic acid initiates astrocyte cell death by activating the mitochondrial route of apoptosis.

  7. The Mechanism of Electropolishing of Niobium in Hydrofluoric-Sulfuric Acid Electrolyte

    Energy Technology Data Exchange (ETDEWEB)

    Tian, Hui; Corcoran, Sean; Reece, Charles; Kelley, Michael


    Niobium surfaces are commonly electropolished in an effort to obtain optimal smoothness for high-field superconducting radio-frequency cavity applications. We report the use of controlled electrochemical analysis techniques to characterize electropolishing of Nb in a sulfuric and hydrofluoric acid electrolyte. Through the use of a reference electrode, we are able to clearly distinguish the anode and cathode polarization potentials as well as the electrolyte voltage drop, which together sum to the applied power supply voltage. We then identify the temperature and HF concentration dependence of each potential. We also report the use of electrochemical impedance spectroscopy (EIS) on this system. EIS results are consistent with the compact salt film mechanism for niobium electropolishing (EP) in this electrolyte and are not consistent with either the porous salt film or the absorbate-acceptor mechanism. Microscopic understanding of the basic Nb EP mechanism is expected to provide an appro

  8. Decrease of intracellular pH as possible mechanism of embryotoxicity of glycol ether alkoxyacetic acid metabolites. (United States)

    Louisse, Jochem; Bai, Yanqing; Verwei, Miriam; van de Sandt, Johannes J M; Blaauboer, Bas J; Rietjens, Ivonne M C M


    Embryotoxicity of glycol ethers is caused by their alkoxyacetic acid metabolites, but the mechanism underlying the embryotoxicity of these acid metabolites is so far not known. The present study investigates a possible mechanism underlying the embryotoxicity of glycol ether alkoxyacetic acid metabolites using the methoxyacetic acid (MAA) metabolite of ethylene glycol monomethyl ether as the model compound. The results obtained demonstrate an MAA-induced decrease of the intracellular pH (pH(i)) of embryonic BALB/c-3T3 cells as well as of embryonic stem (ES)-D3 cells, at concentrations that affect ES-D3 cell differentiation. These results suggest a mechanism for MAA-mediated embryotoxicity similar to the mechanism of embryotoxicity of the drugs valproic acid and acetazolamide (ACZ), known to decrease the pH(i)in vivo, and therefore used as positive controls. The embryotoxic alkoxyacetic acid metabolites ethoxyacetic acid, butoxyacetic acid and phenoxyacetic acid also caused an intracellular acidification of BALB/c-3T3 cells at concentrations that are known to inhibit ES-D3 cell differentiation. Two other embryotoxic compounds, all-trans-retinoic acid and 5-fluorouracil, did not decrease the pH(i) of embryonic cells at concentrations that affect ES-D3 cell differentiation, pointing at a different mechanism of embryotoxicity of these compounds. MAA and ACZ induced a concentration-dependent inhibition of ES-D3 cell differentiation, which was enhanced by amiloride, an inhibitor of the Na(+)/H(+)-antiporter, corroborating an important role of the pH(i) in the embryotoxic mechanism of both compounds. Together, the results presented indicate that a decrease of the pH(i) may be the mechanism of embryotoxicity of the alkoxyacetic acid metabolites of the glycol ethers.

  9. Final report: Hydraulic mechanisms of survival and mortality during drought in pinon-juniper woodlands of southwestern USA

    Energy Technology Data Exchange (ETDEWEB)

    Pockman, William [Univ. of New Mexico, Albuquerque, NM (United States)


    The goal of this project was to use rainfall manipulation of an intact pinon-juniper woodland in central New Mexico to understand the mechanisms that control the response of these species to extremes of rainfall. Experimental plots were installed in a pinon-juniper woodland at the Sevilleta National Wildlife Refuge and treatments were imposed in August 2007. Treatments consisted of 1) a Drought treatment imposed by diverting approximately 45% of precipitation away from the plot, 2) and Irrigation treatment imposed by applying six 19 mm simulated rainfall events at regular intervals during the growing season, 3) a Cover Control treatment designed to assess the impact of the plastic troughs constructed on Drought plots without imposing the rainfall diversion, and 4) an untreated control that received no modification. Extensive pinon mortality was observed beginning one year after the start of drought treatment on hillslope plots, while a third drought plot on deeper soils did not exhibit pinon mortality until the fifth year of drought treatment. Pinon mortality occurred in the context of high levels of bark beetle activity, motivating the installation of two additional plots in 2010: a control plot and a drought plot built to the same standards as the original treatments but with bark beetle control maintained by pesticide application to the bole of target trees from 2010 - 2016. Although the drought treatment created similar conditions to those experienced on hillslope drought plots, the drought plot with bark beetle control exhibited no pinon mortality for 5 years even in the presence of high regional bark beetle activity in 2012/13. One of the goals of the research was to identify the mechanism of drought-induced mortality in pinon and juniper: 1) mortality due to catastrophic failure of water transport through plant tissues (hydraulic failure), 2) mortality due to limitations in carbon uptake (carbon starvation) and 3) either of the first two mechanisms with the

  10. d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology. (United States)

    De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella


    d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles' reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD's mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D₂, Trace Amine Associate receptor 1 (TAAR₁) and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD's effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR₁ receptors.

  11. d-Lysergic Acid Diethylamide (LSD) as a Model of Psychosis: Mechanism of Action and Pharmacology (United States)

    De Gregorio, Danilo; Comai, Stefano; Posa, Luca; Gobbi, Gabriella


    d-Lysergic Acid Diethylamide (LSD) is known for its hallucinogenic properties and psychotic-like symptoms, especially at high doses. It is indeed used as a pharmacological model of psychosis in preclinical research. The goal of this review was to understand the mechanism of action of psychotic-like effects of LSD. We searched Pubmed, Web of Science, Scopus, Google Scholar and articles’ reference lists for preclinical studies regarding the mechanism of action involved in the psychotic-like effects induced by LSD. LSD’s mechanism of action is pleiotropic, primarily mediated by the serotonergic system in the Dorsal Raphe, binding the 5-HT2A receptor as a partial agonist and 5-HT1A as an agonist. LSD also modulates the Ventral Tegmental Area, at higher doses, by stimulating dopamine D2, Trace Amine Associate receptor 1 (TAAR1) and 5-HT2A. More studies clarifying the mechanism of action of the psychotic-like symptoms or psychosis induced by LSD in humans are needed. LSD’s effects are mediated by a pleiotropic mechanism involving serotonergic, dopaminergic, and glutamatergic neurotransmission. Thus, the LSD-induced psychosis is a useful model to test the therapeutic efficacy of potential novel antipsychotic drugs, particularly drugs with dual serotonergic and dopaminergic (DA) mechanism or acting on TAAR1 receptors. PMID:27886063

  12. Variation of mechanical properties with amino acid content in the silk of Nephila clavipes. (United States)

    Zax, David B; Armanios, Daniel E; Horak, Sally; Brodowski, Chris; Malowniak, Chris; Yang, Zhitong


    In this paper, we explore the impact of dietary deprivation, where spiders are provided diets missing one or more of the amino acids, on the properties of the spider dragline silk spun after one month on the diet. Cohorts of female N. clavipes spiders were selected for diets deprived of alanine (Ala) and glycine (Gly), arginine (Arg), leucine (Leu), or tyrosine (Tyr), and their silk was harvested twice weekly during the one-month course of the diet. Significant mechanical differences are observed after as little as 6 days on the diet. Utilizing conventional tensile testing methods, single fibers were strained to break so as to study the influence of diet on the stress/strain properties. Diets deprived of Ala and Gly appear to most directly impact the load-bearing foundation of dragline silk. Diets deprived of Arg, Tyr, and possibly Leu reduce the strength of the silk, and diets missing Tyr and Leu reduce the strain-to-failure. Observations obtained from ESEM photos of the fracture interfaces after tensile testing illustrate the fracture mechanics of spider silk. Both solid-state NMR and amino acid analysis of the digested protein suggest, however, that the relationship between diet and amino acid incorporation into the silk fiber is not straightforward.

  13. Mechanisms of photocatalytical degradation of monomethylarsonic and dimethylarsinic acids using nanocrystalline titanium dioxide. (United States)

    Xu, Zhonghou; Jing, Chuanyong; Li, Fasheng; Meng, Xiaoguang


    Photodegradation mechanisms of monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) with nanocrystalline titanium dioxide under UV irradiation were investigated. In the presence of UV irradiation and 0.02 g/L TiO2, 93% MMA (initial concentration is 10 mg-As/L) was transformed into inorganic arsenate, [As(V)], after 72 h of a batch reaction. The mineralization of DMA to As(V) occurred in two steps with MMA as an intermediate product. The photodegradation rate of MMA and DMA could be described using first-order kinetics, where the apparent rate constant is 0.033/h and 0.013/h for MMA and DMA, respectively. Radical scavengers, including superoxide dimutase (SOD), sodium bicarbonate, tert-butanol, and sodium azide, were used to study the photodegradation mechanisms of MMA and DMA. The results showed that hydroxyl radicals (HO*) was the primary reactive oxygen species for the photodegradation of MMA and DMA. The methyl groups in MMA and DMAweretransformed into organic carbon, including formic acid and possibly methanol, also through photochemical reactions. The results showed that nanocrystalline TiO2 can be used for the photocatalytical degradation of MMA and DMA and subsequent removal of the converted As(V), since the high adsorption capacity of the material for inorganic arsenic species has been demonstrated in previous studies.

  14. Dissolution mechanisms of goethite in the presence of siderophores and organic acids (United States)

    Reichard, P. U.; Kretzschmar, R.; Kraemer, S. M.


    In dynamic natural systems such as soils and surface waters, transient biogeochemical processes can induce strong chemical non-steady-state conditions. In this paper, we investigate the effects of non-steady-state conditions on ligand-controlled iron oxide dissolution. The rates of goethite dissolution at pH 6 in the presence of low molecular weight organic acids (oxalate, citrate or malonate) were observed. Non-steady-state conditions were induced by rapid additions of fungal, bacterial or plant siderophores. In the presence of the low molecular weight organic acids, dissolved iron concentrations are below detection limit as predicted by equilibrium solubility calculations. The rapid addition of the siderophores triggered reproducible, fast dissolution of kinetically labile iron from the iron oxide surface. The same effect was observed upon rapid additions of high citrate concentrations to goethite-oxalate suspensions. The concentration of the labile iron pool at the mineral surface was a function of the surface concentration of the low molecular weight organic acids and of the reaction time before addition of the siderophores. Isotopic exchange with 59Fe independently confirmed the existence of the labile iron pool before addition of the siderophore. A dissolution mechanism was elucidated that is consistent with these observations and with accepted models of ligand-controlled dissolution. We conclude that the fast dissolution reaction observed here is an important process in biological iron acquisition and that it is based on a general geochemical mechanism.

  15. DFT computational study on decarboxylation mechanism of salicylic acid and its derivatives in the anionic state (United States)

    Gao, Lu; Hu, Yanying; Zhang, Huitu; Liu, Yanchun; Song, Zhidan; Dai, Yujie


    The mechanisms of the decarboxylation of salicylic acid anion and its ortho substituted derivatives in gas phase and aqueous solution have been investigated by B3LYP method of DFT theory using the 6-31++G (d,p) basis set. The decarboxylation process includes hydrogen transfers from hydroxyl to carboxyl group and from carboxyl to the α-C of the aryl ring. The mechanism suggested is a pseudo-unimolecular decomposition of the salicylic acid anion and the hydrogen transfer from carboxyl to the α-C of the aryl ring is the rate determining step. Compared with the decarboxylation process in gas phase, the energy barriers in aqueous solution approximately declined by 25%-31%with the water mediation of the hydrogen transfer from carboxyl to the α-C of the aryl ring. The effects of substituents at the ortho position on the decarboxylation process were also investigated. Both the electron donating CH3 and withdrawing group NO2 at the ortho position of carboxyl group can further reduce the reaction energy barriers of the decarboxylation of salicylic acid anions.

  16. Dietary fatty acids affecting hepatic metabolism and atherosclerosis - mechanisms unravelled using a proteomics approach

    Directory of Open Access Journals (Sweden)

    Rodríguez Gutiérrez, Guillermo


    Full Text Available Dietary fatty acids play an important role in the aetiology of coronary heart disease. The effects of dietary fatty acids on lipoprotein metabolism are well described, but additional or alternative mechanisms relating to potential influence on coronary heart disease are not known. This review describes how proteomics techniques have been used to identify proteins that are differentially regulated by dietary fatty acids. Such proteins may reveal pathways by which dietary fatty acids influence disease risk.Los ácidos grasos de la dieta cumplen un importante papel en la etiología de las enfermedades coronarias. A pesar de estar bien descrito el efecto de dichos ácidos grasos sobre el metabolismo lipoproteíco, no se conocen mecanismos alternativos que relacionen su influencia sobre posibles enfermedades coronarias. En esta revisión se describe el uso de técnicas proteómicas para la identificación de proteínas diferencialmente reguladas por dichos ácidos grasos. Tales proteínas pueden revelar rutas metabólicas implicadas en el riesgo de enfermedades y reguladas por los ácidos grasos de la dieta.

  17. Effect of carboxylic acids as compatibilizer agent on mechanical properties of thermoplastic starch and polypropylene blends. (United States)

    Martins, Andréa Bercini; Santana, Ruth Marlene Campomanes


    In this work, polypropylene/thermoplastic starch (PP/TPS) blends were prepared as an alternative material to use in disposable packaging, reducing the negative polymeric environmental impact. Unfortunately, this material displays morphological characteristics typical of immiscible polymer blends and a compatibilizer agent is needed. Three different carboxyl acids: myristic (C14), palmitic (C16) and stearic acids (C18) were used as natural compatibilizer agent (NCA). The effects of NCA on the mechanical, physical, thermal and morphological properties of PP/TPS blends were investigated and compared against PP/TPS with and without PP-grafted maleic anhydride (PPgMA). When compared to PP/TPS, blends with C18, PPgMA and C14 presented an improvement of 25, 22 and 17% in tensile strength at break and of 180, 194 and 259% in elongation at break, respectively. The highest increase, 54%, in the impact strength was achieved with C14 incorporation. Improvements could be seen, through scanning electron microscopy (SEM) images, in the compatibility between the immiscible components by acids incorporation. These results showed that carboxylic acids, specifically C14, could be used as compatibilizer agent and could substitute PPgMA.

  18. Inhibition of fatty acid synthase by Orlistat accelerates gastric tumor cell apoptosis in culture and increases survival rates in gastric tumor bearing mice in vivo. (United States)

    Dowling, Shawn; Cox, James; Cenedella, Richard J


    Orlistat, an anti-obesity drug, is a potent inhibitor of fatty acid synthase (FAS) and tumor cell viability. It can also induce apoptotic cancer cell death. We examined the effects of Orlistat on cultured NUGC-3 gastric cancer cells. We identified that inhibition of FAS via Orlistat exposure results in rapid cellular damage preceded by a direct but short-lived autophagic response. The Orlistat induced damage can be reversed through the addition of lipid containing media in a process that normally leads to cell death. By limiting exogenous lipid availability and inhibiting FAS using Orlistat, we demonstrated both a greater sensitivity and amplified cancer cell death by activation of apoptosis. We have identified "windows of opportunity" at which time apoptosis can be aborted and cells can be reversed from the death pathway. However, when challenged beyond the window of recovery, cell death becomes all but certain as the ability to be rescued decreases considerably. In vivo examination of Orlistat's ability to inhibit gastrointestinal cancer was examined using heterozygous male C57BL/6J APC-Min mice, which spontaneously develop a fatal gastrointestinal cancer. Mice were fed either a high fat (11%) or low fat (1.2%) diet containing no Orlistat or 0.5 mg Orlistat/g of chow. Orlistat treated mice fed the high fat, but not low fat diet, survived 7-10% longer than the untreated controls.

  19. Mass transfer characterization of gamma-aminobutyric acid production by Enterococcus faecium CFR 3003: encapsulation improves its survival under simulated gastro-intestinal conditions. (United States)

    Divyashri, Gangaraju; Prapulla, Siddalingaiya Gurudatt


    Gamma-aminobutyric acid (GABA) production by free and Ca-alginate encapsulated cells of Enterococcus faecium CFR 3003 was investigated. Mass transfer rates characterizing the GABA production process using encapsulated cells were investigated. Experiments were performed to investigate external film and internal pore diffusion mass transfer rates. The Damkohler and Thiele analysis provides a good description of external film and internal pore diffusion resistances, respectively. The experiments revealed that the external film effects could be neglected but the process is affected to the greater extent by internal mass transfer effects and was found to be the principal rate-controlling step. Protective effect of encapsulation on cell survivability was tested under digestive environment, when challenged to salivary α-amylase, simulated gastric fluid and intestinal fluid. Viability of encapsulated cells was significantly higher under simulated gastro-intestinal conditions and could produce higher GABA than those observed with free cells. The results indicate that the Ca-alginate encapsulated probiotics could effectively be delivered to the colonic site for effective inhibitory action.

  20. Effect of sole or combined administration of nitrate and 3-nitro-1-propionic acid on fermentation and Salmonella survivability in alfalfa-fed rumen cultures in vitro. (United States)

    Correa, Alejandro Castañeda; Trachsel, Julian; Allen, Heather K; Corral-Luna, Agustin; Gutierrez-Bañuelos, Hector; Ochoa-Garcia, Pedro Antonia; Ruiz-Barrera, Oscar; Hume, Michael E; Callaway, Todd R; Harvey, Roger B; Beier, Ross C; Anderson, Robin C; Nisbet, David J


    Ruminal methanogenesis is a digestive inefficiency resulting in the loss of dietary energy consumed by the host and contributing to environmental methane emission. Nitrate is being investigated as a feed supplement to reduce rumen methane emissions but safety and efficacy concerns persist. To assess potential synergies of co-administering sub-toxic amounts of nitrate and 3-nitro-1-propionate (NPA) on fermentation and Salmonella survivability with an alfalfa-based diet, ruminal microbes were cultured with additions of 8 or 16mM nitrate, 4 or 12mM NPA or their combinations. All treatments decreased methanogenesis compared to untreated controls but volatile fatty acid production and fermentation of hexose were also decreased. Nitrate was converted to nitrite, which accumulated to levels inhibitory to digestion. Salmonella populations were enriched in nitrate only-treated cultures but not in cultures co- or solely treated with NPA. These results reveal a need for dose optimization to safely reduce methane production with forage-based diets.

  1. [Recent progress of potential effects and mechanisms of chlorogenic acid and its intestinal metabolites on central nervous system diseases]. (United States)

    Xing, Li-na; Zhou, Ming-mei; Li, Yun; Shi, Xiao-wen; Jia, Wei


    Chlorogenic acid displays several important roles in the therapeutic properties of many herbs, such as antioxidant activity, antibacterial, antiviral, scavenging free radicals and exciting central nervous system. Only about one-third of chlorogenic acid was absorbed in its prototype, therefore, its gut metabolites play a more important role in the therapeutic properties of chlorogenic acid. It is necessary to consider not only the bioactivities of chlorogenic acid but also its gut metabolites. This review focuses on the potential activities and mechanisms of chlorogenic acid and its gut metabolites on central nervous system diseases.

  2. Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages (United States)

    Batista-Silva, L. R.; Rodrigues, Luciana Silva; Vivarini, Aislan de Carvalho; Costa, Fabrício da Mota Ramalho; Mattos, Katherine Antunes de; Costa, Maria Renata Sales Nogueira; Rosa, Patricia Sammarco; Toledo-Pinto, T. G.; Dias, André Alves; Moura, Danielle Fonseca; Sarno, Euzenir Nunes; Lopes, Ulisses Gazos; Pessolani, Maria Cristina Vidal


    Mycobacterium leprae (ML), the etiologic agent of leprosy, can subvert macrophage antimicrobial activity by mechanisms that remain only partially understood. In the present study, the participation of hormone insulin-like growth factor I (IGF-I) in this phenomenum was investigated. Macrophages from the dermal lesions of the disseminated multibacillary lepromatous form (LL) of leprosy expressed higher levels of IGF-I than those from the self-limited paucibacillary tuberculoid form (BT). Higher levels of IGF-I secretion by ML-infected macrophages were confirmed in ex vivo and in vitro studies. Of note, the dampening of IGF-I signaling reverted the capacity of ML-infected human and murine macrophages to produce antimicrobial molecules and promoted bacterial killing. Moreover, IGF-I was shown to inhibit the JAK/STAT1-dependent signaling pathways triggered by both mycobacteria and IFN-γ most probably through its capacity to induce the suppressor of cytokine signaling-3 (SOCS3). Finally, these in vitro findings were corroborated by in vivo observations in which higher SOCS3 expression and lower phosphorylation of STAT1 levels were found in LL versus BT dermal lesions. Altogether, our data strongly suggest that IGF-I contributes to the maintenance of a functional program in infected macrophages that suits ML persistence in the host, reinforcing a key role for IGF-I in leprosy pathogenesis. PMID:27282338

  3. Mechanical Properties and Water Absorption Behaviour of Durian Rind Cellulose Reinforced Poly(lactic acid Biocomposites

    Directory of Open Access Journals (Sweden)

    Patpen Penjumras


    Full Text Available Environmental concerns have resulted in replacing petrochemically derived polymer with biodegradable renewable resource. In this study, mechanical properties and water absorption behaviour of durian rind cellulose reinforced poly(lactic acid biocomposites were investigated. Poly(lactic acid was mixed with 25 and 35 wt. % of durian rind cellulose that was derived from durian consumption wastes. The biocomposties were melt-blended at 165 and 175 °C with 15 min using a Brabender internal mixer followed by a hot compression moulding technique. The results showed that impact strength and modulus of Young increased with increasing of cellulose content but decreased at higher mixing temperature. Water absorption behaviour of biocomposites as function of days was also investigated. It was found that the water absorption amount of biocomposites increased with increasing of cellulose content and exposure time.    

  4. Mechanisms of lipid malabsorption in Cystic Fibrosis: the impact of essential fatty acids deficiency

    Directory of Open Access Journals (Sweden)

    Peretti N


    Full Text Available Abstract Transport mechanisms, whereby alimentary lipids are digested and packaged into small emulsion particles that enter intestinal cells to be translocated to the plasma in the form of chylomicrons, are impaired in cystic fibrosis. The purpose of this paper is to focus on defects that are related to intraluminal and intracellular events in this life-limiting genetic disorder. Specific evidence is presented to highlight the relationship between fat malabsorption and essential fatty acid deficiency commonly found in patients with cystic fibrosis that are often related to the genotype. Given the interdependency of pulmonary disease, pancreatic insufficiency and nutritional status, greater attention should be paid to the optimal correction of fat malabsorption and essential fatty acid deficiency in order to improve the quality of life and extend the life span of patients with cystic fibrosis.

  5. Evolution Reveals A Glutathione-dependent Mechanism Of 3-hydroxypropionic Acid Detoxification

    DEFF Research Database (Denmark)

    Kildegaard, Kanchana Rueksomtawin; Hallström, Björn M.; Blicher, Thomas H.;

    Biologically produced 3-hydroxypropionic acid (3HP) is a potential source for sustainable acrylates and can also find direct use as monomer in the production of biodegradable polymers. For industrial-scale production, high titer, rate and yield are essential; thus there is a need for robust cell...... factories tolerant to high concentration of 3HP, preferably at low pH. Through adaptive laboratory evolution we selected S. cerevisiae strains with improved tolerance to 3HP at pH 3.5. Genome sequencing of three independent clones identified single-nucleotide changes in the SFA1 gene encoding S...... as a glutathione-dependent route for detoxification of 3-hydroxypropionic aldehyde (reuterin). The identified molecular response to 3HP and reuterin may well be a general mechanism for handling resistance to organic acids and aldehydes by living cells...


    Directory of Open Access Journals (Sweden)



    Full Text Available The comparative study on the reactive extraction of p-aminobenzoic acid with Amberlite LA-2 and D2EHPA in two solvents with different polarity (n-heptane and dichloromethane indicated that the extractant type and solvent polarity control the extraction mechanism. Thus, the reactive extraction with Amberlite LA-2 occurs by means of the interfacial formation of an aminic adduct with three extractant molecules in low-polar solvent, or of an salt with one extractant molecule in higher polar solvent. Similarly, the extraction with D2EHPA is based on the formation of an acidic adduct with two extractant molecules in n-heptane, or of a salt with one extractant molecule in dichloromethane. The most efficient extraction has been reached for the combination Amberlite LA-2-dichloromethane.

  7. Addition Mechanisms of Phenol toward Formaldehyde under Acidic Condition: a Theoretical Investigation

    Institute of Scientific and Technical Information of China (English)

    XU Wen-Feng; XIONG Shan-Shan; SHI Yu-Qing; LI Tao-Hong; DU Guan-Ben; XIE Xiao-Guang


    The reaction mechanisms of phenol with formaldehyde in the first and second addition at the ortho- and para-position in acid solution were theoretically investigated at the PW91/DNP level with solvent effects included. The reaction of phenol with protonated methanediol firstly forms an adduct intermediate, via a SN2 mechanism with a water molecule as the leaving group. From the adduct intermediate, there are two reaction channels involving a proton transfer to form the addition products. One is that a proton directly transfers via a four-membered ring transition state with a notable energy barrier (Four-member mechanism). Another mechanism involving a water molecule as catalyst to mediate the proton transfer (WCP mechanism), is a barrierless process, indicating that the formation of the adduct intermediate, the first reaction step, is rate-limiting. The reaction products are free hydroxymethyl phenols and/or hydroxybenzy carbocation (HOC6H4CH2+) which plays an important role in the following formation of methylene and methylene ether linkages. The second addition reactions between formaldehyde and hydroxymethyl phenol at all possible reaction sites of the phenol ring in acid solution were also investigated and discussed.

  8. Influence of Mechanical Activation on Acid Leaching Dephosphorization of High-phosphorus Iron Ore Concentrates

    Institute of Scientific and Technical Information of China (English)

    De-qing ZHU; Hao WANG; Jian PAN; Cong-cong YANG


    High pressure roll grinding (HPRG)and ball milling were compared to investigate the influence of me-chanical activation on the acid leaching dephosphorization of a high-phosphorus iron ore concentrate,which was man-ufactured through magnetizing roasting-magnetic separation of high-phosphorus oolitic iron ores.The results indica-ted that when high-phosphorus iron ore concentrates containing 54·92 mass% iron and 0·76 mass% phosphorus were directly processed through acid leaching,iron ore concentrates containing 55·74 mass% iron and 0·33 mass%phosphorus with an iron recovery of 84·64% and dephosphorization of 63·79% were obtained.When high-phosphor-us iron ore concentrates activated by ball milling were processed by acid leaching,iron ore concentrates containing 56·03 mass% iron and 0·21 mass% phosphorus with an iron recovery of 85·65% and dephosphorization of 77·49%were obtained.Meanwhile,when high-phosphorus iron ore concentrates activated by HPRG were processed by acid leaching,iron ore concentrates containing 58·02 mass% iron and 0·10 mass% phosphorus were obtained,with the iron recovery reaching 88·42% and the dephosphorization rate reaching 88·99%.Mechanistic studies demonstrated that ball milling can reduce the particle size,demonstrating a prominent reunion phenomenon.In contrast,HPRG pretreatment contributes to the formation of more cracks within the particles and selective dissociation of iron and P bearing minerals,which can provide the favorable kinetic conditions to accelerate the solid-liquid reaction rate.As such,the crystal structure is destroyed and the surface energy of mineral particles is strengthened by mechanical ac-tivation,further strengthening the dephosphorization.

  9. A transcriptomic computational analysis of mastic oil-treated Lewis lung carcinomas reveals molecular mechanisms targeting tumor cell growth and survival

    Directory of Open Access Journals (Sweden)

    Roussos Charis


    Full Text Available Abstract Background Mastic oil from Pistacia lentiscus variation chia, a blend of bioactive terpenes with recognized medicinal properties, has been recently shown to exert anti-tumor growth activity through inhibition of cancer cell proliferation, survival, angiogenesis and inflammatory response. However, no studies have addressed its mechanisms of action at genome-wide gene expression level. Methods To investigate molecular mechanisms triggered by mastic oil, Lewis Lung Carcinoma cells were treated with mastic oil or DMSO and RNA was collected at five distinct time points (3-48 h. Microarray expression profiling was performed using Illumina mouse-6 v1 beadchips, followed by computational analysis. For a number of selected genes, RT-PCR validation was performed in LLC cells as well as in three human cancer cell lines of different origin (A549, HCT116, K562. PTEN specific inhibition by a bisperovanadium compound was applied to validate its contribution to mastic oil-mediated anti-tumor growth effects. Results In this work we demonstrated that exposure of Lewis lung carcinomas to mastic oil caused a time-dependent alteration in the expression of 925 genes. GO analysis associated expression profiles with several biological processes and functions. Among them, modifications on cell cycle/proliferation, survival and NF-κB cascade in conjunction with concomitant regulation of genes encoding for PTEN, E2F7, HMOX1 (up-regulation and NOD1 (down-regulation indicated some important mechanistic links underlying the anti-proliferative, pro-apoptotic and anti-inflammatory effects of mastic oil. The expression profiles of Hmox1, Pten and E2f7 genes were similarly altered by mastic oil in the majority of test cancer cell lines. Inhibition of PTEN partially reversed mastic oil effects on tumor cell growth, indicating a multi-target mechanism of action. Finally, k-means clustering, organized the significant gene list in eight clusters demonstrating a similar

  10. Using quantum mechanics to improve estimates of amino acid side chain rotamer energies. (United States)

    Renfrew, P Douglas; Butterfoss, Glenn L; Kuhlman, Brian


    Amino acid side chains adopt a discrete set of favorable conformations typically referred to as rotamers. The relative energies of rotamers partially determine which side chain conformations are more often observed in protein structures and accurate estimates of these energies are important for predicting protein structure and designing new proteins. Protein modelers typically calculate side chain rotamer energies by using molecular mechanics (MM) potentials or by converting rotamer probabilities from the protein database (PDB) into relative free energies. One limitation of the knowledge-based energies is that rotamer preferences observed in the PDB can reflect internal side chain energies as well as longer-range interactions with the rest of the protein. Here, we test an alternative approach for calculating rotamer energies. We use three different quantum mechanics (QM) methods (second order Møller-Plesset (MP2), density functional theory (DFT) energy calculation using the B3LYP functional, and Hartree-Fock) to calculate the energy of amino acid rotamers in a dipeptide model system, and then use these pre-calculated values in side chain placement simulations. Energies were calculated for over 36,000 different conformations of leucine, isoleucine, and valine dipeptides with backbone torsion angles from the helical and strand regions of the Ramachandran plot. In a subset of cases these energies differ significantly from those calculated with standard molecular mechanics potentials or those derived from PDB statistics. We find that in these cases the energies from the QM methods result in more accurate placement of amino acid side chains in structure prediction tests.

  11. Impact of citric acid and calcium ions on acid solubilization of mechanically separated turkey meat: effect on lipid and pigment content. (United States)

    Hrynets, Y; Omana, D A; Xu, Y; Betti, M


    Increased demand for poultry products has resulted in an increased availability of by-products, such as the neck, back, and frame, that can be processed into mechanically separated poultry meat. The major problems with mechanically separated poultry meat are its high lipid content, color instability, and high susceptibility to lipid oxidation. The present work was undertaken to determine the effect of different concentrations of citric acid and calcium ions on protein yield, color characteristics, and lipid removal from protein isolates prepared using an acid-aided extraction process. Six levels of citric acid (0, 2, 4, 6, 8, and 10 mmol/L) and 2 levels of calcium chloride (0 and 8 mmol/L) were examined. The entire experiment was replicated 3 times, resulting in 36 extractions (3 × 6 × 2). The highest (P citric acid. In general, all the combinations removed an average of 90.8% of the total lipids from mechanically separated turkey meat, ranging from 86.2 to 94.7%. The lowest amount (1.14%) of total lipids obtained was for samples treated with 4 mmol/L of citric acid. Maximum removal of neutral lipids (96.5%) and polar lipids (96.4%) was attained with the addition of 6 and 2 mmol/L of citric acid, respectively. Polar lipid content was found to be significantly (P = 0.0045) affected by the presence of calcium chloride. The isolated proteins were less (P citric acid. Addition of calcium chloride had a negative effect on total pigment content. The study revealed that acid extractions with the addition of citric acid resulted in substantial removal of lipids and pigments from mechanically separated turkey meat, improved stability of the recovered proteins against lipid oxidation, and appreciable protein recovery yields.

  12. Mechanism of Ascorbic Acid-induced Reversion Against Malignant Phenotype in Human Gastric Cancer Cells

    Institute of Scientific and Technical Information of China (English)



    Objective To find out the mechanisms of redifferentiation and reversion of malignant human gastric cancer cells induced by ascorbic acid. Methods Human gastric cancer cells grown in the laboratory were used. The Trypan blue dye exclusion method was used to determine the cell doubling time. The electrophoresis rate and colonogenic potential were the indices used to measure the rate of redifferentiation. The content of malondialdehyde (MDA) was measured using the thiobarbituric acid(TBA) method. The activities of superoxide dismutase (SOD), catalase (CAT) and the content of H2O2 were evaluated by spectrophotography. Results Six mmol/L ascorbic acid was used as a positive control. Human gastric cancer cells were treated with 75 μm hydrogen peroxide, which alleviated many of the malignant characteristics. For example, the cell surface charge obviously decreased and the electrophoresis rate dropped from 2.21 to 1.10 μm·s-1·V-1·cm-1. The colonogenic potential, a measure of cell differentiation, decreased 90.2%. After treatment with ascorbic acid, there was a concentration- and time-dependent increase in hydrogen peroxide (H2O2) and the activity of superoxide dismutase (SOD). However, the activity of catalase (CAT) resulted in a concentration- and time-dependent decrease. SOD and 3-amino-1,2,4-triazole (AT) exhibited some effects, but there were statistically significant differences between the SOD and AT group and the H2O2 group. Conclusions Ascorbic acid induces growth inhibition and redifferentiation of human gastric cancer cells through the production of hydrogen peroxide.

  13. Antitumor Mechanisms of Amino Acid Hydroxyurea Derivatives in the Metastatic Colon Cancer Model

    Directory of Open Access Journals (Sweden)

    Nina Šaban


    Full Text Available The paper presents a detailed study of the biological effects of two amino acid hydroxyurea derivatives that showed selective antiproliferative effects in vitro on the growth of human tumor cell line SW620. Tested compounds induced cell cycle perturbations and apoptosis. Proteins were identified by proteomics analyses using two-dimensional gel electrophoresis coupled to mass spectrometry, which provided a complete insight into the most probable mechanism of action on the protein level. Molecular targets for tested compounds were analyzed by cheminformatics tools. Zinc-dependent histone deacetylases were identified as potential targets responsible for the observed antiproliferative effect.

  14. Effects of primary dicarboxylic acids on microstructure and mechanical properties of sub-microcrystalline Ni-Co alloys

    Energy Technology Data Exchange (ETDEWEB)

    Vijayakumar, J., E-mail: [Central Electrochemical Research Institute, Karaikudi 630006 (India); Mohan, S., E-mail: [Central Electrochemical Research Institute, Karaikudi 630006 (India); Yadav, S. Sunil [Central Electrochemical Research Institute, Karaikudi 630006 (India)


    Highlights: > The electrodeposited Ni-Co alloys are mostly used in magnetic sensors and it has good mechanical and corrosion resistance properties. > The effect of dicarboxylic acid leads to preferred (2 0 0) crystalline orientation, this may improve magnetic properties dicarboxylic acid can alter the elemental composition of Ni-Co alloy. > Dicarboxylic acid acts as a good brightner. - Abstract: Nickel-cobalt alloys were deposited from sulfate electrolyte with oxalic, malonic and succinic acids as additives and their microstructure and mechanical properties were studied. The crystal structure, surface morphologies, and chemical composition of coatings were investigated using X-ray diffraction, scanning electron microscope, and energy dispersive spectroscopy. The crystal structure and surface morphology analysis showed that the addition of dicarboxylic acid leads to (2 0 0) crystal face and the surface were more compact and uniform due to the grain refining. Ni{sub 60}-Co{sub 40} alloy was achieved when succinic acid is used as additive.

  15. Fulx-pinning mechanism and activation energy in malic acid-doped MgB2

    Directory of Open Access Journals (Sweden)

    SR Ghorbani


    Full Text Available Fulx-pinning mechanism and activation energy of MgB2 doped with 10 wt % malic- acid has been investigated by measurement of critical current density and resistivity as a function of magnetic fields and temperatures. The field dependence of the critical current density, Jc(B, was analyzed within the collective pinning model. A crossover field, Bsb, from the single vortex to the small vortex bundle-pinning regime was observed. For sintered sample, the temperature dependence of Bsb(T at low temperature is in good agreement with the δℓ pinning mechanism, i.e., pinning associated with charge-carrier mean free path fluctuation. The activation energy was decreased linearly by increasing magnetic field.

  16. Poly(acrylic acid surface grafted polypropylene films: Near surface and bulk mechanical response

    Directory of Open Access Journals (Sweden)


    Full Text Available Radical photo-grafting polymerization constitutes a promising technique for introducing functional groups onto surfaces of polypropylene films. According to their final use, surface grafting should be done without affecting overall mechanical properties. In this work the tensile drawing, fracture and biaxial impact response of biaxially oriented polypropylene commercial films grafted with poly(acrylic acid (PAA were investigated in terms of film orientation and surface modification. The variations of surface roughness, elastic modulus, hardness and resistance to permanent deformation induced by the chemical treatment were assessed by depth sensing indentation. As a consequence of chemical modification the optical, transport and wettability properties of the films were successfully varied. The introduced chains generated a PAA-grafted layer, which is stiffer and harder than the neat polypropylene surface. Regardless of the surface changes, it was proven that this kind of grafting procedure does not detriment bulk mechanical properties of the PP film.

  17. Systemic administration of valproic acid and zonisamide promotes the survival and differentiation of induced pluripotent stem cell–derived dopaminergic neurons

    Directory of Open Access Journals (Sweden)

    Tatsuya eYoshikawa


    Full Text Available Cell replacement therapy using embryonic stem cells (ESCs and induced pluripotent stem cells (iPSCs is a promising strategy for the treatment of neurologic diseases such as Parkinson’s disease (PD. However, a limiting factor for effective cell transplantation is the low survival rate of grafted cells, especially neurons. In this study, we modified the host environment and investigated whether the simultaneous administration of soluble factors can improve the survival and differentiation of murine iPSC-derived dopaminergic (DA neurons in host brains. With the goal of applying this technology in clinical settings in the near future, we selected drugs that were already approved for clinical use. The drugs included two commonly used anticonvulsants, valproic acid (VPA and zonisamide (ZNS, and estradiol (E2, also known as biologically active estrogen. Following neural induction of murine iPSCs, we collected neural progenitor cells by sorting PSA-NCAM+ cells, then treated the PSA-NCAM+ cells with drugs for four days. An immunofluorescence study revealed that 0.01 mM and 0.1 mM of VPA and 10 nM of E2 increased the percentage of tyrosine hydroxylase+ (TH: a DA neuron marker cells in vitro. Furthermore, 0.1 mM of VPA increased the percentage of TH+ cells that simultaneously express the midbrain markers FOXA2 and NURR1. Next, in order to determine the effects of the drugs in vivo, the iPSC-derived NPCs were transplanted into the striata of intact SD rats. The animals received intraperitoneal injections of one of the drugs for four weeks, then were subjected to an immunofluorescence study. VPA administration (150 mg/kg/daily increased the number of NeuN+ postmitotic neurons and TH+ DA neurons in the grafts. Furthermore, VPA (150 mg/kg/daily and ZNS (30 mg/kg/daily increased the number of TH+FOXA2+ midbrain DA neurons. These results suggest that the systemic administration of VPA and ZNS may improve the efficiency of cell replacement therapy using i

  18. A novel mechanism for poisoning of metal oxide SCR catalysts: base-acid explanation correlated with redox properties. (United States)

    Chang, Huazhen; Li, Junhua; Su, Wenkang; Shao, Yuankai; Hao, Jiming


    A novel mechanism is proposed for the poisoning effect of acid gases and N2O formation on SCR catalysts involving base-acid properties correlated with redox ability of M-O or M-OH (M = Ce or V) of metal oxides and the strength of their basicity responsible for resistance to HCl and SO2 at medium and low temperatures.

  19. Early differential cell death and survival mechanisms initiate and contribute to the development of OPIDN: A study of molecular, cellular, and anatomical parameters

    Energy Technology Data Exchange (ETDEWEB)

    Damodaran, T.V., E-mail: [Dept of Medicine, Duke University Medical Center, Durham, NC (United States); Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States); Dept of Biology, North Carolina Central University, Durham, NC 27707 (United States); Attia, M.K. [Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States); Abou-Donia, M.B., E-mail: [Pharmacology and Cancer biology, Duke University Medical Center, Durham, NC (United States)


    Organophosphorus-ester induced delayed neurotoxicity (OPIDN) is a neurodegenerative disorder characterized by ataxia progressing to paralysis with a concomitant central and peripheral, distal axonapathy. Diisopropylphosphorofluoridate (DFP) produces OPIDN in the chicken that results in mild ataxia in 7-14 days and severe paralysis as the disease progresses with a single dose. White leghorn layer hens were treated with DFP (1.7 mg/kg, sc) after prophylactic treatment with atropine (1 mg/kg, sc) in normal saline and eserine (1 mg/kg, sc) in dimethyl sulfoxide. Control groups were treated with vehicle propylene glycol (0.1 ml/kg, sc), atropine in normal saline and eserine in dimethyl sulfoxide. The hens were euthanized at different time points such as 1, 2, 5, 10 and 20 days, and the tissues from cerebrum, midbrain, cerebellum, brainstem and spinal cord were quickly dissected and frozen for mRNA (northern) studies. Northern blots were probed with BCL2, GADD45, beta actin, and 28S RNA to investigate their expression pattern. Another set of hens was treated for a series of time points and perfused with phosphate buffered saline and fixative for histological studies. Various staining protocols such as Hematoxylin and Eosin (H and E); Sevier-Munger; Cresyl echt Violet for Nissl substance; and Gallocynin stain for Nissl granules were used to assess various patterns of cell death and degenerative changes. Complex cell death mechanisms may be involved in the neuronal and axonal degeneration. These data indicate altered and differential mRNA expressions of BCL2 (anti apoptotic gene) and GADD45 (DNA damage inducible gene) in various tissues. Increased cell death and other degenerative changes noted in the susceptible regions (spinal cord and cerebellum) than the resistant region (cerebrum), may indicate complex molecular pathways via altered BCL2 and GADD45 gene expression, causing the homeostatic imbalance between cell survival and cell death mechanisms. Semi quantitative

  20. Dynamic mechanical properties of methacrylic-acid-grafted polyethylene films. [Gamma radiation

    Energy Technology Data Exchange (ETDEWEB)

    Nakano, Y.; Omichi, H.; MacKnight, W.J.


    A dynamical mechanical relaxation study has been made of low density polyethylene films to which methacrylic acid has been grafted by ..gamma.. irradiation. The grafted films retain the original degree of crystallinity and show only slight changes in melting points and melt viscosities, indicating that the grafted methacrylic acid side chains are long, few in number, and completely phase separated from the polyethylene matrix. Three dispersion regions are observed in plots of the loss modulus, E'' vs. temperature at constant frequency and these are labeled ..gamma.., ..beta.., ..cap alpha..', in order of increasing temperature. The ..cap alpha..' peak, above 215/sup 0/C, was assigned to microbrownian segmental motions accompanying the T/sub g/ of polymethacrylic acid. The ..beta.. peak, at -20/sup 0/C, was assigned to motions accompanying the T/sub g/ of branched polyethylene, and the ..gamma.. peak, at -120/sup 0/C, was assigned to local motions of a few CH/sub 2/ sequences in polyethylene.

  1. Mechanism of Oxidation of (p-Substituted Phenylthioacetic Acids with N-Bromophthalimide

    Directory of Open Access Journals (Sweden)

    N. M. I. Alhaji


    Full Text Available The kinetics of oxidation of (phenylthioacetic acid (PTAA by N-Bromophthalimide (NBP in acetonitrile-water solvent mixture at 298 K in the presence of perchloric acid has been followed potentiometrically. The reaction is first-order each in NBP and PTAA and inverse fractional-order in H+. Also, it has been found that the reaction rate is not affected by changes in ionic strength of the reaction medium or by the addition of chemicals such as phthalimide, acrylonitrile and potassium bromide. However, an increase in the water content of the solvent mixture causes an increase in the rate of reaction. These observations have been well analyzed in favour of a SN2-type mechanism, involving NBP itself as the reactive species. Effect of substituents on the reaction rate has been analysed by employing various (p-sustituted phenylthioacetic acids. The electron-releasing substituent in the phenyl ring of PTAA accelerates the reaction rate while the electron-withdrawing substituent retards the rate. The excellently linear Hammett plot yields a large negative ρ value, supporting the involvement a bromosulphonium ion intermediate in the rate-determining step.

  2. Unsaturated Fatty Acid Synthesis in the Gastric Pathogen Helicobacter pylori Proceeds via a Backtracking Mechanism. (United States)

    Bi, Hongkai; Zhu, Lei; Jia, Jia; Zeng, Liping; Cronan, John E


    Helicobacter pylori is a Gram-negative bacterium that inhabits the upper gastrointestinal tract in humans, and the presence of this pathogen in the gut microbiome increases the risk of peptic ulcers and stomach cancer. H. pylori depends on unsaturated fatty acid (UFA) biosynthesis for maintaining membrane structure and function. Although some of the H. pylori enzymes involved in UFA biosynthesis are functionally homologous with the enzymes found in Escherichia coli, we show here that an enzyme HP0773, now annotated as FabX, uses an unprecedented backtracking mechanism to not only dehydrogenate decanoyl-acyl carrier protein (ACP) in a reaction that parallels that of acyl-CoA dehydrogenase, the first enzyme of the fatty acid β-oxidation cycle, but also isomerizes trans-2-decenoyl-ACP to cis-3-decenoyl-ACP, the key UFA synthetic intermediate. Thus, FabX reverses the normal fatty acid synthesis cycle in H. pylori at the C10 stage. Overall, this unusual FabX activity may offer a broader explanation for how many bacteria that lack the canonical pathway enzymes produce UFA-containing phospholipids.

  3. Dietary abscisic acid ameliorates influenza-virus-associated disease and pulmonary immunopathology through a PPARγ-dependent mechanism. (United States)

    Hontecillas, Raquel; Roberts, Paul C; Carbo, Adria; Vives, Cristina; Horne, William T; Genis, Sandra; Velayudhan, Binu; Bassaganya-Riera, Josep


    The anti-inflammatory phytohormone abscisic acid (ABA) modulates immune and inflammatory responses in mouse models of colitis and obesity. ABA has been identified as a ligand of lanthionine synthetase C-like 2, a novel therapeutic target upstream of the peroxisome proliferator-activated receptor γ (PPARγ) pathway. The goal of this study was to investigate the immune modulatory mechanisms underlying the anti-inflammatory efficacy of ABA against influenza-associated pulmonary inflammation. Wild-type (WT) and conditional knockout mice with defective PPARγ expression in lung epithelial and hematopoietic cells (cKO) treated orally with or without ABA (100 mg/kg diet) were challenged with influenza A/Udorn (H3N2) to assess ABA's impact in disease, lung lesions and gene expression. Dietary ABA ameliorated disease activity and lung inflammatory pathology, accelerated recovery and increased survival in WT mice. ABA suppressed leukocyte infiltration and monocyte chemotactic protein 1 mRNA expression in WT mice through PPARγ since this effect was abrogated in cKO mice. ABA ameliorated disease when administered therapeutically on the same day of the infection to WT but not mice lacking PPARγ in myeloid cells. We also show that ABA's greater impact is between days 7 and 10 postchallenge when it regulates the expression of genes involved in resolution, like 5-lipoxygenase and other members of the 5-lipoxygenase pathway. Furthermore, ABA significantly increased the expression of the immunoregulatory cytokine interleukin-10 in WT mice. Our results show that ABA, given preventively or therapeutically, ameliorates influenza-virus-induced pathology by activating PPARγ in pulmonary immune cells, suppressing initial proinflammatory responses and promoting resolution.

  4. Acid activation mechanism of the influenza A M2 proton channel. (United States)

    Liang, Ruibin; Swanson, Jessica M J; Madsen, Jesper J; Hong, Mei; DeGrado, William F; Voth, Gregory A


    The homotetrameric influenza A M2 channel (AM2) is an acid-activated proton channel responsible for the acidification of the influenza virus interior, an important step in the viral lifecycle. Four histidine residues (His37) in the center of the channel act as a pH sensor and proton selectivity filter. Despite intense study, the pH-dependent activation mechanism of the AM2 channel has to date not been completely understood at a molecular level. Herein we have used multiscale computer simulations to characterize (with explicit proton transport free energy profiles and their associated calculated conductances) the activation mechanism of AM2. All proton transfer steps involved in proton diffusion through the channel, including the protonation/deprotonation of His37, are explicitly considered using classical, quantum, and reactive molecular dynamics methods. The asymmetry of the proton transport free energy profile under high-pH conditions qualitatively explains the rectification behavior of AM2 (i.e., why the inward proton flux is allowed when the pH is low in viral exterior and high in viral interior, but outward proton flux is prohibited when the pH gradient is reversed). Also, in agreement with electrophysiological results, our simulations indicate that the C-terminal amphipathic helix does not significantly change the proton conduction mechanism in the AM2 transmembrane domain; the four transmembrane helices flanking the channel lumen alone seem to determine the proton conduction mechanism.

  5. Effects of Inorganic Fillers on the Thermal and Mechanical Properties of Poly(lactic acid

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    Xingxun Liu


    Full Text Available Addition of filler to polylactic acid (PLA may affect its crystallization behavior and mechanical properties. The effects of talc and hydroxyapatite (HA on the thermal and mechanical properties of two types of PLA (one amorphous and one semicrystalline have been investigated. The composites were prepared by melt blending followed by injection molding. The molecular weight, morphology, mechanical properties, and thermal properties have been characterized by gel permeation chromatography (GPC, scanning electron microscope (SEM, instron tensile tester, thermogravimetric analysis (TGA, differential scanning calorimetry (DSC, and dynamic mechanical analysis (DMA. It was found that the melting blending led to homogeneous distribution of the inorganic filler within the PLA matrix but decreased the molecular weight of PLA. Regarding the filler, addition of talc increased the crystallinity of PLA, but HA decreased the crystallinity of PLA. The tensile strength of the composites depended on the crystallinity of PLA and the interfacial properties between PLA and the filler, but both talc and HA filler increased the toughness of PLA.

  6. Folic acid supplementation improves microvascular function in older adults through nitric oxide-dependent mechanisms. (United States)

    Stanhewicz, Anna E; Alexander, Lacy M; Kenney, W Larry


    Older adults have reduced vascular endothelial function, evidenced by attenuated nitric oxide (NO)-dependent cutaneous vasodilatation. Folic acid and its metabolite, 5-methyltetrahydrofolate (5-MTHF), are reported to improve vessel function. We hypothesized that (i) local 5-MTHF administration and (ii) chronic folic acid supplementation would improve cutaneous microvascular function in ageing through NO-dependent mechanisms. There were two separate studies in which there were 11 young (Y: 22 ± 1 years) and 11 older (O: 71 ± 3 years) participants. In both studies, two intradermal microdialysis fibres were placed in the forearm skin for local delivery of lactated Ringer's solution with or without 5 mM 5-MTHF. Red cell flux was measured by laser-Doppler flowmetry. Cutaneous vascular conductance [CVC=red cell flux/mean arterial pressure] was normalized as percentage maximum CVC (%CVCmax) (28 mM sodium nitroprusside, local temperature 43°C). In study 1 after CVC plateaued during local heating, 20 mM NG-nitro-L-arginine methyl ester (L-NAME) was perfused at each site to quantify NO-dependent vasodilatation. The local heating plateau (%CVCmax: O = 82 ± 3 vs Y = 96 ± 1, P = 0.002) and NO-dependent vasodilatation (%CVCmax: O = 26 ± 6% vs Y = 49 ± 5, P = 0.03) were attenuated in older participants. 5-MTHF augmented the overall (%CVCmax = 91 ± 2, P = 0.03) and NO-dependent (%CVCmax = 43 ± 9%, P = 0.04) vasodilatation in older but not young participants. In study 2 the participants ingested folic acid (5 mg/day) or placebo for 6 weeks in a randomized, double-blind, crossover design. A rise in oral temperature of 1°C was induced using a water-perfused suit, body temperature was held and 20 mM L-NAME was perfused at each site. Older participants had attenuated reflex (%CVCmax: O = 31 ± 8 vs Y = 44 ± 5, P = 0.001) and NO-dependent (%CVCmax: O = 9 ± 2 vs Y = 21 ± 2, P = 0.003) vasodilatation. Folic acid increased CVC (%CVCmax = 47 ± 5%, P = 0.001) and NO

  7. The EGFR/ErbB3 Pathway Acts as a Compensatory Survival Mechanism upon c-Met Inhibition in Human c-Met+ Hepatocellular Carcinoma.

    Directory of Open Access Journals (Sweden)

    Steven N Steinway

    Full Text Available c-Met, a high-affinity receptor for Hepatocyte Growth Factor (HGF, plays a critical role in tumor growth, invasion, and metastasis. Hepatocellular carcinoma (HCC patients with activated HGF/c-Met signaling have a significantly worse prognosis. Targeted therapies using c-Met tyrosine kinase inhibitors are currently in clinical trials for HCC, although receptor tyrosine kinase inhibition in other cancers has demonstrated early success. Unfortunately, therapeutic effect is frequently not durable due to acquired resistance.We utilized the human MHCC97-H c-Met positive (c-Met+ HCC cell line to explore the compensatory survival mechanisms that are acquired after c-Met inhibition. MHCC97-H cells with stable c-Met knockdown (MHCC97-H c-Met KD cells were generated using a c-Met shRNA vector with puromycin selection and stably transfected scrambled shRNA as a control. Gene expression profiling was conducted, and protein expression was analyzed to characterize MHCC97-H cells after blockade of the c-Met oncogene. A high-throughput siRNA screen was performed to find putative compensatory survival proteins, which could drive HCC growth in the absence of c-Met. Findings from this screen were validated through subsequent analyses.We have previously demonstrated that treatment of MHCC97-H cells with a c-Met inhibitor, PHA665752, results in stasis of tumor growth in vivo. MHCC97-H c-Met KD cells demonstrate slower growth kinetics, similar to c-Met inhibitor treated tumors. Using gene expression profiling and siRNA screening against 873 kinases and phosphatases, we identified ErbB3 and TGF-α as compensatory survival factors that are upregulated after c-Met inhibition. Suppressing these factors in c-Met KD MHCC97-H cells suppresses tumor growth in vitro. In addition, we found that the PI3K/Akt signaling pathway serves as a negative feedback signal responsible for the ErbB3 upregulation after c-Met inhibition. Furthermore, in vitro studies demonstrate that

  8. Association of left ventricular mechanical dyssynchrony with survival benefit from revascularization: a study of gated positron emission tomography in patients with ischemic LV dysfunction and narrow QRS

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    AlJaroudi, Wael [Imaging Institute, Heart and Vascular, Cleveland, OH (United States); Sydell and Arnold Miller Family Heart and Vascular Institute, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, Cleveland, OH (United States); Alraies, M.C. [Cleveland Clinic, Department of Hospital Medicine, Cleveland, OH (United States); Hachamovitch, Rory; Jaber, Wael A.; Brunken, Richard; Cerqueira, Manuel D.; Marwick, Thomas [Imaging Institute, Heart and Vascular, Cleveland, OH (United States)


    LV mechanical dyssynchrony (LVMD) is a risk marker in narrow QRS cardiomyopathy, but its association with treatment outcome is not well defined. We determined the incremental prognostic value of LVMD in ischemic cardiomyopathy, and assessed its interaction with scar, myocardium in jeopardy and subsequent revascularization. Stress and rest {sup 82}Rb gated PET were performed in 486 consecutive patients (66 {+-} 11 years of age, 82 % men, LV ejection fraction 26 {+-} 6 %) with ischemic cardiomyopathy and QRS <120 ms. LVMD was determined as the standard deviation (SD) of the regional time to minimum volume on phase analysis of the gated PET scan. A propensity score was determined to adjust for nonrandomized referral after imaging to coronary artery bypass grafting (CABG). In a Cox proportional hazards model used to determine the association between measures of LVMD and survival time, CABG was included as a time-dependent covariate and the use of an implantable cardiac defibrillator (ICD) after imaging was modeled as a stratification factor. Over 1.9 {+-} 1.4 years, 96 patients (20 %) underwent CABG and 108 (22 %) died. LVMD was a predictor of mortality (HR 1.16. 95 % CI 1.03;1.30, per 10 increase in phase SD, p = 0.02) after adjusting for baseline covariates, prior ICD use, the use of postimaging CABG, and other imaging data. There was a significant interaction between phase SD and CABG. Nested Cox models showed that LVMD carried prognostic information incremental to clinical variables, ejection fraction and CABG. LVMD is an independent predictor of all-cause mortality in ischemic cardiomyopathy, and may identify patients with a differential survival benefit from CABG versus medical therapy. (orig.)

  9. Inherent dynamics of the acid-sensing ion channel 1 correlates with the gating mechanism.

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    Huaiyu Yang


    Full Text Available The acid-sensing ion channel 1 (ASIC1 is a key receptor for extracellular protons. Although numerous structural and functional studies have been performed on this channel, the structural dynamics underlying the gating mechanism remains unknown. We used normal mode analysis, mutagenesis, and electrophysiological methods to explore the relationship between the inherent dynamics of ASIC1 and its gating mechanism. Here we show that a series of collective motions among the domains and subdomains of ASIC1 correlate with its acid-sensing function. The normal mode analysis result reveals that the intrinsic rotation of the extracellular domain and the collective motions between the thumb and finger induced by proton binding drive the receptor to experience a deformation from the extracellular domain to the transmembrane domain, triggering the channel pore to undergo "twist-to-open" motions. The movements in the transmembrane domain indicate that the likely position of the channel gate is around Leu440. These motion modes are compatible with a wide body of our complementary mutations and electrophysiological data. This study provides the dynamic fundamentals of ASIC1 gating.

  10. Molecular mechanisms of the coordination between astaxanthin and fatty acid biosynthesis in Haematococcus pluvialis (Chlorophyceae). (United States)

    Chen, Guanqun; Wang, Baobei; Han, Danxiang; Sommerfeld, Milton; Lu, Yinghua; Chen, Feng; Hu, Qiang


    Astaxanthin, a red ketocarotenoid with strong antioxidant activity and high commercial value, possesses important physiological functions in astaxanthin-producing microalgae. The green microalga Haematococcus pluvialis accumulates up to 4% fatty acid-esterified astaxanthin (by dry weight), and is used as a model species for exploring astaxanthin biosynthesis in unicellular photosynthetic organisms. Although coordination of astaxanthin and fatty acid biosynthesis in a stoichiometric fashion was observed in H. pluvialis, the interaction mechanism is unclear. Here we dissected the molecular mechanism underlying coordination between the two pathways in H. pluvialis. Our results eliminated possible coordination of this inter-dependence at the transcriptional level, and showed that this interaction was feedback-coordinated at the metabolite level. In vivo and in vitro experiments indicated that astaxanthin esterification drove the formation and accumulation of astaxanthin. We further showed that both free astaxanthin biosynthesis and esterification occurred in the endoplasmic reticulum, and that certain diacylglycerol acyltransferases may be the candidate enzymes catalyzing astaxanthin esterification. A model of astaxanthin biosynthesis in H. pluvialis was subsequently proposed. These findings provide further insights into astaxanthin biosynthesis in H. pluvialis.

  11. Valproic acid increases conservative homologous recombination frequency and reactive oxygen species formation: a potential mechanism for valproic acid-induced neural tube defects. (United States)

    Defoort, Ericka N; Kim, Perry M; Winn, Louise M


    Valproic acid, a commonly used antiepileptic agent, is associated with a 1 to 2% incidence of neural tube defects when taken during pregnancy; however, the molecular mechanism by which this occurs has not been elucidated. Previous research suggests that valproic acid exposure leads to an increase in reactive oxygen species (ROS). DNA damage due to ROS can result in DNA double-strand breaks, which can be repaired through homologous recombination (HR), a process that is not error-free and can result in detrimental genetic changes. Because the developing embryo requires tight regulation of gene expression to develop properly, we propose that the loss or dysfunction of genes involved in embryonic development through aberrant HR may ultimately cause neural tube defects. To determine whether valproic acid induces HR, Chinese hamster ovary 3-6 cells, containing a neomycin direct repeat recombination substrate, were exposed to valproic acid for 4 or 24 h. A significant increase in HR after exposure to valproic acid (5 and 10 mM) for 24 h was observed, which seems to occur through a conservative HR mechanism. We also demonstrated that exposure to valproic acid (5 and 10 mM) significantly increased intracellular ROS levels, which were attenuated by preincubation with polyethylene glycol-conjugated (PEG)-catalase. A significant change in the ratio of 8-hydroxy-2'-deoxyguanosine/2'-de-oxyguanosine, a measure of DNA oxidation, was not observed after valproic acid exposure; however, preincubation with PEG-catalase significantly blocked the increase in HR. These data demonstrate that valproic acid increases HR frequency and provides a possible mechanism for valproic acid-induced neural tube defects.

  12. Effect of All-trans Retinoic Acid on Airway Inflammation in Asthmatic Rats and Its Mechanism

    Institute of Scientific and Technical Information of China (English)

    方红; 金红芳; 王宏伟


    Summary: The inhibitive effects of all-trans retinoic acid (ARTA) on airway inflammation in asthmatic rats and its mechanism on the basis of the regulation of nuclear factor kappaB (NF-κB) were explored. Thirty-two SD rats were randomly divided into 4 groups: control group, asthma group,dexamethasone treatment group and retinotic acid treatment group. The total and differential cell counts in the collected bronchoalveolar lavage fluid (BALF) were measured. The pathological changes in lung tissues were estimated by scoring. The expression of NF-κB inhibitor (IκBa), NF-κB,intercellular adhering molecule-1 (ICAM-1) in lung tissue was detected by immunohistochemical method. The results showed that in the two treatment groups, the total cell counts and proportion of inflammatory cells in BALF were significantly reduced, but there was no significant difference in differential cell counts in BALF between, them. The pathological changes in lung tissues in the treatment groups were significantly attenuated as compared with asthma group. Except the epithelial injury in retinotic acid treatment group was milder than in dexamethasone treatment group, the remaining lesions showed no significant difference between them. In the two treatment groups, the expression of IκBa was increased, while the expression of NF-κB and ICAM-1 decreased with the difference between the two groups being not significant. It was concluded that the similar anti-inflammatory effects and mechanism of ATRA on airway in asthmatic rats to those of dexamethasone were contributed to the increase of cytoplasmic IκBa content and suppression of NF-cB activation and expression.

  13. Effect of urine pH changed by dietary intervention on uric acid clearance mechanism of pH-dependent excretion of urinary uric acid

    Directory of Open Access Journals (Sweden)

    Kanbara Aya


    Full Text Available Abstract Background The finding reported in a previous paper - alkalization of urine facilitates uric acid excretion - is contradictory to what one might expect to occur: because food materials for the alkalization of urine contain fewer purine bodies than those for acidification, less uric acid in alkaline urine should have been excreted than in acid urine. To make clear what component of uric acid excretion mechanisms is responsible for this unexpected finding, we simultaneously collected data for the concentration of both creatinine and uric acid in serum as well as in urine, in order to calculate both uric acid and creatinine clearances. Methods Within the framework of the Japanese government’s health promotion program, we made recipes which consisted of protein-rich and less vegetable-fruit food materials for H + -load (acidic diet and others composed of less protein and more vegetable-fruit rich food materials (alkaline diet. This is a crossover study within some limitations. Healthy female students, who had no medical problems at the regular physical examination provided by the university, were enrolled in this consecutive 5-day study for each test. From whole-day collected urine, total volume, pH, organic acid, creatinine, uric acid, titratable acid and all cations (Na+,K+,Ca2+,Mg2+,NH4+ and anions (Cl−,SO42−,PO4− necessary for the estimation of acid–base balance were measured. In the early morning before breakfast of the 1st, 3rd and 5th experimental day, we sampled 5 mL of blood to estimate the creatinine and uric acid concentration in serum. Results and discussion Urine pH reached a steady state 3 days after switching from ordinary daily diets to specified regimens. The amount of acid generated ([SO42−] + organic acid − gut alkaliwas linearly related with the excretion of acid (titratable acid + [NH4+] − [HCO3−], indicating that H + in urine is generated by the metabolic degradation of

  14. Interaction of metal ions and amino acids - Possible mechanisms for the adsorption of amino acids on homoionic smectite clays (United States)

    Gupta, A.; Loew, G. H.; Lawless, J.


    A semiempirical molecular orbital method is used to characterize the binding of amino acids to hexahydrated Cu(2+) and Ni(2+), a process presumed to occur when they are adsorbed in the interlamellar space of homoionic smectite clays. Five alpha-amino acids, beta-alanine, and gamma-aminobutyric acid were used to investigate the metal ion and amino acid specificity in binding. It was assumed that the alpha, beta, and gamma-amino acids would bind as bidentate anionic ligands, forming either 1:1 or 1:2 six-coordinated five, six, and seven-membered-ring chelate complexes, respectively. Energies of complex formation, optimized geometries, and electron and spin distribution were determined; and steric constraints of binding of the amino acids to the ion-exchanged cations in the interlamellar spacing of a clay were examined. Results indicate that hexahydrated Cu(2+) forms more stable complexes than hexahydrated Ni(2+) with all the amino acids studied. However, among these amino acids, complex formation does not favor the adsorption of the biological subset. Calculated energetics of complex formation and steric constraints are shown to predict that 1:1 rather than 1:2 metal-amino acid complexes are generally favored in the clay.

  15. Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics (United States)

    Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng


    Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains.

  16. Global insights into acetic acid resistance mechanisms and genetic stability of Acetobacter pasteurianus strains by comparative genomics. (United States)

    Wang, Bin; Shao, Yanchun; Chen, Tao; Chen, Wanping; Chen, Fusheng


    Acetobacter pasteurianus (Ap) CICC 20001 and CGMCC 1.41 are two acetic acid bacteria strains that, because of their strong abilities to produce and tolerate high concentrations of acetic acid, have been widely used to brew vinegar in China. To globally understand the fermentation characteristics, acid-tolerant mechanisms and genetic stabilities, their genomes were sequenced. Genomic comparisons with 9 other sequenced Ap strains revealed that their chromosomes were evolutionarily conserved, whereas the plasmids were unique compared with other Ap strains. Analysis of the acid-tolerant metabolic pathway at the genomic level indicated that the metabolism of some amino acids and the known mechanisms of acetic acid tolerance, might collaboratively contribute to acetic acid resistance in Ap strains. The balance of instability factors and stability factors in the genomes of Ap CICC 20001 and CGMCC 1.41 strains might be the basis for their genetic stability, consistent with their stable industrial performances. These observations provide important insights into the acid resistance mechanism and the genetic stability of Ap strains and lay a foundation for future genetic manipulation and engineering of these two strains.

  17. Effects of ascorbic acid and sugars on solubility, thermal, and mechanical properties of egg white protein gels. (United States)

    Mohammadi Nafchi, Abdorreza; Tabatabaei, Ramin H; Pashania, Bita; Rajabi, Hadiseh Z; Karim, A A


    The effects of reducing sugars (fructose, glucose, ribose, and arabinose), sucrose, and ascorbic acid were studied on thermo-mechanical properties and crosslinking of egg white proteins (EWP) through Maillard reaction. Sugars (0%, 1%, 5%, and 10%) and ascorbic acid (0%, 0.25%, 0.5%, and 2.5%) were added to EWP solutions. Thermal denaturation and crosslinking of EWP were characterized by differential scanning calorimetry (DSC). Mechanical properties (failure strength, failure strain and Young's modulus) of modified and unmodified EWP gels were evaluated by texture analyzer. Ascorbic acid decreased thermal denaturation temperature of EWP, but the reducing sugars increased the denaturation temperature. DSC thermograms of EWP showed that ascorbic acid exhibited an exothermic transition (≈110 °C) which was attributed to Maillard crosslinking of the protein. The reduction in pH (from 7.21 to ≈6) and protein solubility of egg white protein gel (from ≈70% to ≈10%) provides further evidence of the formation of Maillard cross-linking. Reactive sugars (ribose and arabinose) increased the mechanical properties of EWP gels, whereas ascorbic acid decreased the mechanical properties. Generally, the effect of ascorbic acid was more pronounced than that of various reducing sugars on the thermal and mechanical properties of egg white proteins.

  18. Comparison of sodium hypochlorite-based foam and peroxyacetic acid-based fog sanitizing procedures in a salmon smokehouse: Survival of the general microflora and Listeria monocytogenes

    DEFF Research Database (Denmark)

    Bagge, Dorthe; Gardshodn, K.; Gram, Lone


    in the composition of the flora, with Pseudomonas spp. and Alcaligenes spp. being the dominant gram- negative bacteria and Kurthia spp. and Bacillus spp. being the surviving gram-positive bacteria. Bacteria were very sensitive to fog sanitization, and yeasts accounted for almost half of the surviving flora...

  19. Mechanisms leading to oligomers and SOA through aqueous photooxidation: insights from OH radical oxidation of acetic acid and methylglyoxal

    Directory of Open Access Journals (Sweden)

    Y. Tan


    Full Text Available Previous experiments have demonstrated that the aqueous OH radical oxidation of methylglyoxal produces low volatility products including pyruvate, oxalate and oligomers. These products are found predominantly in the particle phase in the atmosphere, suggesting that methylglyoxal is a precursor of secondary organic aerosol (SOA. Acetic acid plays a central role in the aqueous oxidation of methylglyoxal and it is a ubiquitous product of gas phase photochemistry, making it a potential "aqueous" SOA precursor in its own right. However, the fate of acetic acid upon aqueous-phase oxidation is not well understood. In this research, acetic acid (20 μM–10 mM was oxidized by OH radicals, and pyruvic acid and methylglyoxal experimental samples were analyzed using new analytical methods, in order to better understand the formation of SOA from acetic acid and methylglyoxal. Glyoxylic, glycolic, and oxalic acids formed from acetic acid and OH radicals. In contrast to the aqueous OH radical oxidation of methylglyoxal, the aqueous OH radical oxidation of acetic acid did not produce succinic acid and oligomers. This suggests that the methylgloxal-derived oligomers do not form through the acid catalyzed esterification pathway proposed previously. Using results from these experiments, radical mechanisms responsible for oligomer formation from methylglyoxal oxidation in clouds and wet aerosols are proposed. The importance of acetic acid/acetate as an SOA precursor is also discussed. We hypothesize that this and similar chemistry is central to the daytime formation of oligomers in wet aerosols.

  20. Progress in engineering acid stress resistance of lactic acid bacteria. (United States)

    Wu, Chongde; Huang, Jun; Zhou, Rongqing


    Lactic acid bacteria (LAB) are widely used for the production of a variety of fermented foods, and are considered as probiotic due to their health-promoting effect. However, LAB encounter various environmental stresses both in industrial fermentation and application, among which acid stress is one of the most important survival challenges. Improving the acid stress resistance may contribute to the application and function of probiotic action to the host. Recently, the advent of genomics, functional genomics and high-throughput technologies have allowed for the understanding of acid tolerance mechanisms at a systems level, and many method to improve acid tolerance have been developed. This review describes the current progress in engineering acid stress resistance of LAB. Special emphasis is placed on engineering cellular microenvironment (engineering amino acid metabolism, introduction of exogenous biosynthetic capacity, and overproduction of stress response proteins) and maintaining cell membrane functionality. Moreover, strategies to improve acid tolerance and the related physiological mechanisms are also discussed.

  1. Dipicolinic Acid Release by Germinating Clostridium difficile Spores Occurs through a Mechanosensing Mechanism (United States)

    Francis, Michael B.


    ABSTRACT Classically, dormant endospores are defined by their resistance properties, particularly their resistance to heat. Much of the heat resistance is due to the large amount of dipicolinic acid (DPA) stored within the spore core. During spore germination, DPA is released and allows for rehydration of the otherwise-dehydrated core. In Bacillus subtilis, 7 proteins are encoded by the spoVA operon and are important for DPA release. These proteins receive a signal from the activated germinant receptor and release DPA. This DPA activates the cortex lytic enzyme CwlJ, and cortex degradation begins. In Clostridium difficile, spore germination is initiated in response to certain bile acids and amino acids. These bile acids interact with the CspC germinant receptor, which then transfers the signal to the CspB protease. Activated CspB cleaves the cortex lytic enzyme, pro-SleC, to its active form. Subsequently, DPA is released from the core. C. difficile encodes orthologues of spoVAC, spoVAD, and spoVAE. Of these, the B. subtilis SpoVAC protein was shown to be capable of mechanosensing. Because cortex degradation precedes DPA release during C. difficile spore germination (opposite of what occurs in B. subtilis), we hypothesized that cortex degradation would relieve the osmotic constraints placed on the inner spore membrane and permit DPA release. Here, we assayed germination in the presence of osmolytes, and we found that they can delay DPA release from germinating C. difficile spores while still permitting cortex degradation. Together, our results suggest that DPA release during C. difficile spore germination occurs though a mechanosensing mechanism. IMPORTANCE Clostridium difficile is transmitted between hosts in the form of a dormant spore, and germination by C. difficile spores is required to initiate infection, because the toxins that are necessary for disease are not deposited on the spore form. Importantly, the C. difficile spore germination pathway

  2. Unconjugated secondary bile acids activate the unfolded protein response and induce golgi fragmentation via a src-kinase-dependant mechanism (United States)

    Sharma, Ruchika; Quilty, Francis; Gilmer, John F.; Long, Aideen; Byrne, Anne-Marie


    Bile acids are components of gastro-duodenal refluxate and regarded as causative agents in oesophageal disease but the precise mechanisms are unknown. Here we demonstrate that a specific subset of physiological bile acids affect the protein secretory pathway by inducing ER stress, activating the Unfolded Protein Response (UPR) and causing disassembly of the Golgi apparatus in oesophageal cells. Deoxycholic acid (DCA), Chemodeoxycholic acid (CDCA) and Lithocholic acid (LCA) activated the PERK arm of the UPR, via phosphorylation of eIF2α and up-regulation of ATF3, CHOP and BiP/GRP78. UPR activation by these bile acids is mechanistically linked with Golgi fragmentation, as modulating the UPR using a PERK inhibitor (GSK2606414) or salubrinal attenuated bile acid-induced effects on Golgi structure. Furthermore we demonstrate that DCA, CDCA and LA activate Src kinase and that inhibition of this kinase attenuated both bile acid-induced BiP/GRP78 expression and Golgi fragmentation. This study highlights a novel mechanism whereby environmental factors (bile acids) impact important cellular processes regulating cell homeostasis, including the UPR and Golgi structure, which may contribute to cancer progression in the oesophagus. PMID:27888615

  3. Automated Quantification of the Impact of Defects on the Mechanical Behavior of Deoxyribonucleic acid Origami Nanoplates. (United States)

    Liang, Bowen; Nagarajan, Anand; Hudoba, Michael W; Alvarez, Ricardo; Castro, Carlos E; Soghrati, Soheil


    Deoxyribonucleic acid (DNA) origami is a method for the bottom-up self-assembly of complex nanostructures for applications, such as biosensing, drug delivery, nanopore technologies, and nanomechanical devices. Effective design of such nanostructures requires a good understanding of their mechanical behavior. While a number of studies have focused on the mechanical properties of DNA origami structures, considering defects arising from molecular self-assembly is largely unexplored. In this paper, we present an automated computational framework to analyze the impact of such defects on the structural integrity of a model DNA origami nanoplate. The proposed computational approach relies on a noniterative conforming to interface-structured adaptive mesh refinement (CISAMR) algorithm, which enables the automated transformation of a binary image of the nanoplate into a high fidelity finite element model. We implement this technique to quantify the impact of defects on the mechanical behavior of the nanoplate by performing multiple simulations taking into account varying numbers and spatial arrangements of missing DNA strands. The analyses are carried out for two types of loading: uniform tensile displacement applied on all the DNA strands and asymmetric tensile displacement applied to strands at diagonal corners of the nanoplate.

  4. Enhancement of Mechanical and Thermal Properties of Polylactic Acid/Polycaprolactone Blends by Hydrophilic Nanoclay

    Directory of Open Access Journals (Sweden)

    Chern Chiet Eng


    Full Text Available The effects of hydrophilic nanoclay, Nanomer PGV, on mechanical properties of Polylactic Acid (PLA/Polycaprolactone (PCL blends were investigated and compared with hydrophobic clay, Montmorillonite K10. The PLA/PCL/clay composites were prepared by melt intercalation technique and the composites were characterized by X-ray Diffraction (XRD, Fourier Transform Infrared Spectroscopy (FTIR, Thermogravimetric Analysis (TGA, Dynamic Mechanical Analysis (DMA, Scanning Electron Microscopy (SEM, and Transmission Electron Microscopy (TEM. FTIR spectra indicated that formation of hydrogen bond between hydrophilic clay with the matrix. XRD results show that shifting of basal spacing when clay incorporated into polymer matrix. TEM micrographs reveal the formation of agglomerate in the composites. Based on mechanical properties results, addition of clay Nanomer PGV significantly enhances the flexibility of PLA/PCL blends about 136.26%. TGA showed that the presence of clay improve thermal stability of blends. DMA show the addition of clay increase storage modulus and the presence of clay Nanomer PGV slightly shift two Tg of blends become closer suggest that the presence of clay slightly compatibilizer the PLA/PCL blends. SEM micrographs revealed that presence of Nanomer PGV in blends influence the miscibility of the blends. The PLA/PCL blends become more homogeneous and consist of single phase morphology.

  5. Palladium-atom catalyzed formic acid decomposition and the switch of reaction mechanism with temperature. (United States)

    He, Nan; Li, Zhen Hua


    Formic acid decomposition (FAD) reaction has been an innovative way for hydrogen energy. Noble metal catalysts, especially palladium-containing nanoparticles, supported or unsupported, perform well in this reaction. Herein, we considered the simplest model, wherein one Pd atom is used as the FAD catalyst. With high-level theoretical calculations of CCSD(T)/CBS quality, we investigated all possible FAD pathways. The results show that FAD catalyzed by one Pd atom follows a different mechanism compared with that catalyzed by surfaces or larger clusters. At the initial stage of the reaction, FAD follows a dehydration route and is quickly poisoned by CO due to the formation of very stable PdCO. PdCO then becomes the actual catalyst for FAD at temperatures approximately below 1050 K. Beyond 1050 K, there is a switch of catalyst from PdCO to Pd atom. The results also show that dehydration is always favoured over dehydrogenation on either the Pd-atom or PdCO catalyst. On the Pd-atom catalyst, neither dehydrogenation nor dehydration follows the formate mechanism. In contrast, on the PdCO catalyst, dehydrogenation follows the formate mechanism, whereas dehydration does not. We also systematically investigated the performance of 24 density functional theory methods. We found that the performance of the double hybrid mPW2PLYP functional is the best, followed by the B3LYP, B3PW91, N12SX, M11, and B2PLYP functionals.

  6. Oxalic acid based chemical systems for electrochemical mechanical planarization of copper (United States)

    Lowalekar, Viral Pradeep

    In an ECMP process, a wafer is anodically baised during polishing. The electrical potential is the driving force to oxidize copper metal to ions. Copper ions then react with chemistry in the electrolyte to go in solution or form a passivation layer on the surface. The passivation layer is removed by a very low downforce (0.5--1 psi), causing copper to electrochemically dissolve in solution. Passive film formation during copper ECMP is key to the success of this process, since passivation reduces dissolution in the recessed areas, while elevations on the copper surface in direct contact with the ECMP pad are electrochemically planarized. If no passive film forms, then copper removal will be conformal from the elevated and recessed areas, and planarity will be lost. Chemical formulations for the electrochemical mechanical planarization (ECMP) of copper must contain constituents that are stable at anodic potentials. A key component of the formulation is a corrosion inhibitor, which is required to protect low lying areas while higher areas are selectively removed. Organic compounds, which adsorb on copper at low overpotentials and form a film by oxidation at higher overpotentials, may be particularly useful for ECMP. The main goal of the research reported in this dissertation is to understand and develop oxalic acid-based chemical systems suitable for ECMP of copper through electrochemical and surface investigations. Special attention was paid to the development of an inhibitor, which can function under applied potential conditions. Physical methods such as profilometry and four point probe were used to obtain copper removal rates. An organic compound, thiosalicylic acid (TSA), was identified and tested as a potential corrosion inhibitor for copper. TSA offers better protection than the conventionally used benzotriazole (BTA) by oxidizing at high anodic potentials to form a passive film on the copper surface. The passive film formed on the copper surface by addition of

  7. Transcriptomic analysis reveals the flooding tolerant mechanism in flooding tolerant line and abscisic acid treated soybean. (United States)

    Yin, Xiaojian; Hiraga, Susumu; Hajika, Makita; Nishimura, Minoru; Komatsu, Setsuko


    Soybean is highly sensitive to flooding stress and exhibits markedly reduced plant growth and grain yield under flooding conditions. To explore the mechanisms underlying initial flooding tolerance in soybean, RNA sequencing-based transcriptomic analysis was performed using a flooding-tolerant line and ABA-treated soybean. A total of 31 genes included 12 genes that exhibited similar temporal patterns were commonly changed in these plant groups in response to flooding and they were mainly involved in RNA regulation and protein metabolism. The mRNA expression of matrix metalloproteinase, glucose-6-phosphate isomerase, ATPase family AAA domain-containing protein 1, and cytochrome P450 77A1 was up-regulated in wild-type soybean under flooding conditions; however, no changes were detected in the flooding-tolerant line or ABA-treated soybean. The mRNA expression of cytochrome P450 77A1 was specifically up-regulated in root tips by flooding stress, but returned to the level found in control plants following treatment with the P450 inhibitor uniconazole. The survival ratio and root fresh weight of plants were markedly improved by 3-h uniconazole treatment under flooding stress. Taken together, these results suggest that cytochrome P450 77A1 is suppressed by uniconazole treatment and that this inhibition may enhance soybean tolerance to flooding stress.

  8. Survival Analysis

    CERN Document Server

    Miller, Rupert G


    A concise summary of the statistical methods used in the analysis of survival data with censoring. Emphasizes recently developed nonparametric techniques. Outlines methods in detail and illustrates them with actual data. Discusses the theory behind each method. Includes numerous worked problems and numerical exercises.

  9. Effects and mechanisms of the combined pollution of lanthanum and acid rain on the root phenotype of soybean seedlings. (United States)

    Sun, Zhaoguo; Wang, Lihong; Zhou, Qing; Huang, Xiaohua


    Rare earth pollution and acid rain pollution are both important environmental issues worldwide. In regions which simultaneously occur, the combined pollution of rare earth and acid rain becomes a new environmental issue, and the relevant research is rarely reported. Accordingly, we investigated the combined effects and mechanisms of lanthanum ion (La(3+)) and acid rain on the root phenotype of soybean seedlings. The combined pollution of low-concentration La(3+) and acid rain exerted deleterious effects on the phenotype and growth of roots, which were aggravated by the combined pollution of high-concentration La(3+) and acid rain. The deleterious effects of the combined pollution were stronger than those of single La(3+) or acid rain pollution. These stronger deleterious effects on the root phenotype and growth of roots were due to the increased disturbance of absorption and utilization of mineral nutrients in roots.

  10. Mechanisms of Oxidative Damage in Multiple Sclerosis and Neurodegenerative Diseases: Therapeutic Modulation via Fumaric Acid Esters

    Directory of Open Access Journals (Sweden)

    Ralf Gold


    Full Text Available Oxidative stress plays a crucial role in many neurodegenerative conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis and Parkinson’s as well as Huntington’s disease. Inflammation and oxidative stress are also thought to promote tissue damage in multiple sclerosis (MS. Recent data point at an important role of anti-oxidative pathways for tissue protection in chronic-progressive MS, particularly involving the transcription factor nuclear factor (erythroid-derived 2-related factor 2 (Nrf2. Thus, novel therapeutics enhancing cellular resistance to free radicals could prove useful for MS treatment. Here, fumaric acid esters (FAE are a new, orally available treatment option which had already been tested in phase II/III MS trials demonstrating beneficial effects on relapse rates and magnetic resonance imaging markers. In vitro, application of dimethylfumarate (DMF leads to stabilization of Nrf2, activation of Nrf2-dependent transcriptional activity and abundant synthesis of detoxifying proteins. Furthermore, application of FAE involves direct modification of the inhibitor of Nrf2, Kelch-like ECH-associated protein 1. On cellular levels, the application of FAE enhances neuronal survival and protects astrocytes against oxidative stress. Increased levels of Nrf2 are detected in the central nervous system of DMF treated mice suffering from experimental autoimmune encephalomyelitis (EAE, an animal model of MS. In EAE, DMF ameliorates the disease course and improves preservation of myelin, axons and neurons. Finally, Nrf2 is also up-regulated in the spinal cord of autopsy specimens from untreated patients with MS, probably as part of a naturally occurring anti-oxidative response. In summary, oxidative stress and anti-oxidative pathways are important players in MS pathophysiology and constitute a promising target for future MS therapies like FAE.

  11. Temperature-dependent benzoic acid elimination mechanisms in pyrolysis of (--cocaine

    Directory of Open Access Journals (Sweden)

    Michal Novák


    Full Text Available The thermal elimination of benzoic acid from (--cocaine is shown to be temperature-dependent. In the temperature range of 200-500 °C only a trans-elimination is observed leading to methylecgonidine. Above ca. 500 °C a second mechanism, the cis-elimination, comes up yielding a novel alkaloid methylisoecgonidine which has been characterized by means of mass spectrometry. At 600 °C the cis-elimination predominates. The trans-elimination is postulated a two-step process consisting of a 1,7- and a 1,5-hydrogen shift. The chemistry of cocaine base smoking is explained using the theory of chemical activation.

  12. Mechanical and thermal properties of polylactic acid composites reinforced with cellulose nanoparticles extracted from kenaf fibre (United States)

    Ketabchi, Mohammad Reza; Khalid, Mohammad; Thevy Ratnam, Chantara; Walvekar, Rashmi


    Different approaches have been attempted to use biomass as filler for production of biodegradable polymer composites. In this study, cellulose nanoparticles (CNP) extracted from kenaf fibres were used to produce polylactic acid (PLA) based biodegradable nanocomposites. CNP concentration was varied from 1-5 wt. % and blended with PLA using Brabender twin-screw compounder. Effects of CNP loading on the mechanical, thermal and dynamic properties of PLA were investigated. Studies on the morphological properties and influence of CNP loading on the properties of CNP/PLA nanocomposite were also conducted. The results show an adequate compatibility between CNP and PLA matrix. Moreover, addition of 3 wt. % of CNP improved the PLA tensile strength by 25%.

  13. Mechanism and kinetics in reactions of caffeic acid with radicals by pulse radiolysis and calculation

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xifeng; Cai, Zhongli; Katsumura, Yosuke [Tokyo Univ., Tokai, Ibaraki (Japan). Nuclear Engineering Research Lab


    The interaction of caffeic acid with e{sub aq}{sup -}, (CH{sub 3}){sub 2}(OH) CCH{sub 2}{sup {center_dot}}, CO{sub 2}{sup {center_dot}}{sup -}, H{sup {center_dot}}, {center_dot}OH and N{sub 3}{sup {center_dot}} radicals were studied by {gamma}-, pulse radiolysis and molecular orbital calculation. UV-visible spectra of electron/{center_dot}OH adducts, semi-quinone radicals of caffeic ions, and the stable products from the reactions were derived. The rate constants were determined. The attacked sites and the most favorable structures of the transient radicals were predicted. Reaction mechanisms were proposed. (author)

  14. Polaron conductivity mechanism in potassium acid phthalate crystal: AC-conductivity investigation (United States)

    Filipič, Cene; Levstik, Iva; Levstik, Adrijan; Hadži, Dušan


    The complex dielectric constant, \\varepsilon *(ν ,T), of potassium acid phthalate monocrystal (KAP) was investigated over the broad frequency and temperature range. While the imaginary part of dielectric constant ε‧‧(ν) increases rapidly with increasing temperature in the studied temperature range, the real part of dielectric constant ε‧(ν) increases only at high temperatures; there is almost no change of ε‧(ν) below 200 K. Both values of ε‧ and ε‧‧ are frequency dependent; the values increase with decreasing frequencies. At temperatures below 450 K the ac electrical conductivity and dielectric constant follow simultaneously the universal dielectric response (UDR). The analysis of the temperature dependence of the UDR parameter s in terms of the theoretical model for small polarons revealed that this mechanism governs the charge transport in KAP crystal in the studied temperature range.

  15. Structrue and Characteristics of Mesoporous Silica Synthesized in Acid Medium and Its Reaction Mechanism

    Institute of Scientific and Technical Information of China (English)

    LEI Jia-heng; ZHAO Jun; CHEN Yong-xi; GUO Li-ping; LIU Dan


    Structrue and pore characteristics of the mesoporous silica synthesized in acid medium were studied by means of XRD, HRTEM, BET, FT-IR, DSC-TGA, and the reaction mechanism was also investigated deeply. The results show that mesopores in the sample possess hexagonal arrays obviously, whereas the structure of silica matrix is amorphous. The results also show that the acting mode of silica and CTMA+ inside the mesopores was chemical bonding force. The structure of mesoporous silica was mainly dependent on the aggregational condition of micelle of CTMA+ as well as their liquid-crystallized status. In addition, condensation and dehydration of silicate radicals were accompanied in the process of calcination, which resulted in the mesoporous structure ordered in local range and the pore sizes largening.

  16. Kinetics and Mechanism of the Oxidation of Menthol by Potassium Bromate in Acidic Solution

    Directory of Open Access Journals (Sweden)

    Ravikant na


    Full Text Available No suitable method is available for the estimation of menthol, hence in all kinetic results reported in this chapter, menthol was in excess over potassium bromate and the stoichiometry was also determined under the experimental conditions where menthol (substrate was in excess over potassium bromate (oxidant. Present study was focused on the analysis of kinetics and mechanism of oxidation of neomenthol by potassium bromate in acidic medium. For oxidizing neomenthol, potassium bromate stock solution (5.0×10─2 mol. dm─3 was prepared by dissolving exactly weighed quantity of potassium bromate in doubly distilled water. The suitable reaction mixtures were prepared and left at 313 K for over 24 hours to ensure complete oxidation of neomenthol. The unreacted potassium bromate was determined iodometrically and the results indicate that one mole of potassium bromate is consumed for every three moles of neomenthol and leads to the formation of menthone (ketone.

  17. Molecular mechanisms and clinical applications of nordihydroguaiaretic acid (NDGA) and its derivatives: an update. (United States)

    Lü, Jian-Ming; Nurko, Jacobo; Weakley, Sarah M; Jiang, Jun; Kougias, Panagiotis; Lin, Peter H; Yao, Qizhi; Chen, Changyi


    Creosote bush, Larrea tridentata, is known as chaparral or greasewood in the United States and as gobernadora or hediondilla in Mexico. Nordihydroguaiaretic acid (NDGA), the main metabolite of the creosote bush, has been shown to have promising applications in the treatment of multiple diseases, including cardiovascular diseases, neurological disorders and cancers. Creosote bush is a promising agent of North American herbal medicine, and it has extensive pharmacological effects and specific mechanisms of actions. This review provides an update of recent in vitro and in vivo research about NDGA and describes experimental studies using NDGA as antioxidant. Also, potential medical uses based on the effects of NDGA on the cardiovascular, immune and neurological systems; cancer; tissue engineering; as well as pharmacokinetics and toxicity are discussed.

  18. Mild MPP(+) exposure impairs autophagic degradation through a novel lysosomal acidity-independent mechanism. (United States)

    Miyara, Masatsugu; Kotake, Yaichiro; Tokunaga, Wataru; Sanoh, Seigo; Ohta, Shigeru


    Parkinson's disease (PD) is the second most common neurodegenerative disorder, but its underlying cause remains unknown. Although recent studies using PD-related neurotoxin MPP(+) suggest autophagy involvement in the pathogenesis of PD, the effect of MPP(+) on autophagic processes under mild exposure, which mimics the slow progressive nature of PD, remains largely unclear. We examined the effect of mild MPP(+) exposure (10 and 200 μM for 48 h), which induces a more slowly developing cell death, on autophagic processes and the mechanistic differences with acute MPP(+) toxicity (2.5 and 5 mM for 24 h). In SH-SY5Y cells, mild MPP(+) exposure predominantly inhibited autophagosome degradation, whereas acute MPP(+) exposure inhibited both autophagosome degradation and basal autophagy. Mild MPP(+) exposure reduced lysosomal hydrolase cathepsin D activity without changing lysosomal acidity, whereas acute exposure decreased lysosomal density. Lysosome biogenesis enhancers trehalose and rapamycin partially alleviated mild MPP(+) exposure induced impaired autophagosome degradation and cell death, but did not prevent the pathogenic response to acute MPP(+) exposure, suggesting irreversible lysosomal damage. We demonstrated impaired autophagic degradation by MPP(+) exposure and mechanistic differences between mild and acute MPP(+) toxicities. Mild MPP(+) toxicity impaired autophagosome degradation through novel lysosomal acidity-independent mechanisms. Sustained mild lysosomal damage may contribute to PD. We examined the effects of MPP(+) on autophagic processes under mild exposure, which mimics the slow progressive nature of Parkinson's disease, in SH-SY5Y cells. This study demonstrated impaired autophagic degradation through a reduction in lysosomal cathepsin D activity without altering lysosomal acidity by mild MPP(+) exposure. Mechanistic differences between acute and mild MPP(+) toxicity were also observed. Sustained mild damage of lysosome may be an underlying cause

  19. Mechanism and kinetics of electrochemical degradation of uric acid using conductive-diamond anodes. (United States)

    Dbira, Sondos; Bensalah, Nasr; Bedoui, Ahmed


    Uric acid (UA) is one of the principal effluents of urine wastewaters, widely used in agriculture as fertilizer, which is potentially dangerous and biorefractory. Hence, the degradation of UA (2,6,8-trihydroxy purine) in aqueous solution of pH 3.0 has been studied by conductive-diamond electrochemical oxidation. Hydroxyl radicals formed from water oxidation at the surface of boron-doped diamond anodes were the main oxidizing agents. Effects of current density and supporting electrolyte on the degradation rate and process efficiency are assessed. Results show that the increase of current density from 20 to 60 mA cm(-2) leads to a decrease in the efficiency of the electrochemical process. In addition, the best degradation occurred in the presence of NaCl as conductive electrolyte. Interestingly, an almost total mineralization of 50 ppm UA was obtained when anodic oxidation was performed at low current densities (20 mA cm(-2)) and in the presence of NaCl. This result confirmed that the electrolysis using diamond anodes is a very interesting technology for the treatment of UA. The identification of UA transformation products was performed by high-performance liquid chromatography (HPLC). HPLC analysis of treated solutions revealed that oxalic acid and urea were the two intermediates found. Oxalic acid was the most persistent product. Based on detected intermediates and bibliographic research, a mechanism of UA mineralization by anodic oxidation has been proposed. Ionic chromatography analysis confirmed the release of [Formula: see text] and [Formula: see text] ions during UA mineralization.

  20. Mechanism of antibacterial activity of liposomal linolenic acid against Helicobacter pylori.

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    Sung Woo Jung

    Full Text Available Helicobacter pylori infects approximately half of the world population and is a major cause of gastritis, peptic ulcer, and gastric cancer. Moreover, this bacterium has quickly developed resistance to all major antibiotics. Recently, we developed a novel liposomal linolenic acid (LipoLLA formulation, which showed potent bactericidal activity against several clinical isolated antibiotic-resistant strains of H. pylori including both the spiral and coccoid form. In addition, LipoLLA had superior in vivo efficacy compared to the standard triple therapy. Our data showed that LipoLLA associated with H. pylori cell membrane. Therefore, in this study, we investigated the possible antibacterial mechanism of LipoLLA against H. pylori. The antibacterial activity of LipoLLA (C18:3 was compared to that of liposomal stearic acid (LipoSA, C18:0 and oleic acid (LipoOA, C18:1. LipoLLA showed the most potent bactericidal effect and completely killed H. pylori within 5 min. The permeability of the outer membrane of H. pylori increased when treated with LipoOA and LipoLLA. Moreover, by detecting released adenosine triphosphate (ATP from bacteria, we found that bacterial plasma membrane of H. pylori treated with LipoLLA exhibited significantly higher permeability than those treated with LipoOA, resulting in bacteria cell death. Furthermore, LipoLLA caused structural changes in the bacterial membrane within 5 min affecting membrane integrity and leading to leakage of cytoplasmic contents, observed by both transmission electron microscopy (TEM and scanning electron microscopy (SEM. Our findings showing rapid bactericidal effect of LipoLLA suggest it is a very promising new, effective anti-H. pylori agent.

  1. Listeria monocytogenes: survival and adaptation in the gastrointestinal tract

    Directory of Open Access Journals (Sweden)

    Cormac G.M. Gahan


    Full Text Available The foodborne pathogen Listeria monocytogenes has the capacity to survive and grow in a diverse range of natural environments. The transition from a food environment to the gastrointestinal tract begins a process of adaptation that may culminate in invasive systemic disease. Here we describe recent advances in our understanding of how L. monocytogenes adapts to the gastrointestinal environment prior to initiating systemic infection. We will discuss mechanisms used by the pathogen to survive encounters with acidic environments (which include the glutamate decarboxylase and arginine deiminase systems, and those which enable the organism to cope with bile acids (including bile salt hydrolase and competition with the resident microbiota. An increased understanding of how the pathogen survives in this environment is likely to inform the future design of novel prophylactic approaches that exploit specific pharmabiotics; including probiotics, prebiotics or phages.

  2. Human alpha-lactalbumin made lethal to tumor cells (HAMLET) kills human glioblastoma cells in brain xenografts by an apoptosis-like mechanism and prolongs survival. (United States)

    Fischer, Walter; Gustafsson, Lotta; Mossberg, Ann-Kristin; Gronli, Janne; Mork, Sverre; Bjerkvig, Rolf; Svanborg, Catharina


    Malignant brain tumors present a major therapeutic challenge because no selective or efficient treatment is available. Here, we demonstrate that intratumoral administration of human alpha-lactalbumin made lethal to tumor cells (HAMLET) prolongs survival in a human glioblastoma (GBM) xenograft model, by selective induction of tumor cell apoptosis. HAMLET is a protein-lipid complex that is formed from alpha-lactalbumin when the protein changes its tertiary conformation and binds oleic acid as a cofactor. HAMLET induces apoptosis in a wide range of tumor cells in vitro, but the therapeutic effect in vivo has not been examined. In this study, invasively growing human GBM tumors were established in nude rats (Han:rnu/rnu Rowett, n = 20) by transplantation of human GBM biopsy spheroids. After 7 days, HAMLET was administered by intracerebral convection-enhanced delivery for 24 h into the tumor area; and alpha-lactalbumin, the native, folded variant of the same protein, was used as a control. HAMLET reduced the intracranial tumor volume and delayed the onset of pressure symptoms in the tumor-bearing rats. After 8 weeks, all alpha-lactalbumin-treated rats had developed pressure symptoms, but the HAMLET-treated rats remained asymptomatic. Magnetic resonance imaging scans revealed large differences in tumor volume (456 versus 63 mm(3)). HAMLET caused apoptosis in vivo in the tumor but not in adjacent intact brain tissue or in nontransformed human astrocytes, and no toxic side effects were observed. The results identify HAMLET as a new candidate in cancer therapy and suggest that HAMLET should be additionally explored as a novel approach to controlling GBM progression.

  3. Fracture Mechanisms of Layer-By-Layer Polyurethane/Poly(Acrylic Acid) Nanocomposite (United States)

    Kheng, Eugene R.

    A layer-by-layer(LBL) manufactured material is examined in detail in this thesis. Improvements are made to the method of its manufacture. Efforts are made to understand its fracture mechanisms and take advantage of these fracture mechanisms in the absorption of impact energy. A novel series of experiments has been performed on LBL manufactured thin films to demonstrate their unique fracture mechanisms. Polyurethane/Poly(Acrylic Acid) (PU/PAA) and PU/PAA/(PU/Clay)5 nanocomposite films readily undergo Interlaminar mode II fracture, because of the relatively weak elctrostatic bonds between monolayers. Tensile tests performed while under observation by a scanning electron microscope demonstrate the tendency of these nanocomposite films to undergo interlaminar mode II fracture even when loads are applied in the plane of nanocomposite film. It is concluded that these mechanisms of energy dissipation are responsible for the enhanced toughness of these films when used as layers between glass blocks in the prevention of impact damage to the glass. A novel automated manufacturing facility has been designed and built to deposit large sheets of Layer-by-Layer nanocomposite film. These large sheets are incorporated into a borosillicate glass composite in order to compare the ballistic characteristics of LBL PU based nanocomposite films to a single cast layer of polyurethane. It is demonstrated that shear fracture is the mode of failure in the blocks containing the nanocomposite film. The shear fracture surface in the nanocomposite after it has undergone a ballistic impact is characterized. Additional experiments are performed to characterize the interlaminar fracture stresses and toughnesses of the nanocomposite LBL layers, to assist in the implementation of a numerical crack band model that describes the nanocomposite film. The computational model predicts the failure of the ballistic nanocomposite samples, and the predicted V50 velocity is found to be in good agreement with

  4. Long-term follow-up of myelodysplastic syndrome patients with moderate/severe anaemia receiving human recombinant erythropoietin + 13-cis-retinoic acid and dihydroxylated vitamin D3: independent positive impact of erythroid response on survival. (United States)

    Crisà, Elena; Foli, Cristina; Passera, Roberto; Darbesio, Antonella; Garvey, Kimberly B; Boccadoro, Mario; Ferrero, Dario


    We previously reported a 60% erythroid response rate with recombinant erythropoietin + 13-cis retinoic acid + dihydroxylated vitamin D3 in 63 elderly myelodysplastic patients (median age 75 years) with unfavourable features for response to erythropoietin alone [70% transfusion-dependent, 35% refractory anaemia with ring sideroblasts/refractory anaemia with excess of blasts type 1 (RAEB1), 70% with International Prognostic Scoring System (IPSS) Intermediate-1 or -2]. This report updates that case study at a 7-year follow-up, and compared the impact on overall survival of erythroid response to known prognostic factors. The erythroid response duration (median 17 months; 22 in non-RAEB patients, with 20% patients in response after 6 years of therapy) was longer than in most studies with erythropoietin alone. Overall survival (median 55 months in non-RAEB, 15 in RAEB1 patients) was negatively affected by RAEB1 diagnosis, IPSS and WPSS intermediate scores and transfusion-dependence. In the multivariate analysis, erythroid response maintained an independent positive impact on survival, particularly in non-RAEB patients in the first 3 years from diagnosis (90% survival compared to 50% of non-responders). In conclusion, the long-term follow-up confirmed the achievement, by our combined treatment, of fairly long-lasting erythroid response in the majority of MDS patients with unfavourable prognostic features for response to erythropoietin: this translated in a survival benefit that was independent from other prognostic features.

  5. Adsorption behavior and mechanism of cadmium on strong-acid cation exchange resin

    Institute of Scientific and Technical Information of China (English)

    WANG Fei; WANG Lian-jun; LI Jian-sheng; SUN Xiu-yun; HAN Wei-qing


    The adsorption behavior of Cd2+ on 001×7 strong-acid cation exchange resin was studied with the static adsorption method. The adsorption process was analyzed from thermodynamics and kinetics aspects. The influences of experimental parameters such as pH, temperature, initial concentration and adsorption rate were investigated. The experimental results show that in the studied concentration range, 001×7 resin has a good sorption ability for Cd2+, and the equilibrium adsorption data fit to Freundlich isotherms. The adsorption is an exothermic process which runs spontaneously. Kinetic analysis shows that the adsorption rate is mainly governed by liquid film diffusion. The best adsorption condition is pH 4-5. The saturated resin can be regenerated by 3 mol/L nitric acid, and the desorption efficiency is over 98%. The maximal static saturated adsorption capacity is 355 mg/g (wet resin) at 293 K. The adsorption mechanism of Cd2+ on 001×7 resin was discussed based on IR spectra.

  6. Evolution of the C(4) photosynthetic mechanism: are there really three C(4) acid decarboxylation types? (United States)

    Furbank, Robert T


    Some of the most productive plants on the planet use a variant of photosynthesis known as the C(4) pathway. This photosynthetic mechanism uses a biochemical pump to concentrate CO(2) to levels up to 10-fold atmospheric in specialized cells of the leaf where Rubisco, the primary enzyme of C(3) photosynthesis, is located. The basic biochemical pathways underlying this process, discovered more than 40 years ago, have been extensively studied and, based on these pathways, C(4) plants have been subdivided into two broad groups according to the species of C(4) acid produced in the mesophyll cells and into three groups according to the enzyme used to decarboxylate C(4) acids in the bundle sheath to release CO(2). Recent molecular, biochemical, and physiological data indicate that these three decarboxylation types may not be rigidly genetically determined, that the possibility of flexibility between the pathways exists and that this may potentially be both developmentally and environmentally controlled. This evidence is synthesized here and the implications for C(4) engineering discussed.

  7. Mechanism of Orlistat Hydrolysis by the Thioesterase of Human Fatty Acid Synthase. (United States)

    Fako, Valerie E; Zhang, Jian-Ting; Liu, Jing-Yuan


    Fatty acid synthase (FASN), the sole protein capable of de novo synthesis of free fatty acids, is overexpressed in a wide variety of human cancers and is associated with poor prognosis and aggressiveness of these cancers. Orlistat, an FDA-approved drug for obesity treatment that inhibits pancreatic lipases in the GI tract, also inhibits the thioesterase (TE) of human FASN. The cocrystal structure of TE with orlistat shows a pseudo TE dimer containing two different forms of orlistat in the active site, an intermediate that is covalently bound to a serine residue (Ser(2308)) and a hydrolyzed and inactivated product. In this study, we attempted to understand the mechanism of TE-catalyzed orlistat hydrolysis by examining the role of the hexyl tail of the covalently bound orlistat in water activation for hydrolysis using molecular dynamics simulations. We found that the hexyl tail of the covalently bound orlistat undergoes a conformational transition, which is accompanied by destabilization of a hydrogen bond between a hydroxyl moiety of orlistat and the catalytic His(2481) of TE that in turn leads to an increased hydrogen bonding between water molecules and His(2481) and increased chance for water activation to hydrolyze the covalent bond between orlistat and Ser(2308). Thus, the conformation of the hexyl tail of orlistat plays an important role in orlistat hydrolysis. Strategies that stabilize the hexyl tail may lead to the design of more potent irreversible inhibitors that target FASN and block TE activity with greater endurance.

  8. Mechanism of hepatic targeting via oral administration of DSPE–PEG–cholic acid-modified nanoliposomes (United States)

    Li, Ying; Zhu, Chunyan


    In oral administration, gastrointestinal physiological environment, gastrointestinal epithelial cell membranes, and blood circulation are typical biological barriers to hepatic delivery of ligand-modified nanoparticle drug delivery systems. To elucidate the mechanism of oral hepatic targeting of cholic acid receptor-mediated nanoliposomes (LPs) (distearoyl phosphatidylethanolamine–polyethylene glycol–cholic acid-modified LPs, CA-LPs), evaluations were performed on colon cancer Caco-2 cell monolayers, liver cancer HepG2 cells, and a rat intestinal perfusion model. CA-LPs, ~100 nm in diameter, exhibited sustained-release behavior and had the greatest stability in rat gastrointestinal fluid and serum for both size and entrapment efficiency. CA-LPs demonstrated highest transport across Caco-2 cells and highest cellular uptake by HepG2 cells. The enhanced endocytosis of CA-LPs was found to be mediated by Na+/taurocholate cotransporting polypeptide and involved the caveolin-mediated endocytosis pathway. Further, we used fluorescence resonance energy transfer (FRET) technology to show that the CA-LPs maintained their structural integrity in part during the transport across the Caco-2 cell monolayer and uptake by HepG2 cells.

  9. Biologic plausibility, cellular effects, and molecular mechanisms of eicosapentaenoic acid (EPA) in atherosclerosis. (United States)

    Borow, Kenneth M; Nelson, John R; Mason, R Preston


    Residual cardiovascular (CV) risk remains in dyslipidemic patients despite intensive statin therapy, underscoring the need for additional intervention. Eicosapentaenoic acid (EPA), an omega-3 polyunsaturated fatty acid, is incorporated into membrane phospholipids and atherosclerotic plaques and exerts beneficial effects on the pathophysiologic cascade from onset of plaque formation through rupture. Specific salutary actions have been reported relating to endothelial function, oxidative stress, foam cell formation, inflammation, plaque formation/progression, platelet aggregation, thrombus formation, and plaque rupture. EPA also improves atherogenic dyslipidemia characterized by reduction of triglycerides without raising low-density lipoprotein cholesterol. Other beneficial effects of EPA include vasodilation, resulting in blood pressure reductions, as well as improved membrane fluidity. EPA's effects are at least additive to those of statins when given as adjunctive therapy. In this review, we present data supporting the biologic plausibility of EPA as an anti-atherosclerotic agent with potential clinical benefit for prevention of CV events, as well as its cellular effects and molecular mechanisms of action. REDUCE-IT is an ongoing, randomized, controlled study evaluating whether the high-purity ethyl ester of EPA (icosapent ethyl) at 4 g/day combined with statin therapy is superior to statin therapy alone for reducing CV events in high-risk patients with mixed dyslipidemia. The results from this study are expected to clarify the role of EPA as adjunctive therapy to a statin for reduction of residual CV risk.

  10. Mechanism of Sporicidal Activity for the Synergistic Combination of Peracetic Acid and Hydrogen Peroxide. (United States)

    Leggett, Mark J; Schwarz, J Spencer; Burke, Peter A; McDonnell, Gerald; Denyer, Stephen P; Maillard, Jean-Yves


    There is still great interest in controlling bacterial endospores. The use of chemical disinfectants and, notably, oxidizing agents to sterilize medical devices is increasing. With this in mind, hydrogen peroxide (H2O2) and peracetic acid (PAA) have been used in combination, but until now there has been no explanation for the observed increase in sporicidal activity. This study provides information on the mechanism of synergistic interaction of PAA and H2O2 against bacterial spores. We performed investigations of the efficacies of different combinations, including pretreatments with the two oxidizers, against wild-type spores and a range of spore mutants deficient in the spore coat or small acid-soluble spore proteins. The concentrations of the two biocides were also measured in the reaction vessels, enabling the assessment of any shift from H2O2 to PAA formation. This study confirmed the synergistic activity of the combination of H2O2 and PAA. However, we observed that the sporicidal activity of the combination is largely due to PAA and not H2O2. Furthermore, we observed that the synergistic combination was based on H2O2 compromising the spore coat, which was the main spore resistance factor, likely allowing better penetration of PAA and resulting in the increased sporicidal activity.

  11. Chemical Mechanical Polishing of Glass Substrate with α-Alumina-g-Polystyrene Sulfonic Acid Composite Abrasive

    Institute of Scientific and Technical Information of China (English)

    LEI Hong; BU Naijing; ZHANG Zefang; CHEN Ruling


    Abrasive is the one of key influencing factors during chemical mechanical polishing(CMP) process. Currently, α-Alumina (α-Al2O3) particle, as a kind of abrasive, has been widely used in CMP slurries, but their high hardness and poor dispersion stability often lead to more surface defects. After being polished with composite particles, the surface defects of work pieces decrease obviously. So the composite particles as abrasives in slurry have been paid more attention. In order to reduce defect caused by pure α-Al2O3 abrasive, α-alumina-g-polystyrene sulfonic acid (α-Al2O3-g-PSS) composite abrasive was prepared by surface graft polymerization. The composition, structure and morphology of the product were characterized by Fourier transform infrared spectroscopy(FTIR), X-ray photoelectron spectroscopy(XPS), time-of-flight secondary ion mass spectroscopy(TOF-SIMS), and scanning electron microscopy(SEM), respectively. The results show that polystyrene sulfonic acid grafts onto α-Al2O3, and has well dispersibility. Then, the chemical mechanical polishing performances of the composite abrasive on glass substrate were investigated with a SPEEDFAM-16B-4M CMP machine. Atomic force microscopy(AFM) images indicate that the average roughness of the polished glass substrate surface can be decreased from 0.835 nm for pure α-Al2O3 abrasive to 0.583 nm for prepared α-Al2O3-g-PSS core-shell abrasive. The research provides a new and effect way to improve the surface qualities during CMP.

  12. Mechanism of alcohol-induced impairment in renal development: Could it be reduced by retinoic acid? (United States)

    Gray, Stephen P; Cullen-McEwen, Luise A; Bertram, John F; Moritz, Karen M


    1. Prenatal alcohol exposure impairs kidney development, resulting in a reduced nephron number. However, the mechanism through which alcohol acts to disrupt renal development is largely unknown. Retinoic acid (RA) is critically involved in kidney development and it has been proposed that a diminished concentration of RA is a contributing factor to fetal alcohol syndrome. 2. In the present study we proposed that the ethanol-induced inhibition of ureteric branching morphogenesis and glomerular development in the cultured rat kidney would be ameliorated by coculture with exogenous RA and that examining the expression profile of key genes involved in the development of the kidney would provide insights into the potential molecular pathways involved. 3. Whole rat metanephroi cultured in the presence of exogenous RA (10-20 nmol/L) without ethanol appeared larger and had significantly more ureteric branch points, tips and glomeruli than metanephroi cultured in control media. Those cultured in the presence of ethanol alone (0.2%) had 20% fewer ureteric branch points, tips and glomeruli, which was ameliorated by coculture with retinoic acid. 4. Gene expression analysis identified changes in the expression of enzymes involved in the metabolism of alcohol in conjunction with changes in key regulators of kidney development, including cRET. 5. These results demonstrate that the teratogenic effects of alcohol in vitro on kidney development resulting in reduced ureteric branching morphogenesis and glomerular development can be ameliorated through coculture with RA. These results provide the foundation for future research into the mechanism through which alcohol acts to disrupt kidney development.

  13. Activation of a pro-survival pathway IL-6/JAK2/STAT3 contributes to glial fibrillary acidic protein induction during the cholera toxin-induced differentiation of C6 malignant glioma cells. (United States)

    Shu, Minfeng; Zhou, Yuxi; Zhu, Wenbo; Wu, Sihan; Zheng, Xiaoke; Yan, Guangmei


    Differentiation-inducing therapy has been proposed to be a novel potential approach to treat malignant gliomas. Glial fibrillary acidic protein (GFAP) is a well-known specific astrocyte biomarker and acts as a tumor suppressor gene (TSG) in glioma pathogenesis. Previously we reported that a traditional biotoxin cholera toxin could induce malignant glioma cell differentiation characterized by morphologic changes and dramatic GFAP expression. However, the molecular mechanisms underlying GFAP induction are still largely unknown. Here we demonstrate that an oncogenic pathway interleukin-6/janus kinase-2/signal transducer and activator of transcription 3 (IL-6/JAK2/STAT3) cascade mediates the cholera toxin-induced GFAP expression. Cholera toxin dramatically stimulated GFAP expression at the transcriptional level in C6 glioma cells. Meanwhile, phosphorylation of STAT3 and JAK2 was highly induced in a time-dependent manner after cholera toxin incubation, whereas no changes of STAT3 and JAK2 were observed. Furthermore, the IL-6 gene was quickly induced by cholera toxin and subsequent IL-6 protein secretion was stimulated. Importantly, exogenous recombinant rat IL-6 can also induce phosphorylation of STAT3 concomitant with GFAP expression while JAK2 specific inhibitor AG490 could effectively block both cholera toxin- and IL-6-induced GFAP expression. Given that the methylation of the STAT3 binding element can suppress GFAP expression, we detected the methylation status of the critical recognition sequence of STAT3 in the promoter of GFAP gene (-1518 ∼ -1510) and found that it was unmethylated in C6 glioma cells. In addition, neither DNA methyltransferase1 (DNMT1) inhibitor 5-Aza-2'-deoxycytidine (5-AZa-CdR) nor silencing DNMT1 can stimulate GFAP expression, indicating that the loss of GFAP expression in C6 cells is not caused by its promoter hypermethylation. Taken together, our findings suggest that activation of a pro-survival IL-6/JAK2/STAT3 cascade contributes to

  14. Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid.

    Directory of Open Access Journals (Sweden)

    Jae Sung You

    Full Text Available Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

  15. Mechanical stimulation induces mTOR signaling via an ERK-independent mechanism: implications for a direct activation of mTOR by phosphatidic acid. (United States)

    You, Jae Sung; Frey, John W; Hornberger, Troy A


    Signaling by mTOR is a well-recognized component of the pathway through which mechanical signals regulate protein synthesis and muscle mass. However, the mechanisms involved in the mechanical regulation of mTOR signaling have not been defined. Nevertheless, recent studies suggest that a mechanically-induced increase in phosphatidic acid (PA) may be involved. There is also evidence which suggests that mechanical stimuli, and PA, utilize ERK to induce mTOR signaling. Hence, we reasoned that a mechanically-induced increase in PA might promote mTOR signaling via an ERK-dependent mechanism. To test this, we subjected mouse skeletal muscles to mechanical stimulation in the presence or absence of a MEK/ERK inhibitor, and then measured several commonly used markers of mTOR signaling. Transgenic mice expressing a rapamycin-resistant mutant of mTOR were also used to confirm the validity of these markers. The results demonstrated that mechanically-induced increases in p70(s6k) T389 and 4E-BP1 S64 phosphorylation, and unexpectedly, a loss in total 4E-BP1, were fully mTOR-dependent signaling events. Furthermore, we determined that mechanical stimulation induced these mTOR-dependent events, and protein synthesis, through an ERK-independent mechanism. Similar to mechanical stimulation, exogenous PA also induced mTOR-dependent signaling via an ERK-independent mechanism. Moreover, PA was able to directly activate mTOR signaling in vitro. Combined, these results demonstrate that mechanical stimulation induces mTOR signaling, and protein synthesis, via an ERK-independent mechanism that potentially involves a direct interaction of PA with mTOR. Furthermore, it appears that a decrease in total 4E-BP1 may be part of the mTOR-dependent mechanism through which mechanical stimuli activate protein synthesis.

  16. The mechanism and kinetics of the electrochemical cleavage of azo bond of 2-hydroxy-5-sulfophenyl-azo-benzoic acids

    Energy Technology Data Exchange (ETDEWEB)

    Mandic, Zoran; Nigovic, Biljana; Simunic, Branimir


    The electrochemical reduction of 2-hydroxy-5-[(4-sulfophenyl)azo]benzoic acid, 2-hydroxy-5-[(3-sulfophenyl)azo]benzoic acid, 2-hydroxy-5-[(2-sulfophenyl)azo]benzoic acid and 2-hydroxy-5-azo-benzoic acid has been carried out in aqueous solutions at glassy carbon electrode using cyclic voltammetry and chronoamperometry. The position of sulfo substituent relative to azo bridge as well as pH of the solution have significant impact on the electrochemical behavior of these compounds. It has been proposed that these compounds are reduced predominantly as hydrazone tautomers resulting in corresponding hydrazo compounds. The overall electrochemical reduction follows DISP2 mechanism, ultimately leading to the 5-amino salicylic acid and sulfanilic acid. The rate determining step is the homogenous redox reaction between intermediate hydrazo compound and 5-amino salicylic acid quinoneimine. The mechanism is proposed in which activated complex of 5-amino salicylic acid quinoneimine and intermediate hydrazo compound is formed with the simultaneous loss of one proton.

  17. Kinetics and Mechanism of Electron Transfer Reaction: Oxidation of Sulfanilic Acid by N-Chloro-p-Toluene Sulfonamide in Acid Perchlorate Medium

    Energy Technology Data Exchange (ETDEWEB)

    Sailani, Riya; Bhasin, Meneka; Khandelwal, C. L.; Sharma, P. D. [Univ. of Rajasthan, Jaipur (India)


    The kinetics and mechanism of oxidation of sulfanilic acid by N-chloro-p-toluene sulfonamide (chloramine-T) have been studied in acid medium. The species of chloramine-T were analysed on the basis of experimental observations and predominantly reactive species was taken into account for proposition of most plausible reaction mechanism. The derived rate law (1) conforms to such a mechanism. All kinetic parameters were evaluated. Activation parameters such as energy and entropy of activation were calculated to be (61.67 ± 0.47) kJ mol{sup -1} and (-62.71 ± 2.48) JK{sup -1}mol{sup -1} respectively employing Eyring equation.

  18. Priming for JA-dependent defenses using hexanoic acid is an effective mechanism to protect Arabidopsis against B. cinerea. (United States)

    Kravchuk, Zhana; Vicedo, Begonya; Flors, Víctor; Camañes, Gemma; González-Bosch, Carmen; García-Agustín, Pilar


    Soil drench treatments with hexanoic acid can effectively protect Arabidopsis plants against Botrytis cinerea through a mechanism based on a stronger and faster accumulation of JA-dependent defenses. Plants impaired in ethylene, salicylic acid, abscisic acid or glutathion pathways showed intact protection by hexanoic acid upon B. cinerea infection. Accordingly, no significant changes in the SA marker gene PR-1 in either the SA or ABA hormone balance were observed in the infected and treated plants. In contrast, the JA signaling pathway showed dramatic changes after hexanoic acid treatment, mainly when the pathogen was present. The impaired JA mutants, jin1-2 and jar1, were unable to display hexanoic acid priming against the necrotroph. In addition, hexanoic acid-treated plants infected with B. cinerea showed priming in the expression of the PDF1.2, PR-4 and VSP1 genes implicated in the JA pathways. Moreover, JA and OPDA levels were primed at early stages by hexanoic acid. Treatments also stimulated increased callose accumulation in response to the pathogen. Although callose accumulation has proved an effective IR mechanism against B. cinerea, it is apparently not essential to express hexanoic acid-induced resistance (HxAc-IR) because the mutant pmr4.1 (callose synthesis defective mutant) is protected by treatment. We recently described how hexanoic acid treatments can protect tomato plants against B. cinerea by stimulating ABA-dependent callose deposition and by priming OPDA and JA-Ile production. We clearly demonstrate here that Hx-IR is a dependent plant species, since this acid protects Arabidopsis plants against the same necrotroph by priming JA-dependent defenses without enhancing callose accumulation.

  19. Adsorption Behavior and Mechanism of Macroporous Phosphonic Acid Resin for Lu3+

    Institute of Scientific and Technical Information of China (English)

    WANG Hui-jun; XIONG Chun-hua


    The article is based on a research on the adsorption behavior and adsorption mechanism of macroporous phosphonic acid resin (PAR) for Lu3+ and the influence of the medium's pH, adsorption temperature, adsorption time, etc on adsorbing Lu3 + . The best value of medium's pH to the adsorption of PAR for Lu3 + was found to be 4.92. The static adsorption maximum capacity of PAR for Lu3 + is 220 mg· g-1. The thermodynamic adsorption parameters are respectively △H= 11.3 kJ·mol-1, △S =46.3 J·mol-1 ·K-1, △G = - 2.50 kJ·mol-1 and the apparent activity energy is Ea= 31.4 kJ· mol- 1. The adsorption behavior of PAR for Lu3 + obeys the Freundlich isotherm. The apparent adsorption rate constant is k298 = 4.68 × 10-5 s-1. The coordinate ratio of the functional radical to Lu3 + is approximately 4: 1. The best eluant is 1.0 mol· L- 1 HCl. The adsorption mechanism of PAR for Lu3 + was separately confirmed by chemical analysis and IR spectra.

  20. Kinetics and Mechanism of Oxidation of Diethyl Ether by Chloramine-T in Acidic Medium

    Directory of Open Access Journals (Sweden)

    Y. I. Hassan


    Full Text Available The kinetics of oxidation of diethyl ether (DE with sodium N-chloro-p-toluenesulphonamide (CAT in hydrochloric acid solution has been studied at (313°K.The reaction rate show a first order dependence on [CAT] and fractional order dependence on each [DE] and [H+] .The variation of ionic strength of the medium has no significant effect on the reaction rate , addition of p-toluenesulphonamide (p-TSA affects the reaction rate marginally the rate increased with decreasing dielectric constant of the medium , the stochiometry of the reaction was found to be 1:2 and oxidation products were identified , A Michaelis – Menten type mechanism has been suggested to explain the results.The equilibrium and the decomposition constants of CAT – diethyl ether complex have been evaluated. Thermodynamic parameters were computed by studying reaction at temperatures range ( 308 – 323°K for the rate limiting step and for the observed first order constants by the linear Arrhenius plot. The mechanism proposed and the derived rate law are consistent with observed kinetics.

  1. The effects of sucrose on the mechanical properties of acid milk proteins-kappa-carrageenan gels

    Directory of Open Access Journals (Sweden)

    E. Sabadini


    Full Text Available Mechanical properties have been widely correlated with textural characteristics to determine the interactions during the process formation of dairy gel. These interactions are strongly affected by process conditions and system composition. In the present study, the rheological of acid-induced protein dairy gels with (2(7-3 and without (2(6-2 sucrose and subjected to small and large deformations were studied using an experimental design. The independent variables were the sodium caseinate, whey protein concentrate (WPC, carrageenan and sucrose concentrations as well as stirring speed and heat treatment time and temperature. Mechanical deformation tests were performed at 0.1, 1, 5, and 9 mm/s up to 80% of initial height. A heavy dependence of rupture stress on increasing crosshead speed and the formation of harder gels with the addition of sucrose were observed. Moreover the elastic and viscous moduli, obtained by fitting the Maxwell model to stress relaxation data, increased with increasing addition of sucrose. These results can be explained by preferential hydration of the casein with sucrose, causing an induction of casein-polysaccharide and casein-casein interactions.

  2. Synthesis, growth, optical and mechanical studies of ferroelectric urea-oxalic acid single crystals (United States)

    Vizhi, R. Ezhil; Dhivya, R.; Babu, D. Rajan


    A single crystal of urea oxalic acid was grown by slow evaporation method. The lattice parameters are a=5.13 Å, b=12.48 Å, c=7.07 Å, β=98.13° with V=448.5 Å3 which belongs to monoclinic system with space group P21/c obtained from single crystal X-ray diffraction analysis. UV-visible spectrum was recorded from the wavelength region of 200-800 nm and its cutoff wavelength was found to be 270 nm. Optical energy band gap of 4.57 eV was determined using Tau's plot relation. Fourier transform infrared vibrational spectrum confirmed the presence of N-H asymmetric stretching which occurs at 3444 cm-1 and 1853 cm-1 arising due to the amide C=O symmetric stretching. The emission was observed at 364 nm from the photoluminescence spectrum. The mechanical stability of the grown crystal was estimated by Vickers microhardness studies and it is evident that the grown crystal belongs to soft material category. Hardness related parameters such as elastic stiffness constant, fracture mechanics, brittleness index and yield strength were also evaluated. The dielectric constant and dielectric loss of the grown crystal were carried out as a function of frequency for different temperatures.

  3. Kinetics and mechanism of sphalerite leaching by sodium nitrate in sulphuric acid solution

    Directory of Open Access Journals (Sweden)

    Sokić M.


    Full Text Available Interest for application of hydrometallurgical processes in a processing of complex sulphide ores and concentrates has increased in recent years. Their application provides better metal recoveries and reduced emission of gaseous and toxic ageneses in the environment. The kinetics and mechanism of sphalerite leaching from complex sulphide concentrate with sulphuric acid and sodium nitrate solution at standard conditions was presented in this paper. The influences of temperature and time on the leaching degree of zinc were investigated and kinetic analysis of the process was accomplished. With temperature increasing from 60 to 90°C, the zinc leaching increased from 25.23% to 71.66% after 2 hours, i.e. from 59.40% to 99.83% after 4 hours. The selected kinetic model indicated that the diffusion through the product layer was the rate-controlling step during the sphalerite leaching. The activation energy was determined to be 55 kJ/mol in the temperature range 60-90°C. XRD, light microscopy and SEM/EDX analyses of the complex concentrate and leach residue confirmed formation of elemental sulphur and diffusion-controlled leaching mechanism.

  4. Transcriptomic analysis reveals the metabolic mechanism of L-ascorbic acid in Ziziphus jujuba Mill.

    Directory of Open Access Journals (Sweden)

    Chunmei eZhang


    Full Text Available Chinese jujube (Ziziphus jujuba Mill. is the most economically important member of the Rhamnaceae family and contains a high concentration of ascorbic acid (AsA. To explore the metabolic mechanism of AsA accumulation, we investigated the abundance of AsA in the fruit development stages, the leaf and flower of Z. jujuba cv Junzao, and the mature fruit of one type of wild jujube (Z. jujuba var. spinosa Hu, Yanchuan sour jujube. And the expression patterns of genes involved in AsA biosynthesis, degradation and recycling were analyzed. The result showed that AsA biosynthesis during early fruit development (the enlargement stage is the main reason for jujube high accumulation. The L-galactose pathway plays a predominant role in the biosynthesis of AsA during jujube fruit development, and the genes GMP1, GME1, GGP, and GaLDH involved in the determination of AsA concentration during fruit development and in different genotypes; the myo-inositol pathway along with the genes GME2 and GMP2 in the L-galactose pathway play a compensatory role in maintaining AsA accumulation during the ripening stage. These findings enhance our understanding of the molecular mechanism in regulating AsA accumulation for jujube.

  5. Exopolysaccharides produced by lactic acid bacteria: from health-promoting benefits to stress tolerance mechanisms. (United States)

    Caggianiello, Graziano; Kleerebezem, Michiel; Spano, Giuseppe


    A wide range of lactic acid bacteria (LAB) is able to produce capsular or extracellular polysaccharides, with various chemical compositions and properties. Polysaccharides produced by LAB alter the rheological properties of the matrix in which they are dispersed, leading to typically viscous and "ropy" products. Polysaccharides are involved in several mechanisms such as prebiosis and probiosis, tolerance to stress associated to food process, and technological properties of food. In this paper, we summarize the beneficial properties of exopolysaccharides (EPS) produced by LAB with particular attention to prebiotic properties and to the effect of exopolysaccharides on the LAB-host interaction mechanisms, such as bacterial tolerance to gastrointestinal tract conditions, ability of ESP-producing probiotics to adhere to intestinal epithelium, their immune-modulatory activity, and their role in biofilm formation. The pro-technological aspect of exopolysaccharides is discussed, focusing on advantageous applications of EPS in the food industry, i.e., yogurt and gluten-free bakery products, since it was found that these microbial biopolymers positively affect the texture of foods. Finally, the involvement of EPS in tolerance to stress conditions that are commonly encountered in fermented beverages such as wine is discussed.

  6. [Mechanism of action of combined extremely weak magnetic field on aqueous solution of amino acid]. (United States)

    Zhadin, M N; Bakharev, B V; Bobkova, N V


    The fundamental physical mechanisms of resonance action of an extremely weak (40 nT) alternating magnetic field at the cyclotron frequency combined with a weak (40 μT) static magnetic field, on living systems are analyzed in the present work. The experimental effects of such sort of magnetic fields were described in different papers: the very narrow resonant peaks in electrical conductivity of the aqueous solutions in the in vitro experiments and the biomedical in vivo effects on living animals of magnetic fields with frequencies tuned to some amino acids. The existing experimental in vitro data had a good repeatability in different laboratories and countries. Unfortunately, for free ions such sort of effects are absolutely impossible because the dimensions of an ion rotation radius should be measured by meters at room temperature and at very low static magnetic fields used in all the above experiments. Even for bound ions these effects should be also absolutely impossible from the positions of classic physics because of rather high viscosity of biological liquid media (blood plasma, cerebrospinal liquid, cytoplasm). Only modern quantum electrodynamics of condensed media opens the new ways for solving these problems. The proposed article is devoted to analysis of quantum mechanisms of these effects.

  7. Mechanism and Kinetics Study for Photocatalytic Oxidation Degradation: A Case Study for Phenoxyacetic Acid Organic Pollutant

    Directory of Open Access Journals (Sweden)

    Kian Mun Lee


    Full Text Available Photocatalysis is a rapidly expanding technology for wastewater treatment, including a wide range of organic pollutants. Thus, understanding the kinetics and mechanism of the photocatalytic oxidation (PCO for degradation of phenoxyacetic acid (PAA is an indispensable component of risk assessment. In this study, we demonstrated that the central composite design (CCD coupled with response surface methodology (RSM was successfully employed to probe the kinetics and mechanism of PCO degradation for PAA using an efficient zinc oxide (ZnO photocatalyst. In our current case study, four independent factors such as ZnO dosage, initial concentration of PAA, solution pH, and reaction time on the PCO degradation for PAA were examined in detail. Based on our results obtained from RSM analyses, an efficient pathway leading to the high degradation rate (>90% was applying 0.4 g/L of ZnO dosage with 16 mg/L of concentration of PAA at pH 6.73 for 40 minutes. The experimental results were fitted well with the derived response model with R2 = 0.9922. This study offers a cost-effective way for probing our global environmental water pollution issue.

  8. Studies on the mechanical properties of woven jute fabric reinforced poly(l-lactic acid composites

    Directory of Open Access Journals (Sweden)

    G.M. Arifuzzaman Khan


    Full Text Available Development of ecofriendly biocomposites to replace non-biodegradable synthetic fiber composites is the main objective of this study. To highlight the biocomposites as a perfect replacement, the plain woven jute fabric (WJF reinforced poly(l-lactic acid (PLLA composites were prepared by the hot press molding method. The influence of woven structure and direction on the mechanical properties i.e. tensile, flexural and impact properties was investigated. The average tensile strength (TS, tensile modulus (TM, flexural strength (FS, flexural modulus (FM, and impact strength (IS of untreated woven jute composite (in warp direction were improved about 103%, 211%, 95.2%, 42.4% and 85.9%, respectively and strain at maximum tensile stress for composite samples was enhanced by 11.7%. It was also found that the strengths and modulus of composites in warp direction are higher than those in weft direction. WJF composites in warp and weft directions presented superior mechanical properties than non-woven jute fabric (NWJF composites. Chemical treatment of jute fabric through benzoylation showed a positive effect on the properties of composites. Morphological studies by SEM demonstrated that better adhesion between the treated fabric and PLLA was achieved.

  9. Bioluminescence inhibition of bacterial luciferase by aliphatic alcohol, amine and carboxylic acid: inhibition potency and mechanism. (United States)

    Yamasaki, Shinya; Yamada, Shuto; Takehara, Kô


    The inhibitory effects of hydrophobic molecules on the bacterial luciferase, BL, luminescence reaction were analyzed using an electrochemically-controlled BL luminescence system. The inhibition potency of alkyl amines, C(n)NH(2), and fatty acids, C(m)COOH (m = n - 1), on the BL reaction increased with an increase in the alkyl chain-length of these aliphatic compounds. C(m)COOH showed lower inhibition potency than C(n)NH(2) and alkyl alcohols, C(n)OH, data for which have been previously reported. To make clear the inhibition mechanisms of the aliphatic compounds on the BL reaction, the initial rate of the BL reaction was measured and analyzed using the Dixon plot and Cornish-Bowden plot. The C(12)OH inhibited the BL reaction in competition with the substrate C(11)CHO, while C(12)NH(2) and C(11)COOH inhibited in an uncompetitive manner with the C(11)CHO. These results suggest that the alkyl chain-length and the terminal unit of the aliphatic compound determine the inhibition potency and the inhibition mechanism, respectively.

  10. Caffeic acid, a phyto polyphenol mitigates fluoride induced hepatotoxicity in rats: A possible mechanism. (United States)

    Kanagaraj, Vishnu Vignesh; Panneerselvam, Lakshmikanthan; Govindarajan, Vimal; Ameeramja, Jaishabanu; Perumal, Ekambaram


    Fluoride induced hepatotoxicity has been extensively studied in both humans and animals. However, the mechanism underlying in the hepatotoxicity of experimental fluorosis remains obscure. The severity of fluoride toxicity was reduced by oral administration of certain plant derived antioxidants. Caffeic acid (CA) a polyphenolic compound has diverse range of pharmacological activity in the biological system. Therefore, the present study was aimed to investigate the protective mechanism of CA, against fluoride induced hepatotoxicity in rats. The rats were treated with 300 ppm of NaF via drinking water ad libitum alone and in combination with CA at a dose of 50 mg/kg daily for 30 days by oral intubation. CA treatment significantly prevented fluoride induced hepatic damage as evident from the histopathological studies and declined levels of serum fluoride and liver marker enzymes. A significant decrease in the levels of enzymatic (SOD2, CAT, GPx, and GSTpi class) and nonenzymatic (GSH and Vitamin C) antioxidants along with increased ROS, lipid peroxidation, protein carbonyl content, and nitrate levels by fluoride were also prevented in these groups. In addition, CA inhibits fluoride induced apoptosis by altering the Bax and caspase-3p20 expressions. Further, fluoride induced upregulation of Nox4, p38α MAPK, Hsp60, and downregulation of Hsp27 are the indicators for the detection of oxidative damage, apoptosis, and mitochondrial stress was also modulated by CA. These findings reveal that CA supplementation has a protective effect against fluoride induced hepatotoxicity in rats.

  11. Adsorption Behaviors and Mechanism of Macroporous Phosphonic Acid Resin for Gadolinium

    Institute of Scientific and Technical Information of China (English)

    吴香梅; 熊春华; 姚彩萍


    The adsorption behaviors and mechanism of a novel chelate resin, macroporous phosphonic acid resin(PAR)for Gd(Ⅲ)were investigated. The statically and dynamically saturated adsorption capacity is respectively 308 mg·g-1resin and 296 mg·g-1resin at 298 K in Hac-NaAc medium at pH 5.6. Gd(Ⅲ)adsorbed on PAR can be reductively eluted by 0.5~5.0 mol·L-1 HCl used as eluant and the elution percentage is up to 94.7% in 1.0 mol·L-1 HCl. The resin can be regenerated and reused without apparent decrease in adsorption capacity. The apparent adsorption rate constant is k298=3.96×10-5 s-1. The adsorption behavior of PAR for Gd(Ⅲ) conforms to the Freundlich isotherm. The thermodynamic adsorption parameter, enthalpy change △H of PAR for Gd(Ⅲ)is 22.6kJ·mol-1. The apparent adsorption activation energy(Ea)of PAR for Gd(Ⅲ)is 5.0 kJ·mol-1. The molar coordination ratio of the functional group of PAR to Gd(Ⅲ)is about 3∶1. The adsorption mechanism of PAR for Gd(Ⅲ)was examined by using chemical method and IR spectrometry.

  12. Response of Endogenous Salicylic Acid and Jasmonates to Mechanical Wounding in Pea Leaves

    Institute of Scientific and Technical Information of China (English)

    LIU Yan; PAN Qiu-hong; ZHAN Ji-cheng; TIAN Rong-rong; HUANG Wei-dong


    The roles of on endogenous jasmonates (JAs) and salicylic acid (SA) in wounding response were investigated. Pea (Pisum sativum L.) seedlings were treated with three different methods including mechanical wounding, JAs application,and SA application. The contents of endogenous JAs and SA, as well as the activities of the related enzymes were detected by enzyme-linked immunosorbent assay (ELISA), high performance liquid chromatography (HPLC), and spectrophotometer, respectively. The results showed that endogenous JA rapidly accumulated within 30 min after wounding. The increase in the activities of both lipoxygenase (LOX) and allene oxide synthase (AOS) lagged behind JAs burst. A second slight increase in JAs level was observed at 24 h after wounding treatment, and at the same time point,higher activities of LOX and AOS were also detected. Endogenous free SA content decreased accompanied with JAs burst. Effects of exogenous JA application were similar to those of wounding treatment on endogenous SA level and phenylalanine ammonia lyase (PAL) activity, whereas exogenous SA application led to the significant inhibition of LOX and AOS activities and the decrease of endogenous JAs level at the early stage of treatment. It is thus suggested that JAs burst and SA decrease in early response to wounding may constitute an important mechanism by which plant starts the related defense reaction and adapts to wounding stress.

  13. Antifungal activity of salicylic acid against Penicillium expansum and its possible mechanisms of action. (United States)

    da Rocha Neto, Argus Cezar; Maraschin, Marcelo; Di Piero, Robson Marcelo


    Apple is a fruit widely produced and consumed around the world. Blue mold (Penicillium expansum) is one of the main postharvest diseases in apples, leading to a wide use of fungicides and the search for alternative products. The aim of this study was to assess the effect of salicylic acid (SA) against P. expansum, elucidating its mechanisms of action. The antimicrobial effect was determined by exposing conidia to a 2.5 mM SA solution for 0 to 120 min, followed by incubation. The effect of pH on the efficacy of SA against P. expansum was assessed both in vitro and in situ. The action mechanisms were investigated through fluorescence assays, measurement of protein leakage, lipid damage, and transmission electronic microscopy. SA was capable of inhibiting 90% of the fungal germination after 30 min, causing damage to the conidial plasma membrane and leading to protein leakage up to 3.2 μg of soluble protein per g of mycelium. The pH of the SA solution affected the antimicrobial activity of this secondary metabolite, which inhibited the germination of P. expansum and the blue mold incidence in apples in solutions with pH≤3 by 100%, gradually losing its activity at higher pH.

  14. Mechanically stable thermally crosslinked poly(acrylic acid)/reduced graphene oxide aerogels. (United States)

    Ha, Heonjoo; Shanmuganathan, Kadhiravan; Ellison, Christopher J


    Graphene oxide (GO) aerogels, high porosity (>99%) low density (∼3-10 mg cm(-3)) porous materials with GO pore walls, are particularly attractive due to their lightweight, high surface area, and potential use in environmental remediation, superhydrophobic and superoleophilic materials, energy storage, etc. However, pure GO aerogels are generally weak and delicate which complicates their handling and potentially limits their commercial implementation. The focus of this work was to synthesize highly elastic, mechanically stable aerogels that are robust and easy to handle without substantially sacrificing their high porosity or low density. To overcome this challenge, a small amount of readily available and thermally cross-linkable poly(acrylic acid) (PAA) was intermixed with GO to enhance the mechanical integrity of the aerogel without disrupting other desirable characteristic properties. This method is a simple straightforward procedure that does not include multistep or complicated chemical reactions, and it produces aerogels with mass densities of about 4-6 mg cm(-3) and >99.6% porosity that can reversibly support up to 10,000 times their weight with full recovery of their original volume. Finally, pressure sensing capabilities were demonstrated and their oil absorption capacities were measured to be around 120 g oil per g aerogel(-1) which highlights their potential use in practical applications.

  15. Mechanism of fatty-acid-dependent UCP1 uncoupling in brown fat mitochondria. (United States)

    Fedorenko, Andriy; Lishko, Polina V; Kirichok, Yuriy


    Mitochondrial uncoupling protein 1 (UCP1) is responsible for nonshivering thermogenesis in brown adipose tissue (BAT). Upon activation by long-chain fatty acids (LCFAs), UCP1 increases the conductance of the inner mitochondrial membrane (IMM) to make BAT mitochondria generate heat rather than ATP. Despite being a member of the family of mitochondrial anion carriers (SLC25), UCP1 is believed to transport H(+) by an unusual mechanism that has long remained unresolved. Here, we achieved direct patch-clamp measurements of UCP1 currents from the IMM of BAT mitochondria. We show that UCP1 is an LCFA anion/H(+) symporter. However, the LCFA anions cannot dissociate from UCP1 due to hydrophobic interactions established by their hydrophobic tails, and UCP1 effectively operates as an H(+) carrier activated by LCFA. A similar LCFA-dependent mechanism of transmembrane H(+) transport may be employed by other SLC25 members and be responsible for mitochondrial uncoupling and regulation of metabolic efficiency in various tissues.

  16. Radical and Non-Radical Mechanisms for Alkane Oxidations by Hydrogen Peroxide-Trifluoroacetic Acid

    Energy Technology Data Exchange (ETDEWEB)

    Camaioni, Donald M.; Bays, J. Timothy; Shaw, Wendy J.; Linehan, John C.; Birnbaum, Jerome C.


    The oxidation of cyclohexane by the H2O2-trifluoroacetic acid system is revisited. Consistent with a previous report (Deno, N.; Messer, L. A. Chem. Comm. 1976, 1051), cyclohexanol forms initially but then esterifies to cyclohexyl trifluoroacetate. Small amounts of trans-1,2-cyclohexadiyl bis(trifluoroacetate) also form. Although these products form irrespective of the presence or absence of O2, dual mechanisms are shown to operate. In the absence of O2, the dominant mechanism is a radical chain reaction that is propagated by CF3• abstracting H from C6H12 and SH2 displacement of C6H11• on CF3CO2OH. The intermediacy of C6H11• and CF3• is inferred from production of CHF3 and CO2 along with cyclohexyl trifluoroacetate, or CDF3 when cyclohexane-d12 is used. In the presence of O2, fluoroform and CO2 are suppressed, the reaction rate slows, and the rate law approaches second order (first order in peracid and in C6H12). Trapping of cyclohexyl radicals by quinoxaline is inefficient except at elevated (75 °C) temperatures. Fluoroform and CO2, telltale evidence for the chain pathway, were not produced when quinoxaline was present in room temperature reactions. These observations suggest that a parallel, nonfree radical, oxenoid insertion mechanism dominates when O2 is present. A pathway is discussed in which a biradicaloid-zwiterionic transition state is attained by hydrogen transfer from alkane to peroxide oxygen with synchronous O-O bond scission.

  17. Fabrication and mechanical characterization of graphene oxide-reinforced poly (acrylic acid)/gelatin composite hydrogels (United States)

    Faghihi, Shahab; Gheysour, Mahsa; Karimi, Alireza; Salarian, Reza


    Hydrogels have found many practical uses in drug release, wound dressing, and tissue engineering. However, their applications are restricted due to their weak mechanical properties. The role of graphene oxide nanosheets (GONS) as reinforcement agent in poly (acrylic acid) (PAA)/Gelatin (Gel) composite hydrogels is investigated. Composite hydrogels are synthesized by thermal initiated redox polymerization method. Samples are then prepared with 20 and 40 wt. % of PAA, an increasing amount of GONS (0.1, 0.2, and 0.3 wt. %), and a constant amount of Gel. Subsequently, cylindrical hydrogel samples are subjected to a series of compression tests in order to measure their elastic modulus, maximum stress and strain. The results exhibit that the addition of GONS increases the Young's modulus and maximum stress of hydrogels significantly as compared with control (0.0 wt. % GONS). The highest Young's modulus is observed for hydrogel with GO (0.2 wt. %)/PAA (20 wt. %), whereas the highest maximum stress is detected for GO (0.2 wt. %)/PAA (40 wt. %) specimen. The addition of higher amounts of GONS leads to a decrease in the maximum stress of the hydrogel GO (0.3 wt. %)/PAA (40 wt. %). No significant differences are detected for the maximum strain among the hydrogel samples, as the amount of GONS increased. These results suggest that the application of GONS could be used to improve mechanical properties of hydrogel materials. This study may provide an alternative for the fabrication of low-cost graphene/polymer composites with enhanced mechanical properties beneficial for tissue engineering applications.

  18. Retention Mechanisms of Citric Acid in Ternary Kaolinite-Fe(III)-Citrate Acid Systems Using Fe K-edge EXAFS and L3,2-edge XANES Spectroscopy (United States)

    Yang, Jianjun; Wang, Jian; Pan, Weinan; Regier, Tom; Hu, Yongfeng; Rumpel, Cornelia; Bolan, Nanthi; Sparks, Donald


    Organic carbon (OC) stability in tropical soils is strongly interlinked with multivalent cation interaction and mineral association. Low molecular weight organic acids (LMWOAs) represent the readily biodegradable OC. Therefore, investigating retention mechanisms of LMWOAs in mineral-cation-LMWOAs systems is critical to understanding soil C cycling. Given the general acidic conditions and dominance of kaolinite in tropical soils, we investigated the retention mechanisms of citric acid (CA) in kaolinite-Fe(III)-CA systems with various Fe/CA molar ratios at pH ~3.5 using Fe K-edge EXAFS and L3,2-edge XANES techniques. With Fe/CA molar ratios >2, the formed ferrihydrite mainly contributed to CA retention through adsorption and/or coprecipitation. With Fe/CA molar ratios from 2 to 0.5, ternary complexation of CA to kaolinite via a five-coordinated Fe(III) bridge retained higher CA than ferrihydrite-induced adsorption and/or coprecipitation. With Fe/CA molar ratios ≤0.5, kaolinite-Fe(III)-citrate complexation preferentially occurred, but less CA was retained than via outer-sphere kaolinite-CA complexation. This study highlighted the significant impact of varied Fe/CA molar ratios on CA retention mechanisms in kaolinite-Fe(III)-CA systems under acidic conditions, and clearly showed the important contribution of Fe-bridged ternary complexation on CA retention. These findings will enhance our understanding of the dynamics of CA and other LMWOAs in tropical soils.

  19. Ion pair formation as a possible mechanism for the enhancement effect of lauric acid on the transdermal permeation of ondansetron. (United States)

    Dimas, Dimitrios A; Dallas, Paraskevas P; Rekkas, Dimitrios M


    Transdermal application can be an alternative drug delivery route for ondansetron, an antiemetic drug. Previous studies found that fatty acids, namely oleic and lauric, were the most effective penetration enhancers. The aim of this study was to investigate the formation of an ion pair between ondansetron and lauric acid as a possible mechanism of its enhancing action. Several techniques were used to reveal the formation of an ion pair complex. Partitioning experiments, where the n-octanol/water coefficient was measured, showed an increase in the distribution coefficient in the presence of the acid, possibly as a result of the formation of more lipophilic ion pairs between the charged molecules of ondansetron and lauric acid. Further evidence of complex formation between ondansetron and lauric acid, was gained from the 13C-nuclear magnetic resonance (13C-NMR) spectra of ondansetron, lauric acid, and their mixture (molar ratio 1:1). The NMR spectra revealed alterations to the magnetic environment of the carbon atoms adjacent to the ionized group, which are the carbonyl group of the acid and the nitrogen of the imidazole ring of ondansetron. This evidence substantiates the theory of ion pair formation. Finally, thermal analysis of the binary mixtures of ondansetron and lauric acid revealed the formation of an additional compound, with different melting point from pure ondansetron and lauric acid, which is thermodynamically favored.

  20. CKS1B, overexpressed in aggressive disease, regulates multiple myeloma growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms (United States)

    Colla, Simona; Wu, Xiaosong; Chen, Bangzheng; Stewart, James P.; Kuehl, W. Michael; Barlogie, Bart


    Overexpression of CKS1B, a gene mapping within a minimally amplified region between 153 to 154 Mb of chromosome 1q21, is linked to a poor prognosis in multiple myeloma (MM). CKS1B binds to and activates cyclin-dependent kinases and also interacts with SKP2 to promote the ubiquitination and proteasomal degradation of p27Kip1. Overexpression of CKS1B or SKP2 contributes to increased p27Kip1 turnover, cell proliferation, and a poor prognosis in many tumor types. Using 4 MM cell lines harboring MAF-, FGFR3/MMSET-, or CCND1-activating translocations, we show that lentiviral delivery of shRNA directed against CKS1B resulted in ablation of CKS1B mRNA and protein with concomitant stabilization of p27Kip1, cell cycle arrest, and apoptosis. Although shRNA-mediated knockdown of SKP2 and forced expression of a nondegradable form of p27Kip1 (p27T187A) led to cell cycle arrest, apoptosis was modest. Of importance, while knockdown of SKP2 or overexpression of p27T187A induced cell cycle arrest in KMS28PE, an MM cell line with biallelic deletion of CDKN1B/p27Kip1, CKS1B ablation induced strong apoptosis. These data suggest that CKS1B influences myeloma cell growth and survival through SKP2- and p27Kip1-dependent and -independent mechanisms and that therapeutic strategies aimed at abolishing CKS1B function may hold promise for the treatment of high-risk disease for which effective therapies are currently lacking. PMID:17303695

  1. Microbial iron management mechanisms in extremely acidic environments: comparative genomics evidence for diversity and versatility

    Directory of Open Access Journals (Sweden)

    Nieto Pamela A


    Full Text Available Abstract Background Iron is an essential nutrient but can be toxic at high intracellular concentrations and organisms have evolved tightly regulated mechanisms for iron uptake and homeostasis. Information on iron management mechanisms is available for organisms living at circumneutral pH. However, very little is known about how acidophilic bacteria, especially those used for industrial copper bioleaching, cope with environmental iron loads that can be 1018 times the concentration found in pH neutral environments. This study was motivated by the need to fill this lacuna in knowledge. An understanding of how microorganisms thrive in acidic ecosystems with high iron loads requires a comprehensive investigation of the strategies to acquire iron and to coordinate this acquisition with utilization, storage and oxidation of iron through metal responsive regulation. In silico prediction of iron management genes and Fur regulation was carried out for three Acidithiobacilli: Acidithiobacillus ferrooxidans (iron and sulfur oxidizer A. thiooxidans and A. caldus (sulfur oxidizers that can live between pH 1 and pH 5 and for three strict iron oxidizers of the Leptospirillum genus that live at pH 1 or below. Results Acidithiobacilli have predicted FeoB-like Fe(II and Nramp-like Fe(II-Mn(II transporters. They also have 14 different TonB dependent ferri-siderophore transporters of diverse siderophore affinity, although they do not produce classical siderophores. Instead they have predicted novel mechanisms for dicitrate synthesis and possibly also for phosphate-chelation mediated iron uptake. It is hypothesized that the unexpectedly large number and diversity of Fe(III-uptake systems confers versatility to this group of acidophiles, especially in higher pH environments (pH 4–5 where soluble iron may not be abundant. In contrast, Leptospirilla have only a FtrI-Fet3P-like permease and three TonB dependent ferri-dicitrate siderophore systems. This paucity of iron

  2. Short-chain carboxylic acids, a new class of teratogens: studies of potential biochemical mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Coakley, M.E.; Rawlings, S.J.; Brown, N.A.


    Certain short-chain carboxylic acids (SCCA) appear to share a common teratogenic potential, although the structural requirements for activity remain obscure. By using a whole rat embryo culture model system, several biochemical processes have been examined, either as potential initial sites of teratogenic action or as early steps in the pathway to malformation. Valproate, methoxyacetate, and butyrate were the prototype SCCA examined. Measurement of (/sup 14/C)glucose utilization and lactate production confirmed that energy production by the early organogenesis embryo is predominantly from glycolysis. While the positive control agent, iodoacetate, caused a significant inhibition of lactate production, none of the SCCA affected this process or glucose utilization at teratogenic concentrations. Pinocytosis by the visceral yolk sac (VYS) was measured by the uptake of (/sup 125/I)polyvinylpyrrolidone. This process ultimately supplies the embryo with amino-acids and is essential for normal development. SCCA induce morphological abnormalities of the VYS in embryo culture. Pinocytosis was slightly reduced by valproate, but not the other SCCA. However, comparison with the action of an antiserum, for which inhibition of pinocytosis is the initial teratogenic insult, suggests that this is not the mechanism for valproate. Incorporation of (/sup 3/H)thymidine into embryo or yolk sac was not affected after 3 hr of SCCA exposure, but there was a marked effect of the positive control, hydroxyurea. This suggests that DNA synthesis is not directly influenced by SCCA. It can be concluded that SCCA do not exert their teratogenic effects by actions on glycolysis; maintenance of cellular acetyl CoA; pinocytosis or DNA synthesis. These observations contrast with preliminary results which suggest significant effects of SCCA on embryonic and yolk sac lipid metabolic pathways.

  3. Short-chain carboxylic acids, a new class of teratogens: studies of potential biochemical mechanisms. (United States)

    Coakley, M E; Rawlings, S J; Brown, N A


    Certain short-chain carboxylic acids (SCCA) appear to share a common teratogenic potential, although the structural requirements for activity remain obscure. By using a whole rat embryo culture model system, several biochemical processes have been examined, either as potential initial sites of teratogenic action or as early steps in the pathway to malformation. Valproate, methoxyacetate, and butyrate were the prototype SCCA examined. Measurement of [14C]glucose utilization and lactate production confirmed that energy production by the early organogenesis embryo is predominantly from glycolysis. While the positive control agent, iodoacetate, caused a significant inhibition of lactate production, none of the SCCA affected this process or glucose utilization at teratogenic concentrations. Valproate did not influence embryonic acetyl CoA levels, in marked contrast to the reported response of adult liver, the other major target of valproate toxicity. Pinocytosis by the visceral yolk sac (VYS) was measured by the uptake of [125I]polyvinylpyrrolidone. This process ultimately supplies the embryo with amino-acids and is essential for normal development. SCCA induce morphological abnormalities of the VYS in embryo culture. Pinocytosis was slightly reduced by valporate, but not the other SCCA. However, comparison with the action of an antiserum, for which inhibition of pinocytosis is the initial teratogenic insult, suggests that this is not the mechanism for valproate. Incorporation of [3H]thymidine into embryo or yolk sac was not affected after 3 hr of SCCA exposure, but there was a marked effect of the positive control, hydroxyurea. This suggests that DNA synthesis is not directly influenced by SCCA.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:3830097

  4. Thermodynamic properties of multifunctional oxygenates in atmospheric aerosols from quantum mechanics and molecular dynamics: dicarboxylic acids. (United States)

    Tong, Chinghang; Blanco, Mario; Goddard, William A; Seinfeld, John H


    Ambient particulate matter contains polar multifunctional oxygenates that partition between the vapor and aerosol phases. Vapor pressure predictions are required to determine the gas-particle partitioning of such organic compounds. We present here a method based on atomistic simulations combined with the Clausius-Clapeyron equation to predict the liquid vapor pressure, enthalpies of vaporization, and heats of sublimation of atmospheric organic compounds. The resulting temperature-dependent vapor pressure equation is a function of the heat of vaporization at the normal boiling point [deltaHvap(Tb)], normal boiling point (Tb), and the change in heat capacity (liquid to gas) of the compound upon phase change [deltaCp(Tb)]. We show that heats of vaporization can be estimated from calculated cohesive energy densities (CED) of the pure compound obtained from multiple sampling molecular dynamics. The simulation method (CED) uses a generic force field (Dreiding) and molecular models with atomic charges determined from quantum mechanics. The heats of vaporization of five dicarboxylic acids [malonic (C3), succinic (C4), glutaric (C5), adipic (C6), and pimelic (C7)] are calculated at 500 K. Results are in agreement with experimental values with an averaged error of about 4%. The corresponding heats of sublimation at 298 K are also predicted using molecular simulations. Vapor pressures of the five dicarboxylic acids are also predicted using the derived Clausius-Clapeyron equation. Predicted liquid vapor pressures agree well with available literature data with an averaged error of 29%, while the predicted solid vapor pressures at ambient temperature differ considerably from a recent study by Bilde et al. (Environ. Sci. Technol. 2003, 37, 1371-1378) (an average of 70%). The difference is attributed to the linear dependence assumption thatwe used in the derived Clausius-Clapeyron equation.

  5. Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1

    Directory of Open Access Journals (Sweden)

    Liufeng Zheng


    Full Text Available The mammalian target of rapamycin (mTOR is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs, especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood. Classically, AAs activate mTORC1 by Rag GTPases which recruit mTORC1 to lysosomes, where AA signaling initiates. Plasma membrane transceptor L amino acid transporter 1 (LAT1-4F2hc has dual transporter-receptor function that can sense extracellular AA availability upstream of mTORC1. The lysosomal AA sensors (PAT1 and SLC38A9 and cytoplasmic AA sensors (LRS, Sestrin2 and CASTOR1 also participate in regulating mTORC1 activation. Importantly, AAs can be sensed by plasma membrane receptors, like G protein-coupled receptor (GPCR T1R1/T1R3, and regulate mTORC1 without being transported into the cells. Furthermore, AA-dependent mTORC1 activation also initiates within Golgi, which is regulated by Golgi-localized AA transporter PAT4. This review provides an overview of the research progress of the AA sensing mechanisms that regulate mTORC1 activity.

  6. Recent Advances in Understanding Amino Acid Sensing Mechanisms that Regulate mTORC1 (United States)

    Zheng, Liufeng; Zhang, Wei; Zhou, Yuanfei; Li, Fengna; Wei, Hongkui; Peng, Jian


    The mammalian target of rapamycin (mTOR) is the central regulator of mammalian cell growth, and is essential for the formation of two structurally and functionally distinct complexes: mTORC1 and mTORC2. mTORC1 can sense multiple cues such as nutrients, energy status, growth factors and hormones to control cell growth and proliferation, angiogenesis, autophagy, and metabolism. As one of the key environmental stimuli, amino acids (AAs), especially leucine, glutamine and arginine, play a crucial role in mTORC1 activation, but where and how AAs are sensed and signal to mTORC1 are not fully understood. Classically, AAs activate mTORC1 by Rag GTPases which recruit mTORC1 to lysosomes, where AA signaling initiates. Plasma membrane transceptor L amino acid transporter 1 (LAT1)-4F2hc has dual transporter-receptor function that can sense extracellular AA availability upstream of mTORC1. The lysosomal AA sensors (PAT1 and SLC38A9) and cytoplasmic AA sensors (LRS, Sestrin2 and CASTOR1) also participate in regulating mTORC1 activation. Importantly, AAs can be sensed by plasma membrane receptors, like G protein-coupled receptor (GPCR) T1R1/T1R3, and regulate mTORC1 without being transported into the cells. Furthermore, AA-dependent mTORC1 activation also initiates within Golgi, which is regulated by Golgi-localized AA transporter PAT4. This review provides an overview of the research progress of the AA sensing mechanisms that regulate mTORC1 activity. PMID:27690010

  7. Retinoic acid and 1,25-dihydroxyvitamin D3 stimulate osteoclast formation by different mechanisms

    Energy Technology Data Exchange (ETDEWEB)

    Scheven, B.A.; Hamilton, N.J. (Rowett Research Institute, Bucksburn, Aberdeen (Scotland))


    The effects of retinoic acid (RA) and 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on osteoclast formation were examined in intact fetal long bones of different ages/developmental stages maintained in organ culture using a chemically defined medium with or without the presence of serum. Besides stimulating bone resorption, RA and 1,25-(OH)2D3 increased the number of osteoclasts in 19-day-old fetal rat tibiae. Likewise, these bone-resorbing agents induced and stimulated osteoclast formation in 19- and 18-day-old metatarsal bones which were osteoclast-free at the beginning of the culture. The response to 1,25-(OH)2D3 was greatly enhanced by 10% fetal bovine serum (FBS) irrespective of the developmental stage of the long bone. The response to RA was not. Light microscopic autoradiography after labeling of the cultures with tritiated thymidine showed that both RA and 1,25-(OH)2D3 induced osteoclast differentiation from proliferating and postmitotic precursors. However, neither agent was able to stimulate proliferation of osteoclast progenitor cells in the older bones (19 days). Studies on the formation of osteoclast-like (tartrate-resistant acid phosphatase positive) cells in bone marrow cultures indicated that FBS was a potent inducer of osteoclast-like cell formation. In the presence of FBS, 1,25-(OH)2D3 significantly stimulated this response, but RA did not. The results demonstrate that although both RA and 1,25-(OH)2D3 stimulate osteoclast formation from proliferating and postmitotic precursors in long bones in vitro, they do so by different mechanisms.

  8. Surviving Objects


    Murjas, Teresa


    Surviving Objects (2012) is a devised multi-media practice-as-research performance based on extensive interviews conducted with my elderly mother and recorded on a hand-held device. Our conversations concern her experiences as a child refugee following violent deportation by the Soviet Army from Eastern Poland to Siberia (1941), and her subsequent route, via Persia, to a British-run refugee camp in Northern Rhodesia, where she remained for 6 years before arriving in the UK. In order to aid my...

  9. Ab initio study on the mechanism of rhodium-complexcatalyzed carbonylation of methanol to acetic acid

    Institute of Scientific and Technical Information of China (English)

    LEI; Ming


    [1]Thomas, R., Cundari, T. R., Computational studies of transition metal-main group multiple bonding, Chem. Rev., 2000,100: 807.[2]Maricel Torrent, Miquel Sola, Gernot Frenking, Theoretical studies of some transition-metal-mediated reactions of industrial and synthetic importance, Chem. Rev., 2000, 100: 439.[3]Paulik, F. E., Roth, J. F., Catalysts for the low-pressure carbonylation of menthanol to acetic acid, Chem. Commun., 1968,24: 1578.[4]Jiang Hua, Diao Kaisheng, Pan Pinglai et al., A new class of rhodium complexes containing free donor atoms and their intramolecular substitution reaction, Chin. J. Chem., 2000, 18: 752.[5]Jiang Dazhi, Li Xiaobao, Wang Enlai, Synthesis Chemistry ofCarbonylation, Beijing: Chemical Technology Press, 1996.[6]Adamson, G. W., Daly, J. J., Forster, D., Reduction of iolocarbonyl rhodium ions with methyl iodide, structure of the rho-dium acetyl complex: [Me3PhN+], [Rh2I6-(Me(O)2(CO)2)]2-, J. Organomet. Chem., 1974, 71: C 17.[7]Forster, D., On the mechanism of a rhodium-complex-catalyzed carbonylation of methanol to acetic acid, J. Am. Chem.Soc., 1976, 98: 846.[8]Hjortkjaer, J., Jensen, O. R., Rhodium complexes catalyzed methanol carbonylation, Ind. Eng. Chem. Prod. Dev., 1976, 15:46.[9]Jeffrey, P., Wadt, W. R., Ab initio effective core potentials for molecular calculations, Potentials for the transition metalatoms Sc to Hg, J. Chem. Phys., 1995, 82: 270.[10]Frisch, M. J., Trunks, G. W., Schlegel, H. B. et al., Gaussian 94, Pittsburgh PA: Gaussian, Inc., 1995.[11]Lei Ming, Feng Wenlin, Xu Zhenfeng et al., A theoretical study on the key reactions of hydroformylation cycle by modi-fied carbonyl cobalt, Chemical Journal of Chinese University, 2001, 22: 455.[12]Lei Ming, Feng Wenlin, Xu Zhenfeng, Ab initio MO study on the reaction mechanism for carbonyl insertion catalyzed by the carbonyl cobalt complex, Chemical Research in Chinese University, 2000, 19:31.

  10. Mechanism of fatty acids induced suppression of cardiovascular reflexes in rats. (United States)

    Shaltout, Hossam A; Abdel-Rahman, Abdel A


    A blunted baroreflex sensitivity (BRS), impaired heart rate variability (HRV), and high plasma nonesterified fatty acids (NEFA) are predictors of adverse cardiovascular outcomes. We tested the hypothesis that elevation of NEFA negatively impacts the cardiac baroreflex response and undertook spectral analyses and molecular studies to delineate the mechanism of action. We used two interventions to elevate serum NEFA: 1) overnight fasting (n = 7) and 2) i.v. infusion of 1.2 ml/kg intralipid 20% + heparin (I/H) over 10 min (n = 9) in conscious unrestrained male rats. Elevated NEFA caused by fasting complemented by I/H infusion were associated with a concentration-dependent reduction in spontaneous BRS measured by spectral analysis [low-frequency alpha and high-frequency alpha (HFalpha) indices] and sequence method and HRV measured by frequency domain as power of RR interval (RRI) spectra (low-frequency RRI and high-frequency RRI) and by time domain as standard deviation of beat-to-beat interval and root mean square of successive differences along with increase in blood pressure variability measured as standard deviation of mean arterial pressure and power of systolic arterial pressure spectra (low-frequency systolic arterial pressure). Because elevated NEFA suppressed the vagal component of the baroreflex response (HFalpha), we tested the hypothesis that NEFA-evoked sequestration of myocardial muscarinic receptor (M2-mAChR) contributes to the reduced BRS. High NEFA level was accompanied by increased caveolar sequestration of cardiac M2-mAChRs without changing M2-mAChR protein expression. We report the first detailed analyses of NEFA's effect on the cardiac baroreflex and show that increased caveolar sequestration of cardiac M2-mAChRs constitutes a cellular mechanism for elevated NEFA-related deleterious cardiovascular outcomes.

  11. Conformational mechanics, adsorption, and normal force interactions of lubricin and hyaluronic acid on model surfaces. (United States)

    Chang, Debby P; Abu-Lail, Nehal I; Guilak, Farshid; Jay, Gregory D; Zauscher, Stefan


    Glycoproteins, such as lubricin, and hyaluronic acid (HA) play a prominent role in the boundary lubrication mechanism in diarthrodial joints. Although many studies have tried to elucidate the lubrication mechanisms of articular cartilage, the molecular details of how lubricin and HA interact with cartilage surfaces and mediate their interaction still remain poorly understood. Here we used model substrates, functionalized with self-assembled monolayers terminating in hydroxyl or methyl groups, (1) to determine the effect of surface chemistry on lubricin and HA adsorption using surface plasmon resonance (SPR) and (2) to study normal force interactions between these surfaces as a function of lubricin and HA concentration using colloidal probe microscopy. We found that lubricin is amphiphilic and adsorbed strongly onto both methyl- and hydroxyl-terminated surfaces. On hydrophobic surfaces, lubricin likely adopts a compact, looplike conformation in which its hydrophobic domains at the N and C termini serve as surface anchors. On hydrophilic surfaces, lubricin likely adsorbs anywhere along its hydrophilic central domain and adopts, with increasing solution concentration, an extended tail-like conformation. Overall, lubricin develops strong repulsive interactions when compressing two surfaces into contact. Furthermore, upon surface separation, adhesion occurs between the surfaces as a result of molecular bridging and chain disentanglement. This behavior is in contrast to that of HA, which does not adsorb appreciably on either of the model surfaces and does not develop significant repulsive interactions. Adhesive forces, particularly between the hydrophobic surfaces, are large and not appreciably affected by HA. For a mixture of lubricin and HA, we observed slightly larger adsorptions and repulsions than those found for lubricin alone. Our experiments suggest that this interaction depends on unspecific physical rather than chemical interactions between lubricin and HA. We

  12. Effect of amino acid dopants on the spectral, optical, mechanical and thermal properties of potassium acid phthalate crystals for possible optoelectronic and frequency doubling applications (United States)

    Prakash, J. Thomas Joseph; Gnanaraj, J. Martin Sam; Dhavud, S. Shek; Ekadevasena, S.


    Undoped and amino acid (L-Arginine and L-Valine) doped KAP crystals were grown by slow evaporation solution growth technique. The changes in the structural, spectral, optical, mechanical and thermal properties were observed. The sharp prominent peaks in the indexed powder XRD pattern confirms the crystalline nature of the sample. Optical studies reveal that the crystal is transparent in the entire visible light region. Thermal stability was checked by TG/DTA analysis. The mechanical stability was evaluated from Vicker's microhardness test. The SHG efficiency for the title materials was tested with different particle sizes by the Kurtz and Perry powder method, which established the existence of phase matching.

  13. Reaction mechanism of the acidic hydrolysis of highly twisted amides: Rate acceleration caused by the twist of the amide bond. (United States)

    Mujika, Jon I; Formoso, Elena; Mercero, Jose M; Lopez, Xabier


    We present an ab initio study of the acid hydrolysis of a highly twisted amide and a planar amide analogue. The aim of these studies is to investigate the effect that the twist of the amide bond has on the reaction barriers and mechanism of acid hydrolysis. Concerted and stepwise mechanisms were investigated using density functional theory and polarizable continuum model calculations. Remarkable differences were observed between the mechanism of twisted and planar amide, due mainly to the preference for N-protonation of the former and O-protonation of the latter. In addition, we were also able to determine that the hydrolytic mechanism of the twisted amide will be pH dependent. Thus, there is a preference for a stepwise mechanism with formation of an intermediate in the acid hydrolysis, whereas the neutral hydrolysis undergoes a concerted-type mechanism. There is a nice agreement between the characterized intermediate and available X-ray data and a good agreement with the kinetically estimated rate acceleration of hydrolysis with respect to analogous undistorted amide compounds. This work, along with previous ab initio calculations, describes a complex and rich chemistry for the hydrolysis of highly twisted amides as a function of pH. The theoretical data provided will allow for a better understanding of the available kinetic data of the rate acceleration of amides upon twisting and the relation of the observed rate acceleration with intrinsic differential reactivity upon loss of amide bond resonance.

  14. Mechanisms and potential therapeutic targets for folic acid in cardiovascular disease. (United States)

    Moens, An L; Vrints, Christiaan J; Claeys, Marc J; Timmermans, Jean-Pierre; Champion, Hunter C; Kass, David A


    Folic acid (FA) is a member of the B-vitamin family with cardiovascular roles in homocysteine regulation and endothelial nitric oxide synthase (eNOS) activity. Its interaction with eNOS is thought to be due to the enhancement of tetrahydrobiopterin bioavailability, helping maintain eNOS in its coupled state to favor the generation of nitric oxide rather than oxygen free radicals. FA also plays a role in the prevention of several cardiac and noncardiac malformations, has potent direct antioxidant and antithrombotic effects, and can interfere with the production of the endothelial-derived hyperpolarizing factor. These multiple mechanisms of action have led to studies regarding the therapeutic potential of FA in cardiovascular disease. To date, studies have demonstrated that FA ameliorates endothelial dysfunction and nitrate tolerance and can improve pathological features of atherosclerosis. These effects appear to be homocysteine independent but rather related to their role in eNOS function. Given the growing evidence that nitric oxide synthase uncoupling plays a major role in many cardiovascular disorders, the potential of exogenous FA as an inexpensive and safe oral therapy is intriguing and is stimulating ongoing investigations.

  15. Ab initio Mechanism Study on the Reaction of Chlorine Atom with Formic Acid

    Institute of Scientific and Technical Information of China (English)

    于海涛; 付宏刚; 等


    The potential energy surface(PES) for the reaction of Cl atom with HCOOH is predicted using ab initio molecular orbital calculation methods at UQCIDS(T,full)6-311++G(3df,2p)//UMP2(full)/6-311+G(d,P) level of theory with zero-point vibrational energy (ZPVE) correction.The calculated results show that the reaction mechanism of Cl atom with formic acid is a C-site hydrogen abstraction reaction from cis-HOC(H)O molecule by Cl atom with a 3.73kJ/mol reaction barrier height,leading to the formation of cis-HOCO radical which will reacts with Cl atom or other molecules in such a reaction system.Because the reaction barrier height of O-site hydrogen abstraction reaction from cis-HOC(H)O molecule by Cl atom which leads to the formation of HCO2 radical is 67.95kJ/mol,it is a secondary reaction channel in experiment,This is in good agreement with the prediction based on the previous experiments.

  16. Chromate enhanced visible light driven TiO₂ photocatalytic mechanism on Acid Orange 7 photodegradation. (United States)

    Wang, Yeoung-Sheng; Shen, Jyun-Hong; Horng, Jao-Jia


    When hexavalent chromium (Cr(VI)) is added to a TiO2 photocatalytic reaction, the decolorization and mineralization efficiencies of azo dyes Acid Orange 7 (AO7) are enhanced even though the mechanism is unclear. This study used 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) as the scavenger and the analysis of Electron Spin Resonance (ESR) to investigate this enhancement effect by observing the hydroxyl radical (OH) generation of the Cr(VI)/TiO2 system under UV and visible light (Vis) irradiation. With Cr(VI), the decolorization efficiencies were approximately 95% and 62% under UV and Vis, and those efficiencies were 25% less in the absence of Cr(VI). The phenomena of the DMPO-OH signals during the ESR analysis under Vis 405 and 550 nm irradiation were obviously the enhancement effects of Cr(VI) in aerobic conditions. In anoxic conditions, the catalytic effects of Cr(VI) could not be achieved due to the lack of a redox reaction between Cr(VI) and the adsorbed oxygen at the oxygen vacancy sites on the TiO2 surfaces. The results suggest that by introducing the agents of redox reactions such as chromate ions, we could lower the photoenergy of TiO2 needed and allow Vis irradiation to activate photocatalysis.

  17. Potential Mechanism of Action of meso-Dihydroguaiaretic Acid on Mycobacterium tuberculosis H37Rv

    Directory of Open Access Journals (Sweden)

    Aldo F. Clemente-Soto


    Full Text Available The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents.

  18. A gate-latch-lock mechanism for hormone signalling by abscisic acid receptors

    KAUST Repository

    Melcher, Karsten


    Abscisic acid (ABA) is a ubiquitous hormone that regulates plant growth, development and responses to environmental stresses. Its action is mediated by the PYR/PYL/RCAR family of START proteins, but it remains unclear how these receptors bind ABA and, in turn, how hormone binding leads to inhibition of the downstream type 2C protein phosphatase (PP2C) effectors. Here we report crystal structures of apo and ABA-bound receptors as well as a ternary PYL2-ABA-PP2C complex. The apo receptors contain an open ligand-binding pocket flanked by a gate that closes in response to ABA by way of conformational changes in two highly conserved ?-loops that serve as a gate and latch. Moreover, ABA-induced closure of the gate creates a surface that enables the receptor to dock into and competitively inhibit the PP2C active site. A conserved tryptophan in the PP2C inserts directly between the gate and latch, which functions to further lock the receptor in a closed conformation. Together, our results identify a conserved gate-latch-lock mechanism underlying ABA signalling. © 2009 Macmillan Publishers Limited. All rights reserved.

  19. Polyunsaturated fatty acids and membrane organization: elucidating mechanisms to balance immunotherapy and susceptibility to infection. (United States)

    Shaikh, Saame Raza; Edidin, Michael


    Polyunsaturated fatty acids (PUFAs), notably of the n-3 series, have immunosuppressive effects which make these molecules candidates for treating inflammatory symptoms associated with cardiovascular disease, obesity, arthritis, and asthma. However, immunosuppression by PUFAs could increase susceptibility to bacterial and viral infection. A detailed molecular picture is required in order to understand the balance between the benefits and risks of utilizing PUFAs as adjuvant immunosuppressants. Here we review evidence that incorporation of PUFAs into membrane lipids of antigen presenting cells (APCs) downregulates APC function. We propose that PUFAs modulate antigen presentation by altering the organization of lipid and protein molecules of the plasma membrane and endomembranes; this alters recognition and responses by T cells. The foundation of our hypothesis is built on data from artificial bilayer experiments which provide the physical principles by which PUFA acyl chains affect membrane architecture. This review also reconciles conflicting results in the literature by discussing the advantages and disadvantages of differing methods of PUFA treatment of cells. We suggest that membrane modulation of immune cells may be an important and overlooked mechanism of immunomodulation. In addition, we propose that mechanistic studies with defined experimental protocols will speed the translation of laboratory studies on PUFAs to the clinic.

  20. Effect of pimelic acid on the crystallization, morphology and mechanical properties of polypropylene/wollastonite composites

    Energy Technology Data Exchange (ETDEWEB)

    Meng Mingrui [Department of Polymer Science, College of Materials Science and Engineering, Nangjing University of Technology, Nanjing, Jiangsu Province 210009 (China)], E-mail:; Dou Qiang [Department of Polymer Science, College of Materials Science and Engineering, Nangjing University of Technology, Nanjing, Jiangsu Province 210009 (China)], E-mail:


    The pimelic acid (PA) was used as a new surface modifier for wollastonite. The effects of PA treatment on the crystallization, morphology and mechanical properties of polypropylene/wollastonite composites were investigated. The Fourier transform infrared spectroscopy analysis revealed that the PA bonded to the wollastonite's surface and formed the calcium pimelate after reacting with the wollastonite. The results of wide angle X-ray diffraction, differential scanning calorimetry and polarized light microscopy proved that the PA treated wollastonite induced more {beta}-crystalline form and decreased the spherulites sizes of polypropylene. The results of scanning electron microscopy showed that the PA treatment enhanced the interfacial adhesion between the filler and the matrix, indicating the improvement of the compatibility between polypropylene and wollastonite. The toughness of the composites was improved by the more ductile {beta}-form spherulites. When 2.5 wt% of PA treated wollastonite was added, the Izod notched impact strength reached its maximum, a value of 17.33 kJ/m{sup 2}, which was 3.19 times greater than that of the blank polypropylene.

  1. Mechanism of Growth Inhibition of Prostate Cancer Xenografts by Valproic Acid

    Directory of Open Access Journals (Sweden)

    Abhinav Sidana


    Full Text Available Valproic Acid (VPA, a histone deacetylase inhibitor, has been demonstrated to cause a marked decrease in proliferation of prostate cancer (PCa cells in vitro and a significant reduction in tumor volume in vivo. The goal of this study is to better understand the VPA-induced growth inhibition in vivo, by studying expression of various markers in PCa xenografts. Methods. For in vitro experiments, PCa cells were treated with 0, 0.6, and 1.2 mM VPA for 14 days. For in vivo models, experimental animals received 0.4% VPA in drinking water for 35 days. Tissue microarray was generated using cell pellets and excised xenografts. Results. VPA treatment causes cell cycle arrest in PCa cells in vivo, as determined by increase in p21 and p27 and decrease in cyclin D1 expression. Increased expression of cytokeratin18 was also seen in xenografts. LNCaP xenografts in treated animals had reduced androgen receptor (AR expression. While decreased proliferation was found in vitro, increase in apoptosis was found to be the reason for decreased tumor growth in vivo. Also, an anti-angiogenic effect was observed after VPA treatment. Conclusion. VPA inhibits tumor growth by multiple mechanisms including cell cycle arrest, induction of differentiation, and inhibition of growth of tumor vasculature.

  2. Competing mechanisms for perfluoroalkyl acid accumulation in plants revealed using an Arabidopsis model system. (United States)

    Müller, Claudia E; LeFevre, Gregory H; Timofte, Anca E; Hussain, Fatima A; Sattely, Elizabeth S; Luthy, Richard G


    Perfluoroalkyl acids (PFAAs) bioaccumulate in plants, presenting a human exposure route if present in irrigation water. Curiously, accumulation of PFAAs in plant tissues is greatest for both the short-chain and long-chain PFAAs, generating a U-shaped relationship with chain length. In the present study, the authors decouple competing mechanisms of PFAA accumulation using a hydroponic model plant system (Arabidopsis thaliana) exposed to a suite of 10 PFAAs to determine uptake, depuration, and translocation kinetics. Rapid saturation of root concentrations occurred for all PFAAs except perfluorobutanoate, the least-sorptive (shortest-chain) PFAA. Shoot concentrations increased continuously, indicating that PFAAs are efficiently transported and accumulate in shoots. Tissue concentrations of PFAAs during depuration rapidly declined in roots but remained constant in shoots, demonstrating irreversibility of the translocation process. Root and shoot concentration factors followed the U-shaped trend with perfluoroalkyl chain length; however, when normalized to dead-tissue sorption, this relationship linearized. The authors therefore introduce a novel term, the "sorption normalized concentration factor," to describe PFAA accumulation in plants; because of their hydrophobicity, sorption is the determining factor for long-chain PFAAs, whereas the shortest-chain PFAAs are most effectively transported in the plant. The present study provides a mechanistic explanation for previously unexplained PFAA accumulation trends in plants and suggests that shorter-chained PFAAs may bioaccumulate more readily in edible portions.

  3. Mechanical, Thermal and Morphological Properties of Poly(lactic acid/Epoxidized Palm Olein Blend

    Directory of Open Access Journals (Sweden)

    Hazimah Abu Hassan


    Full Text Available Poly(lactic acid (PLA is known to be a useful material in substituting the conventional petroleum-based polymer used in packaging, due to its biodegradability and high mechanical strength. Despite the excellent properties of PLA, low flexibility has limited the application of this material. Thus, epoxidized palm olein (EPO was incorporated into PLA at different loadings (1, 2, 3, 4 and 5 wt% through the melt blending technique and the product was characterized. The addition of EPO resulted in a decrease in glass transition temperature and an increase of elongation-at-break, which indicates an increase in the PLA chain mobility. PLA/EPO blends also exhibited higher thermal stability than neat PLA. Further, the PLA/1 wt% EPO blend showed enhancement in the tensile, flexural and impact properties. This is due to improved interaction in the blend producing good compatible morphologies, which can be revealed by Scanning Electron Microscopy (SEM analysis. Therefore, PLA can be efficiently plasticized by EPO and the feasibility of its use as flexible film for food packaging should be considered.

  4. Mechanical, thermal and morphological properties of poly(lactic acid)/epoxidized palm olein blend. (United States)

    Silverajah, V S Giita; Ibrahim, Nor Azowa; Zainuddin, Norhazlin; Yunus, Wan Md Zin Wan; Hassan, Hazimah Abu


    Poly(lactic acid) (PLA) is known to be a useful material in substituting the conventional petroleum-based polymer used in packaging, due to its biodegradability and high mechanical strength. Despite the excellent properties of PLA, low flexibility has limited the application of this material. Thus, epoxidized palm olein (EPO) was incorporated into PLA at different loadings (1, 2, 3, 4 and 5 wt%) through the melt blending technique and the product was characterized. The addition of EPO resulted in a decrease in glass transition temperature and an increase of elongation-at-break, which indicates an increase in the PLA chain mobility. PLA/EPO blends also exhibited higher thermal stability than neat PLA. Further, the PLA/1 wt% EPO blend showed enhancement in the tensile, flexural and impact properties. This is due to improved interaction in the blend producing good compatible morphologies, which can be revealed by Scanning Electron Microscopy (SEM) analysis. Therefore, PLA can be efficiently plasticized by EPO and the feasibility of its use as flexible film for food packaging should be considered.

  5. Antitumor activity of a 2-pyridinecarboxaldehyde 2-pyridinecarboxylic acid hydrazone copper complex and the related mechanism. (United States)

    Yang, Yingli; Huang, Tengfei; Zhou, Sufeng; Fu, Yun; Liu, Youxun; Yuan, Yanbin; Zhang, Qiongqing; Li, Shaoshan; Li, Changzheng


    In the present study, 2-pyridinecarboxaldehyde 2-pyridinecarboxylic acid hydrazone (PPAH) was prepared and its antitumor activity was evaluated. The inhibition of proliferation of PPAH against the HepG2 and HCT-116 cell lines was less effective, yet in the presence of copper ions, the mixture demonstrated excellent antitumor activity (IC50 at 2.75±0.30 µM for the HepG2 cell line, and 1.90±0.20 µM for the HCT-116 cell line, respectively) and the new active species was confirmed to be a PPAH copper complex with a 1:1 ratio by spectral analysis. The excellent antitumor activity of the copper complex prompted us to investigate the underlying mechanism. RT-PCR was performed to detect the changes in the expression of apoptotic genes induced by PPAH and its copper complex. However, no changes were observed when the cells were treated by the agents for 24 or 48 h, indicating that ROS were unlikely involved. Cell cycle analysis showed that both PPAH and its copper complex led to S phase arrest of the cells. The sDNA relaxation assay revealed that the PPAH-copper complex displayed dual topoisomerase inhibition for type I and II. The data suggest that the inhibition of proliferation exhibited by the PPAH copper complex may stem from its dual topoisomerase inhibition, which is rarely observed for a metal complex.

  6. Structural, optical, thermal and mechanical properties of Urea tartaric acid single crystals (United States)

    Vinothkumar, P.; Rajeswari, K.; Kumar, R. Mohan; Bhaskaran, A.


    Urea tartaric acid (UT) an organic nonlinear optical (NLO) material was synthesized from aqueous solution and the crystals were grown by the slow evaporation technique. The single crystal X-ray diffraction (XRD) analysis revealed that the UT crystal belongs to the orthorhombic system. The functional groups of UT have been identified by the Fourier transform infrared spectral studies. The optical transparent window in the visible and near the IR regions was investigated. The transmittance of UT has been used to calculate the refractive index (n) as a function of the wavelength. The nonlinear optical property of the grown crystal has been confirmed by the Kurtz powder second harmonic generation test. The birefringence of the crystal was determined using a tungsten halogen lamp source. The laser induced surface damage threshold for the grown crystal was measured using the Nd:YAG laser. The anisotropic in mechanical property of the grown crystals was studied using Vicker's microhardness tester at different planes. The etch pit density of UT crystals was investigated. The thermal behavior of UT was investigated using the TG-DTA and DSC studies.

  7. Biosynthesis of Polyunsaturated Fatty Acids in Marine Invertebrates: Recent Advances in Molecular Mechanisms (United States)

    Monroig, Óscar; Tocher, Douglas R.; Navarro, Juan C.


    Virtually all polyunsaturated fatty acids (PUFA) originate from primary producers but can be modified by bioconversions as they pass up the food chain in a process termed trophic upgrading. Therefore, although the main primary producers of PUFA in the marine environment are microalgae, higher trophic levels have metabolic pathways that can produce novel and unique PUFA. However, little is known about the pathways of PUFA biosynthesis and metabolism in the levels between primary producers and fish that are largely filled by invertebrates. It has become increasingly apparent that, in addition to trophic upgrading, de novo synthesis of PUFA is possible in some lower animals. The unequivocal identification of PUFA biosynthetic pathways in many invertebrates is complicated by the presence of other organisms within them. These organisms include bacteria and algae with PUFA biosynthesis pathways, and range from intestinal flora to symbiotic relationships that can involve PUFA translocation to host organisms. This emphasizes the importance of studying biosynthetic pathways at a molecular level, and the continual expansion of genomic resources and advances in molecular analysis is facilitating this. The present paper highlights recent research into the molecular and biochemical mechanisms of PUFA biosynthesis in marine invertebrates, particularly focusing on cephalopod molluscs. PMID:24152561

  8. Effects of lysophosphatidic acid on human colon cancer cells and its mechanisms of action

    Institute of Scientific and Technical Information of China (English)

    Hong Sun; Juan Ren; Qing Zhu; Fan-Zhong Kong; Lei Wu; Bo-Rong Pan


    AIM: To study the effects of lysophosphatidic acid (LPA) on proliferation, adhesion, migration, and apoptosisin the human colon cancer cell line, SW480, and its mechanisms of action. METHODS: Methyl tetrazolium assay was used to assess cell proliferation. Flow cytometry was employed to detect cell apoptosis. Cell migration was measured by using a Boyden transwell migration chamber. Cell adhesion assay was performed in 96-well plates according to protocol.RESULTS: LPA significantly stimulated SW480 cell proliferation in a dose-dependent and time-dependent manner compared with the control group (P < 0.05) while the mitogen-activated protein kinase (MAPK) inhibitor,PD98059, significantly blocked the LPA stimulation effect on proliferation. LPA also significantly stimulated adhesion and migration of SW480 cells in a dosedependent manner (P < 0.05). Rho kinase inhibitor,Y-27632, significantly inhibited the up-regulatory effect of LPA on adhesion and migration (P < 0.05). LPA significantly protected cells from apoptosis induced by the chemotherapeutic drugs, cisplatin and 5-FU (P < 0.05),but the phosphoinositide 3-kinase (PI3K) inhibitor,LY294002, significantly blocked the protective effect of LPA on apoptosis.CONCLUSION: LPA stimulated proliferation, adhesion,migration of SW480 cells, and protected from apoptosis.The Ras/Raf-MAPK, G12/13-Rho-RhoA and PI3KAKT/ PKB signal pathways may be involved.

  9. Morphology, thermal, mechanical, and barrier properties of graphene oxide/poly(lactic acid) nanocomposite films

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Seong Woo; Choi, Hyun Muk [Kyonggi University, Suwon (Korea, Republic of)


    To improve the physical and gas barrier properties of biodegradable poly(lactic acid) (PLA) film, two graphene nanosheets of highly functionalized graphene oxide (0.3 wt% to 0.7 wt%) and low-functionalized graphene oxide (0.5 wt%) were incorporated into PLA resin via solution blending method. Subsequently, we investigated the effects of material parameters such as loading level and degree of functionalization for the graphene nanosheets on the morphology and properties of the resultant nanocomposites. The highly functionalized graphene oxide (GO) caused more exfoliation and homogeneous dispersion in PLA matrix as well as more sustainable suspensions in THF, compared to low-functionalized graphene oxide (LFGO). When loaded with GO from 0.3 wt% to 0.7 wt%, the glass transition temperature, degree of crystallinity, tensile strength and modulus increased steadily. The GO gave rise to more pronounced effect in the thermal and mechanical reinforcement, relative to LFGO. In addition, the preparation of fairly transparent PLA-based nanocomposite film with noticeably improved barrier performance achieved only when incorporated with GO up to 0.7wt%. As a result, GO may be more compatible with hydrophilic PLA resin, compared to LFGO, resulting in more prominent enhancement of nanocomposites properties.

  10. Mechanism of the OH radical scavenging activity of nordihydroguaiaretic acid: a combined theoretical and experimental study. (United States)

    Galano, Annia; Macías-Ruvalcaba, Norma A; Medina Campos, Omar Noel; Pedraza-Chaverri, José


    The antioxidant nordihydroguaiaretic acid (NDGA) is a plant phenolic lignan originally isolated from the creosote bush (Larrea tridentata). It has been shown that NDGA scavenges efficiently hydroxyl radicals ((*)OH). In the present paper the mechanism by which NDGA scavenges (*)OH is addressed performing a combined experimental and theoretical investigation. We found that NDGA protects, in a concentration-dependent way, bovine serum albumin and DNA from the damage induced by (*)OH generated by the Fenton reaction. In addition, the NDGA + (*)OH reaction is predicted to be diffusion-controlled. The first step of this reaction is proposed to occur mainly by a sequential electron proton transfer from NDGA to (*)OH generating a neutral radical of NDGA, which after a second oxidation step gives a diradical that after a cascade sequential complex reaction produces a cyclic compound. This cyclic product is predicted to have a UV-vis spectrum very similar to that of NDGA, making its identification by this technique very difficult. The electrochemical studies performed in water support the formation of a cyclic compound (C2) as the main product of the reaction. It is concluded that NDGA can scavenge at least two (*)OH.

  11. Potential mechanism of action of meso-dihydroguaiaretic acid on Mycobacterium tuberculosis H37Rv. (United States)

    Clemente-Soto, Aldo F; Balderas-Rentería, Isaías; Rivera, Gildardo; Segura-Cabrera, Aldo; Garza-González, Elvira; del Rayo Camacho-Corona, María


    The isolation and characterization of the lignan meso-dihydroguaiaretic acid (MDGA) from Larrea tridentata and its activity against Mycobacterial tuberculosis has been demonstrated, but no information regarding its mechanism of action has been documented. Therefore, in this study we carry out the gene expression from total RNA obtained from M. tuberculosis H37Rv treated with MDGA using microarray technology, which was validated by quantitative real time polymerase chain reaction. Results showed that the alpha subunit of coenzyme A transferase of M. tuberculosis H37Rv is present in both geraniol and 1-and 2-methylnaphthalene degradation pathways, which are targeted by MDGA. This assumption was supported by molecular docking which showed stable interaction between MDGA with the active site of the enzyme. We propose that inhibition of coenzyme A transferase of M. tuberculosis H37Rv results in the accumulation of geraniol and 1-and 2-methylnaphtalene inside bacteria, causing membrane destabilization and death of the pathogen. The natural product MDGA is thus an attractive template to develop new anti-tuberculosis drugs, because its target is different from those of known anti-tubercular agents.

  12. Effects of support acidity on the reaction mechanisms of selective catalytic reduction of NO by CH4 in excess oxygen

    Institute of Scientific and Technical Information of China (English)

    Shicheng XU; Junhua LI; Dong YANG; Jiming HAO


    The reaction mechanisms of selective catalytic reduction (SCR) of nitric oxide (NO) by methane (CH4)over solid superacid-based catalysts were proposed and testified by DRIFTS studies on transient reaction as well as by kinetic models. Catalysts derived from different supports would lead to different reaction pathways, and the acidity of solid superacid played an important role in determining the reaction mechanisms and the catalytic activities. Higher ratios of Bronsted acid sites to Lewis acid sites would lead to stronger oxidation of methane and then could facilitate the step of methane activation. Strong Bronsted acid sites would not necessarily lead to better catalytic performance, however, since the active surface NOy species and the corresponding reaction routes were determined by the overall acidity strength of the support.The reaction routes where NO2 moiety was engaged as an important intermediate involved moderate oxidation of methane, the rate of which could determine the overall activity. The reaction involving NO moiety was likely to be determined by the step of reduction of NO. Therefore, to enhance the SCR activity of solid superacid catalysts,reactions between appropriate couples of active NOy species and activated hydrocarbon intermediates should be realized by modification of the support acidity.

  13. JA, a new type of polyunsaturated fatty acid isolated from Juglans mandshurica Maxim, limits the survival and induces apoptosis of heptocarcinoma cells. (United States)

    Gao, Xiu-Li; Lin, Hua; Zhao, Wei; Hou, Ya-Qin; Bao, Yong-Li; Song, Zhen-Bo; Sun, Lu-Guo; Tian, Shang-Yi; Liu, Biao; Li, Yu-Xin


    Juglans mandshurica Maxim (Juglandaceae) is a famous folk medicine for cancer treatment and some natural compounds isolated from it have been studied extensively. Previously we isolated a type of ω-9 polyunsaturated fatty acid (JA) from the bark of J. mandshurica, however little is known about its activity and the underlying mechanisms. In this study, we studied anti-tumor activity of JA on several human cancer cell lines. Results showed that JA is cytotoxic to HepG2, MDA-MB-231, SGC-7901, A549 and Huh7 cells at a concentration exerting minimal toxic effects on L02 cells. The selective toxicity of JA was better than other classical anti-cancer drugs. Further investigation indicated that JA could induce cell apoptosis, characterized by chromatin condensation, DNA fragmentation and activation of the apoptosis-associated proteins such as Caspase-3 and PARP-1. Moreover, we investigated the cellular apoptosis pathway involved in the apoptosis process in HepG2 cells. We found that proteins involved in mitochondrion (cleaved-Caspase-9, Apaf-1, HtrA2/Omi, Bax, and Mitochondrial Bax) and endocytoplasmic reticulum (XBP-1s, GRP78, cleaved-Caspase-7 and cleaved-Caspase-12) apoptotic pathways were up-regulated when cells were treated by JA. In addition, a morphological change in the mitochondrion was detected. Furthermore, we found that JA could inhibit DNA synthesis and induce G2/M cell cycle arrest. The expression of G2-to-M transition related proteins, such as CyclinB1 and phosphorylated-CDK1, were reduced. In contrast, the G2-to-M inhibitor p21 was increased in JA-treated cells. Overall, our results suggest that JA can induce mitochondrion- and endocytoplasmic reticulum-mediated apoptosis, and G2/M phase arrest in HepG2 cells, making it a promising therapeutic agent against hepatoma.

  14. Survival of Salmonella enterica in poultry feed is strain dependent. (United States)

    Andino, Ana; Pendleton, Sean; Zhang, Nan; Chen, Wei; Critzer, Faith; Hanning, Irene


    Feed components have low water activity, making bacterial survival difficult. The mechanisms of Salmonella survival in feed and subsequent colonization of poultry are unknown. The purpose of this research was to compare the ability of Salmonella serovars and strains to survive in broiler feed and to evaluate molecular mechanisms associated with survival and colonization by measuring the expression of genes associated with colonization (hilA, invA) and survival via fatty acid synthesis (cfa, fabA, fabB, fabD). Feed was inoculated with 1 of 15 strains of Salmonella enterica consisting of 11 serovars (Typhimurium, Enteriditis, Kentucky, Seftenburg, Heidelberg, Mbandanka, Newport, Bairely, Javiana, Montevideo, and Infantis). To inoculate feed, cultures were suspended in PBS and survival was evaluated by plating samples onto XLT4 agar plates at specific time points (0 h, 4 h, 8 h, 24 h, 4 d, and 7 d). To evaluate gene expression, RNA was extracted from the samples at the specific time points (0, 4, 8, and 24 h) and gene expression measured with real-time PCR. The largest reduction in Salmonella occurred at the first and third sampling time points (4 h and 4 d) with the average reductions being 1.9 and 1.6 log cfu per g, respectively. For the remaining time points (8 h, 24 h, and 7 d), the average reduction was less than 1 log cfu per g (0.6, 0.4, and 0.6, respectively). Most strains upregulated cfa (cyclopropane fatty acid synthesis) within 8 h, which would modify the fluidity of the cell wall to aid in survival. There was a weak negative correlation between survival and virulence gene expression indicating downregulation to focus energy on other gene expression efforts such as survival-related genes. These data indicate the ability of strains to survive over time in poultry feed was strain dependent and that upregulation of cyclopropane fatty acid synthesis and downregulation of virulence genes were associated with a response to desiccation stress.

  15. Basic mechanisms behind the effects of n-3 fatty acids on cardiovascular disease. (United States)

    Massaro, Marika; Scoditti, Egeria; Carluccio, Maria Annunziata; De Caterina, Raffaele


    The epidemiological association between high intakes of n-3 fatty acids (FA) and decreased morbidity and mortality from cardiovascular disease (CVD) can be explained by two main basic mechanisms: (a) an effect on atherothrombosis, and (b) an effect on cardiac arrhythmias. These mechanisms probably reflect different beneficial influences of n-3 FA on cardiovascular biology. Effects on atherothrombosis include the modulation of the expression of pro-atherogenic genes (e.g., endothelial leukocyte adhesion molecules, inflammatory cytokines and cyclooxygenase (COX)-2) and the hepatic synthesis of very low density lipoproteins (VLDL), and are slow in onset, requiring incorporation into cell membrane phospholipids, and usually doses in humans in the order of 3g/day or higher. Effects on cardiac arrhythmias include complex interactions with ion channels (sodium, potassium and calcium channels), typically requiring the presence of free FA in extracellular fluids and usually occurring with lower doses (around 1g/day) of nutritional or pharmacological intake. We have focused most of our research effort in unraveling the pathophysiological background of protection by n-3 FA from atherothrombosis. As the result of incorporation of n-3 FA in the sn-2 position predominantly of the phosphatidyl ethanolamine pool in the inner leaflet of the plasma membrane, n-3 FA appear on the one hand to increase the production of bioactive lipid mediators (protectins and resolvins) affecting cytokine-induced signal transduction; and on the other hand to directly interfere with the generation of reactive oxygen species (mostly hydrogen peroxide), directly responsible for the activation of the transcription factor nuclear factor (NF)-kappaB, which controls the expression of a variety of pro-inflammatory and pro-atherogenic genes, including those encoding for interleukin (IL)-1, IL-6, IL-8, tumor necrosis factor (TNF)alpha, vascular cell adhesion molecule-1 (VCAM-1), E-selectin, and COX-2. The

  16. Cholesterol-lowering effects and mechanisms in view of bile acid pathway of resveratrol and resveratrol-glucuronides (United States)

    Resveratrol (Res) was previously reported to be capable of lowering plasma TC and LDL-C. The mechanism behind Res is not clearly understood, although it is presumed to have an effect on bile acid metabolism in the liver: a significant way in eliminating cholesterol from the body. As one of the major...

  17. Discovery of benzofuran propanoic acid GPR120 agonists: From uHTS hit to mechanism-based pharmacodynamic effects. (United States)

    Lombardo, Matthew; Bender, Kate; London, Clare; Kirkland, Melissa; Mane, Joel; Pachanski, Michele; Geissler, Wayne; Cummings, John; Habulihaz, Bahanu; Akiyama, Taro E; Di Salvo, Jerry; Madeira, Maria; Pols, Joanna; Powles, Mary Ann; Finley, Michael F; Johnson, Eric; Roussel, Thomas; Uebele, Victor N; Crespo, Alejandro; Leung, Dennis; Alleyne, Candice; Trusca, Dorina; Lei, Ying; Howard, Andrew D; Ujjainwalla, Feroze; Tata, James R; Sinz, Christopher J


    The transformation of an aryloxybutanoic acid ultra high-throughput screening (uHTS) hit into a potent and selective series of G-protein coupled receptor 120 (GPR120) agonists is reported. uHTS hit 1 demonstrated an excellent rodent pharmacokinetic profile and selectivity over the related fatty acid receptor GPR40, but only modest GPR120 potency. Optimization of the "left-hand" aryl group led to compound 6, which demonstrated a GPR120 mechanism-based pharmacodynamic effect in a mouse oral glucose tolerance test (oGTT). Further optimization gave rise to the benzofuran propanoic acid series (exemplified by compound 37), which demonstrated acute mechanism-based pharmacodynamic effects. The combination of in vivo efficacy and attractive rodent pharmacodynamic profiles suggests compounds generated from this series may afford attractive candidates for the treatment of Type 2 diabetes.

  18. Structural, optical, thermal, mechanical and dielectric studies of Sulfamic acid single crystals: An influence of dysprosium (Dy3+) doping (United States)

    Singh, Budhendra; Shkir, Mohd.; AlFaify, S.; Kaushal, Ajay; Nasani, Narendar; Bdikin, Igor; Shoukry, H.; Yahia, I. S.; Algarni, H.


    Sulfamic acid is a potential material that exhibits excellent optical properties. A good quality, pure and dysprosium (Dy3+) doped (2.5 and 5 mol %) Sulfamic acid (SA) single crystals were grown successfully by slow cooling method. Structural study revealed a slight change in its lattice parameters and volume, suggesting the successful incorporation of Dy3+ in crystal system. The existence of dysprosium in the system was also confirmed. Presence of various vibrational modes was confirmed. Optical transparency was found to have a significant effect with variation in the doping concentration. Furthermore, a marked enhancement in its mechanical parameters with doping was also identified by nanoindentation technique. Etching study was also performed on the grown crystals to study the etch-pit formation and growth mechanism. Effect of doping on the thermal stability was analysed. All the results were compared and discussed in detail to get insight of the effect of doping concentration on Sulfamic acid crystal.

  19. Gallic Acid as a Complexing Agent for Copper Chemical Mechanical Polishing Slurries at Neutral pH (United States)

    Kim, Yung Jun; Kang, Min Cheol; Kwon, Oh Joong; Kim, Jae Jeong


    Gallic acid was investigated as a new complexing agent for copper (Cu) chemical mechanical polishing slurries at neutral pH. Addition of 0.03 M gallic acid and 1.12 M H2O2 at pH 7 resulted in a Cu removal rate of 560.73±17.49 nm/min, and the ratio of the Cu removal rate to the Cu dissolution rate was 14.8. Addition of gallic acid improved the slurry performance compared to glycine addition. X-ray photoelectron spectroscopy analysis and contact angle measurements showed that addition of gallic acid enhanced the Cu polishing behavior by suppressing the formation of surface Cu oxide.

  20. Absorbability, Mechanism and Structure-Property Relationship of Three Phenolic Acids from the Flowers of Trollius chinensis

    Directory of Open Access Journals (Sweden)

    Xiu-Wen Wu


    Full Text Available The absorption properties, mechanism of action, and structure-property relationship of three phenolic acids isolated from the flowers of Trollius chinensis Bunge, namely, proglobeflowery acid (PA, globeflowery acid (GA and trolloside (TS, were investigated using the human Caco-2 cell monolayer model. The results showed that these three phenolic acids were transported across the Caco-2 cell monolayer in a time and concentration dependent manner at the Papp level of 10−5 cm/s, and their extent of absorption correlated with their polarity and molecular weight. In conclusion, all three of these compounds were easily absorbed through passive diffusion, which implied their high bioavailability and significant contribution to the effectiveness of T. chinensis.

  1. The bioactive compounds alpha-chaconine and gallic acid in potato extracts decrease survival and induce apoptosis in LNCaP and PC3 prostate cancer cells. (United States)

    Reddivari, Lavanya; Vanamala, Jairam; Safe, Stephen H; Miller, J Creighton


    We recently reported that colored potato extracts and an anthocyanin rich fraction suppressed lymph-node carcinoma of the prostate (LNCaP) and prostate cancer-3 (PC-3) prostate cancer cell proliferation and induced apoptosis via caspase-dependent and caspase-independent pathways. Chlorogenic acid, caffeic acid, gallic acid, catechin, malvidin, and glycoalkaloids (alpha-chaconine and solanine) have now been identified as the major bioactive components of potato, and their effects on LNCaP and PC-3 cell proliferation and apoptosis have been investigated. alpha-chaconine (5 microg/ml) and gallic acid (15 microg/ml) exhibited potent antiproliferative properties and increased cyclin-dependent kinase inhibitor p27 levels in both cell lines. Both alpha-chaconine and gallic acid induced poly [adenosine diphosphate (ADP)] ribose polymerase cleavage and caspase-dependent apoptosis in LNCaP cells; however, caspase-independent apoptosis through nuclear translocation of endonuclease G was observed in both LNCaP and PC-3 cells. alpha-chaconine and gallic acid activated c-Jun N-terminal protein kinase (JNK), and this response played a major role in induction of caspase-dependent apoptosis in LNCaP cells; whereas modulation of JNK and mitogen-activated protein kinase did not affect alpha-chaconine- and gallic acid-induced caspase-independent apoptosis. These results suggest that apoptosis induced by whole potato extracts in prostate cancer cell lines may be in part due to alpha-chaconine and gallic acid.

  2. Molecular mechanism of flip-flop in triple-layer oleic-acid membrane: correlation between oleic acid and water. (United States)

    Ngo, Van A; Kalia, Rajiv K; Nakano, Aiichiro; Vashishta, Priya


    We perform all-atom molecular dynamics simulations to study a pure oleic acid (OA) membrane in water that results in a triple-layer structure. We compute the pressure profiles to examine the hydrophobic and hydrophilic regions, and to estimate the surface tension (≈34.5 mN/m), which is similar to those of lipid membranes. We observe that the membrane of OAs having a large diffusion coefficient (0.4 × 10(-7) cm(2)/s) along the normal to the membrane is an ideal model to study oleic acid flip-flop. In the model, the membrane contains a middle layer serving as an intermediate for water and OAs to easily migrate (flip-flop) from one to other leaflets. Water molecules surrounding OA head-groups help to reduce the barriers at the hydrophobic interface to trigger flip-flop events. Within 500 ns, we observe 175 flip-flop events of OAs and 305 events of water traversing the membrane. The ratio of water passing rate (k(H(2)O) = 0.673 ns(-1)) to OA flip-flop rate (k(OA) = 0.446 ns(-1)) is 3/2. The ratio of the totally correlated water-OA events to the totally uncorrelated water-OA events, n(cor)/n(uncor), is also 3/2. The probability of the totally and partially correlated events is 69%. The results indicate that the trans-membrane movement of water and OAs is cooperative and correlated, and agrees with experimentally measured absorption rates. They support the idea that OA flip-flop is more favorable than transport by means of functional proteins. This study might provide further insight into how primitive cell membranes work, and how the interplay and correlation between water and fatty acids may occur.

  3. Mechanisms leading to oligomers and SOA through aqueous photooxidation: insights from OH radical oxidation of acetic acid

    Directory of Open Access Journals (Sweden)

    Y. Tan


    Full Text Available Previous experiments have demonstrated that the aqueous OH radical oxidation of methylglyoxal produces low volatility products including oxalate and oligomers. These products are found predominantly in the particle phase in the atmosphere, suggesting that methylglyoxal is a precursor of secondary organic aerosol (SOA. Acetic acid is an important intermediate in aqueous methylglyoxal oxidation and a ubiquitous product of gas phase photochemistry, making it a potential "aqueous" SOA precursor in its own right. Altieri et al. (2008 proposed that acetic acid was the precursor of oligoesters observed in methylglyoxal oxidation. However, the fate of acetic acid upon aqueous-phase oxidation is not well understood. In this research, acetic acid at concentrations relevant to atmospheric waters (20 μM–10 mM was oxidized by OH radical. Products were analyzed by ion chromatography (IC, electrospray ionization mass spectrometry (ESI-MS, and IC-ESI-MS. The formation of glyoxylic, glycolic, and oxalic acids were observed. In contrast to methylglyoxal oxidation, succinic acid and oligomers were not detected. Using results from these and methylglyoxal + OH radical experiments, radical mechanisms responsible for oligomer formation from methylglyoxal oxidation in clouds and wet aerosols are proposed. The importance of acetic acid/acetate as an SOA precursor is also discussed. We hypothesize that this and similar chemistry is central to the daytime formation of oligomers in wet aerosols.

  4. Relaxation of endothelin-1-induced pulmonary arterial constriction by niflumic acid and NPPB: mechanism(s) independent of chloride channel block. (United States)

    Kato, K; Evans, A M; Kozlowski, R Z


    We investigated the effects of the Cl- channel blockers niflumic acid, 5-nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB) and 4, 4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS) on endothelin-1 (ET-1)-induced constriction of rat small pulmonary arteries (diameter 100-400 microm) in vitro, following endothelium removal. ET-1 (30 nM) induced a sustained constriction of rat pulmonary arteries in physiological salt solution. Arteries preconstricted with ET-1 were relaxed by niflumic acid (IC50: 35.8 microM) and NPPB (IC50: 21.1 microM) in a reversible and concentration-dependent manner. However, at concentrations known to block Ca++-activated Cl- channels, DIDS (acid (30 microM) and NPPB (30 microM) inhibited the ET-1-induced constriction by approximately 53% and approximately 60%, respectively, both in the continued presence of nifedipine and in Ca++-free physiological salt solution. The Ca++ ionophore A23187 (10 microM) also evoked a sustained constriction of pulmonary arteries. Surprisingly, the A23187-induced constriction was also inhibited in a reversible and concentration-dependent manner by niflumic acid (IC50: 18.0 microM) and NPPB (IC50: 8.8 microM), but not by DIDS (mechanism by which niflumic acid and NPPB inhibit pulmonary artery constriction is independent of Cl- channel blockade. One possibility is that these compounds may block the Ca++-dependent contractile processes.

  5. Optimization of the mechanical performance of bacterial cellulose/poly(L-lactic) acid composites. (United States)

    Quero, Franck; Nogi, Masaya; Yano, Hiroyuki; Abdulsalami, Kovo; Holmes, Stuart M; Sakakini, Bahij H; Eichhorn, Stephen J


    Understanding the nature of the interface between nanofibers and polymer resins in composite materials is challenging because of the complexity of interactions that may occur between fibers and between the matrix and the fibers. The ability to select the most efficient amount of reinforcement for stress transfer, making a saving on both cost and weight, is also a key part of composite design. The use of Raman spectroscopy to investigate micromechanical properties of laminated bacterial cellulose (BC)/poly(l-lactic) acid (PLLA) resin composites is reported for the first time as a means for understanding the fundamental stress-transfer processes in these composites, but also as a tool to select appropriate processing and volume fraction of the reinforcing fibers. Two forms of BC networks are investigated, namely, one cultured for 3 days and another for 6 days. The mechanical properties of the latter were found to be higher than the former in terms of Young's modulus, stress at failure, and work of fracture. However, their specific Young's moduli (divided by density) were found to be similar. Young's modulus and stress at failure of transparent predominantly amorphous PLLA films were found to increase by 100 and 315%, respectively, for an 18% volume fraction of BC fibers. BC networks cultured for 3 days were shown to exhibit enhanced interaction with PLLA because of their higher total surface area compared, as measured by nitrogen adsorption, to the material cultured for 6 days. This enhanced interaction is confirmed by using the Raman spectroscopic approach, whereby larger band shift rates, of a peak initially located at 1095 cm(-1), with respect to both strain and stress, are observed, which is a quantitative measure of enhanced stress transfer. Thermal analysis (differential scanning calorimetry) and electron microscopy imaging (scanning electron microscopy) of the samples also confirms the enhanced coupling between the resin and the BC networks cultured for 3 days

  6. Mechanical and moisture barrier properties of titanium dioxide nanoparticles and halloysite nanotubes reinforced polylactic acid (PLA) (United States)

    Alberton, J.; Martelli, S. M.; Fakhouri, F. M.; Soldi, V.


    Polylactic acid (PLA) has been larger used in biomedical field due to its low toxicity and biodegradability. The aim of this study was to produce PLLA nanocomposites, by melt extrusion, containing Halloysite nanotubes (HNT) and/or titanium dioxide (TiO2) nanoparticles. Immediately after drying, PLLA was mechanically homogenized with the nanofillers and then melt blended using a single screw extruder (L/D = 30) at a speed of 110 rpm, with three heating zones in which the following temperatures were maintained: 150, 150 and 160°C (AX Plasticos model AX14 LD30). The film samples were obtained by compression molding in a press with a temperature profile of 235 ± 5°C for 2.5 min, after pressing, films were cooled up to room temperature. The mechanical tests were performed according to ASTM D882-09 and the water vapor permeability (WVP) was measured according to ASTM E-96, in triplicate. The tensile properties indicated that the modulus was improved with increased TiO2 content up to 1g/100g PLLA. The Young's modulus (YM) of the PLA was increased from 3047 MPa to 3222 MPa with the addition of 1g TiO2/100g PLLA. The tensile strength (TS) of films increases with the TiO2 content. In both cases, the YM and TS are achieved at the 1% content of TiO2 and is due to the reinforcing effect of nanoparticles. Pristine PLA showed a strain at break (SB) of 3.56%, while the SB of nanocomposites were significant lower, for instance the SB of composite containing 7.5 g HNT/100g PLLA was around 1.90 %. The WVP of samples was increased by increasing the nano filler content. It should be expected that an increase of nanofiller content would decrease the mass transfer of water molecules throughout the samples due to the increase in the way water molecules will have to cross to permeate the material. However, this was not observed. Therefore, this result can be explained considering the molecular structure of both fillers, which contain several hydroxyl groups in the surface, making the

  7. Mechanism of Synergistic Inhibition of Listeria monocytogenes Growth by Lactic Acid, Monolaurin, and Nisin▿


    Tokarskyy, Oleksandr; Marshall, Douglas L.


    The combined lactic acid, monolaurin, and nisin effects on time-to-detection (optical density at 600 nm) extension were greater (P < 0.05) than any single or paired combination effect, which demonstrates a synergistic interaction among the antimicrobials. Monolaurin exposure caused C12:0 cell membrane incorporation. Lactic acid caused increased monolaurin C12:0 membrane incorporation, while nisin had no influence. We postulate that lactic acid-enhanced monolaurin C12:0 incorporation into the ...

  8. Mechanism of synergistic inhibition of Listeria monocytogenes growth by lactic acid, monolaurin, and nisin. (United States)

    Tokarskyy, Oleksandr; Marshall, Douglas L


    The combined lactic acid, monolaurin, and nisin effects on time-to-detection (optical density at 600 nm) extension were greater (P Monolaurin exposure caused C12:0 cell membrane incorporation. Lactic acid caused increased monolaurin C12:0 membrane incorporation, while nisin had no influence. We postulate that lactic acid-enhanced monolaurin C12:0 incorporation into the cell membrane increased membrane fluidity resulting in increased nisin activity.

  9. Mechanism of Synergistic Inhibition of Listeria monocytogenes Growth by Lactic Acid, Monolaurin, and Nisin▿ (United States)

    Tokarskyy, Oleksandr; Marshall, Douglas L.


    The combined lactic acid, monolaurin, and nisin effects on time-to-detection (optical density at 600 nm) extension were greater (P Monolaurin exposure caused C12:0 cell membrane incorporation. Lactic acid caused increased monolaurin C12:0 membrane incorporation, while nisin had no influence. We postulate that lactic acid-enhanced monolaurin C12:0 incorporation into the cell membrane increased membrane fluidity resulting in increased nisin activity. PMID:18820062

  10. Extraction Mechanism of La3+ from Hydrochloric Acid Solution Using Cyanex 302

    Institute of Scientific and Technical Information of China (English)

    乌东北; 牛春吉; 李德谦


    The solvent extraction of La3+ from hydrochloric acid solutions was investigated using bis(2, 4, 4-trimethylpentyl) monothiophosphinic acid(Cyanex 302, HL) as an extractant. The effect of equilibrium of aqueous acidity on extraction of La3+ using Cyanex 302 in different diluents was discussed. The effects of extractant concentration and chloride ion on the extraction reaction were also studied. Stoichiometry of the extraction reactions and the nature of metal complexes formed were determined using slope analysis technique and IR measurement.

  11. Kinetics and mechanism of the oxidation of formic and oxalic acids by benzyltrimethylammonium dichloroiodate

    Indian Academy of Sciences (India)

    Poonam Gupta; Seema Kothari


    The oxidation of formic and oxalic acids by benzyltrimethylammonium dichloroiodate (BTMACI), in the presence of zinc chloride, leads to the formation of carbon dioxide. The reaction is first order with respect to BTMACI, zinc chloride and organic acid. Oxidation of deuteriated formic acid indicates the presence of a kinetic isotope effect. Addition of benzyltrimethylammonium chloride enhances the rate. It is proposed that the reactive oxidizing species is [(PhCH2Me3N)+ (IZn2Cl6)−]. Suitablemechanisms have been proposed.

  12. Proposed binding mechanism of galbanic acid extracted from Ferula assa-foetida to DNA. (United States)

    Ahmadi, F; Shokoohinia, Y; Javaheri, Sh; Azizian, H


    Recently, galbanic acid (GA), a sesquiterpenoid coumarin, has been introduced as an apoptotic and geno/cytotoxicity agent. In the present study, GA has been extracted from Ferula assa-foetida, a native medicinal plant in Iran, and characterized by (1)H NMR, mass spectroscopy. Additionally, spectroscopic studies have been performed in order to investigate its DNA-interaction mode. The electrochemical behavior of GA has been studied by cyclic voltammetry (CV) in various scan rates. In neutral media (pH=7.3) one irreversible cathodic peak was obtained at -1.46 V, while in higher scan rates an irreversible one was determined at -1.67 V. According to the voltametric data GA can be easily reduced by 2e(-)/2H(+) mechanism at hanging mercury drop electrode (HMDE). The interaction of GA with ct-DNA was evaluated by CV, differential pulse voltammetry (DPV), enhancement fluorescence, UV-Vis, FT-IR spectroscopy and molecular docking. The molecular docking study shows that the GA interacts to DNA on partial intercalation mode via DNA groove binding and forms a complex by van der Waals and electroastatic interactions. In addition, the thermodynamic parameters of GA-DNA complex were investigated with ΔH°, ΔS° and ΔG° values of 15.81KJmol(-1), 133.95Jmol(-1) and -23.10KJmol(-1), respectively. All data revealed that the GA is binding to DNA by van der Waals and electrostatic interactions through the partial intercalations from the DNA's grooves.

  13. Cytotoxicity and comparative binding mechanism of piperine with human serum albumin and α-1-acid glycoprotein. (United States)

    Yeggoni, Daniel Pushparaju; Rachamallu, Aparna; Kallubai, Monika; Subramanyam, Rajagopal


    Human serum albumin (HSA) and α-1-acid glycoprotein (AGP) (acute phase protein) are the plasma proteins in blood system which transports many drugs. To understand the pharmacological importance of piperine molecule, here, we studied the anti-inflammatory activity of piperine on mouse macrophages (RAW 264.7) cell lines, which reveals that piperine caused an increase in inhibition growth of inflammated macrophages. Further, the fluorescence maximum quenching of proteins were observed upon binding of piperine to HSA and AGP through a static quenching mechanism. The binding constants obtained from fluorescence emission were found to be K(piperine) = 5.7 ± .2 × 10(5) M(-1) and K(piperine) = 9.3± .25 × 10(4) M(-1) which correspond to the free energy of -7.8 and -6.71 kcal M(-1)at 25 °C for HSA and AGP, respectively. Further, circular dichrosim studies revealed that there is a marginal change in the secondary structural content of HSA due to partial destabilization of HSA-piperine complexes. Consequently, inference drawn from the site-specific markers (phenylbutazone, site I marker) studies to identify the binding site of HSA noticed that piperine binds at site I (IIA), which was further authenticated by molecular docking and molecular dynamic (MD) studies. The binding constants and free energy corresponding to experimental and computational analysis suggest that there are hydrophobic and hydrophilic interactions when piperine binds to HSA. Additionally, the MD studies have showed that HSA-piperine complex reaches equilibration state at around 3 ns, which prove that the HSA-piperine complex is stable in nature.

  14. Mechanism of hydrodenitrogenation (Part 4) infrared spectroscopy of acidic molybdena catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Miranda, R.


    Mo oxide catalysts supported over a complete series of silica-aluminas have been characterized in the oxidic and reduced states, by means of total acidity measurements and by infrared spectroscopy. Ammonia chemisorption was used to titrate the total acidity of the catalysts, and IR absorption of adsorbed pyridine to distinguish Bronsted from Lewis acid sites. The formation of new acidity upon deposition of molybdena on silica-alumina supports was then explained on the basis of a simple surface model. The new acidity is of both Lewis and Bronsted type, the preponderance of one over the other depending on support composition, as well as loading and state of oxidation of Mo. High-alumina supports and low Mo loading favor dispersed Mo species, in particular bidentate and monodentate di-oxo Mo species. The latter is responsible for the new Bronsted acidity. Coordinative unsaturation of polymolybdates is responsible for the new Lewis acidity, which is increased upon reduction of Mo. High-silica supports favor monodentate species (high Bronsted acidity) up to 4 wt % MoO{sub 3}. Beyond that, polymolybdates species and Lewis acidity predominate. 7 refs., 4 figs.

  15. Species-specific mechanisms for cholesterol 7alpha-hydroxylase (CYP7A1) regulation by drugs and bile acids


    C. Handschin.; Gnerre, C; Fraser, D. J.; Martinez-Jimenez, C.; Jover, R; Meyer, U A


    The gene encoding cholesterol 7alpha-hydroxylase (CYP7A1) is tightly regulated in order to control intrahepatic cholesterol and bile acid levels. Ligands of the xenobiotic-sensing pregnane X receptor inhibit CYP7A1 expression. To retrace the evolution of the molecular mechanisms underlying CYP7A1 inhibition, we used a chicken hepatoma cell system that retains the ability to be induced by phenobarbital and other drugs. Whereas bile acids regulate CYP7A1 via small heterodimer partner and liver ...

  16. Hydrolysis mechanism of anticancer drug lobaplatin in aqueous medium under neutral and acidic conditions: A DFT study (United States)

    Reddy B., Venkata P.; Mukherjee, Subhajit; Mitra, Ishani; Mahata, Sujay; Linert, Wolfgang; Moi, Sankar Ch.


    We have studied the hydrolysis mechanism of lobaplatin in aqueous medium under neutral and acidic conditions using density functional theory combining with CPCM model. The stationary states located on potential energy surface were fully optimized and characterised. The rate limiting step in neutral conditions, ring opening reaction with an activation energy of 110.21 kJ mol-1. The completely hydrolysed complex is expected to be the reactive species towards the DNA purine bases. In acidic conditions, ligand detachment is the rate limiting step with an activation energy of 113.82 kJ mol-1. Consequently, monohydrated complex is expected to be the species reacting with DNA.

  17. Survival of lactic acid and chlorine dioxide treated Campylobacter jejuni under suboptimal conditions of pH, temperature and modified atmosphere

    DEFF Research Database (Denmark)

    Smigic, Nada; Rajkovic, Andreja; Nielsen, Dennis Sandris;


    Campylobacter jejuni cells treated with lactic acid (LA, 3% lactic acid, pH 4.0, 2 min) or chlorine dioxide (ClO(2), 20 ppm, 2 min) were inoculated in Bolton broth (pH 6.0) and incubated under 80% O(2)/20% N(2), 80% CO(2)/20% N(2), air or micro-aerophilic (10% CO(2)/85% N(2)/5% O(2)) atmosphere, at 4 degrees C...

  18. Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms

    NARCIS (Netherlands)

    Al-Lahham, S.H.; Peppelenbosch, M.P.; Roelofsen, H.; Vonk, R.J.; Venema, K.


    Undigested food is fermented in the colon by the microbiota and gives rise to various microbial metabolites. Short-chain fatty acids (SCFA), including acetic, propionic and butyric acid, are the principal metabolites produced. However, most of the literature focuses on butyrate and to a lesser exten

  19. The Role of Fatty Acids in the Mechanical Properties of Beeswax (United States)

    Beeswax is a mixture of many organic compounds, including hydrocarbons, wax esters, and fatty acids. While the composition of beeswax is well known, how each of the components contribute to the overall functions of wax is less well understood. Because fatty acids in beeswax also serve as social si...

  20. Gallic acid-grafted-chitosan inhibits foodborne pathogens by a membrane damage mechanism. (United States)

    Lee, Dae-Sung; Je, Jae-Young


    In this study, antimicrobial activity of gallic acid-grafted-chitosans (gallic acid-g-chitosans) against five Gram-positive and five Gram-negative foodborne pathogens was evaluated. The minimum inhibitory concentrations (MICs) of gallic acid-g-chitosans ranged from 16 to 64 μg/mL against Gram-positive bacteria and ranged from 128 to 512 μg/mL against Gram-negative bacteria. These activities were higher than those of unmodified chitosan. The bactericidal activity of gallic acid-g-chitosan (I), which showed the highest antimicrobial activity, was evaluated by time-killing assay with multiples of MIC, and it was recognized to depend on its dose. The integrity of cell membrane, outer membrane (OM), inner membrane (IM) permeabilization experiments, and transmission electron microscopy (TEM) observation were conducted for elucidation of the detailed antimicrobial mode of action of gallic acid-g-chitosan. Results showed that treatment of gallic acid-g-chitosan (I) quickly increased the release of intracellular components for both Escherichia coli and Staphylococcus aureus. In addition, gallic acid-g-chitosan (I) also rapidly increased the 1-N-phenylanphthylamine (NPN) uptake and the release of β-galactosidase via increasing the permeability of OM and IM in E. coli. TEM observation demonstrated that gallic acid-g-chitosan (I) killed the bacteria via disrupting the cell membrane.

  1. Inhibitory mechanism of l-glutamic acid on spawning of the starfish Patiria (Asterina) pectinifera. (United States)

    Mita, Masatoshi


    l-Glutamic acid was previously identified as an inhibitor of spawning in the starfish Patiria (Asterina) pectinifera; this study examined how l-glutamic acid works. Oocyte release from ovaries of P. pectinifera occurred after germinal vesicle breakdown (GVBD) and follicular envelope breakdown (FEBD) when gonads were incubated ex vivo with either relaxin-like gonad-stimulating peptide (RGP) or 1-methyladenine (1-MeAde). l-Glutamic acid blocked this spawning phenotype, causing the mature oocytes to remain within the ovaries. Neither RGP-induced 1-MeAde production in ovarian follicle cells nor 1-MeAde-induced GVBD and FEBD was affected by l-glutamic acid. l-Glutamic acid may act through metabotropic receptors in the ovaries to inhibit spawning, as l-(+)-2-amino-4-phosphonobutyric acid, an agonist for metabotropic glutamate receptors, also inhibited spawning induced by 1-MeAde. Application of acetylcholine (ACH) to ovaries under inhibitory conditions with l-glutamic acid, however, brought about spawning, possibly by inducing contraction of the ovarian wall to discharge mature oocytes from the ovaries concurrently with GVBD and FEBD. Thus, l-glutamic acid may inhibit ACH secretion from gonadal nerve cells in the ovary. Mol. Reprod. Dev. 2016. © 2016 Wiley Periodicals, Inc.

  2. Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms

    NARCIS (Netherlands)

    Al-Lahham, Sa'ad H.; Peppelenbosch, Maikel P.; Roelofsen, Han; Vonk, Roel J.; Venema, Koen


    Undigested food is fermented in the colon by the microbiota and gives rise to various microbial metabolites. Short-chain fatty acids (SCFA), including acetic, propionic and butyric acid, are the principal metabolites produced However, most of the literature focuses on butyrate and to a lesser extent

  3. Photo-induced oxidative damage to dissolved free amino acids by the photosensitizer polycyclic musk tonalide: Transformation kinetics and mechanisms. (United States)

    Fang, Hansun; Gao, Yanpeng; Wang, Honghong; Yin, Hongliang; Li, Guiying; An, Taicheng


    Residue from the polycyclic musks (PCMs) in household and personal care products may harm human beings through skin exposure. To understand the health effects of PCMs when exposed to sunlight at molecular level, both experimental and computational methods were employed to investigate the photosensitized oxidation performance of 19 natural amino acids, the most basic unit of life. Results showed that a typical PCM, tonalide, acts as a photosensitizer to significantly increase photo-induced oxidative damage to amino acids. Both common and exceptional transformation pathways occurred during the photosensitization damage of amino acids. Experimental tests further identified the different mechanisms involved. The common transformation pathway occurred through the electron transfer from α amino-group of amino acids, accompanying with the formation of O2(•-). This pathway was controlled by the electronic density of N atom in α amino-group. The exceptional transformation pathway was identified only for five amino acids, mainly due to the reactions with reactive oxygen species, e.g. (1)O2 and excited triplet state molecules. Additionally, tonalide photo-induced transformation products could further accelerate the photosensitization of all amino acids with the common pathway. This study may support the protection of human health, and suggests the possible need to further restrict polycyclic musks use.

  4. Escherichia coli K-12 survives anaerobic exposure at pH 2 without RpoS, Gad, or hydrogenases, but shows sensitivity to autoclaved broth products.

    Directory of Open Access Journals (Sweden)

    Daniel P Riggins

    Full Text Available Escherichia coli and other enteric bacteria survive exposure to extreme acid (pH 2 or lower in gastric fluid. Aerated cultures survive via regulons expressing glutamate decarboxylase (Gad, activated by RpoS, cyclopropane fatty acid synthase (Cfa and others. But extreme-acid survival is rarely tested under low oxygen, a condition found in the stomach and the intestinal tract. We observed survival of E. coli K-12 W3110 at pH 1.2-pH 2.0, conducting all manipulations (overnight culture at pH 5.5, extreme-acid exposure, dilution and plating in a glove box excluding oxygen (10% H2, 5% CO2, balance N2. With dissolved O2 concentrations maintained below 6 µM, survival at pH 2 required Cfa but did not require GadC, RpoS, or hydrogenases. Extreme-acid survival in broth (containing tryptone and yeast extract was diminished in media that had been autoclaved compared to media that had been filtered. The effect of autoclaved media on extreme-acid survival was most pronounced when oxygen was excluded. Exposure to H2O2 during extreme-acid treatment increased the death rate slightly for W3110 and to a greater extent for the rpoS deletion strain. Survival at pH 2 was increased in strains lacking the anaerobic regulator fnr. During anaerobic growth at pH 5.5, strains deleted for fnr showed enhanced transcription of acid-survival genes gadB, cfa, and hdeA, as well as catalase (katE. We show that E. coli cultured under oxygen exclusion (<6 µM O2 requires mechanisms different from those of aerated cultures. Extreme acid survival is more sensitive to autoclave products under oxygen exclusion.

  5. Folic acid supplementation during high-fat diet feeding restores AMPK activation via an AMP-LKB1-dependent mechanism. (United States)

    Sid, Victoria; Wu, Nan; Sarna, Lindsei K; Siow, Yaw L; House, James D; O, Karmin


    AMPK is an endogenous energy sensor that regulates lipid and carbohydrate metabolism. Nonalcoholic fatty liver disease (NAFLD) is regarded as a hepatic manifestation of metabolic syndrome with impaired lipid and glucose metabolism and increased oxidative stress. Our recent study showed that folic acid supplementation attenuated hepatic oxidative stress and lipid accumulation in high-fat diet-fed mice. The aim of the present study was to investigate the effect of folic acid on hepatic AMPK during high-fat diet feeding and the mechanisms involved. Male C57BL/6J mice were fed a control diet (10% kcal fat), a high-fat diet (60% kcal fat), or a high-fat diet supplemented with folic acid (26 mg/kg diet) for 5 wk. Mice fed a high-fat diet exhibited hyperglycemia, hepatic cholesterol accumulation, and reduced hepatic AMPK phosphorylation. Folic acid supplementation restored AMPK phosphorylation (activation) and reduced blood glucose and hepatic cholesterol levels. Activation of AMPK by folic acid was mediated through an elevation of its allosteric activator AMP and activation of its upstream kinase, namely, liver kinase B1 (LKB1) in the liver. Consistent with in vivo findings, 5-methyltetrahydrofolate (bioactive form of folate) restored phosphorylation (activation) of both AMPK and LKB1 in palmitic acid-treated HepG2 cells. Activation of AMPK by folic acid might be responsible for AMPK-dependent phosphorylation of HMG-CoA reductase, leading to reduced hepatic cholesterol synthesis during high-fat diet feeding. These results suggest that folic acid supplementation may improve cholesterol and glucose metabolism by restoration of AMPK activation in the liver.

  6. The Pleiotropic Antibacterial Mechanisms of Ursolic Acid against Methicillin-Resistant Staphylococcus aureus (MRSA

    Directory of Open Access Journals (Sweden)

    Chao-Min Wang


    Full Text Available (1 Background: Several triterpenoids were found to act synergistically with classes of antibiotic, indicating that plant-derived chemicals have potential to be used as therapeutics to enhance the activity of antibiotics against multidrug-resistant pathogens. However, the mode of action of triterpenoids against bacterial pathogens remains unclear. The objective of this study is to evaluate the interaction between ursolic acid against methicillin-resistant Staphylococcus aureus (MRSA; (2 Methods: The ability of ursolic acid to damage mammalian and bacterial membranes was examined. The proteomic response of methicillin-resistant S. aureus in ursolic acid treatment was investigated using two-dimensional (2D proteomic analysis; (3 Results: Ursolic acid caused the loss of staphylococcal membrane integrity without hemolytic activity. The comparison of the protein pattern of ursolic acid–treated and normal MRSA cells revealed that ursolic acid affected a variety of proteins involved in the translation process with translational accuracy, ribonuclease and chaperon subunits, glycolysis and oxidative responses; (4 Conclusion: The mode of action of ursolic acid appears to be the influence on the integrity of the bacterial membrane initially, followed by inhibition of protein synthesis and the metabolic pathway. These findings reflect that the pleiotropic effects of ursolic acid against MRSA make it a promising antibacterial agent in pharmaceutical research.

  7. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve A mechanical analysis*

    Institute of Scientific and Technical Information of China (English)

    Tao Yu; Changfu Zhao; Peng Li; Guangyao Liu; Min Luo


    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study col ected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, fol owing which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) con-duit-repaired sciatic nerve fol owing tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Fol owing poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogen-ous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair.

  8. Poly(lactic-co-glycolic acid) conduit for repair of injured sciatic nerve: A mechanical analysis. (United States)

    Yu, Tao; Zhao, Changfu; Li, Peng; Liu, Guangyao; Luo, Min


    Tensile stress and tensile strain directly affect the quality of nerve regeneration after bridging nerve defects by poly(lactic-co-glycolic acid) conduit transplantation and autogenous nerve grafting for sciatic nerve injury. This study collected the sciatic nerve from the gluteus maximus muscle from fresh human cadaver, and established 10-mm-long sciatic nerve injury models by removing the ischium, following which poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts were transplanted. Scanning electron microscopy revealed that the axon and myelin sheath were torn, and the vessels of basilar membrane were obstructed in the poly(lactic-co-glycolic acid) conduit-repaired sciatic nerve following tensile testing. There were no significant differences in tensile tests with autogenous nerve graft-repaired sciatic nerve. Following poly(lactic-co-glycolic acid) conduit transplantation for sciatic nerve repair, tensile test results suggest that maximum tensile load, maximum stress, elastic limit load and elastic limit stress increased compared with autogenous nerve grafts, but elastic limit strain and maximum strain decreased. Moreover, the tendencies of stress-strain curves of sciatic nerves were similar after transplantation of poly(lactic-co-glycolic acid) conduits or autogenous nerve grafts. Results showed that after transplantation in vitro for sciatic nerve injury, poly(lactic-co-glycolic acid) conduits exhibited good intensity, elasticity and plasticity, indicating that poly(lactic-co-glycolic acid) conduits are suitable for sciatic nerve injury repair.

  9. Mechanism of specific influence of L-Glutamic acid on the shape of L-Valine crystals (United States)

    Yoshiura, Hiromu; Nagano, Hiroshi; Hirasawa, Izumi


    The specific interaction between L-valine (L-Val) and L-glutamic acid (L-Glu) in the process of evaporative crystallization from an aqueous solution has been investigated. It was found that only 2.0% (wt/wt) of L-Glu against the total amount of L-Val was required to induce significant agglomeration of L-Val. Interestingly, the agglomeration was only induced under acidic conditions, suggesting that the electrostatic interaction was an effective factor for the agglomeration process. As well as the electrostatic interaction, the length of the amino acid side chain was identified as another important factor. In addition, we confirmed that the incorporation rate of L-Glu into L-Val crystals was different during the nucleation and crystal growth stages. Based on these results, a mechanism has been proposed for the interaction of L-Glu and L-Val during the agglomeration process.

  10. Eicosapentaenoic acid inhibits intestinal β-carotene absorption by downregulation of lipid transporter expression via PPAR-α dependent mechanism. (United States)

    Mashurabad, Purna Chandra; Kondaiah, Palsa; Palika, Ravindranadh; Ghosh, Sudip; Nair, Madhavan K; Raghu, Pullakhandam


    The involvement of lipid transporters, the scavenger receptor class B, type I (SR-BI) and Niemann-Pick type C1 Like 1 protein (NPC1L1) in carotenoid absorption is demonstrated in intestinal cells and animal models. Dietary ω-3 fatty acids are known to possess antilipidemic properties, which could be mediated by activation of PPAR family transcription factors. The present study was conducted to determine the effect of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), on intestinal β-carotene absorption. β-carotene uptake in Caco-2/TC7 cells was inhibited by EPA (p intestinal β-carotene absorption by down regulation of SR B1 expression via PPARα dependent mechanism and provide an evidence for dietary modulation of intestinal β-carotene absorption.

  11. Internal tandem duplication of the FLT3 gene confers poor overall survival in patients with acute promyelocytic leukemia treated with all-trans retinoic acid and anthracycline-based chemotherapy: an International Consortium on Acute Promyelocytic Leukemia study. (United States)

    Lucena-Araujo, Antonio R; Kim, Haesook T; Jacomo, Rafael H; Melo, Raul A; Bittencourt, Rosane; Pasquini, Ricardo; Pagnano, Katia; Fagundes, Evandro M; Chauffaille, Maria de Lourdes; Chiattone, Carlos S; Lima, Ana Silvia; Ruiz-Argüelles, Guillermo; Undurraga, Maria Soledad; Martinez, Lem; Kwaan, Hau C; Gallagher, Robert; Niemeyer, Charlotte M; Schrier, Stanley L; Tallman, Martin S; Grimwade, David; Ganser, Arnold; Berliner, Nancy; Ribeiro, Raul C; Lo-Coco, Francesco; Löwenberg, Bob; Sanz, Miguel A; Rego, Eduardo M


    Activating internal tandem duplication (ITD) mutations in the fms-like tyrosine kinase 3 (FLT3) gene (FLT3-ITD) are associated with poor outcome in acute myeloid leukemia, but their prognostic impact in acute promyelocytic leukemia (APL) remains controversial. Here, we screened for FLT3-ITD mutations in 171 APL patients, treated with all-trans retinoic acid (ATRA) and anthracycline-based chemotherapy. We identified FLT3-ITD mutations in 35 patients (20 %). FLT3-ITD mutations were associated with higher white blood cell counts (P < 0.0001), relapse-risk score (P = 0.0007), higher hemoglobin levels (P = 0.0004), higher frequency of the microgranular morphology (M3v) subtype (P = 0.03), and the short PML/RARA (BCR3) isoform (P < 0.0001). After a median follow-up of 38 months, FLT3-ITD(positive) patients had a lower 3-year overall survival rate (62 %) compared with FLT3-ITD(negative) patients (82 %) (P = 0.006). The prognostic impact of FLT3-ITD on survival was retained in multivariable analysis (hazard ratio: 2.39, 95 % confidence interval [CI] 1.17-4.89; P = 0.017). Nevertheless, complete remission (P = 0.07), disease-free survival (P = 0.24), and the cumulative incidence of relapse (P = 0.94) rates were not significantly different between groups. We can conclude that FLT3-ITD mutations are associated with several hematologic features in APL, in particular with high white blood cell counts. In addition, FLT3-ITD may independently predict a shorter survival in patients with APL treated with ATRA and anthracycline-based chemotherapy.

  12. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, platform randomised controlled trial (United States)

    James, Nicholas D; Sydes, Matthew R; Clarke, Noel W; Mason, Malcolm D; Dearnaley, David P; Spears, Melissa R; Ritchie, Alastair W S; Parker, Christopher C; Russell, J Martin; Attard, Gerhardt; de Bono, Johann; Cross, William; Jones, Rob J; Thalmann, George; Amos, Claire; Matheson, David; Millman, Robin; Alzouebi, Mymoona; Beesley, Sharon; Birtle, Alison J; Brock, Susannah; Cathomas, Richard; Chakraborti, Prabir; Chowdhury, Simon; Cook, Audrey; Elliott, Tony; Gale, Joanna; Gibbs, Stephanie; Graham, John D; Hetherington, John; Hughes, Robert; Laing, Robert; McKinna, Fiona; McLaren, Duncan B; O'Sullivan, Joe M; Parikh, Omi; Peedell, Clive; Protheroe, Andrew; Robinson, Angus J; Srihari, Narayanan; Srinivasan, Rajaguru; Staffurth, John; Sundar, Santhanam; Tolan, Shaun; Tsang, David; Wagstaff, John; Parmar, Mahesh K B


    Summary Background Long-term hormone therapy has been the standard of care for advanced prostate cancer since the 1940s. STAMPEDE is a randomised controlled trial using a multiarm, multistage platform design. It recruits men with high-risk, locally advanced, metastatic or recurrent prostate cancer who are starting first-line long-term hormone therapy. We report primary survival results for three research comparisons testing the addition of zoledronic acid, docetaxel, or their combination to standard of care versus standard of care alone. Methods Standard of care was hormone therapy for at least 2 years; radiotherapy was encouraged for men with N0M0 disease to November, 2011, then mandated; radiotherapy was optional for men with node-positive non-metastatic (N+M0) disease. Stratified randomisation (via minimisation) allocated men 2:1:1:1 to standard of care only (SOC-only; control), standard of care plus zoledronic acid (SOC + ZA), standard of care plus docetaxel (SOC + Doc), or standard of care with both zoledronic acid and docetaxel (SOC + ZA + Doc). Zoledronic acid (4 mg) was given for six 3-weekly cycles, then 4-weekly until 2 years, and docetaxel (75 mg/m2) for six 3-weekly cycles with prednisolone 10 mg daily. There was no blinding to treatment allocation. The primary outcome measure was overall survival. Pairwise comparisons of research versus control had 90% power at 2·5% one-sided α for hazard ratio (HR) 0·75, requiring roughly 400 control arm deaths. Statistical analyses were undertaken with standard log-rank-type methods for time-to-event data, with hazard ratios (HRs) and 95% CIs derived from adjusted Cox models. This trial is registered at (NCT00268476) and (ISRCTN78818544). Findings 2962 men were randomly assigned to four groups between Oct 5, 2005, and March 31, 2013. Median age was 65 years (IQR 60–71). 1817 (61%) men had M+ disease, 448 (15%) had N+/X M0, and 697 (24%) had N0M0. 165 (6

  13. Data of thermal degradation and dynamic mechanical properties of starch–glycerol based films with citric acid as crosslinking agent (United States)

    González Seligra, Paula; Medina Jaramillo, Carolina; Famá, Lucía; Goyanes, Silvia


    Interest in biodegradable edible films as packaging or coating has increased because their beneficial effects on foods. In particular, food products are highly dependents on thermal stability, integrity and transition process temperatures of the packaging. The present work describes a complete data of the thermal degradation and dynamic mechanical properties of starch–glycerol based films with citric acid (CA) as crosslinking agent described in the article titled: “Biodegradable and non-retrogradable eco-films based on starch–glycerol with citric acid as crosslinking agent” González Seligra et al. (2016) [1]. Data describes thermogravimetric and dynamical mechanical experiences and provides the figures of weight loss and loss tangent of the films as a function of the temperature. PMID:27158645

  14. Data of thermal degradation and dynamic mechanical properties of starch–glycerol based films with citric acid as crosslinking agent

    Directory of Open Access Journals (Sweden)

    Paula González Seligra


    Full Text Available Interest in biodegradable edible films as packaging or coating has increased because their beneficial effects on foods. In particular, food products are highly dependents on thermal stability, integrity and transition process temperatures of the packaging. The present work describes a complete data