WorldWideScience

Sample records for translocation potential implications

  1. Advances in chromosomal translocations and fusion genes in sarcomas and potential therapeutic applications.

    Science.gov (United States)

    Xiao, Xin; Garbutt, Cassandra C; Hornicek, Francis; Guo, Zheng; Duan, Zhenfeng

    2018-02-01

    Chromosomal translocations and fusion genes are very common in human cancer especially in subtypes of sarcomas, such as rhabdomyosarcoma, Ewing's sarcoma, synovial sarcoma and liposarcoma. The discovery of novel chromosomal translocations and fusion genes in different tumors are due to the advancement of next-generation sequencing (NGS) technologies such as whole genome sequencing. Recently, many novel chromosomal translocations and gene fusions have been identified in different types of sarcoma through NGS approaches. In addition to previously known sarcoma fusion genes, these novel specific fusion genes and associated molecular events represent important targets for novel therapeutic approaches in the treatment of sarcomas. This review focuses on recent advances in chromosomal translocations and fusion genes in sarcomas and their potential therapeutic applications in the treatment of sarcomas. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Macro- and microhabitat use of Telfair's skink ( Leiolopisma telfairii) on Round Island, Mauritius: implications for their translocation

    Science.gov (United States)

    Pernetta, Angelo P.; Bell, Diana J.; Jones, Carl G.

    2005-11-01

    The successful eradication of introduced rodents from islets off the coast of Mauritius has led to local conservation bodies investigating the possibility of translocation as a measure of safeguarding endemic reptile populations. The present study was the first to determine the habitat and microhabitat requirements of Telfair's skinks ( Leiolopisma telfairii) on Round Island, Mauritius, with a view to aiding future translocation projects to islands within their historic range. Contrasting preferences found for Telfair's skink at macro- and micro- habitat levels underline the importance of sampling at multiple ecological scales in such investigations. Significantly fewer sightings of L. telfairii were recorded in bare rock habitats compared to more vegetated habitats. Conversely, at a microhabitat scale principal component analysis indicated structural characteristics were the primary determinant of microhabitat choice. The first dietary analysis of Telfair's skinks confirmed their status as omnivores. Cockroaches ( Blattodea spp.) appeared to be a primary food source. Four exotic plant species were also present in faecal samples and the potential for L. telfairii to aid their dispersal is discussed. Implications for the long-term management and proposed translocation of Telfair's skinks are discussed.

  3. Biochemical evidence of the interactions of membrane type-1 matrix metalloproteinase (MT1-MMP) with adenine nucleotide translocator (ANT): potential implications linking proteolysis with energy metabolism in cancer cells.

    Science.gov (United States)

    Radichev, Ilian A; Remacle, Albert G; Sounni, Nor Eddine; Shiryaev, Sergey A; Rozanov, Dmitri V; Zhu, Wenhong; Golubkova, Natalya V; Postnova, Tatiana I; Golubkov, Vladislav S; Strongin, Alex Y

    2009-04-28

    Invasion-promoting MT1-MMP (membrane type-1 matrix metalloproteinase) is a key element in cell migration processes. To identify the proteins that interact and therefore co-precipitate with this proteinase from cancer cells, we used the proteolytically active WT (wild-type), the catalytically inert E240A and the C-end truncated (tailless; DeltaCT) MT1-MMP-FLAG constructs as baits. The identity of the pulled-down proteins was determined by LC-MS/MS (liquid chromatography tandem MS) and then confirmed by Western blotting using specific antibodies. We determined that, in breast carcinoma MCF cells (MCF-7 cells), ANT (adenine nucleotide translocator) efficiently interacted with the WT, E240A and DeltaCT constructs. The WT and E240A constructs also interacted with alpha-tubulin, an essential component of clathrin-mediated endocytosis. In turn, tubulin did not co-precipitate with the DeltaCT construct because of the inefficient endocytosis of the latter, thus suggesting a high level of selectivity of our test system. To corroborate these results, we then successfully used the ANT2-FLAG construct as a bait to pull-down MT1-MMP, which was naturally produced by fibrosarcoma HT1080 cells. We determined that the presence of the functionally inert catalytic domain alone was sufficient to cause the proteinase to interact with ANT2, thus indicating that there is a non-proteolytic mode of these interactions. Overall, it is tempting to hypothesize that by interacting with pro-invasive MT1-MMP, ANT plays a yet to be identified role in a coupling mechanism between energy metabolism and pericellular proteolysis in migrating cancer cells.

  4. Conservation implications of wildlife translocations; The state's ability to act as conservation units for wildebeest populations in South Africa

    Directory of Open Access Journals (Sweden)

    Nicole Benjamin-Fink

    2017-10-01

    Full Text Available Wildlife translocations have historically assisted in re-establishing species in areas of extinction and are currently employed in over 50 countries. Ironically, they may also be responsible for the extinction of pure genetic lineages via hybridization, thereby negatively impacting endangered, indigenous, and rare species. Due to recent evolutionary divergence, black wildebeest (Connochaetes gnou and blue wildebeest (Connochaetes taurinus can mate and produce fertile offspring when sympatric. A total of 6929 translocated black and blue wildebeest from 273 private ranches and 3 provincial protected areas protected (PPAs were documented over 5 years, across 5 South African provinces. We analyzed dispersal patterns and wildlife ranching economics to identify conservation implications and to infer if translocations are likely to persist in their current form. Findings indicate (1 58.45% of sampled private ranches manage for both wildebeest populations, (2 blue wildebeest males are primarily translocated, (3 wildebeest are introduced across provincial lines, (4 wildebeest are introduced to within and amongst the private and commercial industry from multiple sources, and (5 wildebeest revenue accounted for 20.8% of revenue generated from all wildlife translocations. Unwanted conservation implications concern ecological integrity, genetic swamping, and regulatory efficiency. We caution against risks posed by the game industry upon the PPA's ability to function as nature conservation units and act as stocking sources and the plausibility that black wildebeest populations incorporate varying degrees of introgressive hybrids. Moreover, wildebeest account for 1/5 of revenue generated from all game translocations. This is indicative of its likelihood to persist in their current form, thereby inducing hybridization and facilitating outbreeding depression. We caution that concerns are likely to worsen if no intervention is taken. Lastly, we coin the concept

  5. Translocations affecting human immunoglobulin heavy chain locus

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    Sklyar I. V.

    2014-03-01

    Full Text Available Translocations involving human immunoglobulin heavy chain (IGH locus are implicated in different leukaemias and lymphomas, including multiple myeloma, mantle cell lymphoma, Burkitt’s lymphoma and diffuse large B cell lymphoma. We have analysed published data and identified eleven breakpoint cluster regions (bcr related to these cancers within the IgH locus. These ~1 kbp bcrs are specific for one or several types of blood cancer. Our findings could help devise PCR-based assays to detect cancer-related translocations, to identify the mechanisms of translocations and to help in the research of potential translocation partners of the immunoglobulin locus at different stages of B-cell differentiation.

  6. Analysis of 1;17 translocation breakpoints in neuroblastoma: implications for mapping of neuroblastoma genes

    NARCIS (Netherlands)

    van Roy, N.; Laureys, G.; van Gele, M.; Opdenakker, G.; Miura, R.; van der Drift, P.; Chan, A.; Versteeg, R.; Speleman, F.

    1997-01-01

    Deletions and translocations resulting in loss of distal 1p-material are known to occur frequently in advanced neuroblastomas. Fluorescence in situ hybridisation (FISH) showed that 17q was most frequently involved in chromosome 1p translocations. A review of the literature shows that 10 of 27 cell

  7. Domain Organization in Clostridium botulinum Neurotoxin Type E is Unique: Its Implication in Faster Translocation

    Energy Technology Data Exchange (ETDEWEB)

    Kumaran, D.; Eswaramoorthy, S; Furey, W; Navaza, J; Sax, M; Swaminathan, S

    2009-01-01

    Clostridium botulinum produces seven antigenically distinct neurotoxins [C. botulinum neurotoxins (BoNTs) A-G] sharing a significant sequence homology. Based on sequence and functional similarity, it was believed that their three-dimensional structures will also be similar. Indeed, the crystal structures of BoNTs A and B exhibit similar fold and domain association where the translocation domain is flanked on either side by binding and catalytic domains. Here, we report the crystal structure of BoNT E holotoxin and show that the domain association is different and unique, although the individual domains are similar to those of BoNTs A and B. In BoNT E, both the binding domain and the catalytic domain are on the same side of the translocation domain, and all three have mutual interfaces. This unique association may have an effect on the rate of translocation, with the molecule strategically positioned in the vesicle for quick entry into cytosol. Botulism, the disease caused by BoNT E, sets in faster than any other serotype because of its speedy internalization and translocation, and the present structure offers a credible explanation. We propose that the translocation domain in other BoNTs follows a two-step process to attain translocation-competent conformation as in BoNT E. We also suggest that this translocation-competent conformation in BoNT E is a probable reason for its faster toxic rate compared to BoNT A. However, this needs further experimental elucidation.

  8. Ecotypic variation in recruitment of reintroduced bighorn sheep: implications for translocation

    Science.gov (United States)

    Wiedmann, Brett P.; Sargeant, Glen A.

    2014-01-01

    European settlement led to extirpation of native Audubon's bighorn sheep (formerly Ovis canadensis auduboni) from North Dakota during the early 20th century. The North Dakota Game and Fish Department subsequently introduced California bighorn sheep (formerly O. c. californiana) that were indigenous to the Williams Lake region of British Columbia, Canada, and Rocky Mountain bighorn sheep (O. c. canadensis) that were indigenous to the Sun River region of Montana. Although California bighorn sheep are no longer recognized as a distinct subspecies, they are smaller and adapted to a milder climate than either the native bighorn sheep of North Dakota or introduced bighorn sheep from Montana. Because reintroductions still play a key role in the management of bighorn sheep and because local adaptation may have substantial demographic consequences, we evaluated causes of variation in recruitment of bighorn sheep reintroduced in North Dakota. During 2006–2011, Montana stock recruited 0.54 juveniles/adult female (n = 113), whereas British Columbia stock recruited 0.24 juveniles/adult female (n = 562). Our most plausible mixed-effects logistic regression model (53% of model weight) attributed variation in recruitment to differences between source populations (odds ratio = 4.5; 90% CI = 1.5, 15.3). Greater recruitment of Montana stock (fitted mean = 0.56 juveniles/adult female; 90% CI = 0.41, 0.70) contributed to a net gain in abundance (r = 0.15), whereas abundance of British Columbia stock declined (fitted mean = 0.24 juveniles/adult female; 90% CI = 0.09, 0.41; r = − 0.04). Translocations have been the primary tool used to augment and restore populations of wild sheep but often have failed to achieve objectives. Our results show that ecotypic differences among source stocks may have long-term implications for recruitment and demographic performance of reintroduced populations.

  9. Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity.

    Science.gov (United States)

    Boyce, Walter M; Weisenberger, Mara E; Penedo, M Cecilia T; Johnson, Christine K

    2011-02-01

    A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.

  10. Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

    Science.gov (United States)

    2011-01-01

    Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis) were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival) among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness. PMID:21284886

  11. Wildlife translocation: the conservation implications of pathogen exposure and genetic heterozygosity

    Directory of Open Access Journals (Sweden)

    Penedo M Cecilia T

    2011-02-01

    Full Text Available Abstract Background A key challenge for conservation biologists is to determine the most appropriate demographic and genetic management strategies for wildlife populations threatened by disease. We explored this topic by examining whether genetic background and previous pathogen exposure influenced survival of translocated animals when captive-bred and free-ranging bighorn sheep (Ovis canadensis were used to re-establish a population that had been extirpated in the San Andres Mountains in New Mexico, USA. Results Although the free-ranging source population had significantly higher multi-locus heterozygosity at 30 microsatellite loci than the captive bred animals, neither source population nor genetic background significantly influenced survival or cause of death. The presence of antibodies to a respiratory virus known to cause pneumonia was associated with increased survival, but there was no correlation between genetic heterozygosity and the presence of antibodies to this virus. Conclusions Although genetic theory predicts otherwise, increased heterozygosity was not associated with increased fitness (survival among translocated animals. While heterosis or genetic rescue effects may occur in F1 and later generations as the two source populations interbreed, we conclude that previous pathogen exposure was a more important marker than genetic heterozygosity for predicting survival of translocated animals. Every wildlife translocation is an experiment, and whenever possible, translocations should be designed and evaluated to test hypotheses that will further improve our understanding of how pathogen exposure and genetic variability influence fitness.

  12. Quantitative risk assessment of antimicrobials in biosolids applied on agricultural land and potential translocation into food.

    Science.gov (United States)

    Clarke, Rachel; Healy, Mark G; Fenton, Owen; Cummins, Enda

    2018-04-01

    The use of biosolids as a fertiliser may be an indirect route for contaminants into the food chain. One of the main concerns regarding the spreading of biosolids on agricultural land is the potential uptake of contaminants into plants which may bio-transfer into grazing animals that supply the food chain directly (e.g. meat and milk) and hence are subsequently consumed. The aim of this project was to create a quantitative risk assessment model to estimate the fate and translocation of triclosan (TCS) and triclocarban (TCC) into the feed (grass) and food chain with subsequent human exposure. The model's results indicate that TCS and TCC have low potential to transfer into milk and beef following the ingestion of contaminated grass by dairy cows. Mean estimated TCS and TCC residues in milk and beef show that TCC had the greatest concentration (mean values of 7.77×10 -6 mgkg -1 in milk and 1.36×10 -4 mgkg -1 in beef). Human exposure results show that TCC was greater for milk consumption in infants (1-4years) (mean value 1.14×10 -7 mgkg -1 bwd -1 ) and for beef consumption by teens (12-17years) (mean value 6.87×10 -8 mgkg -1 bwd -1 ). Concentrations of TCS and TCC were well below the estimated acceptable daily intake (ADI). Human health risk was estimated by evaluation of the hazard quotient (HQ), which used the NOAEL as a toxicity endpoint, combined with milk and beef human exposure estimates. HQ results show that all values were model is a valuable tool in which to ascertain the potential transfer of contaminants in the environment into animal forage with knock on consequences for exposure through the human food chain. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Climate-Driven Reshuffling of Species and Genes: Potential Conservation Roles for Species Translocations and Recombinant Hybrid Genotypes

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    Jon Mark Scriber

    2013-12-01

    Full Text Available Comprising 50%–75% of the world’s fauna, insects are a prominent part of biodiversity in communities and ecosystems globally. Biodiversity across all levels of biological classifications is fundamentally based on genetic diversity. However, the integration of genomics and phylogenetics into conservation management may not be as rapid as climate change. The genetics of hybrid introgression as a source of novel variation for ecological divergence and evolutionary speciation (and resilience may generate adaptive potential and diversity fast enough to respond to locally-altered environmental conditions. Major plant and herbivore hybrid zones with associated communities deserve conservation consideration. This review addresses functional genetics across multi-trophic-level interactions including “invasive species” in various ecosystems as they may become disrupted in different ways by rapid climate change. “Invasive genes” (into new species and populations need to be recognized for their positive creative potential and addressed in conservation programs. “Genetic rescue” via hybrid translocations may provide needed adaptive flexibility for rapid adaptation to environmental change. While concerns persist for some conservationists, this review emphasizes the positive aspects of hybrids and hybridization. Specific implications of natural genetic introgression are addressed with a few examples from butterflies, including transgressive phenotypes and climate-driven homoploid recombinant hybrid speciation. Some specific examples illustrate these points using the swallowtail butterflies (Papilionidae with their long-term historical data base (phylogeographical diversity changes and recent (3-decade climate-driven temporal and genetic divergence in recombinant homoploid hybrids and relatively recent hybrid speciation of Papilio appalachiensis in North America. Climate-induced “reshuffling” (recombinations of species composition, genotypes

  14. Familial cryptic translocation resulting in Angelman syndrome: Implications for imprinting or location of the Angelman gene?

    Energy Technology Data Exchange (ETDEWEB)

    Burke, L.W.; Wiley, J.E.; Smith, A.J.W.; Kushnick, T. [East Carolina Univ. School of Medicine, Greenville, NC (United States)] [and others

    1996-04-01

    Angelman syndrome (AS) is associated with a loss of maternal genetic information, which typically occurs as a result of a deletion at 15q11-q13 or paternal uniparental disomy of chromosome 15. We report a patient with AS as a result of an unbalanced cryptic translocation whose breakpoint, at 15q11.2, falls within this region. The proband was diagnosed clinically as having Angelman syndrome, but without a detectable cytogenetic deletion, by using high-resolution G-banding. FISH detected a deletion of D15S11 (IR4-3R), with an intact GABRB3 locus. Subsequent studies of the proband`s mother and sister detected a cryptic reciprocal translocation between chromosomes 14 and 15 with the breakpoint being between SNRPN and D15S10. The proband was found to have inherited an unbalanced form, being monosomic from 15pter through SNRPN and trisomic for 14pter to 14q11.2. DNA methylation studies showed that the proband had a paternal-only DNA methylation pattern at SNRPN, D15S63 (PW71), and ZNF127. The mother and unaffected sister, both having the balanced translocation, demonstrated normal DNA methylation patterns at all three loci. These data suggest that the gene for AS most likely lies proximal to D15S10, in contrast to the previously published position, although a less likely possibility is that the maternally inherited imprinting center acts in trans in the unaffected balanced translocation carrier sister. 27 refs., 6 figs.

  15. Nuclear energy: potentiality and implications

    International Nuclear Information System (INIS)

    Bahgat, Gawdat

    2008-01-01

    After a discussion about a broad definition of energy security and about the main challenges facing a potential nuclear renaissance, the article analyses how the European Union and the United States have addressed these challenges. There is no doubt that nuclear power will remain an important component of global energy mix, but it should not be seen as a panacea to the flows in the global energy markets [it

  16. Integrated analytical techniques with high sensitivity for studying brain translocation and potential impairment induced by intranasally instilled copper nanoparticles.

    Science.gov (United States)

    Bai, Ru; Zhang, Lili; Liu, Ying; Li, Bai; Wang, Liming; Wang, Peng; Autrup, Herman; Beer, Christiane; Chen, Chunying

    2014-04-07

    Health impacts of inhalation exposure to engineered nanomaterials have attracted increasing attention. In this paper, integrated analytical techniques with high sensitivity were used to study the brain translocation and potential impairment induced by intranasally instilled copper nanoparticles (CuNPs). Mice were exposed to CuNPs in three doses (1, 10, 40 mg/kg bw). The body weight of mice decreased significantly in the 10 and 40 mg/kg group (ptechniques for systematic investigations is a promising direction to better understand the biological activities of nanomaterials. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  17. Ionization potentials some variations, implications and applications

    CERN Document Server

    Ahrens, L H

    1983-01-01

    Ionization Potentials: Some Variations, Implications and Applications covers several aspects of ionization potential that is a highly significant parameter in controlling the properties of electric discharge. Comprised of 17 chapters, the book covers topic relevant to ionization potentials, such as properties, concepts, and applications, in order to understand and fully comprehend all aspects of ionization potential. The opening chapter is a review of ionization potentials and a discussion of trends and features. The succeeding chapters then tackle complex topics such as the s and p electrons;

  18. Disease dynamics during wildlife translocations: disruptions to the host population and potential consequences for transmission in desert tortoise contact networks

    Science.gov (United States)

    Aiello, Christina M.; Nussear, Kenneth E.; Walde, Andrew D.; Esque, Todd C.; Emblidge, Patrick G.; Sah, Pratha; Bansal, S.; Hudson, Peter J.

    2014-01-01

    Wildlife managers consider animal translocation a means of increasing the viability of a local population. However, augmentation may disrupt existing resident disease dynamics and initiate an outbreak that would effectively offset any advantages the translocation may have achieved. This paper examines fundamental concepts of disease ecology and identifies the conditions that will increase the likelihood of a disease outbreak following translocation. We highlight the importance of susceptibility to infection, population size and population connectivity – a characteristic likely affected by translocation but not often considered in risk assessments – in estimating outbreak risk due to translocation. We then explore these features in a species of conservation concern often translocated in the presence of infectious disease, the Mojave Desert tortoise, and use data from experimental tortoise translocations to detect changes in population connectivity that may influence pathogen transmission. Preliminary analyses comparing contact networks inferred from spatial data at control and translocation plots and infection simulation results through these networks suggest increased outbreak risk following translocation due to dispersal-driven changes in contact frequency and network structure. We outline future research goals to test these concepts and aid managers in designing effective risk assessment and intervention strategies that will improve translocation success.

  19. Molecular heterogeneity in glioblastoma: potential clinical implications

    Directory of Open Access Journals (Sweden)

    Nicole Renee Parker

    2015-03-01

    Full Text Available Glioblastomas, (grade 4 astrocytomas, are aggressive primary brain tumors characterized by histopathological heterogeneity. High resolution sequencing technologies have shown that these tumors also feature significant inter-tumoral molecular heterogeneity. Molecular subtyping of these tumors has revealed several predictive and prognostic biomarkers. However, intra-tumoral heterogeneity may undermine the use of single biopsy analysis for determining tumor genotype and has implications for potential targeted therapies. The clinical relevance and theories of tumoral molecular heterogeneity in glioblastoma are discussed.

  20. Development of a high-throughput method for the systematic identification of human proteins nuclear translocation potential

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    Kawai Jun

    2009-09-01

    Full Text Available Abstract Background Important clues to the function of novel and uncharacterized proteins can be obtained by identifying their ability to translocate in the nucleus. In addition, a comprehensive definition of the nuclear proteome undoubtedly represents a key step toward a better understanding of the biology of this organelle. Although several high-throughput experimental methods have been developed to explore the sub-cellular localization of proteins, these methods tend to focus on the predominant localizations of gene products and may fail to provide a complete catalog of proteins that are able to transiently locate into the nucleus. Results We have developed a method for examining the nuclear localization potential of human gene products at the proteome scale by adapting a mammalian two-hybrid system we have previously developed. Our system is composed of three constructs co-transfected into a mammalian cell line. First, it contains a PCR construct encoding a fusion protein composed of a tested protein, the PDZ-protein TIP-1, and the transactivation domain of TNNC2 (referred to as ACT construct. Second, our system contains a PCR construct encoding a fusion protein composed of the DNA binding domain of GAL4 and the PDZ binding domain of rhotekin (referred to as the BIND construct. Third, a GAL4-responsive luciferase reporter is used to detect the reconstitution of a transcriptionally active BIND-ACT complex through the interaction of TIP-1 and rhotekin, which indicates the ability of the tested protein to translocate into the nucleus. We validated our method in a small-scale feasibility study by comparing it to green fluorescent protein (GFP fusion-based sub-cellular localization assays, sequence-based computational prediction of protein sub-cellular localization, and current sub-cellular localization data available from the literature for 22 gene products. Conclusion Our reporter-based system can rapidly screen gene products for their ability

  1. Reciprocal Translocation in Somatic and Germ Cells of Mice Chronically Exposed by Inhalation to Ethylene Oxide: Implication for Risk Assessment

    Science.gov (United States)

    Groups of male B6C3F1 mice were exposed by inhalation to 0, 25, 50, 100 or 200 ppm EO for up to 48 weeks (6 hours/day, 5 days/week). Animals were sacrificed at 6, 12, 24, and 48 weeks after the startt of the exposure for analyses of reciprocal translocations in peripheral blood ...

  2. Epilepsy and menopause: potential implications for pharmacotherapy.

    Science.gov (United States)

    Sveinsson, Olafur; Tomson, Torbjörn

    2014-09-01

    Being a woman with epilepsy is not the same as being a man with the disease. There is a complex multidirectional interaction between sex hormones, seizures and antiepileptic drugs (AEDs) with gender-specific implications. Estrogen can be a potent proconvulsant, whereas progesterone is an anticonvulsant in experimental models. It is well established that women with epilepsy can have changes in seizure propensity related to their menstrual cycle (catamenial epilepsy). There is good evidence that the gonadotropin-releasing hormone cell population in the hypothalamus can be affected by seizures originating in the limbic system, possibly leading to anovulatory menses, possibly contributing to lower fertility, and earlier menopause among women with epilepsy. Data on the effects of menopause on epilepsy are scarce. In general, menopause appears to have limited effects on seizure control, with the possible exception of women with catamenial epilepsy who may experience an increase in seizure frequency during perimenopause and a decrease after menopause. Hormone replacement therapy has the potential to increase seizure frequency and thus cannot be recommended for women with epilepsy. Of particular relevance for menopause is the adverse effect on bone mineral density caused by enzyme inducers and other AEDs. In general, there is a remarkable shortage of studies on the impact of menopause on epilepsy and on its implications for epilepsy treatment.

  3. Translocation of heavy metals from soils into floral organs and rewards of Cucurbita pepo: Implications for plant reproductive fitness.

    Science.gov (United States)

    Xun, Erna; Zhang, Yanwen; Zhao, Jimin; Guo, Jixun

    2017-11-01

    Metals and metalloids in soil could be transferred into reproductive organs and floral rewards of hyperaccumulator plants and influence their reproductive success, yet little is known whether non-hyperaccumulator plants can translocate heavy metals from soil into their floral organs and rewards (i.e., nectar and pollen) and, if so, whether plant reproduction will be affected. In our studies, summer squash (Cucurbita pepo L. cv. Golden Apple) was exposed to heavy-metal treatments during bud stage to investigate the translocation of soil-supplemented zinc, copper, nickel and lead into its floral organs (pistil, anther and nectary) and rewards (nectar and pollen) as well as floral metal accumulation effects on its reproduction. The results showed that metals taken up by squash did translocate into its floral organs and rewards, although metal accumulation varied depending on different metal types and concentrations as well as floral organ/reward types. Mean foraging time of honey bees to each male and female flower of squash grown in metal-supplemented soils was shorter relative to that of plants grown in control soils, although the visitation rate of honeybees to both male and female flowers was not affected by metal treatments. Pollen viability, pollen removal and deposition as well as mean mass per seed produced by metal-treated squash that received pollen from plants grown in control soils decreased with elevated soil-supplemented metal concentrations. The fact that squash could translocate soil-supplemented heavy metals into floral organs and rewards indicated possible reproductive consequences caused either directly (i.e., decreasing pollen viability or seed mass) or indirectly (i.e., affecting pollinators' visitation behavior to flowers) to plant fitness. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Climate change: potential implications for Ireland's biodiversity

    Science.gov (United States)

    Donnelly, Alison

    2018-03-01

    A national biodiversity and climate change adaptation plan is being developed for Ireland by the Department of Communications, Climate Action, and Environment. In order to inform such a plan, it was necessary to review and synthesize some of the recent literature pertaining to the impact of climate change on biodiversity in Ireland. Published research on this topic fell within three broad categories: (i) changes in the timing of life-cycle events (phenology) of plants, birds, and insects; (ii) changes in the geographic range of some bird species; and (iii) changes in the suitable climatic zones of key habitats and species. The synthesis revealed evidence of (i) a trend towards earlier spring activity of plants, birds, and insects which may result in a change in ecosystem function; (ii) an increase in the number of bird species; and (iii) both increases and decreases in the suitable climatic area of key habitats and species, all of which are expected to impact Ireland's future biodiversity. This process identified data gaps and limitations in available information both of which could be used to inform a focused research strategy. In addition, it raises awareness of the potential implications of climate change for biodiversity in Ireland and elsewhere and demonstrates the need for biodiversity conservation plans to factor climate change into future designs.

  5. A potential link between insulin signaling and GLUT4 translocation: Association of Rab10-GTP with the exocyst subunit Exoc6/6b

    Energy Technology Data Exchange (ETDEWEB)

    Sano, Hiroyuki; Peck, Grantley R. [Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755 (United States); Blachon, Stephanie [Hybrigenics Services SAS, 3-5 Impasse Reille, 75014 Paris (France); Lienhard, Gustav E., E-mail: gustav.e.lienhard@dartmouth.edu [Department of Biochemistry, Geisel School of Medicine at Dartmouth, Hanover, NH 03755 (United States)

    2015-09-25

    Insulin increases glucose transport in fat and muscle cells by stimulating the exocytosis of specialized vesicles containing the glucose transporter GLUT4. This process, which is referred to as GLUT4 translocation, increases the amount of GLUT4 at the cell surface. Previous studies have provided evidence that insulin signaling increases the amount of Rab10-GTP in the GLUT4 vesicles and that GLUT4 translocation requires the exocyst, a complex that functions in the tethering of vesicles to the plasma membrane, leading to exocytosis. In the present study we show that Rab10 in its GTP form binds to Exoc6 and Exoc6b, which are the two highly homologous isotypes of an exocyst subunit, that both isotypes are found in 3T3-L1 adipocytes, and that knockdown of Exoc6, Exoc6b, or both inhibits GLUT4 translocation in 3T3-L1 adipocytes. These results suggest that the association of Rab10-GTP with Exoc6/6b is a molecular link between insulin signaling and the exocytic machinery in GLUT4 translocation. - Highlights: • Insulin stimulates the fusion of vesicles containing GLUT4 with the plasma membrane. • This requires vesicular Rab10-GTP and the exocyst plasma membrane tethering complex. • We find that Rab10-GTP associates with the Exoc6 subunit of the exocyst. • We find that knockdown of Exoc6 inhibits fusion of GLUT4 vesicles with the membrane. • The interaction of Rab10-GTP with Exoc6 potentially links signaling to exocytosis.

  6. Simulations of Polymer Translocation

    Science.gov (United States)

    Vocks, H.

    2008-07-01

    Transport of molecules across membranes is an essential mechanism for life processes. These molecules are often long, and the pores in the membranes are too narrow for the molecules to pass through as a single unit. In such circumstances, the molecules have to squeeze -- i.e., translocate -- themselves through the pores. DNA, RNA and proteins are such naturally occuring long molecules in a variety of biological processes. Understandably, the process of translocation has been an active topic of current research: not only because it is a cornerstone of many biological processes, but also due to its relevance for practical applications. Translocation is a complicated process in living organisms -- the presence of chaperone molecules, pH, chemical potential gradients, and assisting molecular motors strongly influence its dynamics. Consequently, the translocation process has been empirically studied in great variety in biological literature. Study of translocation as a biophysical process is more recent. Herein, the polymer is simplified to a sequentially connected string of N monomers as it passes through a narrow pore on a membrane. The quantities of interest are the typical time scale for the polymer to leave a confining cell (the ``escape of a polymer from a vesicle'' time scale), and the typical time scale the polymer spends in the pore (the ``dwell'' time scale) as a function of N and other parameters like membrane thickness, membrane adsorption, electrochemical potential gradient, etc. Our research is focused on computer simulations of translocation. Since our main interest is in the scaling properties, we use a highly simplified description of the translocation process. The polymer is described as a self-avoiding walk on a lattice, and its dynamics consists of single-monomer jumps from one lattice site to another neighboring one. Since we have a very efficient program to simulate such polymer dynamics, which we decribe in Chapter 2, we can perform long

  7. Effects of Dissolved Organic Matter on Uptake and Translocation of Lead in Brassica chinensis and Potential Health Risk of Pb

    Directory of Open Access Journals (Sweden)

    Renying Li

    2016-07-01

    Full Text Available Dissolved organic matter (DOM can affect the bioavailability of heavy metals in soil, especially in soils used for vegetable production, where intensive organic fertilization is applied. The present study examined the effects of DOM derived from commercial organic fertilizers (COF, cow manure (COM and chicken manure (CHM, on uptake and translocation of lead (Pb in Brassica chinensis in a pot experiment. The results indicate that DOM derived from CHM (DOMCHM significantly increased Pb concentrations in roots of B. chinensis (p < 0.05. By contrast, there was no significant increase in shoot Pb concentration for all the DOM treatments except the high DOMCHM treatment in the soil with 800 mg·kg−1 Pb. Consistent with the Pb concentrations in shoots, translocation factor of Pb from soil to shoot and specific lead uptake (SLU by B. chinensis were significantly increased for the high DOMCHM treatment in the high Pb soil, but not for other DOM treatments. Based on the results of this study, the application of DOM to the soil with 800 mg·kg−1 Pb could result in an increase in total Pb annually ingested by the inhabitants of Nanjing City in the range of 2018–9640 kg, with the highest estimates resulting from the high DOMCHM treatment. This study suggests the risk may rise under some conditions as indicated in the high DOMCHM treatment and high Pb pollution level.

  8. Translocation, switching and gating: potential roles for ATP in long-range communication on DNA by Type III restriction endonucleases.

    Science.gov (United States)

    Szczelkun, Mark D

    2011-04-01

    To cleave DNA, the Type III RM (restriction-modification) enzymes must communicate the relative orientation of two recognition sequences, which may be separated by many thousands of base pairs. This long-range interaction requires ATP hydrolysis by a helicase domain, and both active (DNA translocation) and passive (DNA sliding) modes of motion along DNA have been proposed. Potential roles for ATP binding and hydrolysis by the helicase domains are discussed, with a focus on bipartite ATPases that act as molecular switches.

  9. Medicare Part D Roulette, Potential Implications of Random..

    Data.gov (United States)

    U.S. Department of Health & Human Services — Medicare Part D Roulette, Potential Implications of Random Assignment and Plan Restrictions Dual-eligible (Medicare and Medicaid) beneficiaries are randomly assigned...

  10. Dynamics of polymer translocation through kinked nanopores.

    Science.gov (United States)

    Wang, Junfang; Wang, Yilin; Luo, Kaifu

    2015-02-28

    Polymer translocation through nanopore has potential technological applications for DNA sequencing, where one challenge problem is to slow down translocation speed. Inspired by experimental findings that kinked nanopores exhibit a large reduction in translocation velocity compared with their straight counterparts, we investigate the dynamics of polymer translocation through kinked nanopores in two dimensions under an applied external field. With increasing the tortuosity of an array of nanopores, our analytical results show that the translocation probability decreases. Langevin dynamics simulation results support this prediction and further indicate that with increasing the tortuosity, translocation time shows a slow increase followed by a rapid increase after a critical tortuosity. This behavior demonstrates that kinked nanopores can effectively reduce translocation speed. These results are interpreted by the roles of the tortuosity for decreasing the effective nanopore diameter, increasing effective nanopore length, and greatly increasing the DNA-pore friction.

  11. Potential health impact on mice after nasal instillation of nano-sized copper particles and their translocation in mice.

    Science.gov (United States)

    Liu, Yang; Gao, Yuxi; Zhang, Lili; Wang, Tiancheng; Wang, Jiangxue; Jiao, Fang; Li, Wei; Liu, Ying; Li, Yufeng; Li, Bai; Chai, Zhifang; Wu, Gang; Chen, Chunying

    2009-11-01

    The purpose of this study is to evaluate the overall toxicity of nasal instilled nanoscale copper particles (23.5 nm) in mice. Pathological examination, target organs identification, and blood biochemical assay of experimental mice were carried out in comparison with micro-sized copper particles (17 microm). However, only in the high-dose group of copper nanoparticles (40 mg/kg body weight instilled for three times in one week), the body weight of mice were retarded and significant pathological changes were observed. There were hydropic degeneration around the central vein and the spotty necrosis of hepatocytes in the liver and swelling in the renal glomerulus, while, severe lesion associated with the decreased number of olfactory cells and the dilapidated laminated structure were also observed in the olfactory bulb. The serum biochemical assay also indicated the sign of renal and hepatic lesion. However, there were no obvious pathological and physiological damages in the mice after instilling different-sized copper nanoparticles with low dose of 1 mg/kg body weight. The retention and distribution of copper in various tissues show that the liver, kidneys and olfactory bulb are the main accumulated tissues for copper particles, which were determined by high sensitive element-specific technique of ICP-MS. The copper contents of the liver, kidneys and the olfactory bulb increase significantly at the group of 40 mg/kg compared to the control group, which is in agreement with the histological changes. Therefore, the data indicate that nasal inhaled copper particles at very high dosage can translocate to other organs and tissues and further induce certain lesions. The present results are helpful to get better understanding of the risk assessment and evaluation for copper nanoparticles.

  12. Incidence of Bacteria with Potential Public Health Implications in ...

    African Journals Online (AJOL)

    Lycopersicon esculentum (tomato) is a fleshy berry that is highly perishable and prone to microbial spoilage. The presence of some microorganisms of public health significance makes it a potential health hazard to consumers. There is therefore the need to determine the food safety and public health implications of some of ...

  13. A kinetic Monte Carlo approach to investigate antibiotic translocation through bacterial porins

    International Nuclear Information System (INIS)

    Ceccarelli, Matteo; Ruggerone, Paolo; Vargiu, Attilio V

    2012-01-01

    Many relevant biological processes take place on time scales not reachable by standard all-atom computer simulations. The translocation of antibiotics through non-specific bacterial porins is an example. Microscopic effects compete to determine penetration routes and, consequently, free energy barriers to be overcome. Since bacteria can develop resistance to treatment also by reducing their antibiotic permeability, to understand the microscopic aspects of antibiotic translocation is an important step to rationalize drug design. Here, to investigate the translocation we propose a complete numerical model that combines the diffusion-controlled rate theory and a kinetic Monte Carlo scheme based on both experimental data and microscopically well-founded all-atom simulations. Within our model, an antibiotic translocating through an hour-glass-shaped channel can be described as a molecule moving on a potential of mean force featuring several affinity sites and a high central barrier. The implications of our results for the characterization of antibiotic translocation at in vivo concentrations are discussed. The presence of an affinity site close to the mouth of the channel seems to favor the translocation of antibiotics, the affinity site acting as a particle reservoir. Possible connections between results and the appearance of mutations in clinical strains are also outlined. (paper)

  14. The potential of carbon-11 and fluorine-18 chemistry: illustration through the development of positron emission tomography radioligands targeting the translocator protein 18 kDa

    International Nuclear Information System (INIS)

    Damont, Annelaure; Roeda, Dirk; Dolle, Frederic

    2013-01-01

    The TSPO (translocator protein), also known as the peripheral benzodiazepine receptor, is up-regulated in the brain of subjects suffering from neuro-degenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Moreover, this overexpression has been proved to be linked to micro-glia activation making thus the TSPO a marker of choice of neuro-inflammatory processes and therefore a potential target for the development of radioligands for positron emission tomography imaging. The discovery of selective TSPO ligands and their labelling with the short-lived positron-emitter isotopes carbon-11 and fluorine-18 emerged in the mid-1980's with the preparation of the 3-iso-quinolinecarboxamide [ 11 C]PK11195. To date, an impressive number of promising compounds - [ 11 C]PK11195-challengers - have been developed; some radioligands - for example, [ 11 C]PBR28, [ 11 C]DPA-713, [ 18 F]FEDAA1106 and [ 18 F]DPA-714 - are currently used in clinical trials. As illustrated in this review, the methodologies applied for the preparation of these compounds remain mainly [ 11 C]methylations using [ 11 C]MeI or [ 11 C]MeOTf and SN2- type nucleophilic aliphatic [ 18 F]fluorinations - two processes illustrating the state-of-the-art arsenal of reactions that involves these two short-lived radioisotopes - but alternative processes, such as [ 11 C]carbonylations using [ 11 C]CO and [ 11 C]COCl 2 as well as SNAr-type nucleophilic [ 18 F]fluorinations, have also been reported and as such, reviewed herein. (authors)

  15. Ten-eleven translocation 1 (TET1) gene is a potential target of miR-21-5p in human colorectal cancer.

    Science.gov (United States)

    Cheng, Ya-Wen; Chou, Chia-Jung; Yang, Pei-Ming

    2018-03-01

    DNA 5-methylcytosine (5-mC) methylation, a key epigenetic mark, is critical for biological and pathological processes. Aberrant DNA methylation occurs in all tumor types and correlates with tumor suppressor gene silencing. DNA methylation is thought to be very stable, and active DNA demethylation remains a long-standing enigma. Recently, the ten-eleven translocation (TET) family of oxygenases are found to oxidize 5-mC to 5-hydroxymethylcytosine (5-hmC), which is prerequisite for active DNA demethylation. Both TET1 expression and global 5-hmC content are significantly reduced in colorectal cancer (CRC), the top leading cause of cancer-related death in the world. However, the involving molecular mechanisms are still unclear. The oncogenic microRNA (miRNA) miR-21-5p has recently identified as a diagnostic and prognostic biomarker in CRC. In this study, TET1 was predicted as a novel target of miR-21-5p by using a web-based predictive software starBase v2.0. We found that the 3'-UTR region of TET1 gene contains a miR-21-5p-binding site. Examination of tumor tissues from CRC patients found that loss of TET1 was associated with the progression of CRC to advance stages. In addition, negative correlation of miR-21-5p and TET1 expression was also observed. Transfection of the synthetic miR-21-5p mimic or inhibitor into the colorectal cancer cells could inhibit or increase the TET1-3'-UTR luciferase activity, respectively. Our results demonstrate that TET1 is a potential target of miR-21-5p in CRC. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. A novel cantharidin analog N-Benzylcantharidinamide reduces the expression of MMP-9 and invasive potentials of Hep3B via inhibiting cytosolic translocation of HuR

    International Nuclear Information System (INIS)

    Lee, Ji-Yeon; Chung, Tae-Wook; Choi, Hee-Jung; Lee, Chang Hyun; Eun, Jae Soon; Han, Young Taek; Choi, Jun-Yong; Kim, So-Yeon; Han, Chang-Woo; Jeong, Han-Sol; Ha, Ki-Tae

    2014-01-01

    Highlights: • We examined the inhibition of N-Benzylcantharidinamide on MMP-9-mediated invasion. • Unlike cantharidin, N-Benzylcantharidinamide has very low toxicity on Hep3B cells. • The reduced MMP-9 expression was due to HuR-mediated decrease of mRNA stability. • We suggest N-Benzylcantharidinamide as a novel inhibitor of MMP-9-related invasion. - Abstract: Invasion and metastasis are major causes of malignant tumor-associated mortality. The present study aimed to investigate the molecular events underlying inhibitory effect of N-Benzylcantharidinamide, a novel synthetic analog of cantharidin, on matrix metalloproteinase-9 (MMP-9)-mediated invasion in highly metastatic hepatocellular carcinoma Hep3B cells. In this investigation, among six analogs of cantharidin, only N-Benzylcantharidinamide has the inhibitory action on MMP-9 expression at non-toxic dose. The MMP-9 expression and invasion of Hep3B cells were significantly suppressed by treatment of N-Benzylcantharidinamide in a dose-dependent manner. On the other hand, the transcriptional activity of MMP-9 promoter and nuclear levels of NF-κB and AP-1 as the main transcriptional factors inducing MMP-9 expression were not affected by it although the level of MMP-9 mRNA was reduced by treatment of N-Benzylcantharidinamide. Interestingly, the stability of MMP-9 mRNA was significantly reduced by N-Benzylcantharidinamide-treatment. In addition, the cytosolic translocation of human antigen R (HuR), which results in the increase of MMP-9 mRNA stability through interaction of HuR with 3′-untranslated region of MMP-9 mRNA, was suppressed by treatment of N-Benzylcantharidinamide, in a dose-dependent manner. Taken together, it was demonstrated, for the first time, that N-Benzylcantharidinamide suppresses MMP-9 expression by reducing HuR-mediated MMP-9 mRNA stability for the inhibition of invasive potential in highly metastatic Hep3B cells

  17. Simulated degradation of biochar and its potential environmental implications

    International Nuclear Information System (INIS)

    Liu, Zhaoyun; Demisie, Walelign; Zhang, Mingkui

    2013-01-01

    A simulated oxidation technique was used to examine the impacts of degradation on the surface properties of biochar and the potential implications of the changes in biochar properties were discussed. To simulate the short- and long-term environmental degradation, mild and harsh degradation were employed. Results showed that after mild degradation, the biochar samples showed significant reductions in surface area and pore volumes. After harsh degradation, the biochar samples revealed dramatic variations in their surface chemistry, surface area, pore volumes, morphology and adsorption properties. The results clearly indicate that changes of biochar surface properties were affected by biochar types and oxidative conditions. It is suggested that biochar surface properties are likely to be gradually altered during environmental exposure. This implies that these changes have potential effects for altering the physicochemical properties of biochar amended soils. -- Highlights: •Mild and harsh degradation were employed to simulate natural degradation of biochar. •Mild degradation could reduce the surface area and micropore volumes of biochar. •Harsh degradation caused severe changes of all of the biochar surface properties. •Biochar types and oxidative conditions may dominate the changes of its properties. -- The simulated degradation of biochar in this study could provide a mechanism for forecasting short- or long-term environmental degradation of biochar

  18. Problem-elephant translocation: translocating the problem and the elephant?

    Directory of Open Access Journals (Sweden)

    Prithiviraj Fernando

    Full Text Available Human-elephant conflict (HEC threatens the survival of endangered Asian elephants (Elephas maximus. Translocating "problem-elephants" is an important HEC mitigation and elephant conservation strategy across elephant range, with hundreds translocated annually. In the first comprehensive assessment of elephant translocation, we monitored 16 translocations in Sri Lanka with GPS collars. All translocated elephants were released into national parks. Two were killed within the parks where they were released, while all the others left those parks. Translocated elephants showed variable responses: "homers" returned to the capture site, "wanderers" ranged widely, and "settlers" established home ranges in new areas soon after release. Translocation caused wider propagation and intensification of HEC, and increased elephant mortality. We conclude that translocation defeats both HEC mitigation and elephant conservation goals.

  19. Oncogene Translocations and NHL

    Science.gov (United States)

    A colloboration with several large population-based cohorts to determine whether the prevalence or level of t14;18 is associated with risk of NHL and to investigate the clonal relationship between translocation-bearing cells and subsequent tumors

  20. Adsorption-driven translocation of polymer chain into nanopores

    Science.gov (United States)

    Yang, Shuang; Neimark, Alexander V.

    2012-06-01

    The polymer translocation into nanopores is generally facilitated by external driving forces, such as electric or hydrodynamic fields, to compensate for entropic restrictions imposed by the confinement. We investigate the dynamics of translocation driven by polymer adsorption to the confining walls that is relevant to chromatographic separation of macromolecules. By using the self-consistent field theory, we study the passage of a chain trough a small opening from cis to trans compartments of spherical shape with adsorption potential applied in the trans compartment. The chain transfer is modeled as the Fokker-Plank diffusion along the free energy landscape of the translocation pass represented as a sum of the free energies of cis and trans parts of the chain tethered to the pore opening. We investigate how the chain length, the size of trans compartment, the magnitude of adsorption potential, and the extent of excluded volume interactions affect the translocation time and its distribution. Interplay of these factors brings about a variety of different translocation regimes. We show that excluded volume interactions within a certain range of adsorption potentials can cause a local minimum on the free energy landscape, which is absent for ideal chains. The adsorption potential always leads to the decrease of the free energy barrier, increasing the probability of successful translocation. However, the translocation time depends non-monotonically of the magnitude of adsorption potential. Our calculations predict the existence of the critical magnitude of adsorption potential, which separates favorable and unfavorable regimes of translocation.

  1. High Altitude Emissions of Black Carbon Aerosols: Potential Climate Implications

    Science.gov (United States)

    Satheesh, S. K.

    2017-12-01

    these, it is hypothesized that such intrusions of black carbon to lower stratosphere and its consequent longer residence time in the stratosphere, would have significant implications for stratospheric chemistry, considering the known ozone depleting potential of black carbon aerosols.

  2. Factors affecting translocation and sclerotial formation in Morchella esculenta

    International Nuclear Information System (INIS)

    Amir, R.; Levanon, D.; Hadar, Y.; Chet, I.

    1995-01-01

    Amir, R., Levanon, D., Hadar, Y., and Chet, I. 1995. Factors affecting translocation and sclerotial formation in Morchella esculenta. Experimental Mycology 19, 61-70. Morchella esculenta was grown on square split plates, forming sclerotia on one side and mycelium on the other. After the fungus ceased to colonize and before sclerotial initials appeared, [ 14 C]3-O-methyl glucose was added to the edge of the plate on the mycelial side. The effect of various activities in the mycelium (source) and sclerotia (sink) on sclerotial formation and translocation were examined using inhibitors and water potential changes of the media. Sodium azide or cycloheximide applied separately to both sides inhibited both sclerotial formation and translocation, showing that processes in the source and sink depend on metabolic activities as well as protein synthesis. The use of nikkomycin inhibited sclerotial formation, without affecting translocation to the sclerotia. Since the hyphal tips swelled and burst, the translocated compounds were lost to the media. In a strain defective in sclerotial formation, used as a control, no translocation took place, showing that there is a connection between sclerotial formation and translocation. Reversal of the water potential gradient between the two media (lower on the mycelial side), reduced the formation of sclerotia and translocation to them. Translocation to Morchella sclerotia takes place via turgor driven mass flow, but is nevertheless affected by activities in both the source and the sink. (author)

  3. Potential risks of nanotechnology to humans and environment: implications and response mechanisms in Africa

    CSIR Research Space (South Africa)

    Musee, N

    2011-11-01

    Full Text Available www.csir.co.za ENM exposure routes, uptake and potential translocation Dermal Oral Inhalation Ocular Lymphatic System Gastro- intestinal Tract Organs Circulatory System (blood) Respiratory Tract Brain Nasal Cavity Yokel et al. 2011 N... fibrosarcoma cells (left) and human skin/carcinoma cells (right). (A) unexposed cells; (B?F) 24 h after exposure to 3.12, 6.25, 12.5, 25 & 50 ?g/mL nAg respectively (magnification 200?). ? At higher concentrations cells became less polyhedral, more fusiform...

  4. Hydraulic fracturing water use variability in the United States and potential environmental implications.

    Science.gov (United States)

    Gallegos, Tanya J; Varela, Brian A; Haines, Seth S; Engle, Mark A

    2015-07-01

    A U.S. map of water volumes used to hydraulically fracture oil and gas wells, 2011-2014Hydraulic fracturing water volumes differ regionally across the U.S.Discussion of variation in water use and potential environmental implications.

  5. Potential Clinical Implications of the Urotensin II Receptor Antagonists

    Directory of Open Access Journals (Sweden)

    Emilie Kane

    2011-07-01

    Full Text Available Urotensin-II (UII, which binds to its receptor UT, plays an important role in the heart, kidneys, pancreas, adrenal gland and CNS. In the vasculature, it acts as a potent endothelium-independent vasoconstrictor and endothelium-dependent vasodilator. In disease states, this constriction-dilation equilibrium is disrupted. There is an upregulation of the UII system in heart disease, metabolic syndrome and kidney failure. The increase in UII release and UT expression suggest that UII system may be implicated in the pathology and pathogenesis of these diseases by causing an increase in ACAT-1 activity leading to SMC proliferation and foam cell infiltration, insulin resistance (DMII, as well as inflammation, high blood pressure and plaque formation. Recently, UT antagonists such as SB-611812, palosuran, and most recently a piperazino-isoindolinone based antagonist have been developed in the hope of better understanding the UII system and treating its associated diseases.

  6. Translocation of cell-penetrating peptides into Candida fungal pathogens.

    Science.gov (United States)

    Gong, Zifan; Karlsson, Amy J

    2017-09-01

    Cell-penetrating peptides (CPPs) are small peptides capable of crossing cellular membranes while carrying molecular cargo. Although they have been widely studied for their ability to translocate nucleic acids, small molecules, and proteins into mammalian cells, studies of their interaction with fungal cells are limited. In this work, we evaluated the translocation of eleven fluorescently labeled peptides into the important human fungal pathogens Candida albicans and C. glabrata and explored the mechanisms of translocation. Seven of these peptides (cecropin B, penetratin, pVEC, MAP, SynB, (KFF) 3 K, and MPG) exhibited substantial translocation (>80% of cells) into both species in a concentration-dependent manner, and an additional peptide (TP-10) exhibiting strong translocation into only C. glabrata. Vacuoles were involved in translocation and intracellular trafficking of the peptides in the fungal cells and, for some peptides, escape from the vacuoles and localization in the cytosol were correlated to toxicity toward the fungal cells. Endocytosis was involved in the translocation of cecropin B, MAP, SynB, MPG, (KFF) 3 K, and TP-10, and cecropin B, penetratin, pVEC, and MAP caused membrane permeabilization during translocation. These results indicate the involvement of multiple translocation mechanisms for some CPPs. Although high levels of translocation were typically associated with toxicity of the peptides toward the fungal cells, SynB was translocated efficiently into Candida cells at concentrations that led to minimal toxicity. Our work highlights the potential of CPPs in delivering antifungal molecules and other bioactive cargo to Candida pathogens. © 2017 The Protein Society.

  7. Reassessing Wind Potential Estimates for India: Economic and Policy Implications

    Energy Technology Data Exchange (ETDEWEB)

    Phadke, Amol; Bharvirkar, Ranjit; Khangura, Jagmeet

    2011-09-15

    We assess developable on-shore wind potential in India at three different hub-heights and under two sensitivity scenarios – one with no farmland included, the other with all farmland included. Under the “no farmland included” case, the total wind potential in India ranges from 748 GW at 80m hub-height to 976 GW at 120m hub-height. Under the “all farmland included” case, the potential with a minimum capacity factor of 20 percent ranges from 984 GW to 1,549 GW. High quality wind energy sites, at 80m hub-height with a minimum capacity factor of 25 percent, have a potential between 253 GW (no farmland included) and 306 GW (all farmland included). Our estimates are more than 15 times the current official estimate of wind energy potential in India (estimated at 50m hub height) and are about one tenth of the official estimate of the wind energy potential in the US.

  8. Eccentricity samples: Implications on the potential and the velocity distribution

    Directory of Open Access Journals (Sweden)

    Cubarsi R.

    2017-01-01

    Full Text Available Planar and vertical epicycle frequencies and local angular velocity are related to the derivatives up to the second order of the local potential and can be used to test the shape of the potential from stellar disc samples. These samples show a more complex velocity distribution than halo stars and should provide a more realistic test. We assume an axisymmetric potential allowing a mixture of independent ellipsoidal velocity distributions, of separable or Staeckel form in cylindrical or spherical coordinates. We prove that values of local constants are not consistent with a potential separable in addition in cylindrical coordinates and with a spherically symmetric potential. The simplest potential that fits the local constants is used to show that the harmonical and non-harmonical terms of the potential are equally important. The same analysis is used to estimate the local constants. Two families of nested subsamples selected for decreasing planar and vertical eccentricities are used to borne out the relation between the mean squared planar and vertical eccentricities and the velocity dispersions of the subsamples. According to the first-order epicycle model, the radial and vertical velocity components provide accurate information on the planar and vertical epicycle frequencies. However, it is impossible to account for the asymmetric drift which introduces a systematic bias in estimation of the third constant. Under a more general model, when the asymmetric drift is taken into account, the rotation velocity dispersions together with their asymmetric drift provide the correct fit for the local angular velocity. The consistency of the results shows that this new method based on the distribution of eccentricities is worth using for kinematic stellar samples. [Project of the Serbian Ministry of Education, Science and Technological Development, Grant no. No 176011: Dynamics and Kinematics of Celestial Bodies and Systems

  9. Saturation wind power potential and its implications for wind energy.

    Science.gov (United States)

    Jacobson, Mark Z; Archer, Cristina L

    2012-09-25

    Wind turbines convert kinetic to electrical energy, which returns to the atmosphere as heat to regenerate some potential and kinetic energy. As the number of wind turbines increases over large geographic regions, power extraction first increases linearly, but then converges to a saturation potential not identified previously from physical principles or turbine properties. These saturation potentials are >250 terawatts (TW) at 100 m globally, approximately 80 TW at 100 m over land plus coastal ocean outside Antarctica, and approximately 380 TW at 10 km in the jet streams. Thus, there is no fundamental barrier to obtaining half (approximately 5.75 TW) or several times the world's all-purpose power from wind in a 2030 clean-energy economy.

  10. Listeria Occurrence in Poultry Flocks: Detection and Potential Implications

    Science.gov (United States)

    Foodborne pathogens such as Salmonella, Campylobacter, Escherichia coli, and Listeria are a major concern within the food industry due to their pathogenic potential to cause infection. Of these, Listeria monocytogenes, possesses a high mortality rate (approximately20%) and is considered one of the m...

  11. Muskellunge growth potential in northern Wisconsin: implications for trophy management

    Science.gov (United States)

    Faust, Matthew D.; Isermann, Daniel A.; Luehring, Mark A.; Hansen, Michael J.

    2015-01-01

    The growth potential of Muskellunge Esox masquinongy was evaluated by back-calculating growth histories from cleithra removed from 305 fish collected during 1995–2011 to determine whether it was consistent with trophy management goals in northern Wisconsin. Female Muskellunge had a larger mean asymptotic length (49.8 in) than did males (43.4 in). Minimum ultimate size of female Muskellunge (45.0 in) equaled the 45.0-in minimum length limit, but was less than the 50.0-in minimum length limit used on Wisconsin's trophy waters, while the minimum ultimate size of male Muskellunge (34.0 in) was less than the statewide minimum length limit. Minimum reproductive sizes for both sexes were less than Wisconsin's trophy minimum length limits. Mean growth potential of female Muskellunge in northern Wisconsin appears to be sufficient for meeting trophy management objectives and angler expectations. Muskellunge in northern Wisconsin had similar growth potential to those in Ontario populations, but lower growth potential than Minnesota's populations, perhaps because of genetic and environmental differences.

  12. Listeria Occurrence in Poultry Flocks: Detection and Potential Implications

    Directory of Open Access Journals (Sweden)

    Michael J. Rothrock

    2017-08-01

    Full Text Available Foodborne pathogens such as Salmonella, Campylobacter, Escherichia coli, and Listeria are a major concern within the food industry due to their pathogenic potential to cause infection. Of these, Listeria monocytogenes, possesses a high mortality rate (approximately 20% and is considered one of the most dangerous foodborne pathogens. Although the usual reservoirs for Listeria transmission have been extensively studied, little is known about the relationship between Listeria and live poultry production. Sporadic and isolated cases of listeriosis have been attributed to poultry production and Listeria spp. have been isolated from all stages of poultry production and processing. Farm studies suggest that live birds may be an important vector and contributor to contamination of the processing environment and transmission of Listeria to consumers. Therefore, the purpose of this review is to highlight the occurrence, incidence, and potential systemic interactions of Listeria spp. with poultry.

  13. Implication of Heat Shock Factors in Tumorigenesis: Therapeutical Potential

    Energy Technology Data Exchange (ETDEWEB)

    Thonel, Aurelie de [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); Mezger, Valerie, E-mail: valerie.mezger@univ-paris-diderot.fr [CNRS, UMR7216 Epigenetics and Cell Fate, Paris (France); University Paris Diderot, 75013 Paris (France); Garrido, Carmen, E-mail: valerie.mezger@univ-paris-diderot.fr [INSERM U866, Dijon (France); Faculty of Medicine and Pharmacy, University of Burgundy, 21033 Dijon (France); CHU, Dijon BP1542, Dijon (France)

    2011-03-07

    Heat Shock Factors (HSF) form a family of transcription factors (four in mammals) which were named according to the discovery of their activation by a heat shock. HSFs trigger the expression of genes encoding Heat Shock Proteins (HSPs) that function as molecular chaperones, contributing to establish a cytoprotective state to various proteotoxic stresses and in pathological conditions. Increasing evidence indicates that this ancient transcriptional protective program acts genome-widely and performs unexpected functions in the absence of experimentally defined stress. Indeed, HSFs are able to re-shape cellular pathways controlling longevity, growth, metabolism and development. The most well studied HSF, HSF1, has been found at elevated levels in tumors with high metastatic potential and is associated with poor prognosis. This is partly explained by the above-mentioned cytoprotective (HSP-dependent) function that may enable cancer cells to adapt to the initial oncogenic stress and to support malignant transformation. Nevertheless, HSF1 operates as major multifaceted enhancers of tumorigenesis through, not only the induction of classical heat shock genes, but also of “non-classical” targets. Indeed, in cancer cells, HSF1 regulates genes involved in core cellular functions including proliferation, survival, migration, protein synthesis, signal transduction, and glucose metabolism, making HSF1 a very attractive target in cancer therapy. In this review, we describe the different physiological roles of HSFs as well as the recent discoveries in term of non-cogenic potential of these HSFs, more specifically associated to the activation of “non-classical” HSF target genes. We also present an update on the compounds with potent HSF1-modulating activity of potential interest as anti-cancer therapeutic agents.

  14. Recent decrease in typhoon destructive potential and global warming implications

    Science.gov (United States)

    Lin, I.-I.; Chan, Johnny C. L.

    2015-05-01

    Typhoons (tropical cyclones) severely impact the half-billion population of the Asian Pacific. Intriguingly, during the recent decade, typhoon destructive potential (Power Dissipation Index, PDI) has decreased considerably (by ~35%). This decrease, paradoxically, has occurred despite the increase in typhoon intensity and ocean warming. Using the method proposed by Emanuel (in 2007), we show that the stronger negative contributions from typhoon frequency and duration, decrease to cancel the positive contribution from the increasing intensity, controlling the PDI. Examining the typhoons' environmental conditions, we find that although the ocean condition became more favourable (warming) in the recent decade, the atmospheric condition `worsened' at the same time. The `worsened' atmospheric condition appears to effectively overpower the `better' ocean conditions to suppress PDI. This stronger negative contribution from reduced typhoon frequency over the increased intensity is also present under the global warming scenario, based on analysis of the simulated typhoon data from high-resolution modelling.

  15. The human gut microbiota and virome: Potential therapeutic implications.

    Science.gov (United States)

    Scarpellini, Emidio; Ianiro, Gianluca; Attili, Fabia; Bassanelli, Chiara; De Santis, Adriano; Gasbarrini, Antonio

    2015-12-01

    Human gut microbiota is a complex ecosystem with several functions integrated in the host organism (metabolic, immune, nutrients absorption, etc.). Human microbiota is composed by bacteria, yeasts, fungi and, last but not least, viruses, whose composition has not been completely described. According to previous evidence on pathogenic viruses, the human gut harbours plant-derived viruses, giant viruses and, only recently, abundant bacteriophages. New metagenomic methods have allowed to reconstitute entire viral genomes from the genetic material spread in the human gut, opening new perspectives on the understanding of the gut virome composition, the importance of gut microbiome, and potential clinical applications. This review reports the latest evidence on human gut "virome" composition and its function, possible future therapeutic applications in human health in the context of the gut microbiota, and attempts to clarify the role of the gut "virome" in the larger microbial ecosystem. Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. Potential implications of climate change and urbanization on watershed hydrology

    Science.gov (United States)

    Pumo, D.; Arnone, E.; Francipane, A.; Caracciolo, D.; Noto, L. V.

    2017-11-01

    This paper proposes a modeling framework able to analyze the alterations in watershed hydrology induced by two recurrent drivers for hydrological changes: climate change and urbanization. The procedure is based on the coupling of a stochastic weather generator with a land use change model for the generation of some hypothetical scenarios. The generated scenarios are successively used to force a physically-based and spatial distributed hydrological model to reconstruct the basin response under different conditions. Several potential climate alterations are simulated by imposing negative and positive variations in the mean annual precipitation and a simultaneous temperature increase. Urbanization is conceptualized by an increase in the impervious fraction of the basin. The procedure is applied to a large basin and a much smaller sub-basin; the results show how climate and land use changes may interact and affect the fundamental hydrological dynamics and how the processes governing basin hydrological response may change with spatial scale.

  17. [Focus on the Immunoscore and its potential clinical implications].

    Science.gov (United States)

    El Sissy, Carine; Marliot, Florence; Haicheur, Nacilla; Kirilovsky, Amos; Scripcariu, Dragos; Lagorce-Pagès, Christine; Galon, Jérôme; Pagès, Franck

    2017-02-01

    The role of the immune response at the tumor site is now recognized as crucial in the clinical course of patients with cancer. The importance of the immune cell type, their functional orientation, their density and location within the tumor's regions (tumor/invasion margin) has recently been shown and were grouped together under the term "immune contexture". A strong infiltration by cytotoxic and memory T cells in a Th1-polarized tumor microenvironment appears to have a major prognosis impact. A test called Immunoscore taking into account these various parameters has been suggested to measure in a simple, reproducible and robust manner the intra- and peritumoral immune response. The prognostic value of Immunoscore has recently been validated in colon cancers by a large international retrospective study under the aegis of the Society for Immunotherapy of Cancer (SITC). The Immunoscore could have several potential clinical applications such as prognostic as well as theranostic. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Recent decrease in typhoon destructive potential and global warming implications

    Science.gov (United States)

    Lin, I-I; Chan, Johnny C.L.

    2015-01-01

    Typhoons (tropical cyclones) severely impact the half-billion population of the Asian Pacific. Intriguingly, during the recent decade, typhoon destructive potential (Power Dissipation Index, PDI) has decreased considerably (by ∼35%). This decrease, paradoxically, has occurred despite the increase in typhoon intensity and ocean warming. Using the method proposed by Emanuel (in 2007), we show that the stronger negative contributions from typhoon frequency and duration, decrease to cancel the positive contribution from the increasing intensity, controlling the PDI. Examining the typhoons' environmental conditions, we find that although the ocean condition became more favourable (warming) in the recent decade, the atmospheric condition ‘worsened' at the same time. The ‘worsened' atmospheric condition appears to effectively overpower the ‘better' ocean conditions to suppress PDI. This stronger negative contribution from reduced typhoon frequency over the increased intensity is also present under the global warming scenario, based on analysis of the simulated typhoon data from high-resolution modelling. PMID:25990561

  19. Configuration and technology implications of potential nuclear hydrogen system applications.

    Energy Technology Data Exchange (ETDEWEB)

    Conzelmann, G.; Petri, M.; Forsberg, C.; Yildiz, B.; ORNL

    2005-11-05

    Nuclear technologies have important distinctions and potential advantages for large-scale generation of hydrogen for U.S. energy services. Nuclear hydrogen requires no imported fossil fuels, results in lower greenhouse-gas emissions and other pollutants, lends itself to large-scale production, and is sustainable. The technical uncertainties in nuclear hydrogen processes and the reactor technologies needed to enable these processes, as well waste, proliferation, and economic issues must be successfully addressed before nuclear energy can be a major contributor to the nation's energy future. In order to address technical issues in the time frame needed to provide optimized hydrogen production choices, the Nuclear Hydrogen Initiative (NHI) must examine a wide range of new technologies, make the best use of research funding, and make early decisions on which technology options to pursue. For these reasons, it is important that system integration studies be performed to help guide the decisions made in the NHI. In framing the scope of system integration analyses, there is a hierarchy of questions that should be addressed: What hydrogen markets will exist and what are their characteristics? Which markets are most consistent with nuclear hydrogen? What nuclear power and production process configurations are optimal? What requirements are placed on the nuclear hydrogen system? The intent of the NHI system studies is to gain a better understanding of nuclear power's potential role in a hydrogen economy and what hydrogen production technologies show the most promise. This work couples with system studies sponsored by DOE-EE and other agencies that provide a basis for evaluating and selecting future hydrogen production technologies. This assessment includes identifying commercial hydrogen applications and their requirements, comparing the characteristics of nuclear hydrogen systems to those market requirements, evaluating nuclear hydrogen configuration options

  20. Potentials and policy implications of energy and material efficiency improvement

    Energy Technology Data Exchange (ETDEWEB)

    Worrell, Ernst; Levine, Mark; Price, Lynn; Martin, Nathan; van den Broek, Richard; Block, Kornelis

    1997-01-01

    There is a growing awareness of the serious problems associated with the provision of sufficient energy to meet human needs and to fuel economic growth world-wide. This has pointed to the need for energy and material efficiency, which would reduce air, water and thermal pollution, as well as waste production. Increasing energy and material efficiency also have the benefits of increased employment, improved balance of imports and exports, increased security of energy supply, and adopting environmentally advantageous energy supply. A large potential exists for energy savings through energy and material efficiency improvements. Technologies are not now, nor will they be, in the foreseeable future, the limiting factors with regard to continuing energy efficiency improvements. There are serious barriers to energy efficiency improvement, including unwillingness to invest, lack of available and accessible information, economic disincentives and organizational barriers. A wide range of policy instruments, as well as innovative approaches have been tried in some countries in order to achieve the desired energy efficiency approaches. These include: regulation and guidelines; economic instruments and incentives; voluntary agreements and actions, information, education and training; and research, development and demonstration. An area that requires particular attention is that of improved international co-operation to develop policy instruments and technologies to meet the needs of developing countries. Material efficiency has not received the attention that it deserves. Consequently, there is a dearth of data on the qualities and quantities for final consumption, thus, making it difficult to formulate policies. Available data, however, suggest that there is a large potential for improved use of many materials in industrialized countries.

  1. Potential Antidepressant Role of Neurotransmitter CART: Implications for Mental Disorders

    Directory of Open Access Journals (Sweden)

    Peizhong Mao

    2011-01-01

    Full Text Available Depression is one of the most prevalent and debilitating public health concerns. Although no single cause of depression has been identified, it appears that interaction among genetic, epigenetic, biochemical, environmental, and psychosocial factors may explain its etiology. Further, only a fraction of depressed patients show full remission while using current antidepressants. Therefore, identifying common pathways of the disorder and using that knowledge to develop more effective pharmacological treatments are two primary targets of research in this field. Brain-enriched neurotransmitter CART (cocaine- and amphetamine-regulated transcript has multiple functions related to emotions. It is a potential neurotrophic factor and is involved in the regulation of hypothalamic-pituitary-adrenal axis and stress response as well as in energy homeostasis. CART is also highly expressed in limbic system, which is considered to have an important role in regulating mood. Notably, adolescents carrying a missense mutation in the CART gene exhibit increased depression and anxiety. Hence, CART peptide may be a novel promising antidepressant agent. In this paper, we summarize recent progress in depression and CART. In particular, we emphasize a new antidepressant function for CART.

  2. Embryonic–maternal cross-talk via exosomes: potential implications

    Directory of Open Access Journals (Sweden)

    Saadeldin IM

    2015-07-01

    Full Text Available Islam M Saadeldin,1 Hyun Ju Oh,2 Byeong Chun Lee2,3 1Department of Physiology, Faculty of Veterinary Medicine, Zagazig University, Zagazig, Egypt; 2Department of Theriogenology and Biotechnology, College of Veterinary Medicine and the Research Institute for Veterinary Science, Seoul National University, Seoul, Republic of Korea; 3Institute of Green Bio Science and Technology, Seoul National University, Pyeong Chang, Kangwon do, Republic of KoreaAbstract: A myriad of locally produced factors into the microenvironment of the reproductive tract is regulated, not one-way but rather, through embryonic–maternal cross-talk. In this minireview, we focused on the exosomes, which are cell-derived vesicles of 30–100 nm in diameter, as a communicating language facilitating this dialog. These nanovesicles are secreted from preimplantation embryos, oviduct epithelium, and endometrium as well as from the placenta, and contain proteins, messenger RNA (mRNA, microRNA, and DNA cargoes, and have pleiotropic effects on both embryonic and maternal environments. A better understanding of the molecular mechanisms mediating this cross-talk will lead to the development of new regulating agents, with novel diagnostic, biological, and therapeutic potential for either supporting or hindering the normal reproductive functions. Keywords: embryo, endometrium, placenta, mRNA, miRNA

  3. Gender differences in susceptibility to schizophrenia: Potential implication of neurosteroids.

    Science.gov (United States)

    Huang, Yu-Chi; Hung, Chi-Fa; Lin, Pao-Yen; Lee, Yu; Wu, Chih-Ching; Hsu, Su-Ting; Chen, Chien-Chih; Chong, Mian-Yoon; Lin, Chieh-Hsin; Wang, Liang-Jen

    2017-10-01

    Past research has indicated gender differences in the clinical characteristics and course of schizophrenia. In this study, we investigated whether gender differences in the manifestation of schizophrenia are correlated with neurosteroids, including dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEA-S), and pregnenolone. We further explored the potential relationship between the aforementioned neurosteroids and psychopathology. We recruited 65 schizophrenic patients (36 males and 29 females) and 103 healthy control subjects (47 males and 56 females) and obtained blood samples from the subjects in the morning while in a fasting state to determine the serum levels of DHEA, DHEA-S, and pregnenolone. The psychopathology and mood symptoms of patients with schizophrenia were evaluated using the Positive and Negative Syndrome Scale (PANSS) and 17-item Hamilton Depression Rating Scale, respectively. Compared to the male control subjects, male patients with schizophrenia had significantly lower serum levels of DHEA and pregnenolone. In males with schizophrenia, the serum levels of DHEA and DHEA-S were associated with the age of onset and the duration of illness, while pregnenolone levels were associated with general symptoms of the PANSS. However, none of the neurosteroid levels were different between the female patients with schizophrenia and the female controls, and no significant correlation between neurosteroid levels and psychopathology evaluations was found among the schizophrenic females. Neurosteroids, including DHEA, DHEA-S, and pregnenolone, are involved in the pathophysiology of schizophrenia in male patients, but not in female ones. Therefore, our findings suggest that neurosteroids may be associated with gender differences in susceptibility to schizophrenia. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Does translocation influence physiological stress in the desert tortoise?

    Science.gov (United States)

    Drake, K.K.; Nussear, K.E.; Esque, T.C.; Barber, A.M.; Vittum, K.M.; Medica, P.A.; Tracy, C.R.; Hunter, K.W.

    2012-01-01

    Wildlife translocation is increasingly used to mitigate disturbances to animals or habitat due to human activities, yet little is known about the extent to which translocating animals causes stress. To understand the relationship between physiological stress and translocation, we conducted a multiyear study (2007–2009) using a population of desert tortoises (Gopherus agassizii) near Fort Irwin, California. Blood samples were collected from adult tortoises in three treatment groups (resident, translocated and control) for 1 year prior to and 2 years after translocation. Samples were analyzed by radioimmunoassay for plasma total corticosterone (CORT), a glucocorticoid hormone commonly associated with stress responses in reptiles. CORT values were analyzed in relation to potential covariates (animal sex, date, behavior, treatment, handling time, air temperature, home-range size, precipitation and annual plant production) among seasons and years. CORT values in males were higher than in females, and values for both varied monthly throughout the activity season and among years. Year and sex were strong predictors of CORT, and translocation explained little in terms of CORT. Based on these results, we conclude that translocation does not elicit a physiological stress response in desert tortoises.

  5. Abdominal radiation causes bacterial translocation

    International Nuclear Information System (INIS)

    Guzman-Stein, G.; Bonsack, M.; Liberty, J.; Delaney, J.P.

    1989-01-01

    The purpose of this study was to determine if a single dose of radiation to the rat abdomen leads to bacterial translocation into the mesenteric lymph nodes (MLN). A second issue addressed was whether translocation correlates with anatomic damage to the mucosa. The radiated group (1100 cGy) which received anesthesia also was compared with a control group and a third group which received anesthesia alone but no abdominal radiation. Abdominal radiation lead to 100% positive cultures of MLN between 12 hr and 4 days postradiation. Bacterial translocation was almost nonexistent in the control and anesthesia group. Signs of inflammation and ulceration of the intestinal mucosa were not seen until Day 3 postradiation. Mucosal damage was maximal by Day 4. Bacterial translocation onto the MLN after a single dose of abdominal radiation was not apparently dependent on anatomical, histologic damage of the mucosa

  6. Translocation of threatened plants as a conservation measure in China.

    Science.gov (United States)

    Liu, Hong; Ren, Hai; Liu, Qiang; Wen, XiangYing; Maunder, Michael; Gao, JiangYun

    2015-12-01

    We assessed the current status of plant conservation translocation efforts in China, a topic poorly reported in recent scientific literature. We identified 222 conservation translocation cases involving 154 species, of these 87 were Chinese endemic species and 101 (78%) were listed as threatened on the Chinese Species Red List. We categorized the life form of each species and, when possible, determined for each case the translocation type, propagule source, propagule type, and survival and reproductive parameters. A surprisingly large proportion (26%) of the conservation translocations in China were conservation introductions, largely implemented in response to large-scale habitat destruction caused by the Three-Gorge Dam and another hydropower project. Documentation and management of the translocations varied greatly. Less than half the cases had plant survival records. Statistical analyses showed that survival percentages were significantly correlated with plant life form and the type of planting materials. Thirty percent of the cases had records on whether or not individuals flowered or fruited. Results of information theoretic model selection indicated that plant life form, translocation type, propagule type, propagule source, and time since planting significantly influenced the likelihood of flowering and fruiting on the project level. We suggest that the scientific-based application of species conservation translocations should be promoted as part of a commitment to species recovery management. In addition, we recommend that the common practice of within and out of range introductions in nature reserves to be regulated more carefully due to its potential ecological risks. We recommend the establishment of a national office and database to coordinate conservation translocations in China. Our review effort is timely considering the need for a comprehensive national guideline for the newly announced nation-wide conservation program on species with extremely

  7. "Understanding Adam" multiple reciprocal translocations: complex case presentation.

    Science.gov (United States)

    Linder, Carie E; Lu, Xianglan; Kim, Young Mi; Li, Shibo; Pineda, Jose

    2009-01-01

    This article presents a case review of a newborn diagnosed with a complex chromosomal rearrangement, as demonstrated through a painted chromosomal analysis. This infant presented with multiple dysmorphology including cutis aplasia, multiple ocular malformations, bilateral cleft lip and palate, and postnatal hydrocephaly. A chromosomal analysis revealed multiple-ways, balanced translocation involving chromosomes 3, 4, 6, 8, and 9. This case study provides a unique opportunity to, in retrospect, trace each malformation exploring the pathophysiology, etiology, and correlating origin with chromosomal variation. Careful review of this case, enhanced by the visually augmented representation of each translocation, will increase understanding of chromosomal anomalies and their implications in embryological development and clinical presentation.

  8. Biosecurity for Translocations: Cirl Bunting (Emberiza cirlus), Fisher's Estuarine Moth (Gortyna borelii lunata), Short-Haired Bumblebee (Bombus subterraneus) and Pool Frog (Pelophylax lessonae) Translocations as Case Studies.

    Science.gov (United States)

    Vaughan-Higgins, R J; Masters, N; Sainsbury, A W

    2017-03-01

    Exposure to parasites in conservation translocations increases the risks to recipient and translocated populations from disease, and therefore there has been interest in implementing biosecurity methods. Using four case examples we described how biosecurity was applied in practical translocation scenarios prior to and during a translocation and also post-release. We implemented biosecurity, including quarantine barriers, at specific points in the translocation pathway where hazards, identified by the disease risk analysis, had the potential to induce disease. Evidence that biosecurity protected translocated and recipient populations, included an absence of mortality associated with high-risk non-native parasites, a reduction in mortality associated with endemic parasites, the absence of high-risk pathogenic parasites, or associated diseases, at the destination; and the apparent absence of diseases in closely related species at the destination site. The biosecurity protocols did not alter the level or duration of translocated species confinement and therefore probably did not act as a stressor. There is a monetary cost involved in biosecurity but the epidemiological evidence suggests that conservation translocation managers should carefully consider its use. Breakdowns in quarantine have occurred in human hospitals despite considerable investment and training for health professionals, and we therefore judge that there is a need for training in the objectives and maintenance of quarantine barriers in conservation translocations. Biosecurity protocols for conservation translocations should be continually updated in response to findings from disease risk analysis and post-release disease surveillance and we recommend further studies to evaluate their effectiveness.

  9. Effect of cadmium accumulation on mineral nutrient levels in vegetable crops: potential implications for human health.

    Science.gov (United States)

    Yang, Danping; Guo, Zhiqiang; Green, Iain D; Xie, Deti

    2016-10-01

    Consumption of vegetables is often the predominant route whereby humans are exposed to the toxic metal Cd. Health impacts arising from Cd consumption may be influenced by changes in the mineral nutrient content of vegetables, which may occur when plants are exposed to Cd. Here, we subjected model root (carrot) and leaf (lettuce) vegetables to soil Cd concentrations of 0.3, 1.5, 3.3, and 9.6 μg g(-1) for 10 weeks to investigate the effect of Cd exposure on Cd accumulation, growth performance, and mineral nutrient homeostasis. The findings demonstrated that Cd accumulation in lettuce (20.1-71.5 μg g(-1)) was higher than that in carrot (3.2-27.5 μg g(-1)), and accumulation exceeded the maximum permissible Cd concentration in vegetables when soil contained more than 3.3 μg g(-1) of Cd. There was a marked hormetic effect on carrot growth at a soil Cd concentration of 3.3 μg g(-1), but increasing the Cd concentration to 9.6 μg g(-1) caused decreased growth in both crops. Additionally, in most cases, there was a positive correlation between Cd and the mineral nutrient content of vegetables, which was due to physiological changes in the plants causing increased uptake and/or translocation. This may suggest a general mechanism whereby the plant compensated for disrupted mineral nutrient metabolism by increasing nutrient supply to its tissues. Increased nutrient levels could potentially offset some risks posed to humans by increased Cd levels in crops, and we therefore suggest that changes in mineral nutrient levels should be included more widely in the risk assessment of potentially toxic metal contamination. Graphical abstract The Cd concentration (μg g-1 in dry matter) in the root, shoot and translocation factor (TF) of Cd from root to shoot in the carrot and lettuce, and the percentage of root Cd to the gross Cd contents (%) in carrot (C) and lettuce (D) exposed to soil Cd (0 (control), 1, 3, and 9 μg g-1) for 70 days. Values are means ± SD (n = 5).

  10. Electochemical detection of chromosome translocation

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Dimaki, Maria; Silahtaroglu, Asli

    2014-01-01

    impedance spectroscopy was selected as the sensing method on a microfabricated chip with array of 12 electrode sets. Two independent chips (Chip1 and Chip2) were used for targeting the chromosomal fragments involved in the translocation. Each chip was differentially functionalized with DNA probes matching......Cytogenetics is a study of the cell structure with a main focus on chromosomes content and their structure. Chromosome abnormalities, such as translocations may cause various genetic disorders and heametological malignancies. Chromosome translocations are structural rearrangements of two...... chromosomes that results in formation of derivative chromosomes with a mixed DNA sequence. The method currently used for their detection is Fluorescent In Situ Hybridization, which requires a use of expensive, fluorescently labeled probes that target the derivative chromosomes. We present here a double...

  11. Characterization of a t(5;8)(q31;q21) translocation in a patient with mental retardation and congenital heart disease: implications for involvement of RUNX1T1 in human brain and heart development

    DEFF Research Database (Denmark)

    Zhang, Litu; Tümer, Zeynep; Møllgård, Kjeld

    2009-01-01

    The chromosome break points of the t(8;21)(q21.3;q22.12) translocation associated with acute myeloid leukemia disrupt the RUNX1 gene (also known as AML1) and the RUNX1T1 gene (also known as CBFA2T3, MTG8 and ETO) and generate a RUNX1-RUNX1T1 fusion protein. Molecular characterization of the trans...

  12. Direct observation of DNA translocation influenced by electrically gated nanopores

    Science.gov (United States)

    Ando, Genki; Moriya, Hiroki; Tsukahira, Kenta; Yano, Satoshi; Mitsui, Toshiyuki

    2012-02-01

    One of remarkable recent developments in the solid state nanopore based DNA analysis is adding the ability to control electric potential near nanopore as a gate electrode by patterning metal in or on nanopore. In this approach, better control of DNA translocations for example, slowing down the translocation speed might be expected. We have fabricated insulator-metal-insulator nanopores of rather large 100 nm pore in diameter. The 100 nm diameter pores allow us to observe the translocation of lambda-DNA molecules directly by means of fluorescence microscopy without heavy clogging of the DNA molecules into the pores. By controlling ?gate voltage? on metal relative to the cis and trans voltages, the translocation rates of DNA are able to change. Interestingly, applying pulse voltage to the gate metal near 100 ms to reverse the direction of the electric field near the cis side of nanopore reverses the direction of the DNA translocation instantaneously. This in fact provides us a new way to repeat translocation of the same DNA molecule. Furthermore, repeating the pulse tends to clear off the clogged DNA molecules in nanopore. We will present more details of these phenomena caused by the gate voltages.

  13. Slowing DNA Translocation in a Nanofluidic Field-Effect Transistor.

    Science.gov (United States)

    Liu, Yifan; Yobas, Levent

    2016-04-26

    Here, we present an experimental demonstration of slowing DNA translocation across a nanochannel by modulating the channel surface charge through an externally applied gate bias. The experiments were performed on a nanofluidic field-effect transistor, which is a monolithic integrated platform featuring a 50 nm-diameter in-plane alumina nanocapillary whose entire length is surrounded by a gate electrode. The field-effect transistor behavior was validated on the gating of ionic conductance and protein transport. The gating of DNA translocation was subsequently studied by measuring discrete current dips associated with single λ-DNA translocation events under a source-to-drain bias of 1 V. The translocation speeds under various gate bias conditions were extracted by fitting event histograms of the measured translocation time to the first passage time distributions obtained from a simple 1D biased diffusion model. A positive gate bias was observed to slow the translocation of single λ-DNA chains markedly; the translocation speed was reduced by an order of magnitude from 18.4 mm/s obtained under a floating gate down to 1.33 mm/s under a positive gate bias of 9 V. Therefore, a dynamic and flexible regulation of the DNA translocation speed, which is vital for single-molecule sequencing, can be achieved on this device by simply tuning the gate bias. The device is realized in a conventional semiconductor microfabrication process without the requirement of advanced lithography, and can be potentially further developed into a compact electronic single-molecule sequencer.

  14. Home range and movements of male translocated problem tigers in Sumatra

    OpenAIRE

    Dolly Priatna; Yanto Santosa; Lilik B. Prasetyo; Agus P. Kartono

    2012-01-01

    The ranging behaviour of translocated problem tigers is poorly understood. The demand for releasing problem tigers back to the wild increases following the increasing the number of problem tigers that needs to be rescued in Sumatra in the last decade. In this study we estimate the home range size and obtain information on daily range of four translocated problem tigers, as well as discussing some potential factors determining the size of home range and their movement. We translocated four ad...

  15. Oxidative stress in sickle cell disease; pathophysiology and potential implications for disease management.

    Science.gov (United States)

    Nur, Erfan; Biemond, Bart J; Otten, Hans-Martin; Brandjes, Dees P; Schnog, John-John B

    2011-06-01

    Sickle cell disease (SCD) is a hemoglobinopathy characterized by hemolytic anemia, increased susceptibility to infections and vaso-occlusion leading to a reduced quality of life and life expectancy. Oxidative stress is an important feature of SCD and plays a significant role in the pathophysiology of hemolysis, vaso-occlusion and ensuing organ damage in sickle cell patients. Reactive oxygen species (ROS) and the (end-)products of their oxidative reactions are potential markers of disease severity and could be targets for antioxidant therapies. This review will summarize the role of ROS in SCD and their potential implication for SCD management. Copyright © 2011 Wiley-Liss, Inc.

  16. Efficient induction of Wheat-agropyron cristatum 6P translocation lines and GISH detection.

    Directory of Open Access Journals (Sweden)

    Liqiang Song

    Full Text Available The narrow genetic background restricts wheat yield and quality improvement. The wild relatives of wheat are the huge gene pools for wheat improvement and can broaden its genetic basis. Production of wheat-alien translocation lines can transfer alien genes to wheat. So it is important to develop an efficient method to induce wheat-alien chromosome translocation. Agropyroncristatum (P genome carries many potential genes beneficial to disease resistance, stress tolerance and high yield. Chromosome 6P possesses the desirable genes exhibiting good agronomic traits, such as high grain number per spike, powdery mildew resistance and stress tolerance. In this study, the wheat-A. cristatum disomic addition was used as bridge material to produce wheat-A. cristatum translocation lines induced by (60Co-γirradiation. The results of genomic in situ hybridization showed that 216 plants contained alien chromosome translocation among 571 self-pollinated progenies. The frequency of translocation was 37.83%, much higher than previous reports. Moreover, various alien translocation types were identified. The analysis of M2 showed that 62.5% of intergeneric translocation lines grew normally without losing the translocated chromosomes. The paper reported a high efficient technical method for inducing alien translocation between wheat and Agropyroncristatum. Additionally, these translocation lines will be valuable for not only basic research on genetic balance, interaction and expression of different chromosome segments of wheat and alien species, but also wheat breeding programs to utilize superior agronomic traits and good compensation effect from alien chromosomes.

  17. Free energy evaluation in polymer translocation via Jarzynski equality

    Energy Technology Data Exchange (ETDEWEB)

    Mondaini, Felipe, E-mail: fmondaini@if.ufrj.br [Centro Federal de Educação Tecnológica Celso Suckow da Fonseca, Petrópolis, 25.620-003, RJ (Brazil); Moriconi, L., E-mail: moriconi@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970, Rio de Janeiro, RJ (Brazil)

    2014-05-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations, which provide free energy estimates for unbiased three-dimensional polymer translocation. We employ the Jarzynski equality in its rigorous setting, to compute the variation of the free energy in single monomer translocation events. In our three-dimensional Langevin simulations, the excluded-volume and van der Waals interactions between beads (monomers and membrane atoms) are modeled through a repulsive Lennard-Jones (LJ) potential and consecutive monomers are subject to the Finite-Extension Nonlinear Elastic (FENE) potential. Analysing data for polymers with different lengths, the free energy profile is noted to have interesting finite-size scaling properties.

  18. Translocation of a Polymer Chain across a Nanopore: A Brownian Dynamics Simulation Study

    Science.gov (United States)

    Tian, Pu; Smith, Grant D.

    2003-01-01

    We carried out Brownian dynamics simulation studies of the translocation of single polymer chains across a nanosized pore under the driving of an applied field (chemical potential gradient). The translocation process can be either dominated by the entropic barrier resulted from restricted motion of flexible polymer chains or by applied forces (or chemical gradient across the wall), we focused on the latter case in our studies. Calculation of radius of gyrations at the two opposite sides of the wall shows that the polymer chains are not in equilibrium during the translocation process. Despite this fact, our results show that the one-dimensional diffusion and the nucleation model provide an excellent description of the dependence of average translocation time on the chemical potential gradients, the polymer chain length and the solvent viscosity. In good agreement with experimental results and theoretical predictions, the translocation time distribution of our simple model shows strong non-Gaussian characteristics. It is observed that even for this simple tubelike pore geometry, more than one peak of translocation time distribution can be generated for proper pore diameter and applied field strengths. Both repulsive Weeks-Chandler-Anderson and attractive Lennard-Jones polymer-nanopore interaction were studied, attraction facilitates the translocation process by shortening the total translocation time and dramatically improve the capturing of polymer chain. The width of the translocation time distribution was found to decrease with increasing temperature, increasing field strength, and decreasing pore diameter.

  19. Mechanism of ROS scavenging and antioxidant signalling by redox metallic and fullerene nanomaterials: Potential implications in ROS associated degenerative disorders.

    Science.gov (United States)

    Akhtar, Mohd Javed; Ahamed, Maqusood; Alhadlaq, Hisham A; Alshamsan, Aws

    2017-04-01

    The balance between oxidation and anti-oxidation is believed to be critical in maintaining healthy biological systems. However, our endogenous antioxidant defense systems are incomplete without exogenous antioxidants and, therefore, there is a continuous demand for exogenous antioxidants to prevent stress and ageing associated disorders. Nanotechnology has yielded enormous variety of nanomaterials (NMs) of which metallic and carbonic (mainly fullerenes) NMs, with redox property, have been found to be strong scavengers of ROS and antioxidants in preclinical in vitro and in vivo models. Redox activity of metal based NMs and membrane translocation time of fullerene NMs seem to be the major determinants in ROS scavenging potential exhibited by these NMs. A comprehensive knowledge about the effects of ROS scavenging NMs in cellular antioxidant signalling is largely lacking. This review compiles the mechanisms of ROS scavenging as well as antioxidant signalling of the aforementioned metallic and fullerene NMs. Direct interaction between NMs and proteins does greatly affect the corona/adsorption formation dynamics but such interaction does not provide the explanation behind diverse biological outcomes induced by NMs. Indirect interaction, however, that could occur via NMs uptake and dissolution, NMs ROS induction and ROS scavenging property, and NMs membrane translocation time seem to work as a central mode of interaction. The usage of potential antioxidant NMs in biological systems would greatly impact the field of nanomedicine. ROS scavenging NMs hold great promise in the future treatment of ROS related degenerative disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. A Biological Security Motivation System for Potential Threats: Are There Implications for Policy-Making?

    Directory of Open Access Journals (Sweden)

    Erik Z Woody

    2013-09-01

    Full Text Available Research indicates that there is a specially adapted, hard-wired brain circuit, the security motivation system, which evolved to manage potential threats, such as the possibility of contamination or predation. The existence of this system may have important implications for policy-making related to security. The system is sensitive to partial, uncertain cues of potential danger, detection of which activates a persistent, potent motivational state of wariness or anxiety. This state motivates behaviours to probe the potential danger, such as checking, and to correct for it, such as washing. Engagement in these behaviours serves as the terminating feedback for the activation of the system. Because security motivation theory makes predictions about what kinds of stimuli activate security motivation and what conditions terminate it, the theory may have applications both in understanding how policy-makers can best influence others, such as the public, and also in understanding the behavior of policy-makers themselves.

  1. Recents declines in potential evapotranspiration over South Africa: potential causes and implications for maize yield and irrigation demand

    Science.gov (United States)

    Estes, L. D.; Caylor, K. K.; Chaney, N.; Herrera-Estrada, J. E.; Sheffield, J.; Wood, E. F.

    2014-12-01

    Recent work has identified a 31-year (1979-2010) decline in potential evapotranspiration (PET) during the maize growing season in South Africa, the world's 9th largest producer of that crop. Using a newly-developed, bias-corrected meteorological forcing dataset, we apply an attribution analysis to identify the relative role of four key physical drivers (temperature, net radiation, vapor pressure, and windspeed) in reducing atmospheric demand for water. We conduct a statistical analysis to correlate changes in these four key drivers to potential causal mechanisms, including atmospheric aerosol concentration and changes in the extent of irrigated cropland, which we identify using a novel, high accuracy landcover dataset. Finally, we use the DSSAT maize model, together with counter-factual climate scenarios, to investigate the implications of the PET decline on maize yields and maize irrigation demand. This study illustrates how improved meteorological data, better landcover maps, and crop simulation can be combined to 1) improve understanding of the linkages between the land surface and atmosphere, and 2) help inform crop and irrigation management under changing climates.

  2. Proton transfer is rate-limiting for translocation of precursor proteins by the Escherichia coli translocase

    NARCIS (Netherlands)

    Driessen, Arnold J.M.; Wickner, William

    1991-01-01

    The protonmotive force stimulates translocation in vivo, in crude in vitro reactions, and in a purified, reconstituted reaction. Translocation activity is a function of the pH at the inner face of the membrane. Both the transmembrane pH gradient and the transmembrane electrical potential stimulate

  3. [The birth of nanobiotechnologies: new nanomaterials, potential uses, toxic effects and implications for public health].

    Science.gov (United States)

    Petrinca, Anna Rita; Pietroiusti, Antonio; Argentin, Gabriella; Cicchetti, Rosadele; Donia, Domenica; Gabrieli, Rosanna; Vignoli, Isabella; Magrini, Andrea; Divizia, Maurizio

    2009-01-01

    Nanotechnologies hold considerable promise of advances in many sectors especially the biomedical field, since the materials used are of the appropriate dimensions to interact with important biological matter such as proteins, DNA and viruses. In this field the use of nanotechnologies will probably be second in importance only to biotechnologies. However many characteristics of nanomaterials that make them so promising from a technological point of view may also lead to negative effects on the environment and human health. It is important therefore that the environmental and work-related exposure effects to these materials be evaluated. In this article the potential uses, toxic effects and public health implications of nanobiotechnologies are discussed.

  4. Markovian description of unbiased polymer translocation

    Energy Technology Data Exchange (ETDEWEB)

    Mondaini, Felipe [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970 Rio de Janeiro, RJ (Brazil); Centro Federal de Educação Tecnológica Celso Suckow da Fonseca, UnED Angra dos Reis, Angra dos Reis, 23953-030, RJ (Brazil); Moriconi, L., E-mail: moriconi@if.ufrj.br [Instituto de Física, Universidade Federal do Rio de Janeiro, C.P. 68528, 21945-970 Rio de Janeiro, RJ (Brazil)

    2012-10-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations which provide compelling evidence in favor of a general Markovian framework for unbiased three-dimensional polymer translocation. Our statistical analysis consists of careful evaluations of (i) two-point correlation functions of the translocation coordinate and (ii) the empirical probabilities of complete polymer translocation (taken as a function of the initial number of monomers on a given side of the membrane). We find good agreement with predictions derived from the Markov chain approach recently addressed in the literature by the present authors. -- Highlights: ► We investigate unbiased polymer translocation through membrane pores. ► Large statistical ensembles have been produced with the help of cloud computing resources. ► We evaluate the two-point correlation function of the translocation coordinate. ► We evaluate empirical probabilities for complete polymer translocation. ► Unbiased polymer translocation is described as a Markov stochastic process.

  5. Markovian description of unbiased polymer translocation

    International Nuclear Information System (INIS)

    Mondaini, Felipe; Moriconi, L.

    2012-01-01

    We perform, with the help of cloud computing resources, extensive Langevin simulations which provide compelling evidence in favor of a general Markovian framework for unbiased three-dimensional polymer translocation. Our statistical analysis consists of careful evaluations of (i) two-point correlation functions of the translocation coordinate and (ii) the empirical probabilities of complete polymer translocation (taken as a function of the initial number of monomers on a given side of the membrane). We find good agreement with predictions derived from the Markov chain approach recently addressed in the literature by the present authors. -- Highlights: ► We investigate unbiased polymer translocation through membrane pores. ► Large statistical ensembles have been produced with the help of cloud computing resources. ► We evaluate the two-point correlation function of the translocation coordinate. ► We evaluate empirical probabilities for complete polymer translocation. ► Unbiased polymer translocation is described as a Markov stochastic process.

  6. The human minisatellite consensus at breakpoints of oncogene translocations

    Energy Technology Data Exchange (ETDEWEB)

    Krowczynska, A.; Krontiris, T.G. (New England Medical Center Hospitals, Boston, MA (United States) Tufts Univ. School of Medicine, Boston, MA (United States)); Rudders, R.A. (New England Medical Center Hospitals, Boston, MA (United States))

    1990-03-11

    A reexamination of human minisatellite (hypervariable) regions following the cloning and sequencing of the new minisatellite, VTR1. 1, revealed that many of these structures possessed a strongly conserved copy of the chi-like octamer, GC(A/T)GG(A/T)GG. In oncogene translocations apparently created by aberrant VDJ recombinase activity, this VTR octamer was often found within a few bases of the breakpoint. Three bcl2 rearrangements which occurred within 2 bp of one another were located precisely adjacent to this consensus; it defined the 5{prime} border of that oncogene's major breakpoint cluster. Several c-myc translocations also occurred within 2 bp of this sequence. While the appearance of a chi-like element in polymorphic minisatellite sequences is consistent with a role promoting either recombination or replication slippage, the existence of such elements at sites of somatic translocations suggests chi function in site-specific recombination, perhaps as a subsidiary recognition signal in immunoglobulin gene rearrangement. The authors discuss the implications of these observations for mechanisms by which oncogene translocations and minisatellite sequences are generated.

  7. DNA Translocation in Nanometer Thick Silicon Nanopores.

    Science.gov (United States)

    Rodríguez-Manzo, Julio A; Puster, Matthew; Nicolaï, Adrien; Meunier, Vincent; Drndić, Marija

    2015-06-23

    Solid-state nanopores are single-molecule sensors that detect changes in ionic conductance (ΔG) when individual molecules pass through them. Producing high signal-to-noise ratio for the measurement of molecular structure in applications such as DNA sequencing requires low noise and large ΔG. The latter is achieved by reducing the nanopore diameter and membrane thickness. While the minimum diameter is limited by the molecule size, the membrane thickness is constrained by material properties. We use molecular dynamics simulations to determine the theoretical thickness limit of amorphous Si membranes to be ∼1 nm, and we designed an electron-irradiation-based thinning method to reach that limit and drill nanopores in the thinned regions. Double-stranded DNA translocations through these nanopores (down to 1.4 nm in thickness and 2.5 nm in diameter) provide the intrinsic ionic conductance detection limit in Si-based nanopores. In this regime, where the access resistance is comparable to the nanopore resistance, we observe the appearance of two conductance levels during molecule translocation. Considering the overall performance of Si-based nanopores, our work highlights their potential as a leading material for sequencing applications.

  8. Another reptile translocation to a national park

    Directory of Open Access Journals (Sweden)

    W.R. Branch

    1990-10-01

    Full Text Available On 4 May 1988 a sub-adult (50 mm snout-vent length, 42 mm tail Jones' girdled lizard Cordylus tropidosternum jonesi was collected in a pile of wood being off-loaded at the new restcamp in the Karoo National Park, Beaufort West. The wood had been transported by lorry from the Kruger National Park. The specimen is deposited in the herpetological collection of the Port Elizabeth Museum (PEM R 4584. Jones' girdled lizard is a small, arboreal cordylid that shelters under tree bark and in hollow logs. It is common and widely-distributed in the Kruger National Park (Pienaar, Haacke & Jacobsen 1983, The Reptiles of the Kruger National Park, 3rd edition. Pretoria: National Parks Board and adjacent lowveld, being replaced in northern Zimbabwe and East Africa by the nominate race. Hewitt & Power (1913, Transactions of the Royal Society of South Africa 3: 147-176, 1913 reported a similar translocation of the species to Kimberley in association with timber brought to the diamond mining camps. One of us noted recently the ease and danger of the unwitting spread of commensal reptile species into conservation areas (Branch 1978, Koedoe 30: 165, and this is confirmed by this additional example. We recommend that should similar shipments of wood be considered essential, then they be fumigated to prevent the translocation of other alien organisms that may potentially have more dangerous consequences.

  9. Structural instability of sheath potential distribution and its possible implications for the L/H transition in tokamak plasmas

    International Nuclear Information System (INIS)

    Yoshida, Zensho; Yamada, Hiroshi.

    1988-07-01

    The Bohm equation of electrostatic potential distributions in one-dimensional plasmas has been studied for various Mach numbers and plasma potentials. Solvability and structural stability have been discussed using the Sagdeev potential. Implications of the structural stability for the L/H transitions in tokamak plasmas has been also discussed. (author)

  10. Regulatory Potential of the RNA Processing Machinery: Implications for Human Disease.

    Science.gov (United States)

    Carey, Kirstyn T; Wickramasinghe, Vihandha O

    2018-04-01

    Splicing and nuclear export of mRNA are critical steps in the gene expression pathway. While RNA processing factors can perform general, essential functions for intron removal and bulk export of mRNA, emerging evidence highlights that the core RNA splicing and export machineries also display regulatory potential. Here, we discuss recent insights into how this regulatory potential can selectively alter gene expression and regulate important biological processes. We also highlight the participation of RNA processing pathways in the cellular response to DNA damage at multiple levels. These findings have important implications for the contribution of selective mRNA processing and export to the development of human cancers and neurodegenerative disorders. Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.

  11. Sex hormones and adult hippocampal neurogenesis: Regulation, implications, and potential mechanisms.

    Science.gov (United States)

    Mahmoud, Rand; Wainwright, Steven R; Galea, Liisa A M

    2016-04-01

    Neurogenesis within the adult hippocampus is modulated by endogenous and exogenous factors. Here, we review the role of sex hormones in the regulation of adult hippocampal neurogenesis in males and females. The review is framed around the potential functional implications of sex hormone regulation of adult hippocampal neurogenesis, with a focus on cognitive function and mood regulation, which may be related to sex differences in incidence and severity of dementia and depression. We present findings from preclinical studies of endogenous fluctuations in sex hormones relating to reproductive function and ageing, and from studies of exogenous hormone manipulations. In addition, we discuss the modulating roles of sex, age, and reproductive history on the relationship between sex hormones and neurogenesis. Because sex hormones have diverse targets in the central nervous system, we overview potential mechanisms through which sex hormones may influence hippocampal neurogenesis. Lastly, we advocate for a more systematic consideration of sex and sex hormones in studying the functional implications of adult hippocampal neurogenesis. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. An Updated View of Translocator Protein (TSPO

    Directory of Open Access Journals (Sweden)

    Nunzio Denora

    2017-12-01

    Full Text Available Decades of study on the role of mitochondria in living cells have evidenced the importance of the 18 kDa mitochondrial translocator protein (TSPO, first discovered in the 1977 as an alternative binding site for the benzodiazepine diazepam in the kidneys. This protein participates in a variety of cellular functions, including cholesterol transport, steroid hormone synthesis, mitochondrial respiration, permeability transition pore opening, apoptosis, and cell proliferation. Thus, TSPO has become an extremely attractive subcellular target for the early detection of disease states that involve the overexpression of this protein and the selective mitochondrial drug delivery. This special issue was programmed with the aim of summarizing the latest findings about the role of TSPO in eukaryotic cells and as a potential subcellular target of diagnostics or therapeutics. A total of 9 papers have been accepted for publication in this issue, in particular, 2 reviews and 7 primary data manuscripts, overall describing the main advances in this field.

  13. Balanced Reciprocal Translocations Detected at Amniocentesis

    Directory of Open Access Journals (Sweden)

    Chih-Ping Chen

    2010-12-01

    Conclusion: Balanced reciprocal translocations detected at amniocentesis may be associated with fetal anomalies in cases of concomitant aneuploidy, de novo X-autosome translocation or de novo CCR. Genetic counseling of a de novo simple reciprocal translocation at amniocentesis remains difficult because approximately one-fourth of the parents opt for termination of the pregnancy, and detailed ultrasonography and array comparative genomic hybridization are helpful for parental counseling under such circumstances.

  14. Predicting potential global distributions of two Miscanthus grasses: implications for horticulture, biofuel production, and biological invasions.

    Science.gov (United States)

    Hager, Heather A; Sinasac, Sarah E; Gedalof, Ze'ev; Newman, Jonathan A

    2014-01-01

    In many regions, large proportions of the naturalized and invasive non-native floras were originally introduced deliberately by humans. Pest risk assessments are now used in many jurisdictions to regulate the importation of species and usually include an estimation of the potential distribution in the import area. Two species of Asian grass (Miscanthus sacchariflorus and M. sinensis) that were originally introduced to North America as ornamental plants have since escaped cultivation. These species and their hybrid offspring are now receiving attention for large-scale production as biofuel crops in North America and elsewhere. We evaluated their potential global climate suitability for cultivation and potential invasion using the niche model CLIMEX and evaluated the models' sensitivity to the parameter values. We then compared the sensitivity of projections of future climatically suitable area under two climate models and two emissions scenarios. The models indicate that the species have been introduced to most of the potential global climatically suitable areas in the northern but not the southern hemisphere. The more narrowly distributed species (M. sacchariflorus) is more sensitive to changes in model parameters, which could have implications for modelling species of conservation concern. Climate projections indicate likely contractions in potential range in the south, but expansions in the north, particularly in introduced areas where biomass production trials are under way. Climate sensitivity analysis shows that projections differ more between the selected climate change models than between the selected emissions scenarios. Local-scale assessments are required to overlay suitable habitat with climate projections to estimate areas of cultivation potential and invasion risk.

  15. Predicting potential global distributions of two Miscanthus grasses: implications for horticulture, biofuel production, and biological invasions.

    Directory of Open Access Journals (Sweden)

    Heather A Hager

    Full Text Available In many regions, large proportions of the naturalized and invasive non-native floras were originally introduced deliberately by humans. Pest risk assessments are now used in many jurisdictions to regulate the importation of species and usually include an estimation of the potential distribution in the import area. Two species of Asian grass (Miscanthus sacchariflorus and M. sinensis that were originally introduced to North America as ornamental plants have since escaped cultivation. These species and their hybrid offspring are now receiving attention for large-scale production as biofuel crops in North America and elsewhere. We evaluated their potential global climate suitability for cultivation and potential invasion using the niche model CLIMEX and evaluated the models' sensitivity to the parameter values. We then compared the sensitivity of projections of future climatically suitable area under two climate models and two emissions scenarios. The models indicate that the species have been introduced to most of the potential global climatically suitable areas in the northern but not the southern hemisphere. The more narrowly distributed species (M. sacchariflorus is more sensitive to changes in model parameters, which could have implications for modelling species of conservation concern. Climate projections indicate likely contractions in potential range in the south, but expansions in the north, particularly in introduced areas where biomass production trials are under way. Climate sensitivity analysis shows that projections differ more between the selected climate change models than between the selected emissions scenarios. Local-scale assessments are required to overlay suitable habitat with climate projections to estimate areas of cultivation potential and invasion risk.

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

    International Nuclear Information System (INIS)

    Sinclair, W.K.; Fry, R.J.M.

    1987-01-01

    An overview of presentations and discussions which took place at the US Department of Energy/Commission of European Communities (DOE/CEC) workshop on ''Mechanisms of Radiation Interaction with DNA: Potential Implications for Radiation Protection,'' held at San Diego, California, January 21-22, 1987, is provided. The Department has traditionally supported fundamental research on interactions of ionizing radiation with different biological systems and at all levels of biological organization. The aim of this workshop was to review the base of knowledge in the area of mechanisms of radiation action at the DNA level, and to explore ways in which this information can be applied to the development of scientifically sound concepts and procedures for use in the field of radiation protection

  17. China as an Arctic Great Power. Potential Implications for Greenland and the Danish Realm

    DEFF Research Database (Denmark)

    Nørup Sørensen, Camilla Tenna

    In late January 2018, China released its long-awaited White Paper on China’s Arctic Policy. It represents the culmination of the development of a more confident, proactive and sophisticated Chinese diplomacy in the Arctic and reflects how the Arctic has moved up the Chinese leaders’ foreign...... and security policy agenda and is assigned increasing strategic significance. The policy brief analyses China’s Arctic White Paper focusing on the potential implications for Greenland and the Danish Realm. The policy brief concludes that China’s increasing presence in the Arctic constitutes a challenge as well...... as an opportunity depending on whether Copenhagen and Nuuk are able to find stronger common ground in their approach to China in the Arctic and succeed in establishing open, respectful and constructive dialogue and cooperation on this matter....

  18. Lipid modulation of intravascular and cellular sodium handling: mechanistic insights and potential clinical implications.

    Science.gov (United States)

    Amaral, Andre C K B; Sposito, Andrei C

    2006-10-01

    Lipid metabolism can modulate structural and functional characteristics of the vascular system. Recent studies suggested that dyslipidemia may also affect the hemodynamic response to salt intake through the impairment of intravascular volume regulation and cellular sodium handling. Indeed, dyslipidemia may affect sodium homeostasis through several pathways, including defective nitric oxide and eicosanoid production, enhanced renin-angiotensin system activity and increased sympathetic response. Moreover, dyslipidemia directly affects cellular membrane viscosity and modifies membrane ion transport activity. In line with this evidence, attenuation of the above mentioned mechanisms has been demonstrated after lipid-lowering treatment. From the clinical point of view, such interaction between plasma lipids and sodium homeostasis may adversely affect the clinical presentation of diseases such as salt-sensitive hypertension, congestive heart failure, renal diseases with proteinuria or sodium retention. This review considers the interplay between plasma lipids and sodium homeostasis and its potential clinical implication.

  19. Student's corner: potential implications of registered nurse attitudes towards caring for older people.

    Science.gov (United States)

    Marshall, Lynette C

    2010-01-01

    In discussing the potential implications of the attitudes of the registered nurse towards the work of caring for older people, it was helpful to highlight why this work is important, gain some understanding of quality care and how it can be facilitated or hindered. Patient centred care is essential as there is great diversity found amongst older people. It was found that attitudes held by registered nurses and students towards older people have a direct impact on the quality of care provided. Negative attitudes and stereotyping get in the way of quality care while positive attitudes enabled quality care. In identifying the factors that influence these attitudes, registered nurses can take on a leadership role in promoting positive attitudes and challenging negative attitudes towards the care of older people with the goal of providing patient centre care.

  20. Potential implications for expansion of freeze-tolerant eucalyptus plantations on water resources in the southern United States

    Science.gov (United States)

    James M. Vose; Chelcy F. Miniat; Ge Sun; Peter V. Caldwell

    2014-01-01

    The potential expansion of freeze-tolerant (FT) Eucalyptus plantations in the United States has raised concerns about the implications for water resources. Modeling was used to examine the potential effects of expanding the distribution of FT Eucalyptus plantations in US Department of Agriculture Plant Hardiness Zones 8b and...

  1. Beat-to-beat variability of cardiac action potential duration: underlying mechanism and clinical implications.

    Science.gov (United States)

    Nánási, Péter P; Magyar, János; Varró, András; Ördög, Balázs

    2017-10-01

    Beat-to-beat variability of cardiac action potential duration (short-term variability, SV) is a common feature of various cardiac preparations, including the human heart. Although it is believed to be one of the best arrhythmia predictors, the underlying mechanisms are not fully understood at present. The magnitude of SV is basically determined by the intensity of cell-to-cell coupling in multicellular preparations and by the duration of the action potential (APD). To compensate for the APD-dependent nature of SV, the concept of relative SV (RSV) has been introduced by normalizing the changes of SV to the concomitant changes in APD. RSV is reduced by I Ca , I Kr , and I Ks while increased by I Na , suggesting that ion currents involved in the negative feedback regulation of APD tend to keep RSV at a low level. RSV is also influenced by intracellular calcium concentration and tissue redox potential. The clinical implications of APD variability is discussed in detail.

  2. Potential environmental implications of nanoscale zero-valent iron particles for environmental remediation

    Directory of Open Access Journals (Sweden)

    Min-Hee Jang

    2014-12-01

    Full Text Available Objectives Nanoscale zero-valent iron (nZVI particles are widely used in the field of various environmental contaminant remediation. Although the potential benefits of nZVI are considerable, there is a distinct need to identify any potential risks after environmental exposure. In this respect, we review recent studies on the environmental applications and implications of nZVI, highlighting research gaps and suggesting future research directions. Methods Environmental application of nZVI is briefly summarized, focusing on its unique properties. Ecotoxicity of nZVI is reviewed according to type of organism, including bacteria, terrestrial organisms, and aquatic organisms. The environmental fate and transport of nZVI are also summarized with regards to exposure scenarios. Finally, the current limitations of risk determination are thoroughly provided. Results The ecotoxicity of nZVI depends on the composition, concentration, size and surface properties of the nanoparticles and the experimental method used, including the species investigated. In addition, the environmental fate and transport of nZVI appear to be complex and depend on the exposure duration and the exposure conditions. To date, field-scale data are limited and only short-term studies using simple exposure methods have been conducted. Conclusions In this regard, the primary focus of future study should be on 1 the development of an appropriate and valid testing method of the environmental fate and ecotoxicity of reactive nanoparticles used in environmental applications and 2 assessing their potential environmental risks using in situ field scale applications.

  3. 'Underutilised' agricultural land: its definitions, potential use for future biomass production and its environmental implications

    Science.gov (United States)

    Miyake, Saori; Bargiel, Damian

    2017-04-01

    A growing bioeconomy and increased demand for biomass products on food, health, fibre, industrial products and energy require land resources for feedstock production. It has resulted in significant environmental and socio-economic challenges on a global scale. As a result, consideration of such effects of land use change (LUC) from biomass production (particularly for biofuel feedstock) has emerged as an important area of policy and research, and several potential solutions have been proposed to minimise such adverse LUC effects. One of these solutions is the use of lands that are not in production or not suitable for food crop production, such as 'marginal', 'degraded', 'abandoned' and 'surplus' agricultural lands for future biomass production. The terms referring to these lands are usually associated with the potential production of 'marginal crops', which can grow in marginal conditions (e.g. poor soil fertility, low rainfall, drought) without much water and agrochemical inputs. In our research, we referred to these lands as 'underutilised' agricultural land and attempted to define them for our case study areas located in Australia and Central and Eastern Europe (CEE). Our goal is to identify lands that can be used for future biomass production and to evaluate their environmental implications, particularly impacts related to biodiversity, water and soil at a landscape scale. The identification of these lands incorporates remote sensing and spatially explicit approaches. Our findings confirmed that there was no universal or single definition of the term 'underutilised' agricultural land as the definitions significantly vary by country and region depending not only on the biophysical environment but also political, institutional and socio-economic conditions. Moreover, our results highlighted that the environmental implications of production of biomass on 'underutilised' agricultural land for biomass production are highly controversial. Thus land use change

  4. Haloarchaeal Protein Translocation via the Twin Arginine Translocation Pathway

    Energy Technology Data Exchange (ETDEWEB)

    Pohlschroder Mechthild

    2009-02-03

    Protein transport across hydrophobic membranes that partition cellular compartments is essential in all cells. The twin arginine translocation (Tat) pathway transports proteins across the prokaryotic cytoplasmic membranes. Distinct from the universally conserved Sec pathway, which secretes unfolded proteins, the Tat machinery is unique in that it secretes proteins in a folded conformation, making it an attractive pathway for the transport and secretion of heterologously expressed proteins that are Sec-incompatible. During the past 7 years, the DOE-supported project has focused on the characterization of the diversity of bacterial and archaeal Tat substrates as well as on the characterization of the Tat pathway of a model archaeon, Haloferax volcanii, a member of the haloarchaea. We have demonstrated that H. volcanii uses this pathway to transport most of its secretome.

  5. Cloning of a balanced translocation breakpoint mapping in the DiGeorge syndrome critical region

    Energy Technology Data Exchange (ETDEWEB)

    Demczuk, S.; Zucman, J.; Desmaze, C. [Institut Curie, Paris (France)] [and others

    1994-09-01

    DiGeorge syndrome (DGS) is a developmental defect of thymus, parathyroids and heart, which is associated with microdeletions in chromosomal region 22q11.2. A detailed physical map of the region has been established and a shortest region of overlap based on deletions and unbalanced translocations giving rise to DGS has been derived. Moreover, the breakpoint of a balanced translocation borne by a DGS patient has been localized in that critical region; thereby suggesting that the translocation breakpoint interrupts the or one of the major gene(s) implicated in DGS. We have initiated a chromosome walk by establishing cosmid contigs from probes distally flanking the breakpoint. One contig covers 150 kb of genomic DNA and a second one spans 350 kb in the region and contains the balanced translocation breakpoint. Phylogenetically conserved sequences are being searched for in the vicinity of the breakpoint to be used as probes in order to isolate cDNAs.

  6. Chronic Treatment with Escitalopram but Not R-Citalopram Translocates Gαs from Lipid Raft Domains and Potentiates Adenylyl Cyclase: A 5-Hydroxytryptamine Transporter-Independent Action of This Antidepressant Compound

    Science.gov (United States)

    Zhang, Lanqiu

    2010-01-01

    Chronic antidepressant treatment has been shown to increase adenylyl cyclase activity, in part, due to translocation of Gαs from lipid rafts to a nonraft fraction of the plasma membrane where they engage in a more facile stimulation of adenylyl cyclase. This effect holds for multiple classes of antidepressants, and for serotonin uptake inhibitors, it occurs in the absence of the serotonin transporter. In the present study, we examined the change in the amount of Gαs in lipid raft and whole cell lysate after exposing C6 cells to escitalopram. The results showed that chronic (but not acute) escitalopram decreased the content of Gαs in lipid rafts, whereas there was no change in overall Gαs content. These effects were drug dose- and exposure time-dependent. Although R-citalopram has been reported to antagonize some effects of escitalopram, this compound was without effect on Gαs localization in lipid rafts, and R-citalopram did not inhibit these actions of escitalopram. Escitalopram treatment increased cAMP accumulation, and this seemed due to increased coupling between Gαs and adenylyl cyclase. Thus, escitalopram is potent, rapid and efficacious in translocating Gαs from lipid rafts, and this effect seems to occur independently of 5-hydroxytryptamine transporters. Our results suggest that, although antidepressants display distinct affinities for well identified targets (e.g., monoamine transporters), several presynaptic and postsynaptic molecules are probably modified during chronic antidepressant treatment, and these additional targets may be required for clinical efficacy of these drugs. PMID:19996298

  7. Chronic treatment with escitalopram but not R-citalopram translocates Galpha(s) from lipid raft domains and potentiates adenylyl cyclase: a 5-hydroxytryptamine transporter-independent action of this antidepressant compound.

    Science.gov (United States)

    Zhang, Lanqiu; Rasenick, Mark M

    2010-03-01

    Chronic antidepressant treatment has been shown to increase adenylyl cyclase activity, in part, due to translocation of Galpha(s) from lipid rafts to a nonraft fraction of the plasma membrane where they engage in a more facile stimulation of adenylyl cyclase. This effect holds for multiple classes of antidepressants, and for serotonin uptake inhibitors, it occurs in the absence of the serotonin transporter. In the present study, we examined the change in the amount of Galpha(s) in lipid raft and whole cell lysate after exposing C6 cells to escitalopram. The results showed that chronic (but not acute) escitalopram decreased the content of Galpha(s) in lipid rafts, whereas there was no change in overall Galpha(s) content. These effects were drug dose- and exposure time-dependent. Although R-citalopram has been reported to antagonize some effects of escitalopram, this compound was without effect on Galpha(s) localization in lipid rafts, and R-citalopram did not inhibit these actions of escitalopram. Escitalopram treatment increased cAMP accumulation, and this seemed due to increased coupling between Galpha(s) and adenylyl cyclase. Thus, escitalopram is potent, rapid and efficacious in translocating Galpha(s) from lipid rafts, and this effect seems to occur independently of 5-hydroxytryptamine transporters. Our results suggest that, although antidepressants display distinct affinities for well identified targets (e.g., monoamine transporters), several presynaptic and postsynaptic molecules are probably modified during chronic antidepressant treatment, and these additional targets may be required for clinical efficacy of these drugs.

  8. RNase A does not translocate the alpha-hemolysin pore.

    Directory of Open Access Journals (Sweden)

    Besnik Krasniqi

    Full Text Available The application of nanopore sensing utilizing the α-hemolysin pore to probe proteins at single-molecule resolution has expanded rapidly. In some studies protein translocation through the α-hemolysin has been reported. However, there is no direct evidence, as yet, that proteins can translocate the α-hemolysin pore. The biggest challenge to obtaining direct evidence is the lack of a highly sensitive assay to detect very low numbers of protein molecules. Furthermore, if an activity based assay is applied then the proteins translocating by unfolding should refold back to an active confirmation for the assay technique to work. To overcome these challenges we selected a model enzyme, ribonuclease A, that readily refolds to an active conformation even after unfolding it with denaturants. In addition we have developed a highly sensitive reverse transcription polymerase chain reaction based activity assay for ribonuclease A. Initially, ribonuclease A, a protein with a positive net charge and dimensions larger than the smallest diameter of the pore, was subjected to nanopore analysis under different experimental conditions. Surprisingly, although the protein was added to the cis chamber (grounded and a positive potential was applied, the interaction of ribonuclease A with α-hemolysin pore induced small and large blockade events in the presence and the absence of a reducing and/or denaturing agent. Upon measuring the zeta potential, it was found that the protein undergoes a charge reversal under the experimental conditions used for nanopore sensing. From the investigation of the effect of voltage on the interaction of ribonuclease A with the α-hemolysin pore, it was impossible to conclude if the events observed were translocations. However, upon testing for ribonuclease A activity on the trans chamber it was found that ribonuclease A does not translocate the α-hemolysin pore.

  9. Selective bowel decontamination results in gram-positive translocation.

    Science.gov (United States)

    Jackson, R J; Smith, S D; Rowe, M I

    1990-05-01

    Colonization by enteric gram-negative bacteria with subsequent translocation is believed to be a major mechanism for infection in the critically ill patient. Selective bowel decontamination (SBD) has been used to control gram-negative infections by eliminating these potentially pathogenic bacteria while preserving anaerobic and other less pathogenic organisms. Infection with gram-positive organisms and anaerobes in two multivisceral transplant patients during SBD led us to investigate the effect of SBD on gut colonization and translocation. Twenty-four rats received enteral polymixin E, tobramycin, amphotericin B, and parenteral cefotaxime for 7 days (PTA + CEF); 23 received parenteral cefotaxime alone (CEF), 19 received the enteral antibiotics alone (PTA), 21 controls received no antibiotics. Cecal homogenates, mesenteric lymph node (MLN), liver, and spleen were cultured. Only 8% of the PTA + CEF group had gram-negative bacteria in cecal culture vs 52% CEF, 84% PTA, and 100% in controls. Log Enterococcal colony counts were higher in the PTA + CEF group (8.0 + 0.9) vs controls (5.4 + 0.4) P less than 0.01. Translocation of Enterococcus to the MLN was significantly increased in the PTA + CEF group (67%) vs controls (0%) P less than 0.01. SBD effectively eliminates gram-negative organisms from the gut in the rat model. Overgrowth and translocation of Enterococcus suggests that infection with gram-positive organisms may be a limitation of SBD.

  10. Translocations used to generate chromosome segment duplications ...

    Indian Academy of Sciences (India)

    Supplementary figure 1. (a–i) Putative novel genes created by the breakpoints. Translocation chromosomes are shown with the translocated segment indicated in red and the untranslocated segments in black or blue. Purple arrows indicate whether the chromosome is a donor (arrow pointing up) or a recipient (arrow ...

  11. Periarrest intestinal bacterial translocation and resuscitation outcome.

    Science.gov (United States)

    Chalkias, Athanasios; Scheetz, Marc H; Gulati, Anil; Xanthos, Theodoros

    2016-02-01

    During the periarrest period, intestinal ischemia may result in barrier dysfunction and bacterial translocation, which has clear mechanistic links to inflammation and cascade stimulation, especially in patients who are treated with therapeutic hypothermia. Despite optimal management, periarrest bacterial translocation may worsen the outcome of cardiac arrest victims. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Nuclear translocation and retention of growth hormone

    DEFF Research Database (Denmark)

    Mertani, Hichem C; Raccurt, Mireille; Abbate, Aude

    2003-01-01

    We have previously demonstrated that GH is subject to rapid receptor-dependent nuclear translocation. Here, we examine the importance of ligand activation of the GH-receptor (GHR)-associated Janus kinase (JAK) 2 and receptor dimerization for hormone internalization and nuclear translocation by us...

  13. Translocations used to generate chromosome segment duplications ...

    Indian Academy of Sciences (India)

    †Dedicated to the memory of our colleague T Bhavani Prasanna. Abbreviations used: Dp, duplication; Df, deficiency; ITs, insertional translocations; LG, lineage group; OR, Oak Ridge; ORFs, open reading frames; PCR, polymerase chain reaction; QTs, quasiterminal translocations; RIP, repeat-induced point mutation.

  14. Mesenchymal Stem Cells and Metabolic Syndrome: Current Understanding and Potential Clinical Implications

    Directory of Open Access Journals (Sweden)

    Kenichi Matsushita

    2016-01-01

    Full Text Available Metabolic syndrome is an obesity-based, complicated clinical condition that has become a global epidemic problem with a high associated risk for cardiovascular disease and mortality. Dyslipidemia, hypertension, and diabetes or glucose dysmetabolism are the major factors constituting metabolic syndrome, and these factors are interrelated and share underlying pathophysiological mechanisms. Severe obesity predisposes individuals to metabolic syndrome, and recent data suggest that mesenchymal stem cells (MSCs contribute significantly to adipocyte generation by increasing the number of adipocytes. Accordingly, an increasing number of studies have examined the potential roles of MSCs in managing obesity and metabolic syndrome. However, despite the growing bank of experimental and clinical data, the efficacy and the safety of MSCs in the clinical setting are still to be optimized. It is thus hoped that ongoing and future studies can elucidate the roles of MSCs in metabolic syndrome and lead to MSC-based therapeutic options for affected patients. This review discusses current understanding of the relationship between MSCs and metabolic syndrome and its potential implications for patient management.

  15. Nonribosomal peptides and polyketides of Burkholderia: new compounds potentially implicated in biocontrol and pharmaceuticals.

    Science.gov (United States)

    Esmaeel, Qassim; Pupin, Maude; Jacques, Philippe; Leclère, Valérie

    2017-05-25

    Bacteria belonging to the genus Burkholderia live in various ecological niches and present a significant role in the environments through the excretion of a wide variety of secondary metabolites including modular nonribosomal peptides (NRPs) and polyketides (PKs). These metabolites represent a widely distributed biomedically and biocontrol important class of natural products including antibiotics, siderophores, and anticancers as well as biopesticides that are considered as a novel source that can be used to defend ecological niche from competitors and to promote plant growth. The aim of this review is to present all NRPs produced or potentially produced by strains of Burkholderia, as NRPs represent a major source of active compounds implicated in biocontrol. The review is a compilation of results from a large screening we have performed on 48 complete sequenced genomes available in NCBI to identify NRPS gene clusters, and data found in the literature mainly because some interesting compounds are produced by strains not yet sequenced. In addition to NRPs, hybrids NRPs/PKs are also included. Specific features about biosynthetic gene clusters and structures of the modular enzymes responsible for the synthesis, the biological activities, and the potential uses in agriculture and pharmaceutical of NRPs and hybrids NRPs/PKs will also be discussed.

  16. Radiation-induced bystander effect: The important part of ionizing radiation response. Potential clinical implications

    Directory of Open Access Journals (Sweden)

    Maria Wideł

    2009-08-01

    Full Text Available It has long been a central radiobiological dogma that the damaging effects of ionizing radiation, such as cell death, cytogenetic changes, apoptosis, mutagenesis, and carcinogenesis, are the results of the direct ionization of cell structures, particularly DNA, or indirect damage via water radiolysis products. However, several years ago attention turned to a third mechanism of radiation, termed the “bystander effect” or “radiation-induced bystander effect” (RIBE. This is induced by agents and signals emitted by directly irradiated cells and manifests as a lowering of survival, cytogenetic damage, apoptosis enhancement, and biochemical changes in neighboring non-irradiated cells. The bystander effect is mainly observed in in vitro experiments using very low doses of alpha particles (range; mGy, cGy, but also after conventional irradiation (X-rays, gamma rays at low as well as conventional doses. The mechanisms responsible for the bystander effect are complex and still poorly understood. It is believed that molecular signals released from irradiated cells induce different signaling ways in non-irradiated neighboring cells, leading to the observed events. The molecular signals may be transmitted through gap junction intercellular communication and through a medium transfer mechanism. The nature of these transmitted factors are diverse, and still not defi nitely established. It seems that RIBE may have important clinical implications for health risk associated with radiation exposure. Potentially, this effectmay have important implications in the creation of whole-body or localized side effects in tissues beyond the irradiation fi eld and also in low-dose radiological and radioisotope diagnostics. Factors emitted by irradiated cells may result in the risk of genetic instability, mutations, and second primary cancer induction. They might also have their own part in inducing and extending post-radiation side effects in normal tissue. The

  17. Plant selenium hyperaccumulation- Ecological effects and potential implications for selenium cycling and community structure.

    Science.gov (United States)

    Reynolds, R Jason B; Pilon-Smits, Elizabeth A H

    2018-04-25

    Selenium (Se) hyperaccumulation occurs in ~50 plant taxa native to seleniferous soils in Western USA. Hyperaccumulator tissue Se levels, 1000-15,000 mg/kg dry weight, are typically 100 times higher than surrounding vegetation. Relative to other species, hyperaccumulators also transform Se more into organic forms. We review abiotic and biotic factors influencing soil Se distribution and bioavailability, soil being the source of the Se in hyperaccumulators. Next, we summarize the fate of Se in plants, particularly hyperaccumulators. We then extensively review the impact of plant Se accumulation on ecological interactions. Finally, we discuss the potential impact of Se hyperaccumulators on local community composition and Se cycling. Selenium (hyper)accumulation offers ecological advantages: protection from herbivores and pathogens and competitive advantage over other plants. The extreme Se levels in and around hyperaccumulators create a toxic environment for Se-sensitive ecological partners, while offering a niche for Se-resistant partners. Through these dual effects, hyperaccumulators may influence species composition in their local environment, as well as Se cycling. The implied effects of Se hyperaccumulation on community assembly and local Se cycling warrant further investigations into the contribution of hyperaccumulators and general terrestrial vegetation to global Se cycling and may serve as a case study for how trace elements influence ecological processes. Furthermore, understanding ecological implications of plant Se accumulation are vital for safe implementation of biofortification and phytoremediation, technologies increasingly implemented to battle Se deficiency and toxicity. Copyright © 2018. Published by Elsevier B.V.

  18. Prevalence of Jews as subjects in genetic research: figures, explanation, and potential implications.

    Science.gov (United States)

    Carmeli, Daphna Birenbaum

    2004-09-15

    Geneticists' view of 'population isolates' as bearing special utility for research often translates into the targeting of such groups as study populations. This paper aims to outline the prevalence and structure of reference to one such group-that of the Jews-in genetic research publications. The paper uses three prevalence scores, calculated on the basis of a search of the PubMed database, conducted in September-October 2002. A systematic comparison to other population groups shows that in relation to the population size and in relation to the general bioscientific reference to this group, Jews are over-represented in human genetic literature, particularly in mutation-related contexts. This pattern is interpreted as representing geneticists' interest in Jewish communities, which are comparatively endogamous yet sizeable. It is also attributed to geneticists' access to Jewish communities, which is facilitated by the participation of Jewish scientists that alleviates ethical concerns as well. The geographical proximity of the largest Jewish communities to major research centers, and previous acquaintance with the genetic paradigm that many Jewish persons possess, further enhance this trend. The paper ends by pointing at potential extra-medical implications of this increased prevalence. Copyright 2004 Wiley-Liss, Inc.

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

    Energy Technology Data Exchange (ETDEWEB)

    1988-01-01

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

  20. L-ferritin binding to scara5: a new iron traffic pathway potentially implicated in retinopathy.

    Directory of Open Access Journals (Sweden)

    Luísa Mendes-Jorge

    Full Text Available Iron is essential in the retina because the heme-containing enzyme guanylate cyclase modulates phototransduction in rods and cones. Transferrin endocytosis is the classical pathway for obtaining iron from the blood circulation in the retina. However, the iron storage protein ferritin has been also recently proposed as an iron carrier. In this study, the presence of Scara5 and its binding to L-ferritin was investigated in the retina. Our results showed that Scara5, the specific receptor for L-ferritin, was expressed in mouse and human retinas in many cell types, including endothelial cells. Furthermore, we showed that intravenously injected ferritin crossed the blood retinal barrier through L-ferritin binding to Scara5 in endothelial cells. Thus, suggesting the existence of a new pathway for iron delivery and trafficking in the retina. In a murine model of photoreceptor degeneration, Scara5 was downregulated, pointing out this receptor as a potential player implicated in retinopathy and also as a possible therapeutic target.

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

    International Nuclear Information System (INIS)

    1988-01-01

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

  2. An integrated science-based methodology to assess potential risks and implications of engineered nanomaterials.

    Science.gov (United States)

    Tolaymat, Thabet; El Badawy, Amro; Sequeira, Reynold; Genaidy, Ash

    2015-11-15

    There is an urgent need for broad and integrated studies that address the risks of engineered nanomaterials (ENMs) along the different endpoints of the society, environment, and economy (SEE) complex adaptive system. This article presents an integrated science-based methodology to assess the potential risks of engineered nanomaterials. To achieve the study objective, two major tasks are accomplished, knowledge synthesis and algorithmic computational methodology. The knowledge synthesis task is designed to capture "what is known" and to outline the gaps in knowledge from ENMs risk perspective. The algorithmic computational methodology is geared toward the provision of decisions and an understanding of the risks of ENMs along different endpoints for the constituents of the SEE complex adaptive system. The approach presented herein allows for addressing the formidable task of assessing the implications and risks of exposure to ENMs, with the long term goal to build a decision-support system to guide key stakeholders in the SEE system towards building sustainable ENMs and nano-enabled products. Published by Elsevier B.V.

  3. Short report: secondary transmission in porcine cysticercosis: description and their potential implications for control sustainability.

    Science.gov (United States)

    Gonzalez, Armando E; López-Urbina, Teresa; Tsang, Byron Y; Gavidia, César M; Garcia, Héctor H; Silva, María E; Ramos, Daphne D; Manzanedo, Rafael; Sánchez-Hidalgo, Lelia; Gilman, Robert H; Tsang, Victor C W

    2005-09-01

    Taenia solium taeniasis/cysticercosis is one of few potentially eradicable infectious diseases and is the target of control programs in several countries. The larval stage of this zoonotic cestode invades the human brain and is responsible for most cases of adult-onset epilepsy in the world. The pig is the natural intermediate host, harboring the larvae or cysticerci. Our current understanding of the life cycle implicates humans as the only definitive host and tapeworm carrier (developing taeniasis) and thus the sole source of infective eggs that are responsible for cysticercosis in both human and pigs through oral-fecal transmission. Here we show evidence of an alternative pig-to-pig route of transmission, previously not suspected to exist. In a series of four experiments, naive sentinel pigs were exposed to pigs that had been infected orally with tapeworm segments (containing infective eggs) and moved to a clean environment. Consistently in all four experiments, at least one of the sentinel pigs became seropositive or infected with parasite cysts with much lower cyst burdens than did primarily infected animals. Second-hand transmission of Taenia solium eggs could explain the overdispersed pattern of porcine cysticercosis, with few pigs harboring heavy parasite burdens and many more harboring small numbers of parasites. This route of transmission opens new avenues for consideration with respect to control strategies.

  4. Cutaneous vasculitis in systemic lupus erythematosus patients: potential key players and implications.

    Science.gov (United States)

    Gheita, T A; Abaza, N M; Sayed, S; El-Azkalany, G S; Fishawy, H S; Eissa, A H

    2017-01-01

    Objectives The aim of the present work was to study the clinical characteristics of cutaneous vasculitis (CV) in systemic lupus erythematosus (SLE) patients and find possible potential key players in its development and implicated associations with the disease manifestations. Patients and methods Fifty adult female SLE patients underwent full history taking, thorough clinical examination and laboratory investigations. The SLE Disease Activity Index (SLEDAI) and accumulated damage using the Systemic Lupus International Collaborative Clinics/American College of Rheumatology Damage Index (SLICC/ACR DI) were assessed. Results The mean age of the patients was 29.1 ± 6.1 years and was significantly lower in those with CV ( p = 0.018). The disease duration was 4.9 ± 3.7 years. CV was present in 30% of the patients. Musculoskeletal manifestations and hypocomplementemia were present in all patients with CV. The SLEDAI and SLICC/ACR DI tended to be higher in those with CV. Complement (C3 and C4) was significantly consumed in CV patients ( p Lupus nephritis, cardiovascular manifestations and Sjögren syndrome were significantly linked to the development of CV ( p = 0.025, p = 0.023 and p lupus nephritis, musculoskeletal manifestations and Sjögren syndrome.

  5. Neuropathic Pain: Delving into the Oxidative Origin and the Possible Implication of Transient Receptor Potential Channels

    Directory of Open Access Journals (Sweden)

    Cristina Carrasco

    2018-02-01

    Full Text Available Currently, neuropathic pain is an underestimated socioeconomic health problem affecting millions of people worldwide, which incidence may increase in the next years due to chronification of several diseases, such as cancer and diabetes. Growing evidence links neuropathic pain present in several disorders [i.e., spinal cord injury (SCI, cancer, diabetes and alcoholism] to central sensitization, as a global result of mitochondrial dysfunction induced by oxidative and nitrosative stress. Additionally, inflammatory signals and the overload in intracellular calcium ion could be also implicated in this complex network that has not yet been elucidated. Recently, calcium channels namely transient receptor potential (TRP superfamily, including members of the subfamilies A (TRAP1, M (TRPM2 and 7, and V (TRPV1 and 4, have demonstrated to play a role in the nociception mediated by sensory neurons. Therefore, as neuropathic pain could be a consequence of the imbalance between reactive oxygen species and endogen antioxidants, antioxidant supplementation may be a treatment option. This kind of therapy would exert its beneficial action through antioxidant and immunoregulatory functions, optimizing mitochondrial function and even increasing the biogenesis of this vital organelle; on balance, antioxidant supplementation would improve the patient's quality of life. This review seeks to deepen on current knowledge about neuropathic pain, summarizing clinical conditions and probable causes, the relationship existing between oxidative stress, mitochondrial dysfunction and TRP channels activation, and scientific evidence related to antioxidant supplementation.

  6. Cadmium content of commercial and contaminated rice, Oryza sativa, in Thailand and potential health implications.

    Science.gov (United States)

    Zwicker, R; Promsawad, A; Zwicker, B M; Laoharojanaphand, S

    2010-03-01

    Thailand is the number one global exporter and among the top five producers of rice in the world. A significant increase in anthropogenic contamination in agricultural soils over the past few decades has lead to concerns with cadmium and its uptake in rice. The cadmium levels in Thai rice from different sources/areas were determined and used to estimate the potential health risks to consumers. The cadmium concentration in the commercial rice samples ranged from below the detection limit to 0.016 mg/kg. The cadmium concentrations in the contaminated rice samples ranged from a low of 0.007 mg/kg to a high of 0.579 mg/kg. Five of the calculated values exceed the proposed PTWI, with one value almost three times higher and two values almost double. The three highly elevated values are certainly a concern from a health standpoint. Ultimately, action is required to address the health implications resulting from the cadmium contamination in agricultural soils used for rice production in a few select areas of Thailand. Overall, this study indicates that the vast majority of rice produced, consumed and exported by Thailand is safe pertaining to cadmium content.

  7. Selecting for creativity and innovation potential: implications for practice in healthcare education.

    Science.gov (United States)

    Patterson, Fiona; Zibarras, Lara Dawn

    2017-05-01

    The ability to innovate is an important requirement in many organisations. Despite this pressing need, few selection systems in healthcare focus on identifying the potential for creativity and innovation and so this area has been vastly under-researched. As a first step towards understanding how we might select for creativity and innovation, this paper explores the use of a trait-based measure of creativity and innovation potential, and evaluates its efficacy for use in selection for healthcare education. This study uses a sample of 188 postgraduate physicians applying for education and training in UK General Practice. Participants completed two questionnaires (a trait-based measure of creativity and innovation, and a measure of the Big Five personality dimensions) and were also rated by assessors on creative problem solving measured during a selection centre. In exploring the construct validity of the trait-based measure of creativity and innovation, our research clarifies the associations between personality, and creativity and innovation. In particular, our study highlights the importance of motivation in the creativity and innovation process. Results also suggest that Openness to Experience is positively related to creativity and innovation whereas some aspects of Conscientiousness are negatively associated with creativity and innovation. Results broadly support the utility of using a trait-based measure of creativity and innovation in healthcare selection processes, although practically this may be best delivered as part of an interview process, rather than as a screening tool. Findings are discussed in relation to broader implications for placing more priority on creativity and innovation as selection criteria within healthcare education and training in future.

  8. Evaluating spatial patterns of dioxins in sediments to aid determination of potential implications for marine reptiles

    Energy Technology Data Exchange (ETDEWEB)

    Hermanussen, S.; Gaus, C. [National Research Centre for Environmental Toxicology, Brisbane (Australia); Limpus, C.J. [Queensland Environmental Protection Agency, Brisbane (Australia); Paepke, O. [ERGO Forschungsgesellschaft mbH, Hamburg (Germany); Blanshard, W. [Sea World, Gold Coast (Australia); Connell, D. [School of Public Health, Griffith Univ., Brisbane (Australia)

    2004-09-15

    Recent investigations have identified elevated concentrations of polychlorinated dibenzo-p-dioxins (dioxins) in marine sediments and wildlife of Queensland, Australia. While it has been demonstrated that the contamination is widespread and predominantly land-based, limited information exists on the pathways and fate of these compounds within the near-shore marine system. This environment supports unique and threatened species including green sea turtles (Chelonia mydas). Adult green turtles are predominantly herbivorous, feeding on seagrass and algae. Apart from initial migration to feeding grounds (at {proportional_to}10 years of age) and intermittent migrations to breeding grounds (at {proportional_to}30-50 years and thereafter), green turtles remain and feed within relatively small home ranges. Long life-span (50 years or more), near-shore feeding grounds and highly specialized food requirements render green turtles potentially vulnerable to contaminant exposure. Recent studies have shown a relationship between PCDD/F concentrations found in herbivorous marine wildlife and concentrations in sediments of their habitats. Hence, the spatial evaluation of sediment PCDD/F distribution may assist the assessment of green turtle exposure and its potential implications. The present study provides baseline information on green turtle PCDD/F concentrations in Queensland, Australia and investigates exposure pathways. In addition, spatial distribution of PCDD/Fs in sediments from known green turtle feeding regions is assessed using geographic information systems. This represents the first stage of a large scale investigation into the exposure and sensitivity of marine reptiles to dioxins and dioxin-like compounds and to evaluate whether poor health status observed in some populations may be related to contaminant exposure.

  9. 77 FR 44562 - Public Meeting: Potential Regulatory Implications of the Reduction of Lead in Drinking Water Act...

    Science.gov (United States)

    2012-07-30

    ... AGENCY 40 CFR Parts 141 and 142 Public Meeting: Potential Regulatory Implications of the Reduction of Lead in Drinking Water Act of 2011 AGENCY: Environmental Protection Agency (EPA). ACTION: Notice... discuss and solicit input from States, manufacturers, drinking water systems, other interested groups and...

  10. Short-Term Space-Use Patterns of Translocated Mojave Desert Tortoise in Southern California.

    Directory of Open Access Journals (Sweden)

    Matthew L Farnsworth

    Full Text Available Increasingly, renewable energy comprises a larger share of global energy production. Across the western United States, public lands are being developed to support renewable energy production. Where there are conflicts with threatened or endangered species, translocation can be used in an attempt to mitigate negative effects. For the threatened Mojave desert tortoise (Gopherus agassizii, we sought to compare habitat- and space-use patterns between short-distance translocated, resident, and control groups. We tested for differences in home range size based on utilization distributions and used linear mixed-effects models to compare space-use intensity, while controlling for demographic and environmental variables. In addition, we examined mean movement distances as well as home range overlap between years and for male and female tortoises in each study group. During the first active season post-translocation, home range size was greater and space-use intensity was lower for translocated tortoises than resident and control groups. These patterns were not present in the second season. In both years, there was no difference in home range size or space-use intensity between control and resident groups. Translocation typically resulted in one active season of questing followed by a second active season characterized by space-use patterns that were indistinguishable from control tortoises. Across both years, the number of times a tortoise was found in a burrow was positively related to greater space-use intensity. Minimizing the time required for translocated tortoises to exhibit patterns similar to non-translocated individuals may have strong implications for conservation by reducing exposure to adverse environmental conditions and predation. With ongoing development, our results can be used to guide future efforts aimed at understanding how translocation strategies influence patterns of animal space use.

  11. Short-Term Space-Use Patterns of Translocated Mojave Desert Tortoise in Southern California.

    Science.gov (United States)

    Farnsworth, Matthew L; Dickson, Brett G; Zachmann, Luke J; Hegeman, Ericka E; Cangelosi, Amanda R; Jackson, Thomas G; Scheib, Amanda F

    2015-01-01

    Increasingly, renewable energy comprises a larger share of global energy production. Across the western United States, public lands are being developed to support renewable energy production. Where there are conflicts with threatened or endangered species, translocation can be used in an attempt to mitigate negative effects. For the threatened Mojave desert tortoise (Gopherus agassizii), we sought to compare habitat- and space-use patterns between short-distance translocated, resident, and control groups. We tested for differences in home range size based on utilization distributions and used linear mixed-effects models to compare space-use intensity, while controlling for demographic and environmental variables. In addition, we examined mean movement distances as well as home range overlap between years and for male and female tortoises in each study group. During the first active season post-translocation, home range size was greater and space-use intensity was lower for translocated tortoises than resident and control groups. These patterns were not present in the second season. In both years, there was no difference in home range size or space-use intensity between control and resident groups. Translocation typically resulted in one active season of questing followed by a second active season characterized by space-use patterns that were indistinguishable from control tortoises. Across both years, the number of times a tortoise was found in a burrow was positively related to greater space-use intensity. Minimizing the time required for translocated tortoises to exhibit patterns similar to non-translocated individuals may have strong implications for conservation by reducing exposure to adverse environmental conditions and predation. With ongoing development, our results can be used to guide future efforts aimed at understanding how translocation strategies influence patterns of animal space use.

  12. The E Block motif is associated with Legionella pneumophila translocated substrates.

    Science.gov (United States)

    Huang, Li; Boyd, Dana; Amyot, Whitney M; Hempstead, Andrew D; Luo, Zhao-Qing; O'Connor, Tamara J; Chen, Cui; Machner, Matthias; Montminy, Timothy; Isberg, Ralph R

    2011-02-01

    Legionella pneumophila promotes intracellular growth by moving bacterial proteins across membranes via the Icm/Dot system. A strategy was devised to identify large numbers of Icm/Dot translocated proteins, and the resulting pool was used to identify common motifs that operate as recognition signals. The 3' end of the sidC gene, which encodes a known translocated substrate, was replaced with DNA encoding 200 codons from the 3' end of 442 potential substrate-encoding genes. The resulting hybrid proteins were then tested in a high throughput assay, in which translocated SidC antigen was detected by indirect immunofluorescence. Among translocated substrates, regions of 6-8 residues called E Blocks were identified that were rich in glutamates. Analysis of SidM/DrrA revealed that loss of three Glu residues, arrayed in a triangle on an α-helical surface, totally eliminated translocation of a reporter protein. Based on this result, a second strategy was employed to identify Icm/Dot substrates having carboxyl terminal glutamates. From the fusion assay and the bioinformatic queries, carboxyl terminal sequences from 49 previously unidentified proteins were shown to promote translocation into target cells. These studies indicate that by analysing subsets of translocated substrates, patterns can be found that allow predictions of important motifs recognized by Icm/Dot. © 2010 Blackwell Publishing Ltd.

  13. DNA translocation across protein channels: How does a polymer worm through a hole?

    Science.gov (United States)

    Muthukumar, M.

    2001-03-01

    Free energy barriers control the translocation of polymers through narrow channels. Based on an analogy with the classical nucleation and growth process, we have calculated the translocation time and its dependencies on the length, stiffness, and sequence of the polymer, solution conditions, and the strength of the driving electrochemical potential gradient. Our predictions will be compared with experimental results and prospects of reading polymer sequences.

  14. DNA nanopore translocation in glutamate solutions

    NARCIS (Netherlands)

    Plesa, C.; Van Loo, N.; Dekker, C.

    2015-01-01

    Nanopore experiments have traditionally been carried out with chloride-based solutions. Here we introduce silver/silver-glutamate-based electrochemistry as an alternative, and study the viscosity, conductivity, and nanopore translocation characteristics of potassium-, sodium-, and lithium-glutamate

  15. Carbon and nitrogen translocation between seagrass ramets

    NARCIS (Netherlands)

    Marbà, N.; Hemminga, M.A.; Mateo, M.A.; Duarte, C.M.; Maas, Y.E.M.; Terrados, J.; Gacia, E.

    2002-01-01

    The spatial scale and the magnitude of carbon and nitrogen translocation was examined in 5 tropical (Cymodocea serrulata, Halophila stipulacea, Halodule uninervis, Thalassodendron ciliatum, Thalassia hemprichii) and 3 temperate (Cymodocea nodosa, Posidonia oceanica, Zostera noltii) seagrass species

  16. Bioenergy costs and potentials with special attention to implications for the land system

    Science.gov (United States)

    Popp, A.; Lotze-Campen, H.; Dietrich, J.; Klein, D.; Bauer, N.; Krause, M.; Beringer, T.; Gerten, D.

    2011-12-01

    In the coming decades, an increasing competition for global land and water resources can be expected, due to rising demand for agricultural products, goals of nature conservation, and changing production conditions due to climate change. Especially biomass from cellulosic bioenergy crops, such as Miscanthus or poplar, is being proposed to play a substantial role in future energy systems if climate policy aims at stabilizing greenhouse gas (GHG) concentration at low levels. However, the potential of bioenergy for climate change mitigation remains unclear due to large uncertainties about future agricultural yield improvements, land availability for biomass plantations, and implications for the land system. In order to explore the cost-effective contribution of bioenergy to a low carbon transition with special attention to implications for the land system, we present a modeling framework with detailed biophysical and economic representation of the land and energy sector: We have linked the global dynamic vegetation and water balance model LPJmL (Bondeau et al. 2007, Rost et al. 2008), the global land and water use model MAgPIE (Lotze-Campen et al. 2008, Popp et al. 2010), and the global energy-economy-climate model ReMIND (Leimbach et al. 2009). In this modeling framework LPJmL supplies spatially explicit (0.5° resolution) agricultural yields as well as carbon and water stocks and fluxes. Based on this biophysical input MAgPIE delivers cost-optimized land use patterns (0.5° resolution), associated GHG emissions and rates of future yield increases in agricultural production. Moreover, shadow prices are calculated for irrigation water (as an indicator for water scarcity), food commodities, and bioenergy (as an indicator for changes in production costs) under different land use constraints such as forest conservation for climate change mitigation and as a contribution to biodiversity conservation. The energy-economy-climate model ReMIND generates the demand for

  17. Greater sage-grouse science (2015–17)—Synthesis and potential management implications

    Science.gov (United States)

    Hanser, Steven E.; Deibert, Patricia A.; Tull, John C.; Carr, Natasha B.; Aldridge, Cameron L.; Bargsten, Travis D.; Christiansen, Thomas J.; Coates, Peter S.; Crist, Michele R.; Doherty, Kevin E.; Ellsworth, Ethan A.; Foster, Lee J.; Herren, Vicki A.; Miller, Kevin H.; Moser, Ann; Naeve, Robin M.; Prentice, Karen L.; Remington, Thomas E.; Ricca, Mark A.; Shinneman, Douglas J.; Truex, Richard L.; Wiechman , Lief A.; Wilson, Dereck C.; Bowen, Zachary H.

    2018-02-15

    Strategy Actionable Science Plan Team, 2016).In October 2017, after a review of the 2015 Federal plans relative to State sage-grouse plans, in accordance with Secretarial Order 3353, the BLM issued a notice of intent to consider whether to amend some, all, or none of the 2015 land use plans. At that time, the BLM requested the U.S. Geological Survey (USGS) to inform this effort through the development of an annotated bibliography of sage-grouse science published since January 2015 and a report that synthesized and outlined the potential management implications of this new science. Development of the annotated bibliography resulted in the identification and summarization of 169 peer-reviewed scientific publications and reports. The USGS then convened an interagency team (hereafter referred to as the “team”) to develop this report that focuses on the primary topics of importance to the ongoing management of sage-grouse and their habitats.The team developed this report in a three-step process. First, the team identified six primary topic areas for discussion based on the members’ collective knowledge regarding sage-grouse, their habitats, and threats to either or both. Second, the team reviewed all the material in the “Annotated Bibliography of Scientific Research on Greater Sage-Grouse Published since January 2015” to identify the science that addressed the topics. Third, team members discussed the science related to each topic, evaluated the consistency of the science with existing knowledge before 2015, and summarized the potential management implications of this science. The six primary topics identified by the team were:Multiscale habitat suitability and mapping toolsDiscrete anthropogenic activitiesDiffuse activitiesFire and invasive speciesRestoration effectivenessPopulation estimation and genetics

  18. Hemi-bucket-handle tears of the meniscus: appearance on MRI and potential surgical implications

    International Nuclear Information System (INIS)

    Engstrom, Bjorn I.; Vinson, Emily N.; Helms, Clyde A.; Taylor, Dean C.; Garrett, William E.

    2012-01-01

    To describe a type of meniscus flap tear resembling a bucket-handle tear, named a ''hemi-bucket-handle'' tear; to compare its imaging features with those of a typical bucket-handle tear; and to discuss the potential therapeutic implications of distinguishing these two types of tears. Five knee MR examinations were encountered with a type of meniscus tear consisting of a flap of tissue from the undersurface of the meniscus displaced toward the intercondylar notch. A retrospective analysis of 100 MR examinations prospectively interpreted as having bucket-handle type tears yielded 10 additional cases with this type of tear. Cases of hemi-bucket-handle tears were reviewed for tear location and orientation, appearance of the superior articular surface of the meniscus, presence and location of displaced meniscal tissue, and presence of several classic signs of bucket-handle tears. A total of 15/15 tears involved the medial meniscus, had tissue displaced toward the notch, and were mainly horizontal in orientation. The superior surface was intact in 11/15 (73.3%). In 1/15 (6.7%) there was an absent-bow-tie sign; 6/15 (40%) had a double-PCL sign; 14/15 (93.3%) had a double-anterior horn sign. We describe a type of undersurface flap tear, named a hemi-bucket-handle tear, which resembles a bucket-handle tear. Surgeons at our institution feel this tear would likely not heal if repaired given its predominantly horizontal orientation, and additionally speculate the tear could be overlooked at arthroscopy. Thus, we feel it is important to distinguish this type of tear from the typical bucket-handle tear. (orig.)

  19. Laminar shear stress regulates endothelial kinin B1 receptor expression and function: potential implication in atherogenesis

    Science.gov (United States)

    Duchene, Johan; Cayla, Cécile; Vessillier, Sandrine; Scotland, Ramona; Yamashiro, Kazuo; Lecomte, Florence; Syed, Irfan; Vo, Phuong; Marrelli, Alessandra; Pitzalis, Costantino; Cipollone, Francesco; Schanstra, Joost; Bascands, Jean-Loup; Hobbs, Adrian J; Perretti, Mauro; Ahluwalia, Amrita

    2009-01-01

    OBJECTIVE The pro-inflammatory phenotype induced by low laminar shear stress (LSS) is implicated in atherogenesis. The kinin B1 receptor (B1R), known to be induced by inflammatory stimuli, exerts many pro-inflammatory effects including vasodilatation and leukocyte recruitment. We investigated whether low LSS is a stimulus for endothelial B1R expression and function. METHODS AND RESULTS Human and mouse atherosclerotic plaques expressed high level of B1R mRNA and protein. In addition, B1R expression was upregulated in the aortic arch (low LSS region) of ApoE-/- mice fed a high fat diet compared to vascular regions of high LSS and animals fed normal chow. Of interest, a greater expression of B1R was noticed in endothelial cells from regions of low LSS in aortic arch of ApoE-/- mice. B1R was also upregulated in human umbilical vein endothelial cells (HUVEC) exposed to low LSS (0-2dyn/cm2) compared to physiological LSS (6-10dyn/cm2): an effect similarly evident in murine vascular tissue perfused ex vivo. Functionally, B1R activation increased prostaglandin and CXCL5 expression in cells exposed to low, but not physiological, LSS. IL-1β and ox-LDL induced B1R expression and function in HUVECs, a response substantially enhanced under low LSS conditions and inhibited by blockade of NFκB activation. CONCLUSION Herein, we show that LSS is a major determinant of functional B1R expression in endothelium. Furthermore, whilst physiological high LSS is a powerful repressor of this inflammatory receptor, low LSS at sites of atheroma are associated with substantial upregulation, identifying this receptor as a potential therapeutic target. CONDENSED ABSTRACT Low laminar shear stress (LSS) underlies the pro-inflammatory processes in atherogenesis. Herein, we demonstrate that whilst physiological LSS represses inflammatory kinin B1 receptor (B1R) expression/function, low atherogenic LSS is associated with profound upregulation of both in atherosclerosis in both humans and animal

  20. Tolerance, bioavailability, and potential cognitive health implications of a distinct aqueous spearmint extract

    Directory of Open Access Journals (Sweden)

    Kristin M. Nieman

    2015-05-01

    Full Text Available Background: Cognitive function can decline during the aging process and significantly reduce quality of life. Although a number of interventions have been investigated for cognitive dysfunction, including antioxidants, this prominent health concern emphasizes a need to explore methods to support cognitive health later in the life span. An aqueous extract from a proprietary spearmint line has been developed which contains a number of antioxidant compounds, including rosmarinic acid, at levels that are higher than found in commercially-bred spearmint. Therefore, this pilot trial assessed the tolerance, bioavailability, and potential cognitive health implications of a proprietary spearmint extract in men and women with self-reported memory impairment. Methods: Subjects consumed 900 mg/day spearmint extract for 30 days. The sample population (N = 11 was 73% female and 27% male with a mean age of 58.7 ± 1.6 y. Tolerability parameters were assessed at baseline and end of treatment visits. Computerized cognitive function tests were completed and blood was drawn at pre- and post-dose (0.5 to 4 h timepoints during baseline and end of treatment visits. Subjective cognition was also assessed at end of treatment. Results: No serious adverse events or clinically relevant findings were observed in any tolerability parameters. Plasma vanillic, caffeic, and ferulic acid sulfates, rosmarinic acid, and methyl rosmarinic acid glucuronide were detected in plasma following acute administration of the spearmint extract. Computerized cognitive function scores improved in reasoning (P =0.023 and attention/concentration (P = 0.002 after 30 days of supplementation. After acute administration, subjects had improved attention/concentration in two tests at 2 (P = 0.042 and P = 0.025 and 4 h (P = 0.001 and P = 0.002. Conclusions: The results from this pilot trial suggest that the spearmint extract, which contains higher rosmarinic acid content relative to extracts from

  1. Unraveling the Dynamics of Ribosome Translocation

    Science.gov (United States)

    Chen, Jin; Tsai, Albert; O’Leary, Seán E.; Petrov, Alexey; Puglisi, Joseph D.

    2013-01-01

    Translocation is one of the key events in translation, requiring large-scale conformational changes in the ribosome, movements of two transfer RNAs (tRNAs) across a distance of more than 20 Å, and the coupled movement of the messenger RNA (mRNA) by one codon, completing one cycle of peptide-chain elongation. Translocation is catalyzed by elongation factor G (EF-G in bacteria), which hydrolyzes GTP in the process. However, how the conformational rearrangements of the ribosome actually drive the movements of the tRNAs and how EF-G GTP hydrolysis plays a role in this process are still unclear. Fluorescence methods, both single-molecule and bulk, have provided a dynamic view of translocation, allowing us to follow the different conformational changes of the ribosome in real-time. The application of electron microscopy has revealed new conformational intermediates during translocation and important structural rearrangements in the ribosome that drive tRNA movement, while computational approaches have added quantitative views of the translational pathway. These recent advances shed light on the process of translocation, providing insight on how to resolve the different descriptions of translocation in the current literature. PMID:23142574

  2. Production and Identification of Wheat-Agropyron cristatum 2P Translocation Lines

    Science.gov (United States)

    Li, Huanhuan; Lv, Mingjie; Song, Liqiang; Zhang, Jinpeng; Gao, Ainong; Li, Lihui; Liu, Weihua

    2016-01-01

    Agropyron cristatum (L.) Gaertn. (2n = 28, PPPP), a wild relative of common wheat, possesses many potentially valuable traits that can be transferred to common wheat through breeding programs. The wheat-A. cristatum disomic addition and translocation lines can be used as bridge materials to introduce alien chromosomal segments to wheat. Wheat-A. cristatum 2P disomic addition line II-9-3 was highly resistant to powdery mildew and leaf rust, which was reported in our previous study. However, some translocation lines induced from II-9-3 have not been reported. In this study, some translocation lines were induced from II-9-3 by 60Co-γ irradiation and gametocidal chromosome 2C and then identified by cytological methods. Forty-nine wheat-A. cristatum translocation lines were obtained and various translcoation types were identified by GISH (genomic in situ hybridization), such as whole-arm, segmental and intercalary translocations. Dual-color FISH (fluorescent in situ hybridization) was applied to identify the wheat chromosomes involved in the translocations, and the results showed that A. cristatum 2P chromosome segments were translocated to the different wheat chromosomes, including 1A, 2A, 3A, 4A, 5A, 6A, 7A, 3B, 5B, 7B, 1D, 4D and 6D. Many different types of wheat-A. cristatum alien translocation lines would be valuable for not only identifying and cloning A. cristatum 2P-related genes and understanding the genetics and breeding effects of the translocation between A. cristatum chromosome 2P and wheat chromosomes, but also providing new germplasm resources for the wheat genetic improvement. PMID:26731742

  3. Olive Oil-related Anti-inflammatory Effects on Atherosclerosis: Potential Clinical Implications.

    Science.gov (United States)

    Wongwarawipat, Tanakal; Papageorgiou, Nikolaos; Bertsias, Dimitrios; Siasos, Gerasimos; Tousoulis, Dimitris

    2018-01-01

    Atherosclerosis is characterized by a chronic low-grade inflammatory process which can result in atherothrombosis and a number of cardiovascular diseases (CVD). It is believed to be caused by multiple processes that involve inflammation and immunity. Mediterranean Diet (MedD) has been discovered to possess anti-inflammatory properties and associated with a reduction in the CVD risk and mortality. Its main component, extra-virgin olive oil (EVOO), is believed to be largely responsible for these effects and therefore, has been investigated in various studies. The present review article aims to summarize the available literature on the antiinflammatory and cardio-protective effects of EVOO. A search based on the key concepts "olive oil", "atherosclerosis", "inflammation" and "cardiovascular disease" was performed to retrieve relevant studies and articles on the association between the consumption of EVOO and the levels of inflammatory biomarkers as well as CVD incidence and mortality from online databases; Pubmed, Embase and Cochrane Library. Consumption of EVOO is associated with a reduction in inflammatory biomarkers and molecules implicated in atherosclerosis as well as CVD incidence and mortality as well as other complications such as heart failure and atrial fibrillation. Moreover, these anti-inflammatory and cardioprotective effects of EVOO are mostly attributable to its high content of polyphenol molecules. Currently available evidence supports the anti-inflammatory and cardio-protective roles of EVOO. However, there is limited amount of available randomized controlled trials especially lacking those investigating the use of EVOO as secondary prevention, heterogeneity of study design, limited generalization to wide population groups, and inability to determine the minimum intake of EVOO required to clinically achieve the anti-inflammatory and cardioprotective effects. Therefore, more highquality randomized controlled trials still need to be carried out to

  4. Molecular studies of free and translocation trisomy

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Lefort, G. [Univ. of Zuerich (Switzerland)] [and others

    1994-09-01

    Twenty cases of trisomy 13 were examined with molecular markers to determine the origin of the extra chromosome. Six cases had translocation trisomy: two de novo rob(13q;14q), one paternally derived rob(13q;14q), two de novo t(13q;13q), and one mosaic de novo t(13q;14q), one paternally derived rob(13q;14q), two de novo t(13q;13q), and one mosaic de novo t(13q;13q)r(13). Eighteen of nineteen informative patients were consistant with a maternal origin of the extra chromosome. Lack of a third allele at any locus in any of the three t(13q;13q) cases indicate that all were most likely isochromosomes of post-meiotic origin. In addition, two free trisomy cases were compatible with a somatic origin. Two mosaic free trisomy-13 cases, however, were both consistent with a maternal meiotic origin. The patient with a paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13;14) carrier and most trisomies are maternal in origin, this result should not be surprising; however it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. One balanced (non-trisomic) case with a non-mosaic 45,-13,-13,+t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologs, as has been found for all homologous Robertsonian translocations so far investigated. It is therefore also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. We cannot therefore infer anything about the origin of the chromosomes 13 and 14 involved in the two cases with de novo t(13q;14q) plus a maternally derived trisomy 13.

  5. Response to the call by DCMS for views on the potential implications of Brexit for Data Protection stakeholders: Brexit: Potential Implications for Digital and ‘Fintech’ Industries

    OpenAIRE

    Mc Cullagh, Karen

    2016-01-01

    Following the outcome of the historic ‘Brexit’ referendum on 23rd June 2016 in which a majority of eligible voters in the UK voted to ‘Leave,’[1] the United Kingdom is potentially on course to leave the European Union,[2] but to ensure continued economic success it will seek to maintain a favourable trading relationship with the EU. This article identifies and critically evaluates the various types of trade deals the UK might negotiate upon exit with a particular focus on trade in services si...

  6. Nanowire-nanopore transistor sensor for DNA detection during translocation

    Science.gov (United States)

    Xie, Ping; Xiong, Qihua; Fang, Ying; Qing, Quan; Lieber, Charles

    2011-03-01

    Nanopore sequencing, as a promising low cost, high throughput sequencing technique, has been proposed more than a decade ago. Due to the incompatibility between small ionic current signal and fast translocation speed and the technical difficulties on large scale integration of nanopore for direct ionic current sequencing, alternative methods rely on integrated DNA sensors have been proposed, such as using capacitive coupling or tunnelling current etc. But none of them have been experimentally demonstrated yet. Here we show that for the first time an amplified sensor signal has been experimentally recorded from a nanowire-nanopore field effect transistor sensor during DNA translocation. Independent multi-channel recording was also demonstrated for the first time. Our results suggest that the signal is from highly localized potential change caused by DNA translocation in none-balanced buffer condition. Given this method may produce larger signal for smaller nanopores, we hope our experiment can be a starting point for a new generation of nanopore sequencing devices with larger signal, higher bandwidth and large-scale multiplexing capability and finally realize the ultimate goal of low cost high throughput sequencing.

  7. Counting and dynamic studies of the small unilamellar phospholipid vesicle translocation with single conical glass nanopores.

    Science.gov (United States)

    Chen, Lizhen; He, Haili; Jin, Yongdong

    2015-01-06

    Phospholipid vesicles are ubiquitous cellular organelles that perform vital functions including materials transport and information transmission and have found promising biomedical applications. Although the transmembrane translocation (via nanopores) of phospholipid vesicles, especially small unilamellar phospholipid vesicles (SUVs), is recognized to be very important for these processes and applications, the details and dynamics remain not very clear. Herein, we use single conical glass nanopores as a model platform to systematically investigate the translocation dynamics of SUVs (∼50-60 nm in diameter) through small nanopores with orifice diameters ranging from ∼14 to 72 nm. Dynamic translocation of individual SUVs one by one through the nanopores was clearly observed and was analyzed by the occurrence of periodic oscillation in ionic current blockage signal under a negatively applied voltage. Translocation behaviors of the SUVs, in terms of magnitude and duration of ionic current blockage signal, varied and can be modulated by changing nanopore size, solution pH, vesicle concentration, applied voltage, and inner surface charge properties of the nanopores. The translocation rate of the SUVs through an ∼72 nm nanopore is typically on a time scale of a few seconds (per SUV translocation event) and found nonlinearly proportional to the concentration of the SUVs. Moreover, the electrophoretic force has been verified as a main force to drive the SUVs through the nanopore since there is a nearly linear relationship between the current blockage frequency of SUVs translocation and the applied bias potentials ranging from -0.6 to -1 V. The findings provide fundamental insights into the translocation and interactions of SUVs with nanopores, and the reported nanopore platform may find potential useful bioapplications in single-cell and single-vesicle studies.

  8. The relationship between mothers' child abuse potential and current mental health symptoms: implications for screening and referral.

    Science.gov (United States)

    Rinehart, Deborah J; Becker, Marion A; Buckley, Pamela R; Dailey, Kathy; Reichardt, Charles S; Graeber, Carla; VanDeMark, Nancy R; Brown, Ellen

    2005-01-01

    This analysis examined data from mothers at 2 of the 9 sites participating in Substance Abuse and Mental Health Services Administration's (SAMHSA's) national Women Co-occurring Disorders and Violence Study (WCDVS). According to previous literature, it was hypothesized that women in the WCDVS would be at high risk of perpetrating child abuse. This research examined mothers' potential for physical child abuse and assessed the association between child abuse potential, current mental health symptoms, alcohol and drug use severity, and trauma. Results revealed that participants had significant potential for child abuse. Hierarchical regression analyses revealed that current mental health symptoms were the strongest predictor of mothers' scores on the Child Abuse Potential (CAP) Inventory. This study highlights the important relationships between commonly used instruments across the mental health, substance, and child welfare fields and the potential dual use of these instruments. Implications for policy and practice are discussed.

  9. The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22(q24.13;q11.21 in a young girl with dysgerminoma

    Directory of Open Access Journals (Sweden)

    Fiorio Patrizia

    2009-07-01

    Full Text Available Abstract Background RNF139/TRC8 is a potential tumor suppressor gene with similarity to PTCH, a tumor suppressor implicated in basal cell carcinomas and glioblastomas. TRC8 has the potential to act in a novel regulatory relationship linking the cholesterol/lipid biosynthetic pathway with cellular growth control and has been identified in families with hereditary renal (RCC and thyroid cancers. Haploinsufficiency of TRC8 may facilitate development of clear cell-RCC in association with VHL mutations, and may increase risk for other tumor types. We report a paternally inherited balanced translocation t(8;22 in a proposita with dysgerminoma. Methods The translocation was characterized by FISH and the breakpoints cloned, sequenced, and compared. DNA isolated from normal and tumor cells was checked for abnormalities by array-CGH. Expression of genes TRC8 and TSN was tested both on dysgerminoma and in the proposita and her father. Results The breakpoints of the translocation are located within the LCR-B low copy repeat on chromosome 22q11.21, containing the palindromic AT-rich repeat (PATRR involved in recurrent and non-recurrent translocations, and in an AT-rich sequence inside intron 1 of the TRC8 tumor-suppressor gene at 8q24.13. TRC8 was strongly underexpressed in the dysgerminoma. Translin is underexpressed in the dysgerminoma compared to normal ovary. TRC8 is a target of Translin (TSN, a posttranscriptional regulator of genes transcribed by the transcription factor CREM-tau in postmeiotic male germ cells. Conclusion A role for TRC8 in dysgerminoma may relate to its interaction with Translin. We propose a model in which one copy of TRC8 is disrupted by a palindrome-mediated translocation followed by complete loss of expression through suppression, possibly mediated by miRNA.

  10. Translocation pathways for inhaled asbestos fibers

    Directory of Open Access Journals (Sweden)

    Mantegazza F

    2008-01-01

    Full Text Available Abstract We discuss the translocation of inhaled asbestos fibers based on pulmonary and pleuro-pulmonary interstitial fluid dynamics. Fibers can pass the alveolar barrier and reach the lung interstitium via the paracellular route down a mass water flow due to combined osmotic (active Na+ absorption and hydraulic (interstitial pressure is subatmospheric pressure gradient. Fibers can be dragged from the lung interstitium by pulmonary lymph flow (primary translocation wherefrom they can reach the blood stream and subsequently distribute to the whole body (secondary translocation. Primary translocation across the visceral pleura and towards pulmonary capillaries may also occur if the asbestos-induced lung inflammation increases pulmonary interstitial pressure so as to reverse the trans-mesothelial and trans-endothelial pressure gradients. Secondary translocation to the pleural space may occur via the physiological route of pleural fluid formation across the parietal pleura; fibers accumulation in parietal pleura stomata (black spots reflects the role of parietal lymphatics in draining pleural fluid. Asbestos fibers are found in all organs of subjects either occupationally exposed or not exposed to asbestos. Fibers concentration correlates with specific conditions of interstitial fluid dynamics, in line with the notion that in all organs microvascular filtration occurs from capillaries to the extravascular spaces. Concentration is high in the kidney (reflecting high perfusion pressure and flow and in the liver (reflecting high microvascular permeability while it is relatively low in the brain (due to low permeability of blood-brain barrier. Ultrafine fibers (length

  11. Volunteering for College? Potential Implications of Financial Aid Tax Credits Rewarding Community Service

    Science.gov (United States)

    Wells, Ryan S.; Lynch, Cassie M.

    2014-01-01

    President Obama has proposed a financial aid policy whereby students who complete 100 hours of community service would receive a tax credit of US$4,000 for college. After lawmakers cut this proposal from previous legislation, the administration was tasked with studying the feasibility of implementation. However, the implications of the policy for…

  12. Indoor and outdoor airborne particles : an in vitro study on mutagenic potential and toxicological implications

    NARCIS (Netherlands)

    Houdt, van J.J.

    1988-01-01

    Introduction

    Air pollution components are present as gases and as particulate matter. As particle deposition takes place in various parts of the respiratory system particulate matter may have other toxicological implications than gaseous pollutants, which all may

  13. Effects of nucleotides and nucleotide analogue inhibitors of HIV-1 reverse transcriptase in a ratchet model of polymerase translocation.

    Science.gov (United States)

    Götte, Matthias

    2006-01-01

    A single cycle of nucleotide incorporation by the reverse transcriptase of the human immunodeficiency virus type 1 (HIV-1 RT) involves the initial binding of an incoming nucleotide, a conformational change that traps the substrate, the formation of a new phosphodiester bond, the release of pyrophosphate (PPi), and ultimately polymerase translocation, which clears the nucleotide binding site. This article reviews different mechanistic models for polymerase translocation with emphasis placed on HIV-1 RT. Structure-function analyses of stalled complexes of HIV-1 RT provide strong evidence to suggest that the enzyme can oscillate between pre- and post-translocational states. Nucleotide hydrolysis is not required for the movement of the polymerase in a stalled configuration; thermal energy is sufficient to allow random bidirectional sliding. The next complementary nucleotide, following the incorporated chain-terminator, acts like a pawl of a ratchet that traps the enzyme in the post-translocation state and prevents the reverse movement. Quantitative footprinting experiments have shown that the concentration of the templated nucleotide required to shift the translocational equilibrium forward depends crucially on the structure of the 3'end of the primer. Changes in the relative population of pre- and post-translocation complexes can influence rates of excision of incorporated NRTIs, which, in turn, affects drug susceptibility. The concept of a ratchet model of HIV-1 RT translocation and its implications for drug action and resistance, and the discovery and development of novel antiviral compounds is discussed.

  14. Energy Landscape of the Substrate Translocation Equilibrium of Plasma-Membrane Glutamate Transporters.

    Science.gov (United States)

    Wang, Jiali; Albers, Thomas; Grewer, Christof

    2018-01-11

    Glutamate transporters maintain a large glutamate concentration gradient across synaptic membranes and are, thus, critical for functioning of the excitatory synapse. Mammalian glutamate transporters concentrate glutamate inside cells through energetic coupling of glutamate flux to the transmembrane concentration gradient of Na + . Structural models based on an archeal homologue, GltPh, suggest an elevator-like carrier mechanism. However, the energetic determinants of this carrier-based movement are not well understood. Although electrostatics play an important role in governing these energetics, their implication on transport dynamics has not been studied. Here, we combine a pre-steady-state kinetic analysis of the translocation equilibrium with electrostatic computations to gain insight into the energetics of the translocation process. Our results show the biphasic nature of translocation, consistent with the existence of an intermediate on the translocation pathway. In the absence of voltage, the equilibrium is shifted to the outward-facing configuration. Electrostatic computations confirm the intermediate state and show that the elevator-like movement is energetically feasible in the presence of bound Na + ions, whereas a substrate-hopping model is energetically prohibitive. Our results highlight the critical contribution of charge compensation to transport and add to results from previous molecular dynamics simulations for improved understanding of the glutamate translocation process.

  15. Streptococcus pyogenes translocates across an epithelial barrier.

    Science.gov (United States)

    Sumitomo, Tomoko

    2017-01-01

    Streptococcus pyogenes is a β-hemolytic organism responsible for a wide variety of human diseases that commonly occur as self-limiting purulent diseases of the pharynx and skin. Although the occurrence of invasive infections by S. pyogenes is rare, mortality rates remain high even with progressive medical therapy. As a prerequisite for causing the severe invasive disease, S. pyogenes must invade underlying sterile tissues by translocating across the epithelial barrier. In this study, streptolysin S and SpeB were identified as the novel factors that facilitate bacterial translocation via degradation of intercellular junctions. Furthermore, we found that S. pyogenes exploits host plasminogen for acceleration of bacterial invasion into deeper tissues via tricellular tight junctions. Here, I would like to show our study on bacterial translocation across the epithelial barrier through paracellular route.

  16. Translocation of 14C-photosynthates under normal and moisture stress conditions in finger millet (Eleusine coracana) gaertin

    International Nuclear Information System (INIS)

    Udayakumar, M.; Rama Rao, S.; Krishna Sastry, K.S.

    1981-01-01

    Translocation of photosynthates into different sinks was studied following feeding a single leaf with 14 CO 2 in 40 day old stressed and non-stressed plants of Eleusine coracana. The rate of efflux of 14 C-photosynthates was twice as much in non-stressed plants compared to stressed plants. Young developing leaves, stem apex and stem which are the potential sinks under non-stressed conditions received very little activity under stress conditions. Percent activity in the roots was enhanced under stress suggesting the pattern of translocation was altered under stress conditions. In the plants subjected to moisture stress, after feeding with 14 CO 2 the rate of efflux of 14 C-photosynthates from the fed leaf decreased and the pattern of translocation was altered. Though the effect of stress seems to be directly on the translocation system, the photosynthetic rate appears to be more sensitive to stress than translocation. (author)

  17. Movements and survival of black-footed ferrets associated with an experimental translocation in South Dakota

    Science.gov (United States)

    Biggins, D.E.; Godbey, J.L.; Horton, B.M.; Livieri, T.M.

    2011-01-01

    Black-footed ferrets (Mustela nigripes) apparently were extirpated from all native habitats by 1987, and their repatriation requires a combination of captive breeding, reintroductions, and translocations among sites. Improvements in survival rates of released ferrets have resulted from experience in quasi-natural environments during their rearing. Reestablishment of a self-sustaining wild population by 1999 provided the 1st opportunity to initiate new populations by translocating wild-born individuals. Using radiotelemetry, we compared behaviors and survival of 18 translocated wild-born ferrets and 18 pen-experienced captive-born ferrets after their release into a prairie dog colony not occupied previously by ferrets. Translocated wild-born ferrets moved significantly less and had significantly higher short-term survival rates than their captive-born counterparts. Using markrecapture methods, we also assessed potential impacts to the established donor population of removing 37% of its estimated annual production of kits. Annual survival rates for 30 ferret kits remaining at the donor subcomplex were higher than rates for 54 ferret kits at the control subcomplex (unmanipulated) for males (+82%) and females (+32%). Minimum survival of translocated kits did not differ significantly from survival of those at the control subcomplex. Direct translocation of young, wild-born ferrets from site to site appears to be an efficient method to establish new populations. ?? 2011 American Society of Mammalogists.

  18. The impact of transportation and translocation on dispersal behaviour in the invasive cane toad.

    Science.gov (United States)

    Pettit, Lachlan; Greenlees, Matthew; Shine, Richard

    2017-06-01

    Biological invasions transport organisms to novel environments; but how does the translocation process influence movement patterns of the invader? Plausibly, the stress of encountering a novel environment, or of the transport process, might induce rapid dispersal from the release site-potentially enhancing (or reducing) invader success and spread. We investigated the effect of transportation and release to novel environments on dispersal-relevant traits of one of the world's most notorious invaders, the cane toad (Rhinella marina). We collected toads in northern New South Wales from heath and woodland habitats, manipulated the level of transport stress and either returned toads to their exact collection point (residents) or reciprocally translocated them to a novel site. Both translocation and the level of transport stress drastically altered toad dispersal rates for at least 5 days post-release. Translocated toads (depending on their level of transport stress and release habitat) moved on average two to five times further per day (mean range 67-148 m) than did residents (mean range 22-34 m). Translocated toads also moved on more days, and moved further from their release point than did resident toads, but did not move in straighter lines. A higher level of transport stress (simulating long-distance translocation) had no significant effect on movements of resident toads but amplified the dispersal of translocated toads only when released into woodland habitat. These behavioural shifts induced by translocation and transportation may affect an invader's ability to colonise novel sites, and need to be incorporated into plans for invader control.

  19. Reverse translocation of tRNA in the ribosome.

    Science.gov (United States)

    Shoji, Shinichiro; Walker, Sarah E; Fredrick, Kurt

    2006-12-28

    A widely held view is that directional movement of tRNA in the ribosome is determined by an intrinsic mechanism and driven thermodynamically by transpeptidation. Here, we show that, in certain ribosomal complexes, the pretranslocation (PRE) state is thermodynamically favored over the posttranslocation (POST) state. Spontaneous and efficient conversion from the POST to PRE state is observed when EF-G is depleted from ribosomes in the POST state or when tRNA is added to the E site of ribosomes containing P-site tRNA. In the latter assay, the rate of tRNA movement is increased by streptomycin and neomycin, decreased by tetracycline, and not affected by the acylation state of the tRNA. In one case, we provide evidence that complex conversion occurs by reverse translocation (i.e., direct movement of the tRNAs from the E and P sites to the P and A sites, respectively). These findings have important implications for the energetics of translocation.

  20. t(8;14) chromosome translocation of the Burkitt lymphoma cell line Daudi occurred during immunoglobulin gene rearrangement and involved the heavy chain diversity region

    International Nuclear Information System (INIS)

    Haluska, F.G.; Tsujimoto, Y.; Croce, C.M.

    1987-01-01

    Recent molecular analyses of Burkitt lymphomas carrying the t(8;14) chromosome translocation have indicated that a dichotomy exists regarding the molecular mechanisms by which the translocations occur. Most sporadic Burkitt tumors carry translocations that apparently arise due to mistakes in the immunoglobulin isotype-switching process. In contrast, there is evidence that the translocations of most endemic Burkitt lymphomas occur as a consequence of aberrant V-D-J recombination of variable, diversity, and joining gene segments, catalyzed by the recombinase enzymes. This phenomenon was first noted in follicular lymphomas and chronic lymphocytic leukemias of the B-cell lineage and has been described in T-cell malignancies as well. In each of these cases, analysis of the nucleotide sequence at chromosome breakpoints demonstrated the involvement of immunoglobulin heavy chain J/sub H/ or T-cell-receptor α-chain Jα gene segments in the translocation. The authors now have cloned and sequenced both the 8q- and 14q+ translocation breakpoints deriving from the t(8;14) translocation of the endemic Burkitt lymphoma line Daudi. The data show that the translocation resulted from a reciprocal exchange between the D/sub H/ region on chromosome 14 and sequences far 5' of the MYC protooncogene on chromosome 8. Features of the nucleotide sequences surrounding the breakpoint further implicate the V-D-J joining machinery in the genesis of chromosome translocation in endemic Burkitt lymphomas and, more generally, in other lymphoid malignancies as well

  1. The Chemical Potential of Plasma Membrane Cholesterol: Implications for Cell Biology.

    Science.gov (United States)

    Ayuyan, Artem G; Cohen, Fredric S

    2018-02-27

    Cholesterol is abundant in plasma membranes and exhibits a variety of interactions throughout the membrane. Chemical potential accounts for thermodynamic consequences of molecular interactions, and quantifies the effective concentration (i.e., activity) of any substance participating in a process. We have developed, to our knowledge, the first method to measure cholesterol chemical potential in plasma membranes. This was accomplished by complexing methyl-β-cyclodextrin with cholesterol in an aqueous solution and equilibrating it with an organic solvent containing dissolved cholesterol. The chemical potential of cholesterol was thereby equalized in the two phases. Because cholesterol is dilute in the organic phase, here activity and concentration were equivalent. This equivalence allowed the amount of cholesterol bound to methyl-β-cyclodextrin to be converted to cholesterol chemical potential. Our method was used to determine the chemical potential of cholesterol in erythrocytes and in plasma membranes of nucleated cells in culture. For erythrocytes, the chemical potential did not vary when the concentration was below a critical value. Above this value, the chemical potential progressively increased with concentration. We used standard cancer lines to characterize cholesterol chemical potential in plasma membranes of nucleated cells. This chemical potential was significantly greater for highly metastatic breast cancer cells than for nonmetastatic breast cancer cells. Chemical potential depended on density of the cancer cells. A method to alter and fix the cholesterol chemical potential to any value (i.e., a cholesterol chemical potential clamp) was also developed. Cholesterol content did not change when cells were clamped for 24-48 h. It was found that the level of activation of the transcription factor STAT3 increased with increasing cholesterol chemical potential. The cholesterol chemical potential may regulate signaling pathways. Copyright © 2018. Published by

  2. Case Report: Extrauterine Translocated Contraceptive Device: A ...

    African Journals Online (AJOL)

    The most common presenting symptom was inability to feel the device's string (in three patients). Four of the patients presented within one month of the insertion. Three of the five translocated intraperitoneal devices were recovered by laparotomy and the forth by laparoscopy. The fifth patient, pregnant, defaulted with the ...

  3. 11C-methionine translocation in barley

    International Nuclear Information System (INIS)

    Nakanishi, Hiromi; Bughio, Naimatullah; Shigeta Ishioka, Noriko

    2000-01-01

    11 C-methionine was supplied to barley plants through a single leaf or via the roots and real time 11 C movement was monitored using a PETIS (positron emitting tracer imaging system). In Fe-deficient plants, 11 C-methionine was translocated from the tip of the absorbing leaf to the discrimination center' at the basal part of the shoot and then retranslocated to all the chlorotic leaves, while a negligible amount was retranslocated to the roots. In Fe-sufficient plants, methionine was translocated from the absorbing leaf to the discrimination center and then only to the newest leaf on the main shoot. A negligible amount was also retranslocated to the roots. Although, in Fe-sufficient plants, methionine translocation was observed from absorbing roots to shoots, in Fe-deficient plants, only a little amount was translocated from roots to shoots. In conclusion, methionine from the upper portion of a plant is not used as a precursor of mugineic acid under Fe-deficiency conditions. (author)

  4. Familial cryptic translocation in Angelman syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Weyerts, L.K.; Wiley, J.E.; Loud, K.M. [ECU School of Medicine, Greenville, NC (United States)] [and others

    1994-09-01

    The majority of patients with Angelman syndrome have been shown to have a cytogenetic or molecular deletion on the maternally derived chromosome 15. We report on a case of Angelman syndrome in which this deletion occurs as an unbalanced cryptic translocation involving chromosomes 14 and 15. The proband was diagnosed clinically as having Angelman syndrome. Multiple cytogenetic studies were done without detecting any deletion. When DNA probes (Oncor) specific for the Prader Willi/Angelman locus became available, the patient was restudied and found to be deleted for {open_quotes}region A{close_quotes} (D15S11) but not for {open_quotes}region B{close_quotes} (GABRB3). No other abnormality was detected. The proband`s mother was then studied. The chromosome 15 marker probe and D15S11 were detected on different chromosomes. Using alpha-satellite probes, a cryptic 14;15 translocation was uncovered. This balanced translocation was also found to be carried by the sister of the proband. This case, along with a case presented at the 1993 ASHG meeting, illustrates the need for using acrocentric probes when studying Angelman syndrome patients. The proband was studied using additional probes specific for this region and found to be deleted for SNRPN but not for D15S10. The breakpoint of the translocation in this patient delineates the smallest deletion of the Angelman syndrome region reported to date and therefore may represent the specific gene involved.

  5. Translocations used to generate chromosome segment duplications ...

    Indian Academy of Sciences (India)

    generating translocations; ... are summarized in table 1. 2.3 Overview of the method used to define the breakpoint junction sequences .... showed linkage with the nucleolus organizer region (NOR) in LG VL but not to markers on LG VL or LG V ...

  6. Non-specific effects of vaccines: plausible and potentially important, but implications uncertain.

    Science.gov (United States)

    Pollard, Andrew J; Finn, Adam; Curtis, Nigel

    2017-11-01

    Non-specific effects (NSE) or heterologous effects of vaccines are proposed to explain observations in some studies that certain vaccines have an impact beyond the direct protection against infection with the specific pathogen for which the vaccines were designed. The importance and implications of such effects remain controversial. There are several known immunological mechanisms which could lead to NSE, since it is widely recognised that the generation of specific immunity is initiated by non-specific innate immune mechanisms that may also have wider effects on adaptive immune function. However, there are no published studies that demonstrate a mechanistic link between such immunological phenomena and clinically relevant NSE in humans. While it is highly plausible that some vaccines do have NSE, their magnitude and duration, and thus importance, remain uncertain. Although the WHO recently concluded that current evidence does not justify changes to immunisation policy, further studies of sufficient size and quality are needed to assess the importance of NSE for all-cause mortality. This could provide insights into vaccine immunobiology with important implications for infant health and survival. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  7. Fish oil curtails the human action potential dome in a heterogeneous manner: Implication for arrhythmogenesis

    NARCIS (Netherlands)

    Verkerk, Arie O.; den Ruijter, Hester M.; de Jonge, Nicolaas; Coronel, Ruben

    2009-01-01

    Omega-3 polyunsaturated fatty acids (omega3-PUFAs) from fish oil modulate various ion channels, including the L-type calcium current (I(Ca,L)). As a result, fish oil shortens the cardiac action potential and may cause a loss of the dome of the action potential (AP). Under conditions of increased

  8. India’s long-term growth potential and the implications for Australia

    OpenAIRE

    Ben Ralston; Wilson Au-Yeung; Bill Brummitt

    2011-01-01

    After 20 years of economic reform this article discusses India’s long-term growth potential and canvasses some of the challenges that Indian policy makers will need to overcome to realise this potential. Some of the consequences of India’s growth for Australia are also explored.

  9. Extensive Lysine Methylation in Hyperthermophilic Crenarchaea: Potential Implications for Protein Stability and Recombinant Enzymes

    Directory of Open Access Journals (Sweden)

    Catherine H. Botting

    2010-01-01

    Full Text Available In eukarya and bacteria, lysine methylation is relatively rare and is catalysed by sequence-specific lysine methyltransferases that typically have only a single-protein target. Using RNA polymerase purified from the thermophilic crenarchaeum Sulfolobus solfataricus, we identified 21 methyllysines distributed across 9 subunits of the enzyme. The modified lysines were predominantly in α-helices and showed no conserved sequence context. A limited survey of the Thermoproteus tenax proteome revealed widespread modification with 52 methyllysines in 30 different proteins. These observations suggest the presence of an unusual lysine methyltransferase with relaxed specificity in the crenarchaea. Since lysine methylation is known to enhance protein thermostability, this may be an adaptation to a thermophilic lifestyle. The implications of this modification for studies and applications of recombinant crenarchaeal enzymes are discussed.

  10. Environmental Life Cycle Assessment and Cost Analysis of Bath, NY Wastewater Treatment Plant: Potential Upgrade Implications

    Science.gov (United States)

    Many communities across the U.S. are required to upgrade wastewater treatment plants (WWTP) to meet increasingly stringent nutrient effluent standards. However, increased capital, energy and chemical requirements of upgrades create potential trade-offs between eutrophication pot...

  11. The 2008 Financial Crisis and Potential Output in Asia : Impact and Policy Implications

    OpenAIRE

    Cyn-Young Park; Ruperto P. Majuca; Josef T. Yap

    2010-01-01

    Monitoring the behavior of potential output helps policymakers implement appropriate policies in response to an economic crisis. In the short-run, estimates of the output gap can guide the timing of the implementation and withdrawal of stimulus measures. In the medium- to long-term, these estimates can also provide the basis for gauging productive potential and, hence, guide policies to support sustainable, non-inflationary output growth. In this paper, we investigate the post-crisis behavior...

  12. Assessing the manipulative potentials of monkeys, apes and humans from hand proportions: implications for hand evolution.

    Science.gov (United States)

    Liu, Ming-Jin; Xiong, Cai-Hua; Hu, Di

    2016-11-30

    The hand structure possesses a greater potential for performing manipulative skills than is typically observed, whether in humans or non-human anthropoids. However, a precise assessment of the potential manipulative skills of hands has been challenging, which hampers our understanding of the evolution of manipulative abilities in anthropoid hands. Here, we establish a functional model to quantitatively infer the manipulative potentials of anthropoid hands based on hand proportions. Our results reveal a large disparity of manipulative potentials among anthropoid hands. From the aspect of hand proportions, the human hand has the best manipulative potential among anthropoids. However, the species with a manipulative potential closer to that of humans are not our nearest relatives, chimpanzees, but rather, are certain monkey species. In combination with the phylogenetically informed morphometric analyses, our results suggest that the morphological changes of non-human anthropoid hands did not coevolve with the brain to facilitate the manipulative ability during the evolutionary process, although the manipulative ability is a survival skill. The changes in non-human anthropoid hands may have more likely evolved under selective pressure for locomotion than manipulation. © 2016 The Author(s).

  13. HIV-1 gp120 induces NFAT nuclear translocation in resting CD4+ T-cells

    International Nuclear Information System (INIS)

    Cicala, Claudia; Arthos, James; Censoplano, Nina; Cruz, Catherine; Chung, Eva; Martinelli, Elena; Lempicki, Richard A.; Natarajan, Ven; VanRyk, Donald; Daucher, Marybeth; Fauci, Anthony S.

    2006-01-01

    The replication of human immunodeficiency virus (HIV) in CD4+ T-cells is strongly dependent upon the state of activation of infected cells. Infection of sub-optimally activated cells is believed to play a critical role in both the transmission of virus and the persistence of CD4+ T-cell reservoirs. There is accumulating evidence that HIV can modulate signal-transduction pathways in a manner that may facilitate replication in such cells. We previously demonstrated that HIV gp120 induces virus replication in resting CD4+ T cells isolated from HIV-infected individuals. Here, we show that in resting CD4+ T-cells, gp120 activates NFATs and induces their translocation into the nucleus. The HIV LTR encodes NFAT recognition sites, and NFATs may play a critical role in promoting viral replication in sub-optimally activated cells. These observations provide insight into a potential mechanism by which HIV is able to establish infection in resting cells, which may have implications for both transmission of HIV and the persistence of viral reservoirs

  14. An educational path for the magnetic vector potential and its physical implications

    International Nuclear Information System (INIS)

    Barbieri, S; Cavinato, M; Giliberti, M

    2013-01-01

    We present an educational path for the magnetic vector potential A aimed at undergraduate students and pre-service physics teachers. Starting from the generalized Ampère–Laplace law, in the framework of a slowly varying time-dependent field approximation, the magnetic vector potential is written in terms of its empirical references, i.e. the conduction currents. Therefore, once the currents are known, our approach allows for a clear and univocal physical determination of A, overcoming the mathematical indeterminacy due to the gauge transformations. We have no need to fix a gauge, since for slowly varying time-dependent electric and magnetic fields, the ‘natural’ gauge for A is the Coulomb one. We stress the difference between our approach and those usually presented in the literature. Finally, a physical interpretation of the magnetic vector potential is discussed and some examples of the calculation of A are analysed. (paper)

  15. The role of glial cells in Alzheimer disease: potential therapeutic implications.

    Science.gov (United States)

    Lopategui Cabezas, I; Herrera Batista, A; Pentón Rol, G

    2014-06-01

    Alzheimer (AD) disease is a complex neurodegenerative disease characterised by inflammation, neurotoxicity, oxidative stress, and reactive gliosis. Microglia and astrocytes not only act as antigen-presenting cells, but also function as effector cells releasing pro-inflammatory molecules that promote excitotoxicity and neurodegeneration. In the present review we discuss the role of glia, specifically microglia and astrocytes, in the pathophysiology of AD and possible therapeutic implications. The growing body of evidence suggesting that microglia and astrocytes play a pathogenic role and activate inflammation pathways, the neurotoxic factors released by these cells when activated, and the way these factors may disrupt the homeostasis of the central nervous system all support the hypothesis that glia-induced inflammation exacerbates AD. Inhibiting inflammation by deactivating glial cells may reduce the production of factors which contribute to neurotoxicity, and therefore result in clinical improvement. Microglia and astrocytes are therapeutic targets for the development of new drugs to combat this disease. Therapeutic strategies designed to counter the detrimental effects of overactivation of these cell populations should be investigated. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  16. Hydroxymethylation and its potential implication in DNA repair system: A review and future perspectives.

    Science.gov (United States)

    Shukla, Ankita; Sehgal, Manika; Singh, Tiratha Raj

    2015-06-15

    The 5-hydroxymethylcytosine (5-hmC) is known to exist as a predictive indicator for a variety of cancers, neurological abnormalities and other perilous diseases. The precursor of 5-hmC i.e. 5-methylcytosine (5mC) has already gained attention as an important epigenetic regulator whereas 5-hmC remains less explored. The two modified DNA bases (5mC and 5-hmC) have absolute diverse distribution, i.e. 5-hmC is mostly restrained to the 5' end of DNA with levels directing the gene transcription whereas 5mC is mainly located at the intra- or intergenic regions of DNA repeats and within certain gene bodies. It has been reported that levels of 5-hmC in different tissues provide a useful tool for detecting numerous associated diseases and their progression. Therefore, to unravel the role of hydroxymethylation in various resulting diseases in humans, comprehensive information on this crucial process has been explored and compiled for its implication in DNA repair system. The role of miRNAs in cancer through hypo- and hypermethylation has also been explored and discussed. In this review, a broad and exclusive insight into hydroxymethylation and its association with repair mechanisms is extensively presented and it is estimated that the accessible information will be of utmost use to the biological community working in the relevant research area. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Climate change and crop natural defenses: potential implications for food security and food safety

    Science.gov (United States)

    Wheat and corn are an essential part of the world’s grain supply, but climate change has the potential to increase grain susceptibility to toxin producing fungal pathogens. While rising atmospheric [CO2] is a driving force of climate change, our understanding of how elevated [CO2] will effect grain ...

  18. Selecting for Creativity and Innovation Potential: Implications for Practice in Healthcare Education

    Science.gov (United States)

    Patterson, Fiona; Zibarras, Lara Dawn

    2017-01-01

    The ability to innovate is an important requirement in many organisations. Despite this pressing need, few selection systems in healthcare focus on identifying the potential for creativity and innovation and so this area has been vastly under-researched. As a first step towards understanding how we might select for creativity and innovation, this…

  19. Energy conservation potential in China’s petroleum refining industry: Evidence and policy implications

    International Nuclear Information System (INIS)

    Lin, Boqiang; Xie, Xuan

    2015-01-01

    Highlights: • A long-term equilibrium relationship of energy demand in China’s petroleum refining industry is established. • The sectoral energy conservation potential is evaluated by using scenarios analysis. • Energy prices, enterprise scale, R and D investment and ownership structure affect electricity intensity. • Future policy for energy conservation in China’s petroleum refining industry is suggested. - Abstract: China is currently the second largest petroleum refining country in the world due to rapid growth in recent years. Because the petroleum refining industry is energy-intensive, the rapid growth in petroleum refining and development caused massive energy consumption. China’s urbanization process will guarantee sustained growth of the industry for a long time. Therefore, it is necessary to study the energy conservation potential of the petroleum industry. This paper estimates the energy conservation potential of the industry by applying a cointegration model to investigate the long-run equilibrium relationship between energy consumption and some factors such as energy price, enterprise scale, R and D investment and ownership structure. The results show that R and D investment has the greatest reduction impact on energy intensity, and the growth of market participants (i.e. the decline of the share of state-owned companies) can improve energy efficiency of this industry. Under the advanced energy-saving scenario, the accumulated energy conservation potential will reach 230.18 million tons of coal equivalent (tce). Finally, we provide some targeted policy recommendations for industrial energy conservation

  20. Harvest residue removal and soil compaction impact forest productivity and recovery: Potential implications for bioenergy harvests

    Science.gov (United States)

    Miranda T. Curzon; Anthony W. D' Amato; Brian J. Palik

    2014-01-01

    Understanding the effects of management on forest structure and function is increasingly important in light of projected increases in both natural and anthropogenic disturbance severity and frequency with global environmental change. We examined potential impacts of the procurement of forest-derived bioenergy, a change in land use that has been suggested as a climate...

  1. Separation of Electric Fields Into Potential and Inductive Parts, and Implications for Radial Diffusion

    Science.gov (United States)

    Chan, A. A.; Ilie, R.; Elkington, S. R.; Albert, J.; Huie, W.

    2017-12-01

    It has been traditional to separate radiation belt radial-diffusion coefficients into two contributions: an "electrostatic" diffusion coefficient, which is assumed to be due to a potential (non-inductive) electric field, and an "electromagnetic" diffusion coefficient , which is assumed to be due to the combined effect of an inductive electric field and the corresponding time-dependent magnetic field. One difficulty in implementing this separation when using magnetospheric fields obtained from measurements, or from MHD simulations, is that only the total electric field is given; the separation of the electric field into potential and inductive parts is not readily available. In this work we separate the electric field using a numerical method based on the Helmholtz decomposition of the total motional electric field calculated by the BATS-R-US MHD code. The inner boundary for the electric potential is based on the Ridley Ionospheric Model solution and we assume floating boundary conditions in the solar wind. Using different idealized solar wind drivers, including a solar wind density that is oscillating at a single frequency or with a broad spectrum of frequencies, we calculate potential and inductive electric fields, electric and magnetic power spectral densities, and corresponding radial diffusion coefficients. Simulations driven by idealized solar wind conditions show a clear separation of the potential and inductive contributions to the power spectral densities and diffusion coefficients. Simulations with more realistic solar wind drivers are underway to better assess the use of electrostatic and electromagnetic diffusion coefficients in understanding ULF wave-particle interactions in Earth's radiation belts.

  2. Mitochondrial translocation of signal transducer and activator of transcription 5 (STAT5) in leukemic T cells and cytokine-stimulated cells

    Energy Technology Data Exchange (ETDEWEB)

    Chueh, Fu-Yu; Leong, King-Fu [Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064 (United States); Yu, Chao-Lan, E-mail: chaolan.yu@rosalindfranklin.edu [Department of Microbiology and Immunology, H. M. Bligh Cancer Research Laboratories, Chicago Medical School, Rosalind Franklin University of Medicine and Science, North Chicago, IL 60064 (United States)

    2010-11-26

    Research highlights: {yields} STAT5 interacts with a mitochondrial protein PDC-E2 in a leukemic T cell line LSTRA. {yields} Tyrosine-phosphorylated STAT5, but not STAT3, is present in LSTRA mitochondria. {yields} Cytokines induce mitochondrial translocation of STAT5, but not STAT1 or STAT3. {yields} Cytokine-induced mitochondrial translocation of tyrosine-phosphorylated STAT5 is transient. {yields} Mitochondrial STAT5 binds to a putative STAT5 site in the mitochondrial DNA in vitro. -- Abstract: Signal transducers and activators of transcription (STATs) were first identified as key signaling molecules in response to cytokines. Constitutive STAT activation also has been widely implicated in oncogenesis. We analyzed STAT5-associated proteins in a leukemic T cell line LSTRA, which exhibits constitutive tyrosine phosphorylation and activation of STAT5. A cellular protein was found to specifically interact with STAT5 in LSTRA cells by co-immunoprecipitation. Sequencing analysis and subsequent immunoblotting confirmed the identity of this STAT5-associated protein as the E2 component of mitochondrial pyruvate dehydrogenase complex (PDC-E2). Consistent with this interaction, both subcellular fractionation and immunofluorescence microscopy revealed mitochondrial localization of STAT5 in LSTRA cells. Mitochondrial localization of tyrosine-phosphorylated STAT5 also occurred in cytokine-stimulated cells. A time course experiment further demonstrated the transient kinetics of STAT5 mitochondrial translocation after cytokine stimulation. In contrast, cytokine-induced STAT1 and STAT3 activation did not result in their translocation into mitochondria. Furthermore, we showed that mitochondrial STAT5 bound to the D-loop regulatory region of mitochondrial DNA in vitro. It suggests a potential role of STAT5 in regulating the mitochondrial genome. Proliferative metabolism toward aerobic glycolysis is well known in cancer cells as the Warburg effect and is also observed in cytokine

  3. Insulin-induced translocation of IR to the nucleus in insulin responsive cells requires a nuclear translocation sequence.

    Science.gov (United States)

    Kesten, Dov; Horovitz-Fried, Miriam; Brutman-Barazani, Tamar; Sampson, Sanford R

    2018-04-01

    Insulin binding to its cell surface receptor (IR) activates a cascade of events leading to its biological effects. The Insulin-IR complex is rapidly internalized and then is either recycled back to the plasma membrane or sent to lysosomes for degradation. Although most of the receptor is recycled or degraded, a small amount may escape this pathway and migrate to the nucleus of the cell where it might be important in promulgation of receptor signals. In this study we explored the mechanism by which insulin induces IR translocation to the cell nucleus. Experiments were performed cultured L6 myoblasts, AML liver cells and 3T3-L1 adipocytes. Insulin treatment induced a rapid increase in nuclear IR protein levels within 2 to 5 min. Treatment with WGA, an inhibitor of nuclear import, reduced insulin-induced increases nuclear IR protein; IR was, however, translocated to a perinuclear location. Bioinformatics tools predicted a potential nuclear localization sequence (NLS) on IR. Immunofluorescence staining showed that a point mutation on the predicted NLS blocked insulin-induced IR nuclear translocation. In addition, blockade of nuclear IR activation in isolated nuclei by an IR blocking antibody abrogated insulin-induced increases in IR tyrosine phosphorylation and nuclear PKCδ levels. Furthermore, over expression of mutated IR reduced insulin-induced glucose uptake and PKB phosphorylation. When added to isolated nuclei, insulin induced IR phosphorylation but had no effect on nuclear IR protein levels. These results raise questions regarding the possible role of nuclear IR in IR signaling and insulin resistance. Copyright © 2018 Elsevier B.V. All rights reserved.

  4. Obstructive jaundice promotes bacterial translocation in humans.

    Science.gov (United States)

    Kuzu, M A; Kale, I T; Cöl, C; Tekeli, A; Tanik, A; Köksoy, C

    1999-01-01

    Significant bacterial translocation was demonstrated following experimental biliary obstruction, however very little is known about the importance and the prevalence of gut-origin sepsis in obstructive jaundice patients. Therefore, the aim of this study was to investigate the concept of gut-origin sepsis in obstructive jaundiced patients and its clinical importance. Twenty-one patients requiring laparotomy for obstructive jaundice (group I) and thirty patients operated on electively mainly for chronic cholecystitis (group II) were studied. Peritoneal swab, mesenteric lymph node, portal venous blood, liver wedge biopsy and bile were sampled for culture immediately after opening the peritoneum. Additionally, peripheral blood samples were taken pre- and post-operatively from all patients. Post-operatively, patients were monitored for infectious complications. The mean serum bilirubin concentration, gamma glutamyl transferase and alkaline phosphatase levels in jaundiced patients before therapeutic intervention were significantly higher than in control patients. Five patients demonstrated bacterial translocation in group I (24%), whereas only one did so in group II (3.5%, p jaundice significantly promotes bacterial translocation in humans, however, its clinical importance has yet to be defined.

  5. Plasma cadmium and zinc and their interrelationship in adult Nigerians: potential health implications

    Directory of Open Access Journals (Sweden)

    Ugwuja Emmanuel Ike

    2015-06-01

    Full Text Available Zinc (an essential trace element and cadmium (a ubiquitous environmental pollutant with acclaimed toxicity have been found to occur together in nature, with reported antagonism between the two elements. The present study aimed at determination of plasma levels of zinc (Zn and cadmium (Cd and their interrelationship in adult Nigerians. The series comprised adults (n=443 aged ≥18 yrs (mean ± SD 38.4±13.7 yrs, consisting of 117 males, 184 non-pregnant and 140 pregnant females. Sociodemographic data were collected by questionnaire while anthropometrics were determined using standard methods. Plasma Cd and Zn were determined by using an atomic absorption spectrophotometer. The mean plasma zinc and cadmium were 94.7±18.1 μg/dl and 0.150±0.548 μg/dl, respectively. Age, sex, pregnancy, and parity had no effect on either plasma Zn or Cd. Although educational level had no effect on plasma Zn, it had a significant effect on Cd; subjects possessing either secondary or tertiary education had significantly lower plasma Cd than subjects without formal education. Moreover, there seemed to be an inverse relationship between Cd and Zn, but this was not statistically significant (r=–0.089; p=0.061. Although plasma Zn was not related to BMI (r=0.037; p=0.432, Cd was significantly negatively correlated with BMI (r=–0.124; p=0.009. It may be concluded that adult Nigerians in Ebonyi State have elevated plasma levels of Cd, with apparent impact on the levels of plasma Zn. This has important public health implications considering the essential roles of Zn in the protection of Cd mediated adverse health effects. While food diversification is recommended to improve plasma Zn, efforts should be made to reduce exposure to Cd to mitigate partially its possible adverse effects.

  6. Endothelial cell-derived microparticles induce plasmacytoid dendritic cell maturation: potential implications in inflammatory diseases.

    Science.gov (United States)

    Angelot, Fanny; Seillès, Estelle; Biichlé, Sabeha; Berda, Yael; Gaugler, Béatrice; Plumas, Joel; Chaperot, Laurence; Dignat-George, Françoise; Tiberghien, Pierre; Saas, Philippe; Garnache-Ottou, Francine

    2009-11-01

    Increased circulating endothelial microparticles, resulting from vascular endothelium dysfunction, and plasmacytoid dendritic cell activation are both encountered in common inflammatory disorders. The aim of our study was to determine whether interactions between endothelial microparticles and plasmacytoid dendritic cells could contribute to such pathologies. Microparticles generated from endothelial cell lines, platelets or activated T cells were incubated with human plasmacytoid dendritic cells sorted from healthy donor blood or with monocyte-derived dendritic cells. Dendritic cell maturation was evaluated by flow cytometry, cytokine secretion as well as naive T-cell activation and polarization. Labeled microparticles were also used to study cellular interactions. Endothelial microparticles induced plasmacytoid dendritic cell maturation. In contrast, conventional dendritic cells were resistant to endothelial microparticle-induced maturation. In addition to upregulation of co-stimulatory molecules, endothelial microparticle-matured plasmacytoid dendritic cells secreted inflammatory cytokines (interleukins 6 and 8, but no interferon-alpha) and also induced allogeneic naive CD4(+) T cells to proliferate and to produce type 1 cytokines such as interferon-gamma and tumor necrosis factor-alpha. Endothelial microparticle endocytosis by plasmacytoid dendritic cells appeared to be required for plasmacytoid dendritic cell maturation. Importantly, the ability of endothelial microparticles to induce plasmacytoid dendritic cells to mature was specific as microparticles derived from activated T cells or platelets (the major source of circulating microparticules in healthy subjects) did not induce such plasmacytoid dendritic cell maturation. Our data show that endothelial microparticles specifically induce plasmacytoid dendritic cell maturation and production of inflammatory cytokines. This novel activation pathway may be implicated in various inflammatory disorders and

  7. Application of DNA RFLP procedures in interspecific gene transfer: The Lr19 translocation of wheat

    International Nuclear Information System (INIS)

    Prins, R.; Marais, G.F.; Marais, A.S.; Pretorius, Z.A.; Janse, B.J.H.

    1998-01-01

    Twenty-nine lines with deletions in the Lr19 ('Indis') translocated chromosome segment were used to physically map Thinopyrum Restriction Fragment Length Polymorphism (RFLP) loci as well as the Sr25 and Sdl loci. The relative distances between marker loci on the translocation were then calculated. The information was then used as an aid to characterize several recombined forms of the translocation. The data confirmed the reported homoeology between the Lr19 segment and chromosome arm 7DL of wheat. Also, it seems that the Lr19 translocation in 'Indis' is very similar to the Lr19 segment in the T4 source and that the former may not derive from Thinopyrum distichum. Near-isogenic lines of the recombined segments were derived and used to study their expression of leaf rust resistance. It became evident that only one potentially useful recombinant was obtained in an earlier attempt to induce allosyndetic pairing between the Lr19 translocation and 7DL of wheat. (author)

  8. Twitch potentiation induced by two different modalities of neuromuscular electrical stimulation: implications for motor unit recruitment.

    Science.gov (United States)

    Regina Dias Da Silva, Sarah; Neyroud, Daria; Maffiuletti, Nicola A; Gondin, Julien; Place, Nicolas

    2015-03-01

    We tested the hypothesis that twitch potentiation would be greater following conventional (CONV) neuromuscular electrical stimulation (50-µs pulse width and 25-Hz frequency) compared with wide-pulse high-frequency (WPHF) neuromuscular electrical stimulation (1-ms, 100-Hz) and voluntary (VOL) contractions, because of specificities in motor unit recruitment (random in CONV vs. random and orderly in WPHF vs. orderly in VOL). A single twitch was evoked by means of tibial nerve stimulation before and 2 s after CONV, WPHF, and VOL conditioning contractions of the plantar flexors (intensity: 10% maximal voluntary contraction; duration: 10 s) in 13 young healthy subjects. Peak twitch increased (Ptwitch potentiation results. © 2014 Wiley Periodicals, Inc.

  9. Biology and potential clinical implications of tissue inhibitor of metalloproteinases-1 in colorectal cancer treatment

    DEFF Research Database (Denmark)

    Sørensen, Nanna Møller; Sørensen, irene Vejgaard; Würtz, Sidse Ørnbjerg

    2008-01-01

    Colorectal cancer (CRC) is the second leading cause of cancer-related death in the industrialized world. About half of "curatively" resected patients develop recurrent disease within the next 3-5 years despite the lack of clinical, histological and biochemical evidence of remaining overt disease ...... knowledge of the biology of TIMP-1 as well as the potential use of TIMP-1 as a biological marker in the management of CRC patients....

  10. Affective Aspects of Perceived Loss of Control and Potential Implications for Brain-Computer Interfaces

    Directory of Open Access Journals (Sweden)

    Sebastian Grissmann

    2017-07-01

    Full Text Available Most brain-computer interfaces (BCIs focus on detecting single aspects of user states (e.g., motor imagery in the electroencephalogram (EEG in order to use these aspects as control input for external systems. This communication can be effective, but unaccounted mental processes can interfere with signals used for classification and thereby introduce changes in the signal properties which could potentially impede BCI classification performance. To improve BCI performance, we propose deploying an approach that potentially allows to describe different mental states that could influence BCI performance. To test this approach, we analyzed neural signatures of potential affective states in data collected in a paradigm where the complex user state of perceived loss of control (LOC was induced. In this article, source localization methods were used to identify brain dynamics with source located outside but affecting the signal of interest originating from the primary motor areas, pointing to interfering processes in the brain during natural human-machine interaction. In particular, we found affective correlates which were related to perceived LOC. We conclude that additional context information about the ongoing user state might help to improve the applicability of BCIs to real-world scenarios.

  11. Epigenetic and antioxidant effects of dietary isothiocyanates and selenium: potential implications for cancer chemoprevention.

    Science.gov (United States)

    Barrera, Lawrence N; Cassidy, Aedin; Johnson, Ian T; Bao, Yongping; Belshaw, Nigel J

    2012-05-01

    There is evidence from epidemiological studies suggesting that increased consumption of cruciferous vegetables may protect against specific cancers more effectively than total fruit and vegetable intake. These beneficial effects are attributed to the glucosinolate breakdown products, isothiocyanates (ITC). Similarly, selenium (Se) consumption has also been inversely associated with cancer risk and as an integral part of many selenoproteins may influence multiple pathways in the development of cancer. This paper will briefly review the current state of knowledge concerning the effect of Se and ITC in cancer development with a particular emphasis on its antioxidant properties, and will also address whether alterations in DNA methylation may be a potential mechanism whereby these dietary constituents protect against the carcinogenic process. Furthermore, we will discuss the advantages of combining ITC and Se to benefit from their complementary mechanisms of action to potentially protect against the alterations leading to neoplasia. Based on this review it may be concluded that an understanding of the impact of ITC and Se on aberrant DNA methylation in relation to factors modulating gene-specific and global methylation patterns, in addition to the effect of these food constituents as modulators of key selenoenzymes, such as gastrointestinal glutathione peroxidase-2 (GPx2) and thioredoxin reductase-1 (TrxR1), may provide insights into the potential synergy among various components of a plant-based diet that may counteract the genetic and epigenetic alterations that initiate and sustain neoplasia.

  12. Micro-RNAs as Potential Predictors of Response to Breast Cancer Systemic Therapy: Future Clinical Implications

    Science.gov (United States)

    Campos-Parra, Alma D.; Cuamani Mitznahuatl, Gerardo; Pedroza-Torres, Abraham; Vázquez Romo, Rafael; Porras Reyes, Fany Iris; López-Urrutia, Eduardo; Pérez-Plasencia, Carlos

    2017-01-01

    Despite advances in diagnosis and new treatments such as targeted therapies, breast cancer (BC) is still the most prevalent tumor in women worldwide and the leading cause of death. The principal obstacle for successful BC treatment is the acquired or de novo resistance of the tumors to the systemic therapy (chemotherapy, endocrine, and targeted therapies) that patients receive. In the era of personalized treatment, several studies have focused on the search for biomarkers capable of predicting the response to this therapy; microRNAs (miRNAs) stand out among these markers due to their broad spectrum or potential clinical applications. miRNAs are conserved small non-coding RNAs that act as negative regulators of gene expression playing an important role in several cellular processes, such as cell proliferation, autophagy, genomic stability, and apoptosis. We reviewed recent data that describe the role of miRNAs as potential predictors of response to systemic treatments in BC. Furthermore, upon analyzing the collected published information, we noticed that the overexpression of miR-155, miR-222, miR-125b, and miR-21 predicts the resistance to the most common systemic treatments; nonetheless, the function of these particular miRNAs must be carefully studied and further analyses are still necessary to increase knowledge about their role and future potential clinical uses in BC. PMID:28574440

  13. Nanotechnology and glaucoma: a review of the potential implications of glaucoma nanomedicine.

    Science.gov (United States)

    Kim, Nathaniel J; Harris, Alon; Gerber, Austin; Tobe, Leslie Abrams; Amireskandari, Annahita; Huck, Andrew; Siesky, Brent

    2014-04-01

    The purpose of this review is to discuss the evolution of nanotechnology and its potential diagnostic and therapeutic applications in the field of ophthalmology, particularly as it pertains to glaucoma. We reviewed literature using MEDLINE and PubMed databases with the following search terms: glaucoma, nanotechnology, nanomedicine, nanoparticles, ophthalmology and liposomes. We also reviewed pertinent references from articles found in this search. A brief history of nanotechnology and nanomedicine will be covered, followed by a discussion of the advantages and concerns of using this technology in the field of glaucoma. We will look at various studies concerning the development of nanomedicine, its potential applications in ocular drug delivery, diagnostic and imaging modalities and, surgical techniques. In particular, the challenges of assuring safety and efficacy of nanomedicine will be examined. We conclude that nanotechnology offers a novel approach to expanding diagnostic, imaging and surgical modalities in glaucoma and may contribute to the knowledge of disease pathogenesis at a molecular level. However, more research is needed to better elucidate the mechanism of cellular entry, the potential for nanoparticle cytotoxicity and the assurance of clinical efficacy.

  14. Underground autocatalytic-criticality potential and its implications to weapons fissile- material disposition

    International Nuclear Information System (INIS)

    Choi, J.-S.

    1998-01-01

    Several options for weapons fissile-material disposition, such as once-through mixed- oxide (MOX) fuel in reactors or immobilisation in waste glass, would result in end products requiring geologic disposal. The criticality potential of the fissile end products containing U-235 and Pu-239 and the associated consequences in a geologic setting are important considerations for the final disposal of these materials. The possibility of underground criticality, and especially autocatalytic criticality, is affected by (1) groundwater leaking into a failed waste container, (2) preferential leaching of neutron absorbers or of fissile material from a failed container, and (3) preferential deposition of fissile material in the surrounding rock. Bowman and Venneri have pointed out that fissile material mixed with varying compositions of water and silica can undergo a nuclear chain reaction. Some configurations can become autocatalytically supercritical resulting in considerable energy release, terminated finally by disassembly. Some reviews rejected the Bowman and Venneri warning as implausible because of low probabilities of scenarios that could lead to such configurations. Sanchez et al. reported possible supercritical conditions in systems of Pu-SiO 2 -H 2 O and Pu-tuff-H 2 O but concluded that the probability of forming such combinations is extremely low. Kastenberg et al. studied the potential for autocatalytic criticality of plutonium or highly enriched uranium in the proposed Yucca Mountain geologic repository. They concluded that plutonium or uranium could, theoretically, become supercritical, but that such criticality is unlikely given the hydrology, geology and geochemistry of the Yucca Mountain site. These studies are not definitive. The possibility of criticality exists. Detailed mechanisms have not been sufficiently studied for clear conclusions on the probabilities of occurrence. More technical analysis is needed to understand the potential for underground

  15. Financial costs of large carnivore translocations--accounting for conservation.

    Science.gov (United States)

    Weise, Florian J; Stratford, Ken J; van Vuuren, Rudolf J

    2014-01-01

    Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars). Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n = 23), and $2,108 per leopard (n = 6). One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%), followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4%) of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown) with a strong species bias. Four leopards (66.7%) were successfully translocated but only eight of the 20 cheetahs (40.0%) with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC) and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis.

  16. Financial costs of large carnivore translocations--accounting for conservation.

    Directory of Open Access Journals (Sweden)

    Florian J Weise

    Full Text Available Human-carnivore conflict continues to present a major conservation challenge around the world. Translocation of large carnivores is widely implemented but remains strongly debated, in part because of a lack of cost transparency. We report detailed translocation costs for three large carnivore species in Namibia and across different translocation scenarios. We consider the effect of various parameters and factors on costs and translocation success. Total translocation cost for 30 individuals in 22 events was $80,681 (US Dollars. Median translocation cost per individual was $2,393, and $2,669 per event. Median cost per cheetah was $2,760 (n = 23, and $2,108 per leopard (n = 6. One hyaena was translocated at a cost of $1,672. Tracking technology was the single biggest cost element (56%, followed by captive holding and feeding. Soft releases, prolonged captivity and orphaned individuals also increased case-specific costs. A substantial proportion (65.4% of the total translocation cost was successfully recovered from public interest groups. Less than half the translocations were confirmed successes (44.4%, 3 unknown with a strong species bias. Four leopards (66.7% were successfully translocated but only eight of the 20 cheetahs (40.0% with known outcome met these strict criteria. None of the five habituated cheetahs was translocated successfully, nor was the hyaena. We introduce the concept of Individual Conservation Cost (ICC and define it as the cost of one successfully translocated individual adjusted by costs of unsuccessful events of the same species. The median ICC for cheetah was $6,898 and $3,140 for leopard. Translocations are costly, but we demonstrate that they are not inherently more expensive than other strategies currently employed in non-lethal carnivore conflict management. We conclude that translocation should be one available option for conserving large carnivores, but needs to be critically evaluated on a case-by-case basis.

  17. DNA translocation through single-layer boron nitride nanopores.

    Science.gov (United States)

    Gu, Zonglin; Zhang, Yuanzhao; Luan, Binquan; Zhou, Ruhong

    2016-01-21

    Ultra-thin nanopores have become promising biological sensors because of their outstanding signal-to-noise ratio and spatial resolution. Here, we show that boron nitride (BN), which is a new two-dimensional (2D) material similar to graphene, could be utilized for making a nanopore with an atomic thickness. Using an all-atom molecular dynamics simulation, we investigated the dynamics of DNA translocation through the BN nanopore. The results of our simulations demonstrated that it is possible to detect different double-stranded DNA (dsDNA) sequences from the recording of ionic currents through the pore during the DNA translocation. Surprisingly, opposite to results for a graphene nanopore, we found the calculated blockage current for poly(A-T)40 in a BN nanopore to be less than that for poly(G-C)40. Also in contrast with the case of graphene nanopores, dsDNA models moved smoothly and in an unimpeded manner through the BN nanopores in the simulations, suggesting a potential advantage for using BN nanopores to design stall-free sequencing devices. BN nanopores, which display several properties (such as being hydrophilic and non-metallic) that are superior to those of graphene, are thus expected to find applications in the next generation of high-speed and low-cost biological sensors.

  18. The Balanced Budget Act: potential implications for the practice of vascular surgery.

    Science.gov (United States)

    Roddy, S P; O'Donnell, T F; Wilson, A L; Estes, J M; Mackey, W C

    2000-02-01

    and to compensate for the fixed expenses of academic medicine. The Balanced Budget Act raises an equity concern for AMCs because it differentially affects the centers with the best outcomes. The financial implication of this may be a direct incentive for procedures to be done in centers with less optimal outcomes.

  19. Health risk implications of potentially toxic metals in street dust and surface soil of Tehran, Iran.

    Science.gov (United States)

    Dehghani, Sharareh; Moore, Farid; Keshavarzi, Behnam; Hale, Beverley A

    2017-02-01

    In this study a total of 30 street dusts and 10 surface soils were collected in the central district of Tehran and analyzed for major potentially toxic metals. Street dust was found to be greatly enriched in Sb, Pb, Cu and Zn and moderately enriched in Cr, Mn, Mo and Ni. Contamination of Cu, Sb, Pb and Zn was clearly related to anthropogenic sources such as brake wear, tire dust, road abrasion and fossil fuel combustion. Spatial distribution of pollution load index in street dust suggested that industries located south-west of the city intensify street dust pollution. Microscopic studies revealed six dominant group of morphological structures in calculation of the exposurethe street dusts and surface soils, with respect to different geogenic and anthropogenic sources. The BCR (the European Community Bureau of Reference) sequential extraction results showed that Sb, Ni, Mo, As and Cr bonded to silicates and sulfide minerals were highly resistant to dissolution. In contrast, Zn, Cd, and Mn were mostly associated with the exchangeable phase and thus would be easily mobilized in the environment. Cu was the most abundant metal in the reducible fraction, indicating its adsorption to iron and manganese oxy-hydroxides. Pb was equally extracted from exchangeable and reducible fractions. Anthropogenic sources related to traffic apparently play a small role in Cr, Ni and Mo contamination and dispersed them as bioavailable forms but with reduced mobility and bioavailablity due to high potential of complexation and adsorption to organic matter and iron and manganese oxy-hydroxides. Calculated Hazard Index (HI) suggests ingestion as the most important pathway for the majority of PTMs in children and dermal contact as the main exposure route for Cr, Cd and Sb for adults. The HIs and fractionation pattern of elements revealed Pb as the sole element that bears potential health risk in street dust and surface soil. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Control of somatic membrane potential in nociceptive neurons and its implications for peripheral nociceptive transmission

    Science.gov (United States)

    Du, Xiaona; Hao, Han; Gigout, Sylvain; Huang, Dongyang; Yang, Yuehui; Li, Li; Wang, Caixue; Sundt, Danielle; Jaffe, David B.; Zhang, Hailin; Gamper, Nikita

    2014-01-01

    Peripheral sensory ganglia contain somata of afferent fibres conveying somatosensory inputs to the central nervous system. Growing evidence suggests that the somatic/perisomatic region of sensory neurons can influence peripheral sensory transmission. Control of resting membrane potential (Erest) is an important mechanism regulating excitability, but surprisingly little is known about how Erest is regulated in sensory neuron somata or how changes in somatic/perisomatic Erest affect peripheral sensory transmission. We first evaluated the influence of several major ion channels on Erest in cultured small-diameter, mostly capsaicin-sensitive (presumed nociceptive) dorsal root ganglion (DRG) neurons. The strongest and most prevalent effect on Erest was achieved by modulating M channels, K2P and 4-aminopiridine-sensitive KV channels, while hyperpolarization-activated cyclic nucleotide-gated, voltage-gated Na+, and T-type Ca2+ channels to a lesser extent also contributed to Erest. Second, we investigated how varying somatic/perisomatic membrane potential, by manipulating ion channels of sensory neurons within the DRG, affected peripheral nociceptive transmission in vivo. Acute focal application of M or KATP channel enhancers or a hyperpolarization-activated cyclic nucleotide-gated channel blocker to L5 DRG in vivo significantly alleviated pain induced by hind paw injection of bradykinin. Finally, we show with computational modelling how somatic/perisomatic hyperpolarization, in concert with the low-pass filtering properties of the t-junction within the DRG, can interfere with action potential propagation. Our study deciphers a complement of ion channels that sets the somatic Erest of nociceptive neurons and provides strong evidence for a robust filtering role of the somatic and perisomatic compartments of peripheral nociceptive neuron. PMID:25168672

  1. Regulation of gap junction conductance by calcineurin through Cx43 phosphorylation: implications for action potential conduction.

    Science.gov (United States)

    Jabr, Rita I; Hatch, Fiona S; Salvage, Samantha C; Orlowski, Alejandro; Lampe, Paul D; Fry, Christopher H

    2016-11-01

    Cardiac arrhythmias are associated with raised intracellular [Ca 2+ ] and slowed action potential conduction caused by reduced gap junction (GJ) electrical conductance (Gj). Ventricular GJs are composed of connexin proteins (Cx43), with Gj determined by Cx43 phosphorylation status. Connexin phosphorylation is an interplay between protein kinases and phosphatases but the precise pathways are unknown. We aimed to identify key Ca 2+ -dependent phosphorylation sites on Cx43 that regulate cardiac gap junction conductance and action potential conduction velocity. We investigated the role of the Ca 2+ -dependent phosphatase, calcineurin. Intracellular [Ca 2+ ] was raised in guinea-pig myocardium by a low-Na solution or increased stimulation. Conduction velocity and Gj were measured in multicellular strips. Phosphorylation of Cx43 serine residues (S365 and S368) and of the intermediary regulator I1 at threonine35 was measured by Western blot. Measurements were made in the presence and absence of inhibitors to calcineurin, I1 or protein phosphatase-1 and phosphatase-2.Raised [Ca 2 + ] i decreased Gj, reduced Cx43 phosphorylation at S365 and increased it at S368; these changes were reversed by calcineurin inhibitors. Cx43-S368 phosphorylation was reversed by the protein kinase C inhibitor chelerythrine. Raised [Ca 2+ ] i also decreased I1 phosphorylation, also prevented by calcineurin inhibitors, to increase activity of the Ca 2+ -independent phosphatase, PPI. The PP1 inhibitor, tautomycin, prevented Cx43-365 dephosphorylation, Cx43-S368 phosphorylation and Gj reduction in raised [Ca 2+ ] i . PP2A had no role. Conduction velocity was reduced by raised [Ca 2+ ] i and reversed by calcineurin inhibitors. Reduced action potential conduction and Gj in raised [Ca 2+ ] are regulated by calcineurin-dependent Cx43-S365 phosphorylation, leading to Cx43-S368 dephosphorylation. The calcineurin action is indirect, via I1 dephosphorylation and subsequent activation of PP1.

  2. Adaptive genetic potential of coniferous forest tree species under climate change: implications for sustainable forest management

    Science.gov (United States)

    Mihai, Georgeta; Birsan, Marius-Victor; Teodosiu, Maria; Dumitrescu, Alexandru; Daia, Mihai; Mirancea, Ionel; Ivanov, Paula; Alin, Alexandru

    2017-04-01

    Mountain ecosystems are extremely vulnerable to climate change. The real potential for adaptation depends upon the existence of a wide genetic diversity in trees populations, upon the adaptive genetic variation, respectively. Genetic diversity offers the guarantee that forest species can survive, adapt and evolve under the influence of changing environmental conditions. The aim of this study is to evaluate the genetic diversity and adaptive genetic potential of two local species - Norway spruce and European silver fir - in the context of regional climate change. Based on data from a long-term provenance experiments network and climate variables spanning over more than 50 years, we have investigated the impact of climatic factors on growth performance and adaptation of tree species. Our results indicate that climatic and geographic factors significantly affect forest site productivity. Mean annual temperature and annual precipitation amount were found to be statistically significant explanatory variables. Combining the additive genetic model with the analysis of nuclear markers we obtained different images of the genetic structure of tree populations. As genetic indicators we used: gene frequencies, genetic diversity, genetic differentiation, genetic variance, plasticity. Spatial genetic analyses have allowed identifying the genetic centers holding high genetic diversity which will be valuable sources of gene able to buffer the negative effects of future climate change. Correlations between the marginal populations and in the optimal vegetation, between the level of genetic diversity and ecosystem stability, will allow the assessment of future risks arising from current genetic structure. Therefore, the strategies for sustainable forest management have to rely on the adaptive genetic variation and local adaptation of the valuable genetic resources. This work was realized within the framework of the project GENCLIM (Evaluating the adaptive potential of the main

  3. The Potential of the CNS as a Reservoir for HIV-1 Infection: Implications for HIV Eradication.

    Science.gov (United States)

    Fois, Alessandro F; Brew, Bruce J

    2015-06-01

    The ability of HIV-1 to establish latent infection is a key obstacle to its eradication despite the existence of effective antiretroviral drugs. The brain has been postulated as a reservoir for latent infection, but its role in HIV persistence remains unclear. In this review, we discuss the evidence surrounding the role of the central nervous system (CNS) as a viral reservoir and the potential challenges this might present in eradicating HIV. The strategies for eradication of HIV and their application to latent CNS infection are explored. Finally, we outline new developments in drug delivery and new therapeutic modalities designed to target HIV infection in the CNS.

  4. Potential implications of the bystander effect on TCP and EUD when considering target volume dose heterogeneity.

    Science.gov (United States)

    Balderson, Michael J; Kirkby, Charles

    2015-01-01

    In light of in vitro evidence suggesting that radiation-induced bystander effects may enhance non-local cell killing, there is potential for impact on radiotherapy treatment planning paradigms such as the goal of delivering a uniform dose throughout the clinical target volume (CTV). This work applies a bystander effect model to calculate equivalent uniform dose (EUD) and tumor control probability (TCP) for external beam prostate treatment and compares the results with a more common model where local response is dictated exclusively by local absorbed dose. The broad assumptions applied in the bystander effect model are intended to place an upper limit on the extent of the results in a clinical context. EUD and TCP of a prostate cancer target volume under conditions of increasing dose heterogeneity were calculated using two models: One incorporating bystander effects derived from previously published in vitro bystander data ( McMahon et al. 2012 , 2013a); and one using a common linear-quadratic (LQ) response that relies exclusively on local absorbed dose. Dose through the CTV was modelled as a normal distribution, where the degree of heterogeneity was then dictated by changing the standard deviation (SD). Also, a representative clinical dose distribution was examined as cold (low dose) sub-volumes were systematically introduced. The bystander model suggests a moderate degree of dose heterogeneity throughout a target volume will yield as good or better outcome compared to a uniform dose in terms of EUD and TCP. For a typical intermediate risk prostate prescription of 78 Gy over 39 fractions maxima in EUD and TCP as a function of increasing SD occurred at SD ∼ 5 Gy. The plots only dropped below the uniform dose values for SD ∼ 10 Gy, almost 13% of the prescribed dose. Small, but potentially significant differences in the outcome metrics between the models were identified in the clinically-derived dose distribution as cold sub-volumes were introduced. In terms of

  5. Proposed Nuclear Power Plants in the UK-Potential Radiological Implications for Ireland

    International Nuclear Information System (INIS)

    McMahon, C.; Kelleher, K.; McGinnity, P.; Organo, C.; Smith, K.; Currivan, L.; Ryan, T.

    2013-05-01

    The UK Government has identified up to eight locations for the construction of new nuclear power plants by 2025. Five of these locations are on the Irish Sea coast. The Radiological Protection Institute of Ireland, RPII was requested by the Minister for the Environment, Community and Local Government to undertake an assessment of the potential radiological impacts on Ireland from this New Build Programme. This report presents the findings of the potential impacts on Ireland of both the anticipated routine radioactive discharges and of a range of postulated nuclear accident scenarios. The following points are the principal findings of the report. Given the prevailing wind direction in Ireland, radioactive contamination in the air, either from routine operation of the proposed nuclear power plants or accidental releases, will most often be transported away from Ireland. The routine operation of the proposed nuclear power plants will have no measurable radiological impact on Ireland or the Irish marine environment. The severe accident scenarios assessed ranged in their estimated frequency of occurrance from 1 in 50,000 to 1 in 33 million per year. The assessment used a weather pattern that maximised the transfer of radioactivity to Ireland. For the severe accident scenarios assessed, food controls or agriculture protective measures would generally be required in Ireland to reduce exposure of the population so as to mitigate potential long-term health effects. In the accident scenario with an estimated 1 in 33 million chance of occurring, short-term measures such as staying indoors would also be advised as a precautionary measure. In general, the accidents with higher potential impact on Ireland are the ones least likely to occur. Regardless of the radiological impact, any accident at the proposed nuclear power plants leading to an increase of radioactivity levels in Ireland would have a socio-economic impact on Ireland. A major accidental release of radioactivity to

  6. Coarse-grained molecular dynamics simulation of DNA translocation in chemically modified nanopores.

    Science.gov (United States)

    Ramachandran, Abhijit; Guo, Qingjiang; Iqbal, Samir M; Liu, Yaling

    2011-05-19

    Solid-state nanopores provide a direct means to detect and analyze DNA and proteins. In a typical setup, the DNA molecules travel through a nanopore under electrophoretic voltage bias. The nanopore is sandwiched between two chambers that are filled with ionic solution. A major challenge in using solid-state nanopores for DNA sequencing and gene detection is to improve their selectivity and detection sensitivity. To achieve these goals, one solution is to functionalize the nanopores by chemically modifying the pore walls with silanes or nucleic acids. However, little is known about molecular interactions in functionalized nanopores. This paper presents DNA translocation dynamics and the mechanism of DNA sequencing in a functionalized nanopore through a coarse-grained molecular dynamics model. The DNA nucleotide is coarse-grained into two interaction sites: one site corresponds to the base group and the other encompasses the phosphate and sugar groups. The water molecules are included in the model implicitly through Langevin dynamics. The coarse-grained model immensely improves the computational efficiency while still capturing the essential translocation dynamics. The model characterizes important physical properties of functionalized nanopores such as the effective pore diameter and effect of biasing voltage on the DNA translocation dynamics. The model reveals a nonlinear relationship between translocation speed of DNA and applied voltage. Moreover, DNA translocation in nanopores functionalized with hairpin-loop (HPL) DNA and single-stranded DNA (ss-DNA) shows significant differences: a target DNA is found to translocate through a ss-DNA coated nanopore 9 times faster than through an HPL coated one at a bias of 100 mV, putatively from lower stiffness of ss-DNA than that for HPL. The DNA translocation speed is also largely influenced by interaction potential between the DNA and surface-tethered molecules. The results reveal that such selective translocation

  7. Highly delayed systemic translocation of aluminum-based adjuvant in CD1 mice following intramuscular injections.

    Science.gov (United States)

    Crépeaux, Guillemette; Eidi, Housam; David, Marie-Odile; Tzavara, Eleni; Giros, Bruno; Exley, Christopher; Curmi, Patrick A; Shaw, Christopher A; Gherardi, Romain K; Cadusseau, Josette

    2015-11-01

    Concerns regarding vaccine safety have emerged following reports of potential adverse events in both humans and animals. In the present study, alum, alum-containing vaccine and alum adjuvant tagged with fluorescent nanodiamonds were used to evaluate i) the persistence time at the injection site, ii) the translocation of alum from the injection site to lymphoid organs, and iii) the behavior of adult CD1 mice following intramuscular injection of alum (400 μg Al/kg). Results showed for the first time a strikingly delayed systemic translocation of adjuvant particles. Alum-induced granuloma remained for a very long time in the injected muscle despite progressive shrinkage from day 45 to day 270. Concomitantly, a markedly delayed translocation of alum to the draining lymph nodes, major at day 270 endpoint, was observed. Translocation to the spleen was similarly delayed (highest number of particles at day 270). In contrast to C57BL/6J mice, no brain translocation of alum was observed by day 270 in CD1 mice. Consistently neither increase of Al cerebral content, nor behavioral changes were observed. On the basis of previous reports showing alum neurotoxic effects in CD1 mice, an additional experiment was done, and showed early brain translocation at day 45 of alum injected subcutaneously at 200 μg Al/kg. This study confirms the striking biopersistence of alum. It points out an unexpectedly delayed diffusion of the adjuvant in lymph nodes and spleen of CD1 mice, and suggests the importance of mouse strain, route of administration, and doses, for future studies focusing on the potential toxic effects of aluminum-based adjuvants. Copyright © 2015 Elsevier Inc. All rights reserved.

  8. Vaccine Timeliness: A Cost Analysis of the Potential Implications of Delayed Pertussis Vaccination in the US.

    Science.gov (United States)

    Curran, Desmond; Terlinden, Augustin; Poirrier, Jean-Etienne; Masseria, Cristina; Krishnarajah, Girishanthy

    2016-05-01

    Pertussis infection remains an important public health problem, particularly in infants. Despite high coverage, pertussis vaccination delays can leave infants at a vulnerable age with less protection than anticipated. Current diphtheria-tetanus-pertussis (DTaP) vaccination timeliness for the first 3 doses in the US was estimated using National Immunization Survey data. A Markov model estimated the potential impact on outcomes and costs of a hypothetical situation of vaccination at exactly 60, 120 and 180 days, compared with current timeliness. Incidence and unit cost data came from published sources. Age-specific incidence (for month of life) of pertussis and the associated probabilities of hospitalization and death for the US, during 2000-2007, were taken from a recently published US DTaP vaccination cost-effectiveness study. The cost analysis was conducted from the healthcare system's perspective over a 1-year time horizon. A regression analysis was conducted to explore the factors associated with vaccination delay. Current DTaP vaccination was estimated to be delayed by 16, 27 and 44 days, for the first, second and third doses, respectively, relative to vaccination at exactly 60, 120 and 180 days. The model estimated that vaccination at exactly age 60, 120 and 180 days could prevent approximately 278 pertussis cases, 103 hospitalizations and 1 death in infants aged vaccine doses could potentially reduce subsequent pertussis cases, hospitalizations, deaths and medical costs in infants aged <1 year in the US.

  9. Genetic variability in the compatibility between Schistosoma haematobium and its potential vectors in Niger. Epidemiological implications.

    Science.gov (United States)

    Véra, C; Jourdane, J; Sellin, B; Combes, C

    1990-06-01

    A populational study of the compatibility between Schistosoma haematobium and its potential vectors has been carried out in the Niger, confronting samples of S. haematobium populations from three epidemiologic foci with Bulinus populations originating from the same focus (sympatric infection) and with Bulinus populations from other foci (allopatric infections). The three transmission foci selected were irrigation canals in ricefields along the Niger river where one finds: Bulinus truncatus rohlfsi, Bulinus globosus, Bulinus forskalii and Bulinus senegalensis; temporary pools in the Sahel area where one finds B. truncatus and B. senegalensis; permanent pools of the "guelta" type in Sahara area where only B. truncatus occurs. As a compatibility test, the snail infection test was selected, with particular emphasis on optimising its reliability. Snail-infection experiments showed that B. truncatus and B. senegalensis are very good potential vectors, with infection rates ranging between 71.5 and 85.9%. B. globosus and B. forskalii, on the other hand, are totally incompatible. The mean infection percentages in the sympatric and allopatric combinations carried out with the S. haematobium-B. truncatus couple were very similar. This character strongly suggests a lack of isolation in schistosome populations and a circulation of the parasite genome through the mobility of infected human populations (Peuls and Touaregs) in Sahel zone. This study, in relation with snail surveys carried out in parallel, shows that the main types of aquatic environments on the Niger act as high risk areas for schistosome transmission.

  10. Free trade area in southeast Europe: Growth potentials and implications for Croatia

    Directory of Open Access Journals (Sweden)

    Nela Vlahinić-Dizdarević

    2004-11-01

    Full Text Available Paper focuses on preconditions, actual trade flows and growth potentials of the Free Trade Zone in Southeast Europe. Further trade liberalisation and implementation of all 21 bilateral trade agreementswould be important incentive for intra-regional trade, especially within SEE-5, where, according to gravity model results, there exist situations of “under-trade”. Bilateral trade between Croatia and S&MNrepresents such “under-trade” situation that gives large space for Croatian export growth to this market. On the other hand, trade with B&His already above the predicted level and it could even fall in the future because great part of B&H imports was triggered by Western assistance. According to the analysis, the establishment of the Free Trade Area in SEE gives potentials for an increase in intra-regional trade (especially SEE-5, but these benefits could be fully reached only by pursuing parallel trade integration towards the EU in order to avoid trade diversion effect.

  11. Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

    Directory of Open Access Journals (Sweden)

    Vincent J. Miller

    2018-01-01

    Full Text Available Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB, which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations.

  12. Nutritional Ketosis and Mitohormesis: Potential Implications for Mitochondrial Function and Human Health

    Science.gov (United States)

    Villamena, Frederick A.

    2018-01-01

    Impaired mitochondrial function often results in excessive production of reactive oxygen species (ROS) and is involved in the etiology of many chronic diseases, including cardiovascular disease, diabetes, neurodegenerative disorders, and cancer. Moderate levels of mitochondrial ROS, however, can protect against chronic disease by inducing upregulation of mitochondrial capacity and endogenous antioxidant defense. This phenomenon, referred to as mitohormesis, is induced through increased reliance on mitochondrial respiration, which can occur through diet or exercise. Nutritional ketosis is a safe and physiological metabolic state induced through a ketogenic diet low in carbohydrate and moderate in protein. Such a diet increases reliance on mitochondrial respiration and may, therefore, induce mitohormesis. Furthermore, the ketone β-hydroxybutyrate (BHB), which is elevated during nutritional ketosis to levels no greater than those resulting from fasting, acts as a signaling molecule in addition to its traditionally known role as an energy substrate. BHB signaling induces adaptations similar to mitohormesis, thereby expanding the potential benefit of nutritional ketosis beyond carbohydrate restriction. This review describes the evidence supporting enhancement of mitochondrial function and endogenous antioxidant defense in response to nutritional ketosis, as well as the potential mechanisms leading to these adaptations. PMID:29607218

  13. Assessing global potential and implications of Carbon Dioxide Removal: how much, for how long, and where might it take us?

    Science.gov (United States)

    Scott, V.

    2014-12-01

    Aiming to keep cumulative anthropogenic carbon release within the 2 degrees C warming budget, useful energy services and value of fossil carbon might be retained if its extraction is balanced by carbon dioxide capture and carbon storage creation. Here, we examine this proposition: assessing the global resource available for carbon storage, the reliable duration of storage, and exploring the resulting hierarchy of different storage types. The balance between fossil carbon supply, and the sufficiency (size) and capability (technology, security) of candidate carbon stores is assessed. The timescale of carbon retention by the variety of proposed stores has potentially important consequences for future climates. A distinction between 'permanent' and 'temporary' carbon storage is considered, and the results and implications for the usage of 'temporary' stores discussed.

  14. Embedded Fragments from U.S. Military Personnel—Chemical Analysis and Potential Health Implications

    Directory of Open Access Journals (Sweden)

    José A. Centeno

    2014-01-01

    microspectroscopy (CLRM. Quantitative chemical analysis of both fragments and available tissues was conducted employing ICP-MS. Results: Over 800 fragments have been characterized and included as part of the Joint Pathology Center Embedded Fragment Registry. Most fragments were obtained from penetrating wounds sustained to the extremities, particularly soft tissue injuries. The majority of the fragments were primarily composed of a single metal such as iron, copper, or aluminum with traces of antimony, titanium, uranium, and lead. One case demonstrated tungsten in both the fragment and the connected tissue, together with lead. Capsular tissue and fragments from a case from the 1991 Kuwait conflict showed evidence of uranium that was further characterized by uranium isotopic ratios analysis to contain depleted uranium. Conclusions: The present study provides a systematic approach for obtaining a full chemical characterization of retained embedded fragments. Given the vast number of combat casualties with retained fragments, it is expected that fragment analysis will have significant implications for the optimal short and long-term care of wounded service members.

  15. Embedded Fragments from U.S. Military Personnel—Chemical Analysis and Potential Health Implications

    Science.gov (United States)

    Centeno, José A.; Rogers, Duane A.; van der Voet, Gijsbert B.; Fornero, Elisa; Zhang, Lingsu; Mullick, Florabel G.; Chapman, Gail D.; Olabisi, Ayodele O.; Wagner, Dean J.; Stojadinovic, Alexander; Potter, Benjamin K.

    2014-01-01

    microspectroscopy (CLRM). Quantitative chemical analysis of both fragments and available tissues was conducted employing ICP-MS. Results: Over 800 fragments have been characterized and included as part of the Joint Pathology Center Embedded Fragment Registry. Most fragments were obtained from penetrating wounds sustained to the extremities, particularly soft tissue injuries. The majority of the fragments were primarily composed of a single metal such as iron, copper, or aluminum with traces of antimony, titanium, uranium, and lead. One case demonstrated tungsten in both the fragment and the connected tissue, together with lead. Capsular tissue and fragments from a case from the 1991 Kuwait conflict showed evidence of uranium that was further characterized by uranium isotopic ratios analysis to contain depleted uranium. Conclusions: The present study provides a systematic approach for obtaining a full chemical characterization of retained embedded fragments. Given the vast number of combat casualties with retained fragments, it is expected that fragment analysis will have significant implications for the optimal short and long-term care of wounded service members. PMID:24464236

  16. Cognitive behaviour therapy and inflammation: A systematic review of its relationship and the potential implications for the treatment of depression.

    Science.gov (United States)

    Lopresti, Adrian L

    2017-06-01

    There is growing evidence confirming increased inflammation in a subset of adults with depression. The impact of this relationship has mostly been considered in biologically based interventions; however, it also has potential implications for psychological therapies. Cognitive behaviour therapy is the most commonly used psychological intervention for the treatment of depression with theories around its efficacy primarily based on psychological mechanisms. However, cognitive behaviour therapy may have an effect on, and its efficacy influenced by, physiological processes associated with depression. Accordingly, the purpose of this systematic review was to examine the relationship between cognitive behaviour therapy and inflammation. Studies examining the anti-inflammatory effects of cognitive behaviour therapy in people with depression and other medical conditions (e.g. cancer, diabetes and heart disease) were examined. In addition, the relationship between change in inflammatory markers and change in depressive symptoms following cognitive behaviour therapy, and the influence of pre-treatment inflammation on cognitive behaviour therapy treatment response were reviewed. A total of 23 studies investigating the anti-inflammatory effects of cognitive behaviour therapy were identified. In 14 of these studies, at least one reduction in an inflammatory marker was reported, increases were identified in three studies and no change was found in six studies. Three studies examined the relationship between change in inflammation and change in depressive symptoms following cognitive behaviour therapy. In two of these studies, change in depressive symptoms was associated with a change in at least one inflammatory marker. Finally, three studies examined the influence of pre-treatment inflammation on treatment outcome from cognitive behaviour therapy, and all indicated a poorer treatment response in people with higher premorbid inflammation. Preliminary evidence suggests

  17. Life History theory hypotheses on child growth: Potential implications for short and long-term child growth, development and health.

    Science.gov (United States)

    Said-Mohamed, Rihlat; Pettifor, John M; Norris, Shane A

    2018-01-01

    Life history theory integrates ecological, physiological, and molecular layers within an evolutionary framework to understand organisms' strategies to optimize survival and reproduction. Two life history hypotheses and their implications for child growth, development, and health (illustrated in the South African context) are reviewed here. One hypothesis suggests that there is an energy trade-off between linear growth and brain growth. Undernutrition in infancy and childhood may trigger adaptive physiological mechanisms prioritizing the brain at the expense of body growth. Another hypothesis is that the period from conception to infancy is a critical window of developmental plasticity of linear growth, the duration of which may vary between and within populations. The transition from infancy to childhood may mark the end of a critical window of opportunity for improving child growth. Both hypotheses emphasize the developmental plasticity of linear growth and the potential determinants of growth variability (including the role of parent-offspring conflict in maternal resources allocation). Implications of these hypotheses in populations with high burdens of undernutrition and infections are discussed. In South Africa, HIV/AIDS during pregnancy (associated with adverse birth outcomes, short duration of breastfeeding, and social consequences) may lead to a shortened window of developmental plasticity of growth. Furthermore, undernutrition and infectious diseases in children living in South Africa, a country undergoing a rapid nutrition transition, may have adverse consequences on individuals' cognitive abilities and risks of cardio-metabolic diseases. Studies are needed to identify physiological mechanisms underlying energy allocation between biological functions and their potential impacts on health. © 2017 Wiley Periodicals, Inc.

  18. Occurrence and growth of yeasts in processed meat products - implications for potential spoilage

    DEFF Research Database (Denmark)

    Nielsen, Dennis Sandris; Jacobsen, Tomas; Jespersen, Lene

    2008-01-01

    Spoilage of meat products is in general attributed to bacteria but new processing and storage techniques inhibiting growth of bacteria may provide opportunities for yeasts to dominate the microflora and cause spoilage of the product. With the aim of obtaining a deeper understanding of the potential...... role of yeast in spoilage of five different processed meat products (bacon, ham, salami and two different liver patés), yeasts were isolated, enumerated and identified during processing, in the final product and in the final product at the end of shelf life. Yeasts were isolated along the bacon...... of the processed meat products. The yeast microflora was complex with 4-12 different species isolated from the different production sites. In general, Candida zeylanoides, Debaryomyces hansenii and the newly described Candida alimentaria were found to be the dominant yeast species. In addition, three putatively...

  19. Forward-looking farmers owning multiple potential wetland restoration sites: implications for efficient restoration

    Science.gov (United States)

    Schroder (Kushch), Svetlana; Lang, Zhengxin; Rabotyagov, Sergey

    2018-04-01

    Wetland restoration can increase the provision of multiple non-market ecosystem services. Environmental and socio-economic factors need to be accounted for when land is withdrawn from agriculture and wetlands are restored. We build multi-objective optimization models to provide decision support for wetland restoration in the Le Sueur river watershed in Southern Minnesota. We integrate environmental objectives of sediment reduction and habitat protection with socio-economic factors associated with the overlap of private land with potential wetland restoration sites in the watershed and the costs representing forward-looking farmers voluntarily taking land out of agricultural production in favor of wetland restoration. Our results demonstrate that the inclusion of these factors early on in the restoration planning process affects both the total costs of the restoration project and the spatial distribution of optimally selected wetland restoration sites.

  20. Western Pacific Tropospheric Ozone and Potential Vorticity: Implications for Asian Pollution

    Science.gov (United States)

    Browell, Edward V.; Newell, Reginald E.; Davis, Douglas D.; Liu, Shaw C.

    1997-01-01

    Tropospheric ozone (03) cross sections measured with lidar from a DC-8 aircraft over the western Pacific correspond closely with potential vorticity (PV). Both are transported from the middle latitude stratosphere, although this is not the only source of 03, and both have sinks in the tropical boundary layer. 03 and PV are good indicators of photochemical and transport process interactions. In summer, some Asian pollution, raised by convection to the upper troposphere, passes southward into the tropics and to the Southern Hemisphere. In winter, subsidence keeps the pollution at low altitudes where it moves over the ocean towards the Inter-Tropical Convergence Zone (ITCZ), with photochemical destruction and secondary pollutant generation occurring en route. Convection raises this modified air to the upper troposphere, where some re may enter the stratosphere. Thus winter Asian pollution may at have a smaller direct influence on the global atmosphere than it would if injected at other longitudes and seasons.

  1. The maternal brain under stress: Consequences for adaptive peripartum plasticity and its potential functional implications.

    Science.gov (United States)

    Slattery, David A; Hillerer, Katharina M

    2016-04-01

    The peripartum period represents a time during which all mammalian species undergo substantial physiological and behavioural changes, which prepare the female for the demands of motherhood. In addition to behavioural and physiological alterations, numerous brain regions, such as the medial prefrontal cortex, olfactory bulb, medial amygdala and hippocampus are subject to substantial peripartum-associated neuronal, dendritic and synaptic plasticity. These changes, which are temporally- and spatially-distinct, are strongly influenced by gonadal and adrenal hormones, such as estrogen and cortisol/corticosterone, which undergo dramatic fluctuations across this period. In this review, we describe our current knowledge regarding these plasticity changes and describe how stress affects such normal adaptations. Finally, we discuss the mechanisms potentially underlying these neuronal, dendritic and synaptic changes and their functional relevance for the mother and her offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Inhibition of enzyme activity by nanomaterials: potential mechanisms and implications for nanotoxicity testing.

    Science.gov (United States)

    Maccormack, Tyson J; Clark, Rhett J; Dang, Michael K M; Ma, Guibin; Kelly, Joel A; Veinot, Jonathan G C; Goss, Greg G

    2012-08-01

    The objective of this study was to investigate whether nanoparticle-exposure affects enzyme function and to determine the mechanisms responsible. Silicon, Au, and CdSe nanoparticles were synthesized in house and their physicochemical properties were characterized. The activity of purified lactate dehydrogenase (LDH) was inhibited or abolished by all nanoparticles tested. Inhibition was dependent upon particle core and surface-functional group composition. Inhibition of LDH was absent in crude tissue homogenates, in the presence of albumin, and at the isoelectric point of the protein, indicating that nanoparticles bind non-specifically to abundant proteins via a charge interaction. Circular dichroism spectroscopy suggests that the structure of LDH may be altered by nanoparticles in a manner different from that of bulk controls. We present new data on the specific physicochemical properties of nanoparticles that may lead to bioactivity and highlight a number of potentially serious problems with common nanotoxicity testing methods.

  3. Contrasting optical properties of surface waters across the Fram Strait and its potential biological implications

    DEFF Research Database (Denmark)

    Pavlov, Alexey K.; Granskog, Mats A.; Stedmon, Colin A.

    2015-01-01

    Spitsbergen Current (WSC) differ with regards to temperature, salinity and optical properties. We present data on absorption properties of CDOM and particles across the Fram Strait (along 79° N), comparing Polar and Atlantic surface waters in September 2009 and 2010. CDOM absorption of Polar water in the EGC...... budget in the upper 0-10m shifts across Fram Strait. Under water spectral irradiance profiles were generated using ECOLIGHT 5.4.1 and the results indicate that the shift in composition between dissolved and particulate material does not influence substantially the penetration of photosynthetic active...... radiation (PAR, 400-700nm), but does result in notable differences in ultraviolet (UV) light penetration, with higher attenuation in the EGC. Future changes in the Arctic Ocean system will likely affect EGC through diminishing sea-ice cover and potentially increasing CDOM export due to increase in river...

  4. Draft genome sequence of Microbacterium oleivorans strain Wellendorf implicates heterotrophic versatility and bioremediation potential

    Directory of Open Access Journals (Sweden)

    Anton P. Avramov

    2016-12-01

    Full Text Available Microbacterium oleivorans is a predominant member of hydrocarbon-contaminated environments. We here report on the genomic analysis of M. oleivorans strain Wellendorf that was isolated from an indoor door handle. The partial genome of M. oleivorans strain Wellendorf consists of 2,916,870 bp of DNA with 2831 protein-coding genes and 49 RNA genes. The organism appears to be a versatile mesophilic heterotroph potentially capable of hydrolysis a suite of carbohydrates and amino acids. Genomic analysis revealed metabolic versatility with genes involved in the metabolism and transport of glucose, fructose, rhamnose, galactose, xylose, arabinose, alanine, aspartate, asparagine, glutamate, serine, glycine, threonine and cysteine. This is the first detailed analysis of a Microbacterium oleivorans genome.

  5. Sensory action potentials of the maxillary nerve: a methodologic study with clinical implications

    DEFF Research Database (Denmark)

    Thygesen, Torben; Baad-Hansen, Lene; Svensson, Peter

    2009-01-01

    PURPOSE: Recently, recording of sensory nerve action potentials (SNAPs) of the inferior alveolar nerve (IAN) was described and is used as a diagnostic test of traumatic neuropathic trigeminal disorders. The technique is limited to IAN damage; therefore, we adapted the technique to the maxillary...... nerve, which is also frequently injured by either trauma or orthognathic surgery. PATIENTS AND METHODS: Fourteen healthy volunteers participated in this methodologic study in which the infraorbital nerve (ION) was stimulated with 2 needle electrodes. The SNAPs were recorded from the maxillary nerve...... difference. Repeated tests within a session test demonstrated no significant differences in the latency data (ANOVA: P= .225) or amplitude data (ANOVA: P= .44). Stimulus-response curves indicated that the SNAPs saturated at 5.1+/-4.4 mA stimulus intensity. In 1 subject, stimulation of the mental nerve...

  6. Glucose sensing by carotid body glomus cells: potential implications in disease

    Directory of Open Access Journals (Sweden)

    Lin eGao

    2014-10-01

    Full Text Available The carotid body (CB is a key chemoreceptor organ in which glomus cells sense changes in blood O2, CO2, and pH levels. CB glomus cells have also been found to detect hypoglycemia in both non-primate mammals and humans. O2 and low-glucose responses share a common final pathway involving membrane depolarization, extracellular calcium influx, increase in cytosolic calcium concentration, and neurotransmitter secretion, which stimulates afferent sensory fibers to evoke sympathoadrenal activation. On the other hand, hypoxia and low glucose induce separate signal transduction pathways. Unlike O2 sensing, the response of the CB to low glucose is not altered by rotenone, with the low glucose-activated background cationic current unaffected by hypoxia. Responses of the CB to hypoglycemia and hypoxia can be potentiated by each other. The counter-regulatory response to hypoglycemia by the CB is essential for the brain, an organ that is particularly sensitive to low glucose. CB glucose sensing could be altered in diabetic patients, particularly those under insulin treatment, as well as in other medical conditions such as sleep apnea or obstructive pulmonary diseases, where chronic hypoxemia presents with plastic modifications in CB structure and function. The current review will focus on the following main aspects: 1 the CB as a low glucose sensor in both in vitro and in vivo models; 2 molecular and ionic mechanisms of low glucose sensing by glomus cells, 3 the interplay between low glucose and O2 sensing in CB, and 4 the role of CB low glucose sensing in the pathophysiology of cardiorespiratory and metabolic diseases, and how this may serve as a potential therapeutic target.

  7. Measuring the solar potential of a city and its implications for energy policy

    International Nuclear Information System (INIS)

    Byrd, Hugh; Ho, Anna; Sharp, Basil; Kumar-Nair, Nirmal

    2013-01-01

    This research investigates the maximum potential energy that can be made available by efficiently installing photovoltaic (PV) systems on buildings throughout a city, from the central business district (CBD) out to low density suburbs. The purpose of this is to evaluate the contribution that electricity from PVs can make to reduce the electricity load of a city, supply the needs of a mixture of building types, reduce peak electricity demand and contribute towards the charging of electric vehicles (EVs). Having established the maximum potential, intermediate stages in PV penetration can be backcasted. The results indicate that low dense suburbia is not only the most efficient collector of solar energy but that enough excess electricity can be generated to power daily transport needs of suburbia and also contribute to peak daytime electrical loads in the city centre. This challenges conventional thinking that suburbia is energy inefficient. While a compact city may be more efficient for the internal combustion engine vehicles, a dispersed city is more efficient when distributed generation of electricity by PVs is the main energy source and EVs are the means of transport. - Highlights: • A method for analysing the contribution of photovoltaics to a whole city is described. • Maps are presented that compare net-metering of energy throughout a city. • These maps provide a useful tool for renewable energy policy in urban areas. • In the case of Auckland, suburbia can be a net energy provider to the city. • Suburbia can produce electricity to charge all its electric vehicle travel needs

  8. Surface Electrical Potentials of Root Cell Plasma Membranes: Implications for Ion Interactions, Rhizotoxicity, and Uptake

    Directory of Open Access Journals (Sweden)

    Yi-Min Wang

    2014-12-01

    Full Text Available Many crop plants are exposed to heavy metals and other metals that may intoxicate the crop plants themselves or consumers of the plants. The rhizotoxicity of heavy metals is influenced strongly by the root cell plasma membrane (PM surface’s electrical potential (ψ0. The usually negative ψ0 is created by negatively charged constituents of the PM. Cations in the rooting medium are attracted to the PM surface and anions are repelled. Addition of ameliorating cations (e.g., Ca2+ and Mg2+ to the rooting medium reduces the effectiveness of cationic toxicants (e.g., Cu2+ and Pb2+ and increases the effectiveness of anionic toxicants (e.g., SeO42− and H2AsO4−. Root growth responses to ions are better correlated with ion activities at PM surfaces ({IZ}0 than with activities in the bulk-phase medium ({IZ}b (IZ denotes an ion with charge Z. Therefore, electrostatic effects play a role in heavy metal toxicity that may exceed the role of site-specific competition between toxicants and ameliorants. Furthermore, ψ0 controls the transport of ions across the PM by influencing both {IZ}0 and the electrical potential difference across the PM from the outer surface to the inner surface (Em,surf. Em,surf is a component of the driving force for ion fluxes across the PM and controls ion-channel voltage gating. Incorporation of {IZ}0 and Em,surf into quantitative models for root metal toxicity and uptake improves risk assessments of toxic metals in the environment. These risk assessments will improve further with future research on the application of electrostatic theory to heavy metal phytotoxicity in natural soils and aquatic environments.

  9. Potential diagnostic implications of miR-144 overexpression in human oesophageal cancer

    Directory of Open Access Journals (Sweden)

    Priyanka Sharma

    2016-01-01

    Full Text Available Background & objectives: Insidious symptomatology, late clinical presentation and poor prognosis of oesophageal cancer (EC highlight the pressing need for novel non-invasive biomarkers for early tumour diagnosis and better prognosis. The present study was carried out to evaluate the clinical significance of circulating and tissue miR-144 expression in oesophageal cancer. Methods: Clinical significance of miR-144 expression was evaluated in preneoplastic (12 and neoplastic (35 oesophageal cancer tissues as well as matched distant non-malignant tissues using real-time PCR (qPCR. Circulating levels of miR-144 were also analyzed in serum samples of EC patients as well as normal individuals to determine the diagnostic potential of miR-144. Further, targets of miR-144 were predicted using bioinformatic tools and their gene ontology (GO terms were assigned. Results: Real-time PCR analysis revealed significant upregulation of miR-144 in 29 of 35 (83% EC tissues as compared to matched distant non-malignant tissues (P=0.010. a0 ll the dysplastic tissues showed upregulation of miR-144 as compared to their matched distant non-malignant tissues. Relative levels of circulating miR-144 in serum significantly distinguished EC patients from normal controls (P=0.015; AUC = 0.731 with high sensitivity of 94.7 per cent. Bioinformatically predicted target, PUR-aplha (PURA was found to be significantly (P=0.018 downregulated in 81 per cent (26/32 EC patients and its expression was found to be significantly and negatively correlated with miR-144 expression at mRNA level. Interpretation & conclusions: Our findings showed significant upregulation of miR-144 in serum samples of EC patients indicating its potential as minimally invasive marker. Further studies need to be done to understand the role of miR-144 in the pathogenesis of EC.

  10. Low-carbohydrate diets: what are the potential short- and long-term health implications?

    Science.gov (United States)

    Bilsborough, Shane A; Crowe, Timothy C

    2003-01-01

    Low-carbohydrate diets for weight loss are receiving a lot of attention of late. Reasons for this interest include a plethora of low-carbohydrate diet books, the over-sensationalism of these diets in the media and by celebrities, and the promotion of these diets in fitness centres and health clubs. The re-emergence of low-carbohydrate diets into the spotlight has lead many people in the general public to question whether carbohydrates are inherently 'bad' and should be limited in the diet. Although low-carbohydrate diets were popular in the 1970s they have resurged again yet little scientific fact into the true nature of how these diets work or, more importantly, any potential for serious long-term health risks in adopting this dieting practice appear to have reached the mainstream literature. Evidence abounds that low-carbohydrate diets present no significant advantage over more traditional energy-restricted, nutritionally balanced diets both in terms of weight loss and weight maintenance. Studies examining the efficacy of using low-carbohydrate diets for long-term weight loss are few in number, however few positive benefits exist to promote the adoption of carbohydrate restriction as a realistic, and more importantly, safe means of dieting. While short-term carbohydrate restriction over a period of a week can result in a significant loss of weight (albeit mostly from water and glycogen stores), of serious concern is what potential exists for the following of this type of eating plan for longer periods of months to years. Complications such as heart arrhythmias, cardiac contractile function impairment, sudden death, osteoporosis, kidney damage, increased cancer risk, impairment of physical activity and lipid abnormalities can all be linked to long-term restriction of carbohydrates in the diet. The need to further explore and communicate the untoward side-effects of low-carbohydrate diets should be an important public health message from nutrition professionals.

  11. Public health implications of Acanthamoeba and multiple potential opportunistic pathogens in roof-harvested rainwater tanks.

    Science.gov (United States)

    Hamilton, K A; Ahmed, W; Palmer, A; Sidhu, J P S; Hodgers, L; Toze, S; Haas, C N

    2016-10-01

    A study of six potential opportunistic pathogens (Acanthamoeba spp., Legionella spp., Legionella longbeachae, Pseudomonas aeruginosa, Mycobacterium avium and Mycobacterium intracellulare) and an accidental human pathogen (Legionella pneumophila) in 134 roof-harvested rainwater (RHRW) tank samples was conducted using quantitative PCR (qPCR). All five opportunistic pathogens and accidental pathogen L. pneumophila were detected in rainwater tanks except Legionella longbeachae. Concentrations ranged up to 3.1×10(6) gene copies per L rainwater for Legionella spp., 9.6×10(5) gene copies per L for P. aeruginosa, 6.8×10(5) gene copies per L for M. intracellulare, 6.6×10(5) gene copies per L for Acanthamoeba spp., 1.1×10(5) gene copies per L for M. avium, and 9.8×10(3) gene copies per L for L. pneumophila. Among the organisms tested, Legionella spp. (99% tanks) were the most prevalent followed by M. intracellulare (78%). A survey of tank-owners provided data on rainwater end-uses. Fecal indicator bacteria (FIB) Escherichia coli and Enterococcus spp. were enumerated using culture-based methods, and assessed for correlations with opportunistic pathogens and L. pneumophila tested in this study. Opportunistic pathogens did not correlate well with FIB except E. coli vs. Legionella spp. (tau=0.151, P=0.009) and E. coli vs. M. intracellulare (tau=0.14, P=0.015). However, M. avium weakly correlated with both L. pneumophila (Kendall's tau=0.017, P=0.006) and M. intracellulare (tau=0.088, P=0.027), and Legionella spp. also weakly correlated with M. intracellulare (tau=0.128, P=0.028). The presence of these potential opportunistic pathogens in tank water may present health risks from both the potable and non-potable uses documented from the current survey data. Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.

  12. Sorption, Uptake, and Translocation of Pharmaceuticals across Multiple Interfaces in Soil Environment

    Science.gov (United States)

    Zhang, W.; Liu, C. H.; Bhalsod, G.; Zhang, Y.; Chuang, Y. H.; Boyd, S. A.; Teppen, B. J.; Tiedje, J. M.; Li, H.

    2015-12-01

    Pharmaceuticals are contaminants of emerging concern frequently detected in soil and water environments, raising serious questions on their potential impact on human and ecosystem health. Overuse and environmental release of antibiotics (i.e., a group of pharmaceuticals extensively used in human medicine and animal agriculture) pose enormous threats to the health of human, animal, and the environment, due to proliferation of antibiotic resistant bacteria. Recently, we have examined interactions of pharmaceuticals with soil geosorbents, bacteria, and vegetable crops in order to elucidate pathways of sorption, uptake, and translocation of pharmaceuticals across the multiple interfaces in soils. Sorption of pharmaceuticals by biochars was studied to assess the potential of biochar soil amendment for reducing the transport and bioavailability of antibiotics. Our preliminary results show that carbonaceous materials such as biochars and activated carbon had strong sorption capacities for antibiotics, and consequently decreased the uptake and antibiotic resistance gene expression by an Escherichia coli bioreporter. Thus, biochar soil amendment showed the potential for reducing selection pressure on antibiotic resistant bacteria. Additionally, since consumption of pharmaceutical-tainted food is a direct exposure pathway for humans, it is important to assess the uptake and accumulation of pharmaceuticals in food crops grown in contaminated soils or irrigated with reclaimed water. Therefore, we have investigated the uptake and accumulations of pharmaceuticals in greenhouse-grown lettuce under contrasting irrigation practices (i.e., overhead or surface irrigations). Preliminary results indicate that greater pharmaceutical concentrations were measured in overhead irrigated lettuce than in surface irrigated lettuce. This could have important implications when selecting irrigation scheme to use the reclaimed water for crop irrigation. In summary, proper soil and water management

  13. Measurement of background translocation frequencies in individuals with clones

    Energy Technology Data Exchange (ETDEWEB)

    Wade, Marcelle J. [California State Univ. (CalState), Hayward, CA (United States)

    1996-08-01

    In the leukemia case the unseparated B and T lymphocytes had a high translocation frequency even after 0.0014, respectively. After purging all clones from the data, the translocation frequencies for Bio 8 and Bio 23 were 0.00750.0014 and 0.0073 metaphases were scored for chromosomal aberrations,, specifically reciprocal translocations, using fluorescence in situ hybridization (FISH). Metaphase spreads were used from two healthy, unexposed individuals (not exposed to radiation, chemotherapy or radiotherapy) and one early B- precursor acute lymphocytic leukemia (ALL) patient (metaphase spreads from both separated T lymphocytes and unseparated B and T lymphocytes were scored). All three individuals had an abnormally high translocation frequency. The high translocation frequencies resulted from clonal expansion of specific translocated chromosomes. I show in this thesis that by purging (discounting or removing) clones from the data of unexposed individuals, one can obtain true background translocation frequencies. In two cases, Bio 8 and Bio 23, the measured translocation frequency for chromosomes 1, 2 and 4 was 0.0124 purging all of the clones from the data. This high translocation frequency may be due to a low frequency of some clones and may not be recognized. The separated T lymphocytes had a higher translocation frequency than expected.

  14. Implication of Land Use and Belowground Weather on Nitrous Oxide Soil Depth Profiles and Denitrification Potential

    Science.gov (United States)

    Phillips, R. L.; Song, B.; Saliendra, N.; Liebig, M. A.

    2013-12-01

    Agricultural soils are the largest single source of anthropogenic nitrous oxide (N2O) to the atmosphere, which is largely attributed to the expansion in the use of synthetic fertilizer nitrogen (N). Alfalfa crops often do not require synthetic N addition because N is fixed symbiotically belowground. Some biologically fixed N leaks into soil, which could affect production and consumption of N2O. While many studies have reported net fluxes of N2O at the soil surface, few have quantified variation in N2O concentration at multiple soil depths under variable climatic conditions without synthetic N inputs. A no-till crop field, seeded to alfalfa (Medicago sativa) in 2009, was compared to neighboring native prairie in North Dakota, U.S.A. to determine if N2O, CO2 and CH4 concentrations varied with depth between fields for 4 years. Both fields (> 15 ha) were harvested for hay without N-fertilizer inputs between 2009 and 2013. Soils and instrumentation were similar. Sensors and soil gas well collection chambers were buried at near-surface (15 and 30 cm) and sub-surface (60 and 90 cm) soil depths. Temperature, moisture, oxygen, relative humidity, and pressure data were collected every 30 minutes, and gas well concentration data were collected twice weekly until spring 2013. Cores were collected for each depth increment in 2012, and potential rates of denitrification and anammox were measured for the 0-15 cm depth using soil slurry incubation experiments with 15N tracer treatments. We evaluated temporal variability in N2O concentration with depth and found N2O spikes beneath alfalfa tended to be an order of magnitude higher and more persistent than N2O peaks beneath prairie. Median N2O concentrations at sub-surface depths were greater than near-surface depths. Alfalfa median N2O concentrations for near-surface (24 nmols N2O L-1) and sub-soils (30 nmols N2O L-1) were higher than N2O concentrations beneath prairie (15 nmols N2O L-1 and 17 nmols N2O L-1, respectively). Soil

  15. Emerging drugs affecting skeletal muscle function and mitochondrial biogenesis - Potential implications for sports drug testing programs.

    Science.gov (United States)

    Thevis, Mario; Schänzer, Wilhelm

    2016-03-15

    A plethora of compounds potentially leading to drug candidates that affect skeletal muscle function and, more specifically, mitochondrial biogenesis, has been under (pre)clinical investigation for rare as well as more common diseases. Some of these compounds could be the object of misuse by athletes aiming at artificial and/or illicit and drug-facilitated performance enhancement, necessitating preventive and proactive anti-doping measures. Early warnings and the continuous retrieval and dissemination of information are crucial for sports drug testing laboratories as well as anti-doping authorities, as they assist in preparation of efficient doping control analytical strategies for potential future threats arising from new therapeutic developments. Scientific literature represents the main source of information, which yielded the herein discussed substances and therapeutic targets, which might become relevant for doping controls in the future. Where available, mass spectrometric data are presented, supporting the development of analytical strategies and characterization of compounds possibly identified in human sports drug testing samples. Focusing on skeletal muscle and mitochondrial biogenesis, numerous substances exhibiting agonistic or antagonistic actions on different cellular 'control centers' resulting in increased skeletal muscle mass, enhanced performance (as determined with laboratory animal models), and/or elevated amounts of mitochondria have been described. Substances of interest include agonists for REV-ERBα (e.g. SR9009, SR9011, SR10067, GSK4112), sirtuin 1 (e.g. SRT1720, SRT2104), adenosine monophosphate-activated protein kinase (AMPK, e.g. AICAR), peroxisome proliferator-activated receptor (PPAR)δ (e.g. GW1516, GW0742, L165041), and inhibitory/antagonistic agents targeting the methionine-folate cycle (MOTS-c), the general control non-derepressible 5 (GCN5) acetyl transferase (e.g. CPTH2, MB-3), myostatin (e.g. MYO-029), the myostatin receptor

  16. Dietary origin of mycotoxins with estrogenic potential and possible health implications to female dogs.

    Science.gov (United States)

    Golinski, P K; Nowak, T

    2004-01-01

    In Poland, occurrence of toxigenic fungi in cereals, foods, feeds and their components as well as mycotoxins accumulation in such material has been studied by numerous teams including our research group for over thirty years since 1969. Mostly cereal kernels and feeds have been examined for presence of toxigenic fungi, their toxigenic potential and natural contamination with mycotoxins. Ochratoxin A, deoxynivalenol, nivalenol and moniliformin were found to be significant contaminants of agricultural products in high percentage of cereal grain samples. The profile of toxic metabolites was similar but the concentration levels of the toxins were lower when compared to already published data of the same climate zone. Zearalenone (ZEA), a nonsteroidal mycotoxin with estrogen-like activity, is synthesized by molds (Fusarium) commonly contaminating poorly stored agricultural products and foodstuffs. Since in the course of examinations and during surgical procedures performed in dogs, ovarian cysts were detected and because frequently this is the first stage of the endometrica pyometra complex (EPC) found in approximately 30% of the females we assume that both factors, mycotoxins (ZEA) and pathological aberrations are possibly related in these animals. Similar activity of the toxin (possibly present in pelleted dog feed) and effects including infertility of female dogs is speculated with indication and suggestion on necessity of additional studies on the problem.

  17. Virus–Bacteria Interactions: Implications and Potential for the Applied and Agricultural Sciences

    Directory of Open Access Journals (Sweden)

    Matthew D. Moore

    2018-02-01

    Full Text Available Eukaryotic virus–bacteria interactions have recently become an emerging topic of study due to multiple significant examples related to human pathogens of clinical interest. However, such omnipresent and likely important interactions for viruses and bacteria relevant to the applied and agricultural sciences have not been reviewed or compiled. The fundamental basis of this review is that these interactions have importance and deserve more investigation, as numerous potential consequences and applications arising from their discovery are relevant to the applied sciences. The purpose of this review is to highlight and summarize eukaryotic virus–bacteria findings in the food/water, horticultural, and animal sciences. In many cases in the agricultural sciences, mechanistic understandings of the effects of virus–bacteria interactions remain unstudied, and many studies solely focus on co-infections of bacterial and viral pathogens. Given recent findings relative to human viral pathogens, further research related to virus–bacteria interactions would likely result in numerous discoveries and beneficial applications.

  18. Exploring novel candidate genes from the Mouse Genome Informatics database: Potential implications for avian migration research.

    Science.gov (United States)

    Contina, Andrea; Bridge, Eli S; Kelly, Jeffrey F

    2016-07-01

    To search for genes associated with migratory phenotypes in songbirds, we selected candidate genes through annotations from the Mouse Genome Informatics database and assembled an extensive candidate-gene library. Then, we implemented a next-generation sequencing approach to obtain DNA sequences from the Painted Bunting genome. We focused on those sequences that were conserved across avian species and that aligned with candidate genes in our mouse library. We genotyped short sequence repeats from the following candidate genes: ADRA1d, ANKRD17, CISH and MYH7. We studied the possible correlations between allelic variations occurring in these novel candidate migration genes and avian migratory phenotypes available from the published literature. We found that allele variation at MYH7 correlated with a calculated index of speed of migration (km/day) across 11 species of songbirds. We highlight the potential of the Mouse Genome Informatics database in providing new candidate genes that might play a crucial role in regulating migration in birds and possibly in other taxa. Our research effort shows the benefits and limitations of working with extensive genomic datasets and offers a snapshot of the challenges related to cross-species validation in behavioral and molecular ecology studies. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  19. Potential health and economic benefits of three locally grown nuts in Nigeria: implications for developing countries

    Directory of Open Access Journals (Sweden)

    Ayomadewa Mercy Olatunya

    2017-10-01

    Full Text Available Malnutrition and lack of economic sustainability are major problems in developing countries. This study was conducted to evaluate and compare the nutrients‘ contents of three locally grown nuts in Nigeria (local groundnut, Kampala groundnut and breadnut and highlight their health and economic potentials. Proximate analysis, chemical properties, minerals and fatty acids composition of the nuts were determined. The highest protein, crude fibre and carbohydrate contents were found in Kampala groundnut, local groundnut and breadnut respectively. Their sodium-potassium ratios were all less than 1.0 and their oils have mainly unsaturated fatty acids. Their acid values ranged between (2.41–6.34 mgKOH/g while the iodine values were between 36.0 and 93.0 I2 g/100 g. Analysis of the nuts and their oils indicated that they could help in solving malnutrition problem and also boost nations’ economy. Encouraging their large scale production can enhance adequate nutrition and sustain industrial growth in developing countries. Keywords: Nutrition, Food analysis, Food science

  20. Characterization of potential lytic bacteriophage against Vibrio alginolyticus and its therapeutic implications on biofilm dispersal.

    Science.gov (United States)

    Sasikala, Dakshinamurthy; Srinivasan, Pappu

    2016-12-01

    Vibrio alginolyticus is a leading cause of vibriosis, presenting opportunistic infections to humans associated with raw seafood contamination. At present, phage therapy that acts as an alternative sanitizing agent is explored for targeting V. alginolyticus. The study outcome revealed that the phage VP01 with its extreme lytic effect showed a high potential impact on the growth of V. alginolyticus as well as biofilm formation. Electron microscopy revealed the phage resemblance to Myoviridae, based on its morphology. Further study clarified that the phage VP01 possesses a broad host spectrum and amazing phage sensitivity at different pH, high thermal stability, and high burst size of 415 PFU/cell. In addition, the investigation of phage co-culturing against this pathogen resulted in a significant growth reduction even at less MOIs 0.1 and 1. These results suggest that the phage could be a promising candidate for the control of V. alginolyticus infections. Copyright © 2016 Elsevier Ltd. All rights reserved.

  1. Endoscopic appearance of proximal colorectal neoplasms and potential implications for colonoscopy in cancer prevention.

    Science.gov (United States)

    Rondagh, Eveline J A; Bouwens, Mariëlle W E; Riedl, Robert G; Winkens, Bjorn; de Ridder, Rogier; Kaltenbach, Tonya; Soetikno, Roy M; Masclee, Ad A M; Sanduleanu, Silvia

    2012-06-01

    In everyday practice, the use of colonoscopy for the prevention of colorectal cancer (CRC) is less effective in the proximal than the distal colon. A potential explanation for this is that proximal neoplasms have a more subtle endoscopic appearance, making them more likely to be overlooked. To investigate the differences in endoscopic appearance, ie, diminutive size and nonpolypoid shape, of proximal compared with distal colorectal neoplasms. Cross-sectional, single-center study. Endoscopists at the Maastricht University Medical Center in the Netherlands who were previously trained in the detection and classification of nonpolypoid colorectal lesions. Consecutive patients undergoing elective colonoscopy. Endoscopic appearance, ie, diminutive size (colorectal adenomas and serrated polyps (SPs), with a focus on adenomas with advanced histology, ie, high-grade dysplasia or early CRC and SPs with dysplasia or large size. We included 3720 consecutive patients with 2106 adenomas and 941 SPs. We found that in both men and women, proximal adenomas with high-grade dysplasia/early CRC (n = 181) were more likely to be diminutive or nonpolypoid than distal ones (76.3% vs 26.2%; odds ratio [OR] 9.24; 95% CI, 4.45-19.2; P colorectal neoplasms with advanced histology frequently are small or have a nonpolypoid appearance. These findings support careful inspection of the proximal colon, if quality of cancer prevention with the use of colonoscopy is to be optimized. Copyright © 2012 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

  2. Interaction of the 106-126 prion peptide with lipid membranes and potential implication for neurotoxicity

    International Nuclear Information System (INIS)

    Dupiereux, Ingrid; Zorzi, Willy; Lins, Laurence; Brasseur, Robert; Colson, Pierre; Heinen, Ernst; Elmoualij, Benaissa

    2005-01-01

    Prion diseases are fatal neurodegenerative disorders characterized by the accumulation in the brain of an abnormally misfolded, protease-resistant, and β-sheet rich pathogenic isoform (PrP sc ) of the cellular prion protein (PrP c ). In the present work, we were interested to study the mode of prion protein interaction with the membrane using the 106-126 peptide and small unilamellar lipid vesicles as model. As previously demonstrated, we showed by MTS assay that PrP 106-126 induces alterations in the human neuroblastoma SH-SY5Y cell line. We demonstrated for the first time by lipid-mixing assay and by the liposome vesicle leakage test that PrP 106-126, a non-tilted peptide, induces liposome fusion thus a potential cell membrane destabilization, as supported by membrane integrity assay (LDH). By circular dichroism (CD) analysis we showed that the fusogenic property of PrP 106-126 in the presence of liposome is associated with a predominantly β-sheet structure. These data suggest that the fusogenic property associated with a predominant β-sheet structure exhibited by the prion peptides contributes to the neurotoxicity of these peptides by destabilizing cellular membranes. The latter might be attached at the membrane surface in a parallel orientation as shown by molecular modeling

  3. Palladium Nanoparticles: Toxicological Effects and Potential Implications for Occupational Risk Assessment

    Directory of Open Access Journals (Sweden)

    Veruscka Leso

    2018-02-01

    Full Text Available The increasing technological applications of palladium nanoparticles (Pd-NPs and their consequent enhancing release into the community and occupational environments, have raised public health concerns regarding possible adverse effects for exposed subjects, and particularly for workers chronically and highly exposed to these materials, whose toxico-kinetic and dynamic behavior remains to be fully understood. Therefore, this review aimed to critically analyze literature data to achieve a more comprehensive knowledge on the toxicological profile of Pd-NPs. Results from available studies demonstrated the potential for these chemicals to affect the ecosystem function, to exert cytotoxic and pro-inflammatory effects in vitro as well as to induce early alterations in different target organs in in vivo models. However, our revision pointed out the need for future studies aimed to clarify the role of the NP physico-chemical properties in determining their toxicological behavior, as well as the importance to carry out investigations focused on environmental and biological monitoring to verify and validate experimental biomarkers of exposure and early effect in real exposure contexts. Overall, this may be helpful to support the definition of suitable strategies for the assessment, communication and management of Pd-NP occupational risks to protect the health and safety of workers.

  4. Heteroreceptors Modulating CGRP Release at Neurovascular Junction: Potential Therapeutic Implications on Some Vascular-Related Diseases

    Directory of Open Access Journals (Sweden)

    Abimael González-Hernández

    2016-01-01

    Full Text Available Calcitonin gene-related peptide (CGRP is a 37-amino-acid neuropeptide belonging to the calcitonin gene peptide superfamily. CGRP is a potent vasodilator with potential therapeutic usefulness for treating vascular-related disease. This peptide is primarily located on C- and Aδ-fibers, which have extensive perivascular presence and a dual sensory-efferent function. Although CGRP has two major isoforms (α-CGRP and β-CGRP, the α-CGRP is the isoform related to vascular actions. Release of CGRP from afferent perivascular nerve terminals has been shown to result in vasodilatation, an effect mediated by at least one receptor (the CGRP receptor. This receptor is an atypical G-protein coupled receptor (GPCR composed of three functional proteins: (i the calcitonin receptor-like receptor (CRLR; a seven-transmembrane protein, (ii the activity-modifying protein type 1 (RAMP1, and (iii a receptor component protein (RCP. Although under physiological conditions, CGRP seems not to play an important role in vascular tone regulation, this peptide has been strongly related as a key player in migraine and other vascular-related disorders (e.g., hypertension and preeclampsia. The present review aims at providing an overview on the role of sensory fibers and CGRP release on the modulation of vascular tone.

  5. Clinical implication of cervical vestibular evoked myogenic potentials in benign paroxysmal positional vertigo.

    Science.gov (United States)

    Chang, Mun Young; Shin, Ji Ho; Oh, Kyung Hyun; Hong, Young Ho; Mun, Seog-Kyun

    2017-02-01

    To evaluate the value of cervical vestibular evoked myogenic potential (cVEMP) as a prognostic factor for benign paroxysmal positional vertigo (BPPV). We reviewed 65 patients with BPPV who underwent cVEMP. Patients were divided into two groups according to resistance to the repositioning maneuver. Univariable and multivariable analyses were performed with age, gender, affected semicircular canal, affected side and cVEMP parameters to find the associated factors for resistance to the repositioning maneuver. From univariable analysis, cVEMP interaural amplitude difference (IAD) ratio, the affected semicircular canal and the affected side showed a better association (p<0.10) with resistance to the repositioning maneuver. With multivariable analysis, decreased cVEMP IAD ratio at the affected side (⩽-25%) (p=0.043, OR=4.934) and the posterior semicircular canal (p=0.049, OR=3.780) remained as associated factors. Decreased cVEMP IAD ratio at the affected side is associated with resistance to the repositioning maneuver. BPPV patients with decreased cVEMP IAD ratio at the affected side have a higher likelihood of their BPPV persisting after a single repositioning maneuver. cVEMP test may provide a prognosis of BPPV. A decreased cVEMP IAD ratio at the affected side may be prognostic of BPPV not resolving after a single repositioning maneuver. Copyright © 2016 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

  6. Biological Communities in Desert Varnish and Potential Implications for Varnish Formation Mechanisms

    Science.gov (United States)

    Lang-Yona, Naama; Maier, Stefanie; Macholdt, Dorothea; Rodriguez-Caballero, Emilio; Müller-Germann, Isabell; Yordanova, Petya; Jochum, Klaus-Peter; Andreae, Meinrat O.; Pöschl, Ulrich; Weber, Bettina; Fröhlich-Nowoisky, Janine

    2017-04-01

    Desert varnishes are thin, orange to black coatings found on rocks in arid and semi-arid environments on Earth. The formation mechanisms of rock varnish are still under debate and the involvement of microorganisms in this process remains unclear. In this work we aimed to identify the microbial community occurring in rock varnish to potentially gain insights into the varnish formation mechanism. For this purpose, rocks coated with desert varnish were collected from the Anza-Borrego Desert, California, USA, as well as soils from underneath the rocks. DNA from both varnish coatings and soil samples was extracted and subsequently used for metagenomic analysis, as well as for q-PCR analyses for specific species quantification. The element composition of the varnish coatings was analyzed and compared to the soil samples. Rock varnish shows similar depleted elements, compared to soil, but Mn and Pb are 50-60 times enriched compared to the soil samples, and about 100 times enriched compared to the upper continental crust. Our genomic analyses suggest unique populations and different protein functional groups occurring in the varnish compared to soil samples. We discuss these differences and try to shed light on the mechanism of Mn oxyhydroxide production in desert varnish formation.

  7. Ultrasmall Peptides Self-Assemble into Diverse Nanostructures: Morphological Evaluation and Potential Implications

    Directory of Open Access Journals (Sweden)

    Charlotte A.E. Hauser

    2011-09-01

    Full Text Available In this study, we perform a morphological evaluation of the diverse nanostructures formed by varying concentration and amino acid sequence of a unique class of ultrasmall self-assembling peptides. We modified these peptides by replacing the aliphatic amino acid at the C-aliphatic terminus with different aromatic amino acids. We tracked the effect of introducing aromatic residues on self-assembly and morphology of resulting nanostructures. Whereas aliphatic peptides formed long, helical fibers that entangle into meshes and entrap >99.9% water, the modified peptides contrastingly formed short, straight fibers with a flat morphology. No helical fibers were observed for the modified peptides. For the aliphatic peptides at low concentrations, different supramolecular assemblies such as hollow nanospheres and membrane blebs were found. Since the ultrasmall peptides are made of simple, aliphatic amino acids, considered to have existed in the primordial soup, study of these supramolecular assemblies could be relevant to understanding chemical evolution leading to the origin of life on Earth. In particular, we propose a variety of potential applications in bioengineering and nanotechnology for the diverse self-assembled nanostructures.

  8. Voluntary immunomodulation: potentiality and implications for long-duration manned space-flights

    Science.gov (United States)

    Geuna, Stefano

    The influence of psychological and neural factors on immunologic activity has been dedicated a growing interest over the past fifteen years, since the publication ofPsychoneuroimmunology by Robert Ader in 1981. Studies on this topic gave evidence for bi-directional communication between psychosocial, behavioural, neuroanatomical and neuroendocrine processes with the immune system and the detrimental effects of various stressors, physical and psychological, on immune reactions were widely investigated with reports of stress-induced changes in immune paramenters and immunocompetence. Much of the evidence support the notion that stress is associated with an increase in those diseases against which the immune system defends. Recently, several studies showed that immune functions can be influenced voluntarily and the term voluntary immunomodulation was coined to describe the use of various hypnosis-like and relaxation/imagery techniques for the self-regulation of immune activity. Alterations in the immune regulatory system are one of the most critical issues to be addressed in relation to crew health management during space missions, especially long-term ones. Providing crewmembers with a tool to enhance immunocompetence might be of great value to defend against some severe diseases, such as cancer and infectious illness, which may be elicited in outer space. In this view, a critical assessment of the potential usefulness of voluntary immunomodulation for crew health maintenance during manned space-flight is presented and discussed.

  9. Macroscopic electric charge separation during hypervelocity impacts: Potential implications for planetary paleomagnetism

    Science.gov (United States)

    Crawford, D. A.; Schultz, P. H.

    1993-01-01

    The production of transient magnetic fields by hypervelocity meteoroid impact has been proposed to possibly explain the presence of paleomagnetic fields in certain lunar samples as well as across broader areas of the lunar surface. In an effort to understand the lunar magnetic record, continued experiments at the NASA Ames Vertical Gun Range allow characterizing magnetic fields produced by the 5 km/s impacts of 0.32-0.64 cm projectiles over a broad range of impact angles and projectile/target compositions. From such studies, another phenomenon has emerged, macroscopic electric charge separation, that may have importance for the magnetic state of solid-body surfaces. This phenomenon was observed during explosive cratering experiments, but the magnetic consequences of macroscopic electric charge separation (as opposed to plasma production) during explosion and impact cratering have not, to our knowledge, been explored before now. It is straightforward to show that magnetic field production due to this process may scale as a weakly increasing function of impactor kinetic energy, although more work is needed to precisely assess the scaling dependence. The original intent of our experiments was to assess the character of purely electrostatic signals for comparison with inferred electrostatic noise signals acquired by shielded magnetic sensors buried within particulate dolomite targets. The results demonstrated that electrostatic noise does affect the magnetic sensors but only at relatively short distances (less than 4 cm) from the impact point (our magnetic studies are generally performed at distances greater than approximately 5.5 cm). However, to assess models for magnetic field generation during impact, measurements are needed of the magnetic field as close to the impact point as possible; hence, work with an improved magnetic sensor design is in progress. In this paper, we focus on electric charge separation during hypervelocity impacts as a potential transient

  10. Dissolved effluent organic matter: Characteristics and potential implications in wastewater treatment and reuse applications.

    Science.gov (United States)

    Michael-Kordatou, I; Michael, C; Duan, X; He, X; Dionysiou, D D; Mills, M A; Fatta-Kassinos, D

    2015-06-15

    Wastewater reuse is currently considered globally as the most critical element of sustainable water management. The dissolved effluent organic matter (dEfOM) present in biologically treated urban wastewater, consists of a heterogeneous mixture of refractory organic compounds with diverse structures and varying origin, including dissolved natural organic matter, soluble microbial products, endocrine disrupting compounds, pharmaceuticals and personal care products residues, disinfection by-products, metabolites/transformation products and others, which can reach the aquatic environment through discharge and reuse applications. dEfOM constitutes the major fraction of the effluent organic matter (EfOM) and due to its chemical complexity, it is necessary to utilize a battery of complementary techniques to adequately describe its structural and functional character. dEfOM has been shown to exhibit contrasting effects towards various aquatic organisms. It decreases metal uptake, thus potentially reducing their bioavailability to exposed organisms. On the other hand, dEfOM can be adsorbed on cell membranes inducing toxic effects. This review paper evaluates the performance of various advanced treatment processes (i.e., membrane filtration and separation processes, activated carbon adsorption, ion-exchange resin process, and advanced chemical oxidation processes) in removing dEfOM from wastewater effluents. In general, the literature findings reveal that dEfOM removal by advanced treatment processes depends on the type and the amount of organic compounds present in the aqueous matrix, as well as the operational parameters and the removal mechanisms taking place during the application of each treatment technology. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Calcium sensing receptor as a novel mediator of adipose tissue dysfunction: mechanisms and potential clinical implications

    Directory of Open Access Journals (Sweden)

    Roberto Bravo

    2016-09-01

    Full Text Available Obesity is currently a serious worldwide public health problem, reaching pandemic levels. For decades, dietary and behavioral approaches have failed to prevent this disease from expanding, and health authorities are challenged by the elevated prevalence of co-morbid conditions. Understanding how obesity-associated diseases develop from a basic science approach is recognized as an urgent task to face this growing problem. White adipose tissue is an active endocrine organ, with a crucial influence on whole-body homeostasis. White adipose tissue dysfunction plays a key role linking obesity with its associated diseases such as type 2 diabetes mellitus, cardiovascular disease and some cancers. Among the regulators of white adipose tissue physiology, the calcium-sensing receptor has arisen as a potential mediator of white adipose tissue dysfunction. Expression of the receptor has been described in human preadipocytes, adipocytes, and the human adipose cell lines LS14 and SW872. The evidence suggests that calcium-sensing receptor activation in the visceral (i.e. unhealthy white adipose tissue is associated with an increased proliferation of adipose progenitor cells and elevated adipocyte differentiation. In addition, exposure of adipose cells to calcium-sensing receptor activators in vitro elevates proinflammatory cytokine expression and secretion. An increased proinflammatory environment in white adipose tissue plays a key role in the development of white adipose tissue dysfunction that leads to peripheral organ fat deposition and insulin resistance, among other consequences. We propose that calcium-sensing receptor may be one relevant therapeutic target in the struggle to confront the health consequences of the current worldwide obesity pandemic.

  12. Misoprostol modulates cytokine expression through a cAMP Pathway: potential therapeutic implication for liver disease

    Science.gov (United States)

    Gobejishvili, Leila; Ghare, Smita; Khan, Rehan; Cambon, Alexander; Barker, David F.; Barve, Shirish; McClain, Craig; Hill, Daniell

    2015-01-01

    Dysregulated cytokine metabolism plays a critical role in the pathogenesis of many forms of liver disease, including alcoholic and non-alcoholic liver disease. In this study we examined the efficacy of Misoprostol in modulating LPS-inducible TNFα and IL-10 expression in healthy human subjects and evaluated molecular mechanisms for Misoprostol modulation of cytokines in vitro. Healthy subjects were given 14 day courses of Misoprostol at doses of 100, 200, and 300 µg four times a day, in random order. Baseline and LPS-inducible cytokine levels were examined ex vivo in whole blood at the beginning and the end of the study. Additionally, in vitro studies were performed using primary human PBMCs and the murine macrophage cell line, RAW 264.7, to investigate underlying mechanisms of misoprostol on cytokine production. Administration of Misoprostol reduced LPS inducible TNF production by 29%, while increasing IL-10 production by 79% in human subjects with no significant dose effect on ex vivo cytokine activity; In vitro, the effect of Misoprostol was largely mediated by increased cAMP levels and consequent changes in CRE and NFκB activity, which are critical for regulating IL-10 and TNF expression. Additionally, chromatin immunoprecipitation (ChIP) studies demonstrated that Misoprostol treatment led to changes in transcription factor and RNA Polymerase II binding, resulting in changes in mRNA levels. In summary, Misoprostol was effective at beneficially modulating TNF and IL-10 levels both in vivo and in vitro; these studies suggest a potential rationale for Misoprostol use in ALD, NASH and other liver diseases where inflammation plays an etiologic role. PMID:26408955

  13. Temporal Dynamics of Sodic Playa Salt Crust Patterns: Implications for Aeolian Dust Emission Potential

    Science.gov (United States)

    Nield, J. M.; King, J.; Bryant, R. G.; Wiggs, G.; Eckardt, F. D.; Thomas, D. S.; Washington, R.

    2013-12-01

    Salt pans (or playas) are common in arid environments and can be major sources of windblown mineral dust, but there are uncertainties associated with their dust emission potential. These landforms typically form crusts which modify both their erosivity and erodibility by limiting sediment availability, modifying surface and aerodynamic roughness and limiting evaporation rates and sediment production. Here we show the relationship between seasonal surface moisture change and crust pattern development based on both remote-sensing and field surface and atmospheric measurements. We use high resolution (sub-cm) terrestrial laser scanning (TLS; ground-based lidar) surveys over weekly, monthly and annual timescales to accurately characterise crustal ridge thrusting and collapse. This can be as much as 2 mm/day on fresh pan areas that have recently been reset by flooding. Over a two month period, this ridge growth can change aerodynamic roughness length values by 6.5 mm. At the same time, crack densities across the surface increase and this raises the availability of erodible fluffy, low density dust source sediment stored below the crust layer. Ridge spaces are defined in the early stages of crust development, as identified by Fourier Transform analysis, but wider wavelengths become more pronounced over time. We present a conceptual model accounting for the driving forces (subsurface, surface and atmospheric moisture) and feedbacks between these and surface shape that lead to crust pattern trajectories between highly emissive degraded surfaces and less emissive ridged or continuous crusts. These findings improve our understanding of temporal changes in dust availability and supply from playa source regions.

  14. Potential implications of adjuvant endocrine therapy for the oral health of postmenopausal women with breast cancer

    Science.gov (United States)

    Taichman, L. Susan; Havens, Aaron M.

    2012-01-01

    Current adjuvant treatment modalities for breast cancer that express the estrogen receptor or progesterone receptor include adjuvant anti-estrogen therapies, and tamoxifen and aromatase inhibitors. Bone, including the jaw, is an endocrine-sensitive organ, as are other oral structures. This review examines the potential links between adjuvant anti-estrogen treatments in postmenopausal women with hormone receptor positive breast cancer and oral health. A search of PubMed, EMBASE, CENTRAL, and the Web of Knowledge was conducted using combinations of key terms “breast,” “cancer,” “neoplasm,” “Tamoxifen,” “Aromatase Inhibitor,” “chemotherapy,” “hormone therapy,” “alveolar bone loss,” “postmenopausal bone loss,” “estrogen,” “SERM,” “hormone replacement therapy,” and “quality of life.” We selected articles published in peer-reviewed journals in the English. The authors found no studies reporting on periodontal diseases, alveolar bone loss, oral health, or oral health-related quality of life in association with anti-estrogen breast cancer treatments in postmenopausal women. Periodontal diseases, alveolar bone density, tooth loss, and conditions of the soft tissues of the mouth have all been associated with menopausal status supporting the hypothesis that the soft tissues and bone of the oral cavity could be negatively affected by anti-estrogen therapy. As a conclusion, the impact of adjuvant endocrine breast cancer therapy on the oral health of postmenopausal women is undefined. The structures of the oral cavity are influenced by estrogen; therefore, anti-estrogen therapies may carry the risk of oral toxicities. Oral health care for breast cancer patients is an important but understudied aspect of cancer survivorship. PMID:22986813

  15. Cellular models of atherosclerosis and their implication for testing natural substances with anti-atherosclerotic potential.

    Science.gov (United States)

    Orekhov, Alexander N; Ivanova, Ekaterina A

    2016-10-15

    Atherosclerosis remains a major problem in the modern society being a cause of life-threatening cardiovascular diseases. Subclinical atherosclerosis can be present for years before the symptoms become obvious, and first manifestations of the disease in a form of acute ischemia of organs are often fatal. The development of atherosclerosis is characterized by lipid accumulation in the aortic wall and formation of foam cells overloaded with large amounts of lipid inclusions in the cytoplasm. Current therapy of atherosclerosis is aimed mostly at the normalization of the blood lipid profile, and has no direct activity on the atherosclerotic plaque development. It is therefore necessary to continue the search for substances that possess a direct anti-atherosclerotic effect, preventing the cholesterol deposition in the arterial wall cells and reducing the existing plaques. Medicinal plants with potential anti-atherosclerotic activity are especially interesting in that regard, as plant-based medications are often characterized by good tolerability and are suitable for long-term therapy. The evaluation of novel active substances requires the establishment of reliable models of atherogenesis. In this review we discuss cellular models based on cultured human aortic cells. We also discuss several examples of successful application of these models for evaluation of anti-atherosclerotic activity of natural products of botanical origin based on measurable parameters, such as intracellular cholesterol accumulation. We describe several examples of successful screening and clinical studies evaluating natural products that can be beneficial for prevention and treatment of atherosclerosis, including the subclinical (asymptomatic) forms. Several substances of botanical origin have been demonstrated to be active for treatment and prevention of atherosclerosis. The obtained results encourage future studies of naturally occurring anti-atherosclerotic agents. Copyright © 2016 Elsevier Gmb

  16. Delayed translocation of NGFI-B/RXR in glutamate stimulated neurons allows late protection by 9-cis retinoic acid

    International Nuclear Information System (INIS)

    Mathisen, Gro H.; Fallgren, Asa B.; Strom, Bjorn O.; Boldingh Debernard, Karen A.; Mohebi, Beata U.; Paulsen, Ragnhild E.

    2011-01-01

    Highlights: → NGFI-B and RXR translocate out of the nucleus after glutamate treatment. → Arresting NGFI-B/RXR in the nucleus protects neurons from excitotoxicity. → Late protection by 9-cis RA is possible due to a delayed translocation of NGFI-B/RXR. -- Abstract: Nuclear receptor and apoptosis inducer NGFI-B translocates out of the nucleus as a heterodimer with RXR in response to different apoptosis stimuli, and therefore represents a potential pharmacological target. We found that the cytosolic levels of NGFI-B and RXRα were increased in cultures of cerebellar granule neurons 2 h after treatment with glutamate (excitatory neurotransmitter in the brain, involved in stroke). To find a time-window for potential intervention the neurons were transfected with gfp-tagged expressor plasmids for NGFI-B and RXR. The default localization of NGFI-Bgfp and RXRgfp was nuclear, however, translocation out of the nucleus was observed 2-3 h after glutamate treatment. We therefore hypothesized that the time-window between treatment and translocation would allow late protection against neuronal death. The RXR ligand 9-cis retinoic acid was used to arrest NGFI-B and RXR in the nucleus. Addition of 9-cis retinoic acid 1 h after treatment with glutamate reduced the cytosolic translocation of NGFI-B and RXRα, the cytosolic translocation of NGFI-Bgfp observed in live neurons, as well as the neuronal death. However, the reduced translocation and the reduced cell death were not observed when 9-cis retinoic acid was added after 3 h. Thus, late protection from glutamate induced death by addition of 9-cis retinoic acid is possible in a time-window after apoptosis induction.

  17. Hydrogen Peroxide Cycling in Acidic Geothermal Environments and Potential Implications for Oxidative Stress

    Science.gov (United States)

    Mesle, M.; Beam, J.; Jay, Z.; Bodle, B.; Bogenschutz, E.; Inskeep, W.

    2014-12-01

    Hydrogen peroxide (H2O2) may be produced in natural waters via photochemical reactions between dissolved oxygen, organic carbon and light. Other reactive oxygen species (ROS) such as superoxide and hydroxyl radicals are potentially formed in environments with high concentrations of ferrous iron (Fe(II), ~10-100 μM) by reaction between H2O2 and Fe(II) (i.e., Fenton chemistry). Thermophilic archaea and bacteria inhabiting acidic iron-oxide mats have defense mechanisms against both extracellular and intracellular peroxide, such as peroxiredoxins (which can degrade H2O2) and against other ROS, such as superoxide dismutases. Biological cycling of H2O2 is not well understood in geothermal ecosystems, and geochemical measurements combined with molecular investigations will contribute to our understanding of microbial response to oxidative stress. We measured H2O2 and other dissolved compounds (Fe(II), Fe(III), H2S, O2), as well as photon flux, pH and temperature, over time in surface geothermal waters of several acidic springs in Norris Geyser Basin, Yellowstone National Park, WY (Beowulf Spring and One Hundred Spring Plain). Iron-oxide mats were sampled in Beowulf Spring for on-going analysis of metatranscriptomes and RT-qPCR assays of specific stress-response gene transcription (e.g., superoxide dismutases, peroxiredoxins, thioredoxins, and peroxidases). In situ analyses show that H2O2 concentrations are lowest in the source waters of sulfidic systems (ca. 1 μM), and increase by two-fold in oxygenated waters corresponding to Fe(III)-oxide mat formation (ca. 2 - 3 μM). Channel transects confirm increases in H2O2 as a function of oxygenation (distance). The temporal dynamics of H2O2, O2, Fe(II), and H2S in Beowulf geothermal waters were also measured during a diel cycle, and increases in H2O2 were observed during peak photon flux. These results suggest that photochemical reactions may contribute to changes in H2O2. We hypothesize that increases in H2O2 and O2

  18. In vitroinvestigation of orange fleshed sweet potato prebiotic potential and its implication on human gut health

    Directory of Open Access Journals (Sweden)

    Mary N.Muchiri

    2017-10-01

    Full Text Available Background: Some food ingredients (prebiotics have been shown to promote a healthy gut by selectively stimulating growth/activity of beneficial gastrointestinal microbes and metabolites such as short chain fatty acids (SCFA while inhibiting pathogens. Orange fleshed sweet potato (Ipomoea batatas Lam; OFSP root tuber is a starchy tropical crop and highly nutritious in terms of pro-vitamin A (beta carotene, dietary fibre, and natural sugars, with negligible amount of fats and cholesterol. Purpose of study: The aim of the study was to investigate using simulated human gut system whether OFSP may have prebiotic activity derived from their fibre, resistant starch, and/or the sugars. Methodology: In vitro pH controlled stirred batch culture fermentation system was used to compare the effect on human gut microbiota of four substrates: two varieties of OFSP (SPK 004 and Tainung, FOS and sucrose known for positive prebiotic and non-selective change respectively. The system was inoculated with faecal slurry from six different human healthy donors from different ethical backgrounds, age, and the effectual change recorded over 24 hours by monitoring bacterial counts (total bacteria, Bacteroides and Bifidobacterium using qPCR molecular technique and SCFA profiles by gas chromatography. Results: The total bacteria count increased by (0.92-1.7 log10 and Bacteroides genus (1.03-1.8 log10 throughout the experimental period but with no significant differences (p<0.05 between the four substrates. However, there were significant differences (p<0.05 in the beneficial Bifidobacterium (1.66-2.66 log10 between the 2 varieties of OFSP and the two controls (FOS and sucrose. The levels of SCFA increased, with acetate as the predominant acid and lactic acid being the least. The OFSP purees elicited high butyric acid levels, which were comparable to those of positive control FOS. Conclusions: The study demonstrated that OFSP purees may have prebiotic potential that can

  19. Naturally occurring arsenic in the Miocene Hawthorn Group, southwestern Florida: Potential implication for phosphate mining

    International Nuclear Information System (INIS)

    Lazareva, Olesya; Pichler, Thomas

    2007-01-01

    fluorapatite) matrix with As concentrations as high as 3730 mg/kg and as a trace mineral in the sediment matrix concentrations varying from <1 to 8260 mg/kg; (5) hydrous ferric oxides (HFO) contained As concentrations as high as 540 mg/kg; (6) francolite, organic material, and clays contained substantially less As than pyrite; (7) thus, the release of As from pyrite could pose a potential problem for the phosphate industry

  20. Oxidative species-induced excitonic transport in tubulin aromatic networks: Potential implications for neurodegenerative disease.

    Science.gov (United States)

    Kurian, P; Obisesan, T O; Craddock, T J A

    2017-10-01

    Oxidative stress is a pathological hallmark of neurodegenerative tauopathic disorders such as Alzheimer's disease and Parkinson's disease-related dementia, which are characterized by altered forms of the microtubule-associated protein (MAP) tau. MAP tau is a key protein in stabilizing the microtubule architecture that regulates neuron morphology and synaptic strength. When MAP tau is degraded in tauopathic disorders, neuron dysfunction results. The precise role of reactive oxygen species (ROS) in the tauopathic disease process, however, is poorly understood. Classically, mitochondrial dysfunction has been viewed as the major source of oxidative stress and has been shown to precede tau and amyloid pathology in various dementias, but the exact mechanisms are not clear. It is known that the production of ROS by mitochondria can result in ultraweak photon emission (UPE) within cells. While of low intensity, surrounding proteins within the cytosol can still absorb these energetic photons via aromatic amino acids (e.g., tryptophan and tyrosine). One likely absorber of these photons is the microtubule cytoskeleton, as it forms a vast network spanning neurons, is highly co-localized with mitochondria, and shows a high density of aromatic amino acids. Functional microtubule networks may traffic this ROS-generated endogenous photon energy for cellular signaling, or they may serve as dissipaters/conduits of such energy to protect the cell from potentially harmful effects. Experimentally, after in vitro exposure to exogenous photons, microtubules have been shown to reorient and reorganize in a dose-dependent manner with the greatest effect being observed around 280nm, in the tryptophan and tyrosine absorption range. In this paper, recent modeling efforts based on ambient temperature experiment are presented, showing that tubulin polymers can feasibly absorb and channel these photoexcitations via resonance energy transfer, on the order of dendritic length scales and neuronal

  1. Slow CCL2-dependent translocation of biopersistent particles from muscle to brain.

    Science.gov (United States)

    Khan, Zakir; Combadière, Christophe; Authier, François-Jérôme; Itier, Valérie; Lux, François; Exley, Christopher; Mahrouf-Yorgov, Meriem; Decrouy, Xavier; Moretto, Philippe; Tillement, Olivier; Gherardi, Romain K; Cadusseau, Josette

    2013-04-04

    Long-term biodistribution of nanomaterials used in medicine is largely unknown. This is the case for alum, the most widely used vaccine adjuvant, which is a nanocrystalline compound spontaneously forming micron/submicron-sized agglomerates. Although generally well tolerated, alum is occasionally detected within monocyte-lineage cells long after immunization in presumably susceptible individuals with systemic/neurologic manifestations or autoimmune (inflammatory) syndrome induced by adjuvants (ASIA). On the grounds of preliminary investigations in 252 patients with alum-associated ASIA showing both a selective increase of circulating CCL2, the major monocyte chemoattractant, and a variation in the CCL2 gene, we designed mouse experiments to assess biodistribution of vaccine-derived aluminum and of alum-particle fluorescent surrogates injected in muscle. Aluminum was detected in tissues by Morin stain and particle induced X-ray emission) (PIXE) Both 500 nm fluorescent latex beads and vaccine alum agglomerates-sized nanohybrids (Al-Rho) were used. Intramuscular injection of alum-containing vaccine was associated with the appearance of aluminum deposits in distant organs, such as spleen and brain where they were still detected one year after injection. Both fluorescent materials injected into muscle translocated to draining lymph nodes (DLNs) and thereafter were detected associated with phagocytes in blood and spleen. Particles linearly accumulated in the brain up to the six-month endpoint; they were first found in perivascular CD11b+ cells and then in microglia and other neural cells. DLN ablation dramatically reduced the biodistribution. Cerebral translocation was not observed after direct intravenous injection, but significantly increased in mice with chronically altered blood-brain-barrier. Loss/gain-of-function experiments consistently implicated CCL2 in systemic diffusion of Al-Rho particles captured by monocyte-lineage cells and in their subsequent neurodelivery

  2. Gastrointestinal Motility Disorders and Their Clinical Implications in Cirrhosis

    Directory of Open Access Journals (Sweden)

    Eleni Theocharidou

    2017-01-01

    Full Text Available Gastrointestinal motility is impaired in a substantial proportion of patients with cirrhosis. Cirrhosis-related autonomic neuropathy, increased nitric oxide production, and gut hormonal changes have been implicated. Oesophageal dysmotility has been associated with increased frequency of abnormal gastro-oesophageal reflux. Impaired gastric emptying and accommodation may result in early satiety and may have an impact on the nutritional status of these patients. Small intestinal dysmotility might be implicated in small intestinal bacterial overgrowth and increased bacterial translocation. The latter has been implicated in the pathophysiology of hepatic encephalopathy and spontaneous bacterial peritonitis. Enhanced colonic motility is usually associated with the use of lactulose. Pharmacological interventions aiming to alter gastrointestinal motility in cirrhosis could potentially have a beneficial effect reducing the risk of hepatic decompensation and improving prognosis.

  3. Comparison of translocation methods to conserve metallophyte communities in the Southeastern D.R. Congo.

    Science.gov (United States)

    Le Stradic, Soizig; Séleck, Maxime; Lebrun, Julie; Boisson, Sylvain; Handjila, Guylain; Faucon, Michel-Pierre; Enk, Terrence; Mahy, Grégory

    2016-07-01

    In southeastern Democratic Republic of Congo, unique metallophyte communities supporting numerous endemic species occurred on the highly mineralized copper cobalt (Cu-Co) hills throughout the province. These hills are economically valuable mineral reserves; mining activities represent therefore a threat to the long-term persistence of these communities. Ex situ conservation program was set up by a mining company to rescue and conserve the diversity of Cu-Co communities until restoration activities are initiated. Two kinds of Cu-Co communities: the steppe and the steppic savanna, were translocated using topsoil spreading and whole-turf translocation. In this study, we assessed the effectiveness of these two techniques in conserving Cu-Co communities and their potential use in future restoration programs. More than 2 years after the translocation, whole-turf translocation appeared to be the better technique for ex situ conservation of endemic Cu-Co species. Not only did whole-turf successfully translocate numerous target species that were not present in the topsoil areas, but it also resulted in fewer ruderal and non-target species compared to topsoil spreading. Topsoil spreading recorded low seedling emergence from seed bank due to large proportions of dormant seeds or the absence of a seed bank, especially for the steppic savanna. Restoration of the steppe is currently more successful than for steppic savanna where the lack of dominant and structuring species likely contributed to divergence in species composition compared to reference ecosystem. Our study stresses the fact that tropical old-growth grasslands, which require probably several centuries to assemble, are difficult to restore or translocate.

  4. Structural Basis of Chaperone Recognition of Type III Secretion System Minor Translocator Proteins*

    Science.gov (United States)

    Job, Viviana; Matteï, Pierre-Jean; Lemaire, David; Attree, Ina; Dessen, Andréa

    2010-01-01

    The type III secretion system (T3SS) is a complex nanomachine employed by many Gram-negative pathogens, including the nosocomial agent Pseudomonas aeruginosa, to inject toxins directly into the cytoplasm of eukaryotic cells. A key component of all T3SS is the translocon, a proteinaceous channel that is inserted into the target membrane, which allows passage of toxins into target cells. In most bacterial species, two distinct membrane proteins (the “translocators”) are involved in translocon formation, whereas in the bacterial cytoplasm, however, they remain associated to a common chaperone. To date, the strategy employed by a single chaperone to recognize two distinct translocators is unknown. Here, we report the crystal structure of a complex between the Pseudomonas translocator chaperone PcrH and a short region from the minor translocator PopD. PcrH displays a 7-helical tetratricopeptide repeat fold that harbors the PopD peptide within its concave region, originally believed to be involved in recognition of the major translocator, PopB. Point mutations introduced into the PcrH-interacting region of PopD impede translocator-chaperone recognition in vitro and lead to impairment of bacterial cytotoxicity toward macrophages in vivo. These results indicate that T3SS translocator chaperones form binary complexes with their partner molecules, and the stability of their interaction regions must be strictly maintained to guarantee bacterial infectivity. The PcrH-PopD complex displays homologs among a number of pathogenic strains and could represent a novel, potential target for antibiotic development. PMID:20385547

  5. Embracing the void--how much do we really know about targeting and translocation to the endoplasmic reticulum?

    Science.gov (United States)

    Aviram, Naama; Schuldiner, Maya

    2014-08-01

    In order for a protein to enter the secretory pathway, two crucial steps must occur: it first needs to be targeted to the cytosolic surface of the endoplasmic reticulum (ER), and then be translocated across the ER membrane. Although for many years studies of targeting focused on the signal recognition particle, recent findings reveal that several alternative targeting pathways exist, some still undescribed, and some only recently elucidated. In addition, many genes implicated in the translocation step have not been assigned a specific function. Here, we will focus on the open questions regarding ER targeting and translocation, and discuss how combining classical biochemistry with systematic approaches can promote our understanding of these essential cellular steps. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Potential Climate Change Impacts on the Built Environment in the United States and Implications for Sustainability

    Science.gov (United States)

    Quattrochi, D.

    2012-12-01

    should: 1) provide meaningful, authoritative climate-relevant measures about the status, rates, and trends of key physical, ecological, and societal variables and values to inform decisions on management, research, and education at regional to national scales; 2) identify climate-related conditions and impacts to help develop effective mitigation and adaptation measures and reduce costs of management; and 3) document and communicate the climate-driven dynamic nature and condition of Earth's systems and societies, and provide a coordinated. This presentation will provide an overview of possible climate impacts on the built environment. Also, given that spatial analysis and remote sensing techniques will be of paramount importance in assessing these impacts and in preparing adaptation strategies, the presentation will provide examples of how these techniques can be used to identify potential impacts of climate change on the built environment.

  7. Microbial translocation and cardiometabolic risk factors in HIV infection

    DEFF Research Database (Denmark)

    Trøseid, Marius; Manner, Ingjerd W; Pedersen, Karin K

    2014-01-01

    The widespread access to antiretroviral treatment during the past decades has transformed HIV infection from a lethal disease to a chronic condition, in which the relative burden of non-AIDS-related chronic disorders such as cardiovascular disease, malignancy, renal, liver, and bone disease has...... is crucial in order to tailor novel strategies for prophylaxis and treatment. This review will focus on advances in the field that possibly link HIV-induced alterations of the gut mucosa and consequent microbial translocation to cardiometabolic risk factors in HIV infection. Recent work suggests that markers...... increased. The adjusted relative risk for myocardial infarction is reported to be around 2-fold compared to that of the general population, which over time is likely to translate into increased absolute risk in an aging population. Thus, delineating potentially HIV-specific pathogenetic mechanisms...

  8. Reciprocal translocations in Saccharomyces cerevisiae formed by nonhomologous end joining.

    OpenAIRE

    Yu, Xin; Gabriel, Abram

    2004-01-01

    Reciprocal translocations are common in cancer cells, but their creation is poorly understood. We have developed an assay system in Saccharomyces cerevisiae to study reciprocal translocation formation in the absence of homology. We induce two specific double-strand breaks (DSBs) simultaneously on separate chromosomes with HO endonuclease and analyze the subsequent chromosomal rearrangements among surviving cells. Under these conditions, reciprocal translocations via nonhomologous end joining ...

  9. Metallic oxide nanoparticle translocation across the human bronchial epithelial barrier.

    Science.gov (United States)

    George, Isabelle; Naudin, Grégoire; Boland, Sonja; Mornet, Stéphane; Contremoulins, Vincent; Beugnon, Karine; Martinon, Laurent; Lambert, Olivier; Baeza-Squiban, Armelle

    2015-03-14

    Inhalation is the most frequent route of unintentional exposure to nanoparticles (NPs). Our aim was to quantify the translocation of different metallic NPs across human bronchial epithelial cells and to determine the factors influencing this translocation. Calu-3 cells forming a tight epithelial barrier when grown on a porous membrane in a two compartment chamber were exposed to fluorescently labelled NPs to quantify the NP translocation. NP translocation and uptake by cells were also studied by confocal and transmission electron microscopy. Translocation was characterized according to NP size (16, 50, or 100 nm), surface charge (negative or positive SiO2), composition (SiO2 or TiO2), presence of proteins or phospholipids and in an inflammatory context. Our results showed that NPs can translocate through the Calu-3 monolayer whatever their composition (SiO2 or TiO2), but this translocation was increased for the smallest and negatively charged NPs. Translocation was not associated with an alteration of the integrity of the epithelial monolayer, suggesting a transcytosis of the internalized NPs. By modifying the NP corona, the ability of NPs to cross the epithelial barrier differed depending on their intrinsic properties, making positively charged NPs more prone to translocate. NP translocation can be amplified by using agents known to open tight junctions and to allow paracellular passage. NP translocation was also modulated when mimicking an inflammatory context frequently found in the lungs, altering the epithelial integrity and inducing transient tight junction opening. This in vitro evaluation of NP translocation could be extended to other inhaled NPs to predict their biodistribution.

  10. Arf6-Dependent Intracellular Trafficking of Pasteurella multocida Toxin and pH-Dependent Translocation from Late Endosomes

    Directory of Open Access Journals (Sweden)

    Tracy P. M. Chong

    2011-03-01

    Full Text Available The potent mitogenic toxin from Pasteurella multocida (PMT is the major virulence factor associated with a number of epizootic and zoonotic diseases caused by infection with this respiratory pathogen. PMT is a glutamine-specific protein deamidase that acts on its intracellular G-protein targets to increase intracellular calcium, cytoskeletal, and mitogenic signaling. PMT enters cells through receptor-mediated endocytosis and then translocates into the cytosol through a pH-dependent process that is inhibited by NH4Cl or bafilomycin A1. However, the detailed mechanisms that govern cellular entry, trafficking, and translocation of PMT remain unclear. Co-localization studies described herein revealed that while PMT shares an initial entry pathway with transferrin (Tfn and cholera toxin (CT, the trafficking pathways of Tfn, CT, and PMT subsequently diverge, as Tfn is trafficked to recycling endosomes, CT is trafficked retrograde to the ER, and PMT is trafficked to late endosomes. Our studies implicate the small regulatory GTPase Arf6 in the endocytic trafficking of PMT. Translocation of PMT from the endocytic vesicle occurs through a pH-dependent process that is also dependent on both microtubule and actin dynamics, as evidenced by inhibition of PMT activity in our SRE-based reporter assay, with nocodazole and cytochalasin D, respectively, suggesting that membrane translocation and cytotoxicity of PMT is dependent on its transfer to late endosomal compartments. In contrast, disruption of Golgi-ER trafficking with brefeldin A increased PMT activity, suggesting that inhibiting PMT trafficking to non-productive compartments that do not lead to translocation, while promoting formation of an acidic tubulovesicle system more conducive to translocation, enhances PMT translocation and activity.

  11. Intracellular translocation and differential accumulation of cell-penetrating peptides in bovine spermatozoa: evaluation of efficient delivery vectors that do not compromise human sperm motility

    Science.gov (United States)

    Jones, Sarah; Lukanowska, Monika; Suhorutsenko, Julia; Oxenham, Senga; Barratt, Christopher; Publicover, Steven; Copolovici, Dana Maria; Langel, Ülo; Howl, John

    2013-01-01

    discrete intracellular compartments. Mitoparan (INLKKLAKL(Aib)KKIL), for example, specifically accumulated within the mitochondria located in the sperm midpiece. The unique plasma membrane composition of sperm is a critical factor that directly influences the uptake efficacy of structurally diverse CPPs. No correlations in efficacies were observed when comparing CPP uptake into sperm with either uptake into fibroblasts or direct translocation across a phosphatidylcholine membrane. These comparative investigations identified C105Y (CSIPPEVKFNKPFVYLI) as a most efficient pharmacokinetic modifier for general applications in sperm biology. Significantly, CPP uptake induced no detrimental influence upon either bovine sperm viability or the motility of human sperm. As a consequence of the lack of endocytotic machinery, the CPP-mediated delivery of much larger protein complexes into sperm is relatively inefficient when compared with the similar process in fibroblasts. LIMITATIONS, REASONS FOR CAUTION It is possible that some CPPs could directly influence aspects of sperm biology and physiology that were not analysed in this study. WIDER IMPLICATIONS OF THE FINDINGS CPP technologies have significant potential to deliver selected bioactive moieties and so could modulate the biology and physiology of human sperm biology both prior- and post-fertilization. STUDY FUNDING/COMPETING INTERSTS We are pleased to acknowledge financial support from the following sources: the Wellcome Trust, TENOVUS (Scotland), University of Dundee, Medical Research Council, NHS Tayside and Scottish Enterprise and the Research Institute in Healthcare Science, University of Wolverhampton. No conflicts of interest are reported by the authors. PMID:23585561

  12. Longing Itineraries: Building the Translocal Community

    Directory of Open Access Journals (Sweden)

    Gustavo López Angel

    2017-06-01

    Full Text Available Migration has reshaped social practices, the sense of belonging has been rethought, and the membership is renegotiated and contended; this is why strategies for their sustainability have been generated. The translocal community operates through multilocated relationships that reveal the ways in which migrants are adapting to the new demands of the community. We emphasize the emotional impulse of nostalgia as one of the vehicles of sustainability for the community. The community is redefined and understood in a set of socio-cultural relationships its members generate, and where the locality is not central, but the connection. A new dimension of the social community space is not just the community gathered in a specific place, but also that agreements, commitments, and acknowledgments are exhibited and settled in the cyberspace; this cyberspace gives cohesion and brings a dynamic element to preserve the community, despite the fact that it is even less concrete than the spatial notion of territory. Facebook, YouTube and a blog are the web platforms of the virtual space where "neighbors, compatriots and citizens" (categories of ascription from the migration get together, where there is a reproduction of social practices (even the most ancient and fundamental ones, to give a new dimension to a translocal, multilocated and ciberlocated community.

  13. Chromosomal Translocations: Chicken or Egg? | Center for Cancer Research

    Science.gov (United States)

    Many tumor cells have abnormal chromosomes. Some of these abnormalities are caused by chromosomal translocations, which occur when two chromosomes break and incorrectly rejoin, resulting in an exchange of genetic material. Translocations can activate oncogenes, silence tumor suppressor genes, or result in the creation of completely new fusion gene products. While there is little doubt that chromosomal translocations can contribute to cancer, there is an active "chicken and the egg" discussion about the role translocations and other chromosomal abnormalities play—do they actually cause cancer or merely occur because of other changes within the cancer cell.  

  14. Label Free Chromosome Translocation Detection with Silicon nanowires

    DEFF Research Database (Denmark)

    Kwasny, Dorota; Andersen, Karsten Brandt; Frøhling, Kasper Bayer

    HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method is a Fluore......HROMOSOME translocation, which is a rearrangement of arms between two chromosomes, is a major group of chromosome abnormalities leading to cancer. As a result, two derivative chromosomes with sequences coming from both chromosomes are formed. The current translocation detection method...

  15. Microbial Translocation and Inflammation Occur in Hyperacute Immunodeficiency Virus Infection and Compromise Host Control of Virus Replication.

    Directory of Open Access Journals (Sweden)

    Adam J Ericsen

    2016-12-01

    Full Text Available Within the first three weeks of human immunodeficiency virus (HIV infection, virus replication peaks in peripheral blood. Despite the critical, causal role of virus replication in determining transmissibility and kinetics of progression to acquired immune deficiency syndrome (AIDS, there is limited understanding of the conditions required to transform the small localized transmitted founder virus population into a large and heterogeneous systemic infection. Here we show that during the hyperacute "pre-peak" phase of simian immunodeficiency virus (SIV infection in macaques, high levels of microbial DNA transiently translocate into peripheral blood. This, heretofore unappreciated, hyperacute-phase microbial translocation was accompanied by sustained reduction of lipopolysaccharide (LPS-specific antibody titer, intestinal permeability, increased abundance of CD4+CCR5+ T cell targets of virus replication, and T cell activation. To test whether increasing gastrointestinal permeability to cause microbial translocation would amplify viremia, we treated two SIV-infected macaque 'elite controllers' with a short-course of dextran sulfate sodium (DSS-stimulating a transient increase in microbial translocation and a prolonged recrudescent viremia. Altogether, our data implicates translocating microbes as amplifiers of immunodeficiency virus replication that effectively undermine the host's capacity to contain infection.

  16. ABCC9/SUR2 in the brain: Implications for hippocampal sclerosis of aging and a potential therapeutic target.

    Science.gov (United States)

    Nelson, Peter T; Jicha, Gregory A; Wang, Wang-Xia; Ighodaro, Eseosa; Artiushin, Sergey; Nichols, Colin G; Fardo, David W

    2015-11-01

    The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium ("KATP") channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The KATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is a result of ABCC9 mutations; we discuss neurologic manifestations of this genetic syndrome. More common brain disorders linked to ABCC9 gene variants include hippocampal sclerosis of aging (HS-Aging), sleep disorders, and depression. HS-Aging is a prevalent neurological disease with pathologic features of both neurodegenerative (aberrant TDP-43) and cerebrovascular (arteriolosclerosis) disease. As to potential therapeutic intervention, the human pharmacopeia features both SUR2 agonists and antagonists, so ABCC9/SUR2 may provide a "druggable target", relevant perhaps to both HS-Aging and Alzheimer's disease. We conclude that more work is required to better understand the roles of ABCC9/SUR2 in the human brain during health and disease conditions. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. ABCC9/SUR2 in the brain: implications for hippocampal sclerosis of aging and a potential therapeutic target

    Science.gov (United States)

    Nelson, Peter T.; Jicha, Gregory A.; Wang, Wang-Xia; Ighodaro, Eseosa; Artiushin, Sergey; Nichols, Colin G.; Fardo, David W.

    2015-01-01

    The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“KATP”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The KATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is a result of ABCC9 mutations; we discuss neurologic manifestations of this genetic syndrome. More common brain disorders linked to ABCC9 gene variants include hippocampal sclerosis of aging (HS-Aging), sleep disorders, and depression. HS-Aging is a prevalent neurological disease with pathologic features of both neurodegenerative (aberrant TDP-43) and cerebrovascular (arteriolosclerosis) disease. As to potential therapeutic intervention, the human pharmacopeia features both SUR2 agonists and antagonists, so ABCC9/SUR2 may provide a “druggable target”, relevant perhaps to both HS-Aging and Alzheimer’s disease. We conclude that more work is required to better understand the roles of ABCC9/SUR2 in the human brain during health and disease conditions. PMID:26226329

  18. Multiscale visualization of the structural and characteristic changes of sewage sludge biochar oriented towards potential agronomic and environmental implication

    Science.gov (United States)

    Zhang, Jining; Lü, Fan; Zhang, Hua; Shao, Liming; Chen, Dezhen; He, Pinjing

    2015-01-01

    Sewage sludge biochars were obtained at different pyrolysis temperatures from 300°C to 900°C and their macro- and microscale properties were analyzed. The biochar's plant-available nutrients and humus-like substances in the water-extractable phase and fixed nutrients in the solid fraction were evaluated for their potential agronomic implications. FT-IR, Raman, XRD, XPS, and SEM techniques were used to investigate the chemical structure, functional groups, and microcrystal structure on the surface of the biochar. The results revealed minor chemical changes and dramatic mass loss in the biochar obtained at 300–500°C, whereas significant chemical changes in the biochar were obtained at 600–900°C. The concentrations of plant-available nutrients as well as fulvic- and humic-acid-like materials decreased in the biochar samples obtained at higher temperatures. These results implied that the biochar samples pyrolyzed at 300–500°C could be a direct nutrient source and used to neutralize alkaline soil. The surface area and porosity of the biochar samples increased with temperature, which increased their adsorption capacity. Rearrangement occurred at higher temperature 600–900°C, resulting in the biochar becoming increasingly polyaromatic and its graphite-like carbon becoming organized. PMID:25802185

  19. Sink plot for runoff measurements on semi-flat terrains: preliminary data and their potential hydrological and ecological implications

    Directory of Open Access Journals (Sweden)

    Kidron Giora J.

    2014-12-01

    Full Text Available In arid and semiarid regions where water is the main limiting factor, water redistribution is regarded as an important hydrological process of great ecological value. By providing additional water to certain loci, moist pockets of great productivity are formed, characterized by high plant biomass and biological activity. These moist pockets are often a result of runon. Yet, although runoff may take place on semi-flat undulating surfaces, runoff measurements are thus far confined to slopes, where a sufficient gradient facilitates downslope water harvesting. On undulating surfaces of mounds and depressions, such as in interdunes, no quantification of the amount of water reaching depressions is feasible due to the fact that no reliable method for measuring the runoff amounts in semi-flat terrains is available. The current paper describes specific runoff plots, designed to measure runoff in depressions (sinks. These plots, termed sink plots (SPs, were operative in the Hallamish dunefield (Negev Desert, Israel. The paper presents measurements of runoff yield that were carried out between January 2013 and January 2014 on SPs and compared them to runoff obtained from crusted slope plots and fine-grained (playa surfaces. The potential hydrological and ecological implications of water redistribution within semi-flat terrains for this and other arid ecosystems are discussed.

  20. Potential Implications of Research on Genetic or Heritable Contributions to Pedophilia for the Objectives of Criminal Law

    Science.gov (United States)

    Berryessa, Colleen M.

    2015-01-01

    In recent years, there has been increasing scientific research on possible genetic or heritable influences to the etiology of pedophilia, driven by national and public concerns about better understanding the disorder in order to reduce children’s vulnerabilities to pedophilic and child sex offenders. This research has corresponded to growing academic dialogue on how advances in genetic research, especially concerning the causes and development of particular mental disorders or behaviors, may affect traditional practices of criminal law and how the justice system views, manages, and adjudicates different types of criminal behavior and offenders. This paper strives to supplement this dialogue by exploring several of the many possible effects and implications of research surrounding genetic or heritable contributions to pedophilia for the five widely accepted objectives that enforce and regulate the punishment of criminal law. These include retribution, incapacitation, deterrence, rehabilitation, and restoration. Although still currently in early stages, genetic and heritability research on the etiology of pedophilia may have the potential moving forward to influence the current and established punitive methods and strategies of how the justice system perceives, adjudicates, regulates, and punishes pedophilic and sex offenders, as well as how to best prevent sexual offending against children by pedophilic offenders in the future. PMID:25557668

  1. Potential implications of research on genetic or heritable contributions to pedophilia for the objectives of criminal law.

    Science.gov (United States)

    Berryessa, Colleen M

    2014-01-01

    In recent years, there has been increasing scientific research on possible genetic or heritable influences to the etiology of pedophilia, driven by national and public concerns about better understanding the disorder in order to reduce children's vulnerabilities to pedophilic and child sex offenders. This research has corresponded to growing academic dialogue on how advances in genetic research, especially concerning the causes and development of particular mental disorders or behaviors, may affect traditional practices of criminal law and how the justice system views, manages, and adjudicates different types of criminal behavior and offenders. This paper strives to supplement this dialogue by exploring several of the many possible effects and implications of research surrounding genetic or heritable contributions to pedophilia for the five widely accepted objectives that enforce and regulate the punishment of criminal law. These include retribution, incapacitation, deterrence, rehabilitation, and restoration. Although still currently in early stages, genetic and heritability research on the etiology of pedophilia may have the potential moving forward to influence the current and established punitive methods and strategies of how the justice system perceives, adjudicates, regulates, and punishes pedophilic and sex offenders, as well as how to best prevent sexual offending against children by pedophilic offenders in the future.

  2. Epigenetic regulation of non-lymphoid cells by Bisphenol-A, a model endocrine disrupter: Potential Implications for Immunoregulation

    Directory of Open Access Journals (Sweden)

    Deena eKhan

    2015-06-01

    Full Text Available Endocrine disrupting chemicals (EDC abound in the environment since many compounds are released from chemical, agricultural, pharmaceutical and consumer product industries. Many of the EDCs such as Bisphenol A (BPA have estrogenic activity or interfere with endogenous sex hormones. Experimental studies have reported a positive correlation of BPA with reproductive toxicity, altered growth and immune dysregulation. Although the precise relevance of these studies to the environmental levels is unclear, nevertheless, their potential health implications remain a concern. One possible mechanism by which BPA can alter genes is by regulating epigenetics, including microRNA, alteration of methylation and histone acetylation. There is now wealth of information on BPA effects on non-lymphoid cells and by comparison, paucity of data on effects of BPA on the immune system. In this mini review, we will highlight BPA regulation of estrogen receptor-mediated immune cell functions and in different inflammatory conditions. In addition, BPA-mediated epigenetic regulation of non-lymphoid cells is emphasized. We recognize that most of these studies are on non-lymphoid cells, and given that BPA also affects the immune system, it is plausible that BPA could have similar epigenetic regulation in immune cells. It is hoped that this review will stimulate studies in this area to ascertain whether or not BPA epigenetically regulates the cells of the immune system.

  3. Potential impacts of global warming on Australia's unique tropical biodiversity and implications for tropical biodiversity in general

    International Nuclear Information System (INIS)

    Hilbert, David W

    2007-01-01

    Full text: Full text: Globally, forest clearing is often thought to be the greatest threat to biodiversity in the tropics, and rates of clearing are certainly highest there, particularly in tropical South-East Asia. Climate change in the tropics has been less studied in tropical regions than in temperate, boreal or arctic ecosystems. However, modelling studies in Australian rainforests indicate that climate change may be a particularly significant threat to the long-term preservation of the biodiversity of tropical, rainforest biodiversity. Our research has shown that global warming can have a particularly strong impact on the biodiversity of mountainous tropical regions, including the Wet Tropics of north-east Queensland. Here, the mountain tops and higher tablelands are relatively cool islands in a sea of warmer climates. These species-rich islands, mostly limited in their biodiversity by warm interglacial periods, are separated from each other by the warmer valleys and form a scattered archipelago of habitat for organisms that are unable to survive and reproduce in warmer climates. Many of the endemic Australian Wet Tropics species live only in these cooler regions. Similar situations occur throughout south-east Asia and in the highlands of the Neotropics. Unfortunately, these upland and highland areas represent the majority of biodiversity conservation areas because they are less suitable for clearing for agriculture. This presentation will summarise research about the potential impacts of climate change on the biodiversity in Australia's rainforests, the potential implications for tropical biodiversity in general and discuss the limitations of these projections and the need for further research that could reduce uncertainties and inform effective adaptation strategies

  4. Nanopore arrays in a silicon membrane for parallel single-molecule detection: DNA translocation.

    Science.gov (United States)

    Zhang, Miao; Schmidt, Torsten; Jemt, Anders; Sahlén, Pelin; Sychugov, Ilya; Lundeberg, Joakim; Linnros, Jan

    2015-08-07

    Optical nanopore sensing offers great potential in single-molecule detection, genotyping, or DNA sequencing for high-throughput applications. However, one of the bottle-necks for fluorophore-based biomolecule sensing is the lack of an optically optimized membrane with a large array of nanopores, which has large pore-to-pore distance, small variation in pore size and low background photoluminescence (PL). Here, we demonstrate parallel detection of single-fluorophore-labeled DNA strands (450 bps) translocating through an array of silicon nanopores that fulfills the above-mentioned requirements for optical sensing. The nanopore array was fabricated using electron beam lithography and anisotropic etching followed by electrochemical etching resulting in pore diameters down to ∼7 nm. The DNA translocation measurements were performed in a conventional wide-field microscope tailored for effective background PL control. The individual nanopore diameter was found to have a substantial effect on the translocation velocity, where smaller openings slow the translocation enough for the event to be clearly detectable in the fluorescence. Our results demonstrate that a uniform silicon nanopore array combined with wide-field optical detection is a promising alternative with which to realize massively-parallel single-molecule detection.

  5. Response of uptake and translocation of phenanthrene to nitrogen form in lettuce and wheat seedlings.

    Science.gov (United States)

    Zhan, Xinhua; Yuan, Jiahan; Yue, Le; Xu, Guohua; Hu, Bing; Xu, Renkou

    2015-04-01

    Polycyclic aromatic hydrocarbons (PAHs) are widespread chemicals that are potentially carcinogenic and toxic to human due to dietary intake of food crops contaminated by PAHs. To date, the mechanisms underlying root uptake and acropetal translocation of PAHs in crops are poorly understood. Here we describe uptake and translocation of phenanthrene (a model PAH) in relation to nitrogen form and concentration in wheat and lettuce seedlings. At concentrations of 0-15 mM, phenanthrene uptake by roots is enhanced with an increase in ammonium and inhibited with an increment of nitrate. Phenanthrene concentration in shoots is much lower than in roots, suggesting that the direction of phenanthrene transport is acropetal. Ammonium reduces both phenanthrene accumulation and bioconcentration factor in shoots, as well as translocation factor, but nitrate elevates them. Phenanthrene uptake increases nutrient solution pH in the treatments with either nitrate or ammonium. Thus, it is concluded that the root uptake and acropetal translocation of phenanthrene in crops are associated with nitrogen form. Our results provide both a novel insight into the mechanism on PAH transport in higher plants and a promising agronomic strategy to minimize PAH contamination in crops or to improve phytoremediation of PAH-contaminated soils or water via nitrogen management.

  6. Translocation events in a single-walled carbon nanotube

    Energy Technology Data Exchange (ETDEWEB)

    He Jin; Lindsay, Stuart [Biodesign Institute, Arizona State University, Tempe, AZ 85287 (United States); Liu Hao [Department of Chemistry and Biochemistry, Arizona State University, Tempe, AZ 85287 (United States); Pang Pei; Cao Di, E-mail: jinhe@asu.ed [Department of Physics, Arizona State University, Tempe, AZ 85287 (United States)

    2010-11-17

    Translocation of DNA oligomers through a single-walled carbon nanotube was demonstrated recently. Translocation events are accompanied by giant current pulses, the origin of which remains obscure. Here, we show that the introduction of a nucleotide, guanosine triphosphate, alone into the input reservoir of a carbon nanotube nanofluidic device also gives giant current pulses. Taken together with data on oligomer translocation, these new results suggest that the pulse width has a nonlinear, power-law dependence on the number of nucleotides in a DNA molecule. We have also measured the time for the onset of DNA translocation pulses after bias reversal, finding that the time for the onset of translocation is directly proportional to the period of the bias reversal.

  7. Translocation events in a single-walled carbon nanotube

    International Nuclear Information System (INIS)

    He Jin; Lindsay, Stuart; Liu Hao; Pang Pei; Cao Di

    2010-01-01

    Translocation of DNA oligomers through a single-walled carbon nanotube was demonstrated recently. Translocation events are accompanied by giant current pulses, the origin of which remains obscure. Here, we show that the introduction of a nucleotide, guanosine triphosphate, alone into the input reservoir of a carbon nanotube nanofluidic device also gives giant current pulses. Taken together with data on oligomer translocation, these new results suggest that the pulse width has a nonlinear, power-law dependence on the number of nucleotides in a DNA molecule. We have also measured the time for the onset of DNA translocation pulses after bias reversal, finding that the time for the onset of translocation is directly proportional to the period of the bias reversal.

  8. Multistep Current Signal in Protein Translocation through Graphene Nanopores

    KAUST Repository

    Bonome, Emma Letizia

    2015-05-07

    © 2015 American Chemical Society. In nanopore sensing experiments, the properties of molecules are probed by the variation of ionic currents flowing through the nanopore. In this context, the electronic properties and the single-layer thickness of graphene constitute a major advantage for molecule characterization. Here we analyze the translocation pathway of the thioredoxin protein across a graphene nanopore, and the related ionic currents, by integrating two nonequilibrium molecular dynamics methods with a bioinformatic structural analysis. To obtain a qualitative picture of the translocation process and to identify salient features we performed unsupervised structural clustering on translocation conformations. This allowed us to identify some specific and robust translocation intermediates, characterized by significantly different ionic current flows. We found that the ion current strictly anticorrelates with the amount of pore occupancy by thioredoxin residues, providing a putative explanation of the multilevel current scenario observed in recently published translocation experiments.

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

    Directory of Open Access Journals (Sweden)

    Minh-Ha Lieu

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

  10. Opi1p translocation to the nucleus is regulated by hydrogen peroxide in Saccharomyces cerevisiae.

    Science.gov (United States)

    Camelo, Carolina; Vilas-Boas, Filipe; Cepeda, Andreia Pereira; Real, Carla; Barros-Martins, Joana; Pinto, Francisco; Soares, Helena; Marinho, H Susana; Cyrne, Luisa

    2017-09-01

    During exposure of yeast cells to low levels of hydrogen peroxide (H 2 O 2 ), the expression of several genes is regulated for cells to adapt to the surrounding oxidative environment. Such adaptation involves modification of plasma membrane lipid composition, reorganization of ergosterol-rich microdomains and altered gene expression of proteins involved in lipid and vesicle traffic, to decrease permeability to exogenous H 2 O 2 . Opi1p is a transcriptional repressor that is inactive when present at the nuclear membrane/endoplasmic reticulum, but represseses transcription of inositol upstream activating sequence (UAS INO )-containing genes, many of which are involved in the synthesis of phospholipids and fatty acids, when it is translocated to the nucleus. We investigated whether H 2 O 2 in concentrations inducing adaptation regulates Opi1p function. We found that, in the presence of H 2 O 2 , GFP-Opi1p fusion protein translocates to the nucleus and, concomitantly, the expression of UAS INO -containing genes is affected. We also investigated whether cysteine residues of Opi1p were implicated in the H 2 O 2 -mediated translocation of this protein to the nucleus and identified cysteine residue 159 as essential for this process. Our work shows that Opi1p is redox-regulated and establishes a new mechanism of gene regulation involving Opi1p, which is important for adaptation to H 2 O 2 in yeast cells. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

  11. Minimizing the cost of translocation failure with decision-tree models that predict species' behavioral response in translocation sites.

    Science.gov (United States)

    Ebrahimi, Mehregan; Ebrahimie, Esmaeil; Bull, C Michael

    2015-08-01

    The high number of failures is one reason why translocation is often not recommended. Considering how behavior changes during translocations may improve translocation success. To derive decision-tree models for species' translocation, we used data on the short-term responses of an endangered Australian skink in 5 simulated translocations with different release conditions. We used 4 different decision-tree algorithms (decision tree, decision-tree parallel, decision stump, and random forest) with 4 different criteria (gain ratio, information gain, gini index, and accuracy) to investigate how environmental and behavioral parameters may affect the success of a translocation. We assumed behavioral changes that increased dispersal away from a release site would reduce translocation success. The trees became more complex when we included all behavioral parameters as attributes, but these trees yielded more detailed information about why and how dispersal occurred. According to these complex trees, there were positive associations between some behavioral parameters, such as fight and dispersal, that showed there was a higher chance, for example, of dispersal among lizards that fought than among those that did not fight. Decision trees based on parameters related to release conditions were easier to understand and could be used by managers to make translocation decisions under different circumstances. © 2015 Society for Conservation Biology.

  12. Absent endometrium due to balanced translocation [t(4;20] presenting as primary amenorrhea

    Directory of Open Access Journals (Sweden)

    Aruna Nigam

    2014-01-01

    Full Text Available Primary amenorrhea is defined as the absence of menarche by 16-18 years of age in the presence of well-developed secondary sexual characters. An incidence of 1-3% has been reported in women of reproductive age group. The etiology varies with anatomical, genetic and hormonal factors implicated in the causation of primary amenorrhea. We present a case of absent endometrium due to balanced reciprocal translocation (RCPTR, 46 XX t (4;20(q12;q13.1 as primary amenorrhea.

  13. A Protein Rotaxane Controls the Translocation of Proteins Across a ClyA Nanopore.

    Science.gov (United States)

    Biesemans, Annemie; Soskine, Misha; Maglia, Giovanni

    2015-09-09

    Rotaxanes, pseudorotaxanes, and catenanes are supramolecular complexes with potential use in nanomachinery, molecular computing, and single-molecule studies. Here we constructed a protein rotaxane in which a polypeptide thread is encircled by a Cytolysin A (ClyA) nanopore and capped by two protein stoppers. The rotaxane could be switched between two states. At low negative applied potentials (nanopore indefinitely. Under this configuration the rotaxane prevents the diffusion of protein molecules across the lipid bilayer and provides a useful platform for single-molecule analysis. High negative applied potentials (-100 mV) dismantled the interlocked rotaxane system by the forceful translocation of the protein stopper, allowing new proteins to be trapped inside or transported across the nanopore. The observed voltage threshold for the translocation of the protein stopper through the nanopore related well to the biphasic voltage dependence of the residence time measured for the freely diffusing protein stopper. We propose a model in which molecules translocate through a nanopore when the average dwell time decreases with the applied potential.

  14. A framework for assessing the feasibility of native fish conservation translocations: Applications to threatened bull trout

    Science.gov (United States)

    Galloway, Benjamin T.; Muhlfeld, Clint C.; Guy, Christopher S.; Downs, Christopher C.; Fredenberg, Wade A.

    2016-01-01

    There is an urgent need to consider more aggressive and direct interventions for the conservation of freshwater fishes that are threatened by invasive species, habitat loss, and climate change. Conservation introduction (moving a species outside its indigenous range to other areas where conditions are predicted to be more suitable) is one type of translocation strategy that fisheries managers can use to establish new conservation populations in areas of refugia. To date, however, there are few examples of successful conservation-based introductions. Many attempts fail to establish new populations—in part because environmental factors that might influence success are inadequately evaluated before the translocation is implemented. We developed a framework to assess the feasibility of rescuing threatened fish populations through translocation into historically unoccupied stream and lake habitats. The suitability of potential introduction sites was evaluated based on four major components: the recipient habitat, recipient community, donor population, and future threats. Specific questions were then developed to evaluate each major component. The final assessment was based on a scoring system that addressed each question by using criteria developed from characteristics representative of highly suitable habitats and populations. This framework was used to evaluate the proposed within-drainage translocation of three Bull Trout Salvelinus confluentus populations in Glacier National Park, Montana. Our results indicated that within-drainage translocation is a feasible strategy for conserving locally adapted populations of Bull Trout through the creation of new areas of refugia in Glacier National Park. The framework provides a flexible platform that can help managers make informed decisions for moving threatened fishes into new areas of refugia for conservation and recovery programs.

  15. Genomic and Cytogenetic Characterization of a Balanced Translocation Disrupting NUP98.

    Science.gov (United States)

    Thibodeau, My Linh; Steinraths, Michelle; Brown, Lindsay; Zong, Zheyuan; Shomer, Naomi; Taubert, Stefan; Mungall, Karen L; Ma, Yussanne P; Mueller, Rosemary; Birol, Inanc; Lehman, Anna

    2017-01-01

    A 41-year-old Asian woman with bilateral renal angiomyolipomas (AML) was incidentally identified to have a balanced translocation, 46,XX,t(11;12)(p15.4;q15). She had no other features or family history to suggest a diagnosis of tuberous sclerosis. Her healthy daughter had the same translocation and no renal AML at the age of 3 years. Whole-genome sequencing was performed on genomic maternal DNA isolated from blood. A targeted de novo assembly was then conducted with ABySS for chromosomes 11 and 12. Sanger sequencing was used to validate the translocation breakpoints. As a result, genomic characterization of chromosomes 11 and 12 revealed that the 11p breakpoint disrupted the NUP98 gene in intron 1, causing a separation of the promoter and transcription start site from the rest of the gene. The translocation breakpoint on chromosome 12q was located in a gene desert. NUP98 has not yet been associated with renal AML pathogenesis, but somatic NUP98 alterations are recurrently implicated in hematological malignancies, most often following a gene fusion event. We also found evidence for complex structural events involving chromosome 12, which appear to disrupt the TDG gene. We identified a TDGP1 partially processed pseudogene at 12p12.1, which adds complexity to the de novo assembly. In conclusion, this is the first report of a germline constitutional structural chromosome rearrangement disrupting NUP98 that occurred in a generally healthy woman with bilateral renal AML. © 2017 S. Karger AG, Basel.

  16. Forced Translocation of Polymer through Nanopore: Deterministic Model and Simulations

    Science.gov (United States)

    Wang, Yanqian; Panyukov, Sergey; Liao, Qi; Rubinstein, Michael

    2012-02-01

    We propose a new theoretical model of forced translocation of a polymer chain through a nanopore. We assume that DNA translocation at high fields proceeds too fast for the chain to relax, and thus the chain unravels loop by loop in an almost deterministic way. So the distribution of translocation times of a given monomer is controlled by the initial conformation of the chain (the distribution of its loops). Our model predicts the translocation time of each monomer as an explicit function of initial polymer conformation. We refer to this concept as ``fingerprinting''. The width of the translocation time distribution is determined by the loop distribution in initial conformation as well as by the thermal fluctuations of the polymer chain during the translocation process. We show that the conformational broadening δt of translocation times of m-th monomer δtm^1.5 is stronger than the thermal broadening δtm^1.25 The predictions of our deterministic model were verified by extensive molecular dynamics simulations

  17. Slowing down DNA translocation using magnetic and optical tweezers

    Science.gov (United States)

    Peng, Hongbo; Wu, Shanshan; Ryul Park, Sang; Potter, Andrew; Ling, X. S.

    2006-03-01

    Electric-field driven DNA translocation through nanopores can be exploited for DNA sequencing and other applications. However, the DNA translocation under normal patch-clamp-type measurement is too fast to allow detailed measurements of individual or few nucleotides. We propose a concept to slow down the DNA translocation through the nanopore by using magnetic (or optical) tweezers. The 3' end of a single-strand DNA can be attached to a streptavidin-coated magnetic bead through a single biotin molecule. During DNA translocation, the 5' end of DNA will be electrophoretically drawn through the nanopore to the trans side while the 3' end of DNA stays in the cis side with the magnetic bead. A set of permanent magnets or electric coils can be used to generate a magnetic field gradient large enough to pull the bead, hence the DNA out of the nanopore. The net force on the magnetic bead will determine this back-translocation speed. By carefully tuning the magnetic field gradient and the voltage bias on the nanopore, one can make the back-translocation much slower than the conventional forward-translocation in which case the DNA is driven only by the electric force. We will report our experimental design as well as the preliminary results.

  18. Mode of ATM-dependent suppression of chromosome translocation

    Energy Technology Data Exchange (ETDEWEB)

    Yamauchi, Motohiro, E-mail: motoyama@nagasaki-u.ac.jp [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan); Suzuki, Keiji; Oka, Yasuyoshi; Suzuki, Masatoshi; Kondo, Hisayoshi; Yamashita, Shunichi [Graduate School of Biomedical Sciences, Nagasaki University, 1-12-4 Sakamoto, Nagasaki 852-8523 (Japan)

    2011-12-09

    Highlights: Black-Right-Pointing-Pointer We addressed how ATM suppresses frequency of chromosome translocation. Black-Right-Pointing-Pointer We found ATM/p53-dependent G1 checkpoint suppresses translocation frequency. Black-Right-Pointing-Pointer We found ATM and DNA-PKcs function in a common pathway to suppress translocation. -- Abstract: It is well documented that deficiency in ataxia telangiectasia mutated (ATM) protein leads to elevated frequency of chromosome translocation, however, it remains poorly understood how ATM suppresses translocation frequency. In the present study, we addressed the mechanism of ATM-dependent suppression of translocation frequency. To know frequency of translocation events in a whole genome at once, we performed centromere/telomere FISH and scored dicentric chromosomes, because dicentric and translocation occur with equal frequency and by identical mechanism. By centromere/telomere FISH analysis, we confirmed that chemical inhibition or RNAi-mediated knockdown of ATM causes 2 to 2.5-fold increase in dicentric frequency at first mitosis after 2 Gy of gamma-irradiation in G0/G1. The FISH analysis revealed that ATM/p53-dependent G1 checkpoint suppresses dicentric frequency, since RNAi-mediated knockdown of p53 elevated dicentric frequency by 1.5-fold. We found ATM also suppresses dicentric occurrence independently of its checkpoint role, as ATM inhibitor showed additional effect on dicentric frequency in the context of p53 depletion and Chk1/2 inactivation. Epistasis analysis using chemical inhibitors revealed that ATM kinase functions in the same pathway that requires kinase activity of DNA-dependent protein kinase catalytic subunit (DNA-PKcs) to suppress dicentric frequency. From the results in the present study, we conclude that ATM minimizes translocation frequency through its commitment to G1 checkpoint and DNA double-strand break repair pathway that requires kinase activity of DNA-PKcs.

  19. Fitness consequences of northward dispersal as possible adaptation to climate change, using experimental translocation of a migratory passerine.

    Directory of Open Access Journals (Sweden)

    Claudia Burger

    Full Text Available Climate change leads to rapid, differential changes in phenology across trophic levels, often resulting in temporal mismatches between predators and their prey. If a species cannot easily adjust its timing, it can adapt by choosing a new breeding location with a later phenology of its prey. In this study, we experimentally investigated whether long-distance dispersal to northern breeding grounds with a later phenology could be a feasible process to restore the match between timing of breeding and peak food abundance and thus improve reproductive success. Here, we report the successful translocation of pied flycatchers (Ficedula hypoleuca to natural breeding sites 560 km to the Northeast. We expected translocated birds to have a fitness advantage with respect to environmental phenology, but to potentially pay costs through the lack of other locally adapted traits. Translocated individuals started egg laying 11 days earlier than northern control birds, which were translocated only within the northern site. The number of fledglings produced was somewhat lower in translocated birds, compared to northern controls, and fledglings were in lower body condition. Translocated individuals were performing not significantly different to control birds that remained at the original southern site. The lack of advantage of the translocated individuals most likely resulted from the exceptionally cold spring in which the experiment was carried out. Our results, however, suggest that pied flycatchers can successfully introduce their early breeding phenotype after dispersing to more northern areas, and thus that adaptation through dispersal is a viable option for populations that get locally maladapted through climate change.

  20. Absorption and translocation of phosphorus-32 in guava leaves

    International Nuclear Information System (INIS)

    Natale, William

    1997-01-01

    Phosphorus is easily absorbed by the leaves and translocated. The objective of this work was to evaluate the absorption and translocation of P by guava leaves, with time. When a solution containing 2% MAP and specific activity 0.15 μCi/ml was applied. MAP labelled with 32 P was applied in the 3 rd pair of leaves. These and other leaves, roots and stem were collected separately and analyzed accordingly. The results showed that 20 days after application 12% of the applied P was absorbed by the guava leaves. The translocation of P started immediately after its absorption reaching 20% 2fter 20 days. (author). 19 refs., 4 tabs

  1. Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Xu, Aibin; Liu, Jingyi [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China); Institute of Cardiovascular Disease, General Hospital of Beijing Command, PLA, Beijing (China); Liu, Peilin; Jia, Min; Wang, Han [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China); Tao, Ling, E-mail: lingtao2006@gmail.com [Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi’an (China)

    2014-04-18

    Highlights: • Metabolic syndrome exacerbated MI/R induced injury accompanied by decreased Nur77. • ROS led to Nur77 translocation in metabolic syndrome. • Inhibiting relocation of Nur77 to mitochondria reduced ROS-induced cardiomyocyte injury in metabolic syndrome. - Abstract: Metabolic syndrome is a major risk factor for cardiovascular diseases, and increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor, is involved in such various cellular events as apoptosis, proliferation, and glucose and lipid metabolism in several cell types. Apoptosis is positively correlated with mitochondrial translocation of Nur77 in the cancer cells. However, the roles of Nur77 on cardiac myocytes in patients with metabolic syndrome remain unclear. The objective of this study was to determine whether Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome after I/R injury, and, if so, to identify the underlying molecular mechanisms responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome models. In this report, we observed that, accompanied by the substantial decline in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes cultured in a high-glucose and high-fat medium, we found that excessive H{sub 2}O{sub 2} led to the significant alteration in mitochondrial membrane potential and translocation of Nur77 from the nucleus to the mitochondria. However, inhibition of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes in membrane potential mediated by H{sub 2}O{sub 2} and reduced myocardial cell injury. Therefore, these data provide a potential underlying mechanism for cardiac dysfunction in metabolic syndrome and the suppression of Nur77 translocation may provide an effective approach to reduce cardiac injury in the

  2. Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome

    International Nuclear Information System (INIS)

    Xu, Aibin; Liu, Jingyi; Liu, Peilin; Jia, Min; Wang, Han; Tao, Ling

    2014-01-01

    Highlights: • Metabolic syndrome exacerbated MI/R induced injury accompanied by decreased Nur77. • ROS led to Nur77 translocation in metabolic syndrome. • Inhibiting relocation of Nur77 to mitochondria reduced ROS-induced cardiomyocyte injury in metabolic syndrome. - Abstract: Metabolic syndrome is a major risk factor for cardiovascular diseases, and increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor, is involved in such various cellular events as apoptosis, proliferation, and glucose and lipid metabolism in several cell types. Apoptosis is positively correlated with mitochondrial translocation of Nur77 in the cancer cells. However, the roles of Nur77 on cardiac myocytes in patients with metabolic syndrome remain unclear. The objective of this study was to determine whether Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome after I/R injury, and, if so, to identify the underlying molecular mechanisms responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome models. In this report, we observed that, accompanied by the substantial decline in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes cultured in a high-glucose and high-fat medium, we found that excessive H 2 O 2 led to the significant alteration in mitochondrial membrane potential and translocation of Nur77 from the nucleus to the mitochondria. However, inhibition of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes in membrane potential mediated by H 2 O 2 and reduced myocardial cell injury. Therefore, these data provide a potential underlying mechanism for cardiac dysfunction in metabolic syndrome and the suppression of Nur77 translocation may provide an effective approach to reduce cardiac injury in the process

  3. Phylogeography and dispersal in the velvet gecko (Oedura lesueurii, and potential implications for conservation of an endangered snake (Hoplocephalus bungaroides

    Directory of Open Access Journals (Sweden)

    Dubey Sylvain

    2012-05-01

    Full Text Available Abstract Background To conserve critically endangered predators, we also need to conserve the prey species upon which they depend. Velvet geckos (Oedura lesueurii are a primary prey for the endangered broad-headed snake (Hoplocephalus bungaroides, which is restricted to sandstone habitats in southeastern Australia. We sequenced the ND2 gene from 179 velvet geckos, to clarify the lizards’ phylogeographic history and landscape genetics. We also analysed 260 records from a longterm (3-year capture-mark-recapture program at three sites, to evaluate dispersal rates of geckos as a function of locality, sex and body size. Results The genetic analyses revealed three ancient lineages in the north, south and centre of the species’ current range. Estimates of gene flow suggest low dispersal rates, constrained by the availability of contiguous rocky habitat. Mark-recapture records confirm that these lizards are highly sedentary, with most animals moving  Conclusion The low vagility of these lizards suggests that they will be slow to colonise vacant habitat patches; and hence, efforts to restore degraded habitats for broad-headed snakes may need to include translocation of lizards.

  4. Phylogeography and dispersal in the velvet gecko (Oedura lesueurii), and potential implications for conservation of an endangered snake (Hoplocephalus bungaroides)

    Science.gov (United States)

    2012-01-01

    Background To conserve critically endangered predators, we also need to conserve the prey species upon which they depend. Velvet geckos (Oedura lesueurii) are a primary prey for the endangered broad-headed snake (Hoplocephalus bungaroides), which is restricted to sandstone habitats in southeastern Australia. We sequenced the ND2 gene from 179 velvet geckos, to clarify the lizards’ phylogeographic history and landscape genetics. We also analysed 260 records from a longterm (3-year) capture-mark-recapture program at three sites, to evaluate dispersal rates of geckos as a function of locality, sex and body size. Results The genetic analyses revealed three ancient lineages in the north, south and centre of the species’ current range. Estimates of gene flow suggest low dispersal rates, constrained by the availability of contiguous rocky habitat. Mark-recapture records confirm that these lizards are highly sedentary, with most animals moving < 30 m from their original capture site even over multi-year periods. Conclusion The low vagility of these lizards suggests that they will be slow to colonise vacant habitat patches; and hence, efforts to restore degraded habitats for broad-headed snakes may need to include translocation of lizards. PMID:22583676

  5. A Novel Egr-1-Agrin Pathway and Potential Implications for Regulation of Synaptic Physiology and Homeostasis at the Neuromuscular Junction

    Directory of Open Access Journals (Sweden)

    Ryen MacDonald

    2017-08-01

    Full Text Available Synaptic transmission requires intricate coordination of the components involved in processing of incoming signals, formation and stabilization of synaptic machinery, neurotransmission and in all related signaling pathways. Changes to any of these components cause synaptic imbalance and disruption of neuronal circuitry. Extensive studies at the neuromuscular junction (NMJ have greatly aided in the current understanding of synapses and served to elucidate the underlying physiology as well as associated adaptive and homeostatic processes. The heparan sulfate proteoglycan agrin is a vital component of the NMJ, mediating synaptic formation and maintenance in both brain and muscle, but very little is known about direct control of its expression. Here, we investigated the relationship between agrin and transcription factor early growth response-1 (Egr-1, as Egr-1 regulates the expression of many genes involved in synaptic homeostasis and plasticity. Using chromatin immunoprecipitation (ChIP, cell culture with cell lines derived from brain and muscle, and animal models, we show that Egr-1 binds to the AGRN gene locus and suppresses its expression. When compared with wild type (WT, mice deficient in Egr-1 (Egr-1−/− display a marked increase in AGRN mRNA and agrin full-length and cleavage fragment protein levels, including the 22 kDa, C-terminal fragment in brain and muscle tissue homogenate. Because agrin is a crucial component of the NMJ, we explored possible physiological implications of the Egr-1-agrin relationship. In the diaphragm, Egr-1−/− mice display increased NMJ motor endplate density, individual area and area of innervation. In addition to increased density, soleus NMJs also display an increase in fragmented and faint endplates in Egr-1−/− vs. WT mice. Moreover, the soleus NMJ electrophysiology of Egr-1−/− mice revealed increased quantal content and motor testing showed decreased movement and limb muscle strength compared with

  6. MYC translocation partner gene determines survival of patients with large B-cell lymphoma with MYC- or double-hit MYC/BCL2 translocations

    DEFF Research Database (Denmark)

    Pedersen, Mette Ø; Gang, Anne O; Poulsen, Tim S

    2014-01-01

    In large B-cell lymphoma (LBCL) MYC- and MYC/BCL2 double-hit (DH) translocations have been associated with inferior survival. We hypothesised that the negative prognostic impact of MYC translocation was determined by an immunoglobulin MYC translocation partner gene (IG-MYC), as opposed to a non......-immunoglobulin partner gene (nonIG-MYC). In a prospective, unselected cohort of 237 LBCL patients MYC and BCL2 translocations were identified by fluorescent in situ hybridisation (FISH) with split probes. MYC translocation partner gene was identified by IGH/MYC fusion probes and/or kappa/lambda split probes. Clinical...... data were collected from patient files. MYC translocation was identified in 28/225 patients. IG-MYC translocation partner gene was identified in 12/24 patients. DH translocation was identified in 23/228 patients. IG-MYC translocation partner gene was identified in 9/19 DH patients. Neither MYC-nor DH...

  7. A case of posttraumatic splenic translocation into the thorax

    International Nuclear Information System (INIS)

    Sosnowski, P.; Sikorski, L.; Ziemianski, A.

    1993-01-01

    A case of the left diaphragmatic hernia due to blunt thoracic and abdominal trauma is presented. Characteristic radiological signs of splenic translocation into the thorax contributed to quick diagnosis and immediate surgical intervention. (author)

  8. 40 CFR 798.5460 - Rodent heritable translocation assays.

    Science.gov (United States)

    2010-07-01

    ... manifests as balanced reciprocal translocations in progeny descended from parental males treated with... significance desired. (B) (iv) Assignment to groups. Animals shall be randomized and assigned to treatment and...

  9. DNA translocations through solid-state plasmonic nanopores.

    Science.gov (United States)

    Nicoli, Francesca; Verschueren, Daniel; Klein, Misha; Dekker, Cees; Jonsson, Magnus P

    2014-12-10

    Nanopores enable label-free detection and analysis of single biomolecules. Here, we investigate DNA translocations through a novel type of plasmonic nanopore based on a gold bowtie nanoantenna with a solid-state nanopore at the plasmonic hot spot. Plasmonic excitation of the nanopore is found to influence both the sensor signal (nanopore ionic conductance blockade during DNA translocation) and the process that captures DNA into the nanopore, without affecting the duration time of the translocations. Most striking is a strong plasmon-induced enhancement of the rate of DNA translocation events in lithium chloride (LiCl, already 10-fold enhancement at a few mW of laser power). This provides a means to utilize the excellent spatiotemporal resolution of DNA interrogations with nanopores in LiCl buffers, which is known to suffer from low event rates. We propose a mechanism based on plasmon-induced local heating and thermophoresis as explanation of our observations.

  10. DNA-graphene interactions during translocation through nanogaps.

    Directory of Open Access Journals (Sweden)

    Hiral N Patel

    Full Text Available We study how double-stranded DNA translocates through graphene nanogaps. Nanogaps are fabricated with a novel capillary-force induced graphene nanogap formation technique. DNA translocation signatures for nanogaps are qualitatively different from those obtained with circular nanopores, owing to the distinct shape of the gaps discussed here. Translocation time and conductance values vary by ∼ 100%, which we suggest are caused by local gap width variations. We also observe exponentially relaxing current traces. We suggest that slow relaxation of the graphene membrane following DNA translocation may be responsible. We conclude that DNA-graphene interactions are important, and need to be considered for graphene-nanogap based devices. This work further opens up new avenues for direct read of single molecule activitities, and possibly sequencing.

  11. Bioinformatic and mass spectrometry identification of Anaplasma phagocytophilum proteins translocated into host cell nuclei

    Directory of Open Access Journals (Sweden)

    Sara H. G. Sinclair

    2015-02-01

    Full Text Available Obligate intracellular bacteria have an arsenal of proteins that alter host cells to establish and maintain a hospitable environment for replication. Anaplasma phagocytophilum secrets Ankyrin A (AnkA, via a type IV secretion system, which translocates to the nucleus of its host cell, human neutrophils. A. phagocytophilum-infected neutrophils have dramatically altered phenotypes in part explained by AnkA-induced transcriptional alterations. However, it is unlikely that AnkA is the sole effector to account for infection-induced transcriptional changes. We developed a simple method combining bioinformatics and iTRAQ protein profiling to identify potential bacterial-derived nuclear-translocated proteins that could impact transcriptional programming in host cells. This approach identified 50 A. phagocytophilum candidate genes or proteins. The encoding genes were cloned to create GFP fusion protein-expressing clones that were transfected into HEK-293T cells. We confirmed nuclear translocation of six proteins: APH_0062, RplE, Hup, APH_0382, APH_0385, and APH_0455. Of the six, APH_0455 was identified as a type IV secretion substrate and is now under investigation as a potential nucleomodulin. Additionally, application of this approach to other obligate intracellular bacteria such as Mycobacterium tuberculosis, Chlamydia trachomatis and other intracellular bacteria identified multiple candidate genes to be investigated.

  12. Diagnostic X-ray examinations and increased chromosome translocations: evidence from three studies.

    Science.gov (United States)

    Bhatti, Parveen; Yong, Lee C; Doody, Michele M; Preston, Dale L; Kampa, Diane M; Ramsey, Marilyn J; Ward, Elizabeth M; Edwards, Alan A; Ron, Elaine; Tucker, James D; Sigurdson, Alice J

    2010-11-01

    Controversy regarding potential health risks from increased use of medical diagnostic radiologic examinations has come to public attention. We evaluated whether chromosome damage, specifically translocations, which are a potentially intermediate biomarker for cancer risk, was increased after exposure to diagnostic X-rays, with particular interest in the ionizing radiation dose-response below the level of approximately 50 mGy. Chromosome translocation frequency data from three separately conducted occupational studies of ionizing radiation were pooled together. Studies 1 and 2 included 79 and 150 medical radiologic technologists, respectively, and study 3 included 83 airline pilots and 50 university faculty members (total = 155 women and 207 men; mean age = 62 years, range 34-90). Information on personal history of radiographic examinations was collected from a detailed questionnaire. We computed a cumulative red bone marrow (RBM) dose score based on the numbers and types of X-ray examinations reported with 1 unit approximating 1 mGy. Poisson regression analyses were adjusted for age and laboratory method. Mean RBM dose scores were 49, 42, and 11 for Studies 1-3, respectively (overall mean = 33.5, range 0-303). Translocation frequencies significantly increased with increasing dose score (P X-ray examinations, including dose scores of approximately 50 and lower, suggesting the possibility of long-term adverse health effects.

  13. Accurate Breakpoint Mapping in Apparently Balanced Translocation Families with Discordant Phenotypes Using Whole Genome Mate-Pair Sequencing

    DEFF Research Database (Denmark)

    Aristidou, Constantia; Koufaris, Costas; Theodosiou, Athina

    2017-01-01

    -MPS) was applied to map the breakpoints in nine two-way ABT carriers from four families. Translocation breakpoints and patient-specific structural variants were validated by Sanger sequencing and quantitative Real Time PCR, respectively. Identical sequencing patterns and breakpoints were identified in affected...... pathogenic mutations or unique variants in the affected individuals that could explain the phenotypic differences between carriers of the same translocations. In conclusion, we suggest that NGS-based methods, such as WG-MPS, can be successfully used for detailed mapping of translocation breakpoints, which...... excluded. Future whole-exome or whole-genome sequencing will potentially reveal unidentified mutations in the patients underlying the discordant phenotypes within each family. In addition, larger studies are needed to determine the exact percentage for phenotypic risk in families with ABTs....

  14. Mechanism of RNA Translocation by a Viral Packaging Motor

    OpenAIRE

    Lisal, Jiri

    2006-01-01

    Molecular motors are proteins that convert chemical energy into mechanical work. The viral packaging ATPase P4 is a hexameric molecular motor that translocates RNA into preformed viral capsids. P4 belongs to the ubiquitous class of hexameric helicases. Although its structure is known, the mechanism of RNA translocation remains elusive. Here we present a detailed kinetic study of nucleotide binding, hydrolysis, and product release by P4. We propose a stochastic-sequential cooperative model to ...

  15. Electrically facilitated translocation of protein through solid nanopore

    OpenAIRE

    Wu, Lingzhi; Liu, Hang; Zhao, Wenyuan; Wang, Lei; Hou, Chuanrong; Liu, Quanjun; Lu, Zuhong

    2014-01-01

    Nanopores have been proven as versatile single-molecule sensors for individual unlabeled biopolymer detection and characterization. In the present work, a relative large nanopore with a diameter of about 60 nm has been used to detect protein translocation driven by a series of applied voltages. Compared with previous studied small nanopores, a distinct profile of protein translocation through a larger nanopore has been characterized. First, a higher threshold voltage is required to drive prot...

  16. Molecular studies of translocations and trisomy involving chromosome 13

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Dutly, F.; Schinzel, A.A. [Univ. of British Columbia, Vancouver (Canada)] [and others

    1996-01-11

    Twenty-four cases of trisomy 13 and one case with disomy 13, but a de novo dic(13,13)(p12p12) chromosome, were examined with molecular markers to determine the origin of the extra (or rearranged) chromosome. Twenty-one of 23 informative patients were consistent with a maternal origin of the extra chromosome. Lack of a third allele at any locus in both paternal origin cases indicate a somatic duplication of the paternal chromosome occurred. Five cases had translocation trisomy. The patient with a paternal rob(13q14q) had a maternal meiotic origin of the trisomy; thus, the paternal inheritance of the translocation chromosome was purely coincidental. Since there is not a significantly increased risk for unbalanced offspring of a t(13q14q) carrier and most trisomies are maternal in origin, this result should not be surprising; however, it illustrates that one cannot infer the origin of translocation trisomy based on parental origin of the translocation. Lack of a third allele at any locus in one of the three t(13q13q) cases indicates that it was most likely an isochromosome of postmeiotic origin, whereas the other two cases showed evidence of recombination. One balanced (nontrisomic) case with a nonmosaic 45, -13, -13, +t(13;13) karyotype was also investigated and was determined to be a somatic Robertsonian translocation between the maternal and paternal homologues, as has been found for all balanced homologous Robertsonian translocations so far investigated. Thus, it is also incorrect to assume in de novo translocation cases that the two involved chromosomes are even from the same parent. Despite a maternal origin of the trisomy, we cannot therefore infer anything about the parental origin of the chromosomes 13 and 14 involved in the translocation in the de novo t(13q14q) case nor for the two t(13;13) chromosomes showing a meiotic origin of the trisomy. 30 refs., 1 fig., 2 tabs.

  17. A Mathematical Model of Black Rhino Translocation Strategy

    Directory of Open Access Journals (Sweden)

    Dipo Aldila

    2015-03-01

    Full Text Available A deterministic mathematical model of the black rhino population in South Africa will be discussed. The model is constructed by dividing the black rhino population into multiple patches. The impact of human intervention on different translocation strategies is incorporated into the model. It is shown that, when implemented correctly, translocation can accelerate the growth rate of the total black rhino population. Equilibrium points are shown with their local stability criteria.

  18. Role of Interfacial Tensions in the Translocation of Rhodococcus erythropolis during Growth in a Two Phase Culture

    NARCIS (Netherlands)

    Iwabuchi, Noriyuki; Sharma, Prashant K.; Sunairi, Michio; Kishi, Emi; Sugita, Kazushige; van der Mei, Henny C.; Nakajima, Mutsuyasu; Busscher, Henk J.

    2009-01-01

    Rhodococcus erythropolis PR4 is an alkane-degrading bacterium, which grows well in media containing high concentrations of alkanes. These properties give the organism potential in the bioremediation of various environments contaminated by alkanes. In this study, we report the translocation of R.

  19. Carbon translocation in zooanthaellae-coelenterate symbioses

    International Nuclear Information System (INIS)

    Battey, J.F.

    1985-01-01

    When host and algal triglycerides synthesized in the symbiotic sea anemone Condylactis gigantea during light and dark incubations in 14 C-bicarbonate and 14 C-acetate were deacylated, more then 80% of the radioactivity was found in the fatty acid moiety. In contrast, triglycerides isolated from zooxanthellae and host incubated in 14 C-glycerol in the dark were found to have more then 95% of their radioactivity in the glycerol moiety. During 14 C-glycerol incubations in the light, radioactivity in the fatty acid moiety of zooxanthellae triglyceride fatty acid moiety stayed below 5% during 14 C-glycerol incubations in the light. These results show neither the zooxanthellae nor host can rapidly convert glycerol to fatty acid. Radioactivity from 14 C-glycerol that does eventually appear in host lipid may have been respired to 14 CO 2 then photosynthetically fixed by the zooxanthellae and synthesized into lipid fatty acid. The isolated zooxanthellae of C. gigantea contained 3.62 +/- 0.33 mM glycerol, which was 26x the 0.141 +/- 0.02 mM found in the coelenterate tissue. Aposymbiotic coelenterate tissue contained 0.169 +/- 0.05 mM glycerol. The metabolic inhibitors, sodium cyanide, aminooxyacetic acid and cerulenin were used to try and uncouple the production of glycerol by the zooxanthellae from its utilization by the coelenterate host. 10 -5 M NaCN increased the ratio of cross photosynthesis to respiration in both intact tentacles and isolated zooxanthellae, increased translocation from 17.7 +/- 3.5% of total fixed carbon in controls to 43.5 +/- 5.79%, and doubled the amount of photosynthetically fixed carbon accumulating in the coelenterate host over that in controls

  20. Competing uses of biomass for energy and chemicals: Implications for long-term global CO2 mitigation potential

    NARCIS (Netherlands)

    Daioglou, Vasileios; Wicke, Birka; Faaij, André; van Vuuren, Detlef

    2015-01-01

    Biomass is considered a low carbon source for various energy or chemical options. This paper assesses it’s different possible uses, the competition between these uses, and the implications for long-term global energy demand and energy system emissions. A scenario analysis is performed using the

  1. Uptake, translocation, and toxicity of gold nanorods in maize

    Science.gov (United States)

    Moradi Shahmansouri, Nastaran

    Nanomaterials are widely used in many different products, such as electronics, cosmetics, industrial goods, biomedical uses, and other material applications. The heavy emission of nanomaterials into the environment has motived increasing concern regarding the effects on ecosystems, food chains, and, human health. Plants can tolerate a certain amount of natural nanomaterials, but large amounts of ENMs released from a variety of industries could be toxic to plants and possibly threaten the ecosystem. Employing phytoremediation as a contamination treatment method may show promise. However a pre-requisite to successful treatment is a better understanding of the behavior and effects of nanomaterials within plant systems. This study is designed to investigate the uptake, translocation, bioavailability, and toxicity of gold nanorods in maize plants. Maize is an important food and feed crop that can be used to understand the potential hazardous effects of nanoparticle uptake and distribution in the food chain. The findings could be an important contribution to the fields of phytoremediation, agri-nanotechnology, and nanoparticle toxicity on plants. In the first experiment, hydroponically grown maize seedlings were exposed to similar doses of commercial non-coated gold nanorods in three sizes, 10x34 nm, 20x75 nm, and 40x96 nm. The three nanorod species were suspended in solutions at concentrations of 350 mg/l, 5.8 mg/l, and 14 mg/l, respectively. Maize plants were exposed to all three solutions resulting in considerably lower transpiration and wet biomass than control plants. Likewise, dry biomass was reduced, but the effect is less pronounced than that of transpiration and wet biomass. The reduced transpiration and water content, which eventually proved fatal to exposed plants, were most likely a result of toxic effect of gold nanorod, which appeared to physically hinder the root system. TEM images proved that maize plants can uptake gold particles and accumulate them in

  2. Ready Experimental Translocation of Mycobacterium canettii Yields Pulmonary Tuberculosis.

    Science.gov (United States)

    Bouzid, Fériel; Brégeon, Fabienne; Lepidi, Hubert; Donoghue, Helen D; Minnikin, David E; Drancourt, Michel

    2017-12-01

    Mycobacterium canettii , which has a smooth colony morphology, is the tuberculous organism retaining the most genetic traits from the putative last common ancestor of the rough-morphology Mycobacterium tuberculosis complex. To explore whether M. canettii can infect individuals by the oral route, mice were fed phosphate-buffered saline or 10 6 M. canettii mycobacteria and sacrificed over a 28-day experiment. While no M. canettii was detected in negative controls, M. canettii -infected mice yielded granuloma-like lesions for 4/4 lungs at days 14 and 28 postinoculation (p.i.) and positive PCR detection of M. canettii for 5/8 mesenteric lymph nodes at days 1 and 3 p.i. and 5/6 pooled stools collected from day 1 to day 28 p.i. Smooth M. canettii colonies grew from 68% of lungs and 36% of spleens and cervical lymph nodes but fewer than 20% of axillary lymph nodes, livers, brown fat samples, kidneys, or blood samples throughout the 28-day experiment. Ready translocation in mice after digestive tract challenge demonstrates the potential of ingested M. canettii organisms to relocate to distant organs and lungs. The demonstration of this relocation supports the possibility that populations may be infected by environmental M. canettii . Copyright © 2017 American Society for Microbiology.

  3. Lactobacillus plantarum L9 but not Lactobacillus acidophilus LA reduces tumour necrosis factor induced bacterial translocation in Caco-2 cells.

    Science.gov (United States)

    Wang, B; Chen, J; Wang, S; Zhao, X; Lu, G; Tang, X

    2017-05-30

    Translocation of bacteria across the intestinal barrier is important in the pathogenesis of systemic sepsis and multiple organ dysfunction syndromes. Inflammatory cytokines increase paracellular permeability that allows increased luminal bacteria to translocate across mucosal epithelium and further deteriorate the gut barrier. In order to reduce this risk, the prophylactic use of probiotics has been recently addressed. In this paper, we investigate the protective role toward tumour necrosis factor (TNF)-α induced non-pathogenic Escherichia coli translocation across Caco-2 monolayers of Lactobacillus strains. According to our experimental data, Lactobacillus plantarum L9 and Lactobacillus acidophilus LA have good capacities to adhere to Caco-2 cells. Addition of L. plantarum L9 and L. acidophilus LA to the enterocyte monolayer surface result in significant inhibition of E. coli adhesion and cell internalisation. However, L. plantarum L9 and L. acidophilus LA did not inhibit the growth of the non-pathogenic E. coli B5 after 24 h incubation. Exposure to TNF-α for 6 h caused a dramatic increase in E. coli B5 translocation across Caco-2 cells, which was uncoupled from increases in paracellular permeability. Pretreatment with L. plantarum L9 prevent TNF-α induced transcellular bacterial translocation and IL-8 production in Caco-2 cells. L. plantarum L9 also did not affect the integrity of the monolayers, as indicated by lactate dehydrogenase release, horseradish peroxidase permeability, and transepithelial electrical resistance. L. plantarum L9 showed the potential to protect enterocytes from an acute inflammatory response and therefore could be good potential prophylactic agents in counteracting bacterial translocation.

  4. Rapid Development and Characterization of Chromosome Specific Translocation Line of Thinopyrum elongatum with Improved Dough Strength

    Directory of Open Access Journals (Sweden)

    Aman Kumar

    2017-09-01

    Full Text Available The protein content and its type are principal factors affecting wheat (Triticum aestivum end product quality. Among the wheat proteins, glutenin proteins, especially, high molecular weight glutenin subunits (HMW-GS are major determinants of processing quality. Wheat and its primary gene pool have limited variation in terms of HMW-GS alleles. Wild relatives of wheat are an important source of genetic variation. For improvement of wheat processing quality its wild relative Thinopyrum elongatum with significant potential was utilized. An attempt was made to replace Th. elongatum chromosome long arm (1EL carrying HMW-GS genes related to high dough strength with chromosome 1AL of wheat with least or negative effect on dough strength while retaining the chromosomes 1DL and 1BL with a positive effect on bread making quality. To create chromosome specific translocation line [1EL(1AS], double monosomic of chromosomes 1E and 1A were created and further crossed with different cultivars and homoeologous pairing suppressor mutant line PhI. The primary selection was based upon glutenin and gliadin protein profiles, followed by sequential genomic in situ hybridization (GISH and fluorescent in situ hybridization (FISH. These steps significantly reduced time, efforts, and economic cost in the generation of translocation line. In order to assess the effect of translocation on wheat quality, background recovery was carried out by backcrossing with recurrent parent for several generations and then selfing while selecting in each generation. Good recovery of parent background indicated the development of almost near isogenic line (NIL. Morphologically also translocation line was similar to recipient cultivar N61 that was further confirmed by seed storage protein profiles, RP-HPLC and scanning electron microscopy. The processing quality characteristics of translocation line (BC4F6 indicated significant improvement in the gluten performance index (GPI, dough mixing

  5. Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India.

    Science.gov (United States)

    Mukesh; Sharma, Lalit Kumar; Charoo, Samina Amin; Sathyakumar, Sambandam

    2015-01-01

    The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears) returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape.

  6. Conflict bear translocation: investigating population genetics and fate of bear translocation in Dachigam National Park, Jammu and Kashmir, India.

    Directory of Open Access Journals (Sweden)

    Mukesh

    Full Text Available The Asiatic black bear population in Dachigam landscape, Jammu and Kashmir is well recognized as one of the highest density bear populations in India. Increasing incidences of bear-human interactions and the resultant retaliatory killings by locals have become a serious threat to the survivorship of black bears in the Dachigam landscape. The Department of Wildlife Protection in Jammu and Kashmir has been translocating bears involved in conflicts, henceforth 'conflict bears' from different sites in Dachigam landscape to Dachigam National Park as a flagship activity to mitigate conflicts. We undertook this study to investigate the population genetics and the fate of bear translocation in Dachigam National Park. We identified 109 unique genotypes in an area of ca. 650 km2 and observed bear population under panmixia that showed sound genetic variability. Molecular tracking of translocated bears revealed that mostly bears (7 out of 11 bears returned to their capture sites, possibly due to homing instincts or habituation to the high quality food available in agricultural croplands and orchards, while only four bears remained in Dachigam National Park after translocation. Results indicated that translocation success was most likely to be season dependent as bears translocated during spring and late autumn returned to their capture sites, perhaps due to the scarcity of food inside Dachigam National Park while bears translocated in summer remained in Dachigam National Park due to availability of surplus food resources. Thus, the current management practices of translocating conflict bears, without taking into account spatio-temporal variability of food resources in Dachigam landscape seemed to be ineffective in mitigating conflicts on a long-term basis. However, the study highlighted the importance of molecular tracking of bears to understand their movement patterns and socio-biology in tough terrains like Dachigam landscape.

  7. Systematic re-examination of carriers of balanced reciprocal translocations: a strategy to search for candidate regions for common and complex diseases

    DEFF Research Database (Denmark)

    Bache, Iben; Hjorth, Mads; Bugge, Merete

    2006-01-01

    Balanced reciprocal translocations associated with genetic disorders have facilitated the identification of a variety of genes for early-onset monogenic disorders, but only rarely the genes associated with common and complex disorders. To assess the potential of chromosomal breakpoints associated...... linkage data and/or the translocation co-segregated with the reported phenotype, for example, we found a significant linkage (lod score=2.1) of dyslexia and a co-segregating translocation with a breakpoint in a previously confirmed locus for dyslexia. Furthermore, we identified 441 instances of at least...... two unrelated carriers with concordant breakpoints and traits. If applied to other populations, re-examination of translocation carriers may identify additional genotype-phenotype associations, some of which may be novel and others that may coincide with and provide additional support of data...

  8. High-speed detection of DNA translocation in nanopipettes

    Science.gov (United States)

    Fraccari, Raquel L.; Ciccarella, Pietro; Bahrami, Azadeh; Carminati, Marco; Ferrari, Giorgio; Albrecht, Tim

    2016-03-01

    We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface.We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface. Electronic supplementary information (ESI) available: Gel electrophoresis confirming lengths and purity of DNA samples, comparison between Axopatch 200B and custom-built setup, comprehensive low-noise amplifier characterization, representative I-V curves of nanopipettes used, typical scatter plots of τ vs. peak amplitude for the four LDNA's used, table of most probable τ values, a comparison between different fitting models for the DNA translocation time distribution, further details on the stochastic numerical simulation of the scaling statistics and the derivation of the extended

  9. Characterization of cadmium binding, uptake, and translocation in intact seedlings of bread and durum wheat cultivars

    International Nuclear Information System (INIS)

    Hart, J.J.; Welch, R.M.; Norvell, W.A.; Sullivanm, L.A.; Kochian, L.V.

    1998-01-01

    High Cd content in durum wheat (Triticum turgidum L. var durum) grain grown in the United States and Canada presents potential health and economic problems for consumers and growers. In an effort to understand the biological processes that result in excess Cd accumulation, root Cd uptake and xylem translocation to shoots in seedlings of bread wheat (Triticum aestivum L.) and durum wheat cultivars were studied. Whole-plant Cd accumulation was somewhat greater in the bread wheat cultivar, but this was probably because of increased apoplastic Cd binding. Concentration-dependent 109Cd2+-influx kinetics in both cultivars were characterized by smooth, nonsaturating curves that could be dissected into linear and saturable components. The saturable component likely represented carrier-mediated Cd influx across root-cell plasma membranes (Michaelis constant, 20-40 nM; maximum initial velocity, 26-29 nmol g-1 fresh weight h-1), whereas linear Cd uptake represented cell wall binding of 109Cd. Cd translocation to shoots was greater in the bread wheat cultivar than in the durum cultivar because a larger proportion of root-absorbed Cd moved to shoots. Our results indicate that excess Cd accumulation in durum wheat grain is not correlated with seedling-root influx rates or root-to-shoot translocation, but may be related to phloem-mediated Cd transport to the grain

  10. The 18 kDa translocator protein, microglia and neuroinflammation.

    Science.gov (United States)

    Liu, Guo-Jun; Middleton, Ryan J; Hatty, Claire R; Kam, Winnie Wai-Ying; Chan, Ronald; Pham, Tien; Harrison-Brown, Meredith; Dodson, Eoin; Veale, Kelly; Banati, Richard B

    2014-11-01

    The 18 kDa translocator protein (TSPO), previously known as the peripheral benzodiazepine receptor, is expressed in the injured brain. It has become known as an imaging marker of "neuroinflammation" indicating active disease, and is best interpreted as a nondiagnostic biomarker and disease staging tool that refers to histopathology rather than disease etiology. The therapeutic potential of TSPO as a drug target is mostly based on the understanding that it is an outer mitochondrial membrane protein required for the translocation of cholesterol, which thus regulates the rate of steroid synthesis. This pivotal role together with the evolutionary conservation of TSPO has underpinned the belief that any loss or mutation of TSPO should be associated with significant physiological deficits or be outright incompatible with life. However, against prediction, full Tspo knockout mice are viable and across their lifespan do not show the phenotype expected if cholesterol transport and steroid synthesis were significantly impaired. Thus, the "translocation" function of TSPO remains to be better substantiated. Here, we discuss the literature before and after the introduction of the new nomenclature for TSPO and review some of the newer findings. In light of the controversy surrounding the function of TSPO, we emphasize the continued importance of identifying compounds with confirmed selectivity and suggest that TSPO expression is analyzed within specific disease contexts rather than merely equated with the reified concept of "neuroinflammation." © 2014 International Society of Neuropathology.

  11. Dynamic translocation of ligand-complexed DNA through solid-state nanopores with optical tweezers

    International Nuclear Information System (INIS)

    Sischka, Andy; Spiering, Andre; Anselmetti, Dario; Khaksar, Maryam; Laxa, Miriam; Koenig, Janine; Dietz, Karl-Josef

    2010-01-01

    We investigated the threading and controlled translocation of individual lambda-DNA (λ-DNA) molecules through solid-state nanopores with piconewton force sensitivity, millisecond time resolution and picoampere ionic current sensitivity with a set-up combining quantitative 3D optical tweezers (OT) with electrophysiology. With our virtually interference-free OT set-up the binding of RecA and single peroxiredoxin protein molecules to λ-DNA was quantitatively investigated during dynamic translocation experiments where effective forces and respective ionic currents of the threaded DNA molecule through the nanopore were measured during inward and outward sliding. Membrane voltage-dependent experiments of reversible single protein/DNA translocation scans yield hysteresis-free, asymmetric single-molecule fingerprints in the measured force and conductance signals that can be attributed to the interplay of optical trap and electrostatic nanopore potentials. These experiments allow an exact localization of the bound protein along the DNA strand and open fascinating applications for label-free detection of DNA-binding ligands, where structural and positional binding phenomena can be investigated at a single-molecule level.

  12. Spatial blockage of ionic current for electrophoretic translocation of DNA through a graphene nanopore.

    Science.gov (United States)

    Lv, Wenping; Liu, Shengju; Li, Xin; Wu, Ren'an

    2014-04-01

    Graphene nanopore has been promising the ultra-high resolution for DNA sequencing due to the atomic thickness and excellent electronic properties of the graphene monolayer. The dynamical translocation phenomena and/or behaviors underneath the blocked ionic current, however, have not been well unveiled to date for the translocation of DNA electrophoretically through a graphene nanopore. In this report, the assessment on the sensitivity of ionic current to instantaneous statuses of DNA in a 2.4 nm graphene nanopore was carried out based on the all-atom molecular dynamics simulations. By filtering out the thermal noise of ionic current, the instantaneous conformational variations of DNA in a graphene nanopore have been unveiled from the fluctuations of ionic current, because of the spatial blockage effect of DNA against ionic current. Interestingly, the neighborhood effect of DNA against ionic current was also observed within a distance of 1.5 nm nearby the graphene nanopore, suggesting the further precise control for DNA translocation through a graphene nanopore in gene sequencing. Moreover, the sensitivity of the blocked ionic current toward the instantaneous conformations of DNA in a graphene nanopore demonstrates the great potential of graphene nanopores in the dynamics analysis of single molecules. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  13. The metabolic enhancer piracetam attenuates mitochondrion-specific endonuclease G translocation and oxidative DNA fragmentation.

    Science.gov (United States)

    Gupta, Sonam; Verma, Dinesh Kumar; Biswas, Joyshree; Rama Raju, K Siva; Joshi, Neeraj; Wahajuddin; Singh, Sarika

    2014-08-01

    This study was performed to investigate the involvement of mitochondrion-specific endonuclease G in piracetam (P)-induced protective mechanisms. Studies have shown the antiapoptotic effects of piracetam but the mechanism of action of piracetam is still an enigma. To assess the involvement of endonuclease G in piracetam-induced protective effects, astrocyte glial cells were treated with lipopolysaccharide (LPS) and piracetam. LPS treatment caused significantly decreased viability, mitochondrial activity, oxidative stress, chromatin condensation, and DNA fragmentation, which were attenuated by piracetam cotreatment. Cotreatment of astrocytes with piracetam showed its significantly time-dependent absorption as observed with high-performance liquid chromatography. Astrocytes treated with piracetam alone showed enhanced mitochondrial membrane potential (MMP) in comparison to control astrocytes. However, in LPS-treated cells no significant alteration in MMP was observed in comparison to control cells. Protein and mRNA levels of the terminal executor of the caspase-mediated pathway, caspase-3, were not altered significantly in LPS or LPS + piracetam-treated astrocytes, whereas endonuclease G was significantly translocated to the nucleus in LPS-treated astrocytes. Piracetam cotreatment attenuated the LPS-induced endonuclease G translocation. In conclusion this study indicates that LPS treatment of astrocytes caused decreased viability, oxidative stress, mitochondrial dysfunction, chromatin condensation, DNA damage, and translocation of endonuclease G to the nucleus, which was inhibited by piracetam cotreatment, confirming that the mitochondrion-specific endonuclease G is one of the factors involved in piracetam-induced protective mechanisms. Copyright © 2014 Elsevier Inc. All rights reserved.

  14. Translocation of metal ions from soil to tobacco roots and their concentration in the plant parts.

    Science.gov (United States)

    da Silva, Cleber Pinto; de Almeida, Thiago E; Zittel, Rosimara; de Oliveira Stremel, Tatiana R; Domingues, Cinthia E; Kordiak, Januário; de Campos, Sandro Xavier

    2016-12-01

    This paper presents a study on the translocation factors (TFs) and bioconcentration factors (BCFs) of copper (Cu), manganese (Mn), zinc (Zn), cobalt (Co), chromium (Cr), cadmium (Cd), lead (Pb), iron (Fe), nickel (Ni), and arsenic (As) ions in roots, stems, and leaves of tobacco. The results revealed that during the tobacco growth, the roots are able to increase the sensitiveness of the physiological control, reducing the translocation of the metals Ni (0.38) and Pb (0.48) to the leaves. Cd and Zn presented factors TF and BCF >1 in the three tissues under analysis, which indicates the high potential for transportation and accumulation of these metals in all plant tissues. The TF values for Cr (0.65) and As (0.63) revealed low translocation of these ions to the aerial parts, indicating low mobility of ions from the roots. Therefore, tobacco can be considered an efficient accumulator of Ni, Cr, As and Pb in roots and Cd and Zn in all plant parts.

  15. In-vitro photo-translocation of antiretroviral drug delivery into TZMbl cells

    Science.gov (United States)

    Malabi, Rudzani; Manoto, Sello; Ombinda-Lemboumba, Saturnin; Maaza, Malik; Mthunzi-Kufa, Patience

    2017-02-01

    The current human immunodeficiency virus (HIV) treatment regime possesses the ability to diminish the viral capacity to unnoticeable levels; however complete eradication of the virus cannot be achieved while latent HIV-1 reservoirs go unchallenged. Therapeutic targeting of HIV therefore requires further investigation and current therapies need modification in order to address HIV eradication. This deflects research towards investigating potential novel antiretroviral drug delivery systems. The use of femtosecond (fs) laser pulses in promoting targeted optical drug delivery of antiretroviral drugs (ARVs) into TZMbl cells revolves around using ultrafast laser pulses that have high peak powers, which precisely disrupt the cell plasma membrane in order to allow immediate transportation and expression of exogenous material into the live mammalian cells. A photo-translocation optical setup was built and validated by characterisation of the accurate parameters such as wavelength (800 nm) and pulse duration (115 fs). Optimisation of drug translocation parameters were done by performing trypan blue translocation studies. Cellular responses were determined via cell viability (Adenosine Triphosphate activity) and cell cytotoxicity (Lactate Dehydrogenase) assays which were done to study the influence of the drugs and laser exposure on the cells. After laser irradiation, high cell viability was observed and low toxicity levels were observed after exposure of the cells to both the ARVs and the laser. Our results confirmed that, with minimal damage and high therapeutic levels of ARVs, the fs laser assisted drug delivery system is efficient with benefits of non-invasive and non-toxic treatment to the cells.

  16. Translocation of Bioactive Molecules through Carbon Nanotubes Embedded in the Lipid Membrane.

    Science.gov (United States)

    Sahoo, Anil Kumar; Kanchi, Subbarao; Mandal, Taraknath; Dasgupta, Chandan; Maiti, Prabal K

    2018-02-21

    One of the major challenges of nanomedicine and gene therapy is the effective translocation of drugs and genes across cell membranes. In this study, we describe a systematic procedure that could be useful for efficient drug and gene delivery into the cell. Using fully atomistic molecular dynamics (MD) simulations, we show that molecules of various shapes, sizes, and chemistries can be spontaneously encapsulated in a single-walled carbon nanotube (SWCNT) embedded in a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) lipid bilayer, as we have exemplified with dendrimers, asiRNA, ssDNA, and ubiquitin protein. We compute the free energy gain by the molecules upon their entry inside the SWCNT channel to quantify the stability of these molecules inside the channel as well as to understand the spontaneity of the process. The free energy profiles suggest that all molecules can enter the channel without facing any energy barrier but experience a strong energy barrier (≫k B T) to translocate across the channel. We propose a theoretical model for the estimation of encapsulation and translocation times of the molecules. Whereas the model predicts the encapsulation time to be of the order of few nanoseconds, which match reasonably well with those obtained from the simulations, it predicts the translocation time to be astronomically large for each molecule considered in this study. This eliminates the possibility of passive diffusion of the molecules through the CNT-nanopore spanning across the membrane. To counter this, we put forward a mechanical method of ejecting the encapsulated molecules by pushing them with other free-floating SWCNTs of diameter smaller than the pore diameter. The feasibility of the proposed method is also demonstrated by performing MD simulations. The generic strategy described here should work for other molecules as well and hence could be potentially useful for drug- and gene-delivery applications.

  17. Indomethacin-Induced Apoptosis in Esophageal Adenocarcinoma Cells Involves Upregulation of Bax and Translocation of Mitochondrial Cytochrome C Independent of COX-2 Expression

    Directory of Open Access Journals (Sweden)

    Sanjeev Aggarwal

    2000-07-01

    Full Text Available The prolonged use of nonsteroidal anti-inflammatory drugs (NSAIDs has been shown to exert a chemopreventive effect in esophageal and other gastrointestinal tumors. The precise mechanism by which this occurs, however, is unknown. While the inhibition of COX-2 as a potential explanation for this chemopreventive effect has gained a great deal of support, there also exists evidence supporting the presence of cyclooxygenase-independent pathways through which NSAIDs may exert their effects. In this study, immunohistochemical analysis of 29 Barrett's epithelial samples and 60 esophageal adenocarcinomas demonstrated abundant expression of the COX-2 protein in Barrett's epithelium, but marked heterogeneity of expression in esophageal adenocarcinomas. The three esophageal adenocarcinoma cell lines, Flo-1, Bic-1, Seg-1, also demonstrated varying expression patterns for COX-1 and COX-2. Indomethacin induced apoptosis in all three cell lines, however, in both a time- and dose-dependent manner. In Flo-1 cells, which expressed almost undetectable levels of COX-1 and COX-2, in Seg-1, which expressed significant levels of COX-1 and COX-2, indomethacin caused upregulation of the pro-apoptosic protein Bax. The upregulation of Bax was accompanied by the translocation of mitochondrial cytochrome c to the cytoplasm, activation of caspase 9. Pre-treatment of both cell lines with the specific caspase 9 inhibitor, z-LEHD-FMK, as well as the broad-spectrum caspase inhibitor, z-VAD-FMK, blocked the effect of indomethacin-induced apoptosis. These data demonstrate that induction of apoptosis by indomethacin in esophageal adenocarcinoma cells is associated with the upregulation of Bax expression and mitochondrial cytochrome c translocation, does not correlate with the expression of COX-2. This may have important implications for identifying new therapeutic targets in this deadly disease.

  18. [PCR detection of relevant translocations in pediatric acute lymphoblastic leukemia].

    Science.gov (United States)

    Guerra-Castillo, Francisco Xavier; Ramos-Cervantes, María Teresa; Rosel-Pech, Cecilia; Jiménez-Hernández, Elva; Bekker-Méndez, Vilma Carolina

    2016-01-01

    In Mexico, leukemia represents the most common type of cancer in the population under 15 years old with a high incidence rate when compared with developed countries. The etiology of leukemia may be unknown, however different factors are involve such as chromosomal translocations. The aim of this work is to detect the molecular alterations: TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1 in pediatric patients with acute lymphoblastic leukemia. 91 bone marrow samples were collected from pediatric patients with acute lymphoblastic leukemia from january 2012 to march 2013 at the Pediatric Hematology Service, Hospital General "Gaudencio González Garza". Translocations detected (TEL-AML1, MLL-AF4, BCR-ABL minor and E2A-PBX1) using real time PCR, SYBR Green (Qiagen, Alameda, CA). 91 samples were processed, the detected frequencies for each translocation were: TEL-AML1 (7.21%), E2A-PBX1 (5.15%). The MLL-AF4 and the BCR-ABL minor translocations were not detected in this study. The frequencies shown in this study are consistent with the data shown in the literature, where TEL-AML1 is the most common translocation found in pediatric patients. It is of relevance to mention that E2A-PBX1 is found in a high frequency in developing countries when compared with developed countries.

  19. Electrostatics of polymer translocation events in electrolyte solutions.

    Science.gov (United States)

    Buyukdagli, Sahin; Ala-Nissila, T

    2016-07-07

    We develop an analytical theory that accounts for the image and surface charge interactions between a charged dielectric membrane and a DNA molecule translocating through the membrane. Translocation events through neutral carbon-based membranes are driven by a competition between the repulsive DNA-image-charge interactions and the attractive coupling between the DNA segments on the trans and the cis sides of the membrane. The latter effect is induced by the reduction of the coupling by the dielectric membrane. In strong salt solutions where the repulsive image-charge effects dominate the attractive trans-cis coupling, the DNA molecule encounters a translocation barrier of ≈10 kBT. In dilute electrolytes, the trans-cis coupling takes over image-charge forces and the membrane becomes a metastable attraction point that can trap translocating polymers over long time intervals. This mechanism can be used in translocation experiments in order to control DNA motion by tuning the salt concentration of the solution.

  20. A somatic origin of homologous Robertsonian translocations and isochromosomes

    Energy Technology Data Exchange (ETDEWEB)

    Robinson, W.P.; Bernasconi, F.; Schinzel, A.A. (Univ. of Zurich (Switzerland)); Basaran, S.; Yueksel-Apak, M. (Univ. of Istanbul (Turkey)); Neri, G. (Universita Cattolica, Rome (Italy)); Serville, F. (Hopital d' Enfants Pellegrin, Bordeaux (France)); Balicek, P.; Haluza, R. (Univ. Hospital of Hradeck Kralove, Hradec Kralove (Czech Republic)); Farah, L.M.S. (Escuola Paulista de Medicina, Sao Paulo (Brazil)) (and others)

    1994-02-01

    One t(14q 14q), three t(15q 15q), two t(21q21q), and two t(22q22q) nonmosaic, apparently balanced, de novo Robertsonian translocation cases were investigated with polymorphic markers to establish the origin of the translocated chromosomes. Four cases had results indicative of an isochromosome: one t(14q14q) case with mild mental retardation and maternal uniparental disomy (UPD) for chromosome 14, one t(15q15q) case with the Prader-Willi syndrome and UPD(15), a phenotypically normal carrier of t(22q22q) with maternal UPD(22), and a phenotypically normal t(21q21q) case of paternal UPD(21). All UPD cases showed complete homozygosity throughout the involved chromosome, which is supportive of a postmeiotic origin. In the remaining four cases, maternal and paternal inheritance of the involved chromosome was found, which unambiguously implies a somatic origin. One t(15q15q) female had a child with a ring chromosome 15, which was also of probable postmeiotic origin as recombination between grandparental haplotypes had occurred prior to ring formation. UPD might be expected to result from de novo Robertsonian translocations of meiotic origin; however, all de novo homologous translocation cases, so far reported, with UPD of chromosomes 14, 15, 21, or 22 have been isochromosomes. These data provide the first direct evidence that nonmosaic Robertsonian translocations, as well as isochromosomes, are commonly the result of a mitotic exchange. 75 refs., 1 fig., 4 tabs.

  1. Perturbational Profiling of Metabolites in Patient Fibroblasts Implicates α-Aminoadipate as a Potential Biomarker for Bipolar Disorder

    Science.gov (United States)

    Huang, Joanne H.; Berkovitch, Shaunna S.; Iaconelli, Jonathan; Watmuff, Bradley; Park, Hyoungjun; Chattopadhyay, Shrikanta; McPhie, Donna; Öngür, Dost; Cohen, Bruce M.; Clish, Clary B.; Karmacharya, Rakesh

    2016-01-01

    Many studies suggest the presence of aberrations in cellular metabolism in bipolar disorder. We studied the metabolome in bipolar disorder to gain insight into cellular pathways that may be dysregulated in bipolar disorder and to discover evidence of novel biomarkers. We measured polar and nonpolar metabolites in fibroblasts from subjects with bipolar I disorder and matched healthy control subjects, under normal conditions and with two physiologic perturbations: low-glucose media and exposure to the stress-mediating hormone dexamethasone. Metabolites that were significantly different between bipolar and control subjects showed distinct separation by principal components analysis methods. The most statistically significant findings were observed in the perturbation experiments. The metabolite with the lowest p value in both the low-glucose and dexamethasone experiments was α-aminoadipate, whose intracellular level was consistently lower in bipolar subjects. Our study implicates α-aminoadipate as a possible biomarker in bipolar disorder that manifests under cellular stress. This is an intriguing finding given the known role of α-aminoadipate in the modulation of kynurenic acid in the brain, especially as abnormal kynurenic acid levels have been implicated in bipolar disorder. PMID:27606323

  2. Characterization of Elements Regulating the Nuclear-to-Cytoplasmic Translocation of ICP0 in Late Herpes Simplex Virus 1 Infection.

    Science.gov (United States)

    Samrat, Subodh Kumar; Ha, Binh L; Zheng, Yi; Gu, Haidong

    2018-01-15

    HSV-1 infection, we investigated the potential players involved in this nuclear-to-cytoplasmic translocation. We found that there is a nuclear retention force in an ICP0 E3 ubiquitin ligase-dependent manner. In addition, we identified the C terminus of ICP0 as a cis element cooperating with late viral proteins to overcome the nuclear retention and stimulate the nuclear-to-cytoplasmic translocation of ICP0. Copyright © 2018 American Society for Microbiology.

  3. Ozonation and Thermal Pre-Treatment of Municipal Sewage Sludge-Implications for Toxicity and Methane Potential

    DEFF Research Database (Denmark)

    Davidsson, A.; Eriksson, Eva; Fick, J.

    2013-01-01

    The aim of this study was to determine effects on methane potential and overall sludge quality from two different sludge pre-treatment technologies (ozonation high/low dosage and thermal treatment 55/70 degrees C). In general both treatments produced increased methane potential. Thermal treatment...

  4. Translocation of polymers into crowded media with dynamic attractive nanoparticles.

    Science.gov (United States)

    Cao, Wei-Ping; Ren, Qing-Bao; Luo, Meng-Bo

    2015-07-01

    The translocation of polymers through a small pore into crowded media with dynamic attractive nanoparticles is simulated. Results show that the nanoparticles at the trans side can affect the translocation by influencing the free-energy landscape and the diffusion of polymers. Thus the translocation time τ is dependent on the polymer-nanoparticle attraction strength ɛ and the mobility of nanoparticles V. We observe a power-law relation of τ with V, but the exponent is dependent on ɛ and nanoparticle concentration. In addition, we find that the effect of attractive dynamic nanoparticles on the dynamics of polymers is dependent on the time scale. At a short time scale, subnormal diffusion is observed at strong attraction and the diffusion is slowed down by the dynamic nanoparticles. However, the diffusion of polymers is normal at a long time scale and the diffusion constant increases with the increase in V.

  5. Translocation techniques used to establish pen farmed Alaskan reindeer

    Directory of Open Access Journals (Sweden)

    R. A. Dieterich

    1990-09-01

    Full Text Available Small herds of reindeer (Rangifer tarandus frequently have been needed to be established in fenced holding pens for research or commercial reasons in Alaska and other areas. Native ranges of reindeer in Alaska were not on road systems, and the diet of the native reindeer had to be changed when they were translocated to small pens. Economics of transportation and feeding played an important role in the feasibility of translocation. Gathering and holding of reindeer for shipment, transport methods, adjustment of free-ranging reindeer to confinement, and a new diet were primary considerations to insure survival. Minimal psychologic stress of short duration, thermoregulation, and physical comfort were extremely important in carrying out a successful translocation. Receiving facilities, feed, and personnel were equally important. A minimum of one month was required to adjust reindeer to confinement and diet change.

  6. Scintigraphic visualization of bacterial translocation in experimental strangulated intestinal obstruction

    International Nuclear Information System (INIS)

    Galeev, Yu.M.; Popov, M.V.; Salato, O.V.; Lishmanov, Yu.B.; Grigorev, E.G.; Aparcin, K.A.

    2009-01-01

    The purpose of this study was to obtain scintigraphic images depicting translocation of 99m Tc-labelled Escherichia coli bacteria through the intestinal barrier and to quantify this process using methods of nuclear medicine. Thirty male Wistar rats (including 20 rats with modelled strangulated intestinal obstruction and 10 healthy rats) were used for bacterial scintigraphy. 99m Tc-labelled E. coli bacteria ( 99m Ts-E. coli) with an activity of 7.4-11.1 MBq were administered into a section of the small intestine. Scintigraphic visualization of bacterial translocation into organs and tissues of laboratory animals was recorded in dynamic (240 min) and static (15 min) modes. The number of labelled bacteria, which migrated through the intestinal barrier, was quantified by calculating the translocation index (TI). Control indicated no translocation of 99m Ts-E. coli administered into the intestine through the parietes of the small intestine's distal part in healthy animals. Animals with strangulated obstruction demonstrated different migration strength and routes of labelled bacteria from strangulated and superior to strangulation sections of the small intestine. 99m Ts-E. coli migrated from the strangulated loop into the peritoneal cavity later causing systemic bacteraemia through peritoneal resorption. The section of the small intestine, which was superior to the strangulation, demonstrated migration of labelled bacteria first into the portal and then into the systemic circulation. The strangulated section of the small intestine was the main source of bacteria dissemination since the number of labelled bacteria, which migrated from this section significantly, exceeded that of the area superior to the strangulation section of the small intestine (p = 0.0003). Bacterial scintigraphy demonstrated the possibility of visualizing migration routes of labelled bacteria and quantifying their translocation through the intestinal barrier. This approach to study bacterial

  7. Decision-support model to explore the feasibility of using translocation to restore a woodland caribou population in Pukaskwa National Park, Canada

    Directory of Open Access Journals (Sweden)

    Emily K. Gonzales

    2015-12-01

    Full Text Available The distribution and abundance of woodland caribou (Rangifer tarandus caribou have declined dramatically in the past century. Without intervention the most southern population of caribou in eastern North America is expected to disappear within 20 years. Although translocations have reintroduced and reinforced some populations, approximately half of caribou translocation efforts fail. Translocations are resource intensive and risky, and multiple interrelated factors must be considered to assess their potential for success. Structured decision-making tools, such as Bayesian belief networks, provide objective methods to assess different wildlife management scenarios by identifying the key components and relationships in an ecosystem. They can also catalyze dialogue with stakeholders and provide a record of the complex thought processes used in reaching a decision. We developed a Bayesian belief network for a proposed translocation of woodland caribou into a national park on the northeastern coast of Lake Superior, Ontario, Canada. We tested scenarios with favourable (e.g., good physical condition of adult caribou and unfavourable (e.g., high predator densities conditions with low, medium, and high numbers of translocated caribou. Under the current conditions at Pukaskwa National Park, augmenting the caribou population is unlikely to recover the species unless wolf densities remain low (<5.5/1000 km2 or if more than 300 animals could be translocated.

  8. The action spectrum in chloroplast translocation in multilayer leaf cells

    Directory of Open Access Journals (Sweden)

    Zbigniew Lechowski

    2015-01-01

    Full Text Available By measurement of light transmittance through a leaf as criterion of chloroplast translocation, the action spectrum of Ajuga reptans was established. In the spectrum obtained, a correction was introduced for leaf autoabsorption calculated on the basis of the Beer-Lambert law. The action spectrum has two maxima: at λ= 375 nm and λ= 481 nm. The range above 502 nm has no significant effect on chloroplast translocation. Comparison with other objects examined demonstrated that in multilayer leaf cells riboflavin seems also to be a photoreceptor active in this process.

  9. Centrifugally driven microfluidic disc for detection of chromosomal translocations

    DEFF Research Database (Denmark)

    Brøgger, Anna Line; Kwasny, Dorota; Bosco, Filippo G.

    2012-01-01

    and prognosis of patients. In this work we demonstrate a novel, centrifugally-driven microfluidic system for controlled manipulation of oligonucleotides and subsequent detection of chromosomal translocations. The device is fabricated in the form of a disc with capillary burst microvalves employed to control...... and detection chambers. The burst frequencies of the two capillary burst microvalves are separated by 180 rpm enabling precise control of hybridization in each of the chambers. The DNA probes targeting a translocation are immobilized directly on PMMA by a UV-activated procedure, which is compatible...

  10. Role of non-equilibrium conformations on driven polymer translocation.

    Science.gov (United States)

    Katkar, H H; Muthukumar, M

    2018-01-14

    One of the major theoretical methods in understanding polymer translocation through a nanopore is the Fokker-Planck formalism based on the assumption of quasi-equilibrium of polymer conformations. The criterion for applicability of the quasi-equilibrium approximation for polymer translocation is that the average translocation time per Kuhn segment, ⟨τ⟩/N K , is longer than the relaxation time τ 0 of the polymer. Toward an understanding of conditions that would satisfy this criterion, we have performed coarse-grained three dimensional Langevin dynamics and multi-particle collision dynamics simulations. We have studied the role of initial conformations of a polyelectrolyte chain (which were artificially generated with a flow field) on the kinetics of its translocation across a nanopore under the action of an externally applied transmembrane voltage V (in the absence of the initial flow field). Stretched (out-of-equilibrium) polyelectrolyte chain conformations are deliberately and systematically generated and used as initial conformations in translocation simulations. Independent simulations are performed to study the relaxation behavior of these stretched chains, and a comparison is made between the relaxation time scale and the mean translocation time (⟨τ⟩). For such artificially stretched initial states, ⟨τ⟩/N K equilibrium approximation. Nevertheless, we observe a scaling of ⟨τ⟩ ∼ 1/V over the entire range of chain stretching studied, in agreement with the predictions of the Fokker-Planck model. On the other hand, for realistic situations where the initial artificially imposed flow field is absent, a comparison of experimental data reported in the literature with the theory of polyelectrolyte dynamics reveals that the Zimm relaxation time (τ Zimm ) is shorter than the mean translocation time for several polymers including single stranded DNA (ssDNA), double stranded DNA (dsDNA), and synthetic polymers. Even when these data are rescaled

  11. Potential Implications of Approaches to Climate Change on the Clean Water Rule Definition of "Waters of the United States".

    Science.gov (United States)

    Faust, Derek R; Moore, Matthew T; Emison, Gerald Andrews; Rush, Scott A

    2016-05-01

    The 1972 Clean Water Act was passed to protect chemical, physical, and biological integrity of United States' waters. The U.S. Environmental Protection Agency and U.S. Army Corps of Engineers codified a new "waters of the United States" rule on June 29, 2015, because several Supreme Court case decisions caused confusion with the existing rule. Climate change could affect this rule through connectivity between groundwater and surface waters; floodplain waters and the 100-year floodplain; changes in jurisdictional status; and sea level rise on coastal ecosystems. Four approaches are discussed for handling these implications: (1) "Wait and see"; (2) changes to the rule; (3) use guidance documents; (4) Congress statutorily defining "waters of the United States." The approach chosen should be legally defensible and achieved in a timely fashion to provide protection to "waters of the United States" in proactive consideration of scientifically documented effects of climate change on aquatic ecosystems.

  12. Statistical evidence of the geological control over radon soil gas concentrations and its implications for mapping radon potential

    International Nuclear Information System (INIS)

    Badr, I.; Durrani, S.A.; Oliver, M.A.

    1996-01-01

    Determining how radon varies spatially over a given area in the natural environment is important for defining high risk areas and has implications for building practice. To achieve the former, radon concentrations in three areas of the English Midlands were surveyed. The first area comprised a single rock formation near Hereford (described elsewhere). The others, reported here, were areas where elevated concentrations of radon were expected. One was an area comprising two major rock types near Buxton in Derbyshire where a multistage sampling design was used to determine the approximate spatial scale of variation in soil radon concentration. The third was an area of more complex geology near Nottingham, where sampling along a transect enabled the structure and scale of variation to be determined. In all of the areas radon concentrations varied considerably, both over large and small distances. The data were analysed using methods embodied in geostatistics. The results showed that structure in the spatial variation of radon for the Buxton and Nottingham surveys at the longer scale could be attributed to the effect of lithology. The latter appears to account for approximately 50% of the total variation in both surveys. These results have important implications for mapping radon and also for building programmes, insurance, etc. They also suggest that to estimate radon reliably at the local level by interpolation would generally require very intensive sampling, i.e. at a scale of metres rather than kilometres. However, stratification of an area based on geology, with sampling within the strata designed to estimate average radon concentrations optimally, would provide reasonable estimates in certain situations for somewhat less sampling effort. (author)

  13. Implication of post-glacial warming for Northern Alberta heat flow - correcting for the underestimate of the geothermal potential

    Czech Academy of Sciences Publication Activity Database

    Majorowicz, J.; Gosnold, W.; Gray, A.; Šafanda, Jan; Klenner, R.; Unsworth, M.

    2012-01-01

    Roč. 36, č. 1 (2012), s. 693-698 ISSN 0193-5933 Institutional support: RVO:67985530 Keywords : geothermal energy potential * Canadian sedimentary basin * heat flow * paleoclimatic correction Subject RIV: DC - Siesmology, Volcanology, Earth Structure

  14. The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research

    OpenAIRE

    Henningfield, Jack E.; Fant, Reginald V.; Wang, Daniel W.

    2017-01-01

    Rationale Consideration by the US Drug Enforcement Administration and Food and Drug Administration of placing kratom into Schedule I of the Controlled Substances Act (CSA) requires its evaluation of abuse potential in the context of public health. Objective The objective of the study is to provide a review of kratom abuse potential and its evaluation according to the 8 factors of the CSA. Results Kratom leaves and extracts have been used for centuries in Southeast Asia and elsewhere to manage...

  15. Mitochondrial translocation of Nur77 induced by ROS contributed to cardiomyocyte apoptosis in metabolic syndrome.

    Science.gov (United States)

    Xu, Aibin; Liu, Jingyi; Liu, Peilin; Jia, Min; Wang, Han; Tao, Ling

    2014-04-18

    Metabolic syndrome is a major risk factor for cardiovascular diseases, and increased cardiomyocyte apoptosis which contributes to cardiac dysfunction after myocardial ischemia/reperfusion (MI/R) injury. Nur77, a nuclear orphan receptor, is involved in such various cellular events as apoptosis, proliferation, and glucose and lipid metabolism in several cell types. Apoptosis is positively correlated with mitochondrial translocation of Nur77 in the cancer cells. However, the roles of Nur77 on cardiac myocytes in patients with metabolic syndrome remain unclear. The objective of this study was to determine whether Nur77 may contribute to cardiac apoptosis in patients with metabolic syndrome after I/R injury, and, if so, to identify the underlying molecular mechanisms responsible. We used leptin-deficient (ob/ob) mice to make metabolic syndrome models. In this report, we observed that, accompanied by the substantial decline in apoptosis inducer Nur77, MI/R induced cardiac dysfunction was manifested as cardiomyopathy and increased ROS. Using the neonatal rat cardiac myocytes cultured in a high-glucose and high-fat medium, we found that excessive H2O2 led to the significant alteration in mitochondrial membrane potential and translocation of Nur77 from the nucleus to the mitochondria. However, inhibition of the relocation of Nur77 to mitochondria via Cyclosporin A reversed the changes in membrane potential mediated by H2O2 and reduced myocardial cell injury. Therefore, these data provide a potential underlying mechanism for cardiac dysfunction in metabolic syndrome and the suppression of Nur77 translocation may provide an effective approach to reduce cardiac injury in the process. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Invasion and translocation of uropathogenic Escherichia coli isolated from urosepsis and patients with community-acquired urinary tract infection.

    Science.gov (United States)

    Owrangi, B; Masters, N; Kuballa, A; O'Dea, C; Vollmerhausen, T L; Katouli, M

    2018-01-16

    Uropathogenic Escherichia coli (UPEC) strains are found in high numbers in the gut of patients with urinary tract infections (UTIs). We hypothesised that in hospitalised patients, UPEC strains might translocate from the gut to the blood stream and that this could be due to the presence of virulence genes (VGs) that are not commonly found in UPEC strains that cause UTI only. To test this, E. coli strains representing 75 dominant clonal groups of UPEC isolated from the blood of hospitalised patients with UTI (urosepsis) (n = 22), hospital-acquired (HA) UTI without blood infection (n = 24) and strains isolated from patients with community-acquired (CA)-UTIs (n = 29) were tested for their adhesion to, invasion and translocation through Caco-2 cells, in addition to the presence of 34 VGs associated with UPEC. Although there were no differences in the rate and degree of translocation among the groups, urosepsis and HA-UTI strains showed significantly higher abilities to adhere (P = 0.0095 and P UPEC strains, irrespective of their source, are capable of translocating through gut epithelium. However, urosepsis and HA-UTI strains have a much better ability to interact with gut epithelia and have a greater virulence potential than CA-UPEC, which allows them to cause blood infection.

  17. Absence of t(14;18) chromosome translocation in agricultural workers after short-term exposure to pesticides.

    Science.gov (United States)

    Rapisarda, Venerando; Ledda, Caterina; Matera, Serena; Fago, Lucrezia; Arrabito, Giorgio; Falzone, Luca; Marconi, Andrea; Libra, Massimo; Loreto, Carla

    2017-05-01

    Exposure to pesticides represents a potential health risk for the general population and for agricultural workers in particular. Some researchers observed that occupational exposure to pesticides is associated with risk of non‑Hodgkin's lymphoma (NHL). The chromosomal translocation t(14;18)(q32;q21) is one of the most common chromosomal abnormalities in NHL. The aim of this study was to detect the effects of pesticides on t(14;18) chromosome translocation in agricultural workers after short-term exposure. Fifty-two workers occupationally exposed to pesticides (fungicides and insecticides) and 52 non-exposed were recruited. The farm workers were on average exposed to pesticides for ~3.7 h a day for 5 years. The frequency of BCL2-IGH t(14;18) translocation in workers occupationally exposed to pesticides was 10% (5 of 52) vs. 8% (4 of 52) in the control group. Overall, these data suggest that no significant association between occupational exposure to pesticides and an increased frequency of the chromosomal translocation BCL2-IGH t(14;18) in farmers was observed. However, further studies with a higher number of subjects exposed to pesticides are necessary to confirm this observation.

  18. Significant Role of Segmental Duplications and SIDD Sites in Chromosomal Translocations of Hematological Malignancies: A Multi-parametric Bioinformatic Analysis.

    Science.gov (United States)

    Daga, Aditi; Ansari, Afzal; Pandya, Medha; Shah, Krupa; Patel, Shanaya; Rawal, Rakesh; Umrania, Valentina

    2016-11-28

    Recurrent non-random chromosomal translocations are hallmark characteristics of leukemogenesis, and however, molecular mechanisms underlying these rearrangements are less explored. The fundamental question is, why and how chromosomes break and reunite so precisely in the genome. Meticulous understanding of mechanism leading to chromosomal rearrangement can be achieved by characterizing breakpoints. To address this hypothesis, a novel multi-parametric computational approach for characterization of major leukemic translocations within and around breakpoint region was performed. To best of our knowledge, this bioinformatic analysis is unique in finding the presence of segmental duplications (SDs) flanking breakpoints of all major leukemic translocation. Breakpoint islands (BpIs) were analyzed for stress-induced duplex destabilization (SIDD) sites along with other complex genomic architecture and physicochemical properties. Our study distinctly emphasizes on the probable correlative role of SDs, SIDD sites and various genomic features in the occurrence of breakpoints. Further, it also highlights potential features which may be playing a crucial role in causing double-strand breaks, leading to translocation.

  19. Ozonation and Thermal Pre-Treatment of Municipal Sewage Sludge-Implications for Toxicity and Methane Potential

    DEFF Research Database (Denmark)

    Davidsson, A.; Eriksson, Eva; Fick, J.

    2013-01-01

    resulted in higher chemical oxygen demand (COD)-solubilisation, while the highest volatile fatty acids (VFA) increase was obtained with ozonation. Sludges had inhibiting effects in a barley seed germination assay and a yeast oestrogen screen both before and after pre-treatment, but inhibition was reduced......The aim of this study was to determine effects on methane potential and overall sludge quality from two different sludge pre-treatment technologies (ozonation high/low dosage and thermal treatment 55/70 degrees C). In general both treatments produced increased methane potential. Thermal treatment...... by ozone treatment and digestion. No statistical significant reduction in concentrations of included pharmaceuticals could be observed....

  20. Ozonation and thermal pre-treatment of municipal sewage sludge – Implications for toxicity and methane potential

    DEFF Research Database (Denmark)

    Davidsson, A.; Eriksson, Eva; Fick, J.

    The aim of this study was to determine the effects on the methane potential and the overall sludge quality from two different sludge pre-treatment technologies (ozonation high/low dosage and thermal treatment 55/70 °C). In general both treatments gave an increased methane potential. The thermal...... treatment resulted in higher chemical oxygen demand (COD)-solubilisation, while the highest volatile fatty acids (VFA) increase was obtained with ozonation. The sludges had inhibiting effects in a barley seed germination assay and a yeast oestrogen screen both before and after pre...

  1. Potential Implications of Recent and Proposed Changes in the Regulatory Oversight of Solid Organ Transplantation in the United States

    Science.gov (United States)

    Kasiske, BL; Salkowski, N; Wey, A; Israni, AK; Snyder, JJ

    2016-01-01

    Every 6 months, the Scientific Registry of Transplant Recipients (SRTR) publishes evaluations of every solid organ transplant program in the US, including evaluations of 1-year patient and graft survival. The Centers for Medicare & Medicaid Services (CMS) and the Organ Procurement and Transplantation Network (OPTN) Membership and Professional Standards Committee (MPSC) use SRTR’s 1-year evaluations for regulatory review of transplant programs. Concern has been growing that the regulatory scrutiny of transplant programs with lower than expected outcomes is harmful, causing programs to undertake fewer high-risk transplants and leading to unnecessary organ discards. As a result, CMS raised its threshold for a “Condition-Level Deficiency” designation of observed relative to expected 1-year graft or patient survival from 1.50 to 1.85. Exceeding this threshold in the current SRTR outcomes report and in one of the four previous reports leads to scrutiny that may result in loss of Medicare funding. For its part, OPTN is reviewing a proposal from the MPSC to also change its performance criteria thresholds for program review, to review programs with “substantive clinical differences.” We review the details and implications of these changes in transplant program oversight. PMID:27401597

  2. Interpreting potential markers of storage and rehearsal: Implications for studies of verbal short-term memory and neuropsychological cases.

    Science.gov (United States)

    Wang, Xiaoli; Logie, Robert H; Jarrold, Christopher

    2016-08-01

    Neuropsychological studies of verbal short-term memory have often focused on two signature effects - phonological similarity and word length - the absence of which has been taken to indicate problems in phonological storage and rehearsal respectively. In the present study we present a possible alternative reading of such data, namely that the absence of these effects can follow as a consequence of an individual's poor level of recall. Data from a large normative sample of 251 adult participants were re-analyzed under the assumption that the size of phonological similarity and word length effects are proportional to an individual's overall level of recall. For both manipulations, when proportionalized effects were plotted against memory span, the same function fit the data in both auditory and visual presentation conditions. Furthermore, two additional sets of single-case data were broadly comparable to those that would be expected for an individual's level of verbal short-term memory performance albeit with some variation across tasks. These findings indicate that the absolute magnitude of phonological similarity and word length effects depends on overall levels of recall, and that these effects are necessarily eliminated at low levels of verbal short-term memory performance. This has implications for how one interprets any variation in the size of these effects, and raises serious questions about the causal direction of any relationship between impaired verbal short-term memory and the absence of phonological similarity or word length effects.

  3. Considering the Ethical Implications of Space Exploration and Potential Impacts on Planetary Environments and Possible Indigenous Life

    Science.gov (United States)

    Race, Margaret

    Since the early days of the Outer Space Treaty, a primary concern of planetary protection policy has been to avoid contamination of planetary environments by terrestrial microbes that could compromise current or subsequent scientific investigations, particularly those searching for indigenous life. Over the past decade robotic missions and astrobiological research have greatly increased our understanding of diverse planetary landscapes and altered our views about the survivability of terrestrial organisms in extreme environments. They have also expanded notions about the prospect for finding evidence of extraterrestrial life. Recently a number of different groups, including the COSPAR Planetary Protection Workshop in Montreal (January 2008), have questioned whether it is advisable to re-examine current biological planetary protection policy in light of the ethical implications and responsibilities to preserve planetary environments and possible indigenous life. This paper discusses the issues and concerns that have led to recent recommendations for convening an international workshop specifically to discuss planetary protection policy and practices within a broader ethical and practical framework, and to consider whether revisions to policy and practices should be made. In addition to including various international scientific and legal organizations and experts in such a workshop, it will be important to find ways to involve the public in these discussions about ethical aspects of planetary exploration.

  4. The Potential Impacts of Climate Change Factors on Freshwater Eutrophication: Implications for Research and Countermeasures of Water Management in China

    Directory of Open Access Journals (Sweden)

    Rui Xia

    2016-03-01

    Full Text Available Water eutrophication has become one of the most serious aquatic environmental problems around the world. More and more research has indicated climate change as a major natural factor that will lead to the acceleration of eutrophication in rivers and lakes. However, understanding the mechanism of climate change’s effect on water eutrophication is difficult due to the uncertainties caused by its complex, non-linear process. There is considerable uncertainty about the magnitude of future temperature changes, and how these will drive eutrophication in water bodies at regional scales under the effect of human activities. This review collects the existing international and domestic literature from the last 10 years, discussing the most sensitive factors of climate change (i.e., temperature, precipitation, wind, and solar radiation and analyzing their interaction with water eutrophication. Case studies of serious eutrophication and algal bloom problems in China are discussed to further demonstrate the conclusion. Finally, adaptation countermeasures and related implications are proposed in order to foster the development of sustainability strategies for water management in China.

  5. DNA translocating through a carbon nanotube can increase ionic current

    International Nuclear Information System (INIS)

    Park, Jae Hyun; Krstić, Predrag S; He Jin; Gyarfas, Brett; Lindsay, Stuart

    2012-01-01

    Translocation of DNA through a narrow, single-walled carbon nanotube can be accompanied by large increases in ion current, recently observed in contrast to the ion current blockade. We use molecular dynamics simulations to show that large electro-osmotic flow can be turned into a large net current via ion-selective filtering by a DNA molecule inside the carbon nanotube. (paper)

  6. Resource Control: A Translocation Of The Scramble For Africa ...

    African Journals Online (AJOL)

    Adopting a theoretical framework successfully adapted from the biological and medical sciences, namely; translocation analysis, the paper traces the ancestry of the present resource control problem to the scramble, first, and then, the use of fiscal and revenue allocation commissions during the colonial era, and the ...

  7. Evaluation of cadmium bioaccumulation and translocation by Hopea ...

    African Journals Online (AJOL)

    parisa

    2012-04-10

    Apr 10, 2012 ... species selected as phytoremediator, three indicators were used namely, bioconcentration factor (BCF, the metal concentration ratio of plant roots to soil), translocation factor (TF, the metal concentration ratio of plant shoots to ... centration of Cd in soil ranges from 0.01 to 2.0 mg kg-1; however, in urban and ...

  8. Concentration Polarization in Translocation of DNA through Nanopores and Nanochannels

    NARCIS (Netherlands)

    Das, S.; Dubsky, P.; van den Berg, Albert; Eijkel, Jan C.T.

    2012-01-01

    In this Letter we provide a theory to show that high-field electrokinetic translocation of DNA through nanopores or nanochannels causes large transient variations of the ionic concentrations in front and at the back of the DNA due to concentration polarization (CP). The CP causes strong local

  9. Introduction: translocal development, development corridors and development chains.

    NARCIS (Netherlands)

    Zoomers, E.B.; Westen, A.C.M. van

    2011-01-01

    This paper offers an introduction to this Special Issue of International Development Planning Review. It uses the concepts of translocal development, development corridors and development chains to secure a better grasp of what development means in the context of globalisation and how ‘local

  10. Diphtheria toxin translocation across cellular membranes is regulated by sphingolipids

    International Nuclear Information System (INIS)

    Spilsberg, Bjorn; Hanada, Kentaro; Sandvig, Kirsten

    2005-01-01

    Diphtheria toxin is translocated across cellular membranes when receptor-bound toxin is exposed to low pH. To study the role of sphingolipids for toxin translocation, both a mutant cell line lacking the first enzyme in de novo sphingolipid synthesis, serine palmitoyltransferase, and a specific inhibitor of the same enzyme, myriocin, were used. The serine palmitoyltransferase-deficient cell line (LY-B) was found to be 10-15 times more sensitive to diphtheria toxin than the genetically complemented cell line (LY-B/cLCB1) and the wild-type cell line (CHO-K1), both when toxin translocation directly across the plasma membrane was induced by exposing cells with surface-bound toxin to low pH, and when the toxin followed its normal route via acidified endosomes into the cytosol. Toxin binding was similar in these three cell lines. Furthermore, inhibition of serine palmitoyltransferase activity by addition of myriocin sensitized the two control cell lines (LY-B/cLCB1 and CHO-K1) to diphtheria toxin, whereas, as expected, no effect was observed in cells lacking serine palmitoyltransferase (LY-B). In conclusion, diphtheria toxin translocation is facilitated by depletion of membrane sphingolipids

  11. Black Rhino Translocations within Africa | Knight | Africa Insight

    African Journals Online (AJOL)

    The responsibility for the conservation of the critically endangered Black Rhinoceros, Diceros bicornis, lies within Africa. This species is managed at the subspecies level and we document nine international translocation case studies involving South Africa since 1962 aimed at re-establishing or boosting populations ...

  12. Bladder calculus resulting from an intravesical translocation of ...

    African Journals Online (AJOL)

    Although perforation of the uterus by an intrauterine contraceptive device (IUCD) is commonly encountered, intravesical translocation and secondary calculus formation is a very rare complication.We report a case of a 60-year old multiparous woman in whom an intrauterine contraceptive Copper-T device inserted 12 years ...

  13. Translocation of radioactive paraquat in some veld grasses | TD ...

    African Journals Online (AJOL)

    In two pot experiments radioactive paraquat was applied to certain important veld grasses (Experiment I-Aristida junciformis, Themeda triandra, Elyonuris argenteus, Andropogon filifolius, Eragrostis curvula; Experiment II-A. junciformis, E. argenteus) to determine the extent of translocation at a young stage of growth with ...

  14. Modeling potential structure ignitions from flame radiation exposure with implications for wildland/urban interface fire management

    Science.gov (United States)

    Jack D. Cohen; Bret W. Butler

    1998-01-01

    Residential losses associated with wildland fires have become a serious international fire protection problem. The radiant heat flux from burning vegetation adjacent to a structure is a principal ignition factor. A thermal radiation and ignition model estimated structure ignition potential using designated flame characteristics (inferred from various types and...

  15. The effects of elevated CO2 on cereal crop natural defenses and the potential implications for mycotoxin risk

    Science.gov (United States)

    Wheat and corn are an essential part of the world’s grain supply, but climate change has the potential to increase grain susceptibility to toxin producing fungal pathogens. While rising atmospheric [CO2] is a driving force of climate change, our understanding of how elevated [CO2] will effect grain ...

  16. Teaching and Technology Transfer as Alternative Revenue Streams: A Primer on the Potential Legal Implications for UK Universities

    Science.gov (United States)

    Van Hoorebeek, Mark; Marson, James

    2005-01-01

    Purpose: The purpose of this paper is to assess the financial and intellectual issues facing the university sector as many institutions in the UK pursue alternative revenue streams. As a consequence to the increasing financial pressures, university departments are increasingly exposed to new forms of potential litigation and also face the risk to…

  17. High-Potential Electrocatalytic O2 Reduction with Nitroxyl / NOx Mediators: Implications for Fuel Cells and Aerobic Oxidation Catalysis

    Energy Technology Data Exchange (ETDEWEB)

    Gerken, James B.; Stahl, Shannon S.

    2015-07-15

    Efficient reduction of O2 to water is a central challenge in energy conversion and aerobic oxidation catalysis. In the present study, we investigate the electrochemical reduction of O2 with soluble organic nitroxyl and nitrogen oxide (NOx) mediators. When used alone, neither organic nitroxyls, such as TEMPO (2,2,6,6-tetramethyl-1-piperidinyl-N-oxyl), nor NOx species, such as sodium nitrite, are effective mediators of electrochemical O2 reduction. The combination of nitroxyl/NOx species, however, mediates sustained O2 reduction at electrochemical potentials of 0.19–0.33 V (vs. Fc/Fc+) in acetonitrile containing trifluoroacetic acid. Mechanistic analysis of the coupled redox reactions supports a process in which the nitrogen oxide catalyst drives aerobic oxidation of a nitroxyl mediator to an oxoammonium species, which then is reduced back to the nitroxyl at the cathode. The electrolysis potential is dictated by the oxoammonium/nitroxyl reduction potential. The high potentials observed with this ORR system benefit from the mechanism-based specificity for four-electron reduction of oxygen to water mediated by NOx species, together with kinetically efficient reduction of oxidized NOx species by TEMPO and other organic nitroxyls. This research was supported as part of the Center for Molecular Electrocatalysis, an Energy Frontier Research Center, funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences.

  18. Transcuticular translocation of radionuclides on plant leaf surfaces

    Energy Technology Data Exchange (ETDEWEB)

    Matsumoto, Ken-ichi; Watanabe, Tadakazu; Ambe, Shizuko; Yamaguchi, Isamu [Institute of Physical and Chemical Research, Wako, Saitama (Japan)

    1996-12-31

    The cuticle covering all the outermost surfaces of the aerial parts of plants could play a selective role in uptake and translocation of radionuclides from air into plants. In this study, we investigated the transcuticular uptake and translocation behavior via water droplets of various radionuclides in red clover, orchard grass, Japanese radish and mung bean. Ten {mu}l of an aqueous solution of the multitracer generated from Au was applied to the upper surface of the 2nd leaf of the plants at the 5th leaf stage. The plants were then grown for 14 days at 25degC and 70% RH under illumination of artificial solar lights. The transcuticular uptake and translocation throughout the plant were periodically assayed by determining the radioactivity in the surface residue, the cuticle layer beneath the applied site, the leaf area outside the applied site, the other aerial parts and the root of the plant, using an HPGe detector. The applied radionuclides were absorbed into, in turn, the cuticle layer beneath the applied site and then translocated through the cuticle to the inner tissue and eventually to the other aerial parts and finally to the roots, of the plant. The distribution and accumulation in the plant seems to depend upon the characteristics of each radionuclide and plant species. Ca{sup *} and Te{sup *} tended to remain on leaf surfaces without being absorbed into the cuticle. On the other hand, Sc{sup *}, Co{sup *}, Zn{sup *}, Se{sup *}, Rb{sup *}, and Eu{sup *} were easily absorbed and translocated to every part of the plant including the root. The other radionuclides such as Be{sup *}, Mn{sup *}, Sr{sup *}, Y{sup *}, Ba{sup *}, Ce{sup *}, Pm{sup *}, Gd{sup *}, Hf{sup *}, Yb{sup *}, Lu{sup *}, Os{sup *}, Ir{sup *}, and Pt{sup *} remained in the region close to the site of their application. The above results possibly indicate the existence of mechanisms common to these plants for selective transcuticular uptake and translocation of radionuclides within plant

  19. Nuclear translocation of mismatch repair proteins MSH2 and MSH6 as a response of cells to alkylating agents.

    Science.gov (United States)

    Christmann, M; Kaina, B

    2000-11-17

    Mammalian mismatch repair has been implicated in mismatch correction, the prevention of mutagenesis and cancer, and the induction of genotoxicity and apoptosis. Here, we show that treatment of cells specifically with agents inducing O(6)-methylguanine in DNA, such as N-methyl-N'-nitro-N-nitrosoguanidine and N-methyl-N-nitrosourea, elevates the level of MSH2 and MSH6 and increases GT mismatch binding activity in the nucleus. This inducible response occurs immediately after alkylation, is long-lasting and dose-dependent, and results from translocation of the preformed MutSalpha complex (composed of MSH2 and MSH6) from the cytoplasm into the nucleus. It is not caused by an increase in MSH2 gene activity. Cells expressing the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT), thus having the ability to repair O(6)-methylguanine, showed no translocation of MutSalpha, whereas inhibition of MGMT by O(6)-benzylguanine provoked the translocation. The results demonstrate that O(6)-methylguanine lesions are involved in triggering nuclear accumulation of MSH2 and MSH6. The finding that treatment of cells with O(6)-methylguanine-generating mutagens results in an increase of MutSalpha and GT binding activity in the nucleus indicates a novel type of genotoxic stress response.

  20. MiT family translocation renal cell carcinoma.

    Science.gov (United States)

    Argani, Pedram

    2015-03-01

    The MiT subfamily of transcription factors includes TFE3, TFEB, TFC, and MiTF. Gene fusions involving two of these transcription factors have been identified in renal cell carcinoma (RCC). The Xp11 translocation RCCs were first officially recognized in the 2004 WHO renal tumor classification, and harbor gene fusions involving TFE3. The t(6;11) RCCs harbor a specific Alpha-TFEB gene fusion and were first officially recognized in the 2013 International Society of Urologic Pathology (ISUP) Vancouver classification of renal neoplasia. These two subtypes of translocation RCC have many similarities. Both were initially described in and disproportionately involve young patients, though adult translocation RCC may overall outnumber pediatric cases. Both often have unusual and distinctive morphologies; the Xp11 translocation RCCs frequently have clear cells with papillary architecture and abundant psammomatous bodies, while the t(6;11) RCCs frequently have a biphasic appearance with both large and small epithelioid cells and nodules of basement membrane material. However, the morphology of these two neoplasms can overlap, with one mimicking the other. Both of these RCCs underexpress epithelial immunohistochemical markers like cytokeratin and epithelial membrane antigen (EMA) relative to most other RCCs. Unlike other RCCs, both frequently express the cysteine protease cathepsin k and often express melanocytic markers like HMB45 and Melan A. Finally, TFE3 and TFEB have overlapping functional activity as these two transcription factors frequently heterodimerize and bind to the same targets. Therefore, on the basis of clinical, morphologic, immunohistochemical, and genetic similarities, the 2013 ISUP Vancouver classification of renal neoplasia grouped these two neoplasms together under the heading of "MiT family translocation RCC." This review summarizes our current knowledge of these recently described RCCs. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Germination of Acacia harpophylla (Brigalow seeds in relation to soil water potential: implications for rehabilitation of a threatened ecosystem

    Directory of Open Access Journals (Sweden)

    Sven Arnold

    2014-02-01

    Full Text Available Initial soil water conditions play a critical role when seeding is the primary approach to revegetate post-mining areas. In some semi-arid climates, such as the Brigalow Belt Bioregion in eastern Australia, extensive areas are affected by open-cut mining. Together with erratic rainfall patterns and clayey soils, the Brigalow Belt denotes a unique biome which is representative of other water-limited ecosystems worldwide. Apart from other environmental stressors, germination is governed by the water potential of the surrounding soil material. While previous studies have confirmed the high tolerance of Brigalow (Acacia harpophylla seeds to a broad range of temperature and salinity, the question of how soil water potential triggers seed germination remains. In this study, we used three replicates of 50 seeds of Brigalow to investigate germination in relation to water potential as an environmental stressor. Solutions of Polyethylene Glycol (PEG 6000 were applied to expose seeds to nine osmotic water potentials ranging from soil water saturation (0 MPa and field capacity (−.01 to −.03 MPa to the permanent wilting point (−1.5 MPa. We measured germinability (number of germinated seeds relative to total number of seeds per lot and mean germination time (mean time required for maximum germination of a seed lot to quantify germination. Based on the empirical data of the germination we estimated the parameters of the hydrotime model which simulates timing and success of seed emergence. Our findings indicate that Brigalow seeds are remarkably tolerant to water stress, with germination being observed at a water potential as low as −1.5 MPa. Likewise, the average base water potential of a seed population (hydrotime model was very low and ranged between −1.533 and −1.451 MPa. In general, Brigalow seeds germinate opportunistically over a broad range of abiotic conditions related to temperature, salinity, and water availability. Direct seeding and

  2. Germination of Acacia harpophylla (Brigalow) seeds in relation to soil water potential: implications for rehabilitation of a threatened ecosystem.

    Science.gov (United States)

    Arnold, Sven; Kailichova, Yolana; Baumgartl, Thomas

    2014-01-01

    Initial soil water conditions play a critical role when seeding is the primary approach to revegetate post-mining areas. In some semi-arid climates, such as the Brigalow Belt Bioregion in eastern Australia, extensive areas are affected by open-cut mining. Together with erratic rainfall patterns and clayey soils, the Brigalow Belt denotes a unique biome which is representative of other water-limited ecosystems worldwide. Apart from other environmental stressors, germination is governed by the water potential of the surrounding soil material. While previous studies have confirmed the high tolerance of Brigalow (Acacia harpophylla) seeds to a broad range of temperature and salinity, the question of how soil water potential triggers seed germination remains. In this study, we used three replicates of 50 seeds of Brigalow to investigate germination in relation to water potential as an environmental stressor. Solutions of Polyethylene Glycol (PEG 6000) were applied to expose seeds to nine osmotic water potentials ranging from soil water saturation (0 MPa) and field capacity (-.01 to -.03 MPa) to the permanent wilting point (-1.5 MPa). We measured germinability (number of germinated seeds relative to total number of seeds per lot) and mean germination time (mean time required for maximum germination of a seed lot) to quantify germination. Based on the empirical data of the germination we estimated the parameters of the hydrotime model which simulates timing and success of seed emergence. Our findings indicate that Brigalow seeds are remarkably tolerant to water stress, with germination being observed at a water potential as low as -1.5 MPa. Likewise, the average base water potential of a seed population (hydrotime model) was very low and ranged between -1.533 and -1.451 MPa. In general, Brigalow seeds germinate opportunistically over a broad range of abiotic conditions related to temperature, salinity, and water availability. Direct seeding and germination of native

  3. Volumetric relationship between 2-hydroxyglutarate and FLAIR hyperintensity has potential implications for radiotherapy planning of mutant IDH glioma patients.

    Science.gov (United States)

    Jafari-Khouzani, Kourosh; Loebel, Franziska; Bogner, Wolfgang; Rapalino, Otto; Gonzalez, Gilberto R; Gerstner, Elizabeth; Chi, Andrew S; Batchelor, Tracy T; Rosen, Bruce R; Unkelbach, Jan; Shih, Helen A; Cahill, Daniel P; Andronesi, Ovidiu C

    2016-11-01

    Gliomas with mutant isocitrate dehydrogenase (IDH) produce high levels of 2-hydroxyglutarate (2HG) that can be quantitatively measured by 3D magnetic resonance spectroscopic imaging (MRSI). Current glioma MRI primarily relies upon fluid-attenuated inversion recovery (FLAIR) hyperintensity for treatment planning, although this lacks specificity for tumor cells. Here, we investigated the relationship between 2HG and FLAIR in mutant IDH glioma patients to determine whether 2HG mapping is valuable for radiotherapy planning. Seventeen patients with mutant IDH1 gliomas were imaged by 3 T MRI. A 3D MRSI sequence was employed to specifically image 2HG. FLAIR imaging was performed using standard clinical protocol. Regions of interest (ROIs) were determined for FLAIR and optimally thresholded 2HG hyperintensities. The overlap, displacement, and volumes of 2HG and FLAIR ROIs were calculated. In 8 of 17 (47%) patients, the 2HG volume was larger than FLAIR volume. Across the entire cohort, the mean volume of 2HG was 35.3 cc (range, 5.3-92.7 cc), while the mean volume of FLAIR was 35.8 cc (range, 6.3-140.8 cc). FLAIR and 2HG ROIs had mean overlap of 0.28 (Dice coefficients range, 0.03-0.57) and mean displacement of 12.2 mm (range, 3.2-23.5 mm) between their centers of mass. Our results indicate that for a substantial number of patients, the 2HG volumetric assessment of tumor burden is more extensive than FLAIR volume. In addition, there is only partial overlap and asymmetric displacement between the centers of FLAIR and 2HG ROIs. These results may have important implications for radiotherapy planning of IDH mutant glioma. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. High Prevalence of Hyper-Aerotolerant Campylobacter jejuni in Retail Poultry with Potential Implication in Human Infection.

    Science.gov (United States)

    Oh, Euna; McMullen, Lynn; Jeon, Byeonghwa

    2015-01-01

    Campylobacter jejuni is a leading cause of foodborne illnesses around the world. Since C. jejuni is microaerophilic and sensitive to oxygen, aerotolerance is important in the transmission of C. jejuni to humans via foods under aerobic conditions. In this study, 70 C. jejuni strains were isolated from retail raw chicken meats and were subject to multilocus sequence typing (MLST) analysis. In the aerotolerance testing by aerobic shaking at 200 rpm, 50 (71.4%) isolates survived after 12 h (i.e., aerotolerant), whereas 20 (28.6%) isolates did not (i.e., aerosensitive). Interestingly, further aerobic cultivation showed that 25 (35.7%) isolates still survived even after 24 h of vigorous aerobic shaking (i.e., hyper-aerotolerant). Compared to aerosensitive strains, the hyper-aerotolerant strains exhibited increased resistance to oxidative stress, both peroxide and superoxide. A mutation of ahpC in hyper-aerotolerant strains significantly impaired aerotolerance, indicating oxidative stress defense plays an important role in hyper-aerotolerance. The aerotolerant and hyper-aerotolerant strains were primarily classified into MLST clonal complexes (CCs)-21 and -45, which are known to be the major CCs implicated in human gastroenteritis. Compared to the aerosensitive strains, CC-21 was more dominant than CC-45 in aerotolerant and hyper-aerotolerant strains. The findings in this study revealed that hyper-aerotolerant C. jejuni is highly prevalent in raw chicken meats. The enhanced aerotolerance in C. jejuni would impact human infection by increasing possibilities of the foodborne transmission of C. jejuni under aerobic conditions.

  5. Atlas of alien and translocated indigenous aquatic animals in southern Africa

    CSIR Research Space (South Africa)

    De Moor, IJ

    1988-01-01

    Full Text Available This report serves as an introduction to the problem of alien and translocated aquatic animals in southern Africa is given followed by checklists of the different species which have been introduced into or translocated within the subcontinent...

  6. Organic Pollutants in Shale Gas Flowback and Produced Waters: Identification, Potential Ecological Impact, and Implications for Treatment Strategies.

    Science.gov (United States)

    Butkovskyi, Andrii; Bruning, Harry; Kools, Stefan A E; Rijnaarts, Huub H M; Van Wezel, Annemarie P

    2017-05-02

    Organic contaminants in shale gas flowback and produced water (FPW) are traditionally expressed as total organic carbon (TOC) or chemical oxygen demand (COD), though these parameters do not provide information on the toxicity and environmental fate of individual components. This review addresses identification of individual organic contaminants in FPW, and stresses the gaps in the knowledge on FPW composition that exist so far. Furthermore, the risk quotient approach was applied to predict the toxicity of the quantified organic compounds for fresh water organisms in recipient surface waters. This resulted in an identification of a number of FPW related organic compounds that are potentially harmful namely those compounds originating from shale formations (e.g., polycyclic aromatic hydrocarbons, phthalates), fracturing fluids (e.g., quaternary ammonium biocides, 2-butoxyethanol) and downhole transformations of organic compounds (e.g., carbon disulfide, halogenated organic compounds). Removal of these compounds by FPW treatment processes is reviewed and potential and efficient abatement strategies are defined.

  7. Implications of prostaglandin E2 synthesis and phospholipase C activation in potentiation of T-cell proliferation by LF 1695.

    Science.gov (United States)

    Derrepas, P; Annat, J; Dutartre, P; Pascal, M

    1991-01-01

    Murine spleen cells, T-enriched by nylon wool filtration, proliferate in the presence of a protein kinase C stimulator and a calcium ionophore. Using this cell proliferation system, we show that LF 1695 can potentiate phorbol myristate acetate (PMA) action in the presence of A 23187. This potentiation can be due to PGE2 inhibition since it is found that lipopolysaccharide (LPS) or A 23187 induced PGE2 release from spleen cells is inhibited by LF 1695. Indomethacin and LF 1695 gave similar stimulation of spleen cell proliferation, and exogeneously added PGE2 inhibits this phenomenon. Considering two of the main early components of intracellular signal transduction, LF 1695 induces IP3 release and calcium mobilization. However, the compound is not mitogenic per se. These results show that LF 1695 behaves only as a costimulant for T-cell proliferation.

  8. The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research.

    Science.gov (United States)

    Henningfield, Jack E; Fant, Reginald V; Wang, Daniel W

    2018-02-01

    Consideration by the US Drug Enforcement Administration and Food and Drug Administration of placing kratom into Schedule I of the Controlled Substances Act (CSA) requires its evaluation of abuse potential in the context of public health. The objective of the study is to provide a review of kratom abuse potential and its evaluation according to the 8 factors of the CSA. Kratom leaves and extracts have been used for centuries in Southeast Asia and elsewhere to manage pain and other disorders and, by mid-twentieth century, to manage opioid withdrawal. Kratom has some opioid effects but low respiratory depression and abuse potential compared to opioids of abuse. This appears due to its non-opioid-derived and resembling molecular structure recently referred to as biased agonists. By the early 2000s, kratom was increasingly used in the US as a natural remedy to improve mood and quality of life and as substitutes for prescription and illicit opioids for managing pain and opioid withdrawal by people seeking abstinence from opioids. There has been no documented threat to public health that would appear to warrant emergency scheduling of the products and placement in Schedule I of the CSA carries risks of creating serious public health problems. Although kratom appears to have pharmacological properties that support some level of scheduling, if it was an approved drug, placing it into Schedule I, thus banning it, risks creating public health problems that do not presently exist. Furthermore, appropriate regulation by FDA is vital to ensure appropriate and safe use.

  9. The use of green waste from tourist attractions for renewable energy production: The potential and policy implications

    International Nuclear Information System (INIS)

    Shi, Yan; Du, Yuanyuan; Yang, Guofu; Tang, Yuli; Fan, Likun; Zhang, Jun; Lu, Yijun; Ge, Ying; Chang, Jie

    2013-01-01

    Quantifying potential renewable energy sources from tourist attractions is a pivotal initial step in developing energy policies and strategies for low-carbon tourist industry development. Although solar energy and wind power have been in use for providing power for tourist attractions, the value of using waste biomass for energy production is still poorly understood. Here we advocate a promising approach that produces energy from green waste created by tourism attractions currently existing in large numbers and is still increasing dramatically. Using the Yangtze River Delta (YRD) of China as an example, we evaluated the potential of utilizing green waste to produce energy from 385 tourist attractions in 16 cities of this region. Our results showed that the total potential energy production using the green waste biomass was estimated at 6740 TJ/yr (1 TJ=10 12 J) with an average of 137 GJ/ha/yr (1 GJ=10 9 J), accounting for 6% (the average of the Yangtze River Delta, some scenic areas up to 93%) of YRD′s tourism industry′s energy consumption in 2008. The use of green waste for energy production is possible using current technology and could result in a win–win approach by reducing waste and increasing the renewable energy yields. -- Highlights: •Green waste from tourist attractions could help offset the tourist′s fossil fuel consumption. •Economic, technical, and social feasibility analysis of green waste for energy production. •Puts forward policy recommendations, from management regulations, public support etc

  10. Microbial Translocation in HIV Infection is Associated with Dyslipidemia, Insulin Resistance, and Risk of Myocardial Infarction

    DEFF Research Database (Denmark)

    Pedersen, Karin Kaereby; Pedersen, Maria; Trøseid, Marius

    2013-01-01

    Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals.......Microbial translocation has been suggested to be a driver of immune activation and inflammation. We hypothesized that microbial translocation may be related to dyslipidemia, insulin resistance, and the risk of coronary heart disease in HIV-infected individuals....

  11. Age and geochemistry of the Charlestown Group, Ireland: Implications for the Grampian orogeny, its mineral potential and the Ordovician timescale

    Science.gov (United States)

    Herrington, Richard J.; Hollis, Steven P.; Cooper, Mark R.; Stobbs, Iain; Tapster, Simon; Rushton, Adrian; McConnell, Brian; Jeffries, Teresa

    2018-03-01

    Accurately reconstructing the growth of continental margins during episodes of ocean closure has important implications for understanding the formation, preservation and location of mineral deposits in ancient orogens. The Charlestown Group of county Mayo, Ireland, forms an important yet understudied link in the Caledonian-Appalachian orogenic belt located between the well documented sectors of western Ireland and Northern Ireland. We have reassessed its role in the Ordovician Grampian orogeny, based on new fieldwork, high-resolution airborne geophysics, graptolite biostratigraphy, U-Pb zircon dating, whole rock geochemistry, and an examination of historic drillcore from across the volcanic inlier. The Charlestown Group can be divided into three formations: Horan, Carracastle, and Tawnyinah. The Horan Formation comprises a mixed sequence of tholeiitic to calc-alkaline basalt, crystal tuff and sedimentary rocks (e.g. black shale, chert), forming within an evolving peri-Laurentian affinity island arc. The presence of graptolites Pseudisograptus of the manubriatus group and the discovery of Exigraptus uniformis and Skiagraptus gnomonicus favour a latest Dapingian (i.e. Yapeenian Ya 2/late Arenig) age for the Horan Formation (equivalent to c. 471.2-470.5 Ma according to the timescale of Sadler et al., 2009). Together with three new U-Pb zircon ages of 471.95-470.82 Ma from enclosing felsic tuffs and volcanic breccias, this fauna provides an important new constraint for calibrating the Middle Ordovician timescale. Overlying deposits of the Carracastle and Tawnyinah formations are dominated by LILE- and LREE-enriched calc-alkaline andesitic tuffs and flows, coarse volcanic breccias and quartz-feldspar porphyritic intrusive rocks, overlain by more silicic tuffs and volcanic breccias with rare occurrences of sedimentary rocks. The relatively young age for the Charlestown Group in the Grampian orogeny, coupled with high Th/Yb and zircon inheritance (c. 2.7 Ga) in intrusive

  12. The pathogenic mechanism of the Mycobacterium ulcerans virulence factor, mycolactone, depends on blockade of protein translocation into the ER.

    Directory of Open Access Journals (Sweden)

    Belinda S Hall

    2014-04-01

    Full Text Available Infection with Mycobacterium ulcerans is characterised by tissue necrosis and immunosuppression due to mycolactone, the necessary and sufficient virulence factor for Buruli ulcer disease pathology. Many of its effects are known to involve down-regulation of specific proteins implicated in important cellular processes, such as immune responses and cell adhesion. We have previously shown mycolactone completely blocks the production of LPS-dependent proinflammatory mediators post-transcriptionally. Using polysome profiling we now demonstrate conclusively that mycolactone does not prevent translation of TNF, IL-6 and Cox-2 mRNAs in macrophages. Instead, it inhibits the production of these, along with nearly all other (induced and constitutive proteins that transit through the ER. This is due to a blockade of protein translocation and subsequent degradation of aberrantly located protein. Several lines of evidence support this transformative explanation of mycolactone function. First, cellular TNF and Cox-2 can be once more detected if the action of the 26S proteasome is inhibited concurrently. Second, restored protein is found in the cytosol, indicating an inability to translocate. Third, in vitro translation assays show mycolactone prevents the translocation of TNF and other proteins into the ER. This is specific as the insertion of tail-anchored proteins into the ER is unaffected showing that the ER remains structurally intact. Fourth, metabolic labelling reveals a near-complete loss of glycosylated and secreted proteins from treated cells, whereas cytosolic proteins are unaffected. Notably, the profound lack of glycosylated and secreted protein production is apparent in a range of different disease-relevant cell types. These studies provide a new mechanism underlying mycolactone's observed pathological activities both in vitro and in vivo. Mycolactone-dependent inhibition of protein translocation into the ER not only explains the deficit of innate

  13. Mesenteric microcirculatory dysfunctions and translocation of indigenous bacteria in a rat model of strangulated small bowel obstruction

    Directory of Open Access Journals (Sweden)

    Fernando Luiz Zanoni

    2009-01-01

    dysfunction and the occurrence of bacterial translocation. This model parallels the events implicated in multiple organ dysfunction (MOD and death.

  14. Insight into the gastro-duodenal digestion resistance of soybean proteins and potential implications for residual immunogenicity.

    Science.gov (United States)

    De Angelis, Elisabetta; Pilolli, Rosa; Bavaro, Simona L; Monaci, Linda

    2017-04-19

    Soy is an important component of the human diet thanks to its nutritional value and high protein content; however, it also represents a risk for allergenic consumers due to its potential to trigger adverse reactions in sensitized individuals. The putative correlation between immunoreactivity and resistance to the human gastrointestinal (GI) digestion has drawn attention to investigating soybean proteins digestibility. In this work, we provided further insights into this field by performing in vitro simulated GI digestion experiments directly on ground soybean seeds, to provide more realistic results obtained from the digestion of the whole food matrix. Soybean digestion products were analyzed by SDS-PAGE followed by untargeted HPLC-MS/MS analysis and the final data were software treated to enable protein/peptide identification. The latter allowed monitoring the proteolytic degradation of the main soybean proteins during the gastric and duodenal phases. In particular, β-conglycinin and trypsin inhibitors showed the highest resistance to the combined activity of GI enzymes, showing a partial degradation at the end of the duodenal phase as ascertained by the strong electrophoretic bands displayed at 50 kDa and 20 kDa, respectively. Glycinin subunits also presented, even if to a lower extent, resistance to the complete proteolytic degradation, as demonstrated by polypeptide fragments with molecular weight lower than 20 kDa displayed in the gel at the end of duodenal digestion. In addition, by bioinformatics analysis it was demonstrated that the GI resistant fragments of the allergenic proteins, β-conglycinin and glycinin, retained in their primary structure linear epitopes potentially able to trigger an immunoreaction when exposed to the intestinal mucosa. Moreover, such resistant peptides also presented a structural homology with epitope sequences recognized in other legume species, presenting a potential risk of adverse cross-reaction for a larger category of

  15. An atomic string model for a screw dislocation in iron: Implications for the development of interatomic potentials

    International Nuclear Information System (INIS)

    Gilbert, M.R.; Dudarev, S.L.; Chiesa, S.; Derlet, P.M.

    2009-01-01

    Thermally activated motion of screw dislocations is the rate-determining mechanism for plastic deformation and fracture of body centred cubic (bcc) metals and alloys. Recent experimental observations by S.G. Roberts' group at Oxford showed that ductile-brittle behaviour of bcc vanadium, tungsten, pure iron, and iron-chromium alloys is controlled by an Arrhenius process in which the energy for thermal activation is proportional to the formation energy for a double kink on a b= 1/2 screw dislocation, where b is the Burgers vector of the dislocation. Interpreting these experimental observations and extending the analysis to the case of irradiated materials requires developing a full quantitative treatment for perfect and kinked screw dislocations. Modelling screw dislocations also presents a challenge for the development of interatomic potentials. Recent density functional theory (DFT) calculations have revealed that the ground-state structure of the core of screw dislocations in all the bcc transition metals is non-degenerate and symmetric, whereas inter-atomic potentials used in molecular dynamics simulations for these metals often predict a degenerate, symmetry-broken core-structure. In this work we show how, by treating the structure of a screw dislocation within a multistring Frenkel-Kontorova model, we can develop a criterion that guarantees the correct symmetric core of the dislocation. Extending this treatment, we find a systematic recipe for constructing Finnis-Sinclair-type potentials that are able, as a matter of routine, produce non-degenerate core structures of 1/2 screw dislocations. Modelling thermally activated mobility of screw dislocations also requires that the transition pathway between stable core positions of a dislocation is accurately reproduced. DFT data indicates that the shape of the 'Peierls energy barrier' is a single-hump curve, including transitional configurations close to the so-called 'hard' structure. Interatomic potentials have, up

  16. Implications of higher energy - summary of benefits, issues, commissioning cost, SEU, Cryo, QPS margins, Potential availability issues

    CERN Document Server

    Alemany, R

    2012-01-01

    The LHC is technically almost ready to run at 4 TeV per beam in 2012. Nevertheless, a review of the advantages and disadvantages of such an energy step should be carefully made before taking this decision. There fore, this paper will summarize the benefits from the physics point of view; the potential issues like a possible increase of Single Event Errors , Unidentified Flying Objects, or a significant decrease of the quench margin from beam losses that, all in all , could lead to availability issues, compromising the integrated luminosity. And last but not least, the commissioning cost will be addressed.

  17. Meiotic behaviour and spermatogenesis in male mice heterozygous for translocation types also occurring in man

    NARCIS (Netherlands)

    Nijhoff, J.H.

    1981-01-01

    In this thesis a start was made with meiotic observations of mouse translocation types - a Robertsonian translocation and a translocation between a metacentric and an acrocentric chromosome - which also occur in man. It is generally accepted that, when no chromosomal rearrangements are involved, man

  18. Protein translocation across the endoplasmic reticulum membrane in cold-adapted organisms

    NARCIS (Netherlands)

    Römisch, Karin; Collie, Nicola; Soto, Nelyn; Logue, James; Lindsay, Margaret; Scheper, Wiep; Cheng, Chi-Hing C.

    2003-01-01

    Secretory proteins enter the secretory pathway by translocation across the membrane of the endoplasmic reticulum (ER) via a channel formed primarily by the Sec61 protein. Protein translocation is highly temperature dependent in mesophilic organisms. We asked whether the protein translocation

  19. Translocation as a conservation tool for Agassiz's desert tortoises: Survivorship, reproduction, and movements

    Science.gov (United States)

    K. E. Nussear; C. R. Tracy; P. A. Medica; D. S. Wilson; R. W. Marlow; P. S. Corn

    2012-01-01

    We translocated 120 Agassiz's desert tortoises to 5 sites in Nevada and Utah to evaluate the effects of translocation on tortoise survivorship, reproduction, and habitat use. Translocation sites included several elevations, and extended to sites with vegetation assemblages not typically associated with desert tortoises in order to explore the possibility of moving...

  20. The Use of Double-Monotelodisomics to Identify Translocations in Triticum aestivum

    DEFF Research Database (Denmark)

    Linde-Laursen, Ib; Larsen, J.

    1974-01-01

    By analysing metaphase I of double-monotelodisomic hybrids between two varieties of hexaploid wheat differentiated by reciprocal translocations it is possible to establish reliably the chromosomes involved in each translocation. Also the chromosome parts translocated may be identified. The use...

  1. 40 CFR 798.5955 - Heritable translocation test in drosophila melanogaster.

    Science.gov (United States)

    2010-07-01

    ... drosophila melanogaster. 798.5955 Section 798.5955 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY....5955 Heritable translocation test in drosophila melanogaster. (a) Purpose. The heritable translocation test in Drosophila measures the induction of chromosomal translocations in germ cells of insects...

  2. Dek-can rearrangement in translocation (6;9)(p23;q34)

    NARCIS (Netherlands)

    Soekarman, D.; von Lindern, M.; van der Plas, D. C.; Selleri, L.; Bartram, C. R.; Martiat, P.; Culligan, D.; Padua, R. A.; Hasper-Voogt, K. P.; Hagemeijer, A.

    1992-01-01

    The translocation (6;9)(p23;q34) is mainly found in specific subtypes of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS). The diagnosis of this translocation is not easy since the cytogenetic change is quite subtle. The two genes involved in this translocation were recently isolated

  3. Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies

    Science.gov (United States)

    López-Hernández, Luz Berenice; Gómez-Díaz, Benjamín; Luna-Angulo, Alexandra Berenice; Anaya-Segura, Mónica; Bunyan, David John; Zúñiga-Guzman, Carolina; Escobar-Cedillo, Rosa Elena; Roque-Ramírez, Bladimir; Ruano-Calderón, Luis Angel; Rangel-Villalobos, Héctor; López-Hernández, Julia Angélica; Estrada-Mena, Francisco Javier; García, Silvia; Coral-Vázquez, Ramón Mauricio

    2015-01-01

    Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD), a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162) with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001). To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations. PMID:25761239

  4. Comparison of Mutation Profiles in the Duchenne Muscular Dystrophy Gene among Populations: Implications for Potential Molecular Therapies

    Directory of Open Access Journals (Sweden)

    Luz Berenice López-Hernández

    2015-03-01

    Full Text Available Novel therapeutic approaches are emerging to restore dystrophin function in Duchenne Muscular Dystrophy (DMD, a severe neuromuscular disease characterized by progressive muscle wasting and weakness. Some of the molecular therapies, such as exon skipping, stop codon read-through and internal ribosome entry site-mediated translation rely on the type and location of mutations. Hence, their potential applicability worldwide depends on mutation frequencies within populations. In view of this, we compared the mutation profiles of the populations represented in the DMD Leiden Open-source Variation Database with original data from Mexican patients (n = 162 with clinical diagnosis of the disease. Our data confirm that applicability of exon 51 is high in most populations, but also show that differences in theoretical applicability of exon skipping may exist among populations; Mexico has the highest frequency of potential candidates for the skipping of exons 44 and 46, which is different from other populations (p < 0.001. To our knowledge, this is the first comprehensive comparison of theoretical applicability of exon skipping targets among specific populations.

  5. Evidence of genomic adaptation to climate in Eucalyptus microcarpa: Implications for adaptive potential to projected climate change.

    Science.gov (United States)

    Jordan, Rebecca; Hoffmann, Ary A; Dillon, Shannon K; Prober, Suzanne M

    2017-11-01

    Understanding whether populations can adapt in situ or whether interventions are required is of key importance for biodiversity management under climate change. Landscape genomics is becoming an increasingly important and powerful tool for rapid assessments of climate adaptation, especially in long-lived species such as trees. We investigated climate adaptation in Eucalyptus microcarpa using the DArTseq genomic approach. A combination of F ST outlier and environmental association analyses were performed using >4200 genomewide single nucleotide polymorphisms (SNPs) from 26 populations spanning climate gradients in southeastern Australia. Eighty-one SNPs were identified as putatively adaptive, based on significance in F ST outlier tests and significant associations with one or more climate variables related to temperature (70/81), aridity (37/81) or precipitation (35/81). Adaptive SNPs were located on all 11 chromosomes, with no particular region associated with individual climate variables. Climate adaptation appeared to be characterized by subtle shifts in allele frequencies, with no consistent fixed differences identified. Based on these associations, we predict adaptation under projected changes in climate will include a suite of shifts in allele frequencies. Whether this can occur sufficiently rapidly through natural selection within populations, or would benefit from assisted gene migration, requires further evaluation. In some populations, the absence or predicted increases to near fixation of particular adaptive alleles hint at potential limits to adaptive capacity. Together, these results reinforce the importance of standing genetic variation at the geographic level for maintaining species' evolutionary potential. © 2017 John Wiley & Sons Ltd.

  6. Phytochemical Properties and Nutrigenomic Implications of Yacon as a Potential Source of Prebiotic: Current Evidence and Future Directions.

    Science.gov (United States)

    Cao, Yang; Ma, Zheng Feei; Zhang, Hongxia; Jin, Yifan; Zhang, Yihe; Hayford, Frank

    2018-04-12

    The human gut is densely populated with diverse microbial communities that are essential to health. Prebiotics and fiber have been shown to possess the ability to modulate the gut microbiota. One of the plants being considered as a potential source of prebiotic is yacon. Yacon is an underutilized plant consumed as a traditional root-based fruit in South America. Yacon mainly contains fructooligosaccharides (FOS) and inulin. Therefore, it has bifidogenic benefits for gut health, because FOS are not easily broken down by digestive enzymes. Bioactive chemical compounds and extracts isolated from yacon have been studied for their various nutrigenomic properties, including as a prebiotic for intestinal health and their antimicrobial and antioxidant effects. This article reviewed scientific studies regarding the bioactive chemical compounds and nutrigenomic properties of extracts and isolated compounds from yacon. These findings may help in further research to investigate yacon-based nutritional products. Yacon can be considered a potential prebiotic source and a novel functional food. However, more detailed epidemiological, animal, and human clinical studies, particularly mechanism-based and phytopharmacological studies, are lacking for the development of evidence-based functional food products.

  7. Phytochemical Properties and Nutrigenomic Implications of Yacon as a Potential Source of Prebiotic: Current Evidence and Future Directions

    Directory of Open Access Journals (Sweden)

    Yang Cao

    2018-04-01

    Full Text Available The human gut is densely populated with diverse microbial communities that are essential to health. Prebiotics and fiber have been shown to possess the ability to modulate the gut microbiota. One of the plants being considered as a potential source of prebiotic is yacon. Yacon is an underutilized plant consumed as a traditional root-based fruit in South America. Yacon mainly contains fructooligosaccharides (FOS and inulin. Therefore, it has bifidogenic benefits for gut health, because FOS are not easily broken down by digestive enzymes. Bioactive chemical compounds and extracts isolated from yacon have been studied for their various nutrigenomic properties, including as a prebiotic for intestinal health and their antimicrobial and antioxidant effects. This article reviewed scientific studies regarding the bioactive chemical compounds and nutrigenomic properties of extracts and isolated compounds from yacon. These findings may help in further research to investigate yacon-based nutritional products. Yacon can be considered a potential prebiotic source and a novel functional food. However, more detailed epidemiological, animal, and human clinical studies, particularly mechanism-based and phytopharmacological studies, are lacking for the development of evidence-based functional food products.

  8. Breaching Biological Barriers: Protein Translocation Domains as Tools for Molecular Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Benjamin L. Franc

    2003-10-01

    Full Text Available The lipid bilayer of a cell presents a significant barrier for the delivery of many molecular imaging reagents into cells at target sites in the body. Protein translocation domains (PTDs are peptides that breach this barrier. Conjugation of PTDs to imaging agents can be utilized to facilitate the delivery of these agents through the cell wall, and in some cases, into the cell nucleus, and have potential for in vitro and in vivo applications. PTD imaging conjugates have included small molecules, peptides, proteins, DNA, metal chelates, and magnetic nanoparticles. The full potential of the use of PTDs in novel in vivo molecular probes is currently under investigation. Cells have been labeled in culture using magnetic nanoparticles derivatized with a PTD and monitored in vivo to assess trafficking patterns relative to cells expressing a target antigen. In vivo imaging of PTD-mediated gene transfer to cells of the skin has been demonstrated in living animals. Here we review several natural and synthetic PTDs that have evolved in the quest for easier translocation across biological barriers and the application of these peptide domains to in vivo delivery of imaging agents.

  9. Incretin hormones and maturity onset diabetes of the young - pathophysiological implications and anti-diabetic treatment potential

    DEFF Research Database (Denmark)

    Østoft, Signe Harring

    2015-01-01

    . The objectives of this thesis were to study the pathophysiology of GCK-diabetes and HNF1A-diabetes by investigating the incretin effect, the physiological response to food ingestion and to estimate the treatment potential of a glucagon-like peptide-1 receptor agonist (GLP-1RA) in patients with HNF1A-diabetes...... resembling healthy individuals, in spite of fasting hyperglycaemia and subtle glucose intolerance. In contrast, patients with HNF1A-diabetes exhibited noticeable glucose intolerance, beta cell dysfunction, impaired incretin effect, and inappropriate glucagon response to oral stimuli, hence resembling......Maturity onset diabetes of the young (MODY) designates monogenic forms of non-autoimmune diabetes characterised by autosomal dominant inheritance, non-insulin dependent diabetes at onset and diagnosis often before 25 years of age. MODY constitutes genetically and clinically heterogeneous forms...

  10. Geochemical Study on Hydrocarbon Gases in Seafloor Sediments, Southwestern Offshore Taiwan - Implications in the Potential Occurrence of Gas Hydrates

    Directory of Open Access Journals (Sweden)

    Jung-Nan Oung

    2006-01-01

    Full Text Available Seafloor sediment samples collected from southwestern offshore Taiwan have been analyzed for hydrocarbon gases resident in samples by using the technique of headspace gas analysis. The results reveal that the gas content is in tens to thousands ppm (vol. in wet sediments. Both microbial gas (usually called biogenic gas dominated with methane and thermogenic gas containing C2+ hydrocarbons were detected, inferring that the gases involved in the potential gas hydrate occurrence in the study area may have multiple origins. The microbial gas generated by methanogenic archaea in immature sediments is more widely distributed than thermogenic gas generated in sediments of the catagenesis stage. The presence of thermogenic gas infers an effective petroleum system, which may favor the formation of gas hydrate as well as for oil and gas exploration.

  11. Structural differences of matrix metalloproteinases with potential implications for inhibitor selectivity examined by the GRID/CPCA approach

    DEFF Research Database (Denmark)

    Terp, Gitte Elgaard; Cruciani, Gabriele; Christensen, Inge Thøger

    2002-01-01

    The matrix metalloproteinases (MMPs) are a family of proteolytic enzymes, which have been the focus of a lot of research in recent years because of their involvement in various disease conditions. In this study, structures of 10 enzymes (MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, MMP12, MMP13, MMP14......, and MMP20) were examined with the intention of highlighting regions that could be potential sites for obtaining selectivity. For this purpose, the GRID/CPCA approach as implemented in GOLPE was used. Counterions were included to take into account the different electrostatic properties of the proteins......, and the GRID calculations were performed, allowing the protein side chains to move in response to interaction with the probes. In the search for selectivity, the MMPs are known to be a very difficult case because the enzymes of this family are very similar. The well-known differences in the S1' pocket were...

  12. Draft genome sequence of Micrococcus luteus strain O'Kane implicates metabolic versatility and the potential to degrade polyhydroxybutyrates

    Directory of Open Access Journals (Sweden)

    Radwa A. Hanafy

    2016-09-01

    Full Text Available Micrococcus luteus is a predominant member of skin microbiome. We here report on the genomic analysis of Micrococcus luteus strain O'Kane that was isolated from an elevator. The partial genome assembly of Micrococcus luteus strain O'Kane is 2.5 Mb with 2256 protein-coding genes and 62 RNA genes. Genomic analysis revealed metabolic versatility with genes involved in the metabolism and transport of glucose, galactose, fructose, mannose, alanine, aspartate, asparagine, glutamate, glutamine, glycine, serine, cysteine, methionine, arginine, proline, histidine, phenylalanine, and fatty acids. Genomic comparison to other M. luteus representatives identified the potential to degrade polyhydroxybutyrates, as well as several antibiotic resistance genes absent from other genomes.

  13. Characterising low molecular weight dissolved organic carbon compounds in subglacial systems; implications for subglacial metabolic activity and potential downstream export

    Science.gov (United States)

    Lawson, Emily; Wadham, Jemma; Lis, Grzegorz; Telling, Jon

    2010-05-01

    Glaciers and ice sheets represent ~10% of the contemporary global surface coverage, yet remain one of the least explored sectors of the Earth's biosphere. The basal regions of these ice masses, known as subglacial environments, are capable of harbouring a diverse range of microorganisms that are often metabolically active despite the lack of sunlight, the cold temperatures and nutrient scarcity. Here, we consider the potential for such environments to be active components of the Earth's biogeochemical cycles. Subglacial environments have traditionally been excluded from global carbon budgets because they were assumed to be predominantly abiotic. Organic carbon (OC) reservoirs and transformations were also believed to be limited. However, significant stores of bioavailable carbon are thought to be present in glacially-overridden material, providing a potential substrate for in situ microbial metabolism. We examine the molecular characteristics of dissolved OC in basal ice and subglacial runoff from two glacier/ice-sheet systems with contrasting organic carbon substrates; Russell/Leverett Glacier, Greenland ice sheet, and Engabreen, Norway, to determine the range of dissolved low molecular weight OC (LMWOC) compounds and their relative bioavailability. Overridden material beneath the Greenland ice sheet is relatively young and organic-rich, contrasting with the older crystalline bedrock/continental shield that was overridden during glaciation at Engabreen. We first utilise a combination of fluorescence spectroscopy and ion chromatography to identify and quantify volatile fatty acids, carbohydrates and amino acids in basal ice. Volatile fatty acids are key metabolic substrates and their provision is thought to be a primary control on subglacial metabolic activity. We then provide a temporal record of amino acids and carbohydrates in subglacial runoff from Leverett Glacier (June 23rd - August 18th 2009), and compare this with subglacial runoff from Engabreen (2008 melt

  14. The potential of energy behaviours in a smart(er) grid: Policy implications from a Portuguese exploratory study

    International Nuclear Information System (INIS)

    Lopes, Marta A.R.; Henggeler Antunes, Carlos; Janda, Kathryn B.; Peixoto, Paulo; Martins, Nelson

    2016-01-01

    The transition to smart grids is an on-going process that may both shape and be shaped by end-users' energy behavioural adaptations. This study explores current and potential energy behavioural adaptations in Portugal during the smart grid transition process. A web-based survey was made to a representative sample of a specific segment of Portuguese residential end-users. The survey evaluated current energy behaviours and hypothetical future behaviours in a dynamic pricing scenario. Results show this population segment has a positive predisposition towards smart technologies and demand shifting, but it is less likely to accept load control and switch to the liberalised energy market. Factors influencing the behavioural potential are mostly related with market regulation, households' practices and usage behaviours, interference with the private domain, information and technical aspects, and social values. To facilitate behavioural adaptations several strategies are recommended, such as improving the energy market regulation, assessing households' behaviours, prioritising actions already embedded in households daily routines, not interfering with their activities and ensure an override option, and improving energy services, trust and information provided to end-users. The conclusions of the present study are of utmost importance for the design of more effective demand response programmes and energy policies. - Highlights: • Energy behavioural adaptations during the transition to smart grids are explored. • A web-based survey was performed to a representative sample of Portuguese consumers. • Users are prone to adopt smart technologies and shift demand rejecting load control. • Preferences for adopting a demand-responsive energy management system are assessed. • Factors influencing behavioural adaptations are analysed and strategies proposed.

  15. Canine Mesenchymal Stem Cell Potential and the Importance of Dog Breed: Implication for Cell-Based Therapies.

    Science.gov (United States)

    Bertolo, Alessandro; Steffen, Frank; Malonzo-Marty, Cherry; Stoyanov, Jivko

    2015-01-01

    The study of canine bone marrow-derived mesenchymal stem cells (MSCs) has a prominent position in veterinary cell-based applications. Yet the plethora of breeds, their different life spans, and interbreed variations provide unclearness on what can be achieved specifically by such therapies. In this study, we compared a set of morphological, physiological, and genetic markers of MSCs derived from large dog breeds, namely, Border collie, German shepherd, Labrador, Malinois, Golden retriever, and Hovawart. We compared colony-forming units (CFUs) assay, population doubling time (PDT), senescence-associated β-galactosidase (SA-β-gal) activity, telomere length, and gene expression of MSCs, as well as the ability of cells to differentiate to osteogenic, adipogenic, and chondrogenic phenotypes. The influence of the culture media α-MEM, low-glucose DMEM, and high-glucose DMEM, used in cell isolation and expansion, was investigated in the presence and absence of basic fibroblast growth factor (bFGF). Initial cell yield was not affected by culturing medium, but MSCs expanded best in α-MEM supplemented with bFGF. After isolation, the number of MSCs was similar among breeds--as shown by equivalent CFUs--except in the Hovawart samples, which had fivefold less CFU. Telomere lengths were similar among breeds. MSCs divided actively only for 4 weeks in culture (PDT = ∼50 h/division), except Border collie cells divided for a longer time than cells from other groups. The percentage of senescent cells increased linearly in all breeds with time, with a faster rate in German shepherd, Labrador, and Golden retriever. Border collie cells underwent efficient osteogenic differentiation, Hovawart cells performed the best in chondrogenic differentiation, and Labrador cells in both, while German shepherd cells had the lower differentiation potential. MSCs from all breeds preserved the same adipogenic differentiation potential. In conclusion, despite variations, isolated MSCs can be

  16. Environmental hazard assessment of a marine mine tailings deposit site and potential implications for deep-sea mining.

    Science.gov (United States)

    Mestre, Nélia C; Rocha, Thiago L; Canals, Miquel; Cardoso, Cátia; Danovaro, Roberto; Dell'Anno, Antonio; Gambi, Cristina; Regoli, Francesco; Sanchez-Vidal, Anna; Bebianno, Maria João

    2017-09-01

    Portmán Bay is a heavily contaminated area resulting from decades of metal mine tailings disposal, and is considered a suitable shallow-water analogue to investigate the potential ecotoxicological impact of deep-sea mining. Resuspension plumes were artificially created by removing the top layer of the mine tailings deposit by bottom trawling. Mussels were deployed at three sites: i) off the mine tailings deposit area; ii) on the mine tailings deposit beyond the influence from the resuspension plumes; iii) under the influence of the artificially generated resuspension plumes. Surface sediment samples were collected at the same sites for metal analysis and ecotoxicity assessment. Metal concentrations and a battery of biomarkers (oxidative stress, metal exposure, biotransformation and oxidative damage) were measured in different mussel tissues. The environmental hazard posed by the resuspension plumes was investigated by a quantitative weight of evidence (WOE) model that integrated all the data. The resuspension of sediments loaded with metal mine tails demonstrated that chemical contaminants were released by trawling subsequently inducing ecotoxicological impact in mussels' health. Considering as sediment quality guidelines (SQGs) those indicated in Spanish action level B for the disposal of dredged material at sea, the WOE model indicates that the hazard is slight off the mine tailings deposit, moderate on the mine tailings deposit without the influence from the resuspension plumes, and major under the influence of the resuspension plumes. Portmán Bay mine tailings deposit is a by-product of sulphide mining, and despite differences in environmental setting, it can reflect the potential ecotoxic effects to marine fauna from the impact of resuspension of plumes created by deep-sea mining of polymetallic sulphides. A similar approach as in this study could be applied in other areas affected by sediment resuspension and for testing future deep-sea mining sites in

  17. The nonsteroidal anti-inflammatory drug indomethacin induces heterogeneity in lipid membranes: potential implication for its diverse biological action.

    Directory of Open Access Journals (Sweden)

    Yong Zhou

    2010-01-01

    Full Text Available The nonsteroidal anti-inflammatory drug (NSAID, indomethacin (Indo, has a large number of divergent biological effects, the molecular mechanism(s for which have yet to be fully elucidated. Interestingly, Indo is highly amphiphilic and associates strongly with lipid membranes, which influence localization, structure and function of membrane-associating proteins and actively regulate cell signaling events. Thus, it is possible that Indo regulates diverse cell functions by altering micro-environments within the membrane. Here we explored the effect of Indo on the nature of the segregated domains in a mixed model membrane composed of dipalmitoyl phosphatidyl-choline (di16:0 PC, or DPPC and dioleoyl phosphatidyl-choline (di18:1 PC or DOPC and cholesterol that mimics biomembranes.Using a series of fluorescent probes in a fluorescence resonance energy transfer (FRET study, we found that Indo induced separation between gel domains and fluid domains in the mixed model membrane, possibly by enhancing the formation of gel-phase domains. This effect originated from the ability of Indo to specifically target the ordered domains in the mixed membrane. These findings were further confirmed by measuring the ability of Indo to affect the fluidity-dependent fluorescence quenching and the level of detergent resistance of membranes.Because the tested lipids are the main lipid constituents in cell membranes, the observed formation of gel phase domains induced by Indo potentially occurs in biomembranes. This marked Indo-induced change in phase behavior potentially alters membrane protein functions, which contribute to the wide variety of biological activities of Indo and other NSAIDs.

  18. The effect of post-mastectomy radiation therapy on breast implants: Unveiling biomaterial alterations with potential implications on capsular contracture

    Energy Technology Data Exchange (ETDEWEB)

    Ribuffo, Diego; Lo Torto, Federico [Department of Plastic Surgery, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Giannitelli, Sara M. [Tissue Engineering Unit, Department of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome (Italy); Urbini, Marco; Tortora, Luca [Surface Analysis Laboratory, Department of Mathematics and Physics, University “Roma Tre”, Via della Vasca Navale 84, 00146 Rome (Italy); INFN — National Institute of Nuclear Physics, Section of Roma Tre, Via della Vasca Navale 84, 00146 Rome (Italy); Mozetic, Pamela; Trombetta, Marcella [Tissue Engineering Unit, Department of Engineering, Università Campus Bio-Medico di Roma, Via Álvaro del Portillo 21, 00128 Rome (Italy); Basoli, Francesco; Licoccia, Silvia [Department of Chemical Science and Technologies, University of Rome “Tor Vergata”, Via della Ricerca Scientifica 1, 00173 Rome (Italy); Tombolini, Vincenzo [Department of Radiation Oncology, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Spencer-Lorillard Foundation, Viale Regina Elena 291, 00161 Rome (Italy); Cassese, Raffaele [Department of Radiation Oncology, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); Scuderi, Nicolò [Department of Plastic Surgery, “Sapienza” University of Rome, Viale del Policlinico 155, 00166 Rome (Italy); and others

    2015-12-01

    Post-mastectomy breast reconstruction with expanders and implants is recognized as an integral part of breast cancer treatment. Its main complication is represented by capsular contracture, which leads to poor expansion, breast deformation, and pain, often requiring additional surgery. In such a scenario, the debate continues as to whether the second stage of breast reconstruction should be performed before or after post-mastectomy radiation therapy, in light of potential alterations induced by irradiation to silicone biomaterial. This work provides a novel, multi-technique approach to unveil the role of radiotherapy in biomaterial alterations, with potential involvement in capsular contracture. Following irradiation, implant shells underwent mechanical, chemical, and microstructural evaluation by means of tensile testing, Attenuated Total Reflectance Fourier Transform InfraRed spectroscopy (ATR/FTIR), Scanning Electron Microscopy (SEM), high resolution stylus profilometry, and Time of Flight Secondary Ion Mass Spectrometry (ToF-SIMS). Our findings are consistent with radiation-induced modifications of silicone that, although not detectable at the microscale, can be evidenced by more sophisticated nanoscale surface analyses. In light of these results, biomaterial irradiation cannot be ruled out as one of the possible co-factors underlying capsular contracture. - Highlights: • The debate continues whether to perform breast reconstruction before or after PMRT. • Radiation therapy may alter implant material, concurring to capsular contracture. • In this work, irradiated implants were investigated by a multi-technique approach. • Radiation-induced alterations could be evidenced by ATR/FTIR and ToF-SIMS. • Reported alteration might represent a co-factor underlying capsular contracture.

  19. The Role and Potential Therapeutic Implications of the Fibroblast Growth Factors in Energy Balance and Type 2 Diabetes.

    Science.gov (United States)

    Izaguirre, Maitane; Gil, María J; Monreal, Ignacio; Montecucco, Fabrizio; Frühbeck, Gema; Catalán, Victoria

    2017-06-01

    Obesity and its associated metabolic diseases have reached epidemic proportions worldwide, reducing life expectancy and quality of life. Several drugs have been tested to treat these diseases but many of them have damaging side effects. Consequently, there is an urgent need to develop more effective therapies. Recently, endocrine fibroblast growth factors (FGFs) have become attractive targets in the treatment of metabolic diseases. This review summarizes their most important functions as well as FGF-based therapies for the treatment of obesity and type 2 diabetes (T2D). Recent studies demonstrate that circulating levels of FGF19 are reduced in obesity. In fact, exogenous FGF19 administration is associated with a reduction in food intake as well as with improvements in glycaemia. In contrast, FGF21 levels are elevated in subjects with abdominal obesity, insulin resistance and T2D, probably representing a compensatory response. Additionally, elevated levels of circulating FGF23 in individuals with obesity and T2D are reported in most clinical studies. Finally, increased FGF1 levels in obese patients associated with adipogenesis have been described. FGFs constitute important molecules in the treatment of metabolic diseases due to their beneficial effects on glucose and lipid metabolism. Among all members, FGF19 and FGF21 have demonstrated the ability to improve glucose, lipid and energy homeostasis, along with FGF1, which was recently discovered to have beneficial effects on metabolic homeostasis. Additionally, FGF23 may also play a role in insulin resistance or energy homeostasis beyond mineral metabolism control. These results highlight the relevant use of FGFs as potential biomarkers for the early diagnosis of metabolic diseases. In this regard, notable progress has been made in the development of FGF-based therapies and different approaches are being tested in different clinical trials. However, further studies are needed to determine their potential therapeutic

  20. Familial X/Y Translocation Encompassing ARSE in Two Moroccan Siblings with Sensorineural Deafness.

    Science.gov (United States)

    Amasdl, Saadia; Smaili, Wiam; Natiq, Abdelhafid; Hassani, Amale; Sbiti, Aziza; Agadr, Aomar; Sanlaville, Damien; Sefiani, Abdelaziz

    2017-01-01

    Unbalanced translocations involving X and Y chromosomes are rare and associated with a contiguous gene syndrome. The clinical phenotype is heterogeneous including mainly short stature, chondrodysplasia punctata, ichthyosis, hypogonadism, and intellectual disability. Here, we report 2 brothers with peculiar gestalt, short stature, and hearing loss, who harbor an X/Y translocation. Physical examination, brainstem acoustic potential evaluation, bone age, hormonal assessment, and X-ray investigations were performed. Because of their dysmorphic features, karyotyping, FISH, and aCGH were carried out. The probands had short stature, hypertelorism, midface hypoplasia, sensorineural hearing loss, normal intelligence as well as slight radial and ulnar bowing with brachytelephalangy. R-banding identified a derivative X chromosome with an abnormally expanded short arm. The mother was detected as a carrier of the same aberrant X chromosome. aCGH disclosed a 3.1-Mb distal deletion of chromosome region Xp22.33pter. This interval encompasses several genes, especially the short stature homeobox (SHOX) and arylsulfatase (ARSE) genes. The final karyotype of the probands was: 46,Y,der(X),t(X;Y)(p22;q12).ish der(X)(DXYS129-,DXYS153-)mat.arr[hg19] Xp22.33(61091_2689408)×1mat,Xp22.33(2701273_3258404)×0mat,Yq11.222q12 (21412851_59310245)×2. Herein, we describe a Moroccan family with a maternally inherited X/Y translocation and discuss the genotype-phenotype correlations according to the deleted genes. © 2017 S. Karger AG, Basel.

  1. Translocation of Endosulfan from Soil to Ginseng (Panax ginseng C. A. Meyer

    Directory of Open Access Journals (Sweden)

    Jiyoon Kim

    2018-04-01

    Full Text Available This study was conducted to examine the translocation of highly residual agrochemical in soil, the endosulfan (total, to ginseng (Panax ginseng C. A. Meyer. The soil with the level of the amount of 5.0 mg kg−1 of endosulfan (total was prepared in a Wagner pot into which the seedling of ginseng was transplanted and then the specimens of ginseng (root, leaf, and stem were collected quarterly and analyzed through GC-MS. The level of residual of endosulfan (total in the soil has decreased from 4.28 mg kg−1 (April 2013 to 1.94 mg kg−1 (December 2014 while the level in the specimens of leaf and stem of ginseng respectively sampled according to its growth phase in June and September from 2013 and 2014 showed an increase from 0.56 mg kg−1 (June 2013 to 2.46 mg kg−1 (September 2013 and decrease from 0.29 mg kg−1 (June 2014 to 0.18 mg kg−1 (September 2014. For the case of the root of ginseng, the level of the amount of 10.77 mg kg−1 of endosulfan (total was detected in June 2013 and then, the level has decreased to the level of 4.88 mg kg−1 in December 2014. The translocation of residual endosulfan (total in soil to ginseng with time was identified. The amount of residuals of α-endosulfan and β-endosulfan was also decreased with time however, the ratio of endosulfan-sulfate, the main metabolite, was gradually increasing. The retention of metabolite (endosulfan-sulfate in soil identified thereby thus suggests the potential of its translocation to plants in the case of the soils containing the residual of endosulfan (total.

  2. Involvement of glucokinase translocation in the mechanism by which resorcinol inhibits glycolysis in hepatocytes.

    Science.gov (United States)

    Agius, L

    1997-01-01

    Proglycosyn and resorcinol stimulate glycogen synthesis and inhibit glycolysis in hepatocytes. The former effect is attributed to inactivation of phosphorylase mediated by glucuronidated metabolites. This study investigated the mechanism by which resorcinol inhibits glycolysis. Resorcinol (150 microM) inhibited glycolysis in hepatocytes incubated with glucose (15-35 mM) but not with dihydroxyacetone (10 mM). The inhibition of glycolysis at elevated glucose concentration was associated with inhibition of glucose-induced dissociation of glucokinase and aldolase. The resorcinol concentration that caused half-maximal inhibition (20-43 microM) increased with increasing glucose concentration (15-35 mM). Resorcinol inhibited the translocation of glucokinase and the stimulation of detritiation of [2-3H]glucose and [3-3H]glucose caused by sorbitol (10-200 microM), but it potentiated the stimulation of glycogen synthesis. The inhibition of glycolysis by resorcinol could not be accounted for by diversion of substrate to glycogen. The glucose 6-phosphate content correlated with the free glucokinase activity. Resorcinol counteracted the increase in glucose 6-phosphate and fructose 2,6-bisphosphate caused by elevated glucose concentration or by sorbitol. The suppression of glucose 6-phosphate at high glucose concentration (15-35 mM) could be explained by the low activity of free glucokinase. However, the suppression at 5 mM glucose was due in part to an independent mechanism. The effect of resorcinol on glucokinase translocation was partly counteracted by galactosamine, which suppresses UDP-glucose and inhibits glucuronide formation, and was mimicked by phenol and p-nitrophenol but not by p-nitrophenylglucuronide. It is concluded that resorcinol inhibits glycolysis at elevated glucose concentration or when stimulated by sorbitol through increased glucokinase binding. The results indicate a link between glucuronidation and glucokinase translocation. PMID:9271087

  3. Very-low-frequency resistivity, self-potential and ground temperature surveys on Taal volcano (Philippines): Implications for future activity

    Science.gov (United States)

    Zlotnicki, J.; Vargemezis, G.; Johnston, M. J. S.; Sasai, Y.; Reniva, P.; Alanis, P.

    2017-06-01

    Taal volcano is one of the most dangerous volcanoes in the Philippines. Thirty-three eruptions have occurred through historical time with several exhibiting cataclysmic phases. Most recent eruptions are confined to Volcano Island located within the prehistoric Taal collapse caldera that is now filled by Taal Lake. The last eruptive activity from 1965 to 1977 took place from Mt. Tabaro, about 2 km to the southwest of the Main Crater center. Since this time, episodes of seismic activity, ground deformation, gas release, surface fissuring, fumarole activity and temperature changes are recorded periodically around the main crater, but no major eruption has occurred. This period of quiescence is the third longest period without eruptive activity since 1572. In March 2010, a campaign based on Very-Low-Frequency (VLF) resistivity surveys together with repeated surveys of self-potential, ground temperature and fissure activity was intensified and the results compared to a large-scale Electrical Resistivity Tomography experiment. This work fortunately occurred before, within and after a new seismovolcanic crisis from late April 2010 to March 2011. The joint analysis of these new data, together with results from previous magnetotelluric soundings, allows a better description of the electrical resistivity and crustal structure beneath the Main Crater down to a depth of several kilometers. No indication of growth of the two geothermal areas located on both sides of the northern crater rim was apparent from 2005 to March 2010. These areas appear controlled by active fissures, opened during the 1992 and 1994 crises, that dip downward towards the core of the hydrothermal system located at about 2.5 km depth beneath the crater. Older mineralized fissures at lower elevations to the North of the geothermal areas also dip downward under the crater. Repeated self-potential and ground temperature surveys completed between 2005 and 2015 show new geothermal and hydrothermal activity in

  4. The incidence, root-causes, and outcomes of adverse events in surgical units: implication for potential prevention strategies

    Directory of Open Access Journals (Sweden)

    Groenewegen Peter P

    2011-05-01

    Full Text Available Abstract Background We need to know the scale and underlying causes of surgical adverse events (AEs in order to improve the safety of care in surgical units. However, there is little recent data. Previous record review studies that reported on surgical AEs in detail are now more than ten years old. Since then surgical technology and quality assurance have changed rapidly. The objective of this study was to provide more recent data on the incidence, consequences, preventability, causes and potential strategies to prevent AEs among hospitalized patients in surgical units. Methods A structured record review study of 7,926 patient records was carried out by trained nurses and medical specialist reviewers in 21 Dutch hospitals. The aim was to determine the presence of AEs during hospitalizations in 2004 and to consider how far they could be prevented. Of all AEs, the consequences, responsible medical specialty, causes and potential prevention strategies were identified. Surgical AEs were defined as AEs attributable to surgical treatment and care processes and were selected for analysis in detail. Results Surgical AEs occurred in 3.6% of hospital admissions and represented 65% of all AEs. Forty-one percent of the surgical AEs was considered to be preventable. The consequences of surgical AEs were more severe than for other types of AEs, resulting in more permanent disability, extra treatment, prolonged hospital stay, unplanned readmissions and extra outpatient visits. Almost 40% of the surgical AEs were infections, 23% bleeding, and 22% injury by mechanical, physical or chemical cause. Human factors were involved in the causation of 65% of surgical AEs and were considered to be preventable through quality assurance and training. Conclusions Surgical AEs occur more often than other types of AEs, are more often preventable and their consequences are more severe. Therefore, surgical AEs have a major impact on the burden of AEs during hospitalizations

  5. Four degrees and beyond: the potential for a global temperature increase of four degrees and its implications.

    Science.gov (United States)

    New, Mark; Liverman, Diana; Schroeder, Heike; Schroder, Heike; Anderson, Kevin

    2011-01-13

    The 1992 UN Framework Convention on Climate Change commits signatories to preventing 'dangerous anthropogenic interference with the climate system', leaving unspecified the level of global warming that is dangerous. In the late 1990s, a limit of 2°C global warming above preindustrial temperature was proposed as a 'guard rail' below which most of the dangerous climate impacts could be avoided. The 2009 Copenhagen Accord recognized the scientific view 'that the increase in global temperature should be below 2 degrees Celsius' despite growing views that this might be too high. At the same time, the continued rise in greenhouse gas emissions in the past decade and the delays in a comprehensive global emissions reduction agreement have made achieving this target extremely difficult, arguably impossible, raising the likelihood of global temperature rises of 3°C or 4°C within this century. Yet, there are few studies that assess the potential impacts and consequences of a warming of 4°C or greater in a systematic manner. Papers in this themed issue provide an initial picture of the challenges facing a world that warms by 4°C or more, and the difficulties ahead if warming is to be limited to 2°C with any reasonable certainty. Across many sectors--coastal cities, agriculture, water stress, ecosystems, migration--the impacts and adaptation challenges at 4°C will be larger than at 2°C. In some cases, such as farming in sub-Saharan Africa, a +4°C warming could result in the collapse of systems or require transformational adaptation out of systems, as we understand them today. The potential severity of impacts and the behavioural, institutional, societal and economic challenges involved in coping with these impacts argue for renewed efforts to reduce emissions, using all available mechanisms, to minimize the chances of high-end climate change. Yet at the same time, there is a need for accelerated and focused research that improves understanding of how the climate system

  6. aBiofilm: a resource of anti-biofilm agents and their potential implications in targeting antibiotic drug resistance

    Science.gov (United States)

    Rajput, Akanksha; Thakur, Anamika; Sharma, Shivangi

    2018-01-01

    Abstract Biofilms play an important role in the antibiotic drug resistance, which is threatening public health globally. Almost, all microbes mimic multicellular lifestyle to form biofilm by undergoing phenotypic changes to adapt adverse environmental conditions. Many anti-biofilm agents have been experimentally validated to disrupt the biofilms during last three decades. To organize this data, we developed the ‘aBiofilm’ resource (http://bioinfo.imtech.res.in/manojk/abiofilm/) that harbors a database, a predictor, and the data visualization modules. The database contains biological, chemical, and structural details of 5027 anti-biofilm agents (1720 unique) reported from 1988–2017. These agents target over 140 organisms including Gram-negative, Gram-positive bacteria, and fungus. They are mainly chemicals, peptides, phages, secondary metabolites, antibodies, nanoparticles and extracts. They show the diverse mode of actions by attacking mainly signaling molecules, biofilm matrix, genes, extracellular polymeric substances, and many more. The QSAR based predictor identifies the anti-biofilm potential of an unknown chemical with an accuracy of ∼80.00%. The data visualization section summarized the biofilm stages targeted (Circos plot); interaction maps (Cytoscape) and chemicals diversification (CheS-Mapper) of the agents. This comprehensive platform would help the researchers to understand the multilevel communication in the microbial consortium. It may aid in developing anti-biofilm therapeutics to deal with antibiotic drug resistance menace. PMID:29156005

  7. aBiofilm: a resource of anti-biofilm agents and their potential implications in targeting antibiotic drug resistance.

    Science.gov (United States)

    Rajput, Akanksha; Thakur, Anamika; Sharma, Shivangi; Kumar, Manoj

    2018-01-04

    Biofilms play an important role in the antibiotic drug resistance, which is threatening public health globally. Almost, all microbes mimic multicellular lifestyle to form biofilm by undergoing phenotypic changes to adapt adverse environmental conditions. Many anti-biofilm agents have been experimentally validated to disrupt the biofilms during last three decades. To organize this data, we developed the 'aBiofilm' resource (http://bioinfo.imtech.res.in/manojk/abiofilm/) that harbors a database, a predictor, and the data visualization modules. The database contains biological, chemical, and structural details of 5027 anti-biofilm agents (1720 unique) reported from 1988-2017. These agents target over 140 organisms including Gram-negative, Gram-positive bacteria, and fungus. They are mainly chemicals, peptides, phages, secondary metabolites, antibodies, nanoparticles and extracts. They show the diverse mode of actions by attacking mainly signaling molecules, biofilm matrix, genes, extracellular polymeric substances, and many more. The QSAR based predictor identifies the anti-biofilm potential of an unknown chemical with an accuracy of ∼80.00%. The data visualization section summarized the biofilm stages targeted (Circos plot); interaction maps (Cytoscape) and chemicals diversification (CheS-Mapper) of the agents. This comprehensive platform would help the researchers to understand the multilevel communication in the microbial consortium. It may aid in developing anti-biofilm therapeutics to deal with antibiotic drug resistance menace. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  8. Amplified recruitment pressure of biofouling organisms in commercial salmon farms: potential causes and implications for farm management.

    Science.gov (United States)

    Bloecher, Nina; Floerl, Oliver; Sunde, Leif Magne

    2015-01-01

    The development of biofouling on finfish aquaculture farms presents challenges for the industry, but the factors underlying nuisance growths are still not well understood. Artificial settlement surfaces were used to examine two possible explanations for high rates of biofouling in Norwegian salmon farms: (1) increased propagule release during net cleaning operations, resulting in elevated recruitment rates; and (2) potential reservoir effects of farm surfaces. The presence of salmon farms was associated with consistently and substantially (up to 49-fold) elevated recruitment rates. Temporal patterns of recruitment were not driven by net cleaning. Resident populations of biofouling organisms were encountered on all submerged farm surfaces. Calculations indicate that a resident population of the hydroid Ectopleura larynx, a major biofouling species, could release between 0.3 × 10(9) and 4.7 × 10(9) larvae per farm annually. Such resident populations could form propagule reservoirs and be one explanation for the elevated recruitment pressure at salmon farms.

  9. Mucin (Muc expression during pancreatic cancer progression in spontaneous mouse model: potential implications for diagnosis and therapy

    Directory of Open Access Journals (Sweden)

    Rachagani Satyanarayana

    2012-10-01

    Full Text Available Abstract Background Pancreatic cancer (PC is a lethal malignancy primarily driven by activated Kras mutations and characterized by the deregulation of several genes including mucins. Previous studies on mucins have identified their significant role in both benign and malignant human diseases including PC progression and metastasis. However, the initiation of MUC expression during PC remains unknown because of lack of early stage tumor tissues from PC patients. Methods In the present study, we have evaluated stage specific expression patterns of mucins during mouse PC progression in (KrasG12D;Pdx1-Cre (KC murine PC model from pancreatic intraepithelial neoplasia (PanIN to pancreatic ductal adenocarcinoma (PDAC by immunohistochemistry and quantitative real-time PCR. Results In agreement with previous studies on human PC, we observed a progressive increase in the expression of mucins particularly Muc1, Muc4 and Muc5AC in the pancreas of KC (as early as PanIN I mice with advancement of PanIN lesions and PDAC both at mRNA and protein levels. Additionally, mucin expression correlated with the increased expression of inflammatory cytokines IFN-γ (p CXCL1 (p CXCL2 (p  Conclusions Our study reinforces the potential utility of the KC murine model for determining the functional role of mucins in PC pathogenesis by crossing KC mice with corresponding mucin knockout mice and evaluating mucin based diagnostic and therapeutic approaches for lethal PC.

  10. Engineered/designer biochar for contaminant removal/immobilization from soil and water: Potential and implication of biochar modification.

    Science.gov (United States)

    Rajapaksha, Anushka Upamali; Chen, Season S; Tsang, Daniel C W; Zhang, Ming; Vithanage, Meththika; Mandal, Sanchita; Gao, Bin; Bolan, Nanthi S; Ok, Yong Sik

    2016-04-01

    The use of biochar has been suggested as a means of remediating contaminated soil and water. The practical applications of conventional biochar for contaminant immobilization and removal however need further improvements. Hence, recent attention has focused on modification of biochar with novel structures and surface properties in order to improve its remediation efficacy and environmental benefits. Engineered/designer biochars are commonly used terms to indicate application-oriented, outcome-based biochar modification or synthesis. In recent years, biochar modifications involving various methods such as, acid treatment, base treatment, amination, surfactant modification, impregnation of mineral sorbents, steam activation and magnetic modification have been widely studied. This review summarizes and evaluates biochar modification methods, corresponding mechanisms, and their benefits for contaminant management in soil and water. Applicability and performance of modification methods depend on the type of contaminants (i.e., inorganic/organic, anionic/cationic, hydrophilic/hydrophobic, polar/non-polar), environmental conditions, remediation goals, and land use purpose. In general, modification to produce engineered/designer biochar is likely to enhance the sorption capacity of biochar and its potential applications for environmental remediation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. Potential Impact on Freshwater Resources from Agrofuel Feedstock Cultivation in Thailand: Implications of the Alternative Energy Development Plan 2015

    Directory of Open Access Journals (Sweden)

    Pariyapat Nilsalab

    2017-11-01

    Full Text Available The impact of water use in areas with abundant freshwater resources should not be the same as areas with limited resources. This impact is quantified as water scarcity footprint. The monthly water stress index with reference to environmental water requirement is proposed as a characterization factor. The biofuel policies of Thailand—cassava and sugarcane for bioethanol, and oil palm for biodiesel—were selected for the assessment based on land expansion and displacement scenarios. Cultivation was found to be the most water intensive phase in producing both biodiesel and bioethanol. Thus, the proposed index was applied for assessing and selecting areas having low values of the water scarcity footprint. The results showed low values for expanding oil palm plantations on abandoned land and displacing plantation areas with low yields of maize and pineapple with sugarcane and cassava. Additionally, shifting the crop calendar could be considered to reduce the stress situation such as the central region can avoid the water scarcity footprint by 38% from shifting sugarcane cultivation. Consequently mitigating this potential impact and threats to the ecosystem based on specific circumstances and context would be achieved through applying the proposed index in water resource and land suitability planning.

  12. Expression of the SOCS family in human chronic wound tissues: Potential implications for SOCS in chronic wound healing.

    Science.gov (United States)

    Feng, Yi; Sanders, Andrew J; Ruge, Fiona; Morris, Ceri-Ann; Harding, Keith G; Jiang, Wen G

    2016-11-01

    Cytokines play important roles in the wound healing process through various signalling pathways. The JAK-STAT pathway is utilised by most cytokines for signal transduction and is regulated by a variety of molecules, including suppressor of cytokine signalling (SOCS) proteins. SOCS are associated with inflammatory diseases and have an impact on cytokines, growth factors and key cell types involved in the wound‑healing process. SOCS, a negative regulator of cytokine signalling, may hold the potential to regulate cytokine‑induced signalling in the chronic wound‑healing process. Wound edge tissues were collected from chronic venous leg ulcer patients and classified as non-healing and healing wounds. The expression pattern of seven SOCSs members, at the transcript and protein level, were examined in these tissues using qPCR and immunohistochemistry. Significantly higher levels of SOCS3 (P=0.0284) and SOCS4 (P=0.0376) in non-healing chronic wounds compared to the healing/healed chronic wounds were observed at the transcript level. Relocalisation of SOCS3 protein in the non-healing wound environment was evident in the investigated chronic biopsies. Thus, the results show that the expression of SOCS transcript indicated that SOCS members may act as a prognostic biomarker of chronic wounds.

  13. Biodistribution of radioactive organocations and cationic technetium complexes - implications to the uptake mechanism of potential heart-affine radiopharmaceuticals

    International Nuclear Information System (INIS)

    Muenze, R.; Shyre, R.; Seifert, S.; Guethert, I.; Kretschmar, M.; Kampf, G.; Knop, G.; Mohnike, W.; Schmidt, J.

    1986-01-01

    The biodistribution of various 14 C labeled organocations (ammonium, phosphonium) and cationic technetium complexes (TcCl 2 DMPE 2 ,TcDMPE 3 + ) was studied in rats to find potential relations between the chemical composition, structure, molecular size, lipophilicity and heart uptake. All of the radioactive cations were distributed in a similar manner, but with different biokinetics. Molecules containing several electronegative atoms in their ligand structure, e.g. nitrogen or oxygen which enhance polarity, were rapidly accumulated, but washed out again with resultant transient and diminished heart uptake. More highly lipophilic materials, by contrast, showed more extensive accumulation and persistent retention in the heart. The effect of human serum albumin on heart uptake was studied in a perfused heart model. Strong albumin binding prevented extensive heart uptake. This undesirable effect was neutralized by adding detergents to the perfusion bath. Evidence from these animal experiments was considered in the development of a new heart-seeking technetium compound (Tc-DPO), which is characterized by rapid accumulation in the human heart and substantially delayed washout. Heart images with minimal overlap of the inferoposterior wall and the right liver lobe were available in no more than 10 minutes p.i. in both planar and SPECT modes. A deficit in the inferior region was much more clearly defined than on the corresponding Thallium image. (Author)

  14. Unlock the thermogenic potential of adipose tissue: pharmacological modulation and implications for treatment of diabetes and obesity

    Directory of Open Access Journals (Sweden)

    Xiao-Rong ePeng

    2015-11-01

    Full Text Available Brown adipose tissue (BAT is considered an interesting target organ for the treatment of metabolic disease due to its high metabolic capacity. Non-shivering thermogenesis, once activated, can lead to enhanced partitioning and oxidation of fuels in adipose tissues, and reduce the burden of glucose and lipids on other metabolic organs such as liver, pancreas and skeletal muscle. Sustained long-term activation of BAT may also lead to meaningful bodyweight loss. In this review, we discuss three different drug classes (the thiazolidinedione (TZD class of PPAR agonists, 3 adrenergic receptor agonists and fibroblast growth factor 21 (FGF21 analogues that have been proposed to regulate BAT and beige recruitment or activation, or both, and which have been tested in both rodent and human. The learnings from these classes suggest that restoration of functional BAT and beige mass as well as improved activation might be required to fully realize the metabolic potential of these tissues. Whether this can be achieved without the undesired cardiovascular side-effects exhibited by the TZD PPAR agonists and 3 adrenergic receptor agonists remains to be resolved.

  15. Assessment of Anticholinesterase Activity of Gelidiella acerosa: Implications for Its Therapeutic Potential against Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Arif Nisha Syad

    2012-01-01

    Full Text Available The effect of various solvent extracts of Gelidiella acerosa on acetylcholinesterase (AChE and butyrylcholinesterase (BuChE activities was investigated. AChE and BuChE inhibitory activities were analyzed by spectrophotometric method. Phytochemical screening of the compounds present in the solvent extracts was done qualitatively. Characterization of the compounds present in the benzene extract of G. acerosa was done by GC-MS analysis. The results showed that, at 487.80 μg/mL, benzene extract showed significant (P<0.05 inhibitory activity against both AChE and BuChE with the percentage of inhibition 54.18±5.65 % (IC50 = 434.61±26.53 μg/mL and 78.43±0% (IC50 = 163.01±85.35 μg/mL, respectively. The mode of inhibition exhibited by benzene extract against the AChE and BuChE was found to be competitive and uncompetitive type of inhibition, respectively. Preliminary phytochemical analysis coupled with GC-MS illustrates that the benzene extract possesses high amount of terpenoids, which could be the reason for potential cholinesterase inhibitory activity.

  16. Recent actions taken on methyl bromide under the Montreal Protocol: Their potential economic implications on international trade

    International Nuclear Information System (INIS)

    Ross, R.T.; Vail, P.V.

    1993-01-01

    Methyl bromide (MB) produced and used by man is a versatile, highly effective, fastacting fumigant employed in a number of important ways to kill organisms destructive to plants. A wide spectrum of commodities is treated with MB. The compound is unique in that it provides a wide range of pest control, may be applied to a broad spectrum of both food and non-food commodities, can be used for fumigation of large and small quantities of materials, and, when applied properly, leaves no residues of toxicological significance. Recently, this compound has come under scientific scrutiny and has been identified as a potentially potent ozone depleting chemical. As a result, countries operating under the Montreal Protocol will be restricting its use, and, in some cases, eliminating its use altogether. To date there are no alternative chemical fumigants to replace methyl bromide. Non-chemical treatments such as irradiation, hot and cold treatments, modified atmosphere, etc., are the most promising. The paper focuses on the magnitude of the economic consequences on international trade and the necessity to have available alternative treatments that are highly effective, fast-acting, and practical. 8 refs, 12 tabs

  17. Development and use of innovative approaches to waste management and environmental restoration: Potential liability and its implications

    Energy Technology Data Exchange (ETDEWEB)

    Owens, W.L.

    1990-12-01

    The US Department of Energy (DOE) has established as its goal to have all of its facilities cleaned up and in compliance with all applicable environmental laws by the year 2019. As part of its plan to achieve that goal, DOE created, in November 1989, an Office of Environmental Restoration and Waste Management (EM) and, within EM, an Office of Technology Development (OTD). Since the achievement of DOE`s long-term objective in the area of waste management and environmental restoration is not possible utilizing only existing technology, the importance of OTD`s mission is clear. A question has been raised regarding the nature of the potential liability associated with development, testing, and use of new technologies for waste management and environmental restoration; and the impact it may have on the ability or willingness of other parties to participate in DOE`s technology development program. This report is intended to provide at least a preliminary answer to the question. Given the range of activities involved in the technology development process, there are many circumstances that could result in liability. Therefore, the discussion here is somewhat general. It may, however, provide a base for more detailed analysis, at a later time, of liability issues raised by specific circumstances.

  18. Development and use of innovative approaches to waste management and environmental restoration: Potential liability and its implications

    Energy Technology Data Exchange (ETDEWEB)

    Owens, W.L.

    1990-12-01

    The US Department of Energy (DOE) has established as its goal to have all of its facilities cleaned up and in compliance with all applicable environmental laws by the year 2019. As part of its plan to achieve that goal, DOE created, in November 1989, an Office of Environmental Restoration and Waste Management (EM) and, within EM, an Office of Technology Development (OTD). Since the achievement of DOE's long-term objective in the area of waste management and environmental restoration is not possible utilizing only existing technology, the importance of OTD's mission is clear. A question has been raised regarding the nature of the potential liability associated with development, testing, and use of new technologies for waste management and environmental restoration; and the impact it may have on the ability or willingness of other parties to participate in DOE's technology development program. This report is intended to provide at least a preliminary answer to the question. Given the range of activities involved in the technology development process, there are many circumstances that could result in liability. Therefore, the discussion here is somewhat general. It may, however, provide a base for more detailed analysis, at a later time, of liability issues raised by specific circumstances.

  19. Balanced reciprocal translocation 5,18: a case report

    Directory of Open Access Journals (Sweden)

    Shahram Savad

    2014-05-01

    Conclusion: A balanced reciprocal translocation carrier is phenotypically normal, but during meiosis І, carrier chromosomes cant pair normally and form quadrivalant instead of bivalant that depend on type of their segregation (alternate, adjacent 1, adjacent 2,3:1,4:0, produce gametes that are chromosomally unbalanced which can result in early fetus abortion. Considering the number of abnormal gametes, the most effective way to help couples with this problem seems to be PGD 24sure, since it can identify reciprocal and Robertsonian translocation and allows concurrent screening of all chromosomes for aneuploidy. Another technique that can be compared with PGD 24sure is fluorescence in situ hybridization (FISH, but it has several technical limitations such as it is expensive and complexity, in addition it has only few probes (for chromosomes 21, 13, 18, X, Y so sometimes necessary to create patient specific protocols.

  20. The Social Construction of Guangzhou as a Translocal Trading Place

    Directory of Open Access Journals (Sweden)

    Angelo Gilles

    2015-01-01

    Full Text Available Guangzhou has become a key destination for sub-Saharan African traders. These traders have established multilocal forms of business organisation and, in so doing, have developed diverse practices to overcome geographical, political and cultural boundaries. This paper focuses on these practices, looking at the ways in which the movements, relations and interactions within these organisational formations are produced, transformed and lived. A close ethnographic examination was made of the livelihoods of 33 African traders from 13 sub-Saharan African countries. Through the concept of trans-locality, the organisational formations of these Africans are conceptualised as links between different places on a larger geographical scale; these links then meet on a local scale in the specific place of Guangzhou. Following a relational understanding of spatial constructions in social science, these links are conceptualised as one of the main drivers for the social construction and transformation of the city as a trans-local trading place.

  1. Slowing down DNA translocation by a nanofiber meshed layer

    Science.gov (United States)

    Zhao, Yue; Xie, Wanyi; Tian, Enling; Ren, Yiwei; Zhu, Jifeng; Deng, Yunsheng; He, Shixuan; Liang, Liyuan; Wang, Yunjiao; Zhou, Daming; Wang, Deqiang

    2018-01-01

    Due to the weak interaction between DNA molecules and the inner surface of nanopores, DNA translocation is very fast, just leaving a short current drop without sufficient information to recognise the nucleotide sequence in the strand. In this paper, we propose a nanopore-nanofiber mesh hybridized structure to decelerate DNA translocation speed. Experimental results reveal that due to hydrophobic interaction between the DNA fragments and the nanofibers, the DNA moving speed can be retarded to two orders of magnitude slower. Furthermore, according to theory simulations, the additional fiber layer will reduce the electric field in the channel but elongate the capture region at the pore orifice, which will be helpful for increasing the capture rate and extending the DNA dwelling time in the meanwhile.

  2. A strategy for generation and balancing of autosome: Y chromosome translocations.

    Science.gov (United States)

    Joshi, Sonal S; Cheong, Han; Meller, Victoria H

    2014-01-01

    We describe a method for generation and maintenance of translocations that move large autosomal segments onto the Y chromosome. Using this strategy we produced ( 2;Y) translocations that relocate between 1.5 and 4.8 Mb of the 2nd chromosome.. All translocations were easily balanced over a male-specific lethal 1 (msl-1) mutant chromosome. Both halves of the translocation carry visible markers, as well as P-element ends that enable molecular confirmation. Halves of these translocations can be separated to produce offspring with duplications and with lethal second chromosome deficiencies . Such large deficiencies are otherwise tedious to generate and maintain.

  3. Mechanism for translocation of fluoroquinolones across lipid membranes

    DEFF Research Database (Denmark)

    Cramariuc, O.; Rog, T.; Javanainen, M.

    2012-01-01

    Classical atom-scale molecular dynamics simulations, constrained free energy calculations, and quantum mechanical (QM) calculations are employed to study the diffusive translocation of ciprofloxacin (CPFX) across lipid membranes. CPFX is considered here as a representative of the fluoroquinolone...... antibiotics class. Neutral and zwitterionic CPFX coexist at physiological pH, with the latter being predominant. Simulations reveal that only the neutral form permeates the bilayer, and it does so through a novel mechanism that involves dissolution of concerted stacks of zwitterionic ciprofloxacins...

  4. Two translocations of chromosome 15q associated with dyslexia

    OpenAIRE

    Nopola-Hemmi, J.; Taipale, M.; Haltia, T.; Lehesjoki, A.; Voutilainen, A.; Kere, J.

    2000-01-01

    Developmental dyslexia is characterised by difficulties in learning to read. As reading is a complex cognitive process, multiple genes are expected to contribute to the pathogenesis of dyslexia. The genetics of dyslexia has been a target of molecular studies during recent years, but so far no genes have been identified. However, a locus for dyslexia on chromosome 15q21 (DYX1) has been established in previous linkage studies. We have identified two families with balanced translocations involvi...

  5. A nanopore-nanofiber mesh biosensor to control DNA translocation

    OpenAIRE

    Squires, Allison; Hersey, Joseph S.; Grinstaff, Mark W.; Meller, Amit

    2013-01-01

    Solid-state nanopores show promise as single-molecule sensors for biomedical applications, but to increase their resolution and efficiency analyte molecules must remain longer in the nanopore sensing volume. Here we demonstrate a novel, facile, and customizable nanopore sensor modification that reduces double stranded DNA translocation velocity by two orders of magnitude or more via interactions outside the nanopore. This is achieved by electrospinning a copolymer nanofiber mesh (NFM) directl...

  6. "Translocal Express" juba täna! / Rael Artel

    Index Scriptorium Estoniae

    Artel, Rael, 1980-

    2009-01-01

    27. märtsil algab Kumu Kunstimuuseumis "Public Preparation'i" ("Avalik ettevalmistus") sarja rahvusvaheline seminar "Translocal Express. Golden Age" ("Translokaalne ekspress. Kuldaeg"), kus on kõne all ajalookirjutamise ja kollektiivse mälu roll praegu domineerivas natsionalistlikus diskursuses ja selle käsitlemine kaasaegses kunstis. Seminaril on lähtutud eelkõige kunstnike Martin Krenni (Viin) ja Kristina Normani teoste tutvustamisest

  7. International study of factors affecting human chromosome translocations

    Czech Academy of Sciences Publication Activity Database

    Sigurdson, A.J.; Ha, M.; Hauptmann, M.; Bhatti, P.; Šrám, Radim; Beskid, Olena; Tawn, E.J.; Whitehouse, C.A.; Lindholm, C.; Nakano, M.; Kodama, Y.; Nakamura, N.; Vorobtsova, I.; Oestreicher, U.; Stephan, G.; Yong, L.C.; Bauchinger, M.; Schmid, E.; Chung, H.W.; Darroudi, F.; Roy, L.; Voisin, P.; Barquinero, J.F.; Livingston, G.; Blakey, D.; Hayata, I.; Zhang, W.; Wang, Ch.; Benett, L.M.; Littlefield, L.G.; Edwards, A.A.; Kleinerman, R.A.; Tucker, J.D.

    2008-01-01

    Roč. 652, č. 2 (2008), s. 112-121 ISSN 1383-5718 R&D Projects: GA MŽP SL/5/160/05; GA MŽP SI/340/2/00; GA MŽP SL/740/5/03 Institutional research plan: CEZ:AV0Z50390512 Keywords : Chromosome translocations * FISH * Background frequency Subject RIV: DN - Health Impact of the Environment Quality Impact factor: 2.363, year: 2008

  8. Particles translocate from the vagina to the oviducts and beyond

    Energy Technology Data Exchange (ETDEWEB)

    Wehner, A.P.; Hall, A.S.; Weller, R.E.; Lepel, E.A.; Schirmer, R.E.

    1985-03-01

    To investigate whether particles deposited in the vagina translocate to the oviducts, 0.3 ml of a 4% bone black suspension was deposited in the posterior vaginal fornix of each of five cynomolgus monkeys (Macaca fascicularis) during their mid-menstrual cycle. Simultaneously, each animal received 10 units of oxytocin by intramuscular injection. The oviducts of three animals were removed 1 hr after administration of the bone black, while those of the remaining two animals were removed 72 hr after dosing. The removed oviducts were flushed with Hank's solution and then with collagenase solution. The solutions were collected in clean vials and filtered. The filters were examined for bone black particles by light microscopy, as were filters through which solution blanks (negative controls) had been passed. Particles resembling bone black were found on all filters. There were no appreciable differences in the number or shape of these particles between the solution-blank filters and the oviduct-flush filters. The particles on both the solution-blank filters and on the oviduct-flush filters probably originated from environmental contamination by ubiquitous carbon particles. While these results suggested that no translocation took place, translocation could not be ruled out with certainty in the absence of quantitative analyses. A more definitive pilot study was then conducted with two dosed monkeys and one control, using talc labelled by neutron activation to circumvent the problem of environmental contamination. Gamma-Ray analysis of tissue and peritoneal lavage samples for the radionuclides /sup 46/Sc, /sup 59/Fe and /sup 60/Co indicated that no measurable quantities (i.e. greater than 0.5 micrograms) of talc translocated from the deposition site in the vagina to the uterine cavity and beyond.

  9. Potential of VIIRS Data for Regional Monitoring of Gypsy Moth Defoliation: Implications for Forest Threat Early Warning System

    Science.gov (United States)

    Spruce, Joseph P.; Ryan, Robert E.; Smoot, James C.; Prados, Donald; McKellip, Rodney; Sader. Steven A.; Gasser, Jerry; May, George; Hargrove, William

    2007-01-01

    A NASA RPC (Rapid Prototyping Capability) experiment was conducted to assess the potential of VIIRS (Visible/Infrared Imager/Radiometer Suite) data for monitoring non-native gypsy moth (Lymantria dispar) defoliation of forests. This experiment compares defoliation detection products computed from simulated VIIRS and from MODIS (Moderate Resolution Imaging Spectroradiometer) time series products as potential inputs to a forest threat EWS (Early Warning System) being developed for the USFS (USDA Forest Service). Gypsy moth causes extensive defoliation of broadleaved forests in the United States and is specifically identified in the Healthy Forest Restoration Act (HFRA) of 2003. The HFRA mandates development of a national forest threat EWS. This system is being built by the USFS and NASA is aiding integration of needed satellite data products into this system, including MODIS products. This RPC experiment enabled the MODIS follow-on, VIIRS, to be evaluated as a data source for EWS forest monitoring products. The experiment included 1) assessment of MODIS-simulated VIIRS NDVI products, and 2) evaluation of gypsy moth defoliation mapping products from MODIS-simulated VIIRS and from MODIS NDVI time series data. This experiment employed MODIS data collected over the approximately 15 million acre mid-Appalachian Highlands during the annual peak defoliation time frame (approximately June 10 through July 27) during 2000-2006. NASA Stennis Application Research Toolbox software was used to produce MODIS-simulated VIIRS data and NASA Stennis Time Series Product Tool software was employed to process MODIS and MODIS-simulated VIIRS time series data scaled to planetary reflectance. MODIS-simulated VIIRS data was assessed through comparison to Hyperion-simulated VIIRS data using data collected during gypsy moth defoliation. Hyperion-simulated MODIS data showed a high correlation with actual MODIS data (NDVI R2 of 0.877 and RMSE of 0.023). MODIS-simulated VIIRS data for the same

  10. Cyanotoxins at low doses induce apoptosis and inflammatory effects in murine brain cells: Potential implications for neurodegenerative diseases

    Directory of Open Access Journals (Sweden)

    Larissa Takser

    2016-01-01

    Full Text Available Cyanotoxins have been shown to be highly toxic for mammalian cells, including brain cells. However, little is known about their effect on inflammatory pathways. This study investigated whether mammalian brain and immune cells can be a target of certain cyanotoxins, at doses approximating those in the guideline levels for drinking water, either alone or in mixtures. We examined the effects on cellular viability, apoptosis and inflammation signalling of several toxins on murine macrophage-like RAW264.7, microglial BV-2 and neuroblastoma N2a cell lines. We tested cylindrospermopsin (CYN, microcystin-LR (MC-LR, and anatoxin-a (ATX-a, individually as well as their mixture. In addition, we studied the neurotoxins β-N-methylamino-l-alanine (BMAA and its isomer 2,4-diaminobutyric acid (DAB, as well as the mixture of both. Cellular viability was determined by the MTT assay. Apoptosis induction was assessed by measuring the activation of caspases 3/7. Cell death and inflammation are the hallmarks of neurodegenerative diseases. Thus, our final step was to quantify the expression of a major proinflammatory cytokine TNF-α by ELISA. Our results show that CYN, MC-LR and ATX-a, but not BMAA and DAB, at low doses, especially when present in a mixture at threefold less concentrations than individual compounds are 3–15 times more potent at inducing apoptosis and inflammation. Our results suggest that common cyanotoxins at low doses have a potential to induce inflammation and apoptosis in immune and brain cells. Further research of the neuroinflammatory effects of these compounds in vivo is needed to improve safety limit levels for cyanotoxins in drinking water and food.

  11. Differences in Motor Evoked Potentials Induced in Rats by Transcranial Magnetic Stimulation under Two Separate Anesthetics: Implications for Plasticity Studies.

    Science.gov (United States)

    Sykes, Matthew; Matheson, Natalie A; Brownjohn, Philip W; Tang, Alexander D; Rodger, Jennifer; Shemmell, Jonathan B H; Reynolds, John N J

    2016-01-01

    Repetitive transcranial magnetic stimulation (rTMS) is primarily used in humans to change the state of corticospinal excitability. To assess the efficacy of different rTMS stimulation protocols, motor evoked potentials (MEPs) are used as a readout due to their non-invasive nature. Stimulation of the motor cortex produces a response in a targeted muscle, and the amplitude of this twitch provides an indirect measure of the current state of the cortex. When applied to the motor cortex, rTMS can alter MEP amplitude, however, results are variable between participants and across studies. In addition, the mechanisms underlying any change and its locus are poorly understood. In order to better understand these effects, MEPs have been investigated in vivo in animal models, primarily in rats. One major difference in protocols between rats and humans is the use of general anesthesia in animal experiments. Anesthetics are known to affect plasticity-like mechanisms and so may contaminate the effects of an rTMS protocol. In the present study, we explored the effect of anesthetic on MEP amplitude, recorded before and after intermittent theta burst stimulation (iTBS), a patterned rTMS protocol with reported facilitatory effects. MEPs were assessed in the brachioradialis muscle of the upper forelimb under two anesthetics: a xylazine/zoletil combination and urethane. We found MEPs could be induced under both anesthetics, with no differences in the resting motor threshold or the average baseline amplitudes. However, MEPs were highly variable between animals under both anesthetics, with the xylazine/zoletil combination showing higher variability and most prominently a rise in amplitude across the baseline recording period. Interestingly, application of iTBS did not facilitate MEP amplitude under either anesthetic condition. Although it is important to underpin human application of TMS with mechanistic examination of effects in animals, caution must be taken when selecting an

  12. Differences in motor evoked potentials induced in rats by transcranial magnetic stimulation under two separate anesthetics: implications for plasticity studies

    Directory of Open Access Journals (Sweden)

    Matthew Sykes

    2016-10-01

    Full Text Available Repetitive transcranial magnetic stimulation (rTMS is primarily used in humans to change the state of corticospinal excitability. To assess the efficacy of different rTMS stimulation protocols, motor evoked potentials (MEPs are used as a readout due to their non-invasive nature. Stimulation of the motor cortex produces a response in a targeted muscle, and the amplitude of this twitch provides an indirect measure of the current state of the cortex. When applied to the motor cortex, rTMS can alter MEP amplitude, however results are variable between participants and across studies. In addition, the mechanisms underlying any change and its locus are poorly understood. In order to better understand these effects, MEPs have been investigated in vivo in animal models, primarily in rats. One major difference in protocols between rats and humans is the use of general anesthesia in animal experiments. Anesthetics are known to affect plasticity-like mechanisms and so may contaminate the effects of an rTMS protocol. In the present study, we explored the effect of anesthetic on MEP amplitude, recorded before and after intermittent theta burst stimulation (iTBS, a patterned rTMS protocol with reported facilitatory effects. MEPs were assessed in the brachioradialis muscle of the upper forelimb under two anesthetics: a xylazine/zoletil combination and urethane. We found MEPs could be induced under both anesthetics, with no differences in the resting motor threshold or the average baseline amplitudes. However, MEPs were highly variable between animals under both anesthetics, with the xylazine/zoletil combination showing higher variability and most prominently a rise in amplitude across the baseline recording period. Interestingly, application of iTBS did not facilitate MEP amplitude under either anesthetic condition. Although it is important to underpin human application of TMS with mechanistic examination of effects in animals, caution must be taken when

  13. Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential.

    Science.gov (United States)

    Huo, Xiaokui; Wang, Chao; Yu, Zhenlong; Peng, Yulin; Wang, Shumei; Feng, Shengnan; Zhang, Shouji; Tian, Xiangge; Sun, Chengpeng; Liu, Kexin; Deng, Sa; Ma, Xiaochi

    2017-05-01

    Melatonin is present in virtually all organisms from bacteria to mammals, and it exhibits a broad spectrum of biological functions, including synchronization of circadian rhythms and oncostatic activity. Several functions of melatonin are mediated by its membrane receptors, but others are receptor-independent. For the latter, melatonin is required to penetrate membrane and enters intracellular compartments. However, the mechanism by which melatonin enters cells remains debatable. In this study, it was identified that melatonin and its sulfation metabolites were the substrates of oligopeptide transporter (PEPT) 1/2 and organic anion transporter (OAT) 3, respectively. The docking analysis showed that the binding of melatonin to PEPT1/2 was attributed to their low binding energy and suitable binding conformation in which melatonin was embedded in the active site of PEPT1/2 and fitted well with the cavity in three-dimensional space. PEPT1/2 transporters play a pivotal role in melatonin uptake in cells. Melatonin's membrane transportation via PEPT1/2 renders its oncostatic effect in malignant cells. For the first time, PEPT1/2 were identified to localize in the mitochondrial membrane of human cancer cell lines of PC3 and U118. PEPT1/2 facilitated the transportation of melatonin into mitochondria. Melatonin accumulation in mitochondria induced apoptosis of PC3 and U118 cells. Thus, PEPT1/2 can potentially be used as a cancer cell-targeted melatonin delivery system to improve the therapeutic effects of melatonin in cancer treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Complex mutations & subpopulations of deletions at exon 19 of EGFR in NSCLC revealed by next generation sequencing: potential clinical implications.

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    Antonio Marchetti

    Full Text Available Microdeletions at exon 19 are the most frequent genetic alterations affecting the Epidermal Growth Factor Receptor (EGFR gene in non-small cell lung cancer (NSCLC and they are strongly associated with response to treatment with tyrosine kinase inhibitors. A series of 116 NSCLC DNA samples investigated by Sanger Sequencing (SS, including 106 samples carrying exon 19 EGFR deletions and 10 without deletions (control samples, were subjected to deep next generation sequencing (NGS. All samples with deletions at SS showed deletions with NGS. No deletions were seen in control cases. In 93 (88% cases, deletions detected by NGS were exactly corresponding to those identified by SS. In 13 cases (12% NGS resolved deletions not accurately characterized by SS. In 21 (20% cases the NGS showed presence of complex (double/multiple frameshift deletions producing a net in-frame change. In 5 of these cases the SS could not define the exact sequence of mutant alleles, in the other 16 cases the results obtained by SS were conventionally considered as deletions plus insertions. Different interpretative hypotheses for complex mutations are discussed. In 46 (43% tumors deep NGS showed, for the first time to our knowledge, subpopulations of DNA molecules carrying EGFR deletions different from the main one. Each of these subpopulations accounted for 0.1% to 17% of the genomic DNA in the different tumors investigated. Our findings suggest that a region in exon 19 is highly unstable in a large proportion of patients carrying EGFR deletions. As a corollary to this study, NGS data were compared with those obtained by immunohistochemistry using the 6B6 anti-mutant EGFR antibody. The immunoreaction was E746-A750del specific. In conclusion, NGS analysis of EGFR exon 19 in NSCLCs allowed us to formulate a new interpretative hypothesis for complex mutations and revealed the presence of subpopulations of deletions with potential pathogenetic and clinical impact.

  15. Transport and removal of viruses in saturated sand columns under oxic and anoxic conditions--Potential implications for groundwater protection.

    Science.gov (United States)

    Frohnert, Anne; Apelt, Susann; Klitzke, Sondra; Chorus, Ingrid; Szewzyk, Regine; Selinka, Hans-Christoph

    2014-11-01

    To protect groundwater as a drinking water resource from microbiological contamination, protection zones are installed. While travelling through these zones, concentrations of potential pathogens should decline to levels that pose no risks to human health. Removal of viruses during subsurface passage is influenced by physicochemical conditions, such as oxygen concentration, which also affects virus survival. The aim of our study was to evaluate the effect of redox conditions on the removal of viruses during sand filtration. Experiments in glass columns filled with medium-grained sand were conducted to investigate virus removal in the presence and absence of dissolved oxygen. Bacteriophages MS2 and PhiX174, as surrogates for human enteric viruses were spiked in pulsed or in continuous mode and pumped through the columns at a filter velocity of about 1m/d. Virus breakthrough curves were analyzed by calculating total viral elimination and fitted using one-dimensional transport models (CXTFIT and HYDRUS-1D). While short-term experiments with pulsed virus application showed only small differences with regard to virus removal under oxic and anoxic conditions, a long-term experiment with continuous dosing revealed a clearly lower elimination of viruses under anoxic conditions. These findings suggest that less inactivation and less adsorption of viruses in anoxic environments affect their removal. Therefore, in risk assessment studies aimed to secure drinking water resources from viral contamination and optimization of protection zones, the oxic and anoxic conditions in the subsurface should also be considered. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. Potential to enhance the prescribing of generic drugs in patients with mental health problems in Austria; implications for the future

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    Brian eGodman

    2013-01-01

    Full Text Available Introduction: Scrutiny over pharmaceutical expenditure is increasing leading to multiple reforms. This includes Austria with measures to lower generic prices and enhance their utilisation. However the situation for newer antidepressants and atypical antipsychotic drugs (AAPs is different to PPIs, statins and renin-angiotensin drugs with greater tailoring of therapy and no wish to switch products in stable patients. Authorities welcome generics though given high costs particularly of patented AAPs. Objective: Assess (a changes in utilisation of venlafaxine versus other newer anti-depressants before and after availability of generics, (b utilisation of generic versus originator venlafaxine, (c price reductions of venlafaxine over time and influence on total expenditure, (d utilisation of risperidone versus other AAPs, (e suggest potential additional reforms that could be introduced if pertinent. Methodology: A quasi-experimental study design with a segmented time series and an observational study. Utilisation measured in defined daily doses (DDDs and total expenditure per DDD and over time. Results: No appreciable changes in the utilization patterns of venlafaxine and risperidone after generics. The reduction in expenditure/ DDD for venlafaxine decreased overall expenditure on antidepressants by 5% by the end of the study versus just before generics despite a 37% increase in utilization. Expenditure will further decrease if there was reduced prescribing of duloxetine. Conclusion: Depression, schizophrenia and bipolar diseases are complex diseases. As a result, specific measures are needed to encourage prescribing of generic risperidone and venlafaxine when multiple choices are appropriate, and authorities cannot rely on a ´Hawthorne´ effect between classes to enhance use of generics first line. Measures may include prescribing restrictions for duloxetine. No specific measures planned for AAPs with more generics becoming available.

  17. Implication of the intestinal microbiome as a potential surrogate marker of immune responsiveness to experimental therapies in autoimmune diabetes.

    Science.gov (United States)

    Needell, James C; Dinarello, Charles A; Ir, Diana; Robertson, Charles E; Ryan, Sarah M; Kroehl, Miranda E; Frank, Daniel N; Zipris, Danny

    2017-01-01

    Type 1 diabetes (T1D) is an autoimmune proinflammatory disease with no effective intervention. A major obstacle in developing new immunotherapies for T1D is the lack of means for monitoring immune responsiveness to experimental therapies. The LEW1.WR1 rat develops autoimmunity following infection with the parvovirus Kilham rat virus (KRV) via mechanisms linked with activation of proinflammatory pathways and alterations in the gut bacterial composition. We used this animal to test the hypothesis that intervention with agents that block innate immunity and diabetes is associated with a shift in the gut microbiota. We observed that infection with KRV results in the induction of proinflammatory gene activation in both the spleen and pancreatic lymph nodes. Furthermore, administering animals the histone deacetylase inhibitor ITF-2357 and IL-1 receptor antagonist (Anakinra) induced differential STAT-1 and the p40 unit of IL-12/IL-23 gene expression. Sequencing of bacterial 16S rRNA genes demonstrated that both ITF-2357 and Anakinra alter microbial diversity. ITF-2357 and Anakinra modulated the abundance of 23 and 8 bacterial taxa in KRV-infected animals, respectively, of which 5 overlapped between the two agents. Lastly, principal component analysis implied that ITF-2357 and Anakinra induce distinct gut microbiomes compared with those from untreated animals or rats provided KRV only. Together, the data suggest that ITF-2357 and Anakinra differentially influence the innate immune system and the intestinal microbiota and highlight the potential use of the gut microbiome as a surrogate means of assessing anti-inflammatory immune effects in type 1 diabetes.

  18. C5a enhances dysregulated inflammatory and angiogenic responses to malaria in vitro: potential implications for placental malaria.

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    Andrea Conroy

    Full Text Available Placental malaria (PM is a leading cause of maternal and infant mortality. Although the accumulation of parasitized erythrocytes (PEs and monocytes within the placenta is thought to contribute to the pathophysiology of PM, the molecular mechanisms underlying PM remain unclear. Based on the hypothesis that excessive complement activation may contribute to PM, in particular generation of the potent inflammatory peptide C5a, we investigated the role of C5a in the pathogenesis of PM in vitro and in vivo.Using primary human monocytes, the interaction between C5a and malaria in vitro was assessed. CSA- and CD36-binding PEs induced activation of C5 in the presence of human serum. Plasmodium falciparum GPI (pfGPI enhanced C5a receptor expression (CD88 on monocytes, and the co-incubation of monocytes with C5a and pfGPI resulted in the synergistic induction of cytokines (IL-6, TNF, IL-1beta, and IL-10, chemokines (IL-8, MCP-1, MIP1alpha, MIP1beta and the anti-angiogenic factor sFlt-1 in a time and dose-dependent manner. This dysregulated response was abrogated by C5a receptor blockade. To assess the potential role of C5a in PM, C5a plasma levels were measured in malaria-exposed primigravid women in western Kenya. Compared to pregnant women without malaria, C5a levels were significantly elevated in women with PM.These results suggest that C5a may contribute to the pathogenesis of PM by inducing dysregulated inflammatory and angiogenic responses that impair placental function.

  19. Regional molecular and cellular differences in the female rabbit Achilles tendon complex: potential implications for understanding responses to loading.

    Science.gov (United States)

    Huisman, Elise S; Andersson, Gustav; Scott, Alexander; Reno, Carol R; Hart, David A; Thornton, Gail M

    2014-05-01

    The aim of this study was: (i) to analyze the morphology and expression of extracellular matrix genes in six different regions of the Achilles tendon complex of intact normal rabbits; and (ii) to assess the effect of ovariohysterectomy (OVH) on the regional expression of these genes. Female New Zealand White rabbits were separated into two groups: (i) intact normal rabbits (n = 4); and (ii) OVH rabbits (n = 8). For each rabbit, the Achilles tendon complex was dissected into six regions: distal gastrocnemius (DG); distal flexor digitorum superficialis; proximal lateral gastrocnemius (PLG); proximal medial gastrocnemius; proximal flexor digitorum superficialis; and paratenon. For each of the regions, hematoxylin and eosin staining was performed for histological evaluation of intact normal rabbit tissues and mRNA levels for proteoglycans, collagens and genes associated with collagen regulation were assessed by real-time reverse transcription-quantitative polymerase chain reaction for both the intact normal and OVH rabbit tissues. The distal regions displayed a more fibrocartilaginous phenotype. For intact normal rabbits, aggrecan mRNA expression was higher in the distal regions of the Achilles tendon complex compared with the proximal regions. Collagen Type I and matrix metalloproteinase-2 expression levels were increased in the PLG compared to the DG in the intact normal rabbit tissues. The tendons from OVH rabbits had lower gene expressions for the proteoglycans aggrecan, biglycan, decorin and versican compared with the intact normal rabbits, although the regional differences of increased aggrecan expression in distal regions compared with proximal regions persisted. The tensile and compressive forces experienced in the examined regions may be related to the regional differences found in gene expression. The lower mRNA expression of the genes examined in the OVH group confirms a potential effect of systemic estrogen on tendon. © 2014 Anatomical Society.

  20. Fatty-acid binding protein 4 gene variants and childhood obesity: potential implications for insulin sensitivity and CRP levels

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    Bhattacharjee Rakesh

    2010-02-01

    Full Text Available Abstract Introduction Obesity increases the risk for insulin resistance and metabolic syndrome in both adults and children. FABP4 is a member of the intracellular lipid-binding protein family that is predominantly expressed in adipose tissue, and plays an important role in maintaining glucose and lipid homeostasis. The purpose of this study was to measure FABP4 plasma levels, assess FABP4 allelic variants, and explore potential associations with fasting glucose and insulin levels in young school-age children with and without obesity. Methods A total of 309 consecutive children ages 5-7 years were recruited. Children were divided based on BMI z score into Obese (OB; BMI z score >1.65 and non-obese (NOB. Fasting plasma glucose, lipids, insulin, hsCRP, and FABP4 levels were measured. HOMA was used as correlate of insulin sensitivity. Four SNPs of the human FABP4 gene (rs1051231, rs2303519, rs16909233 and rs1054135, corresponding to several critical regions of the encoding FABP4 gene sequence were genotyped. Results Compared to NOB, circulating FABP4 levels were increased in OB, as were LDL, hsCRP and HOMA. FABP4 levels correlated with BMI, and also contributed to the variance of HOMA and hsCRP, but not serum lipids. The frequency of rs1054135 allelic variant was increased in OB, and was associated with increased FABP4 levels, while the presence of rs16909233 variant allele, although similar in OB and NOB, was associated with increased HOMA values. Conclusions Childhood obesity is associated with higher FABP4 levels that may promote cardiometabolic risk. The presence of selective SNPs in the FABP4 gene may account for increased risk for insulin resistance or systemic inflammation in the context of obesity.

  1. The release of organic material from clay based buffer materials and its potential implications for radionuclide transport

    International Nuclear Information System (INIS)

    Vilks, P.; Stroes-Gascoyne, S.; Goulard, M.; Haveman, S.A.; Bachinski, D.B.

    1998-01-01

    In the Canadian nuclear fuel waste disposal concept used fuel would be placed in corrosion resistant containers which would be surrounded by clay-based buffer and backfill materials in an engineered vault excavated at 500 to 1000 m depth in crystalline rock formations in the Canadian shield. Organic substances could affect radionuclide mobility due to the effects of redox and complexation reactions that increase solubility and alter mobility. The purpose of this study was to determine whether the buffer and backfill materials, proposed for use in a disposal vault, contain organics that could be leached by groundwater in large enough quantities to affect radionuclide mobility within the disposal vault and surrounding geosphere complex. Buffer material, made from a mixture of 50 wt.% Avonlea sodium bentonite and 50 wt.% silica sand, was extracted with deionized water to determine the release of dissolved organic carbon (DOC), humic acid and fulvic acid. The effect of radiation and heat from the used fuel was simulated by treating samples of buffer before leaching to various amounts of heat (60 and 90 C) for periods of 2, 4 and 6 weeks, and to ionizing radiation with doses of 25 kGy and 50 kGy. The results showed that groundwater would leach significant amounts of organics from buffer that complex with radionuclides such as the actinides, potentially affecting their solubility and transport within the disposal vault and possibly the surrounding geosphere. In addition, the leached organics would likely stimulate microbial growth by several orders of magnitude. Heating and radiation affect the amount and nature of leachable organics. (orig.)

  2. The changing epidemiology of meningococcal disease in Quebec, Canada, 1991-2011: potential implications of emergence of new strains.

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    Rodica Gilca

    Full Text Available BACKGROUND: In order to inform meningococcal disease prevention strategies, we analysed the epidemiology of invasive meningococcal disease (IMD in the province of Quebec, Canada, 10 years before and 10 years after the introduction of serogroup C conjugate vaccination. METHODOLOGY: IMD cases reported to the provincial notifiable disease registry in 1991-2011 and isolates submitted for laboratory surveillance in 1997-2011 were analysed. Serogrouping, PCR testing and assignment of isolates to sequence types (ST by using multilocus sequence typing (MLST were performed. RESULTS: Yearly overall IMD incidence rates ranged from 2.2-2.3/100,000 in 1991-1992 to 0.49/100,000 in 1999-2000, increasing to 1.04/100,000 in 2011. Among the 945 IMD cases identified by laboratory surveillance in 1997-2011, 68%, 20%, 8%, and 3% were due to serogroups B, C, Y, and W135, respectively. Serogroup C IMD almost disappeared following the implementation of universal childhood immunization with monovalent C conjugate vaccines in 2002. Serogroup B has been responsible for 88% of all IMD cases and 61% of all IMD deaths over the last 3 years. The number and proportion of ST-269 clonal complex has been steadily increasing among the identified clonal complexes of serogroup B IMD since its first identification in 2003, representing 65% of serogroup B IMD in 2011. This clonal complex was first introduced in adolescent and young adults, then spread to other age groups. CONCLUSION: Important changes in the epidemiology of IMD have been observed in Quebec during the last two decades. Serogroup C has been virtually eliminated. In recent years, most cases have been caused by the serogroup B ST-269 clonal complex. Although overall burden of IMD is low, the use of a vaccine with potential broad-spectrum coverage could further reduce the burden of disease. Acceptability, feasibility and cost-effectiveness studies coupled with ongoing clinical and molecular surveillance are necessary in

  3. Tiechanshan-Tunghsiao anticline earthquake analysis: Implications for northwestern Taiwan potential carbon dioxide storage site seismic hazard

    Directory of Open Access Journals (Sweden)

    Ruey-Juin Rau

    2017-01-01

    Full Text Available We analyze the seismicity and earthquake focal mechanisms beneath the Tiechanshan-Tunghsiao (TCS-TH anticline over the last two decades for seismic hazard evaluation of a potential carbon dioxide storage site in northwestern Taiwan. Seismicity in the TCS-TH anticline indicates both spatial and temporal clustering at a depth range of 7 - 12 km. Thirteen 3.0 ≤ ML ≤ 5.2 earthquake focal mechanisms show a combination of thrust, strike-slip, and normal faulting mechanisms under the TCS-TH anticline. A 1992 ML 5.2 earthquake with a focal depth of ~10 km, the largest event ever recorded beneath the TCS-TH anticline during the last two decades, has a normal fault mechanism with the T-axis trending NNE-SSW and nodal planes oriented NNW-SSE, dipping either gently to the NNE or steeply to the SSW. Thrust fault mechanisms that occurred with mostly E-W or NWW-SEE striking P-axes and strike-slip faulting events indicate NWW-SEE striking P-axes and NNE-SSW trending T-axes, which are consistent with the regional plate convergence direction. For the strike-slip faulting events, if we take the N-S or NNW-SSE striking nodal planes as the fault planes, the strike-slip faults are sinistral motions and correspond to the Tapingting fault, which is a strike-slip fault reactivated from the inherited normal fault and intersects the Tiechanshan and Tunghsiao anticlines.

  4. Growth hormone reduces mortality and bacterial translocation in irradiated rats

    Energy Technology Data Exchange (ETDEWEB)

    Gomez-de-Segura, I.A.; Miguel, E. de [`La Paz` Hospital, Madrid (Spain). Dept. of Experimental Surgery; Prieto, I. [`La Paz` Hospital, Madrid (Spain). Dept. of General and Digestive Surgery; Grande, A.G. [`La Paz` Hospital, Madrid (Spain). Dept. of Oncology Radiotherapy; Garcia, P.; Mendez, J. [`La Paz` Hospital, Madrid (Spain). Dept. of Clinical Biochemistry; Guerra, A. [`La Paz` Hospital, Madrid (Spain). Dept. of Microbiology

    1998-09-01

    Growth hormone stimulates the growth of intestinal mucosa and may reduce the severity of injury caused by radiation. Male Wistar rats underwent abdominal irradiation (12 Gy) and were treated with either human growth hormone (hGH) or saline, and sacrificed at day 4 or 7 post-irradiation. Bacterial translocation, and the ileal mucosal thickness, proliferation, and disaccharidase activity were assessed. Mortality was 65% in irradiated animals, whereas hGH caused a decrement (29%, p<0.05). Bacterial translocation was also reduced by hGH (p<0.05). Treating irradiated rats with hGH prevented body weight loss (p<0.05). Mucosal thickness increased faster in irradiated hGH-treated animals. The proliferative index showed an increment in hGH-treated animals (p<0.05). Giving hGH to irradiated rats prevented decrease in sucrose activity, and increment in lactase activity. In conclusion, giving hGH to irradiated rats promotes the adaptative process of the intestine and acute radiation-related negative effects, including mortality, bacterial translocation, and weight loss. (orig.)

  5. Dominant-lethal mutations and heritable translocations in mice

    Energy Technology Data Exchange (ETDEWEB)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed.

  6. Growth factor deprivation induces cytosolic translocation of SIRT1

    Science.gov (United States)

    Meng, Chengbo; Xing, Da; Wu, Shengnan; Huang, Lei

    2010-02-01

    Sirtuin type 1 (SIRT1), a NAD+-dependent histone deacetylases, plays a critical role in cellular senescence, aging and longevity. In general, SIRT1 is localized in nucleus and is believed as a nuclear protein. Though overexpression of SIRT1 delays senescence, SIRT1-protein levels decline naturally in thymus and heart during aging. In the present studies, we investigated the subcellular localization of SIRT1 in response to growth factor deprivation in African green monkey SV40-transformed kidney fibroblast cells (COS-7). Using SIRT1-EGFP fluorescence reporter, we found that SIRT1 localized to nucleus in physiological conditions. We devised a model enabling cell senescence via growth factor deprivation, and we found that SIRT1 partially translocated to cytosol under the treatment, suggesting a reduced level of SIRT1's activity. We found PI3K/Akt pathway was involved in the inhibition of SIRT1's cytosolic translocation, because inhibition of these kinases significantly decreased the amount of SIRT1 maintained in nucleus. Taken together, we demonstrated that growth factor deprivation induces cytosolic translocation of SIRT1, which suggesting a possible connection between cytoplasm-localized SIRT1 and the aging process.

  7. Dominant-lethal mutations and heritable translocations in mice

    International Nuclear Information System (INIS)

    Generoso, W.M.

    1983-01-01

    Chromosome aberrations are a major component of radiation or chemically induced genetic damage in mammalian germ cells. The types of aberration produced are dependent upon the mutagen used and the germ-cell stage treated. For example, in male meiotic and postmeiotic germ cells certain alkylating chemicals induce both dominant-lethal mutations and heritable translocations while others induce primarily dominant-lethal mutations. Production of these two endpoints appears to be determined by the stability of alkylation products with the chromosomes. If the reaction products are intact in the male chromosomes at the time of sperm entry, they may be repaired in fertilized eggs. If repair is not effected and the alkylation products persist to the time of pronuclear chromosome replication, they lead to chromatid-type aberrations and eventually to dominant-lethality. The production of heritable translocations, on the other hand, requires a transformation of unstable alkylation products into suitable intermediate lesions. The process by which these lesions are converted into chromosome exchange within the male genome takes place after sperm enters the egg but prior to the time of pronuclear chromosome replication (i.e., chromosome-type). Thus, dominant-lethal mutations result from both chromatid- and chromosome-type aberrations while heritable translocations result primarily from the latter type. DNA target sites associated with the production of these two endpoints are discussed

  8. Molecular diagnosis of sarcomas: chromosomal translocations in sarcomas.

    Science.gov (United States)

    Lazar, Alexander; Abruzzo, Lynne V; Pollock, Raphael E; Lee, Sangkyou; Czerniak, Bogdan

    2006-08-01

    Sarcomas are rare, numerous in type, and often difficult to definitively classify. Work in the last 2 decades has revealed that a significant subset of sarcomas are associated with specific chromosomal translocations producing chimeric (fusion) genes that play a role in the sarcomas' biology and are helpful in their differential diagnosis. To briefly review the sarcomas associated with specific translocations presenting Ewing sarcoma and synovial sarcoma as archetypes and to further explain how cytogenetic and molecular biologic approaches are being used in the diagnosis of sarcomas. This work is based on a selected review of the relevant medical and scientific literature and our extensive experience with molecular testing in sarcomas. In addition to, and complementing, the traditional diagnostic methods of examination of hematoxylin-eosin stained slides, immunohistochemistry, and sound clinical-pathologic correlation, additional cytogenetic and molecular biologic methods are being increasingly utilized and relied on in sarcoma pathology. These methods include chromosomal karyotyping, fluorescence in-situ hybridization, spectral karyotyping, and polymerase chain reaction- based methods for demonstrating specific chromosomal translocations and fusion genes. Understanding the basis of these methods and their application is critical to better provide accurate and validated specific diagnoses of sarcomas.

  9. Bacterial translocation and intestinal injury in experimental necrotizing enterocolitis model.

    Science.gov (United States)

    Ciftci, I; Ozdemir, M; Aktan, M; Aslan, K

    2012-01-01

    To study the occurrence of bacterial translocation and to assess the impact of breastfeeding on bacterial translocation in the animal model of necrotizing enterocolitis. A total of 20 neonate Sprague-Dawley rats were enrolled in the study. Rats were randomly allocated into either control or study group just after birth. Ten newborn rats in the control group were left with their mother to be breast-fed. In contrary, necrotizing enterocolitis group consisted of neonates that were separated from their mothers, housed in an incubator and were gavaged with a special rodent formula three times daily. Survival rates, weight changes, and morphologic scoring obtained after microscopic evaluation were determined as microbiologic evaluation criteria. All the rats in the control group survived, while 1 (10 %) rat died in the necrotizing enterocolitis group. Mortality rates of the two groups were similar. All the formula-fed animals in the necrotizing enterocolitis group had significant weight loss compared to the breast milk-fed rats in the control group (pmicrorganisms in the bowel pass through the intestinal barrier and reach the liver and the spleen via the hematogenous route. This condition is closely related to the impairment of physiological and functional features of the intestinal barrier and is independent from the degree of intestinal injury. Bacterial translocation should be remembered in cases suspected of necrotizing enterocolitis, and a rapid and effective treatment algorithm should be applied in such circumstances (Tab. 3, Fig. 3, Ref. 21). Full Text in PDF www.elis.sk.

  10. Twin-arginine-dependent translocation of folded proteins

    Science.gov (United States)

    Fröbel, Julia; Rose, Patrick; Müller, Matthias

    2012-01-01

    Twin-arginine translocation (Tat) denotes a protein transport pathway in bacteria, archaea and plant chloroplasts, which is specific for precursor proteins harbouring a characteristic twin-arginine pair in their signal sequences. Many Tat substrates receive cofactors and fold prior to translocation. For a subset of them, proofreading chaperones coordinate maturation and membrane-targeting. Tat translocases comprise two kinds of membrane proteins, a hexahelical TatC-type protein and one or two members of the single-spanning TatA protein family, called TatA and TatB. TatC- and TatA-type proteins form homo- and hetero-oligomeric complexes. The subunits of TatABC translocases are predominantly recovered from two separate complexes, a TatBC complex that might contain some TatA, and a homomeric TatA complex. TatB and TatC coordinately recognize twin-arginine signal peptides and accommodate them in membrane-embedded binding pockets. Advanced binding of the signal sequence to the Tat translocase requires the proton-motive force (PMF) across the membranes and might involve a first recruitment of TatA. When targeted in this manner, folded twin-arginine precursors induce homo-oligomerization of TatB and TatA. Ultimately, this leads to the formation of a transmembrane protein conduit that possibly consists of a pore-like TatA structure. The translocation step again is dependent on the PMF. PMID:22411976

  11. Single-strand DNA molecule translocation through nanoelectrode gaps

    International Nuclear Information System (INIS)

    Zhao Xiongce; Payne, Christina M; Cummings, Peter T; Lee, James W

    2007-01-01

    Molecular dynamics simulations were performed to investigate the translocation of single-strand DNA through nanoscale electrode gaps under the action of a constant driving force. The application behind this theoretical study is a proposal to use nanoelectrodes as a screening gap as part of a rapid genomic sequencing device. Preliminary results from a series of simulations using various gap widths and driving forces suggest that the narrowest electrode gap that a single-strand DNA can pass is ∼1.5 nm. The minimum force required to initiate the translocation within nanoseconds is ∼0.3 nN. Simulations using DNA segments of various lengths indicate that the minimum initiation force is insensitive to the length of DNA. However, the average threading velocity of DNA varies appreciably from short to long DNA segments. We attribute such variation to the different nature of drag force experienced by the short and long DNA segments in the environment. It is found that DNA molecules deform significantly to fit in the shape of the nanogap during the translocation

  12. Confirmation of translocated gastrointestinal bacteria in a neonatal model.

    Science.gov (United States)

    Moy, J; Lee, D J; Harmon, C M; Drongowski, R A; Coran, A G

    1999-11-01

    The hypothesis that enteric bacteria translocate from the gastrointestinal (GI) tract to extraintestinal sites has been extensively studied. However, definitive evidence that spontaneous bacterial translocation and dissemination from the GI tract to extraintestinal sites occur in a neonatal model has been lacking. The aim of this study was to confirm this phenomenon by tracking enterally administered, plasmid-labeled bacteria to extraintestinal sites. Escherichia coli 07:K1 (E. coli K1) with and without a nontransferable, ampicillin resistance plasmid (pGEM-7) were used in this study. Newborn New Zealand white rabbit pups were separated into three treatment groups: transformed E. coli K1 (E. coli K1 + pGEM-7, n = 20), nontransformed E. coli K1 (n = 12), and control pups (no bacteria, n = 7). Pups were enterally fed 10% Formulac solution supplemented with a suspension of bacteria respective to their group. After the pups fed twice daily for 2 days, representative tissue specimens from the small bowel (SB), mesenteric lymph nodes (MLNs), spleen (SPL), and liver (LIV) were aseptically harvested and tested for culture growth in ampicillin-supplemented medium. Positive growths of plasmid-induced ampicillin-resistant bacteria were detected in tissue specimens harvested from rabbits fed transformed E. coli K1, but were not detected in the other groups. This experiment demonstrated conclusively that transformed E. coli K1 fed to healthy rabbit pups spontaneously translocated from the intestinal lumen and subsequently disseminated to the mesenteric lymph nodes, spleen, and liver. Copyright 1999 Academic Press.

  13. Cenozoic pulsed compression of Da'an-Dedu Fault Zone in Songliao Basin (NE China) and its implications for earthquake potential: Evidence from seismic data

    Science.gov (United States)

    Yu, Zhongyuan; Zhang, Peizhen; Min, Wei; Wei, Qinghai; Zhao, Bin

    2018-01-01

    The Da'an-Dedu Fault Zone (DDFZ) is a major tectonic feature cutting through the Songliao Basin from south to north in NE China. Pulsed compression deformation of DDFZ during the Cenozoic implies a complex geodynamic process, and the latest stage of which occurred in the Quaternary directly influences the present seismicity of the interior basin. Although most of the evidence for Quaternary deformation about the Songliao Basin in the past decades was concentrated in marginal faults, all five earthquake swarms with magnitudes over 5.0 along the buried DDFZ with no surface expression during the past 30 years suggest it is a main seismogenic structure with seismic potential, which should deserve more attention of geologists. However, limited by the coverage of the Quaternary sedimentary and absence of strong historic and instrumental earthquakes records (M > 7), the geometric pattern, Quaternary activity and seismic potential of the DDFZ remain poorly understood. Thus, unlike previous geophysical studies focused on crust/mantle velocity structure across the fault and the aim of exploring possible mineral resources in the basin, in this study we have integrated a variety of the latest seismic data and drilling holes from petroleum explorations and shallow-depth seismic reflection profiles, to recognize the Cenozoic pulsed compression deformation of the DDFZ, and to discuss its implication for earthquake potential. The results show that at least four stages of compression deformation have occurred along the DDFZ in the Cenozoic: 65 Ma, 23 Ma, 5.3 Ma, and 1.8 Ma, respectively, although the geodynamic process behind which still in dispute. The results also imply that the tectonic style of the DDFZ fits well with the occurrence of modern seismic swarms. Moderate earthquake potential (M ≤ 7.0) is suggested along the DDFZ.

  14. Bacterial translocation and enteral nutrition in humans: an outsider looks in.

    Science.gov (United States)

    Lipman, T O

    1995-01-01

    To assess the literature documenting the existence of bacterial translocation in humans, the effects of enteral nutrition on bacterial translocation in humans, and the hypothesis that enteral nutrition prevents bacterial translocation in humans. Sources included Medline search, references from review articles, and references from animal and human studies. The goal was to include all animal and human studies directly addressing questions of bacterial translocation and nutritional status or nutritional support. An attempt was made to briefly summarize methodology and findings of relevent studies. No general attempt was made to assess quality of individual studies. Bacterial translocation is a well documented phenomenon in animal models. Starvation and malnutrition of themselves do not induce bacterial translocation, but may facilitate translocation in the presence of other systemic insults. Parenteral nutrition and many forms of enteral nutrition may induce and/or facilitate bacterial translocation. Chow and certain fiber sources seem protective. Moderate direct and several lines of indirect evidence support the existence of bacterial translocation in humans. There is no direct evidence and questionable indirect evidence suggesting that enteral nutrition prevents or modifies bacterial translocation in humans. The hypothesis relating enteral nutrition and bacterial translocation in critically ill patients remains attractive, but unproven.

  15. Petrogenesis of the Baishan granite stock, Eastern Tianshan, NW China: Geodynamic setting and implications for potential mineralization

    Science.gov (United States)

    Cao, MingJian; Qin, KeZhang; Li, GuangMing; Evans, Noreen J.; McInnes, Brent I. A.; Lu, WeiWei; Deng, Gang

    2017-11-01

    low (La/Yb)N, and reduced oxidation state (≤ NNO) in the granitic stock are signatures of infertility for the Early Permian granite. This study implies high Mo mineralization potential for granitic rocks with high Sr/Y, (La/Yb)N and highly oxidized conditions.

  16. Volatile organic compounds from vegetation in southern Yunnan Province, China: Emission rates and some potential regional implications

    Science.gov (United States)

    Geron, Chris; Owen, Sue; Guenther, Alex; Greenberg, Jim; Rasmussen, Rei; Hui Bai, Jian; Li, Qing-Jun; Baker, Brad

    -emitting species in the genera Bambusa, Elaeis, Eucalyptus, Hevea, Pinus, and Populus (among others). This could result in profound changes in atmospheric chemistry in these regions, for instance, terpene emissions from H. brasiliensis could increase wet season biogenic organic aerosol burdens by approximately a factor of 2 in the Xishuangbanna region. Increases in plantation area established with high isoprene emitting species, (e.g. Bambusa spp. and Eucalyptus spp.) are also projected for China and other parts of Southeast Asia in the near future. Thus, landcover change in South Asian landscapes is usually associated with large increases in BVOC flux with the potential to alter the atmospheric chemical composition and air quality over this rapidly developing region.

  17. (+-Rutamarin as a dual inducer of both GLUT4 translocation and expression efficiently ameliorates glucose homeostasis in insulin-resistant mice.

    Directory of Open Access Journals (Sweden)

    Yu Zhang

    Full Text Available Glucose transporter 4 (GLUT4 is a principal glucose transporter in response to insulin, and impaired translocation or decreased expression of GLUT4 is believed to be one of the major pathological features of type 2 diabetes mellitus (T2DM. Therefore, induction of GLUT4 translocation or/and expression is a promising strategy for anti-T2DM drug discovery. Here we report that the natural product (+-Rutamarin (Rut functions as an efficient dual inducer on both insulin-induced GLUT4 translocation and expression. Rut-treated 3T3-L1 adipocytes exhibit efficiently enhanced insulin-induced glucose uptake, while diet-induced obese (DIO mice based assays further confirm the Rut-induced improvement of glucose homeostasis and insulin sensitivity in vivo. Subsequent investigation of Rut acting targets indicates that as a specific protein tyrosine phosphatase 1B (PTP1B inhibitor Rut induces basal GLUT4 translocation to some extent and largely enhances insulin-induced GLUT4 translocation through PI3 kinase-AKT/PKB pathway, while as an agonist of retinoid X receptor α (RXRα, Rut potently increases GLUT4 expression. Furthermore, by using molecular modeling and crystallographic approaches, the possible binding modes of Rut to these two targets have been also determined at atomic levels. All our results have thus highlighted the potential of Rut as both a valuable lead compound for anti-T2DM drug discovery and a promising chemical probe for GLUT4 associated pathways exploration.

  18. Assessments of wind-energy potential in selected sites from three geopolitical zones in Nigeria: implications for renewable/sustainable rural electrification.

    Science.gov (United States)

    Okeniyi, Joshua Olusegun; Ohunakin, Olayinka Soledayo; Okeniyi, Elizabeth Toyin

    2015-01-01

    Electricity generation in rural communities is an acute problem militating against socioeconomic well-being of the populace in these communities in developing countries, including Nigeria. In this paper, assessments of wind-energy potential in selected sites from three major geopolitical zones of Nigeria were investigated. For this, daily wind-speed data from Katsina in northern, Warri in southwestern and Calabar in southeastern Nigeria were analysed using the Gumbel and the Weibull probability distributions for assessing wind-energy potential as a renewable/sustainable solution for the country's rural-electrification problems. Results showed that the wind-speed models identified Katsina with higher wind-speed class than both Warri and Calabar that were otherwise identified as low wind-speed sites. However, econometrics of electricity power simulation at different hub heights of low wind-speed turbine systems showed that the cost of electric-power generation in the three study sites was converging to affordable cost per kWh of electric energy from the wind resource at each site. These power simulations identified cost/kWh of electricity generation at Kaduna as €0.0507, at Warri as €0.0774, and at Calabar as €0.0819. These bare positive implications on renewable/sustainable rural electrification in the study sites even as requisite options for promoting utilization of this viable wind-resource energy in the remote communities in the environs of the study sites were suggested.

  19. Anti-rancidity effect of essential oils, application in the lipid stability of cooked turkey meat patties and potential implications for health.

    Science.gov (United States)

    Loizzo, Monica R; Tundis, Rosa; Menichini, Francesco; Duthie, Garry

    2015-02-01

    Twenty-three commercial essential oils were tested for their anti-rancidity effect and potential implications to prolong the induction time of corn oil and extend the shelf life of cooked turkey patties. Moreover, the potential health benefit was investigated through DPPH, ABTS, β-carotene bleaching, FRAP, and α-amylase inhibitory assays. Essential oils' composition was investigated by GC-MS. Cumin, thyme, clove, and cinnamon oils improved oxidative stability and increased the induction time of the corn oil 1.5-3 fold. Clove and cinnamon oils were particularly effective in delaying lipid oxidation of cooked turkey patties (time of induction 11.04 and 9.43 h) compared with the plain burger (5.04 h). Both oils are also characterized by a potent radical scavenging activity in ABTS test (IC(50) values of 1.43 and 2.05 μg/ml for cinnamon and clove, respectively). In the α-amylase inhibitory assay, cumin and grape fruits were the most potent with IC(50) values of 21.88 and 23.95 μg/ml, respectively.

  20. Assessments of Wind-Energy Potential in Selected Sites from Three Geopolitical Zones in Nigeria: Implications for Renewable/Sustainable Rural Electrification

    Directory of Open Access Journals (Sweden)

    Joshua Olusegun Okeniyi

    2015-01-01

    Full Text Available Electricity generation in rural communities is an acute problem militating against socioeconomic well-being of the populace in these communities in developing countries, including Nigeria. In this paper, assessments of wind-energy potential in selected sites from three major geopolitical zones of Nigeria were investigated. For this, daily wind-speed data from Katsina in northern, Warri in southwestern and Calabar in southeastern Nigeria were analysed using the Gumbel and the Weibull probability distributions for assessing wind-energy potential as a renewable/sustainable solution for the country’s rural-electrification problems. Results showed that the wind-speed models identified Katsina with higher wind-speed class than both Warri and Calabar that were otherwise identified as low wind-speed sites. However, econometrics of electricity power simulation at different hub heights of low wind-speed turbine systems showed that the cost of electric-power generation in the three study sites was converging to affordable cost per kWh of electric energy from the wind resource at each site. These power simulations identified cost/kWh of electricity generation at Kaduna as €0.0507, at Warri as €0.0774, and at Calabar as €0.0819. These bare positive implications on renewable/sustainable rural electrification in the study sites even as requisite options for promoting utilization of this viable wind-resource energy in the remote communities in the environs of the study sites were suggested.