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Sample records for primary human natural

  1. Views of Nature and the Human-Nature Relations: An Analysis of the Visual Syntax of Pictures about the Environment in Greek Primary School Textbooks—Diachronic Considerations

    NASA Astrophysics Data System (ADS)

    Lemoni, Rea; Lefkaditou, Ageliki; Stamou, Anastasia G.; Schizas, Dimitrios; Stamou, George P.

    2013-02-01

    This paper explores the function of the visual syntax of images in Greek primary school textbooks. By using a model for the formal analysis of the visual material, which will allow us to disclose the mechanisms through which meanings are manifested, our aim is to investigate the discursive transition relating to the view of nature and the human-nature relationship between two series of natural science textbooks. The model is applied to a total of 635 pictures; 434 coming from the old series of textbooks introduced in the early 1980s and 201 from the new introduced in 2006. The results show that a) no differences in the codes of the visual representation of nature or human-nature relationship were recorded between the two series of textbooks, b) the environmental rhetoric mediated by the pictorial material of the textbooks appears closer to its lay counterpart than to scientific rhetoric, c) both series of textbooks favor a viewer-picture relation which diverges from the epistemological (subject/object) ideas of the romantic worldview and comes closer to the baroque one that depicts the world as non-linear and disconnected, while gives more freedom to the viewer to proceed to subjective interpretations. Thus, we assert that the baroque approach adopted by both series of textbooks does not aim at the initiation of students to the highly conventionalized ways of expression, and ultimately to the formalized and scientific rhetoric. On the contrary, within a constructionist context, the textbooks' visual mode allows students to equally share power with a quite familiar world.

  2. Views of Nature and the Human-Nature Relations: An Analysis of the Visual Syntax of Pictures about the Environment in Greek Primary School Textbooks--Diachronic Considerations

    ERIC Educational Resources Information Center

    Lemoni, Rea; Lefkaditou, Ageliki; Stamou, Anastasia G.; Schizas, Dimitrios; Stamou, George P.

    2013-01-01

    This paper explores the function of the visual syntax of images in Greek primary school textbooks. By using a model for the formal analysis of the visual material, which will allow us to disclose the mechanisms through which meanings are manifested, our aim is to investigate the discursive transition relating to the view of nature and the…

  3. Human nature and enhancement.

    PubMed

    Buchanan, Allen

    2009-03-01

    Appeals to the idea of human nature are frequent in the voluminous literature on the ethics of enhancing human beings through biotechnology. Two chief concerns about the impact of enhancements on human nature have been voiced. The first is that enhancement may alter or destroy human nature. The second is that if enhancement alters or destroys human nature, this will undercut our ability to ascertain the good because, for us, the good is determined by our nature. The first concern assumes that altering or destroying human nature is in itself a bad thing. The second concern assumes that human nature provides a standard without which we cannot make coherent, defensible judgments about what is good. I will argue (1) that there is nothing wrong, per se, with altering or destroying human nature, because, on a plausible understanding of what human nature is, it contains bad as well as good characteristics and there is no reason to believe that eliminating some of the bad would so imperil the good as to make the elimination of the bad impermissible, and (2) that altering or destroying human nature need not result in the loss of our ability to make judgments about the good, because we possess a conception of the good by which we can and do evaluate human nature. I will argue that appeals to human nature tend to obscure rather than illuminate the debate over the ethics of enhancement and can be eliminated in favor of more cogent considerations.

  4. Natural mannosylation of HIV-1 gp120 imposes no immunoregulatory effects in primary human plasmacytoid dendritic cells.

    PubMed

    Søndergaard, Jonas Nørskov; Vinner, Lasse; Brix, Susanne

    2014-06-01

    Plasmacytoid dendritic cells (pDCs) play a vital role in activation of anti-HIV-1 immunity, and suppression of pDCs might mitigate immune responses against HIV-1. HIV-1 gp120 high-mannose has been attributed immunosuppressive roles in human myeloid DCs, but no receptors for high-mannose have so far been reported on human pDCs. Here we show that upon activation with HIV-1 or by a synthetic compound triggering the same receptor in human pDCs as single-stranded RNA, human pDCs upregulate the mannose receptor (MR, CD206). To examine the functional outcome of this upregulation, inactivated intact or viable HIV-1 particles with various degrees of mannosylation were cultured with pDCs. Activation of pDCs was determined by assaying secretion of IFN-alpha, viability, and upregulation of several pDC-activation markers: CD40, CD86, HLA-DR, CCR7, and PD-L1. The level of activation negatively correlated with degree of mannosylation, however, subsequent reduction in the original mannosylation level had no effect on the pDC phenotype. Furthermore, two of the infectious HIV-1 strains induced profound necrosis in pDCs, also in a mannose-independent manner. We therefore conclude that natural mannosylation of HIV-1 is not involved in HIV-1-mediated immune suppression of pDCs.

  5. Positive Selection in Bone Morphogenetic Protein 15 Targets a Natural Mutation Associated with Primary Ovarian Insufficiency in Human

    PubMed Central

    Meslin, Camille; Monestier, Olivier; Di Pasquale, Elisa; Pascal, Géraldine; Persani, Luca; Fabre, Stéphane

    2013-01-01

    Bone Morphogenetic Protein 15 (BMP15) is a TGFβ-like oocyte-derived growth factor involved in ovarian folliculogenesis as a critical regulator of many granulosa cell processes. Alterations of the BMP15 gene have been found associated with different ovarian phenotypic effects depending on the species, from sterility to increased prolificacy in sheep, slight subfertility in mouse or associated with primary ovarian insufficiency (POI) in women. To investigate the evolving role of BMP15, a phylogenetic analysis of this particular TGFβ family member was performed. A maximum likelihood phylogenetic tree of several TGFβ/BMP family members expressed by the ovary showed that BMP15 has a very strong divergence and a rapid evolution compared to others. Moreover, among 24 mammalian species, we detected signals of positive selection in the hominidae clade corresponding to F146, L189 and Y235 residues in human BMP15. The biological importance of these residues was tested functionally after site directed-mutagenesis in a COV434 cells luciferase assay. By replacing the positively selected amino acid either by alanine or the most represented residue in other studied species, only L189A, Y235A and Y235C mutants showed a significant increase of BMP15 signaling when compared to wild type. Additionally, the Y235C mutant was more potent than wild type in inhibiting progesterone secretion of ovine granulosa cells in primary culture. Interestingly, the Y235C mutation was previously identified in association with POI in women. In conclusion, this study evidences that the BMP15 gene has evolved faster than other members of the TGFß family and was submitted to a positive selection pressure in the hominidae clade. Some residues under positive selection are of great importance for the normal function of the protein and thus for female fertility. Y235 represents a critical residue in the determination of BMP15 biological activity, thus indirectly confirming its role in the onset of POI in

  6. Positive selection in bone morphogenetic protein 15 targets a natural mutation associated with primary ovarian insufficiency in human.

    PubMed

    Auclair, Sylvain; Rossetti, Raffaella; Meslin, Camille; Monestier, Olivier; Di Pasquale, Elisa; Pascal, Géraldine; Persani, Luca; Fabre, Stéphane

    2013-01-01

    Bone Morphogenetic Protein 15 (BMP15) is a TGFβ-like oocyte-derived growth factor involved in ovarian folliculogenesis as a critical regulator of many granulosa cell processes. Alterations of the BMP15 gene have been found associated with different ovarian phenotypic effects depending on the species, from sterility to increased prolificacy in sheep, slight subfertility in mouse or associated with primary ovarian insufficiency (POI) in women. To investigate the evolving role of BMP15, a phylogenetic analysis of this particular TGFβ family member was performed. A maximum likelihood phylogenetic tree of several TGFβ/BMP family members expressed by the ovary showed that BMP15 has a very strong divergence and a rapid evolution compared to others. Moreover, among 24 mammalian species, we detected signals of positive selection in the hominidae clade corresponding to F146, L189 and Y235 residues in human BMP15. The biological importance of these residues was tested functionally after site directed-mutagenesis in a COV434 cells luciferase assay. By replacing the positively selected amino acid either by alanine or the most represented residue in other studied species, only L189A, Y235A and Y235C mutants showed a significant increase of BMP15 signaling when compared to wild type. Additionally, the Y235C mutant was more potent than wild type in inhibiting progesterone secretion of ovine granulosa cells in primary culture. Interestingly, the Y235C mutation was previously identified in association with POI in women. In conclusion, this study evidences that the BMP15 gene has evolved faster than other members of the TGFß family and was submitted to a positive selection pressure in the hominidae clade. Some residues under positive selection are of great importance for the normal function of the protein and thus for female fertility. Y235 represents a critical residue in the determination of BMP15 biological activity, thus indirectly confirming its role in the onset of POI in

  7. Primary case of human pneumonic plague occurring in a Himalayan marmot natural focus area Gansu Province, China.

    PubMed

    Ge, Pengfei; Xi, Jinxiao; Ding, Jun; Jin, Fachang; Zhang, Hong; Guo, Limin; Zhang, Jie; Li, Junlin; Gan, Zhiqiang; Wu, Bin; Liang, Junrong; Wang, Xin; Wang, Xinhua

    2015-04-01

    A case of primary pneumonic plague (PPP) caused by Yersinia pestis is reported. This case occurred in the largest plague area in China. The patient died after contact with a dog that had captured an infected marmot. Three of 151 contacts were shown to be positive for antibody against F1 antigen by indirect hemagglutination assay, but none had clinical symptoms. There was no secondary case.

  8. Primary case of human pneumonic plague occurring in a Himalayan marmot natural focus area Gansu Province, China.

    PubMed

    Ge, Pengfei; Xi, Jinxiao; Ding, Jun; Jin, Fachang; Zhang, Hong; Guo, Limin; Zhang, Jie; Li, Junlin; Gan, Zhiqiang; Wu, Bin; Liang, Junrong; Wang, Xin; Wang, Xinhua

    2015-04-01

    A case of primary pneumonic plague (PPP) caused by Yersinia pestis is reported. This case occurred in the largest plague area in China. The patient died after contact with a dog that had captured an infected marmot. Three of 151 contacts were shown to be positive for antibody against F1 antigen by indirect hemagglutination assay, but none had clinical symptoms. There was no secondary case. PMID:25555623

  9. Natural and socioeconomic determinants of the embodied human appropriation of net primary production and its relation to other resource use indicators

    PubMed Central

    Haberl, Helmut; Steinberger, Julia K.; Plutzar, Christoph; Erb, Karl-Heinz; Gaube, Veronika; Gingrich, Simone; Krausmann, Fridolin

    2012-01-01

    Indicators of resource use such as material and energy flow accounts, emission data and the ecological footprint inform societies about their performance by evaluating resource use efficiency and the effectiveness of sustainability policies. The human appropriation of net primary production (HANPP) is an indicator of land-use intensity on each nation's territory used in research as well as in environmental reports. ‘Embodied HANPP’ (eHANPP) measures the HANPP anywhere on earth resulting from a nation's domestic biomass consumption. The objectives of this article are (i) to study the relation between eHANPP and other resource use indicators and (ii) to analyse socioeconomic and natural determinants of global eHANPP patterns in the year 2000. We discuss a statistical analysis of >140 countries aiming to better understand these relationships. We found that indicators of material and energy throughput, fossil-energy related CO2 emissions as well as the ecological footprint are highly correlated with each other as well as with GDP, while eHANPP is neither correlated with other resource use indicators nor with GDP, despite a strong correlation between final biomass consumption and GDP. This can be explained by improvements in agricultural efficiency associated with GDP growth. Only about half of the variation in eHANPP can be explained by differences in national land-use systems, suggesting a considerable influence of trade on eHANPP patterns. eHANPP related with biomass trade can largely be explained by differences in natural endowment, in particular the availability of productive area. We conclude that eHANPP can deliver important complimentary information to indicators that primarily monitor socioeconomic metabolism. PMID:23470886

  10. Perturbation of the natural killer cell compartment during primary human immunodeficiency virus 1 infection primarily involving the CD56bright subset

    PubMed Central

    Mantegani, Paola; Tambussi, Giuseppe; Galli, Laura; Din, Chiara Tassan; Lazzarin, Adriano; Fortis, Claudio

    2010-01-01

    We investigated the distribution of natural killer (NK) cell subsets, their activating and inhibitory receptors, and their cytolytic potential, in primary human immunodeficiency virus (HIV)-infected (PHI) individuals at baseline and during 1 year of follow-up with or without antiretroviral therapy, and compared the results with those obtained in treatment-naïve, chronically HIV-infected (CHI) individuals, and HIV-seronegative (HN) healthy individuals. The proportion of the CD56dim and CD56bright subsets decreased with disease progression, whereas that of the CD56− CD16+ subset increased. In the CD56dim subset, the proportion of cells with natural cytotoxicity receptors (NCRs) decreased with disease progression, and their cytolytic potential was reduced. Conversely, the CD56bright subset was characterized by a high proportion of NCR-positive, killer cell immunoglobulin-like receptor (KIR)-positive NKG2A+ cells in both CHI and PHI individuals, which was associated with an increase in their cytolytic potential. During the 1 year of follow-up, the PHI individuals with high viraemia levels and low CD4+ T-cell counts who received highly active antiretroviral therapy (HAART) had a similar proportion of NK subsets to CHI individuals, while patients with low viraemia levels and high CD4+ T-cell counts who remained untreated had values similar to those of the HN individuals. Our results indicate a marked perturbation of the NK cell compartment during HIV-1 infection that is multifaceted, starts early and is progressive, primarily involves the CD56bright subset, and is partially corrected by effective HAART. PMID:19824914

  11. Human Nature and the Nature of Science.

    ERIC Educational Resources Information Center

    Stevens, Richard J.

    1988-01-01

    Examines the procedural and philosophical perspectives taken by science in examining human characteristics. Discusses the different levels of accuracy of various scientific fields. Encourages discussion of what biological and behavioral sciences can and cannot reveal about complex human nature. Considers some characteristics of quality science…

  12. Rx: human nature.

    PubMed

    Ashraf, Nava

    2013-04-01

    Why doesn't a woman who continues to have unwanted pregnancies avail herself of the free contraception at a nearby clinic? What keeps people from using free chlorine tablets to purify their drinking water? Behavioral economics has shown us that we don't always act in our own best interests. This is as true of health decisions as it is of economic ones. An array of biases, limits on cognition, and motivations leads people all over the world to make suboptimal health choices. The good news is that human nature can also be a source of solutions. Through her studies in Zambia exploring the reasons for unwanted pregnancies and the incentives that would motivate hairdressers to sell condoms to their clients, the author has found that designing effective health programs requires more than providing accessible, affordable care; it requires understanding what makes both end users and providers tick. By understanding the cognitive processes underlying our choices and applying the tools of behavioral economics--such as commitment devices, material incentives, defaults, and tools that tap our desire to help others--it's possible to design simple, inexpensive programs that encourage good health decisions and long-term behavior change.

  13. Human Immunodeficiency Virus (HIV) Primary Infection

    MedlinePlus

    ... rashes clinical tools newsletter | contact Share | Human Immunodeficiency Virus (HIV) Primary Infection Information for adults A A ... weeks following exposure to HIV (the human immunodeficiency virus). Chronic infection with this virus can cause AIDS ( ...

  14. Infection of macrophages and dendritic cells with primary R5-tropic human immunodeficiency virus type 1 inhibited by natural polyreactive anti-CCR5 antibodies purified from cervicovaginal secretions.

    PubMed

    Eslahpazir, Jobin; Jenabian, Mohammad-Ali; Bouhlal, Hicham; Hocini, Hakim; Carbonneil, Cédric; Grésenguet, Gérard; Mbopi Kéou, François-Xavier; LeGoff, Jérôme; Saïdi, Héla; Requena, Mary; Nasreddine, Nadine; de Dieu Longo, Jean; Kaveri, Srinivas V; Bélec, Laurent

    2008-05-01

    Heterosexual contact is the primary mode of human immunodeficiency virus (HIV) type 1 (HIV-1) transmission worldwide. The chemokine receptor CCR5 is the major coreceptor that is associated with the mucosal transmission of R5-tropic HIV-1 during sexual intercourse. The CCR5 molecule is thus a target for antibody-based therapeutic strategies aimed at blocking HIV-1 entry into cells. We have previously demonstrated that polyreactive natural antibodies (NAbs) from therapeutic preparations of immunoglobulin G and from human breast milk contain NAbs directed against CCR5. Such antibodies inhibit the infection of human macrophages and T lymphocytes by R5-tropic isolates of HIV in vitro. In the present study, we demonstrate that human immunoglobulins from the cervicovaginal secretions of HIV-seronegative or HIV-seropositive women contain NAbs directed against the HIV-1 coreceptor CCR5. Natural affinity-purified anti-CCR5 antibodies bound to CCR5 expressed on macrophages and dendritic cells and further inhibited the infection of macrophages and dendritic cells with primary and laboratory-adapted R5-tropic HIV but not with X4-tropic HIV. Natural anti-CCR5 antibodies moderately inhibited R5-tropic HIV transfer from monocyte-derived dendritic cells to autologous T cells. Our results suggest that mucosal anti-CCR5 antibodies from healthy immunocompetent donors may hamper the penetration of HIV and may be suitable for use in the development of novel passive immunotherapy regimens in specific clinical settings of HIV infection. PMID:18353923

  15. Images of nature in greek primary school textbooks

    NASA Astrophysics Data System (ADS)

    Korfiatis, Kostas J.; Stamou, Anastasia G.; Paraskevopoulos, Stephanos

    2004-01-01

    In this article, the environmental content of the textbooks used for the teaching of natural sciences in Greek primary schools was examined. Specifically, by employing the method of content analysis, both representational (metaphors, depictions, values, etc.) and cognitive (ecological concepts) elements, building images of nature, and shaping our opinion and attitudes towards the environment were examined. The results of the analysis revealed that a coherent whole was produced, where nature was in a condition of oscillating balance, with everything being connected with something else, and humans having absolute control over a nature whose only value was its usefulness as a resource for food and raw material. However, seen qualitatively, the edifice included many contradictory elements and inconsistencies, which, having evolved out of a specific context, might spread confusion and deprive pupils from critical thinking. On the other hand, the image of nature dominating disagreed with both a standpoint advocating an equal relationship between humans and nature and with that supporting a relationship of stewardship and care for nature, while it failed to provide students with proper and sufficient environmental knowledge.

  16. Young Scientists Explore the Human Body. Book 11 Primary Level.

    ERIC Educational Resources Information Center

    Penn, Linda

    Designed to present interesting facts about science and to heighten the curiosity of primary age students, this book contains activities about the natural world and numerous black and white illustrations. The activities specifically focus on the human body and encourage a positive self-concept. The theme of the first section is air--the breath of…

  17. The multisensory function of the human primary visual cortex.

    PubMed

    Murray, Micah M; Thelen, Antonia; Thut, Gregor; Romei, Vincenzo; Martuzzi, Roberto; Matusz, Pawel J

    2016-03-01

    It has been nearly 10 years since Ghazanfar and Schroeder (2006) proposed that the neocortex is essentially multisensory in nature. However, it is only recently that sufficient and hard evidence that supports this proposal has accrued. We review evidence that activity within the human primary visual cortex plays an active role in multisensory processes and directly impacts behavioural outcome. This evidence emerges from a full pallet of human brain imaging and brain mapping methods with which multisensory processes are quantitatively assessed by taking advantage of particular strengths of each technique as well as advances in signal analyses. Several general conclusions about multisensory processes in primary visual cortex of humans are supported relatively solidly. First, haemodynamic methods (fMRI/PET) show that there is both convergence and integration occurring within primary visual cortex. Second, primary visual cortex is involved in multisensory processes during early post-stimulus stages (as revealed by EEG/ERP/ERFs as well as TMS). Third, multisensory effects in primary visual cortex directly impact behaviour and perception, as revealed by correlational (EEG/ERPs/ERFs) as well as more causal measures (TMS/tACS). While the provocative claim of Ghazanfar and Schroeder (2006) that the whole of neocortex is multisensory in function has yet to be demonstrated, this can now be considered established in the case of the human primary visual cortex. PMID:26275965

  18. [Primary human demodicosis. A disease sui generis].

    PubMed

    Hsu, C-K; Zink, A; Wei, K-J; Dzika, E; Plewig, G; Chen, W

    2015-03-01

    Human Demodex mites (Demodex folliculorum and Demodex brevis) are unique in that they are an obligate human ectoparasite that can inhabit the pilosebaceous unit lifelong without causing obvious host immune response in most cases. The mode of symbiosis between humans and human Demodex mites is unclear, while the pathogenicity of human Demodex mites in many inflammatory skin diseases is now better understood. Primary human demodicosis is a skin disease sui generis not associated with local or systemic immunosuppression. Diagnosis is often underestimated and differentiation from folliculitis, papulopustular rosacea and perioral dermatitis is not always straightforward. Dependent on the morphology and degree of inflammation, the clinical manifestations can be classified into spinulate, papulopustular, nodulocystic, crustic and fulminant demodicosis. Therapy success can be achieved only with acaricides/arachidicides. The effective doses, optimal regimen and antimicrobial resistance remain to be determined. PMID:25744530

  19. Regulations against the human nature

    NASA Astrophysics Data System (ADS)

    Elizondo-Garza, Fernando J.

    2001-05-01

    The discussion around the concept of the addiction to noise has evidenced the importance of noise for the human being and explains why in some cases the regulations fail to control the noise in cities. In this presentation the different uses, consciously or unconsciously, of the noise will be analyzed, uses that go from habits to maybe addictions. Also discussed are the implications of establishing regulations against the human nature as well as the importance of education to manage the noise and design acoustically instead of trying to ban the noise in some social circumstances.

  20. Treatment of primary Sjögren's syndrome with low-dose natural human interferon-alpha administered by the oral mucosal route: a phase II clinical trial. IFN Protocol Study Group.

    PubMed

    Ship, J A; Fox, P C; Michalek, J E; Cummins, M J; Richards, A B

    1999-08-01

    The purpose of this investigation was to examine the safety and efficacy of four dosages of natural human interferon-alpha (nHuIFN-alpha) delivered over a 12-week period orally in lozenges (150 IU and 450 IU, once [QD] or three times [TID] daily) compared to placebo in subjects with primary Sjögren's syndrome. This randomized, double-blinded clinical trial demonstrated that nHuIFN-alpha at a dose of 150 IU administered TID by oral lozenge significantly improved stimulated whole saliva output compared to placebo after 12 weeks of treatment. The 150 IU TID dose also was suggestive of benefit for 5 of 7 subjective measures of oral and ocular comfort. IFN lozenges demonstrated a good safety profile, with no serious adverse events found in any treatment group. There were no significant differences between the placebo and the four doses of IFN for adverse events by total number, organ system, severity, dropouts, and number judged to be related to treatment. In conclusion, these results demonstrated that the use of 150 IU IFN lozenges TID for 12 weeks in subjects with primary Sjögren's syndrome improved salivary output and decreased complaints of xerostomia without causing significant adverse medical events. PMID:10476942

  1. Natural Evolution and Human Consciousness

    PubMed Central

    Holmgren, Jan

    2014-01-01

    A visual conscious experience is my empirical basis. All that we know comes to us through conscious experiences. Thanks to natural evolution, we have nearly direct perception, and can largely trust the information we attain. There is full integration, with no gaps, of organisms in the continuous world. Human conscious experiences, on the other hand, are discrete. Consciousness has certain limits for its resolution. This is illustrated by the so-called light-cone, with consequences for foundations in physics. Traditional universals are replaced by feels and distributions. Conscious experiences can be ordered within a framework of conceptual spaces. Triple Aspect Monism (TAM) can represent the dynamics of conscious systems. However, to fully represent the creative power of human consciousness, an all-inclusive view is suggested: Multi Aspect Monism (MAM). PMID:24891802

  2. The Nature of Primary Teaching: Body, Time, Space, and Relationships

    ERIC Educational Resources Information Center

    Brown, Pamela U.; Castle, Kathryn; Rogers, Karen M.; Feuerhelm, Caren; Chimblo, Sarah

    2007-01-01

    The purpose of this qualitative study was to examine the lived experiences of a primary teacher in order to illuminate the nature of primary teaching. Using qualitative methods, five university researchers spent nine months during the course of one school year with a second grade teacher and her students. This inquiry took a multiple lens…

  3. The Nature of Primary Students' Conversation in Technology Education

    ERIC Educational Resources Information Center

    Fox-Turnbull, Wendy H.

    2016-01-01

    Classroom conversations are core to establishing successful learning for students. This research explores the nature of conversation in technology education in the primary classroom and the implications for teaching and learning. Over a year, two units of work in technology were taught in two primary classrooms. Most data was gathered in Round 2…

  4. Images of Nature in Greek Primary School Textbooks

    ERIC Educational Resources Information Center

    Korfiatis, Kostas J.; Stamou, Anastasia G.; Paraskevopoulos, Stephanos

    2004-01-01

    In this article, the environmental content of the textbooks used for the teaching of natural sciences in Greek primary schools was examined. Specifically, by employing the method of content analysis, both representational (metaphors, depictions, values, etc.) and cognitive ecological concepts) elements, building images of nature, and shaping our…

  5. Nature, Human Nature, and Solutions to Problems.

    ERIC Educational Resources Information Center

    Pedrini, D. T.; Pedrini, B. C.

    This paper promotes an undergraduate course that would discuss the great ideas of Plato, St. Paul, Karl Marx, Sigmund Freud, Jean Paul Sartre, B. F. Skinner, and Konrad Lorenz. This course would help students understand human values and behaviors while focusing on historical, world, and national problems. Tentative solutions would then be…

  6. Turkish Primary Students' Conceptions about the Particulate Nature of Matter

    ERIC Educational Resources Information Center

    Ozmen, Haluk

    2011-01-01

    This study was conducted to determine 4th, 5th, and 6th grade primary students' conceptions about the particulate nature of matter in daily-life events. Five questions were asked of students and interviews were used to collect data. The interviews were conducted with 12 students, four students from each grade, after they finished the formal…

  7. Immortalization of primary human smooth muscle cells.

    PubMed Central

    Perez-Reyes, N; Halbert, C L; Smith, P P; Benditt, E P; McDougall, J K

    1992-01-01

    Primary human aortic and myometrial smooth muscle cells (SMCs) were immortalized using an amphotropic recombinant retroviral construct containing the E6 and E7 open reading frames (ORFs) of human papillomavirus type 16. The SMCs expressing the E6/E7 ORFs have considerably elevated growth rates when compared with nonimmortalized control cells and show no signs of senescence with long-term passage. The first SMC line derived in this study has been maintained in continuous tissue culture for greater than 1 year (greater than 180 population doublings). The immortalized SMCs have decreased cell size and decreased content of muscle-specific alpha-actin filaments as determined by indirect immunofluorescence. Southern blot analysis has demonstrated the stable integration of the E6/E7 ORFs in the retrovirally infected cells, and radioimmunoprecipitation has confirmed the continued expression of the E6 and E7 genes. Cytogenetic studies of the SMC lines have revealed essentially diploid populations except for the myometrial clonal line, which became aneuploid at late passage (greater than 125 doublings). These cell lines were not tumorigenic in nude mice. Images PMID:1311088

  8. Humans and the Natural Environment.

    ERIC Educational Resources Information Center

    Intercom, 1982

    1982-01-01

    Suggests activities focusing on the relationship between meeting human survival needs and the environment for use with junior high students in geography courses. Students learn about human survival needs, the earth's systems, and the sun's roles as an energy producer. (RM)

  9. Global patterns in human consumption of net primary production

    NASA Astrophysics Data System (ADS)

    Imhoff, Marc L.; Bounoua, Lahouari; Ricketts, Taylor; Loucks, Colby; Harriss, Robert; Lawrence, William T.

    2004-06-01

    The human population and its consumption profoundly affect the Earth's ecosystems. A particularly compelling measure of humanity's cumulative impact is the fraction of the planet's net primary production that we appropriate for our own use. Net primary production-the net amount of solar energy converted to plant organic matter through photosynthesis-can be measured in units of elemental carbon and represents the primary food energy source for the world's ecosystems. Human appropriation of net primary production, apart from leaving less for other species to use, alters the composition of the atmosphere, levels of biodiversity, energy flows within food webs and the provision of important ecosystem services. Here we present a global map showing the amount of net primary production required by humans and compare it to the total amount generated on the landscape. We then derive a spatial balance sheet of net primary production `supply' and `demand' for the world. We show that human appropriation of net primary production varies spatially from almost zero to many times the local primary production. These analyses reveal the uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations depend on net primary production `imports' and suggest policy options for slowing future growth of human appropriation of net primary production.

  10. Global patterns in human consumption of net primary production.

    PubMed

    Imhoff, Marc L; Bounoua, Lahouari; Ricketts, Taylor; Loucks, Colby; Harriss, Robert; Lawrence, William T

    2004-06-24

    The human population and its consumption profoundly affect the Earth's ecosystems. A particularly compelling measure of humanity's cumulative impact is the fraction of the planet's net primary production that we appropriate for our own use. Net primary production--the net amount of solar energy converted to plant organic matter through photosynthesis--can be measured in units of elemental carbon and represents the primary food energy source for the world's ecosystems. Human appropriation of net primary production, apart from leaving less for other species to use, alters the composition of the atmosphere, levels of biodiversity, energy flows within food webs and the provision of important ecosystem services. Here we present a global map showing the amount of net primary production required by humans and compare it to the total amount generated on the landscape. We then derive a spatial balance sheet of net primary production 'supply' and 'demand' for the world. We show that human appropriation of net primary production varies spatially from almost zero to many times the local primary production. These analyses reveal the uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations depend on net primary production 'imports' and suggest policy options for slowing future growth of human appropriation of net primary production.

  11. Global Patterns in Human Consumption of Net Primary Production

    NASA Technical Reports Server (NTRS)

    Imhoff, Marc L.; Bounoua, Lahouari; Ricketts, Taylor; Loucks, Colby; Harriss, Robert; Lawrence William T.

    2004-01-01

    The human population and its consumption profoundly affect the Earth's ecosystems. A particularly compelling measure of humanity's cumulative impact is the fraction of the planet's net primary production that we appropriate for our Net primary production-the net amount of solar energy converted to plant organic matter through photosynthesis-can be measured in units of elemental carbon and represents the primary food energy source for the world's ecosystems. Human appropriation of net primary production, apart from leaving less for other species to use, alters the composition of the atmosphere, levels of biodiversity, flows within food webs and the provision of important primary production required by humans and compare it to the total amount generated on the landscape. We then derive a spatial ba!mce sheet of net primary production supply and demand for the world. We show that human appropriation of net primary production varies spatially from almost zero to many times the local primary production. These analyses reveal the uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations depend on net primary production "imports" and suggest policy options for slowing future growth of human appropriation of net primary production.

  12. Primary Bioassay of Human Myeloma Stem Cells

    PubMed Central

    Hamburger, Anne; Salmon, Sydney E.

    1977-01-01

    The ability to clone primary tumors in soft agar has proven useful in the study of the kinetics and biological properties of tumor stem cells. We report the development of an in vitro assay which permits formation of colonies of human monoclonal plasma cells in soft agar. Colony growth has been observed from bone marrow aspirates from 75% of the 70 patients with multiple myeloma or related monoclonal disorders studied. Growth was induced with either 0.02 ml of human type O erythrocytes or 0.25 ml of medium conditioned by the adherent spleen cells of mineral oil-primed BALB/c mice. 5-500 colonies appeared after 2-3 wk in culture yielding a plating efficiency of 0.001-0.1%. The number of myeloma colonies was proportional to the number of cells plated between concentrations of 105-106 and back-extrapolated through zero, suggesting that colonies were clones derived from single myeloma stem cells. Morphological, histochemical, and functional criteria showed the colonies to consist of immature plasmablasts and mature plasma cells. 60-80% of cells picked from colonies contained intracytoplasmic monoclonal immunoglobulin. Colony growth was most easily achieved from the bone marrow cells of untreated patients or those in relapse. Only 50% of bone marrow samples from patients in remission were successfully cultured. Tritiated thymidine suicide studies provided evidence that for most myeloma patients, a very high proportion of myeloma colony-forming cells was actively in transit through the cell cycle. Velocity sedimentation at 1 g showed myeloma stem cells sedimented in a broad band with a peak at 13 mm/h. Antibody to granulocyte colony-stimulating factor did not reduce the number or size of the colonies. Increased numbers of myeloma colonies were seen when the marrow was depleted of colony-stimulating factor elaborating adherent cells before plating. This bioassay should prove useful in studying the in vitro biological behavior of certain bone marrow-derived (B

  13. The nature of human altruism.

    PubMed

    Fehr, Ernst; Fischbacher, Urs

    2003-10-23

    Some of the most fundamental questions concerning our evolutionary origins, our social relations, and the organization of society are centred around issues of altruism and selfishness. Experimental evidence indicates that human altruism is a powerful force and is unique in the animal world. However, there is much individual heterogeneity and the interaction between altruists and selfish individuals is vital to human cooperation. Depending on the environment, a minority of altruists can force a majority of selfish individuals to cooperate or, conversely, a few egoists can induce a large number of altruists to defect. Current gene-based evolutionary theories cannot explain important patterns of human altruism, pointing towards the importance of both theories of cultural evolution as well as gene-culture co-evolution.

  14. Planning, Decisions, and Human Nature.

    ERIC Educational Resources Information Center

    Keller, George

    1998-01-01

    Brings the perspectives of five individuals (Sigmund Freud, Karl Marx, Charles Darwin, Johann von Herder, James Madison) to the question of why humans behave as they do when faced with the need for decision making and change in higher education. Argues that effecting change is easier if leaders attend to the concerns and fears of those affected by…

  15. The Nonscience of Human Nature

    ERIC Educational Resources Information Center

    Gould, Stephen Jay

    1974-01-01

    Possible reasons for the current resurgence of biological determinism are discussed. Deterministic arguments are classified as being based on the general human species or based on presumed differences among racial groups. The first type of argument is presented and some alternate interpretations proposed. (LS)

  16. Youth who sexual offended: primary human goods and offense pathways.

    PubMed

    Chu, Chi Meng; Koh, Li Lian; Zeng, Gerald; Teoh, Jennifer

    2015-04-01

    There has been an increased focus on understanding youth sexual offending in recent years, but there has been limited empirical research on the causes, pathways, and treatment of youth who have sexually offended-especially within a non-Western context. The Good Lives and Self-Regulation Models have often been used to understand and rehabilitate adult sexual offenders, but (unfortunately) there is scant research on youth who sexually offended using these models. The present study aims to describe the different primary goods that are associated with youth sexual offending behaviors in an Asian context. In addition, the study sought to explore whether the age of victim (child vs. nonchild) and nature of sexual offense (penetrative vs. nonpenetrative) influenced the youth's engagement in offense pathways. The results suggest that pleasure, relatedness, and inner peace were the primary human goods that were most sought after by a sample of 168 youth who sexually offended in Singapore. In addition, offender classification (in relation to the age of victim and nature of sexual offense) influenced the pathways to sexual offending. Therefore, these findings have important clinical implications for assessment, management, and intervention planning for youth who sexually offended. PMID:24048701

  17. Youth who sexual offended: primary human goods and offense pathways.

    PubMed

    Chu, Chi Meng; Koh, Li Lian; Zeng, Gerald; Teoh, Jennifer

    2015-04-01

    There has been an increased focus on understanding youth sexual offending in recent years, but there has been limited empirical research on the causes, pathways, and treatment of youth who have sexually offended-especially within a non-Western context. The Good Lives and Self-Regulation Models have often been used to understand and rehabilitate adult sexual offenders, but (unfortunately) there is scant research on youth who sexually offended using these models. The present study aims to describe the different primary goods that are associated with youth sexual offending behaviors in an Asian context. In addition, the study sought to explore whether the age of victim (child vs. nonchild) and nature of sexual offense (penetrative vs. nonpenetrative) influenced the youth's engagement in offense pathways. The results suggest that pleasure, relatedness, and inner peace were the primary human goods that were most sought after by a sample of 168 youth who sexually offended in Singapore. In addition, offender classification (in relation to the age of victim and nature of sexual offense) influenced the pathways to sexual offending. Therefore, these findings have important clinical implications for assessment, management, and intervention planning for youth who sexually offended.

  18. Human nature: a foundation for palliative care.

    PubMed

    Whelton, Beverly J B

    2008-04-01

    The Aristotelian-Thomist philosopher holds that human intellectual knowledge is possible because of the order in the world and natural human capacities. It is the position of this paper that there is a shared human form or nature that unites all humanity as members of the same kind. Moral treatment is due to every human being because they are human, and is not based upon expression of abilities. Humans have substantial dynamic existence in the world, an existence which overflows in expressive relationships. As both patient and health professional are human, human nature forms the natural foundation of health care. This paper looks towards human nature for moral guidance. The therapeutic relationship is seen as a part of the interpersonal moral space formed by human relationality, which tends towards community - in this case, the healthcare system. The therapeutic relationship is also a source of moral responsibility, as illness makes the patient vulnerable, while knowledge and nursing capacities generate in the nurse a duty to care. Nursing theory serves to connect philosophical reflection and nursing practice. Imogene King's conceptual system and theory of Goal Attainment is the theory that follows from the perspective of human person being presented. This synthesis of philosophy and theory is developed with the goal of shedding light on healthcare decisions in palliative care. The article concludes with the acknowledgement that the complexity of contextualized individual decisions requires the insight and discipline of the moral practitioner, and provides some thoughts on how education, development, and refinement transform an individual into a nurse. PMID:18336705

  19. Radon Natural Radioactivity Measurements for Evaluation of Primary Pollutants

    PubMed Central

    Zhang, Zhenyi; Ancora, Maria Pia; Deng, Xiaodong; Zhang, Hua

    2013-01-01

    Radon is naturally released from the soil into the surface layer of the atmosphere, and by monitoring the natural radioactivity data of radon and its shot-live decay products we can get valuable information about the dilution properties of the lower boundary layer. This paper explores the dispersion characteristics of the lower layer of the atmosphere in Lanzhou, China, and the close relationship with the patterns of primary pollutants' concentrations. Measurements were conducted from July 2007 to May 2008 at one station and a fifty-day campaign was carried out at two stations in Lanzhou. The interpretation of radon radioactivity measurement showed that the measured atmospheric stability index (ASI) data at two stations in Lanzhou had statistically significant correlation, and well described the lower atmospheric layer mixing property in the area. The temporal trend of PM10 data was consistent with the temporal trend of ASI, with almost twice as high values in December than it in August. The results show that the ASI allows to highlight the dilution factor playing an important role in determining primary pollution events, and the mixing properties of the lower boundary layer is the key factor determining PM10 concentration in urban areas. PMID:23935426

  20. Radon natural radioactivity measurements for evaluation of primary pollutants.

    PubMed

    Wang, Fenjuan; Zhang, Zhenyi; Ancora, Maria Pia; Deng, Xiaodong; Zhang, Hua

    2013-01-01

    Radon is naturally released from the soil into the surface layer of the atmosphere, and by monitoring the natural radioactivity data of radon and its shot-live decay products we can get valuable information about the dilution properties of the lower boundary layer. This paper explores the dispersion characteristics of the lower layer of the atmosphere in Lanzhou, China, and the close relationship with the patterns of primary pollutants' concentrations. Measurements were conducted from July 2007 to May 2008 at one station and a fifty-day campaign was carried out at two stations in Lanzhou. The interpretation of radon radioactivity measurement showed that the measured atmospheric stability index (ASI) data at two stations in Lanzhou had statistically significant correlation, and well described the lower atmospheric layer mixing property in the area. The temporal trend of PM10 data was consistent with the temporal trend of ASI, with almost twice as high values in December than it in August. The results show that the ASI allows to highlight the dilution factor playing an important role in determining primary pollution events, and the mixing properties of the lower boundary layer is the key factor determining PM10 concentration in urban areas.

  1. Integrated Modular Teaching of Human Biology for Primary Care Practitioners

    ERIC Educational Resources Information Center

    Glasgow, Michael S.

    1977-01-01

    Describes the use of integrated modular teaching of the human biology component of the Health Associate Program at Johns Hopkins University, where the goal is to develop an understanding of the sciences as applied to primary care. Discussion covers the module sequence, the human biology faculty, goals of the human biology faculty, laboratory…

  2. Human enamel veneer restoration: an alternative technique to restore anterior primary teeth.

    PubMed

    Oliveira, Luciana Butini; Tamay, Tereza Keiko; Oliveira, Marta Dutra Machado; Rodrigues, Célia Martins Delgado; Wanderley, Marcia Turolla

    2006-01-01

    Restoration of severely decayed primary teeth is a clinical challenge in Pediatric Dentistry. Among the restorative treatment options, the use of prefabricated crowns and resin composite restorations, either by means of direct or indirect techniques is mentioned in the literature. The purpose of this article is to describe the rehabilitation of primary anterior teeth in a 5-year-old patient. Dental treatment consisted on an anterior space maintainer prosthesis made with natural primary teeth, plus human dental enamel veneer (facet) restorations. The advantages of this technique are better esthetics and the natural enamel has physiologic wear and offers superficial smoothness and cervical adaptation compatible with those of the surrounding teeth.

  3. Human enamel veneer restoration: an alternative technique to restore anterior primary teeth.

    PubMed

    Oliveira, Luciana Butini; Tamay, Tereza Keiko; Oliveira, Marta Dutra Machado; Rodrigues, Célia Martins Delgado; Wanderley, Marcia Turolla

    2006-01-01

    Restoration of severely decayed primary teeth is a clinical challenge in Pediatric Dentistry. Among the restorative treatment options, the use of prefabricated crowns and resin composite restorations, either by means of direct or indirect techniques is mentioned in the literature. The purpose of this article is to describe the rehabilitation of primary anterior teeth in a 5-year-old patient. Dental treatment consisted on an anterior space maintainer prosthesis made with natural primary teeth, plus human dental enamel veneer (facet) restorations. The advantages of this technique are better esthetics and the natural enamel has physiologic wear and offers superficial smoothness and cervical adaptation compatible with those of the surrounding teeth. PMID:16937849

  4. Nature and Nurture of Human Pain

    PubMed Central

    2013-01-01

    Humans are very different when it comes to pain. Some get painful piercings and tattoos; others can not stand even a flu shot. Interindividual variability is one of the main characteristics of human pain on every level including the processing of nociceptive impulses at the periphery, modification of pain signal in the central nervous system, perception of pain, and response to analgesic strategies. As for many other complex behaviors, the sources of this variability come from both nurture (environment) and nature (genes). Here, I will discuss how these factors contribute to human pain separately and via interplay and how epigenetic mechanisms add to the complexity of their effects. PMID:24278778

  5. Nature and nurture of human pain.

    PubMed

    Belfer, Inna

    2013-01-01

    Humans are very different when it comes to pain. Some get painful piercings and tattoos; others can not stand even a flu shot. Interindividual variability is one of the main characteristics of human pain on every level including the processing of nociceptive impulses at the periphery, modification of pain signal in the central nervous system, perception of pain, and response to analgesic strategies. As for many other complex behaviors, the sources of this variability come from both nurture (environment) and nature (genes). Here, I will discuss how these factors contribute to human pain separately and via interplay and how epigenetic mechanisms add to the complexity of their effects.

  6. Homosexuals' and Lesbians' Philosophies of Human Nature.

    ERIC Educational Resources Information Center

    Weller, Leonard; Benozio, Motti

    1987-01-01

    Compared 57 homosexual men and 45 lesbians on six dimensions of beliefs about human nature. On only one dimension was significant difference found: lesbians saw people as more altruistic and less selfish than did homosexual men. Findings are consistent with the few personality studies which report no differences between homosexuals and lesbians.…

  7. Human Appropriation of Net Primary Production - Can Earth Keep Up?

    NASA Technical Reports Server (NTRS)

    Imhoff, Marc L.

    2006-01-01

    The amount of Earth's vegetation or net primary production required to support human activities is powerful measure of aggregate human impacts on the biosphere. Biophysical models applied to consumption statistics were used to estimate the annual amount of net primary production in the form of elemental carbon required for food, fibre, and fuel-wood by the global population. The calculations were then compared to satellite-based estimates of Earth's average net primary production to produce a geographically explicit balance sheet of net primary production "supply" and "demand". Humans consume 20% of Earth's net primary production (11.5 petagrams carbon) annually and this percentage varies regionally from 6% (South America) to over 70% (Europe and Asia), and locally from near 0% (central Australia) to over 30,000% (New York City, USA). The uneven footprint of human consumption and related environmental impacts, indicate the degree to which human populations are vulnerable to climate change and suggest policy options for slowing future growth of NPP demand.

  8. Natural human antibodies to amyloid beta peptide.

    PubMed

    Szabo, Paul; Relkin, Norman; Weksler, Marc E

    2008-06-01

    Properties of human, natural anti-Abeta antibodies and commercially available intravenous immunoglobulin (IVIg) have been examined in light of the beneficial effects of passive immunotherapy with IVIg for patients with mild to moderate Alzheimer's disease (AD). Anti-Abeta antibodies in IVIg recognize conformation-specific epitopes as well as linear epitopes from different regions of the Abeta peptide. Anti-Abeta antibodies in circulation, especially those with high avidity, are often masked by ligands and the avidity of these antibodies increases upon dissociation of the bound ligands from the antibodies. Such natural anti-Abeta antibodies have the capacity to prevent Abeta oligomer-induced neurotoxicity in N2A neuroblastoma cells. This neuro-protective effect may reflect the therapeutic potential of the natural anti-Abeta antibodies found in IVIg for the treatment of patients with AD.

  9. Natural frequencies of human corticothalamic circuits.

    PubMed

    Rosanova, Mario; Casali, Adenauer; Bellina, Valentina; Resta, Federico; Mariotti, Maurizio; Massimini, Marcello

    2009-06-17

    The frequency tuning of a system can be directly determined by perturbing it and by observing the rate of the ensuing oscillations, the so called natural frequency. This approach is used, for example, in physics, in geology, and also when one tunes a musical instrument. In the present study, we employ transcranial magnetic stimulation (TMS) to directly perturb a set of selected corticothalamic modules (Brodmann areas 19, 7, and 6) and high-density electroencephalogram to measure their natural frequency. TMS consistently evoked dominant alpha-band oscillations (8-12 Hz) in the occipital cortex, beta-band oscillations (13-20 Hz) in the parietal cortex, and fast beta/gamma-band oscillations (21-50 Hz) in the frontal cortex. Each cortical area tended to preserve its own natural frequency also when indirectly engaged by TMS through brain connections and when stimulated at different intensities, indicating that the observed oscillations reflect local physiological mechanisms. These findings were reproducible across individuals and represent the first direct characterization of the coarse electrophysiological properties of three associative areas of the human cerebral cortex. Most importantly, they indicate that, in healthy subjects, each corticothalamic module is normally tuned to oscillate at a characteristic rate. The natural frequency can be directly measured in virtually any area of the cerebral cortex and may represent a straightforward and flexible way to probe the state of human thalamocortical circuits at the patient's bedside.

  10. Themes in the human experience of nature.

    PubMed

    Pollio, Howard R; Heaps, Christopher

    2004-02-01

    To identify themes in the human experience of nature, a three-part study was run. In the first part, 100 undergraduate students were asked to list three situations in which they are or were aware of nature and to describe one of these in detail. In the second part, 26 descriptions were selected from these responses, summarized to a 2- to 5-sentence format, and presented to a different group of 30 subjects who sorted them into groups on the basis of cross-item similarity. These groupings were then analyzed by hierarchical clustering and multidimensional scaling procedures to produce thematic meanings. In the third part, a qualitative analysis of themes was performed over the unabridged initial versions of the same set of descriptions. Results of both qualitative and quantitative procedures led to the identification of four themes--Power and Scale, Danger and Safety, Beauty, and Connection and Alienation --and to a smaller number of themes unique to each mode of analysis. All themes were related to the everyday meanings of nature and to the more abstract definitions of nature employed in scientific or aesthetic analyses of the human response to this domain.

  11. Matching theory in natural human environments.

    PubMed

    McDowell, J J

    1988-01-01

    Matching theory is a mathematical account of behavior, many aspects of which have been confirmed in laboratory experiments with nonhuman and human subjects. The theory asserts that behavior is distributed across concurrently available response alternatives in the same proportion that reinforcement is distributed across those alternatives. The theory also asserts that behavior on a single response alternative is a function not only of reinforcement contingent on that behavior, but also of reinforcement contingent on other behaviors and of reinforcement delivered independently of behavior. These assertions constitute important advances in our understanding of the effects of reinforcement on behavior. Evidence from the applied literature suggests that matching theory holds not only in laboratory environments, but also in natural human environments. In addition, the theory has important therapeutic implications. For example, it suggests four new intervention strategies, and it can be used to improve treatment planning and management. Research on matching theory illustrates the progression from laboratory experimentation with nonhuman subjects to therapeutic applications in natural human environments.

  12. Exploring the folkbiological conception of human nature

    PubMed Central

    Linquist, Stefan; Machery, Edouard; Griffiths, Paul E.; Stotz, Karola

    2011-01-01

    Integrating the study of human diversity into the human evolutionary sciences requires substantial revision of traditional conceptions of a shared human nature. This process may be made more difficult by entrenched, ‘folkbiological’ modes of thought. Earlier work by the authors suggests that biologically naive subjects hold an implicit theory according to which some traits are expressions of an animal's inner nature while others are imposed by its environment. In this paper, we report further studies that extend and refine our account of this aspect of folkbiology. We examine biologically naive subjects' judgments about whether traits of an animal are ‘innate’, ‘in its DNA’ or ‘part of its nature’. Subjects do not understand these three descriptions to be equivalent. Both innate and in its DNA have the connotation that the trait is species-typical. This poses an obstacle to the assimilation of the biology of polymorphic and plastic traits by biologically naive audiences. Researchers themselves may not be immune to the continuing pull of folkbiological modes of thought. PMID:21199848

  13. Primary structure of the human M2 mitochondrial autoantigen of primary biliary cirrhosis: Dihydrolipoamide acetyltransferase

    SciTech Connect

    Coppel, R.L.; McNeilage, L.J.; Surh, C.D.; Van De Water, J.; Spithill, T.W.; Whittingham, S.; Gershwin, M.E. )

    1988-10-01

    Primary biliary cirrhosis is a chronic, destructive autoimmune liver disease of humans. Patient sera are characterized by a high frequency of autoantibodies to a M{sub r} 70,000 mitochondrial antigen a component of the M2 antigen complex. The authors have identified a human cDNA clone encoding the complete amino acid sequence of this autoantigen. The predicted structure has significant similarity with the dihydrolipoamide acetyltransferase of the Escherichia coli pyruvate dehydrogenase multienzyme complex. The human sequence preserves the Glu-Thr-Asp-Lys-Ala motif of the lipoyl-binding site and has two potential binding sites. Expressed fragments of the cDNA react strongly with sera from patients with primary biliary cirrhosis but not with sera from patients with autoimmune chronic active hepatitis or sera from healthy subjects.

  14. Content and Student Factors in Mastering Environmental Studies--Nature in Primary Education: Evidence from a National Assessment in Flanders (Belgium)

    ERIC Educational Resources Information Center

    Janssen, Rianne; Crauwels, Marion

    2011-01-01

    A large-scale paper-and-pencil assessment of the attainment targets of environmental studies with a focus on the subject area nature was held in primary education in Flanders (Belgium). The tests on different subfields of nature, i.e. the human body, healthcare, organisms, ecosystems, environmental care and non-living nature, were administered to…

  15. RANK and RANK ligand expression in primary human osteosarcoma.

    PubMed

    Branstetter, Daniel; Rohrbach, Kathy; Huang, Li-Ya; Soriano, Rosalia; Tometsko, Mark; Blake, Michelle; Jacob, Allison P; Dougall, William C

    2015-09-01

    Receptor activator of nuclear factor kappa-B ligand (RANKL) is an essential mediator of osteoclast formation, function and survival. In patients with solid tumor metastasis to the bone, targeting the bone microenvironment by inhibition of RANKL using denosumab, a fully human monoclonal antibody (mAb) specific to RANKL, has been demonstrated to prevent tumor-induced osteolysis and subsequent skeletal complications. Recently, a prominent functional role for the RANKL pathway has emerged in the primary bone tumor giant cell tumor of bone (GCTB). Expression of both RANKL and RANK is extremely high in GCTB tumors and denosumab treatment was associated with tumor regression and reduced tumor-associated bone lysis in GCTB patients. In order to address the potential role of the RANKL pathway in another primary bone tumor, this study assessed human RANKL and RANK expression in human primary osteosarcoma (OS) using specific mAbs, validated and optimized for immunohistochemistry (IHC) or flow cytometry. Our results demonstrate RANKL expression was observed in the tumor element in 68% of human OS using IHC. However, the staining intensity was relatively low and only 37% (29/79) of samples exhibited≥10% RANKL positive tumor cells. RANK expression was not observed in OS tumor cells. In contrast, RANK expression was clearly observed in other cells within OS samples, including the myeloid osteoclast precursor compartment, osteoclasts and in giant osteoclast cells. The intensity and frequency of RANKL and RANK staining in OS samples were substantially less than that observed in GCTB samples. The observation that RANKL is expressed in OS cells themselves suggests that these tumors may mediate an osteoclastic response, and anti-RANKL therapy may potentially be protective against bone pathologies in OS. However, the absence of RANK expression in primary human OS cells suggests that any autocrine RANKL/RANK signaling in human OS tumor cells is not operative, and anti-RANKL therapy

  16. Megascale processes: Natural disasters and human behavior

    USGS Publications Warehouse

    Kieffer, S.W.; Barton, P.; Chesworth, W.; Palmer, A.R.; Reitan, P.; Zen, E.-A.

    2009-01-01

    Megascale geologic processes, such as earthquakes, tsunamis, volcanic eruptions, floods, and meteoritic impacts have occurred intermittently throughout geologic time, and perhaps on several planets. Unlike other catastrophes discussed in this volume, a unique process is unfolding on Earth, one in which humans may be the driving agent of megadisasters. Although local effects on population clusters may have been catastrophic in the past, human societies have never been interconnected globally at the scale that currently exists. We review some megascale processes and their effects in the past, and compare present conditions and possible outcomes. We then propose that human behavior itself is having effects on the planet that are comparable to, or greater than, these natural disasters. Yet, unlike geologic processes, human behavior is potentially under our control. Because the effects of our behavior threaten the stability, or perhaps even existence, of a civilized society, we call for the creation of a body to institute coherent global, credible, scientifi cally based action that is sensitive to political, economic, religious, and cultural values. The goal would be to institute aggressive monitoring, identify and understand trends, predict their consequences, and suggest and evaluate alternative actions to attempt to rescue ourselves and our ecosystems from catastrophe. We provide a template modeled after several existing national and international bodies. ?? 2009 The Geological Society of America.

  17. Characterization of primary human keratinocytes transformed by human papillomavirus type 18

    SciTech Connect

    Kaur, P.; McDougall, J.K. )

    1988-06-01

    Primary human epithelial cells were cotransfected with pHPV-18 and pSV2neo, and cell strains were generated by selecting in G418. Southern blot analysis revealed the presence of at least one intact, integrated viral genome in these cells. FE-A cells showed altered growth properties, characterized by a change in morphology, and clonal density. Differentiation markers analyzed by Western blotting (immunoblotting), such as cytokeratins and involucrin, indicated that the cells resembled a partially differentiated epithelial population. Increased expression of the 40-kilodalton cytokeratin was observed in FE-A cells, similar to that observed in simian virus 40-immortalized human keratinocytes. Calcium and 12-O-tetradecanoyl-phorbol-13-acetate treatment induced normal epithelial cells to differentiate, whereas the human papillomavirus 18 (HPV-18)-containing keratinocytes were resistant to these signals, indicating their partially transformed nature. These cells were not able to induce tumors in nude mice over a period of up to 8 months. A second cell strain, FE-H18L, also generated by transfecting HPV-18, also exhibited an extended life span and similar alterations in morphology. Viral RNA transcribed from the early region of HPV-18 was detected in both cell strains by Northern (RNA) blot analysis. These cell strains should provide a useful model for determining the role of HPV in carcinogenesis.

  18. Natural sweeteners in a human diet.

    PubMed

    Grembecka, Małgorzata

    2015-01-01

    Sweeteners, both natural and artificial, play an important role in a human diet as well as are of great importance to the food industry and dieticians. Many people associate sweet taste with sucrose, which is commonly known as table sugar. However, there are many sweet substances that food manufacturers add to food products because none of them is ideal for all applications. Besides sucrose there are also other sugars such as glucose and fructose that originate both from natural sources such as fruits and honey or from added sugars. Among sweeteners there are also compounds which have a sweet taste and contain no calories or those which sweetness is so intense so can be used at very low concentrations, thus, their impact on the total caloric value of the product is negligible. They can be classified due to their origin (natural or synthetic agents), the technological function (sweeteners and fillers), texture (powders and syrups), and nutritional value (caloric and non-caloric). Natural sweetening substances include carbohydrates, sugar alcohols, thaumatin and stevia. Besides providing well tasting foods, they might have an impact on products' texture, color, preservation and caloric value. Sugar alcohols, which belong to carbohydrates, are both natural sugar substitutes and food additives. They are becoming more and more popular among consumers mainly due to their lower caloric values and glycemic indexes as well as anticariogenic effects. Sugar alcohols are often combined with other sweeteners to enhance food products' sweetness. Stevia, which is 200 times sweeter than sucrose, is a non caloric substance whereas thaumatin, a sweet protein, provides 4 kcal/g but characterizes with sweetness about 2000 times higher than sucrose (on a weight basis). PMID:26400114

  19. Ecosocietal Restoration: Reestablishing Humanity's Relationship with Natural Systems.

    ERIC Educational Resources Information Center

    Cairns, John, Jr.

    1995-01-01

    Examines the need for ecological and societal restoration to mitigate the consequences of historical changes in the relationship between human societies and natural systems. Ecosocietal restoration, or the process of reexamining human society's relationship with natural systems, is discussed. (LZ)

  20. Humanization policy in primary health care: a systematic review

    PubMed Central

    Nora, Carlise Rigon Dalla; Junges, José Roque

    2013-01-01

    OBJECTIVE To analyze humanization practices in primary health care in the Brazilian Unified Health System according to the principles of the National Humanization Policy. METHODS A systematic review of the literature was carried out, followed by a meta-synthesis, using the following databases: BDENF (nursing database), BDTD (Brazilian digital library of theses and dissertations), CINAHL (Cumulative Index to nursing and allied health literature), LILACS (Latin American and Caribbean health care sciences literature), MedLine (International health care sciences literature), PAHO (Pan-American Health Care Organization Library) and SciELO (Scientific Electronic Library Online). The following descriptors were used: Humanization; Humanizing Health Care; Reception: Humanized care: Humanization in health care; Bonding; Family Health Care Program; Primary Care; Public Health and Sistema Único de Saúde (the Brazilian public health care system). Research articles, case studies, reports of experiences, dissertations, theses and chapters of books written in Portuguese, English or Spanish, published between 2003 and 2011, were included in the analysis. RESULTS Among the 4,127 publications found on the topic, 40 studies were evaluated and included in the analysis, producing three main categories: the first referring to the infrastructure and organization of the primary care service, made clear the dissatisfaction with the physical structure and equipment of the services and with the flow of attendance, which can facilitate or make difficult the access. The second, referring to the health work process, showed issues about the insufficient number of professionals, fragmentation of the work processes, the professional profile and responsibility. The third category, referring to the relational technologies, indicated the reception, bonding, listening, respect and dialog with the service users. CONCLUSIONS Although many practices were cited as humanizing they do not produce changes

  1. Human milk: mother nature's prototypical probiotic food?

    PubMed

    McGuire, Michelle K; McGuire, Mark A

    2015-01-01

    The concept of "probiotic" is generally attributed to Dr. Ilya Mechnikov, who hypothesized that longevity could be enhanced by manipulating gastrointestinal microbes using naturally fermented foods. In 2001, a report of the FAO and WHO (2001 Oct, http://www.who.int/foodsafety/publications/fs_-management/en/probiotics.pdf) proposed a more restrictive definition of probiotic, as follows: "a live micro-organism which, when administered in adequate amounts, confers a health benefit on the host." As such, answering the fundamental question posed here-"Is human milk a probiotic?"-requires first grappling with the concept and meaning of the term probiotic. Nonetheless, one must also be convinced that human milk contains bacteria. Indeed, there are scores of publications providing evidence of a paradigm shift in this regard. Variation in the human-milk microbiome may be associated with maternal weight, mode of delivery, lactation state, gestation age, antibiotic use, and maternal health. Milk constituents (e.g., fatty acids and complex carbohydrates) might also be related to the abundance of specific bacterial taxa in milk. Whether these bacteria affect infant health is likely, but more studies are needed to test this hypothesis. In summary, a growing literature suggests that human milk, like all other fluids produced by the body, indeed contains viable bacteria. As such, and recognizing the extensive literature relating breastfeeding to optimal infant health, we propose that human milk should be considered a probiotic food. Determining factors that influence which bacteria are present in milk and if and how they influence the mother's and/or the recipient infant's health remain basic science and public health realms in which almost nothing is known. PMID:25593150

  2. Human milk: mother nature's prototypical probiotic food?

    PubMed

    McGuire, Michelle K; McGuire, Mark A

    2015-01-01

    The concept of "probiotic" is generally attributed to Dr. Ilya Mechnikov, who hypothesized that longevity could be enhanced by manipulating gastrointestinal microbes using naturally fermented foods. In 2001, a report of the FAO and WHO (2001 Oct, http://www.who.int/foodsafety/publications/fs_-management/en/probiotics.pdf) proposed a more restrictive definition of probiotic, as follows: "a live micro-organism which, when administered in adequate amounts, confers a health benefit on the host." As such, answering the fundamental question posed here-"Is human milk a probiotic?"-requires first grappling with the concept and meaning of the term probiotic. Nonetheless, one must also be convinced that human milk contains bacteria. Indeed, there are scores of publications providing evidence of a paradigm shift in this regard. Variation in the human-milk microbiome may be associated with maternal weight, mode of delivery, lactation state, gestation age, antibiotic use, and maternal health. Milk constituents (e.g., fatty acids and complex carbohydrates) might also be related to the abundance of specific bacterial taxa in milk. Whether these bacteria affect infant health is likely, but more studies are needed to test this hypothesis. In summary, a growing literature suggests that human milk, like all other fluids produced by the body, indeed contains viable bacteria. As such, and recognizing the extensive literature relating breastfeeding to optimal infant health, we propose that human milk should be considered a probiotic food. Determining factors that influence which bacteria are present in milk and if and how they influence the mother's and/or the recipient infant's health remain basic science and public health realms in which almost nothing is known.

  3. Nature at Your Doorstep: Real World Investigation for Primary Students.

    ERIC Educational Resources Information Center

    Basile, Carole G.; And Others

    "Nature at Your Doorstep" is an outgrowth of a successful environmental education program offered as a school field trip at a Nature Discovery Center. It was developed and used with thousands of students throughout Bellaire, Texas and the surrounding Houston metroplex. The purpose of this program is to kindle students' curiosity and wonder about…

  4. The human nature of culture and education.

    PubMed

    Trevarthen, Colwyn; Gratier, Maya; Osborne, Nigel

    2014-03-01

    Human cultures educate children with different strategies. Ancient hunter-gatherers 200,000 years ago, with bodies and brains like our own, in bands of a hundred well-known individuals or less, depended on spontaneous cooperative practice of knowledge and skills in a natural world. Before creating language, they appreciated beautiful objects and music. Anthropologists observe that similar living cultures accept that children learn in playful 'intent participation'. Large modern industrial states with millions of citizens competing in a global economy aim to instruct young people in scientific concepts and the rules of literacy and numeracy deemed important for employment with elaborate machines. Our psychobiological theories commonly assume that an infant starts with a body needing care and emotional regulation and a mind that assimilates concepts of objects by sensorimotor action and requires school instruction in rational principles after several years of cognitive development. Evidence from archeology and evolutionary anthropology indicates that Homo sapiens are born with an imaginative and convivial brain ready for the pleasure of shared invention and with a natural sense of beauty in handmade objects and music. In short, there are innate predispositions for culture for practicing meaningful habits and artful performances that are playfully inventive and seductive for companionship in traditions, and soon capable of grasping the clever purpose of shared tasks and tools. This knowledge of inventive human nature with esthetic and moral sensibilities has important implications for educational policy in our schools. WIREs Cogn Sci 2014, 5:173-192. doi: 10.1002/wcs.1276 CONFLICT OF INTEREST: The authors have declared no conflicts of interest for this article. For further resources related to this article, please visit the WIREs website. PMID:26304307

  5. Impacts of Temperature on Primary Productivity and Respiration in Naturally Structured Macroalgal Assemblages

    PubMed Central

    Tait, Leigh W.; Schiel, David R.

    2013-01-01

    Rising global temperatures caused by human-mediated change has already triggered significant responses in organismal physiology, distribution and ecosystem functioning. Although the effects of rising temperature on the physiology of individual organisms are well understood, the effect on community-wide processes has remained elusive. The fixation of carbon via primary productivity is an essential ecosystem function and any shifts in the balance of primary productivity and respiration could alter the carbon balance of ecosystems. Here we show through a series of tests that respiration of naturally structured algal assemblages in southern New Zealand greatly increases with rising temperature, with implications for net primary productivity (NPP). The NPP of in situ macroalgal assemblages was minimally affected by natural temperature variation, possibly through photo-acclimation or temperature acclimation responses, but respiration rates and compensating irradiance were negatively affected. However, laboratory experiments testing the impacts of rising temperature on several photosynthetic parameters showed a decline in NPP, increasing respiration rates and increasing compensating irradiance. The respiration Q10 of laboratory assemblages (the difference in metabolic rates over 10°C) averaged 2.9 compared to a Q10 of 2 often seen in other autotrophs. However, gross primary productivity (GPP) Q10 averaged 2, indicating that respiration was more severely affected by rising temperature. Furthermore, combined high irradiance and high temperature caused photoinhibition in the laboratory, and resulted in 50% lower NPP at high irradiance. Our study shows that communities may be more severely affected by rising global temperatures than would be expected by responses of individual species. In particular, enhanced respiration rates and rising compensation points have the potential to greatly affect the carbon balance of macroalgal assemblages through declines in sub-canopy NPP

  6. Theorising Learning and Nature: Post-Human Possibilities and Problems

    ERIC Educational Resources Information Center

    Quinn, Jocey

    2013-01-01

    In their predominantly theoretical turn to the material, post-humanist feminists often focus on "nature", arguing that the nature/culture binary has collapsed and that fixed distinctions between human and non-human spheres no longer hold. Conversely, outdoor learning sees nature as a space where humans act and has been more concerned…

  7. Primary pulmonary hypertension associated with human immunodeficiency virus infection.

    PubMed Central

    Golpe, R.; Fernandez-Infante, B.; Fernandez-Rozas, S.

    1998-01-01

    Several cardiorespiratory diseases can complicate human immunodeficiency virus infection. Primary pulmonary hypertension is a rare clinical disorder which carries a bad prognosis. More than 90 cases of HIV-associated primary pulmonary hypertension have been reported to date. Although its pathogenesis remains unknown, some evidence suggests a possible role for the virus itself in its development. Genetic susceptibility may also be implicated. The clinical and histopathologic features of this entity do not differ from those of classic primary pulmonary hypertension. The diagnosis requires a high degree of clinical suspicion and a careful evaluation to rule out causes of secondary pulmonary hypertension. In addition to supportive measures, anticoagulation and vasodilators have been used to treat this disorder, although sufficient data regarding long-term results with these therapies are lacking. PMID:9799910

  8. Arrhenius parameters for primary thermal injury in human tonsillar tissue

    NASA Astrophysics Data System (ADS)

    McMillan, Kathleen; Radabaugh, Rebecca; Coad, James E.

    2011-03-01

    Clinical implementation of a thermal therapy requires the ability to predict tissue injury following exposures to specific thermal histories. As part of an effort to develop a nonexcisional alternative to tonsillectomy, the degree of primary hyperthermic tissue injury in human tonsil was characterized. Fifteen fresh pediatric hypertrophic tonsillectomy specimens were sectioned and treated in a NIST-calibrated saline bath at temperatures of 40 to 70°C with hold times of one to seven minutes. The treated tissues were subsequently nitroblue tetrazolium (NBT) stained to assess for thermal respiratory enzyme inactivation as a marker of cellular injury/death. The NBT stains were quantitatively image analyzed and used to calculate Arrhenius parameters for primary thermal injury in human tonsils.

  9. "Human Nature": Chemical Engineering Students' Ideas about Human Relationships with the Natural World

    ERIC Educational Resources Information Center

    Goldman, Daphne; Assaraf, Orit Ben-Zvi; Shemesh, Julia

    2014-01-01

    While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The…

  10. Science, human nature, and a new paradigm for ethics education.

    PubMed

    Lampe, Marc

    2012-09-01

    For centuries, religion and philosophy have been the primary basis for efforts to guide humans to be more ethical. However, training in ethics and religion and imparting positive values and morality tests such as those emanating from the categorical imperative and the Golden Rule have not been enough to protect humankind from its bad behaviors. To improve ethics education educators must better understand aspects of human nature such as those that lead to "self-deception" and "personal bias." Through rationalizations, faulty reasoning and hidden bias, individuals trick themselves into believing there is little wrong with their own unethical behavior. The application of science to human nature offers the possibility of improving ethics education through better self-knowledge. The author recommends a new paradigm for ethics education in contemporary modern society. This includes the creation of a new field called "applied evolutionary neuro-ethics" which integrates science and social sciences to improve ethics education. The paradigm can merge traditional thinking about ethics from religious and philosophical perspectives with new ideas from applied evolutionary neuro-ethics.

  11. Science, human nature, and a new paradigm for ethics education.

    PubMed

    Lampe, Marc

    2012-09-01

    For centuries, religion and philosophy have been the primary basis for efforts to guide humans to be more ethical. However, training in ethics and religion and imparting positive values and morality tests such as those emanating from the categorical imperative and the Golden Rule have not been enough to protect humankind from its bad behaviors. To improve ethics education educators must better understand aspects of human nature such as those that lead to "self-deception" and "personal bias." Through rationalizations, faulty reasoning and hidden bias, individuals trick themselves into believing there is little wrong with their own unethical behavior. The application of science to human nature offers the possibility of improving ethics education through better self-knowledge. The author recommends a new paradigm for ethics education in contemporary modern society. This includes the creation of a new field called "applied evolutionary neuro-ethics" which integrates science and social sciences to improve ethics education. The paradigm can merge traditional thinking about ethics from religious and philosophical perspectives with new ideas from applied evolutionary neuro-ethics. PMID:22711449

  12. The Human Natural Killer Cell Immune Synapse

    NASA Astrophysics Data System (ADS)

    Davis, Daniel M.; Chiu, Isaac; Fassett, Marlys; Cohen, George B.; Mandelboim, Ofer; Strominger, Jack L.

    1999-12-01

    Inhibitory killer Ig-like receptors (KIR) at the surface of natural killer (NK) cells induced clustering of HLA-C at the contacting surface of target cells. In this manner, inhibitory immune synapses were formed as human NK cells surveyed target cells. At target/NK cell synapses, HLA-C/KIR distributed into rings around central patches of intercellular adhesion molecule-1/lymphocyte function-associated antigen-1, the opposite orientation to mature murine T cell-activating synapses. This organization of protein was stable for at least 20 min. Cells could support multiple synapses simultaneously, and clusters of HLA-C moved as NK cells crawled over target cells. Clustering required a divalent metal cation, explaining how metal chelators inhibit KIR function. Surprisingly, however, formation of inhibitory synapses was unaffected by ATP depletion and the cytoskeletal inhibitors, colchicine and cytochalsins B and D. Clearly, supramolecular organization within plasma membranes is critical for NK cell immunosurveillance.

  13. Neurocysticercosis: A natural human model of epileptogenesis

    PubMed Central

    Nash, T.E.; Mahanty, S.; Loeb, J.A.; Theodore, W.H.; Friedman, A.; Sander, J.W.; Singh, E. G.; Cavalheiro, E.; Del Brutto, O.H.; Takayanagui, O.; Fleury, A.; Verastegui, M.; Preux, PM.; Montano, E.J.S.; Pretell, E.J.; White, A.C.; Gonzales, A. E.; Gilman, R.H.; Garcia, H.H.

    2014-01-01

    Objective To develop a better understanding on mechanisms of seizures and long-term epileptogenesis caused by neurocysticercosis. Methods A workshop was held bringing together experts in epilepsy and epileptogenesis and neurocysticercosis Results Human neurocysticercosis and parallel animal models offer a unique opportunity to understand basic mechanisms of seizures. Inflammatory responses to degenerating forms and in later stage calcified parasite granulomas are associated with seizures and epilepsy. Other mechanisms may also be involved in epileptogenesis as well. Conclusions Naturally occurring brain infections with neurocysticercosis offer a unique opportunity to develop treatments for one of the world’s most common causes of epilepsy and for the development of more general anti-epileptogenic treatments. Key advantages stem from the time course where an acute seizure heralds a start of the epileptogenic process and radiographic changes of calcification and perilesional edema provide biomarkers of a chronic epileptic state. PMID:25534640

  14. Zinc oxide nanoparticle induced genotoxicity in primary human epidermal keratinocytes.

    PubMed

    Sharma, Vyom; Singh, Suman K; Anderson, Diana; Tobin, Desmond J; Dhawan, Alok

    2011-05-01

    Zinc oxide (ZnO) nanoparticles are widely used in cosmetics and sunscreens. Human epidermal keratinocytes may serve as the first portal of entry for these nanoparticles either directly through topically applied cosmetics or indirectly through any breaches in the skin integrity. Therefore, the objective of the present study was to assess the biological interactions of ZnO nanoparticles in primary human epidermal keratinocytes (HEK) as they are the most abundant cell type in the human epidermis. Cellular uptake of nanoparticles was investigated by scanning electron microscopy using back scattered electrons imaging as well as transmission electron microscopy. The electron microscopy revealed the internalization of ZnO nanoparticles in primary HEK after 6 h exposure at 14 microg/ml concentration. ZnO nanoparticles exhibited a time (6-24 h) as well as concentration (8-20 microg/ml) dependent inhibition of mitochondrial activity as evident by the MTT assay. A significant (p < 0.05) induction in DNA damage was observed in cells exposed to ZnO nanoparticles for 6 h at 8 and 14 microg/ml concentrations compared to control as evident in the Comet assay. This is the first study providing information on biological interactions of ZnO nanoparticles with primary human epidermal keratinocytes. Our findings demonstrate that ZnO nanoparticles are internalized by the human epidermal keratinocytes and elicit a cytotoxic and genotoxic response. Therefore, caution should be taken while using consumer products containing nanoparticles as any perturbation in the skin barrier could expose the underlying cells to nanoparticles.

  15. Are Human and Natural Systems Decoupling?

    NASA Astrophysics Data System (ADS)

    Ehrlich, P. R.; Ehrlich, A. H.

    2012-12-01

    Typically, studies of coupled human and natural systems focus on reciprocating interactions and feedbacks between social systems and their biophysical environments. A major challenge today for CHANS scholars is to determine whether significant coupling remains or whether society is simply plunging ahead without reacting effectively to the deterioration of the environment. Thresholds for serious climate disruption are passing, toxification of Earth is proceeding apace and producing worrying symptoms, losses of vital biodiversity are at a 65 million-year high with serious consequences for ecosystem services, the epidemiological environment is deteriorating and a race is building to control water flows and extract the last high-quality resources, increasing the chances of ending civilization in an environment-wrecking nuclear war. The social system has attempted to respond to this perfect storm of problems. In the 1960s, building on much earlier work, scientists began assessing the consequences of an ever-growing human population and expanding consumption, overuse of pesticides, radioactive fallout, air and water pollution, and other environmental issues - and to recommend ameliorative steps. In the mid-1980s, biologists formed the discipline of conservation biology with the explicit purpose of stemming the hemorrhage of biodiversity. In the late 1980s, perhaps the single most important reaction to the worsening environmental situation was the development of the Montreal Protocol to preserve the vital stratospheric ozone layer. Around the same time, it dawned on the scientific community that climate disruption was going to be more immediate and dangerous than previously thought, but attempts by the world community to take mitigating steps have been pathetic. Action to deal with other dimensions of the environmental dilemma has been utterly inadequate. To see the growing disconnect, one only has to consider the attention paid in public discourse to the relatively

  16. About Being Pure and Natural: Understandings of Pre-Service Primary Teachers

    ERIC Educational Resources Information Center

    Lake, David

    2005-01-01

    In an investigation of 149 pre-service primary teachers' understanding of the terms "pure" and "natural," the participants were asked to provide definitions of the two words, and classify various substances including drugs of abuse, pharmaceuticals, nutriceuticals, and household substances as either natural or not natural, and as pure or not pure.…

  17. Transcriptional comparison of human induced and primary midbrain dopaminergic neurons

    PubMed Central

    Xia, Ninuo; Zhang, Pengbo; Fang, Fang; Wang, Zhengyuan; Rothstein, Megan; Angulo, Benjamin; Chiang, Rosaria; Taylor, James; Reijo Pera, Renee A.

    2016-01-01

    Generation of induced dopaminergic (iDA) neurons may provide a significant step forward towards cell replacement therapy for Parkinson’s disease (PD). To study and compare transcriptional programs of induced cells versus primary DA neurons is a preliminary step towards characterizing human iDA neurons. We have optimized a protocol to efficiently generate iDA neurons from human pluripotent stem cells (hPSCs). We then sequenced the transcriptomes of iDA neurons derived from 6 different hPSC lines and compared them to that of primary midbrain (mDA) neurons. We identified a small subset of genes with altered expression in derived iDA neurons from patients with Parkinson’s Disease (PD). We also observed that iDA neurons differ significantly from primary mDA neurons in global gene expression, especially in genes related to neuron maturation level. Results suggest iDA neurons from patient iPSCs could be useful for basic and translational studies, including in vitro modeling of PD. However, further refinement of methods of induction and maturation of neurons may better recapitulate full development of mDA neurons from hPSCs. PMID:26842779

  18. The nature of primary consciousness. A new synthesis.

    PubMed

    Feinberg, Todd E; Mallatt, Jon

    2016-07-01

    While the philosophical puzzles about "life" that once confounded biology have all been solved by science, much of the "mystery of consciousness" remains unsolved due to multiple "explanatory gaps" between the brain and conscious experience. One reason for this impasse is that diverse brain architectures both within and across species can create consciousness, thus making any single neurobiological feature insufficient to explain it. We propose instead that an array of general biological features that are found in all living things, combined with a suite of special neurobiological features unique to animals with consciousness, evolved to create subjective experience. Combining philosophical, neurobiological and evolutionary approaches to consciousness, we review our theory of neurobiological naturalism that we argue closes the "explanatory gaps" between the brain and subjective experience and naturalizes the "experiential gaps" between subjectivity and third-person observation of the brain. PMID:27262691

  19. Are Humans Still Evolving? A Natural Selection Discussion Lesson

    ERIC Educational Resources Information Center

    Shields, Martin

    2004-01-01

    A study is conducted to develop sound comprehension of natural selection theory by prompting students to use its concept to explain the evolutionary status of humans. In relation to the current existence of human it is stated that human populations currently undergo microevolutionary changes in allele frequencies due to natural selection and other…

  20. Human Bocavirus 1 Primary Infection and Shedding in Infants

    PubMed Central

    Martin, Emily T.; Kuypers, Jane; McRoberts, John P.; Englund, Janet A.; Zerr, Danielle M.

    2015-01-01

    Background. Human bocavirus 1 (HBoV-1) is frequently detected in young children. The role of HBoV-1 in respiratory illness is unclear, owing to frequent detection in asymptomatic children. Methods. Weekly oral fluid samples from a longitudinal cohort of infants were tested by quantitative polymerase chain reaction for HBoV-1 DNA. Symptoms during HBoV-1 primary shedding events were compared to those during 14-day control periods occurring 1 month prior to and following the primary event. Eight single-nucleotide polymorphisms were analyzed to assess HBoV-1 variants. Results. Sixty-six of 87 children (76%), followed for at least 18 months from birth, had a primary HBoV-1 infection. HBoV-1 was consistently detected for >1 month (maximum duration, 402 days) following 42 of 66 primary shedding events. Children were more likely to experience new cough symptoms (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.4–5.5) and to visit a healthcare provider (OR, 2.8; 95% CI, 1.02–7.7) during the 14 days surrounding the time of initial detection of HBoV-1. Recurrent HBoV-1 shedding events were found in 33 children (50%). Twelve of 48 children with HBoV-1 variant data had multiple viral allelic patterns over time. Conclusions. HBoV-1 primary shedding events are associated with mild respiratory illness with subsequent prolonged detection of HBoV-1 DNA for up to a year. HBoV-1 reinfection contributes to long-term shedding. PMID:25632039

  1. Expression of androgen and progesterone receptors in primary human meningiomas.

    PubMed

    Maxwell, M; Galanopoulos, T; Neville-Golden, J; Antoniades, H N

    1993-03-01

    Meningiomas are common brain tumors that show a predilection for females and become more aggressive during pregnancy and menses. The existence of gender-specific hormone receptors in meningiomas has long been a matter of controversy; the recent cloning of androgen, estrogen, and progesterone receptors has facilitated their direct evaluation. The authors have demonstrated the expression of androgen and progesterone receptor messenger ribonucleic acid and protein product in nine primary human meningiomas by Northern blot analysis. Cellular localization was achieved by in situ hybridization analysis. Estrogen receptor expression was not detected. Normal adult meninges were shown to express very low levels of both androgen and progesterone receptors.

  2. Purification and primary structure determination of human lysosomal dipeptidase.

    PubMed

    Dolenc, Iztok; Mihelic, Marko

    2003-02-01

    The lysosomal metallopeptidase is an enzyme that acts preferentially on dipeptides with unsubstituted N- and C-termini. Its activity is highest in slightly acidic pH. Here we describe the isolation and characterization of lysosomal dipeptidase from human kidney. The isolated enzyme has the amino-terminal sequence DVAKAIINLAVY and is a homodimer with a molecular mass of 100 kDa. So far no amino acid sequence has been determined for this metallopeptidase. The complete primary structure as deduced from the nucleotide sequence revealed that the isolated dipeptidase is similar to blood plasma glutamate carboxypeptidase.

  3. Matching in an undisturbed natural human environment.

    PubMed

    McDowell, J J; Caron, Marcia L

    2010-05-01

    Data from the Oregon Youth Study, consisting of the verbal behavior of 210 adolescent boys determined to be at risk for delinquency (targets) and 210 of their friends (peers), were analyzed for their conformance to the complete family of matching theory equations in light of recent findings from the basic science, and using recently developed analytic techniques. Equations of the classic and modern theories of matching were fitted as ensembles to rates and time allocations of the boys' rule-break and normative talk obtained from conversations between pairs of boys. The verbal behavior of each boy in a conversation was presumed to be reinforced by positive social responses from the other boy. Consistent with recent findings from the basic science, the boys' verbal behavior was accurately described by the modern but not the classic theory of matching. These findings also add support to the assertion that basic principles and processes that are known to govern behavior in laboratory experiments also govern human social behavior in undisturbed natural environments. PMID:21119854

  4. The Nature of Io's Primary Atmosphere: Collapse in Jupiter Eclipse

    NASA Astrophysics Data System (ADS)

    Tsang, Constantine; Spencer, John R.; Lellouch, Emmanuel; Lopez-Valverde, Miguel A.; Richter, Matthew

    2016-10-01

    Io's SO2 atmosphere on the dayside is collisionally thick and inhomogeneous. This atmosphere is thought to be sustained by the combination of direct volcanic injection and SO2 frost sublimation off the surface. The degree to which frost sublimation contributes to the overall atmosphere has been a long-standing problem in studying Io's atmosphere and its interactions with the surface and plasma environment. A key observation is determining the behavior of Io's atmosphere going into and during eclipses by Jupiter, which helps separate the sublimation component of the atmosphere in vapor pressure equilibrium with the surface from the volcanic component.We present high-time (10 mins) and high spectral resolution (R~67,000) spectra of Io's primary molecular SO2 atmosphere from the Gemini telescope with the TEXES spectrometer, as Io enters eclipses by Jupiter. The mid-IR spectra, which are the first ever observation of Io's bulk atmosphere going into and in eclipse, show significant change in the absorption bands of SO2. With further modeling, we show the atmosphere collapses onto the surface as frost. This study presents a strong case for atmospheric support by vapor pressure from surface frost. This daily atmospheric collapse has implications on the supply of material to the plasma environment around Io and Jupiter, and should also be viewed in the context of the larger scale seasonal changes of the atmosphere that occur on Io.

  5. Natural organic matter as global antennae for primary production.

    PubMed

    Van Trump, J Ian; Rivera Vega, Fransheska J; Coates, John D

    2013-05-01

    Humic substances (HS) are high-molecular-weight complex refractory organics that are ubiquitous in terrestrial and aquatic environments. While resistant to microbial degradation, these compounds nevertheless support microbial metabolism via oxidation or reduction of their (hydro)quinone moieties. As such, they are known to be important electron sinks for respiratory and fermentative bacteria and electron sources for denitrifying and perchlorate-reducing bacteria. HS also strongly promote abiotic reduction of Fe(III) when irradiated with light. Here, we show that HS-enhanced Fe(III) photoreduction can also drive chemolithotrophic microbial respiration by producing Fe(II), which functions as a respiratory electron donor. Due to their molecular complexity, HS absorb most of the electromagnetic spectrum and can act as broad-spectrum antennae converting radiant energy into bioavailable chemical energy. The finding that chemolithotrophic organisms can utilize this energy has important implications for terrestrial, and possibly extraterrestrial, microbial processes and offers an alternative mechanism of radiation-driven primary productivity to that of phototrophy.

  6. The nature and behavior of particulates in PWR primary coolant

    SciTech Connect

    Bridle, D.A.; Butter, K.R.; Cake, P.; Comley, G.C.W.; Mitchell, C.R. )

    1989-12-01

    A study of particle size distributions, nature and behavior of insoluble species carried by PWR coolants has been carried out over a four year period in Belgian reactors. Comparative data was obtained by the use of improved sampling systems designed to overcome the inadequacies of standard facilities. Coolant data is presented from commissioning and early operation of new plant to that in established PWR circuits. Results arising from reactors transients are also included, which refer to shutdown and start-up phases, power changes and scram situations. The information obtained includes chemical and radiochemical characteristics of particulates and their contribution to total activity carried by reactor coolant. The implications for plant operations are discussed. 16 refs., 55 figs., 24 tabs.

  7. [Human nature and the enhancement of human beings in the light of the transhumanist program].

    PubMed

    Goffi, Jean-Yves

    2011-01-01

    There are three main approaches about the question of Human Nature. essentialists consider that there exists a permanent Human Nature, shared by every human being. Existentialists consider that there is no such thing as human nature, but inescapable modes of being in the world. A moderate approach would consider that Human Nature can be modified within the limits of anthropological invariants. Transhumanists are conservative in that they think that there is a Human Nature; but they are radical in that they believe that it can (and must) be transcended by bio-technnologies and computer technologies. This project is evaluated as a caricature of suitable human enhancement.

  8. Regulation of human renin expression in chorion cell primary cultures

    SciTech Connect

    Duncan, K.G.; Haidar, M.A.; Baxter, J.D.; Reudelhuber, T.L. )

    1990-10-01

    The human renin gene is expressed in the kidney, placenta, and several other sites. The release of renin or its precursor, prorenin, can be affected by several regulatory agents. In this study, primary cultures of human placental cells were used to examine the regulation of prorenin release and renin mRNA levels and of the transfected human renin promoter linked to chloramphenicol acetyltransferase reporter sequences. Treatment of the cultures with a calcium ionophore alone, calcium ionophore plus forskolin (that activates adenylate cyclase), or forskolin plus a phorbol ester increased prorenin release and renin mRNA levels 1.3{endash} to 6{endash}fold, but several classes of steroids did not affect prorenin secretion or renin RNA levels. These results suggest that (i) the first 584 base pairs of the renin gene 5'{endash}flanking DNA do not contain functional glucocorticoid or estrogen response elements, (ii) placental prorenin release and renin mRNA are regulated by calcium ion and by the combinations of cAMP with either C kinase or calcium ion, and (iii) the first 100 base pairs of the human renin 5'{endash}flanking DNA direct accurate initiation of transcription and can be regulated by cAMP. Thus, some control of renin release in the placenta (and by inference in other tissues) occurs via transcriptional influences on its promoter.

  9. Primary human bronchial epithelial cells grown from explants.

    PubMed

    Yaghi, Asma; Zaman, Aisha; Dolovich, Myrna

    2010-01-01

    Human bronchial epithelial cells are needed for cell models of disease and to investigate the effect of excipients and pharmacologic agents on the function and structure of human epithelial cells. Here we describe in detail the method of growing bronchial epithelial cells from bronchial airway tissue that is harvested by the surgeon at the times of lung surgery (e.g. lung cancer or lung volume reduction surgery). With ethics approval and informed consent, the surgeon takes what is needed for pathology and provides us with a bronchial portion that is remote from the diseased areas. The tissue is then used as a source of explants that can be used for growing primary bronchial epithelial cells in culture. Bronchial segments about 0.5-1cm long and < or =1cm in diameter are rinsed with cold EBSS and excess parenchymal tissue is removed. Segments are cut open and minced into 2-3mm(3) pieces of tissue. The pieces are used as a source of primary cells. After coating 100mm culture plates for 1-2 hr with a combination of collagen (30 microg/ml), fibronectin (10 microg/ml), and BSA (10 microg/ml), the plates are scratched in 4-5 areas and tissue pieces are placed in the scratched areas, then culture medium (DMEM/Ham F-12 with additives) suitable for epithelial cell growth is added and plates are placed in an incubator at 37 degrees C in 5% CO(2) humidified air. The culture medium is changed every 3-4 days. The epithelial cells grow from the pieces forming about 1.5 cm diameter rings in 3-4 weeks. Explants can be re-used up to 6 times by moving them into new pre-coated plates. Cells are lifted using trypsin/EDTA, pooled, counted, and re-plated in T75 Cell Bind flasks to increase their numbers. T75 flasks seeded with 2-3 million cells grow to 80% confluence in 4 weeks. Expanded primary human epithelial cells can be cultured and allowed to differentiate on air-liquid interface. Methods described here provide an abundant source of human bronchial epithelial cells from freshly

  10. Effects of Simulated Microgravity on Primary Human NK Cells

    PubMed Central

    Li, Qi; Mei, Qibing; Huyan, Ting; Xie, Li; Che, Su; Yang, Hui; Zhang, Mingjie

    2013-01-01

    Abstract The deleterious effects of microgravity on lymphocytes have been demonstrated in previous studies. However, research on the effects of microgravity on human natural killer (NK) cells remains exceedingly limited. In this study, we demonstrated that NK cell cytotoxicity was significantly decreased under simulated microgravity (SMG) conditions (p<0.05). Several processes, including apoptosis, receptor expression, and cytokine secretion, were investigated in human NK cells under SMG. We observed decreased cytotoxicity, concurrent with increased apoptosis and necrosis, in NK cells after exposure to SMG (p<0.05). Additionally, interferon (IFN)-γ and perforin expression decreased significantly, and the expression of granzyme-B was only slightly reduced. Meanwhile, SMG selectively inhibited the expression of certain surface receptors on NK cells. Specifically, the expression of NKG2A and NKG2D were significantly downregulated under SMG, but the expression of NKp30 and NKp44 was not affected. We also found that interleukin (IL)–15 alone or in combination with IL-12 could counteract the inhibition of NK cell cytotoxicity under SMG. Our findings indicate that human NK cells were sensitive to SMG, as reflected by their decreased cytotoxicity. Factors such as increased early apoptosis and late apoptosis/necrosis and the decreased expression of INF-γ, cytolytic proteins, and cell surface receptors may be responsible for the loss of cytotoxicity in human NK cells under SMG. A combination of IL-12 and IL-15 may be useful as a therapeutic strategy for overcoming the effects of microgravity on human NK cells during long space missions. Key Words: Simulated microgravity (SMG)—Natural killer (NK) cells—Cytotoxicity. Astrobiology 13, 703–714. PMID:23919749

  11. Primary human monocyte differentiation regulated by Nigella sativa pressed oil

    PubMed Central

    2011-01-01

    Background Oxidized low density lipoprotein plays an important role in development of foam cells in atherosclerosis. The study was focused on regulation of primary human monocyte growth and CD11b expression in presence of Nigella sativa oil. Methods Primary human monocytes were isolated from whole blood and grown at 37°C and 5% CO2 saturation for five days prior to treatment with Nigella sativa oil. The cells were plated and washed before treatment with ox-LDL (10 μg/ml) as positive control and combined treatment of ox-LDL (10 μg/ml) and (140 ng/ml) Nigella sativa oil. The growth progression was monitored every 24 hours for 3 days. Results Macrophages showed reduced growth in comparison to monocytes 24 hours after treatment with Nigella sativa oil. The mean cell diameter was significantly different between untreated and treated condition in monocytes and macrophages (p < 0.001). Similarly, intracellular lipid accumulation was hindered in combined treatment with Nigella sativa oil. This was further supported by cell surface expression analysis, where CD11b was markedly reduced in cells treated with combination oxLDL and Nigella sativa oil compared to oxLDL alone. More cells differentiated into macrophage-like cells when monocytes were supplemented with oxidized LDL alone. Conclusions The finding provides preliminary evidence on regulation of cell growth and differentiation in monocyte and monocyte-derived macrophages by Nigella sativa oil. Further investigations need to be conducted to explain its mechanism in human monocyte. PMID:22104447

  12. Nature, Humans, and the Coastal Zone.

    ERIC Educational Resources Information Center

    Walker, H. Jesse

    1990-01-01

    Considers the interface of humans and seacoasts over time. Explains how coastal zones are formed and human attempts to defend against sea level changes. Charts the percentage of major world cities that also are ports. Postulates how the greenhouse effect could influence sea level, examining potential human responses to changes in coastal zones.…

  13. The Nature of Effective Human Resource Planning.

    ERIC Educational Resources Information Center

    Don, Daniel; Kleiner, Brian H.

    1991-01-01

    The general structure of the human resource planning function in organizations and the responsibilities at each level of management are discussed. A framework for constructing and implementing a human resource planning system is outlined, and several approaches for human resource forecasting are examined. (MSE)

  14. 18 CFR 2.400 - Statement of interpretation of waste concerning natural gas as the primary energy source for...

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... interpretation of waste concerning natural gas as the primary energy source for qualifying small power production... concerning natural gas as the primary energy source for qualifying small power production facilities. For purposes of deciding whether natural gas may be considered as waste as the primary energy source...

  15. The Many Faces of Human Participation with Nature.

    ERIC Educational Resources Information Center

    Maser, Chris

    1994-01-01

    This article presents two stories of human participation with nature and one another. The stories focus on the natural and human history of interaction in two places: (1) the Salt Creek Pupfish in Death Valley, and (2) the Valley of Fire. (LZ)

  16. Human Nature and Research Paradigms: Theory Meets Physical Therapy Practice

    ERIC Educational Resources Information Center

    Plack, Margaret M.

    2005-01-01

    Human nature is a very complex phenomenon. In physical therapy this complexity is enhanced by the need to understand the intersection between the art and science of human behavior and patient care. A paradigm is a set of basic beliefs that represent a worldview, defines the nature of the world and the individual's place in it, and helps to…

  17. Zika virus productively infects primary human placenta-specific macrophages

    PubMed Central

    Jurado, Kellie Ann; Simoni, Michael K.; Tang, Zhonghua; Uraki, Ryuta; Hwang, Jesse; Householder, Sarah; Wu, Mingjie; Lindenbach, Brett D.; Abrahams, Vikki M.; Guller, Seth

    2016-01-01

    The strong association of Zika virus infection with congenital defects has led to questions of how a flavivirus is capable of crossing the placental barrier to reach the fetal brain. Here, we demonstrate permissive Zika virus infection of primary human placental macrophages, commonly referred to as Hofbauer cells, and placental villous fibroblasts. We also demonstrate Zika virus infection of Hofbauer cells within the context of the tissue ex vivo using term placental villous explants. In addition to amplifying infectious virus within a usually inaccessible area, the putative migratory activities of Hofbauer cells may aid in dissemination of Zika virus to the fetal brain. Understanding the susceptibility of placenta-specific cell types will aid future work around and understanding of Zika virus–associated pregnancy complications. PMID:27595140

  18. Zika virus productively infects primary human placenta-specific macrophages

    PubMed Central

    Jurado, Kellie Ann; Simoni, Michael K.; Tang, Zhonghua; Uraki, Ryuta; Hwang, Jesse; Householder, Sarah; Wu, Mingjie; Lindenbach, Brett D.; Abrahams, Vikki M.; Guller, Seth; Fikrig, Erol

    2016-01-01

    The strong association of Zika virus infection with congenital defects has led to questions of how a flavivirus is capable of crossing the placental barrier to reach the fetal brain. Here, we demonstrate permissive Zika virus infection of primary human placental macrophages, commonly referred to as Hofbauer cells, and placental villous fibroblasts. We also demonstrate Zika virus infection of Hofbauer cells within the context of the tissue ex vivo using term placental villous explants. In addition to amplifying infectious virus within a usually inaccessible area, the putative migratory activities of Hofbauer cells may aid in dissemination of Zika virus to the fetal brain. Understanding the susceptibility of placenta-specific cell types will aid future work around and understanding of Zika virus–associated pregnancy complications.

  19. Effect of silver nanoparticles on human primary keratinocytes.

    PubMed

    Szmyd, Radoslaw; Goralczyk, Anna Grazyna; Skalniak, Lukasz; Cierniak, Agnieszka; Lipert, Barbara; Filon, Francesca Larese; Crosera, Matteo; Borowczyk, Julia; Laczna, Eliza; Drukala, Justyna; Klein, Andrzej; Jura, Jolanta

    2013-01-01

    Silver nanoparticles (AgNPs) have many biological applications in biomedicine, biotechnology and other life sciences. Depending on the size, shape and the type of carrier, AgNPs demonstrate different physical and chemical properties. AgNPs have strong antimicrobial, antiviral and antifungal activity, thus they are used extensively in a range of medical settings, particularly in wound dressings but also in cosmetics. This study was undertaken to examine the potential toxic effects of 15 nm polyvinylpyrrolidone-coated AgNPs on primary normal human epidermal keratinocytes (NHEK). Cells were treated with different concentrations of AgNPs and then cell viability, metabolic activity and other biological and biochemical aspects of keratinocytes functioning were studied. We observed that AgNPs decrease keratinocyte viability, metabolism and also proliferatory and migratory potential of these cells. Moreover, longer exposure resulted in activation of caspase 3/7 and DNA damage. Our studies show for the first time, that AgNPs may present possible danger for primary keratinocytes, concerning activation of genotoxic and cytotoxic processes depending on the concentration.

  20. `Human nature': Chemical engineering students' ideas about human relationships with the natural world

    NASA Astrophysics Data System (ADS)

    Goldman, Daphne; Ben-Zvi Assaraf, Orit; Shemesh, Julia

    2014-05-01

    While importance of environmental ethics, as a component of sustainable development, in preparing engineers is widely acknowledged, little research has addressed chemical engineers' environmental concerns. This study aimed to address this void by exploring chemical engineering students' values regarding human-nature relationships. The study was conducted with 247 3rd-4th year chemical engineering students in Israeli Universities. It employed the New Ecological Paradigm (NEP)-questionnaire to which students added written explanations. Quantitative analysis of NEP-scale results shows that the students demonstrated moderately ecocentric orientation. Explanations to the NEP-items reveal diverse, ambivalent ideas regarding the notions embodied in the NEP, strong scientific orientation and reliance on technology for addressing environmental challenges. Endorsing sustainability implies that today's engineers be equipped with an ecological perspective. The capacity of Higher Education to enable engineers to develop dispositions about human-nature interrelationships requires adaptation of curricula towards multidisciplinary, integrative learning addressing social-political-economic-ethical perspectives, and implementing critical-thinking within the socio-scientific issues pedagogical approach.

  1. Human nature, cultural diversity and evolutionary theory

    PubMed Central

    Plotkin, Henry

    2011-01-01

    Incorporating culture into an expanded theory of evolution will provide the foundation for a universal account of human diversity. Two requirements must be met. The first is to see learning as an extension of the processes of evolution. The second is to understand that there are specific components of human culture, viz. higher order knowledge structures and social constructions, which give rise to culture as invented knowledge. These components, which are products of psychological processes and mechanisms, make human culture different from the forms of shared knowledge observed in other species. One serious difficulty for such an expanded theory is that social constructions may not add to the fitness of all humans exposed to them. This may be because human culture has existed for only a relatively short time in evolutionary terms. Or it may be that, as some maintain, adaptation is a limited, even a flawed, aspect of evolutionary theory. PMID:21199849

  2. Steroid synthesis by primary human keratinocytes; implications for skin disease

    SciTech Connect

    Hannen, Rosalind F.; Michael, Anthony E.; Jaulim, Adil; Bhogal, Ranjit; Burrin, Jacky M.; Philpott, Michael P.

    2011-01-07

    Research highlights: {yields} Primary keratinocytes express the steroid enzymes required for cortisol synthesis. {yields} Normal primary human keratinocytes can synthesise cortisol. {yields} Steroidogenic regulators, StAR and MLN64, are expressed in normal epidermis. {yields} StAR expression is down regulated in eczema and psoriatic epidermis. -- Abstract: Cortisol-based therapy is one of the most potent anti-inflammatory treatments available for skin conditions including psoriasis and atopic dermatitis. Previous studies have investigated the steroidogenic capabilities of keratinocytes, though none have demonstrated that these skin cells, which form up to 90% of the epidermis are able to synthesise cortisol. Here we demonstrate that primary human keratinocytes (PHK) express all the elements required for cortisol steroidogenesis and metabolise pregnenolone through each intermediate steroid to cortisol. We show that normal epidermis and cultured PHK express each of the enzymes (CYP11A1, CYP17A1, 3{beta}HSD1, CYP21 and CYP11B1) that are required for cortisol synthesis. These enzymes were shown to be metabolically active for cortisol synthesis since radiometric conversion assays traced the metabolism of [7-{sup 3}H]-pregnenolone through each steroid intermediate to [7-{sup 3}H]-cortisol in cultured PHK. Trilostane (a 3{beta}HSD1 inhibitor) and ketoconazole (a CYP17A1 inhibitor) blocked the metabolism of both pregnenolone and progesterone. Finally, we show that normal skin expresses two cholesterol transporters, steroidogenic acute regulatory protein (StAR), regarded as the rate-determining protein for steroid synthesis, and metastatic lymph node 64 (MLN64) whose function has been linked to cholesterol transport in steroidogenesis. The expression of StAR and MLN64 was aberrant in two skin disorders, psoriasis and atopic dermatitis, that are commonly treated with cortisol, suggesting dysregulation of epidermal steroid synthesis in these patients. Collectively these data

  3. Global human appropriation of net primary production doubled in the 20th century

    PubMed Central

    Krausmann, Fridolin; Erb, Karl-Heinz; Gingrich, Simone; Haberl, Helmut; Bondeau, Alberte; Gaube, Veronika; Lauk, Christian; Plutzar, Christoph; Searchinger, Timothy D.

    2013-01-01

    Global increases in population, consumption, and gross domestic product raise concerns about the sustainability of the current and future use of natural resources. The human appropriation of net primary production (HANPP) provides a useful measure of human intervention into the biosphere. The productive capacity of land is appropriated by harvesting or burning biomass and by converting natural ecosystems to managed lands with lower productivity. This work analyzes trends in HANPP from 1910 to 2005 and finds that although human population has grown fourfold and economic output 17-fold, global HANPP has only doubled. Despite this increase in efficiency, HANPP has still risen from 6.9 Gt of carbon per y in 1910 to 14.8 GtC/y in 2005, i.e., from 13% to 25% of the net primary production of potential vegetation. Biomass harvested per capita and year has slightly declined despite growth in consumption because of a decline in reliance on bioenergy and higher conversion efficiencies of primary biomass to products. The rise in efficiency is overwhelmingly due to increased crop yields, albeit frequently associated with substantial ecological costs, such as fossil energy inputs, soil degradation, and biodiversity loss. If humans can maintain the past trend lines in efficiency gains, we estimate that HANPP might only grow to 27–29% by 2050, but providing large amounts of bioenergy could increase global HANPP to 44%. This result calls for caution in refocusing the energy economy on land-based resources and for strategies that foster the continuation of increases in land-use efficiency without excessively increasing ecological costs of intensification. PMID:23733940

  4. Effect of matrine on primary human hepatocytes in vitro.

    PubMed

    Gong, Xiaobing; Gao, Yuan; Guo, Guoqing; Vondran, Florian W R; Schwartlander, Ruth; Efimova, Ekaterina; Pless, Gesine; Sauera, Igor M; Neuhaus, Peter

    2015-03-01

    Matrine is a bioactive component of the traditional Chinese medical herb Sophora flavescens that has been used in China to treat various kinds of diseases including virus hepatitis. However, the molecular mechanisms underlying its hepatoprotective effects remains elusive. In the present study, primary human hepatocytes were employed to elucidate the protective effects and molecular mechanisms of matrine. We observed that low concentrations of matrine had no significant impact on albumin secretion, but high concentrations (>140 mg/L) of matrine decreased the albumin secretion in hepatocytes. Western blot data indicated that matrine at 140 mg/L at 72 h induced protein expression of CYP2A6, CYP2B6 and CYP3A4. Furthermore, high concentrations of matrine reduced LDH and AST levels and were cytotoxic to hepatocytes, leading to a decreased cell viability and total protein amount. Moreover, low concentrations of matrine, enhanced the ECOD activity and decreased the level of NO2 (-) induced by cytokines in human hepatocytes. Taken together, the present study sheds novel light on the molecular mechanisms of matrine and potential application of matrine in hepatic diseases.

  5. Transcranial focused ultrasound stimulation of human primary visual cortex

    PubMed Central

    Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

    2016-01-01

    Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications. PMID:27658372

  6. Transcranial focused ultrasound stimulation of human primary visual cortex

    NASA Astrophysics Data System (ADS)

    Lee, Wonhye; Kim, Hyun-Chul; Jung, Yujin; Chung, Yong An; Song, In-Uk; Lee, Jong-Hwan; Yoo, Seung-Schik

    2016-09-01

    Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.

  7. Interferon Alpha as a Primary Pathogenic Factor in Human Lupus

    PubMed Central

    2011-01-01

    Interferon alpha (IFN-α) is a critical mediator of human systemic lupus erythematosus (SLE). This review will summarize evidence supporting the role for IFN-α in the initiation of human SLE. IFN-α functions in viral immunity at the interface of innate and adaptive immunity, a position well suited to setting thresholds for autoimmunity. Some individuals treated with IFN-α for chronic viral infections develop de novo SLE, which frequently resolves when IFN-α is withdrawn, supporting the idea that IFN-α was causal. Abnormally high IFN-α levels are clustered within SLE families, suggesting that high serum IFN-α is a heritable risk factor for SLE. Additionally, SLE-risk genetic variants in the IFN-α pathway are gain of function in nature, resulting in either higher circulating IFN-α levels or greater sensitivity to IFN-α signaling in SLE patients. A recent genome-wide association study has identified additional novel genetic loci associated with high serum IFN-α in SLE patients. These data support the idea that genetically determined endogenous elevations in IFN-α predispose to human SLE. It is possible that some of these gain-of-function polymorphisms in the IFN-α pathway are useful in viral defense, and that risk of SLE is a burden we have taken on in the fight to defend ourselves against viral infection. PMID:21923413

  8. Human Rights Texts: Converting Human Rights Primary Source Documents into Data

    PubMed Central

    Fariss, Christopher J.; Linder, Fridolin J.; Jones, Zachary M.; Crabtree, Charles D.; Biek, Megan A.; Ross, Ana-Sophia M.; Kaur, Taranamol; Tsai, Michael

    2015-01-01

    We introduce and make publicly available a large corpus of digitized primary source human rights documents which are published annually by monitoring agencies that include Amnesty International, Human Rights Watch, the Lawyers Committee for Human Rights, and the United States Department of State. In addition to the digitized text, we also make available and describe document-term matrices, which are datasets that systematically organize the word counts from each unique document by each unique term within the corpus of human rights documents. To contextualize the importance of this corpus, we describe the development of coding procedures in the human rights community and several existing categorical indicators that have been created by human coding of the human rights documents contained in the corpus. We then discuss how the new human rights corpus and the existing human rights datasets can be used with a variety of statistical analyses and machine learning algorithms to help scholars understand how human rights practices and reporting have evolved over time. We close with a discussion of our plans for dataset maintenance, updating, and availability. PMID:26418817

  9. Human Rights Texts: Converting Human Rights Primary Source Documents into Data.

    PubMed

    Fariss, Christopher J; Linder, Fridolin J; Jones, Zachary M; Crabtree, Charles D; Biek, Megan A; Ross, Ana-Sophia M; Kaur, Taranamol; Tsai, Michael

    2015-01-01

    We introduce and make publicly available a large corpus of digitized primary source human rights documents which are published annually by monitoring agencies that include Amnesty International, Human Rights Watch, the Lawyers Committee for Human Rights, and the United States Department of State. In addition to the digitized text, we also make available and describe document-term matrices, which are datasets that systematically organize the word counts from each unique document by each unique term within the corpus of human rights documents. To contextualize the importance of this corpus, we describe the development of coding procedures in the human rights community and several existing categorical indicators that have been created by human coding of the human rights documents contained in the corpus. We then discuss how the new human rights corpus and the existing human rights datasets can be used with a variety of statistical analyses and machine learning algorithms to help scholars understand how human rights practices and reporting have evolved over time. We close with a discussion of our plans for dataset maintenance, updating, and availability.

  10. Empowering Learning through Natural, Human, and Building Ecologies.

    ERIC Educational Resources Information Center

    Kobet, Robert J.

    This article asserts that it is critical to understand the connections between human ecology and building ecology to create humane environments that show inspiration and creativity and that also serve diverse needs. It calls for efforts to: (1) construct an environmental education approach that fuses the three ecologies (natural, human, and…

  11. The historical character of human nature in Freud's theories.

    PubMed

    Zilbersheid, Uri

    2013-06-01

    In Freud' theories of human development, human nature is described and analyzed as essentially historical. At the core of human history is the restructuring of the sexual instinct and the death instinct (or its unique form as destructive impulses). The conscious, asked-for shaping of these two instincts, under the rule of the "reality principle", forms the basis of human society at all stages. This conscious restructuring has also unintended, unasked-for results, which are part of the historically developing human nature. The historical choice has been the building of human society as a social complex based on the de-eroticization of both the individual and society. Freud suggested that the historical process of changing human nature and maintaining the achieved new structure has mainly been an enterprise of enlightened political elite, which has imposed (in all societies) the various elements of the new nature upon the ordinary people. Human history is essentially a deed of the political sphere. In viewing human nature as consisting of both asked-for and unasked-for results of human conscious purposeful activity Freud belongs to the same historical school as Marx.

  12. Trehalose-Mediated Autophagy Impairs the Anti-Viral Function of Human Primary Airway Epithelial Cells

    PubMed Central

    Wu, Qun; Jiang, Di; Huang, Chunjian; van Dyk, Linda F.; Li, Liwu; Chu, Hong Wei

    2015-01-01

    Human rhinovirus (HRV) is the most common cause of acute exacerbations of chronic lung diseases including asthma. Impaired anti-viral IFN-λ1 production and increased HRV replication in human asthmatic airway epithelial cells may be one of the underlying mechanisms leading to asthma exacerbations. Increased autophagy has been shown in asthmatic airway epithelium, but the role of autophagy in anti-HRV response remains uncertain. Trehalose, a natural glucose disaccharide, has been recognized as an effective autophagy inducer in mammalian cells. In the current study, we used trehalose to induce autophagy in normal human primary airway epithelial cells in order to determine if autophagy directly regulates the anti-viral response against HRV. We found that trehalose-induced autophagy significantly impaired IFN-λ1 expression and increased HRV-16 load. Inhibition of autophagy via knockdown of autophagy-related gene 5 (ATG5) effectively rescued the impaired IFN-λ1 expression by trehalose and subsequently reduced HRV-16 load. Mechanistically, ATG5 protein interacted with retinoic acid-inducible gene I (RIG-I) and IFN-β promoter stimulator 1 (IPS-1), two critical molecules involved in the expression of anti-viral interferons. Our results suggest that induction of autophagy in human primary airway epithelial cells inhibits the anti-viral IFN-λ1 expression and facilitates HRV infection. Intervention of excessive autophagy in chronic lung diseases may provide a novel approach to attenuate viral infections and associated disease exacerbations. PMID:25879848

  13. Defensins: natural component of human innate immunity.

    PubMed

    Jarczak, Justyna; Kościuczuk, Ewa M; Lisowski, Paweł; Strzałkowska, Nina; Jóźwik, Artur; Horbańczuk, Jarosław; Krzyżewski, Józef; Zwierzchowski, Lech; Bagnicka, Emilia

    2013-09-01

    The widespread use of antibiotics has contributed to a huge increase in the number of resistant bacteria. New classes of drugs are therefore being developed of which defensins are a potential source. Defensins are a group of antimicrobial peptides found in different living organisms, involved in the first line of defense in their innate immune response against pathogens. This review summarizes the results of studies of this family of human antimicrobial peptides (AMPs). There is a special emphasis on describing the entire group and individual peptides, history of their discovery, their functions and expression sites. The results of the recent studies on the use of the biologically active peptides in human medicine are also presented. The pharmaceutical potential of human defensins cannot be ignored, especially considering their strong antimicrobial activity and properties such as low molecular weight, reduced immunogenicity, broad activity spectrum and resistance to proteolysis, but there are still many challenges and questions regarding the possibilities of their practical application.

  14. Antibiotics: natural products essential to human health.

    PubMed

    Demain, Arnold L

    2009-11-01

    For more than 50 years, natural products have served us well in combating infectious bacteria and fungi. Microbial and plant secondary metabolites helped to double our life span during the 20th century, reduced pain and suffering, and revolutionized medicine. Most antibiotics are either (i) natural products of microorganisms, (ii) semi-synthetically produced from natural products, or (iii) chemically synthesized based on the structure of the natural products. Production of antibiotics began with penicillin in the late 1940s and proceeded with great success until the 1970-1980s when it became harder and harder to discover new and useful products. Furthermore, resistance development in pathogens became a major problem, which is still with us today. In addition, new pathogens are continually emerging and there are still bacteria that are not eliminated by any antibiotic, e.g., Pseudomonas aeruginosa. In addition to these problems, many of the major pharmaceutical companies have abandoned the antibiotic field, leaving much of the discovery efforts to small companies, new companies, and the biotechnology industries. Despite these problems, development of new antibiotics has continued, albeit at a much lower pace than in the last century. We have seen the (i) appearance of newly discovered antibiotics (e.g., candins), (ii) development of old but unutilized antibiotics (e.g., daptomycin), (iii) production of new semi-synthetic versions of old antibiotics (e.g., glycylcyclines, streptogrammins), as well as the (iv) very useful application of old but underutilized antibiotics (e.g., teicoplanin).

  15. Liberal eugenics and human nature. Against Habermas.

    PubMed

    Fenton, Elizabeth

    2006-01-01

    In the course of developing his arguments against making genetic enhancements to one's children, Habermas assumes that a clear line can be drawn between the natural and the manufactured. But given the current state of medical science, this is precisely what we can no longer take for granted.

  16. Predictive Factors for Natural Pregnancy after Microsurgical Reconstruction in Patients with Primary Epididymal Obstructive Azoospermia

    PubMed Central

    Harza, Mihai; Gagiu, Cristian; Baston, Catalin; Preda, Adrian; Manea, Ioan; Priporeanu, Tiberiu

    2014-01-01

    Primary epididymal obstructive azoospermia (OA) is the most prevalent form of OA in nonvasectomized patients and has been less studied. We aim to assess the results with microsurgical vasoepididymostomy used in the treatment of men diagnosed with primary epididymal obstructive azoospermia and to identify the factors associated with natural pregnancy occurring after microsurgical reconstruction. This prospective study included consecutive patients with epididymal OA who underwent microsurgical reconstruction in our center. Clinical and biological data were obtained every three months during follow-up. Occurrence of natural pregnancy was the primary study outcome. In total, 36 patients underwent microsurgical reconstruction. The mean age was 34 ± 4.5 years (range 24–46 years). Median follow-up time was 15 [IQR 12–21] months. The total patency rate was 77.7% (n = 28). During follow-up, 8 (22.2%) natural pregnancies occurred. The overall live birth rate was 100%. Low FSH levels (HR: 0.22; 95% CI: 0.052–0.88; P = 0.032) and higher total motile sperm count (TMSC) (HR: 1.001; 95% CI 1–1.001; P = 0.012) were associated with a higher rate of natural pregnancy. Our data suggest that microsurgical vasoepididymostomy is an effective therapy of primary epididymal OA. Baseline lower FSH and higher TMSC were independent predictors for natural pregnancy occurrence. PMID:24987417

  17. Autoreactivity of primary human immunoglobulins ancestral to hypermutated human antibodies that neutralize HCMV.

    PubMed

    McLean, Gary R; Cho, Chin-wen; Schrader, John W

    2006-05-01

    The human antibody response to the AD-2S1 epitope of glycoprotein B (gB) of human cytomegalovirus (HCMV) is dominated by a family of closely related somatically mutated antibodies. These antibodies neutralize viral infectivity and the genes encoding them are derived from two commonly used germ-line variable (V) region genes, IGHV3-30 and IGKV3-11. Recombination of these V genes with the appropriate junctional diversity generates genes that encode primary immunoglobulins that bind to AD-2S1. To further understand the initial primary immunoglobulin response to AD-2S1 we synthesized the germ-line-based ancestor of one such family of antibodies and showed that it bound gB at the AD-2S1 epitope. Here we show that the germ-line ancestor of a second family of antibodies likewise binds to gB. We further show that one of the ancestral primary immunoglobulins, but not the other, also recognized autoantigens. In contrast, the hypermutated derivatives did not demonstrate autoreactivity and minor structural changes in the primary immunoglobulin were sufficient to generate or abolish autoreactivity or to change specificity. Thus, our demonstration that the ancestor of a highly mutated, non-autoreactive antiviral IgG antibody binds nuclear and cell-surface autoantigens indicates for the first time that self-reactivity is not necessarily a barrier to development into a follicular B lymphocyte that undergoes antigen-initiated affinity maturation.

  18. Noradrenaline release and the pathophysiology of primary human hypertension

    SciTech Connect

    Esler, M.; Jennings, G.; Lambert, G.

    1989-03-01

    Measurements of the overflow of norepinephrine to plasma from individual organs (using radiotracer methodology) were used to delineate the pattern of sympathetic nervous system activation present in primary human hypertension. Mean total norepinephrine (NE) spillover in hypertensive patients was 418 ng/min, 42% (124 ng/min) higher than in subjects with normal blood pressure (BP)(P less than .05). Norepinephrine spillover among hypertensive patients was a function of age, only being elevated in patients under 40 years of age. Half of the excess in total norepinephrine release in hypertensive patients was accounted for by increased cardiorenal spillover. Mean renal norepinephrine spillover was 120 ng/min, compared with 69 ng/min in healthy subjects (P less than .02). Renal spillover was highest in younger patients. Corresponding cardiac norepinephrine spillover values were 12.6 ng/min and 5.1 ng/min (P less than .01). The balance of the excess total norepinephrine spillover comes from undetermined sites, but not the lungs or hepatomesenteric circulation. These measurements of regional norepinephrine overflow suggest that sympathetic nervous outflow to the kidneys and heart is selectively activated in early hypertension. 21 references.

  19. Punicalagin promotes autophagy to protect primary human syncytiotrophoblasts from apoptosis.

    PubMed

    Wang, Ying; Chen, Baosheng; Longtine, Mark S; Nelson, D Michael

    2016-02-01

    Punicalagin is a prominent polyphenol in pomegranate juice that protects cultured syncytiotrophoblasts from stress-induced apoptosis. Here, we test the hypothesis that punicalagin has this effect by inhibiting the mTOR kinase pathway to enhance autophagic turnover and limit apoptosis in cultured primary human syncytiotrophoblasts. In syncytiotrophoblasts, starvation, rapamycin, or punicalagin all decreased the expression of phosphorylated ribosomal protein S6, a downstream target of the mTOR kinase, and of the autophagy markers, LC3-II and p62. In contrast, in the presence of bafilomycin, an inhibitor of late stages of autophagy and degradation in the autophagolysosome, syncytiotrophoblasts exposed to starvation, rapamycin, or punicalagin all showed increased levels of LC3-II and p62. The number of LC3-II punctae also increased in punicalagin-treated syncytiotrophoblasts exposed to chloroquine, another inhibitor of autophagic degradation, and punicalagin increased the number of lysosomes. The apoptosis-reducing effect of punicalagin was attenuated by inhibition of autophagy using bafilomycin or knockdown of the autophagy related gene, ATG16L1. Collectively, these data support the hypothesis that punicalagin modulates the crosstalk between autophagy and apoptosis to promote survival in cultured syncytiotrophoblasts. PMID:26659860

  20. Biased Allelic Expression in Human Primary Fibroblast Single Cells

    PubMed Central

    Borel, Christelle; Ferreira, Pedro G.; Santoni, Federico; Delaneau, Olivier; Fort, Alexandre; Popadin, Konstantin Y.; Garieri, Marco; Falconnet, Emilie; Ribaux, Pascale; Guipponi, Michel; Padioleau, Ismael; Carninci, Piero; Dermitzakis, Emmanouil T.; Antonarakis, Stylianos E.

    2015-01-01

    The study of gene expression in mammalian single cells via genomic technologies now provides the possibility to investigate the patterns of allelic gene expression. We used single-cell RNA sequencing to detect the allele-specific mRNA level in 203 single human primary fibroblasts over 133,633 unique heterozygous single-nucleotide variants (hetSNVs). We observed that at the snapshot of analyses, each cell contained mostly transcripts from one allele from the majority of genes; indeed, 76.4% of the hetSNVs displayed stochastic monoallelic expression in single cells. Remarkably, adjacent hetSNVs exhibited a haplotype-consistent allelic ratio; in contrast, distant sites located in two different genes were independent of the haplotype structure. Moreover, the allele-specific expression in single cells correlated with the abundance of the cellular transcript. We observed that genes expressing both alleles in the majority of the single cells at a given time point were rare and enriched with highly expressed genes. The relative abundance of each allele in a cell was controlled by some regulatory mechanisms given that we observed related single-cell allelic profiles according to genes. Overall, these results have direct implications in cellular phenotypic variability. PMID:25557783

  1. 3D Cultivation Techniques for Primary Human Hepatocytes

    PubMed Central

    Bachmann, Anastasia; Moll, Matthias; Gottwald, Eric; Nies, Cordula; Zantl, Roman; Wagner, Helga; Burkhardt, Britta; Sánchez, Juan J. Martínez; Ladurner, Ruth; Thasler, Wolfgang; Damm, Georg; Nussler, Andreas K.

    2015-01-01

    One of the main challenges in drug development is the prediction of in vivo toxicity based on in vitro data. The standard cultivation system for primary human hepatocytes is based on monolayer cultures, even if it is known that these conditions result in a loss of hepatocyte morphology and of liver-specific functions, such as drug-metabolizing enzymes and transporters. As it has been demonstrated that hepatocytes embedded between two sheets of collagen maintain their function, various hydrogels and scaffolds for the 3D cultivation of hepatocytes have been developed. To further improve or maintain hepatic functions, 3D cultivation has been combined with perfusion. In this manuscript, we discuss the benefits and drawbacks of different 3D microfluidic devices. For most systems that are currently available, the main issues are the requirement of large cell numbers, the low throughput, and expensive equipment, which render these devices unattractive for research and the drug-developing industry. A higher acceptance of these devices could be achieved by their simplification and their compatibility with high-throughput, as both aspects are of major importance for a user-friendly device.

  2. Proteomic and Bioinformatic Profile of Primary Human Oral Epithelial Cells

    PubMed Central

    Ghosh, Santosh K.; Yohannes, Elizabeth; Bebek, Gurkan; Weinberg, Aaron; Jiang, Bin; Willard, Belinda; Chance, Mark R.; Kinter, Michael T.; McCormick, Thomas S.

    2012-01-01

    Wounding of the oral mucosa occurs frequently in a highly septic environment. Remarkably, these wounds heal quickly and the oral cavity, for the most part, remains healthy. Deciphering the normal human oral epithelial cell (NHOEC) proteome is critical for understanding the mechanism(s) of protection elicited when the mucosal barrier is intact, as well as when it is breached. Combining 2D gel electrophoresis with shotgun proteomics resulted in identification of 1662 NHOEC proteins. Proteome annotations were performed based on protein classes, molecular functions, disease association and membership in canonical and metabolic signaling pathways. Comparing the NHOEC proteome with a database of innate immunity-relevant interactions (InnateDB) identified 64 common proteins associated with innate immunity. Comparison with published salivary proteomes revealed that 738/1662 NHOEC proteins were common, suggesting that significant numbers of salivary proteins are of epithelial origin. Gene ontology analysis showed similarities in the distributions of NHOEC and saliva proteomes with regard to biological processes, and molecular functions. We also assessed the inter-individual variability of the NHOEC proteome and observed it to be comparable with other primary cells. The baseline proteome described in this study should serve as a resource for proteome studies of the oral mucosa, especially in relation to disease processes. PMID:23035736

  3. The ethics of impossible and possible changes to human nature.

    PubMed

    Murphy, Timothy F

    2012-05-01

    Some commentators speak freely about genetics being poised to change human nature. Contrary to such rhetoric, Norman Daniels believes no such thing is plausible since 'nature' describes characteristic traits of human beings as a whole. Genetic interventions that do their work one individual at a time are unlikely to change the traits of human beings as a class. Even so, one can speculate about ways in which human beings as a whole could be genetically altered, and there is nothing about that venture that could not be deliberated in the way other high-impact questions can be evaluated. There might well come a time when it would be defensible to use genetics to change human beings as a class, in order to protect people in the face of changed environmental circumstances or to enhance existing capacities. Moreover, if one understands human nature not in an empirically descriptive way but in a metaphysical way having implications about human behavior, it can make sense to talk about de-naturing individuals through genetic changes. Even under a metaphysical conception of human nature, however, one can still imagine that people in the future might want to alter their traits in pursuit of another normative idea of a good and valuable life, and genetic modifications might function as a pathway to that change.

  4. Virulent Coxiella burnetii pathotypes productively infect primary human alveolar macrophages.

    PubMed

    Graham, Joseph G; MacDonald, Laura J; Hussain, S Kauser; Sharma, Uma M; Kurten, Richard C; Voth, Daniel E

    2013-06-01

    The intracellular bacterial pathogen Coxiella burnetii is a category B select agent that causes human Q fever. In vivo, C. burnetii targets alveolar macrophages wherein the pathogen replicates in a lysosome-like parasitophorous vacuole (PV). In vitro, C. burnetii infects a variety of cultured cell lines that have collectively been used to model the pathogen's infectious cycle. However, differences in the cellular response to infection have been observed, and virulent C. burnetii isolate infection of host cells has not been well defined. Because alveolar macrophages are routinely implicated in disease, we established primary human alveolar macrophages (hAMs) as an in vitro model of C. burnetii-host cell interactions. C. burnetii pathotypes, including acute disease and endocarditis isolates, replicated in hAMs, albeit with unique PV properties. Each isolate replicated in large, typical PV and small, non-fused vacuoles, and lipid droplets were present in avirulent C. burnetii PV. Interestingly, a subset of small vacuoles harboured single organisms undergoing degradation. Prototypical PV formation and bacterial growth in hAMs required a functional type IV secretion system, indicating C. burnetii secretes effector proteins that control macrophage functions. Avirulent C. burnetii promoted sustained activation of Akt and Erk1/2 pro-survival kinases and short-termphosphorylation of stress-related p38. Avirulent organisms also triggered a robust, early pro-inflammatory response characterized by increased secretion of TNF-α and IL-6, while virulent isolates elicited substantially reduced secretion of these cytokines. A corresponding increase in pro- and mature IL-1β occurred in hAMs infected with avirulent C. burnetii, while little accumulation was observed following infection with virulent isolates. Finally, treatment of hAMs with IFN-γ controlled intracellular replication, supporting a role for this antibacterial insult in the host response to C

  5. Young Scientists Explore the World of Nature. Book 1 Primary Level.

    ERIC Educational Resources Information Center

    Penn, Linda

    Designed to present interesting facts about science and to heighten the curiosity of primary age students, this book contains activities about the natural world and numerous black and white illustrations. The first section focuses on trees and investigates types common to all states and climates. A tiny seed mascot, known as Ollie Acorn,…

  6. Determination of the Turkish Primary Students' Views about the Particulate Nature of Matter

    ERIC Educational Resources Information Center

    Ozmen, Haluk; Kenan, Osman

    2007-01-01

    This study was conducted to determine 4th, 5th, and 6th grade Turkish primary students' conceptions about the particulate nature of matter via a test. The test consists of 36 items related to the changes of microscopic properties of solid, liquid and gas matters during phase changing, cooling, heating and pressing of them. The sample of the study…

  7. The human impact on the natural environment

    SciTech Connect

    Goudie, A.

    1990-01-01

    The transformation of the environment and of landscapes by human actions has become one of the most critical issues on any agenda for the 21st century. This book is a source of information to students in environmental studies, offering an expanded treatment of atmospheric effects - particularly acid deposition, ozone depletion, and the buildup of greenhouse gases - and of future scenarios relating to global warming trends. The author focuses on the critical man/land relationships that result in environmental change, hazards, or degradation, covering plants, animals, soil, waters, geomorphology, climate, and atmosphere.

  8. Inhibition of human natural killer cell functional activity by human aspartyl β-hydroxylase.

    PubMed

    Huyan, Ting; Li, Qi; Ye, Lin-Jie; Yang, Hui; Xue, Xiao-Ping; Zhang, Ming-Jie; Huang, Qing-Sheng; Yin, Da-Chuan; Shang, Peng

    2014-12-01

    Natural killer (NK) cells are a key component of the innate immune system and play pivotal roles as inflammatory regulators and in tumor surveillance. Human aspartyl β-hydroxylase (HAAH) is a plasma membrane and endoplasmic reticulum protein with hydroxylation activity, which is over-expressed in many malignant neoplasms and can be detected from the sera of tumor patients. HAAH is involved in regulating tumor cell infiltration and metastasis. Escaping from immune surveillance may help tumor cell infiltration and metastasis. However, the effects of HAAH on tumor immune surveillance have not yet been investigated carefully. The present study investigated the potential use of HAAH as an immune regulator of human NK cells. We assessed the effects of recombinant HAAH (r-HAAH) on primary human NK cell morphology, viability, cytotoxicity, apoptosis, receptors expression and cytokine/cytolytic proteins production. Our results demonstrated that r-HAAH negatively affects NK cell activity in a time and dose-dependent manner. It noticeably reduces the viability of the NK cells by increasing apoptosis and necrosis via caspase signaling pathways. Moreover, r-HAAH reduces the NK cell cytotoxicity by inhibiting surface expression of NKG2D, NKp44 and IFN-γ secretion. These findings suggest that one of the ways by which HAAH actively promotes tumor formation and proliferation is by inhibiting NK cell-surveillance activity.

  9. Human/Nature Discourse in Environmental Science Education Resources

    ERIC Educational Resources Information Center

    Chambers, Joan M.

    2008-01-01

    It is argued that the view of nature and the relationship between human beings and nature that each of us holds impacts our decisions, actions, and notions of environmental responsibility and consciousness. In this study, I investigate the discursive patterns of selected environmental science classroom resources produced by three disparate…

  10. Maslow Revisited: Constructing a Road Map of Human Nature

    ERIC Educational Resources Information Center

    O'Connor, Dennis; Yballe, Leodones

    2007-01-01

    Given the scope and intent of Maslow's work, the current textbook treatment is wanting. Therefore, an inductive exercise has been created and is offered here to build "the road map of human nature." This age-old, philosophic focus on our true nature has been a way to successfully engage and inspire both our students and our pedagogy. In the spirit…

  11. Natural and human impacts on ecosystem services in Guanzhong - Tianshui economic region of China.

    PubMed

    Li, Jing; Zhou, Z X

    2016-04-01

    Due to the accelerated growth of society, the gaps between the capacity of ecosystems to provide services and human needs are steadily widening. Natural, semi-natural, or managed ecosystems had been able to provide ecosystem services to meet the needs of social development. Four agricultural ecosystem services (net primary production (NPP), carbon sequestration and oxygen production (CSOP), water interception, soil conservation and agriculture production) were quantified in Guanzhong-Tianshui economic region. Estimates of ecosystem services were obtained from the analysis of satellite imagery and the use of well-known models. Based on the ecological services in Guanzhong-Tianshui economic region, this study mainly analysed the driving mechanism of the changes from the two aspects of natural drivers and human drivers. Natural drivers (climate, soil, elevation, land cover) had incentive to the ecological services. Human activity was quantified by an integrated human activity index (HAI) based on population density, farmland ratio, and the influence of road networks and residential areas. We found relationships between ecosystem services, human activities and many natural factors, however these varied according to the service studied. Human activities were mostly negatively related to each ecosystem services, while population and residential land ware positively related to agricultural production. Land use change had made a contribution to ecosystem services. Based on the selected ecosystem services and HAI, we provided sustainable ecosystem management suggestions.

  12. Radiosensitivity of human natural killer cells: Binding and cytotoxic activities of natural killer cell subsets

    SciTech Connect

    Rana, R.; Vitale, M.; Mazzotti, G.; Manzoli, L.; Papa, S. )

    1990-10-01

    The sensitivity of human natural killer (NK) cell activities (both binding and killing) after exposure of peripheral blood mononuclear cells to different doses of gamma radiation was studied. A panel of monoclonal antibodies was used to identify the NK and T-lymphocyte subsets and to evaluate their radiosensitivity. Peripheral blood mononuclear cells were irradiated with low (2-6 Gy) and high (10-30 Gy) doses and NK cell binding and cytotoxic activity against K562 target cells were studied after 3 h and 48 h in culture. The primary damage to NK cell activity was identified at the postbinding level and affected mainly the lytic machinery. After 48 h culture postirradiation, an overall depression of cytotoxic activity was observed, but ionizing radiation produced either a selection of the more cytotoxic NK cell subsets, which therefore might be considered more resistant to radiation damage than the less cytotoxic NK cells, or a long-term stimulation of cytotoxic activity in surviving cells.

  13. Antibacterial activity of human natural killer cells

    PubMed Central

    1989-01-01

    The in vitro effects of human NK cells on viability of Gram-negative and Gram-positive bacteria was investigated. PBLs depleted of glass- adherent cells showed a significant antibacterial activity that was increased as the concentration of NK cells became higher. Leu-11- enriched cells exhibited the most efficient bactericidal activity. Stimulation of NK cells with staphylococcal enterotoxin B for 16 h produced a significant increase in the antibacterial activity of all NK cells tested. The antibacterial activity of monocyte-depleted cells and Leu-11-enriched cells was also enhanced after culturing in vitro for 16- 24 h without exogenous cytokines. Dependence of the antibacterial activity on the presence of serum in the culture medium was not found. Ultrastructural studies revealed close contact between NK cell membranes and bacteria, no evidence of phagocytosis, and extracellular bacterial ghosts, after incubation at 37 degrees C. Supernatants from purified NK cells exhibited potent bactericidal activity with kinetics and target specificity similar to that of effector cells. These results document the potent antibacterial activity of purified NK cells and suggest an extracellular mechanism of killing. PMID:2642532

  14. Natural auditory scene statistics shapes human spatial hearing

    PubMed Central

    Parise, Cesare V.; Knorre, Katharina; Ernst, Marc O.

    2014-01-01

    Human perception, cognition, and action are laced with seemingly arbitrary mappings. In particular, sound has a strong spatial connotation: Sounds are high and low, melodies rise and fall, and pitch systematically biases perceived sound elevation. The origins of such mappings are unknown. Are they the result of physiological constraints, do they reflect natural environmental statistics, or are they truly arbitrary? We recorded natural sounds from the environment, analyzed the elevation-dependent filtering of the outer ear, and measured frequency-dependent biases in human sound localization. We find that auditory scene statistics reveals a clear mapping between frequency and elevation. Perhaps more interestingly, this natural statistical mapping is tightly mirrored in both ear-filtering properties and in perceived sound location. This suggests that both sound localization behavior and ear anatomy are fine-tuned to the statistics of natural auditory scenes, likely providing the basis for the spatial connotation of human hearing. PMID:24711409

  15. Optimal speed estimation in natural image movies predicts human performance.

    PubMed

    Burge, Johannes; Geisler, Wilson S

    2015-01-01

    Accurate perception of motion depends critically on accurate estimation of retinal motion speed. Here we first analyse natural image movies to determine the optimal space-time receptive fields (RFs) for encoding local motion speed in a particular direction, given the constraints of the early visual system. Next, from the RF responses to natural stimuli, we determine the neural computations that are optimal for combining and decoding the responses into estimates of speed. The computations show how selective, invariant speed-tuned units might be constructed by the nervous system. Then, in a psychophysical experiment using matched stimuli, we show that human performance is nearly optimal. Indeed, a single efficiency parameter accurately predicts the detailed shapes of a large set of human psychometric functions. We conclude that many properties of speed-selective neurons and human speed discrimination performance are predicted by the optimal computations, and that natural stimulus variation affects optimal and human observers almost identically.

  16. Relational Human Ecology: Reconciling the Boundaries of Humans and Nature

    NASA Astrophysics Data System (ADS)

    McNiel, J.; Lopes, V. L.

    2010-12-01

    Global change is transforming the planet at unprecedented rates. Global warming, massive species extinction, increasing land degradation, overpopulation, poverty and injustice, are all the result of human choices and non-sustainable ways of life. What do we have to do and how much do we have to change to allow a transition to a more ecologically-conscious and just society? While these questions are of central concern, they cannot be fully addressed under the current paradigm, which hinders both our collection of knowledge and derivation of solutions. This paper attempts to develop a new variant of ecological thinking based on a relational ontological/epistemological approach. This is offered as a foundation for the political initiative to strive for a more fulfilling, sustainable and just society. This new approach, theoretically conceptualized as ‘relational human ecology,’ offers a relational (holistic) framework for overcoming mechanistic thinking and exploring questions regarding the long-term attainment of sustainability. Once established, we illustrate how the relational framework offers a new holistic approach centered on participatory inquiry within the context of a community workshop. We conclude with discussing possible directions for future relational human ecological participatory research, conducted from the intersection of myriad participants (i.e. agencies, academics, and community residents), and the ways in which this will allow for the derivation of accurate and sustainable solutions for global change. Key words: relational thinking, human ecology, complex adaptive systems, participatory inquiry, sustainability Vicente L. Lopes (corresponding author) Department of Biology Texas State University San Marcos, TX, USA e-mail: vlopes@txstate.edu Jamie N. McNiel Department of Sociology Texas State University San Marcos, TX, USATable 2 - Comparing Orthodox versus Relational Approaches to Ecological Inquiry * Retroduction, logical reasoning that

  17. Digital technology and human development: a charter for nature conservation.

    PubMed

    Maffey, Georgina; Homans, Hilary; Banks, Ken; Arts, Koen

    2015-11-01

    The application of digital technology in conservation holds much potential for advancing the understanding of, and facilitating interaction with, the natural world. In other sectors, digital technology has long been used to engage communities and share information. Human development-which holds parallels with the nature conservation sector-has seen a proliferation of innovation in technological development. Throughout this Perspective, we consider what nature conservation can learn from the introduction of digital technology in human development. From this, we derive a charter to be used before and throughout project development, in order to help reduce replication and failure of digital innovation in nature conservation projects. We argue that the proposed charter will promote collaboration with the development of digital tools and ensure that nature conservation projects progress appropriately with the development of new digital technologies. PMID:26508341

  18. Digital technology and human development: a charter for nature conservation.

    PubMed

    Maffey, Georgina; Homans, Hilary; Banks, Ken; Arts, Koen

    2015-11-01

    The application of digital technology in conservation holds much potential for advancing the understanding of, and facilitating interaction with, the natural world. In other sectors, digital technology has long been used to engage communities and share information. Human development-which holds parallels with the nature conservation sector-has seen a proliferation of innovation in technological development. Throughout this Perspective, we consider what nature conservation can learn from the introduction of digital technology in human development. From this, we derive a charter to be used before and throughout project development, in order to help reduce replication and failure of digital innovation in nature conservation projects. We argue that the proposed charter will promote collaboration with the development of digital tools and ensure that nature conservation projects progress appropriately with the development of new digital technologies.

  19. Fieldwork: man in the system of nature and priority of natural laws in human life.

    PubMed

    Tinyakova, Elena

    2007-06-01

    Fieldwork is a branch of inseparable unity of natural and humanitarian sciences; it is aimed at the cultural origin of humanity on the maximum level of its variety. Practically all natural sciences have some space determined by ethnic conscience in nature cognition: ethnodemography, ethnobotany, ethnozoology, etc. Fieldwork guides the research of human culture from the laws of nature. This kind of knowledge is useful to balance human relations with nature and avoid conflicts. Peoples should exchange their wisdom in the dialogue with nature to be more safe. Fieldwork understood as traditional culture only, explaining the variety of ethnoses on our earth, is just the narrow and diachronic level of this branch of knowledge. The cosmological knowledge, where fantasy and not exhausted in its cognition understanding the world of nature are mixed, forms the source of fieldwork and in many respects explains the direction of knowledge: the man finds himself under the open sky, he is the child of nature. Then as time went on there appeared a gradual transition--first nature was creating the man, then by and by he began turning to answer nature by his activity. Nowadays the man is actively creating nature. There are two levels of fieldwork: the ancient one which deals with the origin of ethnoses and the modern one which explores how contemporary life is determined by ethnic specific traits. Fieldwork is the core of multidisciplinary situation in man's knowledge. It is related to such humanitarian sciences: semiotics, culturology, sociology, history, philosophy, literature, linguistics. In the cycle of natural sciences fieldwork stands close to anthropology, geography, biology, demography. Fieldwork as a science has the two main levels--the "sophy" level and the logos "level". The first one discovers wisdom of human life, the second one is aimed at logical structuring of knowledge, here proceed various classifications of peoples.

  20. Attachment of human primary osteoblast cells to modified polyethylene surfaces.

    PubMed

    Poulsson, Alexandra H C; Mitchell, Stephen A; Davidson, Marcus R; Johnstone, Alan J; Emmison, Neil; Bradley, Robert H

    2009-04-01

    Ultra-high-molecular-weight polyethylene (UHMWPE) has a long history of use in medical devices, primarily for articulating surfaces due to its inherent low surface energy which limits tissue integration. To widen the applications of UHMWPE, the surface energy can be increased. The increase in surface energy would improve the adsorption of proteins and attachment of cells to allow tissue integration, thereby allowing UHMWPE to potentially be used for a wider range of implants. The attachment and function of human primary osteoblast-like (HOB) cells to surfaces of UHMWPE with various levels of incorporated surface oxygen have been investigated. The surface modification of the UHMWPE was produced by exposure to a UV/ozone treatment. The resulting surface chemistry was studied using X-ray photoelectron spectroscopy (XPS), and the topography and surface structure were probed by atomic force microscopy (AFM) and scanning electron microscopy (SEM), which showed an increase in surface oxygen from 11 to 26 atom % with no significant change to the surface topography. The absolute root mean square roughness of both untreated and UV/ozone-treated surfaces was within 350-450 nm, and the water contact angles decreased with increasing oxygen incorporation, i.e., showing an increase in surface hydrophilicity. Cell attachment and functionality were assessed over a 21 day period for each cell-surface combination studied; these were performed using SEM and the alamarBlue assay to study cell attachment and proliferation and energy-dispersive X-ray (EDX) analysis to confirm extracellular mineral deposits, and total protein assay to examine the intra- and extracellular protein expressed by the cells. HOB cells cultured for 21 days on the modified UHMWPE surfaces with 19 and 26 atom % oxygen incorporated showed significantly higher cell densities compared to cells cultured on tissue culture polystyrene (TCPS) from day 3 onward. This indicated that the cells attached and proliferated more

  1. Missing an opportunity: the embedded nature of weight management in primary care

    PubMed Central

    Osunlana, A. M.; Ogunleye, A. A.; Sharma, A. M.; Campbell‐Scherer, D.

    2015-01-01

    Summary The 5As Team study was designed to create, implement and evaluate a flexible intervention to improve the quality and quantity of weight management visits in primary care. The objective of this portion of the study was to explore how primary care providers incorporate weight management in their practice. 5AsT is a randomized controlled trial (RCT) on the implementation of a 6‐month 5 As Team (5AsT) intervention designed to operationalize the 5As of obesity management in primary care. Data for the qualitative portion of the study presented here included semi‐structured interviews with 29 multidisciplinary team providers and field notes of intervention sessions. Thematic analysis was undertaken. A key pattern that emerged from the data was that healthcare providers usually do not address obesity as a primary focus for a visit. Rather, obesity is embedded in a wide range of primary care encounters for other conditions. Implications were it can take extra time to discuss weight, it can be inappropriate to bring up weight as a topic, and treating risk factors and root causes of obesity have indirect benefits to patient weight management. Our findings have implications for obesity treatment approaches and tools that assume a discreet weight management visit. The embedded nature of obesity management in primary care can be harnessed to leverage multiple opportunities for asking and assessing root causes of obesity, and working longitudinally towards individual health goals. PMID:26303812

  2. Inquiry-Based Learning in Teacher Education: A Primary Humanities Example

    ERIC Educational Resources Information Center

    Preston, Lou; Harvie, Kate; Wallace, Heather

    2015-01-01

    Inquiry-based learning features strongly in the new Australian Humanities and Social Sciences curriculum and increasingly in primary school practice. Yet, there is little research into, and few exemplars of, inquiry approaches in the primary humanities context. In this article, we outline and explain the implementation of a place-based simulation…

  3. Orientation anisotropies in human primary visual cortex depend on contrast.

    PubMed

    Maloney, Ryan T; Clifford, Colin W G

    2015-10-01

    Orientation processing in visual cortex appears matched to the environment, such that larger neural populations are tuned to cardinal (horizontal/vertical) than oblique orientations. This may be manifested perceptually as a cardinal bias: poorer sensitivity to oblique compared to cardinal orientations (the "oblique effect"). However, a growing body of psychophysical data reveals the opposite pattern of anisotropy: a bias towards the oblique over the cardinal orientations (the "horizontal effect"), something matched by recent functional magnetic resonance imaging (fMRI) studies that have found an increased response to the oblique over the cardinal orientations in early visual cortex. This may reveal the operation of an efficient coding strategy optimised to the diet of orientations encountered during natural viewing. From consideration of coding efficiency, it might be expected that the anisotropies would change as the quality/strength of the oriented stimulus changes. In two experiments, fMRI response modulations were measured in retinotopically-defined human early visual cortex as a function of the contrast and orientation of sinusoidal gratings. Both experiments revealed a marked change in the V1 response from a cardinal (vertical) bias at low contrast to an oblique bias at high contrast. In Experiment 2, this was also apparent in areas V2 and V3. On average, there was no systematic "radial bias" (a preference for orientations aligned with the visual field meridian) in V1, although it was present in some individual subjects. The change in orientation anisotropies with contrast is consistent with an adaptive stimulus coding strategy in cortex that shifts according to the strength of the sensory inputs. PMID:26093331

  4. Matrigel improves functional properties of primary human salivary gland cells.

    PubMed

    Maria, Ola M; Zeitouni, Anthony; Gologan, Olga; Tran, Simon D

    2011-05-01

    Currently, there is no effective treatment available to patients with irreversible loss of functional salivary acini caused by Sjogren's syndrome or after radiotherapy for head and neck cancer. A tissue-engineered artificial salivary gland would help these patients. The graft cells for this device must establish tight junctions in addition to being of fluid-secretory nature. This study analyzed a graft source from human salivary glands (huSG) cultured on Matrigel. Cells were obtained from parotid and submandibular glands, expanded in vitro, and then plated on either Matrigel-coated (2 mg/mL) or uncoated culture dish. Immunohistochemistry, transmission electron microscopy, quantitative real-time-polymerase chain reaction, Western blot, and transepithelial electrical resistance were employed. On Matrigel, huSG cells adopted an acinar phenotype by forming three-dimensional acinar-like units (within 24 h of plating) as well as a monolayer of cells. On uncoated surfaces (plastic), huSG cells only formed monolayers of ductal cells. Both types of culture conditions allowed huSG cells to express tight junction proteins (claudin-1, -2, -3, -4; occludin; JAM-A; and ZO-1) and adequate transepithelial electrical resistance. Importantly, 99% of huSG cells on Matrigel expressed α-amylase and the water channel protein Aquaporin-5, as compared to <5% of huSG cells on plastic. Transmission electron microscopy confirmed an acinar phenotype with many secretory granules. Matrigel increased the secretion of α-amylase two to five folds into the media, downregulated certain salivary genes, and regulated the translation of acinar proteins. This three-dimensional in vitro serum-free cell culture method allows the organization and differentiation of huSG cells into salivary cells with an acinar phenotype.

  5. Intravenous immunoglobulin treatment preserves and protects primary rat hippocampal neurons and primary human brain cultures against oxidative insults.

    PubMed

    Lahiri, Debomoy K; Ray, Balmiki

    2014-01-01

    Alzheimer's disease (AD) is characterized by deleterious accumulation of amyloid-β (Aβ) peptide into senile plaque, neurofibrillary tangles formed from hyperphosphorylated tau protein, and loss of cholinergic synapses in the cerebral cortex. The deposition of Aβ-loaded plaques results in microglial activation and subsequent production of reactive oxygen species (ROS), including free radicals. Neurons in aging and AD brains are particularly vulnerable to ROS and other toxic stimuli. Therefore, agents that decrease the vulnerability of neurons against ROS may provide therapeutic values for the treatment or prevention of AD. In the present study, our goal was to test whether intravenous immunoglobulin (IVIG) treatment could preserve as well as protect neurons from oxidative damage. We report that treatment with IVIG protects neuronal viability and synaptic proteins in primary rat hippocampal neurons. Further, we demonstrate the tolerability of IVIG treatment in the primary human fetal mixed brain cultures. Indeed, a high dose (20 mg/ml) of IVIG treatment was well-tolerated by primary human brain cultures that exhibit a normal neuronal phenotype. We also observed a potent neuropreservatory effect of IVIG against ROS-mediated oxidative insults in these human fetal brain cultures. These results indicate that IVIG treatment has great potential to preserve and protect primary human neuronal-enriched cultures and to potentially rescue dying neurons from oxidative insults. Therefore, our findings suggest that IVIG treatment may represent an important therapeutic agent for clinical trials designed to prevent and delay the onset of neurodegeneration as well as AD pathology. PMID:25115544

  6. About being pure and natural: understandings of pre-service primary teachers

    NASA Astrophysics Data System (ADS)

    Lake, David

    2005-04-01

    In an investigation of 149 pre-service primary teachers' understanding of the terms pure and natural, the participants were asked to provide definitions of the two words, and classify various substances including drugs of abuse, pharmaceuticals, nutriceuticals, and household substances as either natural or not natural, and as pure or not pure. A common scale of purity and naturalness could be constructed consistent with the Rasch model, suggesting that the participants conflate the two terms. This conflation is consistent with the qualitative data that suggested participants associated both concepts within a common spiritual metaphor, heavily laden with emotive content. Purity was not seen as relating to the composition of a substance, but to its history. The findings may help explain the development of persistent non-scientific chemical taxonomies observed in secondary students. Furthermore, as health educators, the participants may become the source of inappropriate messages about the use of medicines, or the abuse of drugs.

  7. The nature and perception of fluctuations in human musical rhythms

    NASA Astrophysics Data System (ADS)

    Hennig, Holger; Fleischmann, Ragnar; Fredebohm, Anneke; Hagmayer, York; Nagler, Jan; Witt, Annette; Theis, Fabian; Geisel, Theo

    2012-02-01

    Although human musical performances represent one of the most valuable achievements of mankind, the best musicians perform imperfectly. Musical rhythms are not entirely accurate and thus inevitably deviate from the ideal beat pattern. Nevertheless, computer generated perfect beat patterns are frequently devalued by listeners due to a perceived lack of human touch. Professional audio editing software therefore offers a humanizing feature which artificially generates rhythmic fluctuations. However, the built-in humanizing units are essentially random number generators producing only simple uncorrelated fluctuations. Here, for the first time, we establish long-range fluctuations as an inevitable natural companion of both simple and complex human rhythmic performances [1]. Moreover, we demonstrate that listeners strongly prefer long-range correlated fluctuations in musical rhythms. Thus, the favorable fluctuation type for humanizing interbeat intervals coincides with the one generically inherent in human musical performances. [1] HH et al., PLoS ONE,6,e26457 (2011)

  8. Microtubule plus end–associated CLIP-170 initiates HSV-1 retrograde transport in primary human cells

    PubMed Central

    Jovasevic, Vladimir

    2015-01-01

    Dynamic microtubules (MTs) continuously explore the intracellular environment and, through specialized plus end–tracking proteins (+TIPs), engage a variety of targets. However, the nature of cargoes that require +TIP-mediated capture for their movement on MTs remains poorly understood. Using RNA interference and dominant-negative approaches, combined with live cell imaging, we show that herpes simplex virus particles that have entered primary human cells exploit a +TIP complex comprising end-binding protein 1 (EB1), cytoplasmic linker protein 170 (CLIP-170), and dynactin-1 (DCTN1) to initiate retrograde transport. Depletion of these +TIPs completely blocked post-entry long-range transport of virus particles and suppressed infection ∼5,000-fold, whereas transferrin uptake, early endosome organization, and dynein-dependent movement of lysosomes and mitochondria remained unaffected. These findings provide the first insights into the earliest stages of viral engagement of MTs through specific +TIPs, akin to receptors, with therapeutic implications, and identify herpesvirus particles as one of a very limited number of cargoes absolutely dependent on CLIP-170–mediated capture to initiate transport in primary human cells. PMID:26504169

  9. Primary prevention of human papillomavirus-dependent neoplasia: no condom, no sex.

    PubMed

    Epstein, Richard J

    2005-11-01

    Cervix cancer is one of several neoplastic disorders that arise following transfer of human papillomavirus (HPV) during unprotected sexual intercourse, and like most other sexually transmitted diseases (STDs), is largely preventable by consistent condom use. This primary prevention strategy has received little support, however, when compared with massive secondary prevention initiatives involving cervical screening. The reasons for this anomalous situation are complex, and include: (i) the asymptomatic nature of most primary HPV infections; (ii) widespread ignorance concerning the venereal aetiology of HPV-related cancers; (iii) the common but incorrect belief that condom use does not reduce HPV transmission; (iv) the perceived irrelevance of safe sex campaigns based on reducing transmission of human immunodeficiency virus (HIV) in high-HPV but low-HIV countries such as the Philippines; (v) the promotion of oral contraception by the medical and pharmaceutical sectors as the sexual prophylaxis of choice; and (vi) the assumption that HPV vaccines will solve the problem. Here it is proposed that the high prevalence of non-HIV STDs, including distressing disorders such as genital warts and herpes simplex, can be exploited with greater efficacy as a public health deterrent to unsafe sex and HPV transmission. Targeting a "mutually assured infection" campaign at vulnerable subgroups such as teenagers and oral contraceptive users could help reverse the global expansion of HPV-related cancers. PMID:16223580

  10. Impacts of Natural Hazards on Primary Health Care Facilities of Iran: A 10-Year Retrospective Survey

    PubMed Central

    Ardalan, Ali; Mowafi, Hani; Yousefi, Homa

    2013-01-01

    Public health facilities in Iran are exposed to a wide range of natural hazards. This article presents the first survey of the impacts of such natural hazards on primary health care (PHC) centers in Iran from 2001 to 2011. A retrospective survey was conducted in 25 out of 30 provinces of Iran. Archival reports at provincial public health departments were cross-referenced with key informant interviews. During a 10-year period, 119 natural hazard events were recorded that led to physical damage and/or functional failure in 1,401 health centers, 127 deaths and injury or illness in 644 health staff. Earthquakes accounted for the most physical damage and all health-worker deaths. However, there was an increasing trend of impacts due to hydro-meteorological hazards. Iran’s health system needs to establish a registry to track the impact of natural hazards on health facilities, conduct regular hazard and vulnerability assessments and increase mitigation and preparedness measures. Keywords: Disaster, primary health care, facility, Iran, natural hazard Corresponding author: Ali Ardalan MD, PhD. Iran’s National Institute of Health Research, Tehran University of Medical Sciences. Harvard Humanitarian Initiative. Email: aardalan@tums.ac.ir PMID:23863871

  11. Immunology of experimental and natural human hookworm infection.

    PubMed

    Gaze, S; Bethony, J M; Periago, M V

    2014-08-01

    Human hookworm infection is one amongst the most prevalent of the neglected tropical diseases. An informative experimental animal model, that is, one that parallels a human infection, is not available for the study of human hookworm infection. Much of our current understanding of the human immune response during hookworm infection relies on the studies from experimental infection of hookworm-naïve individuals or the natural infections from individuals residing in hookworm-endemic areas. The experimental human infections tend to be acute, dose-controlled infections, often with a low larval inoculum so that they are well tolerated by human volunteers. Natural hookworm infections usually occur in areas where hookworm transmission is constant and infection is chronic. In cases where there has been drug administration in an endemic area, re-infection often occurs quickly even amongst those who were treated. Hence, although many of the characteristics of experimental and natural hookworm infection differ, both models have elements in common: mainly an intense Th2 response with the production of total and specific IgE as well as elevated levels of eosinophilia, IL-5, IL-10 and TNF. While hookworm infection affects millions of individuals worldwide, much of the human immunology of this infection still needs to be studied and understood.

  12. HIV-1 Interacts with Human Endogenous Retrovirus K (HML-2) Envelopes Derived from Human Primary Lymphocytes

    PubMed Central

    Brinzevich, Daria; Young, George R.; Sebra, Robert; Ayllon, Juan; Maio, Susan M.; Deikus, Gintaras; Chen, Benjamin K.; Fernandez-Sesma, Ana; Simon, Viviana

    2014-01-01

    ABSTRACT Human endogenous retroviruses (HERVs) are viruses that have colonized the germ line and spread through vertical passage. Only the more recently acquired HERVs, such as the HERV-K (HML-2) group, maintain coding open reading frames. Expression of HERV-Ks has been linked to different pathological conditions, including HIV infection, but our knowledge on which specific HERV-Ks are expressed in primary lymphocytes currently is very limited. To identify the most expressed HERV-Ks in an unbiased manner, we analyzed their expression patterns in peripheral blood lymphocytes using Pacific Biosciences (PacBio) single-molecule real-time (SMRT) sequencing. We observe that three HERV-Ks (KII, K102, and K18) constitute over 90% of the total HERV-K expression in primary human lymphocytes of five different donors. We also show experimentally that two of these HERV-K env sequences (K18 and K102) retain their ability to produce full-length and posttranslationally processed envelope proteins in cell culture. We show that HERV-K18 Env can be incorporated into HIV-1 but not simian immunodeficiency virus (SIV) particles. Moreover, HERV-K18 Env incorporation into HIV-1 virions is dependent on HIV-1 matrix. Taken together, we generated high-resolution HERV-K expression profiles specific for activated human lymphocytes. We found that one of the most abundantly expressed HERV-K envelopes not only makes a full-length protein but also specifically interacts with HIV-1. Our findings raise the possibility that these endogenous retroviral Env proteins could directly influence HIV-1 replication. IMPORTANCE Here, we report the HERV-K expression profile of primary lymphocytes from 5 different healthy donors. We used a novel deep-sequencing technology (PacBio SMRT) that produces the long reads necessary to discriminate the complexity of HERV-K expression. We find that primary lymphocytes express up to 32 different HERV-K envelopes, and that at least two of the most expressed Env proteins

  13. Interaction between arsenic trioxide and human primary cells: emphasis on human cells of myeloid origin.

    PubMed

    Binet, François; Antoine, Francis; Girard, Denis

    2009-03-01

    Arsenic trioxide (As(2)O(3); ATO) is considered to be one of the most potent drugs in cancer chemotherapy and is highly effective in the treatment of acute promyelocytic leukemia (APL). It is well established that treatment of APL patients with ATO is associated with the disappearance of the PML-RARalpha fusion transcript, the characteristic APL gene product of the chromosomal translocation t(15;17). Although its mode of action is still not fully understood, ATO is known to induce cell apoptosis via generation of reactive oxygen species and activation of caspases. Several reports have indicated that ATO acts principally by inducing cell apoptosis not only in APL, but in a variety of non-APL cells including myeloma cells, chronic myeloid leukemia cells and cells of immune origin, including B or T lymphocytes, macrophages and, more recently, neutrophils. There is an increasing amount of data, including some from our laboratory, concerning the interaction between ATO and human primary cells. The focus of this review will be to cover the role of ATO in human immune primary cells with special emphasis on cells of myeloid origin.

  14. 18 CFR 2.400 - Statement of interpretation of waste concerning natural gas as the primary energy source for...

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... interpretation of waste concerning natural gas as the primary energy source for qualifying small power production... Under the Public Utility Regulatory Policies Act of 1978 § 2.400 Statement of interpretation of waste concerning natural gas as the primary energy source for qualifying small power production facilities....

  15. [Human ecology and interdisciplinary cooperation for primary prevention of environmental risk factors for public health].

    PubMed

    Dobrowolski, Jan W

    2007-01-01

    training activity in ecologically-based primary prevention. Training in this important field is not adequate in medical, technological, and also natural subjects of studies. There is not enough opportunity for education of the students and graduates toward the application of integrated system approach of new achievements in different sciences and technologies. Interesting are experiences connected with long-term case studies in highly polluted regions in Poland, Japan, India, as well as exchange of methodological experiences during the series of International Summer Schools on the Human Environment from 1972, as well as during series of 11 International Conferences on Sustainable Development organized at AGH-UST from 1989 to 2006 and Polish Conferences in 2004 and 2007. It seems necessary not only to develop a training of experts that would be adequate to present needs, but also education of the whole society (including formal activities at all levels of education) as well as informal education (e.g. at Open Universities and Distance Education, based on the Internet) to achieve the integration of activity of scientists, practitioners and the whole society. It would be useful to focus this activity on crucial problems and selected regions. Let me propose as the top priority for inhabitants of Tarnow region as well as pilot projects for Poland; utilization of all possible achievements of science and technology for primary prevention of health hazard for inhabitants of Gmina Szczucin that is very polluted by asbestos, and also model management reducing risk factors for the natural environment and health of inhabitants in the regions of new motor-ways, as well as better primary prevention against flood accidents and connected with their effects (higher humidity of housing environment and its contamination by toxinogenic moulds) risk factors for health of communities living in rivers regions. For the purpose of optimisation of preventive action, it is necessary not only to

  16. [Human ecology and interdisciplinary cooperation for primary prevention of environmental risk factors for public health].

    PubMed

    Dobrowolski, Jan W

    2007-01-01

    training activity in ecologically-based primary prevention. Training in this important field is not adequate in medical, technological, and also natural subjects of studies. There is not enough opportunity for education of the students and graduates toward the application of integrated system approach of new achievements in different sciences and technologies. Interesting are experiences connected with long-term case studies in highly polluted regions in Poland, Japan, India, as well as exchange of methodological experiences during the series of International Summer Schools on the Human Environment from 1972, as well as during series of 11 International Conferences on Sustainable Development organized at AGH-UST from 1989 to 2006 and Polish Conferences in 2004 and 2007. It seems necessary not only to develop a training of experts that would be adequate to present needs, but also education of the whole society (including formal activities at all levels of education) as well as informal education (e.g. at Open Universities and Distance Education, based on the Internet) to achieve the integration of activity of scientists, practitioners and the whole society. It would be useful to focus this activity on crucial problems and selected regions. Let me propose as the top priority for inhabitants of Tarnow region as well as pilot projects for Poland; utilization of all possible achievements of science and technology for primary prevention of health hazard for inhabitants of Gmina Szczucin that is very polluted by asbestos, and also model management reducing risk factors for the natural environment and health of inhabitants in the regions of new motor-ways, as well as better primary prevention against flood accidents and connected with their effects (higher humidity of housing environment and its contamination by toxinogenic moulds) risk factors for health of communities living in rivers regions. For the purpose of optimisation of preventive action, it is necessary not only to

  17. Natural Tendency towards Beauty in Humans: Evidence from Binocular Rivalry

    PubMed Central

    Mo, Lei

    2016-01-01

    Although human preference for beauty is common and compelling in daily life, it remains unknown whether such preference is essentially subserved by social cognitive demands or natural tendency towards beauty encoded in the human mind intrinsically. Here we demonstrate experimentally that humans automatically exhibit preference for visual and moral beauty without explicit cognitive efforts. Using a binocular rivalry paradigm, we identified enhanced gender-independent perceptual dominance for physically attractive persons, and the results suggested universal preference for visual beauty based on perceivable forms. Moreover, we also identified perceptual dominance enhancement for characters associated with virtuous descriptions after controlling for facial attractiveness and vigilance-related attention effects, which suggested a similar implicit preference for moral beauty conveyed in prosocial behaviours. Our findings show that behavioural preference for beauty is driven by an inherent natural tendency towards beauty in humans rather than explicit social cognitive processes. PMID:26930202

  18. Natural selection and infectious disease in human populations

    PubMed Central

    Karlsson, Elinor K.; Kwiatkowski, Dominic P.; Sabeti, Pardis C.

    2015-01-01

    The ancient biological 'arms race' between microbial pathogens and humans has shaped genetic variation in modern populations, and this has important implications for the growing field of medical genomics. As humans migrated throughout the world, populations encountered distinct pathogens, and natural selection increased the prevalence of alleles that are advantageous in the new ecosystems in both host and pathogens. This ancient history now influences human infectious disease susceptibility and microbiome homeostasis, and contributes to common diseases that show geographical disparities, such as autoimmune and metabolic disorders. Using new high-throughput technologies, analytical methods and expanding public data resources, the investigation of natural selection is leading to new insights into the function and dysfunction of human biology. PMID:24776769

  19. Natural Tendency towards Beauty in Humans: Evidence from Binocular Rivalry.

    PubMed

    Mo, Ce; Xia, Tiansheng; Qin, Kaixin; Mo, Lei

    2016-01-01

    Although human preference for beauty is common and compelling in daily life, it remains unknown whether such preference is essentially subserved by social cognitive demands or natural tendency towards beauty encoded in the human mind intrinsically. Here we demonstrate experimentally that humans automatically exhibit preference for visual and moral beauty without explicit cognitive efforts. Using a binocular rivalry paradigm, we identified enhanced gender-independent perceptual dominance for physically attractive persons, and the results suggested universal preference for visual beauty based on perceivable forms. Moreover, we also identified perceptual dominance enhancement for characters associated with virtuous descriptions after controlling for facial attractiveness and vigilance-related attention effects, which suggested a similar implicit preference for moral beauty conveyed in prosocial behaviours. Our findings show that behavioural preference for beauty is driven by an inherent natural tendency towards beauty in humans rather than explicit social cognitive processes.

  20. Natural Tendency towards Beauty in Humans: Evidence from Binocular Rivalry.

    PubMed

    Mo, Ce; Xia, Tiansheng; Qin, Kaixin; Mo, Lei

    2016-01-01

    Although human preference for beauty is common and compelling in daily life, it remains unknown whether such preference is essentially subserved by social cognitive demands or natural tendency towards beauty encoded in the human mind intrinsically. Here we demonstrate experimentally that humans automatically exhibit preference for visual and moral beauty without explicit cognitive efforts. Using a binocular rivalry paradigm, we identified enhanced gender-independent perceptual dominance for physically attractive persons, and the results suggested universal preference for visual beauty based on perceivable forms. Moreover, we also identified perceptual dominance enhancement for characters associated with virtuous descriptions after controlling for facial attractiveness and vigilance-related attention effects, which suggested a similar implicit preference for moral beauty conveyed in prosocial behaviours. Our findings show that behavioural preference for beauty is driven by an inherent natural tendency towards beauty in humans rather than explicit social cognitive processes. PMID:26930202

  1. Functional expression of voltage-gated sodium channels in primary cultures of human cervical cancer.

    PubMed

    Diaz, Daniel; Delgadillo, Dulce Maria; Hernández-Gallegos, Elizabeth; Ramírez-Domínguez, Martha Eugenia; Hinojosa, Luz María; Ortiz, Cindy Sharon; Berumen, Jaime; Camacho, Javier; Gomora, Juan Carlos

    2007-02-01

    Cervical cancer (CaC) is the third most frequent cause of death from cancer among women in the world and the first in females of developing countries. Several ion channels are upregulated in cancer, actually potassium channels have been suggested as tumor markers and therapeutic targets for CaC. Voltage-gated sodium channels (VGSC) activity is involved in proliferation, motility, and invasion of prostate and breast cancer cells; however, the participation of this type of channels in CaC has not been explored. In the present study, we identified both at the molecular and electrophysiological level VGSC in primary cultures from human cervical carcinoma biopsies. With the whole cell patch clamp technique, we isolated and identified a voltage-gated Na(+) current as the main component of the inward current in all investigated cells. Sodium current was characterized by its kinetics, voltage dependence, sensitivity to tetrodotoxin (TTX) block and dependence to [Na(+)](o). By analyzing the expression of mRNAs encoding TTX-sensitive Na(+) channel alpha subunits with standard RT-PCR and specific primers, we detected Na(v)1.2, Na(v)1.4, Na(v)1.6, and Na(v)1.7 transcripts in total RNA obtained from primary cultures and biopsies of CaC. Restriction enzyme analysis of PCR products was consistent with the molecular nature of the corresponding genes. Notably, only transcripts for Na(v)1.4 sodium channels were detected in biopsies from normal cervix. The results show for the first time the functional expression of VGSC in primary cultures from human CaC, and suggest that these channels might be considered as potential molecular markers for this type of cancer.

  2. Primary human chorionic gonadotropin secreting germinoma of the corpus callosum

    PubMed Central

    Chuan Aaron, Foo Song; Dawn, Chong Q. Q.; Kenneth, Chang T. E.; Hoe, Ng Wai; Yen, Soh Shui; Chee Kian, Tham

    2013-01-01

    Background: Primary intracranial germinomas are a rare subset of intracranial tumors derived from mis-incorporated germ cells within the folding neural plate during embryogenesis. Though known to arise from midline structures in the central nervous system (CNS), occurrence within the corpus callosum is exceedingly rare. Case Description: We present a rare case of secreting primary intracranial germinoma with extensive intraventricular metastasis presenting as a multi-cystic butterfly lesion in the genu of the corpus callosum in a young boy. Conclusion: Intracranial germ cell tumors must be considered for any multi-cystic lesion arising from midline structures in the CNS in the preadult population. PMID:24233184

  3. Serodiagnosis of primary infections with human parvovirus 4, Finland.

    PubMed

    Lahtinen, Anne; Kivelä, Pia; Hedman, Lea; Kumar, Arun; Kantele, Anu; Lappalainen, Maija; Liitsola, Kirsi; Ristola, Matti; Delwart, Eric; Sharp, Colin; Simmonds, Peter; Söderlund-Venermo, Maria; Hedman, Klaus

    2011-01-01

    To determine the prevalence of parvovirus 4 infection and its clinical and sociodemographic correlations in Finland, we used virus-like particle-based serodiagnostic procedures (immunoglobulin [Ig] G, IgM, and IgG avidity) and PCR. We found 2 persons with parvovirus 4 primary infection who had mild or asymptomatic clinical features among hepatitis C virus-infected injection drug users.

  4. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease.

    PubMed

    Chernova, T; Sun, X M; Powley, I R; Galavotti, S; Grosso, S; Murphy, F A; Miles, G J; Cresswell, L; Antonov, A V; Bennett, J; Nakas, A; Dinsdale, D; Cain, K; Bushell, M; Willis, A E; MacFarlane, M

    2016-07-01

    Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the 'gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies.

  5. Molecular profiling reveals primary mesothelioma cell lines recapitulate human disease

    PubMed Central

    Chernova, T; Sun, X M; Powley, I R; Galavotti, S; Grosso, S; Murphy, F A; Miles, G J; Cresswell, L; Antonov, A V; Bennett, J; Nakas, A; Dinsdale, D; Cain, K; Bushell, M; Willis, A E; MacFarlane, M

    2016-01-01

    Malignant mesothelioma (MM) is an aggressive, fatal tumor strongly associated with asbestos exposure. There is an urgent need to improve MM patient outcomes and this requires functionally validated pre-clinical models. Mesothelioma-derived cell lines provide an essential and relatively robust tool and remain among the most widely used systems for candidate drug evaluation. Although a number of cell lines are commercially available, a detailed comparison of these commercial lines with freshly derived primary tumor cells to validate their suitability as pre-clinical models is lacking. To address this, patient-derived primary mesothelioma cell lines were established and characterized using complementary multidisciplinary approaches and bioinformatic analysis. Clinical markers of mesothelioma, transcriptional and metabolic profiles, as well as the status of p53 and the tumor suppressor genes CDKN2A and NF2, were examined in primary cell lines and in two widely used commercial lines. Expression of MM-associated markers, as well as the status of CDKN2A, NF2, the ‘gatekeeper' in MM development, and their products demonstrated that primary cell lines are more representative of the tumor close to its native state and show a degree of molecular diversity, thus capturing the disease heterogeneity in a patient cohort. Molecular profiling revealed a significantly different transcriptome and marked metabolic shift towards a greater glycolytic phenotype in commercial compared with primary cell lines. Our results highlight that multiple, appropriately characterised, patient-derived tumor cell lines are required to enable concurrent evaluation of molecular profiles versus drug response. Furthermore, application of this approach to other difficult-to-treat tumors would generate improved cellular models for pre-clinical evaluation of novel targeted therapies. PMID:26891694

  6. Mathematical Thinking and Human Nature: Consonance and Conflict

    ERIC Educational Resources Information Center

    Leron, Uri

    2004-01-01

    Human nature had traditionally been the realm of novelists, philosophers, and theologicians, but has recently been studied by cognitive science, neuroscience, research on babies and on animals, anthropology, and evolutionary psychology. In this paper I will show--by surveying relevant research and by analyzing some mathematical "case studies"--how…

  7. Oscillatory neural responses evoked by natural vestibular stimuli in humans.

    PubMed

    Gale, Steven; Prsa, Mario; Schurger, Aaron; Gay, Annietta; Paillard, Aurore; Herbelin, Bruno; Guyot, Jean-Philippe; Lopez, Christophe; Blanke, Olaf

    2016-03-01

    While there have been numerous studies of the vestibular system in mammals, less is known about the brain mechanisms of vestibular processing in humans. In particular, of the studies that have been carried out in humans over the last 30 years, none has investigated how vestibular stimulation (VS) affects cortical oscillations. Here we recorded high-density electroencephalography (EEG) in healthy human subjects and a group of bilateral vestibular loss patients (BVPs) undergoing transient and constant-velocity passive whole body yaw rotations, focusing our analyses on the modulation of cortical oscillations in response to natural VS. The present approach overcame significant technical challenges associated with combining natural VS with human electrophysiology and reveals that both transient and constant-velocity VS are associated with a prominent suppression of alpha power (8-13 Hz). Alpha band suppression was localized over bilateral temporo-parietal scalp regions, and these alpha modulations were significantly smaller in BVPs. We propose that suppression of oscillations in the alpha band over temporo-parietal scalp regions reflects cortical vestibular processing, potentially comparable with alpha and mu oscillations in the visual and sensorimotor systems, respectively, opening the door to the investigation of human cortical processing under various experimental conditions during natural VS. PMID:26683063

  8. Beyond toxicity: human health and the natural environment.

    PubMed

    Frumkin, H

    2001-04-01

    Research and teaching in environmental health have centered on the hazardous effects of various environmental exposures, such as toxic chemicals, radiation, and biological and physical agents. However, some kinds of environmental exposures may have positive health effects. According to E.O. Wilson's "biophilia" hypothesis, humans are innately attracted to other living organisms. Later authors have expanded this concept to suggest that humans have an innate bond with nature more generally. This implies that certain kinds of contact with the natural world may benefit health. Evidence supporting this hypothesis is presented from four aspects of the natural world: animals, plants, landscapes, and wilderness. Finally, the implications of this hypothesis for a broader agenda for environmental health, encompassing not only toxic outcomes but also salutary ones, are discussed. This agenda implies research on a range of potentially healthful environmental exposures, collaboration among professionals in a range of disciplines from public health to landscape architecture to city planning, and interventions based on research outcomes.

  9. Chromosomal translocation engineering to recapitulate primary events of human cancer.

    PubMed

    Forster, A; Pannell, R; Drynan, L; Cano, F; Chan, N; Codrington, R; Daser, A; Lobato, N; Metzler, M; Nam, C-H; Rodriguez, S; Tanaka, T; Rabbitts, T

    2005-01-01

    Mouse models of human cancers are important for understanding determinants of overt disease and for "preclinical" development of rational therapeutic strategies; for instance, based on macrodrugs. Chromosomal translocations underlie many human leukemias, sarcomas, and epithelial tumors. We have developed three technologies based on homologous recombination in mouse ES cells to mimic human chromosome translocations. The first, called the knockin method, allows creation of fusion genes like those typical of translocations of human leukemias and sarcomas. Two new conditional chromosomal translocation mimics have been developed. The first is a method for generating reciprocal chromosomal translocations de novo using Cre-loxP recombination (translocator mice). In some cases, there is incompatible gene orientation and the translocator model cannot be applied. We have developed a different model (invertor mice) for these situations. This method consists of introducing an inverted cDNA cassette into the intron of a target gene and bringing the cassette into the correct transcriptional orientation by Cre-loxP recombination. We describe experiments using the translocator model to generate MLL-mediated neoplasias and the invertor method to generate EWS-ERG-mediated cancer. These methods mimic the situation found in human chromosome translocations and provide the framework for design and study of human chromosomal translocations in mice.

  10. Connectedness to Nature and to Humanity: their association and personality correlates

    PubMed Central

    Lee, Kibeom; Ashton, Michael C.; Choi, Julie; Zachariassen, Kayla

    2015-01-01

    People differ in the extent to which they identify with humans beyond their ingroup and with non-human living things. We refer to the former as the Connectedness to Humanity (CH) and to the latter as the Connectedness to Nature (CN). In a sample of 324 undergraduate students, CH and CN were operationalized using the Identification with All Humanity Scale (McFarland et al., 2012) and the CN Scale (Mayer and Frantz, 2004), respectively. These variables correlated moderately with each other (r = 0.44) and shared Openness to Experience and Honesty–Humility as their primary personality correlates. CN was found to play an important role in mediating the relationships between the two personality variables and some specific pro-environmental/pro-animal attitudes and ecological behaviors. PMID:26257669

  11. Large-Scale Culture and Genetic Modification of Human Natural Killer Cells for Cellular Therapy.

    PubMed

    Lapteva, Natalia; Parihar, Robin; Rollins, Lisa A; Gee, Adrian P; Rooney, Cliona M

    2016-01-01

    Recent advances in methods for the ex vivo expansion of human natural killer (NK) cells have facilitated the use of these powerful immune cells in clinical protocols. Further, the ability to genetically modify primary human NK cells following rapid expansion allows targeting and enhancement of their immune function. We have successfully adapted an expansion method for primary NK cells from peripheral blood mononuclear cells or from apheresis products in gas permeable rapid expansion devices (G-Rexes). Here, we describe an optimized protocol for rapid and robust NK cell expansion as well as a method for highly efficient retroviral transduction of these ex vivo expanded cells. These methodologies are good manufacturing practice (GMP) compliant and could be used for clinical-grade product manufacturing. PMID:27177667

  12. Large-Scale Culture and Genetic Modification of Human Natural Killer Cells for Cellular Therapy.

    PubMed

    Lapteva, Natalia; Parihar, Robin; Rollins, Lisa A; Gee, Adrian P; Rooney, Cliona M

    2016-01-01

    Recent advances in methods for the ex vivo expansion of human natural killer (NK) cells have facilitated the use of these powerful immune cells in clinical protocols. Further, the ability to genetically modify primary human NK cells following rapid expansion allows targeting and enhancement of their immune function. We have successfully adapted an expansion method for primary NK cells from peripheral blood mononuclear cells or from apheresis products in gas permeable rapid expansion devices (G-Rexes). Here, we describe an optimized protocol for rapid and robust NK cell expansion as well as a method for highly efficient retroviral transduction of these ex vivo expanded cells. These methodologies are good manufacturing practice (GMP) compliant and could be used for clinical-grade product manufacturing.

  13. Do natural landscapes reduce future discounting in humans?

    PubMed Central

    van der Wal, Arianne J.; Schade, Hannah M.; Krabbendam, Lydia; van Vugt, Mark

    2013-01-01

    An important barrier to enduring behavioural change is the human tendency to discount the future. Drawing on evolutionary theories of life history and biophilia, this study investigates whether exposure to natural versus urban landscapes affects people's temporal discount rates. The results of three studies, two laboratory experiments and a field study reveal that individual discount rates are systematically lower after people have been exposed to scenes of natural environments as opposed to urban environments. Further, this effect is owing to people placing more value on the future after nature exposure. The finding that nature exposure reduces future discounting—as opposed to exposure to urban environments—conveys important implications for a range of personal and collective outcomes including healthy lifestyles, sustainable resource use and population growth. PMID:24197412

  14. Do natural landscapes reduce future discounting in humans?

    PubMed

    van der Wal, Arianne J; Schade, Hannah M; Krabbendam, Lydia; van Vugt, Mark

    2013-12-22

    An important barrier to enduring behavioural change is the human tendency to discount the future. Drawing on evolutionary theories of life history and biophilia, this study investigates whether exposure to natural versus urban landscapes affects people's temporal discount rates. The results of three studies, two laboratory experiments and a field study reveal that individual discount rates are systematically lower after people have been exposed to scenes of natural environments as opposed to urban environments. Further, this effect is owing to people placing more value on the future after nature exposure. The finding that nature exposure reduces future discounting-as opposed to exposure to urban environments-conveys important implications for a range of personal and collective outcomes including healthy lifestyles, sustainable resource use and population growth.

  15. Natural image classification driven by human brain activity

    NASA Astrophysics Data System (ADS)

    Zhang, Dai; Peng, Hanyang; Wang, Jinqiao; Tang, Ming; Xue, Rong; Zuo, Zhentao

    2016-03-01

    Natural image classification has been a hot topic in computer vision and pattern recognition research field. Since the performance of an image classification system can be improved by feature selection, many image feature selection methods have been developed. However, the existing supervised feature selection methods are typically driven by the class label information that are identical for different samples from the same class, ignoring with-in class image variability and therefore degrading the feature selection performance. In this study, we propose a novel feature selection method, driven by human brain activity signals collected using fMRI technique when human subjects were viewing natural images of different categories. The fMRI signals associated with subjects viewing different images encode the human perception of natural images, and therefore may capture image variability within- and cross- categories. We then select image features with the guidance of fMRI signals from brain regions with active response to image viewing. Particularly, bag of words features based on GIST descriptor are extracted from natural images for classification, and a sparse regression base feature selection method is adapted to select image features that can best predict fMRI signals. Finally, a classification model is built on the select image features to classify images without fMRI signals. The validation experiments for classifying images from 4 categories of two subjects have demonstrated that our method could achieve much better classification performance than the classifiers built on image feature selected by traditional feature selection methods.

  16. Conducting Museum Education Activities within the Context of Developing a Nature Culture in Primary School Students: MTA Natural History Museum Example

    ERIC Educational Resources Information Center

    Dilli, Rukiye

    2016-01-01

    The present study, aiming to develop nature culture in primary school students and to help them to become acquainted with their close environment, is a quasi-experimental study. Museum education activities were conducted with the study group which consisted of 128 fourth-grade primary school students. At the end of the study, the students gained…

  17. Primary Sources of Cognate Research in Human Performance Technology

    ERIC Educational Resources Information Center

    Johnsen, Liz V.; Huglin, Linda M.; Marker, Anthony

    2008-01-01

    This article is third in a series written to address questions regarding the need for more empirical research in the field of human performance technology (HPT) and the need to determine the future direction of HPT research. The call for more empirical research has been published in journals such as "Performance Improvement Quarterly" and…

  18. Capsaicin-like activity of some natural pungent substances on peripheral endings of visceral primary afferents.

    PubMed

    Patacchini, R; Maggi, C A; Meli, A

    1990-07-01

    1. The effects of some naturally occurring pungent substances, piperine, mustard oil, eugenol and curcumin, were compared to those of capsaicin in the rat isolated urinary bladder. 2. All test compounds dose-dependently contracted the rat bladder and produced desensitization toward capsaicin (1 mumol/l). Development of cross-tachyphylaxis among the natural pungent substances on one hand and capsaicin on the other, suggested a common site of action on visceral primary afferents. 3. Contractile responses to piperine, mustard oil and eugenol were partially tetrodotoxin and ruthenium red-sensitive, suggesting that activation of sensory terminals by these agents takes place indirectly, as well as by a direct action on sensory receptors. 4. The presence of the secondary acrylamide linkage (present in the backbone of capsaicin, but not in that of test compounds) does not appear to be essential to produce desensitization of sensory nerve terminals.

  19. Natural sniffing gives optimum odour perception for humans.

    PubMed

    Laing, D G

    1983-01-01

    The characteristics of human sniffing episodes during odour perception have been described in an earlier paper, where it has been suggested that the techniques used by individuals may be close to those providing optimum perception. To investigate this suggestion, threshold and intensity tests with butanol, cyclohexanone, and pentyl acetate have been carried out on twenty-one subjects. Olfactory responses obtained by using natural sniffing techniques were compared with those where the number of sniffs, interval between sniffs, and size of sniffs were varied. The results indicate that it is very difficult to improve on the efficiency of sniffing techniques of individuals and that a single natural sniff provides as much information about the presence and intensity of an odour as do seven or more sniffs. A single natural sniff and the first sniff of a a natural sniffing episode were shown to have similar characteristics and most significantly both were unaffected by changes in the concentration and type of odour. Overall, the results indicate that humans achieve optimum odour perception during threshold and intensity measures with their natural multiple-sniff technique or with a single sniff. For the 'average' human this occurs with a sniff of inhalation rate 30 1 min-1, volume 200 cm3, and duration 0.4 s. The use of several sniffs in a sniffing episode appears to be a confirmatory action rather than a necessary one, except for the perception of odour mixtures where several sniffs are likely to be needed to aid discrimination of the components. Data from the present and earlier study provide the information necessary for the development of a standard olfactometer and standard procedures for measuring the olfactory responses of humans. PMID:6657430

  20. RTTN Mutations Cause Primary Microcephaly and Primordial Dwarfism in Humans

    PubMed Central

    Shamseldin, Hanan; Alazami, Anas M.; Manning, Melanie; Hashem, Amal; Caluseiu, Oana; Tabarki, Brahim; Esplin, Edward; Schelley, Susan; Innes, A. Micheil; Parboosingh, Jillian S.; Lamont, Ryan; Majewski, Jacek; Bernier, Francois P.; Alkuraya, Fowzan S.

    2015-01-01

    Primary microcephaly is a developmental brain anomaly that results from defective proliferation of neuroprogenitors in the germinal periventricular zone. More than a dozen genes are known to be mutated in autosomal-recessive primary microcephaly in isolation or in association with a more generalized growth deficiency (microcephalic primordial dwarfism), but the genetic heterogeneity is probably more extensive. In a research protocol involving autozygome mapping and exome sequencing, we recruited a multiplex consanguineous family who is affected by severe microcephalic primordial dwarfism and tested negative on clinical exome sequencing. Two candidate autozygous intervals were identified, and the second round of exome sequencing revealed a single intronic variant therein (c.2885+8A>G [p.Ser963∗] in RTTN exon 23). RT-PCR confirmed that this change creates a cryptic splice donor and thus causes retention of the intervening 7 bp of the intron and leads to premature truncation. On the basis of this finding, we reanalyzed the exome file of a second consanguineous family affected by a similar phenotype and identified another homozygous change in RTTN as the likely causal mutation. Combined linkage analysis of the two families confirmed that RTTN maps to the only significant linkage peak. Finally, through international collaboration, a Canadian multiplex family affected by microcephalic primordial dwarfism and biallelic mutation of RTTN was identified. Our results expand the phenotype of RTTN-related disorders, hitherto limited to polymicrogyria, to include microcephalic primordial dwarfism with a complex brain phenotype involving simplified gyration. PMID:26608784

  1. Natural User Interface Sensors for Human Body Measurement

    NASA Astrophysics Data System (ADS)

    Boehm, J.

    2012-08-01

    The recent push for natural user interfaces (NUI) in the entertainment and gaming industry has ushered in a new era of low cost three-dimensional sensors. While the basic idea of using a three-dimensional sensor for human gesture recognition dates some years back it is not until recently that such sensors became available on the mass market. The current market leader is PrimeSense who provide their technology for the Microsoft Xbox Kinect. Since these sensors are developed to detect and observe human users they should be ideally suited to measure the human body. We describe the technology of a line of NUI sensors and assess their performance in terms of repeatability and accuracy. We demonstrate the implementation of a prototype scanner integrating several NUI sensors to achieve full body coverage. We present the results of the obtained surface model of a human body.

  2. Devolution and human resources in primary healthcare in rural Mali

    PubMed Central

    2011-01-01

    Devolution, as other types of decentralization (e.g. deconcentration, delegation, privatization), profoundly changes governance relations in the health system. Devolution is meant to affect performance of the health system by transferring responsibilities and authority to locally elected governments. The key question of this article is: what does devolution mean for human resources for health in Mali? This article assesses the key advantages and dilemmas associated with devolution such as responsiveness to local needs, downward accountability and health worker retention. Challenges of politics and capacities are also addressed in relation to human resources for health at the local level. Examples are derived from experiences in Mali with a capacity development programme and from case studies of other countries. It is not research findings that are presented, but highlights of key issues at stake aimed at inspiring the debate in Mali and elsewhere. A first lesson from the discussion suggests that in the context of human resources for health, decentralization of authority and resources is not the main issue. The challenge is to develop or strengthen accountability of those who decide and act, whether they are local politicians, bureaucrats or community representatives. If decentralization policies do not address public accountability, they will not fundamentally change human resource management, quality and equity of staffing. A second lesson is that successful devolution requires innovations in capacity development of all actors involved and in designing effective incentive measures. A final key conclusion is that the topic of devolution policy and its effects on human resources for health, and vice versa, merit more attention. A better understanding may lead to more appropriate policy designs and better preparation for the actors involved in countries that are embarking on decentralization, as is the case in Mali. PMID:21651817

  3. Devolution and human resources in primary healthcare in rural Mali.

    PubMed

    Lodenstein, Elsbet; Dao, Dramane

    2011-06-08

    Devolution, as other types of decentralization (e.g. deconcentration, delegation, privatization), profoundly changes governance relations in the health system. Devolution is meant to affect performance of the health system by transferring responsibilities and authority to locally elected governments. The key question of this article is: what does devolution mean for human resources for health in Mali?This article assesses the key advantages and dilemmas associated with devolution such as responsiveness to local needs, downward accountability and health worker retention. Challenges of politics and capacities are also addressed in relation to human resources for health at the local level. Examples are derived from experiences in Mali with a capacity development programme and from case studies of other countries. It is not research findings that are presented, but highlights of key issues at stake aimed at inspiring the debate in Mali and elsewhere.A first lesson from the discussion suggests that in the context of human resources for health, decentralization of authority and resources is not the main issue. The challenge is to develop or strengthen accountability of those who decide and act, whether they are local politicians, bureaucrats or community representatives. If decentralization policies do not address public accountability, they will not fundamentally change human resource management, quality and equity of staffing. A second lesson is that successful devolution requires innovations in capacity development of all actors involved and in designing effective incentive measures. A final key conclusion is that the topic of devolution policy and its effects on human resources for health, and vice versa, merit more attention. A better understanding may lead to more appropriate policy designs and better preparation for the actors involved in countries that are embarking on decentralization, as is the case in Mali.

  4. Patterns of invasive growth in vitro. Human decidua graviditatis confronted with established human cell lines and primary human explants.

    PubMed

    Schleich, A B; Frick, M; Mayer, A

    1976-02-01

    Human decidua graviditatis was used as a receptor tissue to demonstrate invasive properties of human cells in vitro. In the confrontation between decidua and established cell lines of tumors and of normal origin as well as primary explanted cells, we noted differences in the cells' interactions with decidual tissue. The two original tumor cell lines, HeLa (carcinoma) and AFi (sarcoma), and a spontaneously transformed lymphoblastoid cell line showed aggressiveness, i.e., invasion, rapid proliferation, injury, and destruction of the decidual tissue. Strain HeLa S3 and two established cell lines, FL (amnion) and Girardi Heart, which are regarded as transformed cells because of their increased mitotic rate and polyploidy, exhibited various degrees of aggressiveness but did not invade. Freshly explanted fetal lung and endometrium caused no injury to the receptor tissue and were included in the decidual tissue.

  5. Development of an Advanced Primary Human In Vitro Model of the Small Intestine.

    PubMed

    Schweinlin, Matthias; Wilhelm, Sabine; Schwedhelm, Ivo; Hansmann, Jan; Rietscher, Rene; Jurowich, Christian; Walles, Heike; Metzger, Marco

    2016-09-01

    Intestinal in vitro models are valuable tools in drug discovery and infection research. Despite several advantages, the standard cell line-based Transwell(®) models based for example on colonic epithelial Caco-2 cells, lack the cellular complexity and transport activity associated with native small intestinal tissue. An additional experimental set-back arises from the most commonly used synthetic membranes, on which the cells are routinely cultured. These can lead to an additional barrier activity during in vitro testing. To overcome these limitations, we developed an alternative primary human small intestinal tissue model. This novel approach combines previously established gut organoid technology with a natural extracellular matrix (ECM) based on porcine small intestinal scaffold (SIS). Intestinal crypts from healthy human small intestine were expanded as gut organoids and seeded as single cells on SIS in a standardized Transwell-like setting. After only 7 days on the ECM scaffold, the primary cells formed an epithelial barrier while a subpopulation differentiated into intestinal specific cell types such as mucus-producing goblet cells or hormone-secreting enteroendocrine cells. Furthermore, we tested the influence of subepithelial fibroblasts and dynamic culture conditions on epithelial barrier function. The barrier integrity was stabilized by coculture in the presence of gut-derived fibroblasts. Compared to static or dynamic culture on an orbital shaker, dynamic culture in a defined perfusion bioreactor had an additional significant impact on epithelial cell differentiation, indicated by high prismatic cell morphology and upregulation of CYP3A4 enzyme and Mdr1 transporter activity. In summary, more physiological tissue models as presented in our study might be useful tools in preclinical research and development. PMID:27481569

  6. Simulating forest landscape disturbances as coupled human and natural systems

    USGS Publications Warehouse

    Wimberly, Michael; Sohl, Terry L.; Liu, Zhihua; Lamsal, Aashis

    2015-01-01

    Anthropogenic disturbances resulting from human land use affect forest landscapes over a range of spatial and temporal scales, with diverse influences on vegetation patterns and dynamics. These processes fall within the scope of the coupled human and natural systems (CHANS) concept, which has emerged as an important framework for understanding the reciprocal interactions and feedbacks that connect human activities and ecosystem responses. Spatial simulation modeling of forest landscape change is an important technique for exploring the dynamics of CHANS over large areas and long time periods. Landscape models for simulating interactions between human activities and forest landscape dynamics can be grouped into two main categories. Forest landscape models (FLMs) focus on landscapes where forests are the dominant land cover and simulate succession and natural disturbances along with forest management activities. In contrast, land change models (LCMs) simulate mosaics of different land cover and land use classes that include forests in addition to other land uses such as developed areas and agricultural lands. There are also several examples of coupled models that combine elements of FLMs and LCMs. These integrated models are particularly useful for simulating human–natural interactions in landscapes where human settlement and agriculture are expanding into forested areas. Despite important differences in spatial scale and disciplinary scope, FLMs and LCMs have many commonalities in conceptual design and technical implementation that can facilitate continued integration. The ultimate goal will be to implement forest landscape disturbance modeling in a CHANS framework that recognizes the contextual effects of regional land use and other human activities on the forest ecosystem while capturing the reciprocal influences of forests and their disturbances on the broader land use mosaic.

  7. Redundant information encoding in primary motor cortex during natural and prosthetic motor control.

    PubMed

    So, Kelvin; Ganguly, Karunesh; Jimenez, Jessica; Gastpar, Michael C; Carmena, Jose M

    2012-06-01

    Redundant encoding of information facilitates reliable distributed information processing. To explore this hypothesis in the motor system, we applied concepts from information theory to quantify the redundancy of movement-related information encoded in the macaque primary motor cortex (M1) during natural and neuroprosthetic control. Two macaque monkeys were trained to perform a delay center-out reaching task controlling a computer cursor under natural arm movement (manual control, 'MC'), and using a brain-machine interface (BMI) via volitional control of neural ensemble activity (brain control, 'BC'). During MC, we found neurons in contralateral M1 to contain higher and more redundant information about target direction than ipsilateral M1 neurons, consistent with the laterality of movement control. During BC, we found that the M1 neurons directly incorporated into the BMI ('direct' neurons) contained the highest and most redundant target information compared to neurons that were not incorporated into the BMI ('indirect' neurons). This effect was even more significant when comparing to M1 neurons of the opposite hemisphere. Interestingly, when we retrained the BMI to use ipsilateral M1 activity, we found that these neurons were more redundant and contained higher information than contralateral M1 neurons, even though ensembles from this hemisphere were previously less redundant during natural arm movement. These results indicate that ensembles most associated to movement contain highest redundancy and information encoding, which suggests a role for redundancy in proficient natural and prosthetic motor control.

  8. Genomic responses to hepatitis B virus (HBV) infection in primary human hepatocytes

    PubMed Central

    Ancey, Pierre-Benoit; Testoni, Barbara; Gruffaz, Marion; Cros, Marie-Pierre; Durand, Geoffroy; Le Calvez-Kelm, Florence; Durantel, David; Herceg, Zdenko; Hernandez-Vargas, Hector

    2015-01-01

    Viral infections are able to modify the host's cellular programs, with DNA methylation being a biological intermediate in this process. The extent to which viral infections deregulate gene expression and DNA methylation is not fully understood. In the case of Hepatitis B virus (HBV), there is evidence for an interaction between viral proteins and the host DNA methylation machinery. We studied the ability of HBV to modify the host transcriptome and methylome, using naturally infected primary human hepatocytes to better mimic the clinical setting. Gene expression was especially sensitive to culture conditions, independently of HBV infection. However, we identified non-random changes in gene expression and DNA methylation occurring specifically upon HBV infection. There was little correlation between expression and methylation changes, with transcriptome being a more sensitive marker of time-dependent changes induced by HBV. In contrast, a set of differentially methylated sites appeared early and were stable across the time course experiment. Finally, HBV-induced DNA methylation changes were defined by a specific chromatin context characterized by CpG-poor regions outside of gene promoters. These data support the ability of HBV to modulate host cell expression and methylation programs. In addition, it may serve as a reference for studies addressing the genome-wide consequences of HBV infection in human hepatocytes. PMID:26565721

  9. Genomic responses to hepatitis B virus (HBV) infection in primary human hepatocytes.

    PubMed

    Ancey, Pierre-Benoit; Testoni, Barbara; Gruffaz, Marion; Cros, Marie-Pierre; Durand, Geoffroy; Le Calvez-Kelm, Florence; Durantel, David; Herceg, Zdenko; Hernandez-Vargas, Hector

    2015-12-29

    Viral infections are able to modify the host's cellular programs, with DNA methylation being a biological intermediate in this process. The extent to which viral infections deregulate gene expression and DNA methylation is not fully understood. In the case of Hepatitis B virus (HBV), there is evidence for an interaction between viral proteins and the host DNA methylation machinery. We studied the ability of HBV to modify the host transcriptome and methylome, using naturally infected primary human hepatocytes to better mimic the clinical setting.Gene expression was especially sensitive to culture conditions, independently of HBV infection. However, we identified non-random changes in gene expression and DNA methylation occurring specifically upon HBV infection. There was little correlation between expression and methylation changes, with transcriptome being a more sensitive marker of time-dependent changes induced by HBV. In contrast, a set of differentially methylated sites appeared early and were stable across the time course experiment. Finally, HBV-induced DNA methylation changes were defined by a specific chromatin context characterized by CpG-poor regions outside of gene promoters.These data support the ability of HBV to modulate host cell expression and methylation programs. In addition, it may serve as a reference for studies addressing the genome-wide consequences of HBV infection in human hepatocytes.

  10. Expression of GD2 ganglioside by untreated primary human neuroblastomas.

    PubMed

    Wu, Z L; Schwartz, E; Seeger, R; Ladisch, S

    1986-01-01

    Primary neuroblastomas obtained before therapy from 36 patients were studied to determine the frequency of tumors expressing a specific glycosphingolipid, GD2 ganglioside. Total tissue gangliosides were purified by a new partition method, quantitated, and analyzed by high-performance thin-layer chromatography. All 36 neuroblastoma tumors, representing all clinical stages, contained GD2 ganglioside. The mean relative and absolute concentrations of GD2 were substantial (12% of the total tissue gangliosides and 50 nmol/g of tissue) and were independent of the clinical stage of the tumor. In contrast, 6 samples of related but more differentiated tumors (ganglioneuroblastoma and ganglioneuroma) had little or no detectable GD2 (less than or equal to 1.5% of total gangliosides and less than or equal to 4 nmol/g of tissue). These results suggest that GD2 is a sensitive marker for neuroblastoma tissue and may be an excellent target antigen for immunotherapy of this tumor.

  11. Nature-Culture Constructs in Science Learning: Human/Non-Human Agency and Intentionality

    ERIC Educational Resources Information Center

    Bang, Megan; Marin, Ananda

    2015-01-01

    The field of science education has struggled to create robust, meaningful forms of education that effectively engage students from historically non-dominant communities and women. This paper argues that a primary issue underlying this on-going struggle pivots on constructions of nature-culture relations. We take up structuration theory (Giddens,…

  12. Stealth and Natural Disasters: Science, Policy and Human Behavior

    NASA Astrophysics Data System (ADS)

    Kieffer, S. W.

    2008-12-01

    Geophysicists, earth scientists, and other natural scientists play a key role in studying disasters, and are challenged to convey the science to the public and policy makers (including government and business). I have found it useful to introduce the concept of two general types of disasters to these audiences: natural and stealth. Natural disasters are geological phenomena over which we humans have some, but relatively little, control. Earthquakes, tsunamis, floods and volcanic eruptions are the most familiar examples, but exogenous events such as meteorite impacts, solar flares, and supernovae are also possibly disruptive. Natural disasters typically have an abrupt onset, cause immediate major change, are familiar from the historic record, and get much media and public attention. They cannot be prevented, but preplanning can ameliorate their effects. Natural disasters are increasingly amplified by us (humans), and we are increasingly affected by them due to our expanding presence on the planet. Less familiar disasters are unfolding in the near-term, but they are not happening in the minds of most people. They are approaching us stealthily, and for this reason I propose that we call them stealth disasters. They differ from natural disasters in several important ways: stealth disasters are primarily caused by, or driven by, the interaction of humans with complex cycles of processes on the planet. Examples are: fresh water shortages and contamination, soil degradation and loss, climate changes, ocean degradation. The onset of stealth disasters is incremental rather than abrupt. They may not unfold significantly during the course of one term of political office, but they are unfolding in our lifetime. We as individuals may or may not escape their consequences, but they will affect our children and grandchildren. If humans are familiar with stealth disasters at all, it is from a relatively local experience, e.g., flooding of the Mississippi or the Dust Bowl in the U

  13. Natural and sexual selection in a monogamous historical human population.

    PubMed

    Courtiol, Alexandre; Pettay, Jenni E; Jokela, Markus; Rotkirch, Anna; Lummaa, Virpi

    2012-05-22

    Whether and how human populations exposed to the agricultural revolution are still affected by Darwinian selection remains controversial among social scientists, biologists, and the general public. Although methods of studying selection in natural populations are well established, our understanding of selection in humans has been limited by the availability of suitable datasets. Here, we present a study comparing the maximum strengths of natural and sexual selection in humans that includes the effects of sex and wealth on different episodes of selection. Our dataset was compiled from church records of preindustrial Finnish populations characterized by socially imposed monogamy, and it contains a complete distribution of survival, mating, and reproductive success for 5,923 individuals born 1760-1849. Individual differences in early survival and fertility (natural selection) were responsible for most variation in fitness, even among wealthier individuals. Variance in mating success explained most of the higher variance in reproductive success in males compared with females, but mating success also influenced reproductive success in females, allowing for sexual selection to operate in both sexes. The detected opportunity for selection is in line with measurements for other species but higher than most previous reports for human samples. This disparity results from biological, demographic, economic, and social differences across populations as well as from failures by most previous studies to account for variation in fitness introduced by nonreproductive individuals. Our results emphasize that the demographic, cultural, and technological changes of the last 10,000 y did not preclude the potential for natural and sexual selection in our species.

  14. An empirically informed critique of Habermas' argument from human nature.

    PubMed

    Morar, Nicolae

    2015-02-01

    In a near-future world of bionics and biotechnology, the main ethical and political issue will be the definition of who we are. Could biomedical enhancements transform us to such an extent that we would be other than human? Habermas argues that any genetic enhancement intervention that could potentially alter 'human nature' should be morally prohibited since it alters the child's nature or the very essence that makes the child who he is. This practice also commits the child to a specific life project or, in any case, it puts specific restrictions on his freedom to choose a life of his own. Ultimately, genetic enhancement jeopardizes the very foundations of moral equality. I contend that Habermas' argument is based either on a series of presuppositions that imply a gross misunderstanding of evolution or the relevant factual information concerning the action we are about to morally assess is not empirically supported. Hence, the argument from human nature is based on a series of false or problematic assumptions, and, as such, it fails to play the normative role intended by Habermas.

  15. A Critical Investigation of the Nature and Extent of Cyberbullying in Two Post-Primary Schools in Northern Ireland

    ERIC Educational Resources Information Center

    Purdy, Noel; York, Leanne

    2016-01-01

    This study aimed to investigate internet usage among post-primary pupils in years 9, 11 and 13 in two contrasting post-primary schools in Northern Ireland, the nature and incidence of cyberbullying among these pupils, and the ways in which their schools are currently addressing the problem. A mixed methodological approach was adopted: a paper…

  16. Molecular genetics of human primary microcephaly: an overview.

    PubMed

    Faheem, Muhammad; Naseer, Muhammad Imran; Rasool, Mahmood; Chaudhary, Adeel G; Kumosani, Taha A; Ilyas, Asad Muhammad; Pushparaj, Peter; Ahmed, Farid; Algahtani, Hussain A; Al-Qahtani, Mohammad H; Saleh Jamal, Hasan

    2015-01-01

    Autosomal recessive primary microcephaly (MCPH) is a neurodevelopmental disorder that is characterised by microcephaly present at birth and non-progressive mental retardation. Microcephaly is the outcome of a smaller but architecturally normal brain; the cerebral cortex exhibits a significant decrease in size. MCPH is a neurogenic mitotic disorder, though affected patients demonstrate normal neuronal migration, neuronal apoptosis and neural function. Twelve MCPH loci (MCPH1-MCPH12) have been mapped to date from various populations around the world and contain the following genes: Microcephalin, WDR62, CDK5RAP2, CASC5, ASPM, CENPJ, STIL, CEP135, CEP152, ZNF335, PHC1 and CDK6. It is predicted that MCPH gene mutations may lead to the disease phenotype due to a disturbed mitotic spindle orientation, premature chromosomal condensation, signalling response as a result of damaged DNA, microtubule dynamics, transcriptional control or a few other hidden centrosomal mechanisms that can regulate the number of neurons produced by neuronal precursor cells. Additional findings have further elucidated the microcephaly aetiology and pathophysiology, which has informed the clinical management of families suffering from MCPH. The provision of molecular diagnosis and genetic counselling may help to decrease the frequency of this disorder. PMID:25951892

  17. SEASONAL EFFECTS OF ULTRAFINE, FINE, AND COARSE PARTICULATE MATTER (PM) ON HUMAN PRIMARY AIRWAY EPITHELIAL CELLS

    EPA Science Inventory

    SEASONAL EFFECTS OF ULTRAFINE, FINE, AND COARSE PARTICULATE MATTER (PM) ON HUMAN PRIMARY AIRWAY EPITHELIAL CELLS

    Exposure of humans to PM results in increased mortality and morbidity. Recent toxicology studies have shown a number of pathophysiological pulmonary and car...

  18. Neuronal activity in the primary visual cortex of the cat freely viewing natural images.

    PubMed

    Maldonado, P E; Babul, C M

    2007-02-23

    Many studies have now demonstrated that neurons in the visual cortex of cats and monkeys change their activity when stimuli are presented beyond their classical receptive field, and that these responses are not readily apparent from their receptive field properties. However few studies have been conducted to investigate the discharge properties of neurons in the visual cortex of animals when they are allow to freely view natural images. We employ tetrodes, which enable simultaneous and separable recordings of small numbers of neighboring neurons, to record 102 single units from 59 sites from areas 17 and 18 of two alert cats. While the animals viewed either natural images or black screens, they made frequent saccadic eye movements and gaze fixations. Fixations onto an image's location increased neuronal firing peaking at 80-100 ms after the fixation onset, to then decrease steadily with time despite continuous fixation. Saccades trigger a fast decrease in firing rate for both images and darkness. When we examined the incidence of correlated firing, we observed significant synchrony during the initial phases of visual fixations when the animals viewed natural scenes. Such synchrony was absent during saccadic eye movements and during eye movements in darkness. Our data revealed that scanning of natural scenes is associated with a rapid succession of distinct fixation-related activation patterns that included transient rate changes and excess coincident firing. The transient nature of these synchronization phenomena suggests a fast acting mechanism, which is in good agreement with the evidence that basic operations of scene analysis must be accomplished within a few tens of milliseconds in primary visual cortex.

  19. Macaques Exhibit a Naturally-Occurring Depression Similar to Humans

    PubMed Central

    Xu, Fan; Wu, Qingyuan; Xie, Liang; Gong, Wei; Zhang, Jianguo; Zheng, Peng; Zhou, Qinmin; Ji, Yongjia; Wang, Tao; Li, Xin; Fang, Liang; Li, Qi; Yang, Deyu; Li, Juan; Melgiri, Narayan D.; Shively, Carol; Xie, Peng

    2015-01-01

    Rodent models have dominated preclinical investigations into the mechanisms of depression. However, these models-which rely on subjecting individual rodents to physical stressors - do not realistically resemble the etiopathological development of depression, which occurs naturally in a social context. A non-human primate model that better reflects the social ethological aspects of depression would be more advantageous to investigating pathophysiological mechanisms and developing antidepressant therapeutics. Here, we describe and model a naturally-occurring depressive state in a non-human primate species, the cynomolgus monkey (Macaca fascicularis), in a realistic social ethological context and associate the depressed behavioral phenotype with significant serum metabolic perturbations. One to two subjects per stable social colony (17–22 subjects) manifested a depressive phenotype that may be attributed to psychosocial stress. In accordance with rodent and human studies, the serum metabolic phenotype of depressed and healthy subjects significantly differed, supporting the model's face validity. However, application of the fast-acting antidepressant ketamine failed to demonstrate predictive validity. This study proposes a non-human primate depression model in a realistic social ethological context that can better approximate the psychosocial stressors underlying depression. PMID:25783476

  20. Synthetic vs natural scaffolds for human limbal stem cells

    PubMed Central

    Tominac Trcin, Mirna; Dekaris, Iva; Mijović, Budimir; Bujić, Marina; Zdraveva, Emilija; Dolenec, Tamara; Pauk-Gulić, Maja; Primorac, Dragan; Crnjac, Josip; Špoljarić, Branimira; Mršić, Gordan; Kuna, Krunoslav; Špoljarić, Daniel; Popović, Maja

    2015-01-01

    Aim To investigate the impact of synthetic electrospun polyurethane (PU) and polycaprolactone (PCL) nanoscaffolds, before and after hydrolytic surface modification, on viability and differentiation of cultured human eye epithelial cells, in comparison with natural scaffolds: fibrin and human amniotic membrane. Methods Human placenta was taken at elective cesarean delivery. Fibrin scaffolds were prepared from commercial fibrin glue kits. Nanoscaffolds were fabricated by electrospinning. Limbal cells were isolated from surpluses of human cadaveric cornea and seeded on feeder 3T3 cells. The scaffolds used for viability testing and immunofluorescence analysis were amniotic membrane, fibrin, PU, and PCL nanoscaffolds, with or without prior NaOH treatment. Results Scanning electron microscope photographs of all tested scaffolds showed good colony spreading of seeded limbal cells. There was a significant difference in viability performance between cells with highest viability cultured on tissue culture plastic and cells cultured on all other scaffolds. On the other hand, electrospun PU, PCL, and electrospun PCL treated with NaOH had more than 80% of limbal cells positive for stem cell marker p63 compared to only 27%of p63 positive cells on fibrin. Conclusion Natural scaffolds, fibrin and amniotic membrane, showed better cell viability than electrospun scaffolds. On the contrary, high percentages of p63 positive cells obtained on these scaffolds still makes them good candidates for efficient delivery systems for therapeutic purposes. PMID:26088849

  1. Human natural killer cell development in secondary lymphoid tissues.

    PubMed

    Freud, Aharon G; Yu, Jianhua; Caligiuri, Michael A

    2014-04-01

    For nearly a decade it has been appreciated that critical steps in human natural killer (NK) cell development likely occur outside of the bone marrow and potentially necessitate distinct microenvironments within extramedullary tissues. The latter include the liver and gravid uterus as well as secondary lymphoid tissues such as tonsils and lymph nodes. For as yet unknown reasons these tissues are naturally enriched with NK cell developmental intermediates (NKDI) that span a maturation continuum starting from an oligopotent CD34(+)CD45RA(+) hematopoietic precursor cell to a cytolytic mature NK cell. Indeed despite the detection of NKDI within the aforementioned tissues, relatively little is known about how, why, and when these tissues may be most suited to support NK cell maturation and how this process fits in with other components of the human immune system. With the discovery of other innate lymphoid subsets whose immunophenotypes overlap with those of NKDI, there is also need to revisit and potentially re-characterize the basic immunophenotypes of the stages of the human NK cell developmental pathway in vivo. In this review, we provide an overview of human NK cell development in secondary lymphoid tissues and discuss the many questions that remain to be answered in this exciting field.

  2. Human task animation from performance models and natural language input

    NASA Technical Reports Server (NTRS)

    Esakov, Jeffrey; Badler, Norman I.; Jung, Moon

    1989-01-01

    Graphical manipulation of human figures is essential for certain types of human factors analyses such as reach, clearance, fit, and view. In many situations, however, the animation of simulated people performing various tasks may be based on more complicated functions involving multiple simultaneous reaches, critical timing, resource availability, and human performance capabilities. One rather effective means for creating such a simulation is through a natural language description of the tasks to be carried out. Given an anthropometrically-sized figure and a geometric workplace environment, various simple actions such as reach, turn, and view can be effectively controlled from language commands or standard NASA checklist procedures. The commands may also be generated by external simulation tools. Task timing is determined from actual performance models, if available, such as strength models or Fitts' Law. The resulting action specification are animated on a Silicon Graphics Iris workstation in real-time.

  3. A Coupled Human-Natural Systems Approach to Valuing Natural Capital

    NASA Astrophysics Data System (ADS)

    Fenichel, E. P.; Abbott, J.; Fujitani, M.

    2012-12-01

    The idea that geological and biological natural resources provide ecosystem services and that the physical geological and biological stocks, referred to as ecological stocks, are forms of capital is not new, but has attracted increased attention since the Millennium Ecosystem Assessment was released in 2005. Yet, the exact meaning of these terms, the connection between natural capital and ecosystem services, and the broader links between biophysical science and economics is often vague. The conceptual connection between ecosystem services and natural capital is that ecosystem services are the flow of goods and services that people receive from natural resources, and these flows are generated by an endowment of ecological stocks. While individuals derive benefits from a flow of services, the extent that people value the underlying natural capital asset depends on institutional arrangements in addition to the ecological properties of the stocks, because the value of capital relates to the future flow of services. A coupled human-natural systems modeling approach can help understand the value of natural capital in addition to helping scientist and policy makers better manage earth's resources. The value of a capital asset is the net present value of the flow of service, often calculated by the NPV rule. The NPV rule almost always assumes perfectly functioning markets for services and capital, but for many important ecosystem services such markets simply do not exist. The NPV rule can be derived by maximizing the net present value of capital. Indeed, the NPV rule comes from the adjoint condition of an optimal control problem where the flow of services from the capital asset are the benefits, and the dynamics of the capital stock are the constraints. Yet, trying to apply the traditional NPV rule to ecosystem services and natural capital can be frustrated by not knowing where pieces of the puzzle fit. We compare the standard NPV rule with a modified NPV rule derived by

  4. Quantification of regenerative potential in primary human mammary epithelial cells

    PubMed Central

    Linnemann, Jelena R.; Miura, Haruko; Meixner, Lisa K.; Irmler, Martin; Kloos, Uwe J.; Hirschi, Benjamin; Bartsch, Harald S.; Sass, Steffen; Beckers, Johannes; Theis, Fabian J.; Gabka, Christian; Sotlar, Karl; Scheel, Christina H.

    2015-01-01

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49fhi/EpCAM− population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis. PMID:26071498

  5. Quantification of regenerative potential in primary human mammary epithelial cells.

    PubMed

    Linnemann, Jelena R; Miura, Haruko; Meixner, Lisa K; Irmler, Martin; Kloos, Uwe J; Hirschi, Benjamin; Bartsch, Harald S; Sass, Steffen; Beckers, Johannes; Theis, Fabian J; Gabka, Christian; Sotlar, Karl; Scheel, Christina H

    2015-09-15

    We present an organoid regeneration assay in which freshly isolated human mammary epithelial cells are cultured in adherent or floating collagen gels, corresponding to a rigid or compliant matrix environment. In both conditions, luminal progenitors form spheres, whereas basal cells generate branched ductal structures. In compliant but not rigid collagen gels, branching ducts form alveoli at their tips, express basal and luminal markers at correct positions, and display contractility, which is required for alveologenesis. Thereby, branched structures generated in compliant collagen gels resemble terminal ductal-lobular units (TDLUs), the functional units of the mammary gland. Using the membrane metallo-endopeptidase CD10 as a surface marker enriches for TDLU formation and reveals the presence of stromal cells within the CD49f(hi)/EpCAM(-) population. In summary, we describe a defined in vitro assay system to quantify cells with regenerative potential and systematically investigate their interaction with the physical environment at distinct steps of morphogenesis.

  6. [Variation trends of natural vegetation net primary productivity in China under climate change scenario].

    PubMed

    Zhao, Dong-sheng; Wu, Shao-hong; Yin, Yun-he

    2011-04-01

    Based on the widely used Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ) for climate change study, and according to the features of natural environment in China, the operation mechanism of the model was adjusted, and the parameters were modified. With the modified LPJ model and taking 1961-1990 as baseline period, the responses of natural vegetation net primary productivity (NPP) in China to climate change in 1991-2080 were simulated under the Special Report on Emissions Scenarios (SRES) B2 scenario. In 1961-1990, the total NPP of natural vegetation in China was about 3.06 Pg C a(-1); in 1961-2080, the total NPP showed a fluctuant decreasing trend, with an accelerated decreasing rate. Under the condition of slight precipitation change, the increase of mean air temperature would have definite adverse impact on the NPP. Spatially, the NPP decreased from southeast coast to northwest inland, and this pattern would have less variation under climate change. In eastern China with higher NPP, especially in Northeast China, east of North China, and Loess Plateau, the NPP would mainly have a decreasing trend; while in western China with lower NPP, especially in the Tibetan Plateau and Tarim Basin, the NPP would be increased. With the intensive climate change, such a variation trend of NPP would be more obvious. PMID:21774310

  7. [Variation trends of natural vegetation net primary productivity in China under climate change scenario].

    PubMed

    Zhao, Dong-sheng; Wu, Shao-hong; Yin, Yun-he

    2011-04-01

    Based on the widely used Lund-Potsdam-Jena Dynamic Global Vegetation Model (LPJ) for climate change study, and according to the features of natural environment in China, the operation mechanism of the model was adjusted, and the parameters were modified. With the modified LPJ model and taking 1961-1990 as baseline period, the responses of natural vegetation net primary productivity (NPP) in China to climate change in 1991-2080 were simulated under the Special Report on Emissions Scenarios (SRES) B2 scenario. In 1961-1990, the total NPP of natural vegetation in China was about 3.06 Pg C a(-1); in 1961-2080, the total NPP showed a fluctuant decreasing trend, with an accelerated decreasing rate. Under the condition of slight precipitation change, the increase of mean air temperature would have definite adverse impact on the NPP. Spatially, the NPP decreased from southeast coast to northwest inland, and this pattern would have less variation under climate change. In eastern China with higher NPP, especially in Northeast China, east of North China, and Loess Plateau, the NPP would mainly have a decreasing trend; while in western China with lower NPP, especially in the Tibetan Plateau and Tarim Basin, the NPP would be increased. With the intensive climate change, such a variation trend of NPP would be more obvious.

  8. The Natural History and Prognosis of Primary Biliary Cirrhosis with Clinical Features of Autoimmune Hepatitis.

    PubMed

    Yang, Fan; Wang, Qixia; Wang, Zhaoyue; Miao, Qi; Xiao, Xiao; Tang, Ruqi; Chen, Xiaoyu; Bian, Zhaolian; Zhang, Haiyan; Yang, Yue; Sheng, Li; Fang, Jingyuan; Qiu, Dekai; Krawitt, Edward L; Gershwin, M Eric; Ma, Xiong

    2016-02-01

    Although a variant of primary biliary cirrhosis (PBC) characterized by features of autoimmune hepatitis (AIH) has been recognized for many years, few studies with ample numbers of patients have focused on its natural history. This study aimed to clarify the natural history, prognosis, and response to therapy in a cohort of patients with PBC with AIH features. We retrospectively analyzed 277 PBC patients without AIH features and 46 PBC patients with AIH features seen between September 2004 and April 2014. The 5-year adverse outcome-free survival of PBC patients with AIH features was 58% compared to 81% in PBC patients without AIH features. Multivariate analysis in the patients with AIH features indicated that total bilirubin ≥ 2.70× the upper limit of normal predicted a poor prognosis (p = 0.008, relative risk 8.39, 95% confidence interval (CI) 1.73, 40.73). Combination therapy with ursodeoxycholic acid (UDCA) and immunosuppression provided better short-term responses in PBC patients with AIH features, defined by multiple criteria. Higher aspartate aminotransferase (AST) level at accession suggested better prognosis for PBC patients with AIH features while worse prognosis for PBC patients without AIH features. PBC patients with AIH features differ from those without AIH features in terms of natural history, prognostic indicators, and response to therapy.

  9. Primary school children and teachers discover the nature and science of planet Earth and Mars

    NASA Astrophysics Data System (ADS)

    Kleinhans, Maarten; Verkade, Alex; Bastings, Mirjam; Reichwein, Maarten

    2016-04-01

    For various reasons primary schools emphasise language and calculus rather than natural sciences. When science is taught at all, examination systems often favour technological tricks and knowledge of the 'right' answer over the process of investigation and logical reasoning towards that answer. Over the long term, this is not conducive to curiosity and scientific attitude in large parts of the population. Since the problem is more serious in primary than in secondary education, and as children start their school career with a natural curiosity and great energy to explore their world, we focus our efforts on primary school teachers in close collaboration with teachers and researchers. Our objective was to spark children's curiosity and their motivation to learn and discover, as well as to help teachers develop self-afficacy in science education. To this end we developed a three-step program with a classroom game and sand-box experiments related to planet Earth and Mars. The classroom game Expedition Mundus simulates science in its focus on asking questions, reasoning towards answers on the basis of multiple sources and collaboration as well as growth of knowledge. Planet Mundus is entirely fictitional to avoid differences in foreknowledge between pupils. The game was tested in hundreds of classes in primary schools and the first years of secondary education and was printed (in Dutch) and distributed over thousands of schools as part of teacher education through university science hubs. Expedition Mundus was developed by the Young Academy of the Royal Netherlands Academy of Arts and Sciences and De Praktijk. The tested translations in English and German are available on http://www.expeditionmundus.org. Following the classroom game, we conducted simple landscape experiments in sand boxes supported by google earth imagery of real rivers, fans and deltas on Earth and Mars. This was loosely based on our fluvial morphodynamics research. This, in the presence of a

  10. Characteristic Fracture Spacing in Primary and Secondary Recovery from Naturally Fractured Reservoirs

    NASA Astrophysics Data System (ADS)

    Gong, J.; Rossen, W.

    2015-12-01

    We showed previously (Gong and Rossen, 2014a,b) that, if the fracture aperture distribution is broad enough in a naturally fractured reservoir, even one where the fracture network is well-connected, most fractures can be eliminated without significantly affecting the flow through the fracture network. During a waterflood or enhanced-oil-recovery (EOR) process, the production of oil depends on the supply of injected water or EOR agent. This suggests that the characteristic fracture spacing for the dual-porosity/dual-permeability simulation of waterflood or EOR in a naturally fractured reservoir should account not for all fractures but only the relatively small portion of the fracture network carrying almost all the injected water or EOR agent. In contrast, in primary production even a relatively small fracture represents an effective path for oil to flow to a production well. Thus in primary production the effective fracture spacing should include all the fractures. This distinction means that the "shape factor" in dual-porosity/dual-permeability reservoir simulators and the repeating unit in homogenization should depend on the process involved: specifically, it should be different for primary and secondary or tertiary recovery. We test this hypothesis in a simple representation of a fractured reservoir with a non-uniform distribution of fracture flow conductivities. We compare oil production, flow patterns in matrix, and the pattern of oil recovery around fractures with and without the "unimportant" fractures present. In primary production, all fractures which are much more permeable than matrix play a significant role in production. The shape factor or repeating-unit size should reflect the entire fracture distribution. In secondary or tertiary production, the role of fractures that carry relatively little flow depends on injection rate, the ratio of flow carried by the different fractures, and the permeability of matrix. In some cases, the appropriate shape

  11. Effects of Rosmarinus officinalis extract on human primary omental preadipocytes and adipocytes

    PubMed Central

    Stefanon, Bruno; Pomari, Elena

    2015-01-01

    The prevalence of obesity is increasing all over the world. Although it has been shown that natural substances influence fat metabolism, little is known about the effect on cellular and molecular mechanisms in human. In this in vitro study, the activity of Rosmarinus officinalis (RO) standardized extract in modulating human primary visceral preadipocytes differentiation, lipolysis, and apoptosis was investigated. Moreover, gene expression of key adipogenesis modulators and microRNAs-seq were evaluated. Preadipocytes treated with RO extract significantly reduced triglyceride incorporation during maturation in a dose-dependent manner without affecting cell viability. In addition, RO extract stimulated lipolytic activity in differentiating preadipocytes and mature adipocytes in treated cells compared to controls. Differentiating preadipocytes incubated in the presence of RO extract showed a decreased expression of cell cycle genes such as cyclin D1, cyclin-dependent kinase 4, cyclin-dependent kinase inhibitor 1A (p21, Cip1) and an increased expression of GATA binding protein 3, wingless-type MMTV integration site family, member 3A mRNA levels. Recent studies have demonstrated that some phytochemicals alter the expression of specific genes and microRNAs that play a fundamental role in the pathogenesis of obesity and related diseases. Interestingly, genes modulated in RO-treated cells were found to be validated miRNAs targets, such as let-7f-1, miR-17, and miR-143. The results indicated that RO extract modulates human adipocyte differentiation and significantly interferes with adipogenesis and lipid metabolism, supporting its interest as dietary supplement. PMID:25710930

  12. Overview of naturally occurring Earth materials and human health concerns

    NASA Astrophysics Data System (ADS)

    Ernst, W. G.

    2012-10-01

    The biosphere and the Earth's critical zone have maintained a dynamic equilibrium for more than 3.5 billion years. Except for solar energy, almost all terrestrial substances necessary for life have been derived from near-surface portions of the land, hydrosphere, and atmosphere. If aggregate biological activities are less than the rate of nutrient supply and/or resource renewal, sustained population growth is possible. Where the replenishment rate of a life-sustaining Earth material is finite, usage may reach a condition of dynamic equilibrium in which biological consumption equals but on average cannot exceed the overall supply. Although large, most natural resources are present in finite abundances; for such commodities, excessive present-day human utilization reduces future availability, and thus the ultimate planetary carrying capacity for civilization. Intensive use of Earth materials has enhanced the quality of life, especially in the developed nations. Still, natural background levels, and Earth processes such as volcanic eruptions, as well as human activities involving agriculture, construction, and the extraction, refining, and transformation of mineral resources have led to harmful side effects involving environmental degradation and public health hazards. Among naturally and anthropogenically induced risks are bioaccessible airborne dusts and gases, soluble pollutants in agricultural, industrial, and residential waters, and toxic chemical species in foods and manufactured products. At appropriate levels of ingestion, many Earth materials are necessary for existence, but underdoses and overdoses have mild to serious consequences for human health and longevity. This overview briefly sketches several natural resource health hazards. Included are volcanic ash + aerosols + gases, mineral dusts, non-volcanic aerosols + nanoparticles, asbestos + fibrous zeolites, arsenic, fluorine, iodine, uranium + thorium + radium + radon + polonium, selenium, mercury, copper

  13. Effect of extracellular human immunodeficiency virus type 1 glycoprotein 120 on primary human vascular endothelial cell cultures.

    PubMed

    Huang, M B; Hunter, M; Bond, V C

    1999-09-20

    During the course of an HIV-1 infection, free infectious and noninfectious virus particles, and free HIV-1 proteins, circulate within the host, exposing the host endothelium to these viral factors, even if the endothelium is not infected. This suggests that extracellular HIV-1 proteins could influence endothelial cell function, leading to pathogenesis. In light of this, we have used primary cultured human vascular endothelial cells (HUVECs) to screen for effects of the HIV-1 protein gp120 on endothelial cell function. The results of this study show that short exposure of HUVEC cultures to this protein causes significant levels of cytotoxicity. Further, using several different assays, we have shown that this cytotoxic effect on HUVECs appears to be due to induction of an apoptotic program. The biphasic nature of gp120 titration curves suggests that multiple cellular factors are mediating these gp120-induced effects. Competition studies appear to confirm this by showing that the apoptotic effect is mediated through two cell surface receptors on HUVECs, CCR5 and CXCR4. Alternatively, competition studies examining CD4 receptors suggests that CD4 played no role in gp12O-induced effects on HUVECs.

  14. Experience in primary culture of human peritoneal mesothelial cell.

    PubMed

    Chen, Kuo-Su; Chen, Wen-Shiang

    2012-08-31

    To compare the growth condition between different sources and different culture environments, mesothelial cells were isolated from omentum and peritoneal dialysate effluent (PDE), seeded at different densities (5 × 10⁵, 1 × 10⁵, 5 × 10⁴, 1 × 10⁴, 5 × 10³, 1 × 10³ and 5 × 10² cells/cm², respectively), supported with different fetal calf serum (FCS) concentrations (3%, 6%, 10% and 15%) and grown in dishes with and without gelatin pre-coating. Growth condition was evaluated by simple morphological observation. Cells phenotype was examined by immunofluorescent staining. The results showed that omentum-derived mesothelial cells generally showed a uniform growth pattern with good quality. Alternatively, there was a wide patient-to-patient variation in PDE-derived culture. Heterogeneous colonies composed of a mixture of large, small or abortive mesothelial colonies as well as fibroblastoid colonies were frequently observed. A minimum seeding density of 5 × 10³ cells/cm² is required for the omentum-derived mesothelial cells to grow to confluent monolayer (1-5 × 10⁴ cells/cm² for initial culture from fresh PDE). Appropriate seeding density is always associated with successful culture in omentumbased culture, but not in PDE-based culture. Mesothelial cells could grow to confluency regardless of FCS concentration and gelatin pre-coating. However, growth rate was slower in lower FCS concentrations and on dishes without gelatin coating. Most cells in culture expressed cytokeratin and vimentin, but not VWF. Alpha-smooth muscle actin frequently appeared in cytokeratin+ mesothelial cells, especially in higher FCS concentrations and in PDE-derived culture. Our data demonstrate that PDE, in contrast to omentum, provides a source of mesothelial cells with poor and unstable quality for primary culture. Healthy cell quality and sufficient seeding density seem to be the most important factors for successful culture of mesothelial cells. The frequent occurrence

  15. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo.

    PubMed

    Greening, David W; Ji, Hong; Chen, Maoshan; Robinson, Bruce W S; Dick, Ian M; Creaney, Jenette; Simpson, Richard J

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.

  16. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

    NASA Astrophysics Data System (ADS)

    Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

    2016-09-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets.

  17. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo

    PubMed Central

    Greening, David W.; Ji, Hong; Chen, Maoshan; Robinson, Bruce W. S.; Dick, Ian M.; Creaney, Jenette; Simpson, Richard J.

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

  18. Secreted primary human malignant mesothelioma exosome signature reflects oncogenic cargo.

    PubMed

    Greening, David W; Ji, Hong; Chen, Maoshan; Robinson, Bruce W S; Dick, Ian M; Creaney, Jenette; Simpson, Richard J

    2016-01-01

    Malignant mesothelioma (MM) is a highly-aggressive heterogeneous malignancy, typically diagnosed at advanced stage. An important area of mesothelioma biology and progression is understanding intercellular communication and the contribution of the secretome. Exosomes are secreted extracellular vesicles shown to shuttle cellular cargo and direct intercellular communication in the tumour microenvironment, facilitate immunoregulation and metastasis. In this study, quantitative proteomics was used to investigate MM-derived exosomes from distinct human models and identify select cargo protein networks associated with angiogenesis, metastasis, and immunoregulation. Utilising bioinformatics pathway/network analyses, and correlation with previous studies on tumour exosomes, we defined a select mesothelioma exosomal signature (mEXOS, 570 proteins) enriched in tumour antigens and various cancer-specific signalling (HPGD/ENO1/OSMR) and secreted modulators (FN1/ITLN1/MAMDC2/PDGFD/GBP1). Notably, such circulating cargo offers unique insights into mesothelioma progression and tumour microenvironment reprogramming. Functionally, we demonstrate that oncogenic exosomes facilitate the migratory capacity of fibroblast/endothelial cells, supporting the systematic model of MM progression associated with vascular remodelling and angiogenesis. We provide biophysical and proteomic characterisation of exosomes, define a unique oncogenic signature (mEXOS), and demonstrate the regulatory capacity of exosomes in cell migration/tube formation assays. These findings contribute to understanding tumour-stromal crosstalk in the context of MM, and potential new diagnostic and therapeutic extracellular targets. PMID:27605433

  19. The role of arginine vasopressin in electroacupuncture treatment of primary sciatica in human.

    PubMed

    Zhao, Xue-Yan; Zhang, Qi-Shun; Yang, Jun; Sun, Fang-Jie; Wang, Da-Xin; Wang, Chang-Hong; He, Wei-Ya

    2015-08-01

    It has been implicated that electroacupuncture can relieve the symptoms of sciatica with the increase of pain threshold in human, and arginine vasopressin (AVP) in the brain rather than the spinal cord and blood circulation participates in antinociception. Our previous study has proven that AVP in the brain played a role in the process of electroacupuncture analgesia in rat. The goal of the present study was to investigate the role of AVP in electroacupuncture in treating primary sciatica in human. The results showed that (1) AVP concentration of cerebrospinal fluid (CSF) (7.5 ± 2.5 pg/ml), not plasma (13.2 ± 4.2 pg/ml) in primary sciatica patients was lower than that in health volunteers (16.1 ± 3.8 pg/ml and 12.3 ± 3.4 pg/ml), although the osmotic pressure in CSF and plasma did not change; (2) electroacupuncture of the bilateral "Zusanli" points (St. 36) for 60 min relieved the pain sensation in primary sciatica patients; (3) electroacupuncture increased the AVP level of CSF, not plasma in primary sciatica patients; and (4) there was the positive correlation between the effect of electroacupuncture relieving the pain and the AVP level of CSF in the primary sciatica patients. The data suggested that central AVP, not peripheral AVP might improve the effect of electroacupuncture treatment of primary sciatica in human, i.e., central AVP might take part in the electroacupuncture relieving the pain sensation in primary sciatica patients.

  20. Distancing Students From Nature: Science Camp and the Representation of the Human-Nature Relationship

    NASA Astrophysics Data System (ADS)

    Terrill, Laura Anne

    This study investigated the curricular representations of the environment and the human-environment relationship at one residential school sponsored science camp. Data gathered included field notes from observational time at the camp, interviews with staff and classroom teachers, and documents from the site's website, guides, manuals, and curricular guides. These data were analyzed to understand how the camp represented the human-environment relationship and the "proper" human-environment relationship to its participants. Analysis indicated that the camp's official and enacted curriculum was shaped in response to two perceived problems, (1) students were perceived as having a disconnected relationship with the outdoors and lacking in outdoor experiences; and (2) staff members of the camp believed that time for science during the school day had diminished and that students were not receiving adequate science instruction at school. In response, the goal of the camp was to connect students to the outdoors through hands-on, sensory, experience based science and outdoor education experiences. However, key aspects of the camp experience and the formal and enacted curriculum unintentionally positioned students as separate from nature. The camp experience presented a vacation like understanding of the human-environment relationship as students became tourists of the outdoors. Despite the site's goal of connecting students to the outdoors, the science camp experience worked to distance students from the outdoors by unintentionally representing the outdoors as a place that existed away from home and students' everyday lives. Notably, nature became a place that existed in the past, separate from modernity. Students were tourists in an exotic location - nature. They received tours of the foreign outdoors, had fun, and returned home to their ordinary lives that were separate and distinct from the natural world.

  1. Higher Energy Expenditure in Humans Predicts Natural Mortality

    PubMed Central

    Hanson, Robert L.; Sievers, Maurice L.; Bennett, Peter H.; Nelson, Robert G.; Krakoff, Jonathan

    2011-01-01

    Context: Higher metabolic rates increase free radical formation, which may accelerate aging and lead to early mortality. Objective: Our objective was to determine whether higher metabolic rates measured by two different methods predict early natural mortality in humans. Design: Nondiabetic healthy Pima Indian volunteers (n = 652) were admitted to an inpatient unit for approximately 7 d as part of a longitudinal study of obesity and diabetes risk factors. Vital status of study participants was determined through December 31, 2006. Twenty-four-hour energy expenditure (24EE) was measured in 508 individuals, resting metabolic rate (RMR) was measured in 384 individuals, and 240 underwent both measurements on separate days. Data for 24EE were collected in a respiratory chamber between 1985 and 2006 with a mean (sd) follow-up time of 11.1 (6.5) yr and for RMR using an open-circuit respiratory hood system between 1982 and 2006 with a mean follow-up time of 15.4 (6.3) yr. Cox regression models were used to test the effect of EE on natural mortality, controlled for age, sex, and body weight. Results: In both groups, 27 natural deaths occurred during the study period. For each 100-kcal/24 h increase in EE, the risk of natural mortality increased by 1.29 (95% confidence interval = 1.00–1.66; P < 0.05) in the 24EE group and by 1.25 (95% confidence interval = 1.01–1.55; P < 0.05) in the RMR group, after adjustment for age, sex, and body weight in proportional hazard analyses. Conclusions: Higher metabolic rates as reflected by 24EE or RMR predict early natural mortality, indicating that higher energy turnover may accelerate aging in humans. PMID:21450984

  2. Type I interferon regulation of natural killer cell function in primary and secondary infections.

    PubMed

    Stackaruk, Michele L; Lee, Amanda J; Ashkar, Ali A

    2013-08-01

    The priming of natural killer (NK) cells by type I interferon (IFN) is necessary for protection against primary and secondary viral infections. However, the pathway by which type I IFN activates NK cells to elicit antiviral responses is controversial. There is evidence to suggest that type I IFN priming of NK cells occurs through both direct and indirect pathways. As with many innate mechanisms, type I IFN and NK cells also orchestrate the adaptive immune response and thus aid in protection against secondary infections. Type I IFN can shape CD4(+) T cell, B cell and humoral memory formation. In addition, long-lived NK cells can perform specific and enhanced memory-like protection in secondary infections. This review outlines the different mechanisms underlying type I IFN regulation of NK cells and how type I IFN and NK cells can be used as a therapeutic target in vaccinations.

  3. Management of an intruded primary central incisor with a natural crown under general anesthesia

    PubMed Central

    Altunsoy, Mustafa; Bilgin, Mehmet Selim

    2014-01-01

    Tooth intrusion is the most common trauma during early infancy. Primary maxillary central incisors are the most affected teeth. There are a few treatment approaches which depend upon the severity of the trauma, and the treatment must be managed professionally. In this case report, a 3-year-old girl with a history of trauma 40 days before referring to our pediatric clinic is presented. Deciduous maxillary right central incisor was intruded through labial and alveolar socket and completely covered with soft tissue. The intruded deciduous incisor tooth was surgically extracted and impression was taken under general anesthesia. The removable partial prosthesis was completed by using the patient's own extracted tooth. Using natural crown on removable prosthesis gives psychological satisfaction to the patient and his/her family, and can be better tolerated since its shape, size, and color are exactly in harmony. PMID:24966781

  4. Natural mummification of the human gut preserves bacteriophage DNA.

    PubMed

    Santiago-Rodriguez, Tasha M; Fornaciari, Gino; Luciani, Stefania; Dowd, Scot E; Toranzos, Gary A; Marota, Isolina; Cano, Raul J

    2016-01-01

    The natural mummification process of the human gut represents a unique opportunity to study the resulting microbial community structure and composition. While results are providing insights into the preservation of bacteria, fungi, pathogenic eukaryotes and eukaryotic viruses, no studies have demonstrated that the process of natural mummification also results in the preservation of bacteriophage DNA. We characterized the gut microbiome of three pre-Columbian Andean mummies, namely FI3, FI9 and FI12, and found sequences homologous to viruses. From the sequences attributable to viruses, 50.4% (mummy FI3), 1.0% (mummy FI9) and 84.4% (mummy FI12) were homologous to bacteriophages. Sequences corresponding to the Siphoviridae, Myoviridae, Podoviridae and Microviridae families were identified. Predicted putative bacterial hosts corresponded mainly to the Firmicutes and Proteobacteria, and included Bacillus, Staphylococcus, Clostridium, Escherichia, Vibrio, Klebsiella, Pseudomonas and Yersinia. Predicted functional categories associated with bacteriophages showed a representation of structural, replication, integration and entry and lysis genes. The present study suggests that the natural mummification of the human gut results in the preservation of bacteriophage DNA, representing an opportunity to elucidate the ancient phageome and to hypothesize possible mechanisms of preservation.

  5. Stream primary producers relate positively to watershed natural gas measures in north-central Arkansas streams.

    PubMed

    Austin, Bradley J; Hardgrave, Natalia; Inlander, Ethan; Gallipeau, Cory; Entrekin, Sally; Evans-White, Michelle A

    2015-10-01

    Construction of unconventional natural gas (UNG) infrastructure (e.g., well pads, pipelines) is an increasingly common anthropogenic stressor that increases potential sediment erosion. Increased sediment inputs into nearby streams may decrease autotrophic processes through burial and scour, or sediment bound nutrients could have a positive effect through alleviating potential nutrient limitations. Ten streams with varying catchment UNG well densities (0-3.6 wells/km(2)) were sampled during winter and spring of 2010 and 2011 to examine relationships between landscape scale disturbances associated with UNG activity and stream periphyton [chlorophyll a (Chl a)] and gross primary production (GPP). Local scale variables including light availability and water column physicochemical variables were measured for each study site. Correlation analyses examined the relationships of autotrophic processes and local scale variables with the landscape scale variables percent pasture land use and UNG metrics (well density and well pad inverse flow path length). Both GPP and Chl a were primarily positively associated with the UNG activity metrics during most sample periods; however, neither landscape variables nor response variables correlated well with local scale factors. These positive correlations do not confirm causation, but they do suggest that it is possible that UNG development can alleviate one or more limiting factors on autotrophic production within these streams. A secondary manipulative study was used to examine the link between nutrient limitation and algal growth across a gradient of streams impacted by natural gas activity. Nitrogen limitation was common among minimally impacted stream reaches and was alleviated in streams with high UNG activity. These data provide evidence that UNG may stimulate the primary production of Fayetteville shale streams via alleviation of N-limitation. Restricting UNG activities from the riparian zone along with better enforcement of

  6. Stream primary producers relate positively to watershed natural gas measures in north-central Arkansas streams.

    PubMed

    Austin, Bradley J; Hardgrave, Natalia; Inlander, Ethan; Gallipeau, Cory; Entrekin, Sally; Evans-White, Michelle A

    2015-10-01

    Construction of unconventional natural gas (UNG) infrastructure (e.g., well pads, pipelines) is an increasingly common anthropogenic stressor that increases potential sediment erosion. Increased sediment inputs into nearby streams may decrease autotrophic processes through burial and scour, or sediment bound nutrients could have a positive effect through alleviating potential nutrient limitations. Ten streams with varying catchment UNG well densities (0-3.6 wells/km(2)) were sampled during winter and spring of 2010 and 2011 to examine relationships between landscape scale disturbances associated with UNG activity and stream periphyton [chlorophyll a (Chl a)] and gross primary production (GPP). Local scale variables including light availability and water column physicochemical variables were measured for each study site. Correlation analyses examined the relationships of autotrophic processes and local scale variables with the landscape scale variables percent pasture land use and UNG metrics (well density and well pad inverse flow path length). Both GPP and Chl a were primarily positively associated with the UNG activity metrics during most sample periods; however, neither landscape variables nor response variables correlated well with local scale factors. These positive correlations do not confirm causation, but they do suggest that it is possible that UNG development can alleviate one or more limiting factors on autotrophic production within these streams. A secondary manipulative study was used to examine the link between nutrient limitation and algal growth across a gradient of streams impacted by natural gas activity. Nitrogen limitation was common among minimally impacted stream reaches and was alleviated in streams with high UNG activity. These data provide evidence that UNG may stimulate the primary production of Fayetteville shale streams via alleviation of N-limitation. Restricting UNG activities from the riparian zone along with better enforcement of

  7. A Simple Model for Human and Nature Interaction

    NASA Astrophysics Data System (ADS)

    Motesharrei, S.; Rivas, J.; Kalnay, E.

    2012-12-01

    There are widespread concerns that current trends in population and resource-use are unsustainable, but the possibilities of an overshoot and collapse remain unclear and controversial. Collapses of civilizations have occurred many times in the past 5000 years, often followed by centuries of economic, intellectual, and population decline. Many different natural and social phenomena have been invoked to explain specific collapses, but a general explanation remains elusive. Two important features seem to appear across societies that have collapsed: Ecological Strain and Economic Stratification. Our new model (Human And Nature DYnamics, HANDY) has just four equations that describe the evolution of Elites, Commoners, Nature, and Wealth. Mechanisms leading to collapse are discussed and the measure "Carrying Capacity" is developed and defined. The model shows that societal collapse can happen due to either one of two independent factors: (1) over-consumption of natural resources, and/or (2) deep inequity between Elites and Commoners. The model also portrays two distinct types of collapse: (i) collapse followed by recovery of nature, and (ii) full collapse. The model suggests that the estimation of Carrying Capacity is a practical means for early detection of a collapse. Collapse can be avoided, and population can reach a sustainable equilibrium, if the rate of depletion of nature is reduced to a sustainable level, and if resources are distributed in a reasonably equitable fashion.; A type-ii (full) collapse is shown in this figure. With high inequality and high depletion, societies are doomed to collapse. Wealth starts to decrease when population rises above the carrying capacity. The large gap between carrying capacity and its maximum is a result of depletion factor being much larger than the sustainable limit. ; It is possible to overshoot, oscillate, and eventually converge to an equilibrium, even in an inequitable society. However, it requires policies that control

  8. Food safety: are human activities really worse than nature's?

    PubMed

    Clayson, D B

    1993-04-01

    Those chemicals that are added to food during modern processing are most stringently examined for toxic effects and, if they demonstrate toxicity, are strictly controlled. Despite this, a considerable proportion of the North American human cancer burden has been associated with diet and nutrition. The possible contributions of excess calories, excess and wrongly balanced fats, natural contaminants, and naturally occurring carcinogens within the food supply to this horrendous burden of cancer is considered. The theoretically possible use of bioengineering techniques to modify the composition of food crops and thus to minimize the levels of carcinogens in the food supply is discussed. This is considered important since failure to monitor the effect of bioengineering may lead to an increase in the level of such noxious agents, especially if the goal of such bioengineering is to develop food crops with increased intrinsic resistance to pests and other spoilage organisms.

  9. 'Nature and the Greeks' and 'Science and Humanism'

    NASA Astrophysics Data System (ADS)

    Schrödinger, Erwin

    2014-11-01

    Foreword; Part I. Nature and the Greeks: 1. The motives for returning to ancient thought; 2. The competition, reason v. senses; 3. The Pythagoreans; 4. The Ionian enlightenment; 5. The religion of Xenophanes, Heraclitus of Ephesus; 6. The atomists; 7. What are the special features?; Part II. Science and Humanism: 1. The spiritual bearing of science on life; 2. The practical achievements of science tending to obliterate its true import; 3. A radical change in our ideas of matter; 4. Form, not substance, the fundamental concept; 5. The nature of our 'models'; 6. Continuous descriptions and causality; 7. The intricacy of the continuum; 8. The makeshift of wave mechanics; 9. The alleged breakdown of the barrier between subject and object; 10. Atoms or quanta - the counter-spell of old standing, to escape the intricacy of the continuum; 11. Would physical indeterminacy give free will a chance?; 12. The bar to prediction, according to Niels Bohr; Literature.

  10. Naturally occurring animal models of human hepatitis E virus infection.

    PubMed

    Yugo, Danielle M; Cossaboom, Caitlin M; Meng, Xiang-Jin

    2014-01-01

    Hepatitis E virus (HEV) is a single-stranded, positive-sense RNA virus in the family Hepeviridae. Hepatitis E caused by HEV is a clinically important global disease. There are currently four well-characterized genotypes of HEV in mammalian species, although numerous novel strains of HEV likely belonging to either new genotypes or species have recently been identified from several other animal species. HEV genotypes 1 and 2 are limited to infection in humans, whereas genotypes 3 and 4 infect an expanding host range of animal species and are zoonotic to humans. Historical animal models include various species of nonhuman primates, which have been indispensable for the discovery of human HEV and for understanding its pathogenesis and course of infection. With the genetic identification and characterization of animal strains of HEV, a number of naturally occurring animal models such as swine, chicken, and rabbit have recently been developed for various aspects of HEV research, including vaccine trials, pathogenicity, cross-species infection, mechanism of virus replication, and molecular biology studies. Unfortunately, the current available animal models for HEV are still inadequate for certain aspects of HEV research. For instance, an animal model is still lacking to study the underlying mechanism of severe and fulminant hepatitis E during pregnancy. Also, an animal model that can mimic chronic HEV infection is critically needed to study the mechanism leading to chronicity in immunocompromised individuals. Genetic identification of additional novel animal strains of HEV may lead to the development of better naturally occurring animal models for HEV. This article reviews the current understanding of animal models of HEV infection in both natural and experimental infection settings and identifies key research needs and limitations.

  11. Natural and human dimensions of a quasi-wild species: The case of kudzu

    USGS Publications Warehouse

    Li, Z.; Dong, Q.; Albright, T.P.; Guo, Q.

    2011-01-01

    The human dimensions of biotic invasion are generally poorly understood, even among the most familiar invasive species. Kudzu (Pueraria montana (Lour.) Merr.) is a prominent invasive plant and an example of quasi-wild species, which has experienced repeated introduction, cultivation, and escape back to the wild. Here, we review a large body of primary scientific and historic records spanning thousands of years to characterize the complex relationships among kudzu, its natural enemies, and humans, and provide a synthesis and conceptual model relevant to the ecology and management of quasi-wild invasive species. We documented over 350, mostly insect, natural enemy species and their impacts on kudzu in its native East Asian range. These natural enemies play a minor role in limiting kudzu in its native range, rarely generating severe impacts on populations of wild kudzu. We identified a number of significant influences of humans including dispersal, diverse cultural selection, and facilitation through disturbances, which catalyzed the expansion and exuberance of kudzu. On the other hand, harvest by humans appears to be the major control mechanism in its native areas. Humans thus have a complex relationship with kudzu. They have acted as both friend and foe, affecting the distribution and abundance of kudzu in ways that vary across its range and over time. Our conceptual model of kudzu emphasizes the importance of multiple human dimensions in shaping the biogeography of a species and illustrates how kudzu and other quasi-wild species are more likely to be successful invaders. ?? 2011 Springer Science+Business Media B.V.(outside the USA).

  12. Responses of Neurons in Primary and Inferior Temporal Visual Cortices to Natural Scenes

    NASA Astrophysics Data System (ADS)

    Baddeley, Roland; Abbott, L. F.; Booth, Michael C. A.; Sengpiel, Frank; Freeman, Tobe; Wakeman, Edward A.; Rolls, Edmund T.

    1997-12-01

    The primary visual cortex (V1) is the first cortical area to receive visual input, and inferior temporal (IT) areas are among the last along the ventral visual pathway. We recorded, in area V1 of anaesthetized cats and area IT of awake macaque monkeys, responses of neurons to videos of natural scenes. Responses were analysed to test various hypotheses concerning the nature of neural coding in these two regions. A variety of spike-train statistics were measured including spike-count distributions, interspike interval distributions, coefficients of variation, power spectra, Fano factors and different sparseness measures. All statistics showed non-Poisson characteristics and several revealed self-similarity of the spike trains. Spike-count distributions were approximately exponential in both visual areas for eight different videos and for counting windows ranging from 50 ms to 5 seconds. The results suggest that the neurons maximize their information carrying capacity while maintaining a fixed long-term-average firing rate, or equivalently, minimize their average firing rate for a fixed information carrying capacity.

  13. hIFN-α gene modification augments human natural killer cell line anti-human hepatocellular carcinoma function.

    PubMed

    Jiang, W; Zhang, C; Tian, Z; Zhang, J

    2013-11-01

    Natural killer (NK) cells are characterized by an efficient antitumor activity, and this activity has been exploited as the basis of cancer immunotherapy strategies. Interferon-α (IFN-α) is an important cytokine required for induction of the durable antitumor immune response and is an important stimulator of NK cells. In this study, to augment the efficiency of NK cell cytotoxicity to tumor cells, human IFN-α gene-modified natural killer cell line (NKL) (NKL-IFNα) cells, which could stably secrete IFN-α, were established. We investigated the natural cytotoxicity of NKL-IFNα cells against human hepatocarcinoma cells (HCCs) in vitro and in vivo. NKL-IFNα cells displayed a significantly stronger cytolytic activity against both human HCC cell lines and primary human hepatoma cancer cells compared with parental NKL cells. The increased cytolytic activity of NKL-IFNα cells was associated with the upregulation of cytotoxicity-related genes, such as perforin, granzyme B and Fas ligand, in the NK cells. Moreover, cytokines secreted by NKL-IFNα cells, such as tumor necrosis factor-α and IFN-γ, induced increased expression of Fas on the target HCC cells, and resulted in increased susceptibility of the HCC cells to NK-mediated cytolysis. Encouragingly, NKL-IFNα cells could significantly inhibit HCC tumor growth in a xenograft model and prolonged the survival of tumor-bearing nude mice. These results suggest that IFN-α gene-modified NKL cells could be suitable for the future development of cell-based immunotherapeutic strategies for hepatocellular carcinoma.

  14. Natural Human Mobility Patterns and Spatial Spread of Infectious Diseases

    NASA Astrophysics Data System (ADS)

    Belik, Vitaly; Geisel, Theo; Brockmann, Dirk

    2011-08-01

    We investigate a model for spatial epidemics explicitly taking into account bidirectional movements between base and destination locations on individual mobility networks. We provide a systematic analysis of generic dynamical features of the model on regular and complex metapopulation network topologies and show that significant dynamical differences exist to ordinary reaction-diffusion and effective force of infection models. On a lattice we calculate an expression for the velocity of the propagating epidemic front and find that, in contrast to the diffusive systems, our model predicts a saturation of the velocity with an increasing traveling rate. Furthermore, we show that a fully stochastic system exhibits a novel threshold for the attack ratio of an outbreak that is absent in diffusion and force of infection models. These insights not only capture natural features of human mobility relevant for the geographical epidemic spread, they may serve as a starting point for modeling important dynamical processes in human and animal epidemiology, population ecology, biology, and evolution.

  15. Non-reductive continental naturalism in the contemporary humanities

    PubMed Central

    Van der Tuin, Iris

    2013-01-01

    This article engages with the philosophical reflections of the French historian of science Hélène Metzger (1886–1944) in order to develop a vocabulary for understanding the rise of non-reductive Continental naturalism in the contemporary humanities. The bibliography of current naturalist approaches in the arts and the human sciences is still in the making, but it is altogether clear that the trend is not scientist or historicist or relativist. This epistemological diagnosis refers us to Metzger, who found herself surrounded with the logical positivism of the Wiener Kreis, on the one hand, and the historicism of her French colleagues, on the other, as well as with the infiltration of the history of science by a chronological empiricism. In this article I will take the most recent book of Vicki Kirby – Quantum Anthropologies: Life at Large from 2011 – as an exemplary case of non-reductive Continental naturalist scholarship in the humanities today and by reading it through the concepts of Metzger, I will demonstrate how this type of research leads to refreshing insights in what constitutes positive humanities knowledge and what is the role of the a priori in the field. PMID:23908566

  16. Infections of neonatal and adult mice with murine CMV HaNa1 strain upon oronasal inoculation: New insights in the pathogenesis of natural primary CMV infections.

    PubMed

    Xiang, Jun; Zhang, Shunchuan; Nauwynck, Hans

    2016-01-01

    In healthy individuals, naturally acquired infections of human cytomegalovirus (HCMV) are generally asymptomatic. Animal models mimicking the natural primary HCMV infections in infants and adults are scarce. Here, neonatal and adult BALB/c mice were inoculated oronasally with a Belgian isolate HaNa1 of murine cytomegalovirus (MCMV). None of the mice showed clinical symptoms. In neonatal mice, a typical systemic infection occurred. In adult mice, viral replication was restricted to the nasal mucosa and submandibular glands. Infectious virus was not detected in trachea, oral mucosa, pharynx, esophagus, small intestines of both neonatal and adult mice at all time points. Nose was demonstrated to be the entry site. Double immunofluorescence staining showed that in nose infected cells were olfactory neurons and sustentacular cells in olfactory epithelium and were macrophages and dendritic cells in nasopharynx-associated lymphoid tissues (NALT). Neonatal and adult mice developed similar antibody response pattern, though former magnitude was lower. In summary, we have established intranasal (without anesthesia) infections of neonatal and adult mice with murine CMV HaNa1 strain, which mimic the range and extent of virus replication during natural primary HCMV infections in healthy infants and adults. These findings might bring new insights in the pathogenesis of natural primary CMV infections. PMID:26474525

  17. Bile acid-induced necrosis in primary human hepatocytes and in patients with obstructive cholestasis

    SciTech Connect

    Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.; Clarke, Joanna I.; Gholami, Parviz; Li, Feng; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Fan, Fang; Jenkins, Rosalind E.; Park, B. Kevin; Hagenbuch, Bruno; Olyaee, Mojtaba; Jaeschke, Hartmut

    2015-03-15

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box 1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. - Highlights: • Cholestatic liver injury is due to cytoplasmic bile acid accumulation in hepatocytes. • Primary human hepatocytes are resistant to BA-induced injury

  18. Cutting Edge: Inflammasome Activation in Primary Human Macrophages Is Dependent on Flagellin

    PubMed Central

    Kortmann, Jens; Brubaker, Sky W.

    2015-01-01

    Murine NLR family, apoptosis inhibitory protein (Naip)1, Naip2, and Naip5/6 are host sensors that detect the cytosolic presence of needle and rod proteins from bacterial type III secretion systems and flagellin, respectively. Previous studies using human-derived macrophage-like cell lines indicate that human macrophages sense the cytosolic needle protein, but not bacterial flagellin. In this study, we show that primary human macrophages readily sense cytosolic flagellin. Infection of primary human macrophages with Salmonella elicits robust cell death and IL-1β secretion that is dependent on flagellin. We show that flagellin detection requires a full-length isoform of human Naip. This full-length Naip isoform is robustly expressed in primary macrophages from healthy human donors, but it is drastically reduced in monocytic tumor cells, THP-1, and U937, rendering them insensitive to cytosolic flagellin. However, ectopic expression of full-length Naip rescues the ability of U937 cells to sense flagellin. In conclusion, human Naip functions to activate the inflammasome in response to flagellin, similar to murine Naip5/6. PMID:26109648

  19. The catalytic and the RNA subunits of human telomerase are required to immortalize equid primary fibroblasts.

    PubMed

    Vidale, Pamela; Magnani, Elisa; Nergadze, Solomon G; Santagostino, Marco; Cristofari, Gael; Smirnova, Alexandra; Mondello, Chiara; Giulotto, Elena

    2012-10-01

    Many human primary somatic cells can be immortalized by inducing telomerase activity through the exogenous expression of the human telomerase catalytic subunit (hTERT). This approach has been extended to the immortalization of cell lines from several mammals. Here, we show that hTERT expression is not sufficient to immortalize primary fibroblasts from three equid species, namely donkey, Burchelli's zebra and Grevy's zebra. In vitro analysis of a reconstituted telomerase composed by hTERT and an equid RNA component of telomerase (TERC) revealed a low activity of this enzyme compared to human telomerase, suggesting a low compatibility of equid and human telomerase subunits. This conclusion was also strengthened by comparison of human and equid TERC sequences, which revealed nucleotide differences in key regions for TERC and TERT interaction. We then succeeded in immortalizing equid fibroblasts by expressing hTERT and hTERC concomitantly. Expression of both human telomerase subunits led to telomerase activity and telomere elongation, indicating that human telomerase is compatible with the other equid telomerase subunits and proteins involved in telomere metabolism. The immortalization procedure described herein could be extended to primary cells from other mammals. The availability of immortal cells from endangered species could be particularly useful for obtaining new information on the organization and function of their genomes, which is relevant for their preservation.

  20. Cutting Edge: Inflammasome Activation in Primary Human Macrophages Is Dependent on Flagellin.

    PubMed

    Kortmann, Jens; Brubaker, Sky W; Monack, Denise M

    2015-08-01

    Murine NLR family, apoptosis inhibitory protein (Naip)1, Naip2, and Naip5/6 are host sensors that detect the cytosolic presence of needle and rod proteins from bacterial type III secretion systems and flagellin, respectively. Previous studies using human-derived macrophage-like cell lines indicate that human macrophages sense the cytosolic needle protein, but not bacterial flagellin. In this study, we show that primary human macrophages readily sense cytosolic flagellin. Infection of primary human macrophages with Salmonella elicits robust cell death and IL-1β secretion that is dependent on flagellin. We show that flagellin detection requires a full-length isoform of human Naip. This full-length Naip isoform is robustly expressed in primary macrophages from healthy human donors, but it is drastically reduced in monocytic tumor cells, THP-1, and U937, rendering them insensitive to cytosolic flagellin. However, ectopic expression of full-length Naip rescues the ability of U937 cells to sense flagellin. In conclusion, human Naip functions to activate the inflammasome in response to flagellin, similar to murine Naip5/6. PMID:26109648

  1. Human nature and the nature of reality: conceptual challenges from consciousness research.

    PubMed

    Grof, S

    1998-01-01

    Holotropic states (a large special subgroup of nonordinary states of consciousness) have been the focus of many fields of modern research, such as experiential psychotherapy, clinical and laboratory work with psychedelic substances, field anthropology, thanatology, and therapy with individuals undergoing psychospiritual crises ("spiritual emergencies"). This research has generated a plethora of extraordinary observations that have undermined some of the most fundamental assumptions of modern psychiatry, psychology, and psychotherapy. Some of these new findings seriously challenge the most basic philosophical tenets of Western science concerning the relationship between matter, life, and consciousness. This article summarizes the most important major revisions that would have to be made in our understanding of consciousness and of the human psyche in health and disease to accommodate these conceptual challenges. These areas of changes include: a new understanding and cartography of the human psyche; the nature and architecture of emotional and psychosomatic disorders; therapeutic mechanisms and the process of healing; the strategy of psychotherapy and self-exploration; the role of spirituality in human life; and the nature of reality. PMID:9924840

  2. Human nature and the nature of reality: conceptual challenges from consciousness research.

    PubMed

    Grof, S

    1998-01-01

    Holotropic states (a large special subgroup of nonordinary states of consciousness) have been the focus of many fields of modern research, such as experiential psychotherapy, clinical and laboratory work with psychedelic substances, field anthropology, thanatology, and therapy with individuals undergoing psychospiritual crises ("spiritual emergencies"). This research has generated a plethora of extraordinary observations that have undermined some of the most fundamental assumptions of modern psychiatry, psychology, and psychotherapy. Some of these new findings seriously challenge the most basic philosophical tenets of Western science concerning the relationship between matter, life, and consciousness. This article summarizes the most important major revisions that would have to be made in our understanding of consciousness and of the human psyche in health and disease to accommodate these conceptual challenges. These areas of changes include: a new understanding and cartography of the human psyche; the nature and architecture of emotional and psychosomatic disorders; therapeutic mechanisms and the process of healing; the strategy of psychotherapy and self-exploration; the role of spirituality in human life; and the nature of reality.

  3. The idea of human prehistory: the natural sciences, the human sciences, and the problem of human origins in Victorian Britain.

    PubMed

    Goodrum, Matthew R

    2012-01-01

    The idea of human prehistory was a provocative and profoundly influential new notion that took shape gradually during the nineteenth century. While archaeology played an important role in providing the evidence for this idea many other sciences such as geology, paleontology, ethnology, and physical anthropology all made critical contributions to discussions about human prehistory. Many works have explored the history of prehistoric archaeology but this paper examines the conceptual content of the idea of "human prehistory" as it developed in the British scientific community. Both the natural and the human sciences contributed to what was in fact a complex collection of individual elements that together constituted the prevailing idea of human prehistory, although there were other competing conceptions of human prehistory endorsed by various scientists and critics of the new view of early human history.

  4. Mechanical loading and the synthesis of 1,25(OH)2D in primary human osteoblasts.

    PubMed

    van der Meijden, K; Bakker, A D; van Essen, H W; Heijboer, A C; Schulten, E A J M; Lips, P; Bravenboer, N

    2016-02-01

    The metabolite 1,25-dihydroxyvitamin D (1,25(OH)2D) is synthesized from its precursor 25-hydroxyvitamin D (25(OH)D) by human osteoblasts leading to stimulation of osteoblast differentiation in an autocrine or paracrine way. Osteoblast differentiation is also stimulated by mechanical loading through activation of various responses in bone cells such as nitric oxide signaling. Whether mechanical loading affects osteoblast differentiation through an enhanced synthesis of 1,25(OH)2D by human osteoblasts is still unknown. We hypothesized that mechanical loading stimulates the synthesis of 1,25(OH)2D from 25(OH)D in primary human osteoblasts. Since the responsiveness of bone to mechanical stimuli can be altered by various endocrine factors, we also investigated whether 1,25(OH)2D or 25(OH)D affect the response of primary human osteoblasts to mechanical loading. Primary human osteoblasts were pre-incubated in medium with/without 25(OH)D3 (400 nM) or 1,25(OH)2D3 (100 nM) for 24h and subjected to mechanical loading by pulsatile fluid flow (PFF). The response of osteoblasts to PFF was quantified by measuring nitric oxide, and by PCR analysis. The effect of PFF on the synthesis of 1,25(OH)2D3 was determined by subjecting osteoblasts to PFF followed by 24h post-incubation in medium with/without 25(OH)D3 (400 nM). We showed that 1,25(OH)2D3 reduced the PFF-induced NO response in primary human osteoblasts. 25(OH)D3 did not significantly alter the NO response of primary human osteoblasts to PFF, but 25(OH)D3 increased osteocalcin and RANKL mRNA levels, similar to 1,25(OH)2D3. PFF did not increase 1,25(OH)2D3 amounts in our model, even though PFF did increase CYP27B1 mRNA levels and reduced VDR mRNA levels. CYP24 mRNA levels were not affected by PFF, but were strongly increased by both 25(OH)D3 and 1,25(OH)2D3. In conclusion, 1,25(OH)2D3 may affect the response of primary human osteoblasts to mechanical stimuli, at least with respect to NO production. Mechanical stimuli may affect

  5. Human APOBEC3 Induced Mutation of Human Immunodeficiency Virus Type-1 Contributes to Adaptation and Evolution in Natural Infection

    PubMed Central

    Kim, Eun-Young; Lorenzo-Redondo, Ramon; Little, Susan J.; Chung, Yoon-Seok; Phalora, Prabhjeet K.; Maljkovic Berry, Irina; Archer, John; Penugonda, Sudhir; Fischer, Will; Richman, Douglas D.; Bhattacharya, Tanmoy; Malim, Michael H.; Wolinsky, Steven M.

    2014-01-01

    Human APOBEC3 proteins are cytidine deaminases that contribute broadly to innate immunity through the control of exogenous retrovirus replication and endogenous retroelement retrotransposition. As an intrinsic antiretroviral defense mechanism, APOBEC3 proteins induce extensive guanosine-to-adenosine (G-to-A) mutagenesis and inhibit synthesis of nascent human immunodeficiency virus-type 1 (HIV-1) cDNA. Human APOBEC3 proteins have additionally been proposed to induce infrequent, potentially non-lethal G-to-A mutations that make subtle contributions to sequence diversification of the viral genome and adaptation though acquisition of beneficial mutations. Using single-cycle HIV-1 infections in culture and highly parallel DNA sequencing, we defined trinucleotide contexts of the edited sites for APOBEC3D, APOBEC3F, APOBEC3G, and APOBEC3H. We then compared these APOBEC3 editing contexts with the patterns of G-to-A mutations in HIV-1 DNA in cells obtained sequentially from ten patients with primary HIV-1 infection. Viral substitutions were highest in the preferred trinucleotide contexts of the edited sites for the APOBEC3 deaminases. Consistent with the effects of immune selection, amino acid changes accumulated at the APOBEC3 editing contexts located within human leukocyte antigen (HLA)-appropriate epitopes that are known or predicted to enable peptide binding. Thus, APOBEC3 activity may induce mutations that influence the genetic diversity and adaptation of the HIV-1 population in natural infection. PMID:25080100

  6. Flame Retardant BDE-47 Effectively Activates Nuclear Receptor CAR in Human Primary Hepatocytes

    PubMed Central

    Sueyoshi, Tatsuya

    2014-01-01

    Polybrominated diphenyl ether BDE-47 (2,2′,4,4′-tetrabromodiphenyl ether) is a thyroid hormone disruptor in mice; hepatic induction of various metabolic enzymes and transporters has been suggested as the mechanism for this disruption. Utilizing Car −/− and Pxr −/− mice as well as human primary hepatocytes, here we have demonstrated that BDE-47 activated both mouse and human nuclear receptor constitutive activated/androstane receptor (CAR). In mouse livers, CAR, not PXR, was responsible for Cyp2b10 mRNA induction by BDE-47. In human primary hepatocytes, BDE-47 was able to induce translocation of YFP-tagged human CAR from the cytoplasm to the nucleus andCYP2B6 and CYP3A4 mRNAs expressions. BDE-47 activated human CAR in a manner akin to the human CAR ligand CITCO (6-(4-Chlorophenyl)imidazo[2,1-b][1,3]thiazole-5-carbaldehyde-O-(3,4-dichlorobenzyl)oxime) in luciferase-reporter assays using Huh-7 cells. In contrast, mouse CAR was not potently activated by BDE-47 in the same reporter assays. Furthermore, human pregnane X receptor (PXR) was effectively activated by BDE-47 while mouse PXR was weakly activated in luciferase-reporter assays. Our results indicate that BDE-47 induces CYP genes through activation of human CAR in addition to the previously identified pathway through human PXR. PMID:24218150

  7. Normal human serum contains a natural IgM antibody cytotoxic for human neuroblastoma cells.

    PubMed Central

    Ollert, M W; David, K; Schmitt, C; Hauenschild, A; Bredehorst, R; Erttmann, R; Vogel, C W

    1996-01-01

    Neuroblastoma (NB) is characterized by the second highest spontaneous regression of any human malignant disorder, a phenomenon that remains to be elucidated. In this study, a survey of 94 normal human adult sera revealed a considerable natural humoral cytotoxicity against human NB cell lines in approximately one-third of the tested sera of both genders. Specific cell killing by these sera was in the range of 40% to 95%. Serum cytotoxicity was dependent on an intact classical pathway of complement. By several lines of evidence, IgM antibodies were identified as the cytotoxic factor in the sera. Further analyses revealed that a 260-kDa protein was recognized by natural IgM of cytotoxic sera in Western blots of NB cell extracts. The antigen was expressed on the surface of seven human NB cell lines but not on human melanoma or other control tumor cell lines derived from kidney, pancreas, colon, bone, skeletal muscle, lymphatic system, and bone marrow. Furthermore, no reactivity was observed with normal human fibroblasts, melanocytes, and epidermal keratinocytes. The antigen was expressed in vivo as detected by immunohistochemistry in both the tumor of a NB patient and NB tumors established in nude rats from human NB cell lines. Most interestingly, the IgM anti-NB antibody was absent from the sera of 11 human NB patients with active disease. The anti-NB IgM also could not be detected in tumor tissue obtained from a NB patient. Collectively, our data suggest the existence of a natural humoral immunological tumor defense mechanism, which could account for the in vivo phenomenon of spontaneous NB tumor regression. Images Fig. 1 Fig. 3 Fig. 4 Fig. 5 Fig. 6 PMID:8633097

  8. Absolute Depth Sensitivity in Cat Primary Visual Cortex under Natural Viewing Conditions.

    PubMed

    Pigarev, Ivan N; Levichkina, Ekaterina V

    2016-01-01

    Mechanisms of 3D perception, investigated in many laboratories, have defined depth either relative to the fixation plane or to other objects in the visual scene. It is obvious that for efficient perception of the 3D world, additional mechanisms of depth constancy could operate in the visual system to provide information about absolute distance. Neurons with properties reflecting some features of depth constancy have been described in the parietal and extrastriate occipital cortical areas. It has also been shown that, for some neurons in the visual area V1, responses to stimuli of constant angular size differ at close and remote distances. The present study was designed to investigate whether, in natural free gaze viewing conditions, neurons tuned to absolute depths can be found in the primary visual cortex (area V1). Single-unit extracellular activity was recorded from the visual cortex of waking cats sitting on a trolley in front of a large screen. The trolley was slowly approaching the visual scene, which consisted of stationary sinusoidal gratings of optimal orientation rear-projected over the whole surface of the screen. Each neuron was tested with two gratings, with spatial frequency of one grating being twice as high as that of the other. Assuming that a cell is tuned to a spatial frequency, its maximum response to the grating with a spatial frequency twice as high should be shifted to a distance half way closer to the screen in order to attain the same size of retinal projection. For hypothetical neurons selective to absolute depth, location of the maximum response should remain at the same distance irrespective of the type of stimulus. It was found that about 20% of neurons in our experimental paradigm demonstrated sensitivity to particular distances independently of the spatial frequencies of the gratings. We interpret these findings as an indication of the use of absolute depth information in the primary visual cortex. PMID:27547179

  9. Primary paranasal sinus lymphoma: natural history and improved outcome with central nervous system chemoprophylaxis.

    PubMed

    Laskin, Janessa J; Savage, Kerry J; Voss, Nicholas; Gascoyne, Randy D; Connors, Joseph M

    2005-12-01

    Non-Hodgkin's lymphoma of the paranasal sinus is an uncommon presentation of extranodal lymphoma. Its natural history, treatment and prognosis have been infrequently characterized in the medical literature; however, a tendency to involve the central nervous system (CNS) has been noted. In British Columbia (population 4 million), a central database for lymphomas has allowed us to accurately track cases of paranasal sinus lymphoma diagnosed since 1980. A retrospective review was performed on the 44 patients who presented with primary paranasal sinus lymphoma (stage I or II) between 1980 and 1999. Histologic features were identified and immunophenotypic classification performed. Complete diagnostic and follow-up data including stage, treatment, response rates, sites of relapse and survival data were available for all patients. There were 26 men and 18 women. The types of lymphoma found were: diffuse large B cell (including immunoblastic), n = 37 (84%); T/NK nasal type, n = 3 (8%); peripheral T cell, not otherwise classified, n = 2 (4%); and others, n = 2 (4%). The median age at presentation was 66 years (range 27-97 years). The median follow-up for living patients was 114 months. For all 44 patients, the 5- and 10-year overall survivals were 48% and 41% and the disease-specific survivals 62% and 62%, respectively. Beginning in May 1985, intrathecal chemotherapy was added to our standard treatment plan of multi-agent chemotherapy and local irradiation. Before 1985, 2 of 5 patients developed leptomeningeal metastasis. Following the institution of intrathecal chemotherapy, only 8% (3 of 39) of patients have developed CNS disease. Introduction of intrathecal chemoprophylaxis was also associated with an improvement in overall survival from 20% to 51% and disease-specific survival from 40% to 65%. Primary paranasal sinus lymphoma is an uncommon presentation of lymphoma that carries the potential risk of spreading to the leptomeninges. Treatment with combined modality

  10. Absolute Depth Sensitivity in Cat Primary Visual Cortex under Natural Viewing Conditions

    PubMed Central

    Pigarev, Ivan N.; Levichkina, Ekaterina V.

    2016-01-01

    Mechanisms of 3D perception, investigated in many laboratories, have defined depth either relative to the fixation plane or to other objects in the visual scene. It is obvious that for efficient perception of the 3D world, additional mechanisms of depth constancy could operate in the visual system to provide information about absolute distance. Neurons with properties reflecting some features of depth constancy have been described in the parietal and extrastriate occipital cortical areas. It has also been shown that, for some neurons in the visual area V1, responses to stimuli of constant angular size differ at close and remote distances. The present study was designed to investigate whether, in natural free gaze viewing conditions, neurons tuned to absolute depths can be found in the primary visual cortex (area V1). Single-unit extracellular activity was recorded from the visual cortex of waking cats sitting on a trolley in front of a large screen. The trolley was slowly approaching the visual scene, which consisted of stationary sinusoidal gratings of optimal orientation rear-projected over the whole surface of the screen. Each neuron was tested with two gratings, with spatial frequency of one grating being twice as high as that of the other. Assuming that a cell is tuned to a spatial frequency, its maximum response to the grating with a spatial frequency twice as high should be shifted to a distance half way closer to the screen in order to attain the same size of retinal projection. For hypothetical neurons selective to absolute depth, location of the maximum response should remain at the same distance irrespective of the type of stimulus. It was found that about 20% of neurons in our experimental paradigm demonstrated sensitivity to particular distances independently of the spatial frequencies of the gratings. We interpret these findings as an indication of the use of absolute depth information in the primary visual cortex. PMID:27547179

  11. Absolute Depth Sensitivity in Cat Primary Visual Cortex under Natural Viewing Conditions.

    PubMed

    Pigarev, Ivan N; Levichkina, Ekaterina V

    2016-01-01

    Mechanisms of 3D perception, investigated in many laboratories, have defined depth either relative to the fixation plane or to other objects in the visual scene. It is obvious that for efficient perception of the 3D world, additional mechanisms of depth constancy could operate in the visual system to provide information about absolute distance. Neurons with properties reflecting some features of depth constancy have been described in the parietal and extrastriate occipital cortical areas. It has also been shown that, for some neurons in the visual area V1, responses to stimuli of constant angular size differ at close and remote distances. The present study was designed to investigate whether, in natural free gaze viewing conditions, neurons tuned to absolute depths can be found in the primary visual cortex (area V1). Single-unit extracellular activity was recorded from the visual cortex of waking cats sitting on a trolley in front of a large screen. The trolley was slowly approaching the visual scene, which consisted of stationary sinusoidal gratings of optimal orientation rear-projected over the whole surface of the screen. Each neuron was tested with two gratings, with spatial frequency of one grating being twice as high as that of the other. Assuming that a cell is tuned to a spatial frequency, its maximum response to the grating with a spatial frequency twice as high should be shifted to a distance half way closer to the screen in order to attain the same size of retinal projection. For hypothetical neurons selective to absolute depth, location of the maximum response should remain at the same distance irrespective of the type of stimulus. It was found that about 20% of neurons in our experimental paradigm demonstrated sensitivity to particular distances independently of the spatial frequencies of the gratings. We interpret these findings as an indication of the use of absolute depth information in the primary visual cortex.

  12. Lysozyme: primary bactericidin in human plasma serum active against Bacillus subtilis.

    PubMed Central

    Selsted, M E; Martinez, R J

    1978-01-01

    The in vitro bactericidal reaction of human plasma serum against Bacillus subtilis was investigated. Human lysozyme was purified to homogeneity, and antiserum was prepared against the enzyme. The anti-lysozyme immunoglobulin G was used as a specific inhibitor in bactericidal and bacteriolytic reactions. It was found that at low serum concentrations lysozyme was the primary bactericide active against B. subtilis. At appreciably higher serum concentrations, a lysozyme-independent bactericidal activity was also demonstrated. Images PMID:97236

  13. Natural Course of Cutaneous Warts Among Primary Schoolchildren: A Prospective Cohort Study

    PubMed Central

    Bruggink, Sjoerd C.; Eekhof, Just A. H.; Egberts, Paulette F.; van Blijswijk, Sophie C. E.; Assendelft, Willem J. J.; Gussekloo, Jacobijn

    2013-01-01

    PURPOSE Because cutaneous warts resolve spontaneously and available treatments often fail, family physicians and patients may consider a wait-and-see policy. We examined the natural course of cutaneous warts and treatment decisions in a prospective observational cohort of primary schoolchildren. METHODS We inspected the hands and feet of children aged 4 to 12 years from 3 Dutch primary schools for the presence of warts at baseline and after a mean follow-up of 15 months. Parental questionnaires at follow-up provided information on inconvenience caused by warts and any treatments used. RESULTS Of the 1,134 eligible children, 1,099 (97%) participated, of whom 366 (33%) had cutaneous warts at baseline. Among these children with warts, loss to follow-up was 9% and the response rate to the parental questionnaires was 83%. The complete resolution rate was 52 per 100 person-years at risk (95% CI, 44–60). Younger age (hazard ratio = 1.1 per year decrease; 95% CI, 1.0–1.2) and non-Caucasian skin type (hazard ratio = 2.0; 95% CI, 1.3–2.9) increased the likelihood of resolution. During follow-up, 38% of children with warts at baseline treated their warts: 18% used over-the-counter treatment only, 15% used a family physician–provided treatment only, and 5% used both. Children were more likely to initiate treatment if the warts measured at least 1 cm in diameter (odds ratio = 3.2; 95% CI, 1.9–5.3) and especially if parents reported that the warts caused inconvenience (odds ratio = 38; 95% CI, 16–90). CONCLUSIONS One-half of primary schoolchildren with warts will be free of warts within 1 year. Young age and non-Caucasian skin type enhance resolution. Children with large or inconvenient warts are more likely to start treatment. These findings will be useful in the process of shared decision making with parents and children. PMID:24019275

  14. The Concept of Human Nature in Three Cultures: A Developmental Approach.

    ERIC Educational Resources Information Center

    Oerter, Rolf

    This study compares the concept of human nature in Germany, Java, and the United States. The study assumes cross-cultural similarities in the formal structure of the concept of human nature, while hypothesizing variation in content, for example, in the value systems. Four components of the concept of human nature were presented (personality…

  15. Characterization of a primary brown adipocyte culture system derived from human fetal interscapular fat

    PubMed Central

    Seiler, Sarah E; Xu, Dan; Ho, Jia-Pei; Lo, Kinyui Alice; Buehrer, Benjamin M; Ludlow, Y John W; Kovalik, Jean-Paul; Sun, Lei

    2015-01-01

    Brown fat has gained widespread attention as a potential therapeutic target to treat obesity and associated metabolic disorders. Indeed, the anti-obesity potential of multiple targets to stimulate both brown adipocyte differentiation and recruitment have been verified in rodent models. However, their therapeutic potential in humans is unknown due to the lack of a human primary brown adipocyte cell culture system. Likewise, the lack of a well-characterized human model has limited the discovery of novel targets for the activation of human brown fat. To address this current need, we aimed to identify and describe the first primary brown adipocyte cell culture system from human fetal interscapular brown adipose tissue. Pre-adipocytes isolated from non-viable human fetal interscapular tissue were expanded and cryopreserved. Cells were then thawed and plated alongside adult human subcutaneous and omental pre-adipocytes for subsequent differentiation and phenotypic characterization. Interscapular pre-adipocytes in cell culture differentiated into mature adipocytes that were morphologically indistinguishable from the adult white depots. Throughout differentiation, cultured human fetal interscapular adipocytes demonstrated increased expression of classical brown fat markers compared to subcutaneous and omental cells. Further, functional analysis revealed an elevation in fatty acid oxidation as well as maximal and uncoupled oxygen consumption in interscapular brown adipocytes compared to white control cells. These data collectively identify the brown phenotype of these cells. Thus, our primary cell culture system derived from non-viable human fetal interscapular brown adipose tissue provides a valuable tool for the study of human brown adipocyte biology and for the development of anti-obesity therapeutics. PMID:26451287

  16. The consuming instinct. What Darwinian consumption reveals about human nature.

    PubMed

    Saad, Gad

    2013-01-01

    Editor's note: In this engaging talk given last February on a particularly cold and blustery day at Texas Tech University, Professor Gad Saad of Concordia University discusses his work in the area of evolutionary consumption. In making the case for understanding consumerism from a Darwinian perspective, Saad addresses several key tenets from his books The Consuming Instinct (1) and The Evolutionary Bases of Consumption. (2) In particular, Saad argues that: (1) many consumption acts can be mapped onto four key Darwinian modules (survival, mating, kin selection, and reciprocal altruism); and, (2) cultural products such as song lyrics and movie plotlines are fossils of the human mind that highlight a shared, biologically based human nature. In this wide-ranging inquiry, Saad summarizes several of his other empirical works, including the effects of conspicuous consumption on men's testosterone levels (3) and how the ovulatory cycle in the human female influences consumption. (4) Overall, Professor Saad contends that an infusion of evolutionary and biologically based perspectives into the discipline of consumer behavior and related government regulatory policies yields myriad benefits, notably greater consilience, more effective practices, an ethos of interdisciplinarity, and methodological pluralism. PMID:24047091

  17. Resolvin D1 Polarizes Primary Human Macrophages toward a Proresolution Phenotype through GPR32.

    PubMed

    Schmid, Mattia; Gemperle, Claudio; Rimann, Nicole; Hersberger, Martin

    2016-04-15

    Resolvin D1 (RvD1) was shown to be a potent anti-inflammatory and proresolution lipid mediator in several animal models of inflammation, but its mechanism of action in humans is not clear. We show that the RvD1 receptor GPR32 is present on resting, proinflammatory M(LPS) and alternatively activated primary human M(IL-4) macrophages, whereas TGF-β and IL-6 reduce its membrane expression. Accordingly, stimulation of resting primary human macrophages with 10 nM RvD1 for 48 h maximally reduced the secretion of the proinflammatory cytokines IL-1β and IL-8; abolished chemotaxis to several chemoattractants like chemerin, fMLF, and MCP-1; and doubled the phagocytic activity of these macrophages toward microbial particles. In contrast, these functional changes were not accompanied by surface expression of markers specific for alternatively activated M(IL-4) macrophages. Similar proresolution effects of RvD1 were observed when proinflammatory M(LPS) macrophages were treated with RvD1. In addition, we show that these RvD1-mediated effects are GPR32 dependent because reduction of GPR32 expression by small interfering RNA, TGF-β, and IL-6 treatment ablated these proresolution effects in primary human macrophages. Taken together, our results indicate that in humans RvD1 triggers GPR32 to polarize and repolarize macrophages toward a proresolution phenotype, supporting the role of this mediator in the resolution of inflammation in humans.

  18. The natural immunity to evolutionary atavistic endotoxin for human cancer.

    PubMed

    Moncevičiūtė-Eringienė, Elena; Rotkevič, Kristina; Grikienis, Ruta Grikienyte

    2015-11-01

    We propose a new theory of the immunological control of cancer corresponding to the hypothesis that the specific natural immunity to evolutionary atavistic endotoxin has a potential role in human cancer prevention. The results of our studies have shown that IgMNAE, i.e. endogenous or spontaneous IgM class antibodies to enterobacterial lipopolysaccharide molecules (lipid A), control the immune mechanisms responsible for the internal medium stability not only against the damaging impact of the carcinogenic factors, but also against the malignant transformation of its own degenerated cells. Among people who in 1979 and 1982 had IgMNAE in their blood serum, after 15-30years fell ill with cancer 10%, versus 15% among people who had no IgMNAE (p<0.05). Therefore, it is possible to maintain that the stimulation of IgMNAE synthesis would help in the destruction and elimination of damaged somatic cells or prevent their mechanisms from the formation of invasiveness, metastatic and other properties of their parasitism. In the mechanism of the natural immunity to endotoxin it is possible to see the formation of the respective evolutionary protective reactions which protect the damaged cells from acquiring resistance to damaging factors and thus from becoming an independent new parasitic population. Thereby the presented theory of the immunological control of cancer has a causal connection with our evolutionary resistance theory of the origin of cancer. Collectively, these data suggest that activation of natural immunity to endotoxin and production of vaccines against evolutionary atavistic endotoxin or gram-negative bacterial endotoxin can be helpful when applied in cancer prophylaxis for persons with a low level of natural immunity to endotoxin and perhaps in creating immunotherapeutic methods for stopping the endogenous parasitism of tumour cells by binding IgMNAE to atavistic endotoxin in cancer patients.

  19. The AT-hook motif-encoding gene METABOLIC NETWORK MODULATOR 1 underlies natural variation in Arabidopsis primary metabolism

    PubMed Central

    Li, Baohua; Kliebenstein, Daniel J.

    2014-01-01

    Regulation of primary metabolism is a central mechanism by which plants coordinate their various responses to biotic and abiotic challenge. To identify genes responsible for natural variation in primary metabolism, we focused on cloning a locus from Arabidopsis thaliana that influences the level of TCA cycle metabolites in planta. We found that the Met.V.67 locus was controlled by natural variation in METABOLIC NETWORK MODULATOR 1 (MNM1), which encoded an AT-hook motif-containing protein that was unique to the Brassicales lineage. MNM1 had wide ranging effects on plant metabolism and displayed a tissue expression pattern that was suggestive of a function in sink tissues. Natural variation within MNM1 had differential effects during a diurnal time course, and this temporal dependency was supported by analysis of T-DNA insertion and over-expression lines for MNM1. Thus, the cloning of a natural variation locus specifically associated with primary metabolism allowed us to identify MNM1 as a lineage-specific modulator of primary metabolism, suggesting that the regulation of primary metabolism can change during evolution. PMID:25202318

  20. Primary human cervical carcinoma cells require human papillomavirus E6 and E7 expression for ongoing proliferation

    SciTech Connect

    Magaldi, Thomas G.; Almstead, Laura L.; Bellone, Stefania; Prevatt, Edward G.; Santin, Alessandro D.; DiMaio, Daniel

    2012-01-05

    Repression of human papillomavirus (HPV) E6 and E7 oncogenes in established cervical carcinoma cell lines causes senescence due to reactivation of cellular tumor suppressor pathways. Here, we determined whether ongoing expression of HPV16 or HPV18 oncogenes is required for the proliferation of primary human cervical carcinoma cells in serum-free conditions at low passage number after isolation from patients. We used an SV40 viral vector expressing the bovine papillomavirus E2 protein to repress E6 and E7 in these cells. To enable efficient SV40 infection and E2 gene delivery, we first incubated the primary cervical cancer cells with the ganglioside GM1, a cell-surface receptor for SV40 that is limiting in these cells. Repression of HPV in primary cervical carcinoma cells caused them to undergo senescence, but the E2 protein had little effect on HPV-negative primary cells. These data suggest that E6 and E7 dependence is an inherent property of human cervical cancer cells.

  1. Primary Human Ovarian Epithelial Cancer Cells Broadly Express HER2 at Immunologically-Detectable Levels

    PubMed Central

    Lanitis, Evripidis; Dangaj, Denarda; Hagemann, Ian S.; Song, De-Gang; Best, Andrew; Sandaltzopoulos, Raphael; Coukos, George; Powell, Daniel J.

    2012-01-01

    The breadth of HER2 expression by primary human ovarian cancers remains controversial, which questions its suitability as a universal antigen in this malignancy. To address these issues, we performed extensive HER2 expression analysis on a wide panel of primary tumors as well as established and short-term human ovarian cancer cell lines. Conventional immunohistochemical (IHC) analysis of multiple tumor sites in 50 cases of high-grade ovarian serous carcinomas revealed HER2 overexpression in 29% of evaluated sites. However, more sensitive detection methods including flow cytometry, western blot analysis and q-PCR revealed HER2 expression in all fresh tumor cells derived from primary ascites or solid tumors as well as all established and short-term cultured cancer cell lines. Cancer cells generally expressed HER2 at higher levels than that found in normal ovarian surface epithelial (OSE) cells. Accordingly, genetically-engineered human T cells expressing an HER2-specific chimeric antigen receptor (CAR) recognized and reacted against all established or primary ovarian cancer cells tested with minimal or no reactivity against normal OSE cells. In conclusion, all human ovarian cancers express immunologically-detectable levels of HER2, indicating that IHC measurement underestimates the true frequency of HER2-expressing ovarian cancers and may limit patient access to otherwise clinically meaningful HER2-targeted therapies. PMID:23189165

  2. Humanities-Oriented Accents in Teaching Mathematics to Prospective Primary School Teachers

    ERIC Educational Resources Information Center

    Tabov, Jordan; Gortcheva, Iordanka

    2016-01-01

    Our research includes undergraduate students who major in primary school education. Their academic background is prevailingly in the humanities. This poses specific demands on their mathematics instruction at university. To attract them to their mathematics course and raise its effectiveness, we use a series of activities. Writing assignments…

  3. MiR-191 Regulates Primary Human Fibroblast Proliferation and Directly Targets Multiple Oncogenes.

    PubMed

    Polioudakis, Damon; Abell, Nathan S; Iyer, Vishwanath R

    2015-01-01

    miRNAs play a central role in numerous pathologies including multiple cancer types. miR-191 has predominantly been studied as an oncogene, but the role of miR-191 in the proliferation of primary cells is not well characterized, and the miR-191 targetome has not been experimentally profiled. Here we utilized RNA induced silencing complex immunoprecipitations as well as gene expression profiling to construct a genome wide miR-191 target profile. We show that miR-191 represses proliferation in primary human fibroblasts, identify multiple proto-oncogenes as novel miR-191 targets, including CDK9, NOTCH2, and RPS6KA3, and present evidence that miR-191 extensively mediates target expression through coding sequence (CDS) pairing. Our results provide a comprehensive genome wide miR-191 target profile, and demonstrate miR-191's regulation of primary human fibroblast proliferation.

  4. Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014

    PubMed Central

    Alraddadi, Basem M.; Watson, John T.; Almarashi, Abdulatif; Abedi, Glen R.; Turkistani, Amal; Sadran, Musallam; Housa, Abeer; Almazroa, Mohammad A.; Alraihan, Naif; Banjar, Ayman; Albalawi, Eman; Alhindi, Hanan; Choudhry, Abdul Jamil; Meiman, Jonathan G.; Paczkowski, Magdalena; Curns, Aaron; Mounts, Anthony; Feikin, Daniel R.; Marano, Nina; Swerdlow, David L.; Gerber, Susan I.; Hajjeh, Rana

    2016-01-01

    Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March–November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case–control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2–4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV. PMID:26692185

  5. Risk Factors for Primary Middle East Respiratory Syndrome Coronavirus Illness in Humans, Saudi Arabia, 2014.

    PubMed

    Alraddadi, Basem M; Watson, John T; Almarashi, Abdulatif; Abedi, Glen R; Turkistani, Amal; Sadran, Musallam; Housa, Abeer; Almazroa, Mohammad A; Alraihan, Naif; Banjar, Ayman; Albalawi, Eman; Alhindi, Hanan; Choudhry, Abdul Jamil; Meiman, Jonathan G; Paczkowski, Magdalena; Curns, Aaron; Mounts, Anthony; Feikin, Daniel R; Marano, Nina; Swerdlow, David L; Gerber, Susan I; Hajjeh, Rana; Madani, Tariq A

    2016-01-01

    Risk factors for primary Middle East respiratory syndrome coronavirus (MERS-CoV) illness in humans are incompletely understood. We identified all primary MERS-CoV cases reported in Saudi Arabia during March-November 2014 by excluding those with history of exposure to other cases of MERS-CoV or acute respiratory illness of unknown cause or exposure to healthcare settings within 14 days before illness onset. Using a case-control design, we assessed differences in underlying medical conditions and environmental exposures among primary case-patients and 2-4 controls matched by age, sex, and neighborhood. Using multivariable analysis, we found that direct exposure to dromedary camels during the 2 weeks before illness onset, as well as diabetes mellitus, heart disease, and smoking, were each independently associated with MERS-CoV illness. Further investigation is needed to better understand animal-to-human transmission of MERS-CoV. PMID:26692185

  6. The effect of increased primary schooling on adult women's HIV status in Malawi and Uganda: Universal Primary Education as a natural experiment.

    PubMed

    Behrman, Julia Andrea

    2015-02-01

    This paper explores the causal relationship between primary schooling and adult HIV status in Malawi and Uganda, two East African countries with some of the highest HIV infection rates in the world. Using data from the 2010 Malawi Demographic Health Survey and the 2011 Uganda AIDS Indicator Survey, the paper takes advantage of a natural experiment, the implementation of Universal Primary Education policies in the mid 1990s. An instrumented regression discontinuity approach is used to model the relationship between increased primary schooling and adult women's HIV status. Results indicate that a one-year increase in schooling decreases the probability of an adult woman testing positive for HIV by 0.06 (p < 0.01) in Malawi and by 0.03 (p < 0.05) in Uganda. These results are robust to a variety of model specifications. In a series of supplementary analyses a number of potential pathways through which such effects may occur are explored. Findings indicate increased primary schooling positively affects women's literacy and spousal schooling attainment in Malawi and age of marriage and current household wealth in Uganda. However primary schooling has no effect on recent (adult) sexual behavior.

  7. Does enhanced solar UV-B radiation affect marine primary producers in their natural habitats?

    PubMed

    Häder, Donat-P

    2011-01-01

    This article is a highlight of the paper by Li et al. in this issue of Photochemistry and Photobiology as well as a short summary of the research on the effects of solar UV-B radiation on primary production in the oceans. Laboratory experiments under controlled conditions using artificial light sources indicate species-specific damage of many phytoplankton groups. Mesocosm studies in enclosures of limited volume allow analyzing UV effects in multigeneration monitoring of natural assemblages. Field studies to determine the effects of short-wavelength solar radiation require sensitive instrumentation and measurements over extended areas of the open ocean to yield significant results. Results from a cruise described in the paper by Li et al. indicate clear effects of UV-B and UV-A on the photosynthetic carbon fixation of phytoplankton communities with spatial differences between coastal and open-ocean waters. Increasing temperatures and acidification in the ocean due to global climate change may exacerbate the detrimental effects of solar UV-B radiation. PMID:21208211

  8. New Insights into the Natural History of Asthma: Primary Prevention on the Horizon

    PubMed Central

    Martinez, Fernando D.

    2014-01-01

    Recent studies of the natural history of asthma have shifted attention towards viral respiratory illness in early life as a major risk factor associated with the development of the most persistent forms of the disease. Although early aeroallergen sensitization is strongly associated with chronic asthma, several trials in which single aeroallergen exposure in pregnancy and early childhood was successfully accomplished and compared with sham avoidance have failed to show any decrease in asthma incidence. New evidence suggests that complex interactions occur between viral infection and aeroallergen sensitization in genetically susceptible subjects, which trigger the immune responses and airway changes that are characteristic of persistent asthma. The finding that exposure to bacterial products among children raised on farms is associated with diminished asthma prevalence during the school years has now been replicated, and experimental studies have suggested that these effects are mediated by the activation of T-regulatory cells in the airway. It is thus plausible to hypothesize that primary prevention of asthma could be attained through surrogate therapeutic interventions that activate similar mechanisms in young children at high risk for asthma. PMID:22036094

  9. Molecular Evidence for a Natural Primary Triple Hybrid in Plants Revealed from Direct Sequencing

    PubMed Central

    Kaplan, Zdenek; Fehrer, Judith

    2007-01-01

    Background and Aims Molecular evidence for natural primary hybrids composed of three different plant species is very rarely reported. An investigation was therefore carried out into the origin and a possible scenario for the rise of a sterile plant clone showing a combination of diagnostic morphological features of three separate, well-defined Potamogeton species. Methods The combination of sequences from maternally inherited cytoplasmic (rpl20-rps12) and biparentally inherited nuclear ribosomal DNA (ITS) was used to identify the exact identity of the putative triple hybrid. Key Results Direct sequencing showed ITS variants of three parental taxa, P. gramineus, P. lucens and P. perfoliatus, whereas chloroplast DNA identified P. perfoliatus as the female parent. A scenario for the rise of the triple hybrid through a fertile binary hybrid P. gramineus × P. lucens crossed with P. perfoliatus is described. Conclusions Even though the triple hybrid is sterile, it possesses an efficient strategy for its existence and became locally successful even in the parental environment, perhaps as a result of heterosis. The population investigated is the only one known of this hybrid, P. × torssanderi, worldwide. Isozyme analysis indicated the colony to be genetically uniform. The plants studied represented a single clone that seems to have persisted at this site for a long time. PMID:17478544

  10. Human natural chimerism: an acquired character or a vestige of evolution?

    PubMed

    Rinkevich, B

    2001-06-01

    Analysis on five common classes of human natural chimeras (cytomictical, whole body, fetal-maternal, germ cell, and tumor chimeras) reveals that (1) they initiate only during pregnancy, (2) the most common class are chimeras which contain maternal cells, and (3) the primary mechanisms that are involved in their formation and establishment are still elusive. These classes of natural chimerism, are involved only with maladaptive phenomena such as malignancy and autoimmune diseases and without any documented benefit. A recent review has challenged the accepted dogma that the evolution of immunity is pathogen-directed and asserted that preserving individuality from littering the soma and the germline by conspecific alien cells might have been the original function of the innate immunity. Following this tenet, I propose here that human natural chimerism is a by-product of the new role evolved from primitive components of immunity to "educate" the developing embryo with the armamentarium of effector mechanisms, dedicated to purge the individual from pervasive somatic and germline variants, and is not a vestige of evolution.

  11. Neisseria gonorrhoeae phagosomes delay fusion with primary granules to enhance bacterial survival inside human neutrophils.

    PubMed

    Johnson, M Brittany; Criss, Alison K

    2013-08-01

    Symptomatic infection with Neisseria gonorrhoeae (Gc) promotes inflammation driven by polymorphonuclear leucocytes (PMNs, neutrophils), yet some Gc survive PMN exposure during infection. Here we report a novel mechanism of gonococcal resistance to PMNs: Gc phagosomes avoid maturation into phagolysosomes by delayed fusion with primary (azurophilic) granules, which contain antimicrobial components including serine proteases. Reduced phagosome-primary granule fusion was observed in gonorrheal exudates and human PMNs infected ex vivo. Delayed phagosome-granule fusion could be overcome by opsonizing Gc with immunoglobulin. Using bacterial viability dyes along with antibodies to primary granules revealed that Gc survival in PMNs correlated with early residence in primary granule-negative phagosomes. However, when Gc was killed prior to PMN exposure, dead bacteria were also found in primary granule-negative phagosomes. These results suggest that Gc surface characteristics, rather than active bacterial processes, influence phagosome maturation and that Gc death inside PMNs occurs after phagosome-granule fusion. Ectopically increasing primary granule-phagosome fusion, by immunoglobulin opsonization or PMN treatment with lysophosphatidylcholine, reduced intracellular Gc viability, which was attributed in part to serine protease activity. We conclude that one method for Gc to avoid PMN clearance in acute gonorrhoea is by delaying primary granule-phagosome fusion, thus preventing formation of a degradative phagolysosome. PMID:23374609

  12. Rich-and-Poor Model for Human and Nature Interaction

    NASA Astrophysics Data System (ADS)

    Motesharrei, S.; Kalnay, E.; Rivas, J.; Rich-n-Poor

    2011-12-01

    Historical evidence shows collapse of several civilizations in different regions of the world. Jared Diamond presents an account of such societal failures in his 2005 book "Collapse: How Societies Choose to Fail or Succeed." As a precursor to building a complex model for interaction of human and environment, we developed a "thought-experiment" model based on Lotka-Volterra equations for the interaction of two species, known as the Predator-Prey model. We constructed a fairly simple rich-and-poor model that includes only four state variables (or stocks): Rich Population, Poor Population, Nature, and Rich Savings. We observed several scenarios for growth of societies by varying the model's parameter values, including scenarios that resemble the catastrophic fall of ancient civilizations such as the Maya and Anasazi.

  13. Water: Challenges at the Intersection of Human and Natural Systems

    SciTech Connect

    Futrell, J.H.; Gephart, R. E.; Kabat-Lensch, E.; McKnight, D. M.; Pyrtle, A.; Schimel, J. P.; Smyth, R. L.; Skole, D. L. Wilson, J. L.; Gephart, J. M.

    2005-09-01

    There is a growing recognition about the critical role water plays in sustaining people and society. This workshop established dialog between disciplinary scientists and program managers from diverse backgrounds in order to share perspectives and broaden community understanding of ongoing fundamental and applied research on water as a complex environmental problem. Three major scientific themes emerged: (1) coupling of cycles and process, with emphasis on the role of interfaces; (2) coupling of human and natural systems across spatial and temporal scales; and (3) prediction in the face of uncertainty. In addition, the need for observation systems, sensors, and infrastructure; and the need for data management and synthesis were addressed. Current barriers to progress were noted as educational and institutional barriers and the integration of science and policy.

  14. Natural Good Theories and the Value of Human Dignity.

    PubMed

    Muders, Sebastian

    2016-04-01

    One of the widely recognized facts about human dignity is its vastly divergent applicability-from highly controversial issues in bioethics to broader topics in political philosophy. A group of theories that this article subsumes under the header "natural good theories" appears to be especially fitted for normatively multifaceted notions like dignity. However, the heavy normative weight the concept of dignity has to bear due to the central position it occupies within these theories creates its own difficulties. As is shown in a discussion of Martha Nussbaum's capability conception of dignity, dignity appears to be unable to mirror the special normative relevance people want to assign to it in cases of great moral misconduct. The article provides a suggestion on how to solve this problem by means of paradigmatic cases that work as material constraints regarding the exact boundaries of dignity violations. PMID:26957449

  15. Epigenetics and the human brain: where nurture meets nature.

    PubMed

    Mansuy, Isabelle M; Mohanna, Safa

    2011-05-01

    While our genetic code determines a great deal of who and what we are, it does not act alone. It depends heavily on the epigenome, an elaborate marking of the DNA that controls the genome's functions. Because it is sensitive to the environment, the epigenome is a powerful link and relay between our genes and our surroundings. Epigenetic marks drive biological functions and features as diverse as memory, development, and disease susceptibility; thus, the nurture aspect of the nature/nurture interaction makes essential contributions to our body and behaviors. As scientists have learned more about how the epigenome works, they have begun to develop therapies that may lead to new approaches to treating common human conditions.

  16. Natural Good Theories and the Value of Human Dignity.

    PubMed

    Muders, Sebastian

    2016-04-01

    One of the widely recognized facts about human dignity is its vastly divergent applicability-from highly controversial issues in bioethics to broader topics in political philosophy. A group of theories that this article subsumes under the header "natural good theories" appears to be especially fitted for normatively multifaceted notions like dignity. However, the heavy normative weight the concept of dignity has to bear due to the central position it occupies within these theories creates its own difficulties. As is shown in a discussion of Martha Nussbaum's capability conception of dignity, dignity appears to be unable to mirror the special normative relevance people want to assign to it in cases of great moral misconduct. The article provides a suggestion on how to solve this problem by means of paradigmatic cases that work as material constraints regarding the exact boundaries of dignity violations.

  17. Quantifying and mapping the human appropriation of net primary production in earth's terrestrial ecosystems

    PubMed Central

    Haberl, Helmut; Erb, K. Heinz; Krausmann, Fridolin; Gaube, Veronika; Bondeau, Alberte; Plutzar, Christoph; Gingrich, Simone; Lucht, Wolfgang; Fischer-Kowalski, Marina

    2007-01-01

    Human appropriation of net primary production (HANPP), the aggregate impact of land use on biomass available each year in ecosystems, is a prominent measure of the human domination of the biosphere. We present a comprehensive assessment of global HANPP based on vegetation modeling, agricultural and forestry statistics, and geographical information systems data on land use, land cover, and soil degradation that localizes human impact on ecosystems. We found an aggregate global HANPP value of 15.6 Pg C/yr or 23.8% of potential net primary productivity, of which 53% was contributed by harvest, 40% by land-use-induced productivity changes, and 7% by human-induced fires. This is a remarkable impact on the biosphere caused by just one species. We present maps quantifying human-induced changes in trophic energy flows in ecosystems that illustrate spatial patterns in the human domination of ecosystems, thus emphasizing land use as a pervasive factor of global importance. Land use transforms earth's terrestrial surface, resulting in changes in biogeochemical cycles and in the ability of ecosystems to deliver services critical to human well being. The results suggest that large-scale schemes to substitute biomass for fossil fuels should be viewed cautiously because massive additional pressures on ecosystems might result from increased biomass harvest. PMID:17616580

  18. Quantifying and mapping the human appropriation of net primary production in earth's terrestrial ecosystems.

    PubMed

    Haberl, Helmut; Erb, K Heinz; Krausmann, Fridolin; Gaube, Veronika; Bondeau, Alberte; Plutzar, Christoph; Gingrich, Simone; Lucht, Wolfgang; Fischer-Kowalski, Marina

    2007-07-31

    Human appropriation of net primary production (HANPP), the aggregate impact of land use on biomass available each year in ecosystems, is a prominent measure of the human domination of the biosphere. We present a comprehensive assessment of global HANPP based on vegetation modeling, agricultural and forestry statistics, and geographical information systems data on land use, land cover, and soil degradation that localizes human impact on ecosystems. We found an aggregate global HANPP value of 15.6 Pg C/yr or 23.8% of potential net primary productivity, of which 53% was contributed by harvest, 40% by land-use-induced productivity changes, and 7% by human-induced fires. This is a remarkable impact on the biosphere caused by just one species. We present maps quantifying human-induced changes in trophic energy flows in ecosystems that illustrate spatial patterns in the human domination of ecosystems, thus emphasizing land use as a pervasive factor of global importance. Land use transforms earth's terrestrial surface, resulting in changes in biogeochemical cycles and in the ability of ecosystems to deliver services critical to human well being. The results suggest that large-scale schemes to substitute biomass for fossil fuels should be viewed cautiously because massive additional pressures on ecosystems might result from increased biomass harvest.

  19. Multidimensional Genome-wide Analyses Show Accurate FVIII Integration by ZFN in Primary Human Cells

    PubMed Central

    Sivalingam, Jaichandran; Kenanov, Dimitar; Han, Hao; Nirmal, Ajit Johnson; Ng, Wai Har; Lee, Sze Sing; Masilamani, Jeyakumar; Phan, Toan Thang; Maurer-Stroh, Sebastian; Kon, Oi Lian

    2016-01-01

    Costly coagulation factor VIII (FVIII) replacement therapy is a barrier to optimal clinical management of hemophilia A. Therapy using FVIII-secreting autologous primary cells is potentially efficacious and more affordable. Zinc finger nucleases (ZFN) mediate transgene integration into the AAVS1 locus but comprehensive evaluation of off-target genome effects is currently lacking. In light of serious adverse effects in clinical trials which employed genome-integrating viral vectors, this study evaluated potential genotoxicity of ZFN-mediated transgenesis using different techniques. We employed deep sequencing of predicted off-target sites, copy number analysis, whole-genome sequencing, and RNA-seq in primary human umbilical cord-lining epithelial cells (CLECs) with AAVS1 ZFN-mediated FVIII transgene integration. We combined molecular features to enhance the accuracy and activity of ZFN-mediated transgenesis. Our data showed a low frequency of ZFN-associated indels, no detectable off-target transgene integrations or chromosomal rearrangements. ZFN-modified CLECs had very few dysregulated transcripts and no evidence of activated oncogenic pathways. We also showed AAVS1 ZFN activity and durable FVIII transgene secretion in primary human dermal fibroblasts, bone marrow- and adipose tissue-derived stromal cells. Our study suggests that, with close attention to the molecular design of genome-modifying constructs, AAVS1 ZFN-mediated FVIII integration in several primary human cell types may be safe and efficacious. PMID:26689265

  20. Consistency of the Proteome in Primary Human Keratinocytes With Respect to Gender, Age, and Skin Localization*

    PubMed Central

    Sprenger, Adrian; Weber, Sebastian; Zarai, Mostafa; Engelke, Rudolf; Nascimento, Juliana M.; Gretzmeier, Christine; Hilpert, Martin; Boerries, Melanie; Has, Cristina; Busch, Hauke; Bruckner-Tuderman, Leena; Dengjel, Jörn

    2013-01-01

    Keratinocytes account for 95% of all cells of the epidermis, the stratified squamous epithelium forming the outer layer of the skin, in which a significant number of skin diseases takes root. Immortalized keratinocyte cell lines are often used as research model systems providing standardized, reproducible, and homogenous biological material. Apart from that, primary human keratinocytes are frequently used for medical studies because the skin provides an important route for drug administration and is readily accessible for biopsies. However, comparability of these cell systems is not known. Cell lines may undergo phenotypic shifts and may differ from the in vivo situation in important aspects. Primary cells, on the other hand, may vary in biological functions depending on gender and age of the donor and localization of the biopsy specimen. Here we employed metabolic labeling in combination with quantitative mass spectrometry-based proteomics to assess A431 and HaCaT cell lines for their suitability as model systems. Compared with cell lines, comprehensive profiling of the primary human keratinocyte proteome with respect to gender, age, and skin localization identified an unexpected high proteomic consistency. The data were analyzed by an improved ontology enrichment analysis workflow designed for the study of global proteomics experiments. It enables a quick, comprehensive and unbiased overview of altered biological phenomena and links experimental data to literature. We guide through our workflow, point out its advantages compared with other methods and apply it to visualize differences of cell lines compared with primary human keratinocytes. PMID:23722187

  1. The psychiatric sequelae of human rights violations: a challenge for primary health care.

    PubMed

    Zungu-Dirwayi, Nompumelelo; Kaminer, Debra; Mbanga, Irene; Stein, Dan J

    2004-04-01

    High rates of psychiatric morbidity have been documented in survivors of gross human rights abuses. Nevertheless, there has been relatively little focus on such patients in the context of primary care medicine. A sample of 134 survivors of gross human rights violations was assessed using a structured interview to determine exposure to violations and psychiatric status. In addition, psychiatric treatment history was probed with an open-ended interview. The study found that of the 95 of 134 (72%) participants who were assessed and found to have a current psychiatric diagnosis, only three were receiving treatment for such a disorder. Many subjects had presented to primary care clinics with somatic symptoms and had been prescribed benzodiazepines. Reasons for not reporting trauma or not seeking treatment included issues revolving around fear and mistrust, privacy and confidentiality, re-experiencing the trauma, and lack of awareness. Misdiagnosis and ineffective treatment of survivors of human rights abuses are likely to pose a significant drain on primary care resources. Accurate diagnosis and appropriate treatment are important challenges in primary care settings.

  2. Effective Connectivity within Human Primary Visual Cortex Predicts Interindividual Diversity in Illusory Perception

    PubMed Central

    Schwarzkopf, D. Samuel; Lutti, Antoine; Li, Baojuan; Kanai, Ryota; Rees, Geraint

    2013-01-01

    Visual perception depends strongly on spatial context. A classic example is the tilt illusion where the perceived orientation of a central stimulus differs from its physical orientation when surrounded by tilted spatial contexts. Here we show that such contextual modulation of orientation perception exhibits trait-like interindividual diversity that correlates with interindividual differences in effective connectivity within human primary visual cortex. We found that the degree to which spatial contexts induced illusory orientation perception, namely, the magnitude of the tilt illusion, varied across healthy human adults in a trait-like fashion independent of stimulus size or contrast. Parallel to contextual modulation of orientation perception, the presence of spatial contexts affected effective connectivity within human primary visual cortex between peripheral and foveal representations that responded to spatial context and central stimulus, respectively. Importantly, this effective connectivity from peripheral to foveal primary visual cortex correlated with interindividual differences in the magnitude of the tilt illusion. Moreover, this correlation with illusion perception was observed for effective connectivity under tilted contextual stimulation but not for that under iso-oriented contextual stimulation, suggesting that it reflected the impact of orientation-dependent intra-areal connections. Our findings revealed an interindividual correlation between intra-areal connectivity within primary visual cortex and contextual influence on orientation perception. This neurophysiological-perceptual link provides empirical evidence for theoretical proposals that intra-areal connections in early visual cortices are involved in contextual modulation of visual perception. PMID:24285885

  3. Human Fertility, Molecular Genetics, and Natural Selection in Modern Societies

    PubMed Central

    Tropf, Felix C.; Stulp, Gert; Barban, Nicola; Visscher, Peter M.; Yang, Jian; Snieder, Harold; Mills, Melinda C.

    2015-01-01

    Research on genetic influences on human fertility outcomes such as number of children ever born (NEB) or the age at first childbirth (AFB) has been solely based on twin and family-designs that suffer from problematic assumptions and practical limitations. The current study exploits recent advances in the field of molecular genetics by applying the genomic-relationship-matrix based restricted maximum likelihood (GREML) methods to quantify for the first time the extent to which common genetic variants influence the NEB and the AFB of women. Using data from the UK and the Netherlands (N = 6,758), results show significant additive genetic effects on both traits explaining 10% (SE = 5) of the variance in the NEB and 15% (SE = 4) in the AFB. We further find a significant negative genetic correlation between AFB and NEB in the pooled sample of –0.62 (SE = 0.27, p-value = 0.02). This finding implies that individuals with genetic predispositions for an earlier AFB had a reproductive advantage and that natural selection operated not only in historical, but also in contemporary populations. The observed postponement in the AFB across the past century in Europe contrasts with these findings, suggesting an evolutionary override by environmental effects and underscoring that evolutionary predictions in modern human societies are not straight forward. It emphasizes the necessity for an integrative research design from the fields of genetics and social sciences in order to understand and predict fertility outcomes. Finally, our results suggest that we may be able to find genetic variants associated with human fertility when conducting GWAS-meta analyses with sufficient sample size. PMID:26039877

  4. Potassium channels mediate killing by human natural killer cells

    SciTech Connect

    Schlichter, L.; Sidell N.; Hagiwara, S.

    1986-01-01

    Human natural killer (NK) cells in peripheral blood spontaneously recognize and kill a wide variety of target cells. It has been suggested that ion channels are involved in the killing process because there is a Ca-dependent stage and because killing by presensitized cytotoxic T lymphocytes, which in many respects resembles NK killing, is associated with changes in K and Na transport in the target cell. Using the whole-cell variation of the patch-clamp technique, the authors found a voltage-dependent potassium (K/sup +/) current in NK cells. The K/sup +/ current was reduced in a dose-dependent manner by the K-channel blockers 4-aminopyridine and quinidine and by the traditional Ca-channel blockers verapamil and Cd/sup 2 +/. They tested the effects of ion-channel blockers on killing of two commonly used target cell lines: K562, which is derived from a human myeloid leukemia, and U937, which is derived from a human histiocytic leukemia. Killing of K562 target cells, determined in a standard /sup 51/Cr-release assay, was inhibited in a dose-dependent manner by verapamil, quinidine, Cd/sup 2 +/, and 4-aminopyridine at concentrations comparable to those that blocked the K/sup +/ current in NK cells. In K562 target cells only a voltage-dependent Na= current was found and it was blocked by concentrations of tetrodotoxin that had no effect on killing. Killing of U937 target cells was also inhibited by the two ion-channel blockers tested, quinidine and verapamil. In this cell line only a small K/sup +/ current was found that was similar to the one in NK cells. The findings show that there are K channels in NK cells and that these channels play a necessary role in the killing process.

  5. Potassium Channels Mediate Killing by Human Natural Killer Cells

    NASA Astrophysics Data System (ADS)

    Schlichter, Lyanne; Sidell, Neil; Hagiwara, Susumu

    1986-01-01

    Human natural killer (NK) cells in peripheral blood spontaneously recognize and kill a wide variety of target cells. It has been suggested that ion channels are involved in the killing process because there is a Ca-dependent stage and because killing by presensitized cytotoxic T lymphocytes, which in many respects resembles NK killing, is associated with changes in K and Na transport in the target cell. However, no direct evidence exists for ion channels in NK cells or in their target cells. Using the whole-cell variation of the patch-clamp technique, we found a voltage-dependent potassium (K+) current in NK cells. The K+ current was reduced in a dose-dependent manner by the K-channel blockers 4-aminopyridine and quinidine and by the traditional Ca-channel blockers verapamil and Cd2+. We tested the effects of ion-channel blockers on killing of two commonly used target cell lines: K562, which is derived from a human myeloid leukemia, and U937, which is derived from a human histiocytic leukemia. Killing of K562 target cells, determined in a standard 51Cr-release assay, was inhibited in a dose-dependent manner by verapamil, quinidine, Cd2+, and 4-aminopyridine at concentrations comparable to those that blocked the K+ current in NK cells. In K562 target cells only a voltage-dependent Na+ current was found and it was blocked by concentrations of tetrodotoxin that had no effect on killing. Killing of U937 target cells was also inhibited by the two ion-channel blockers tested, quinidine and verapamil. In this cell line only a small K+ current was found that was similar to the one in NK cells. We could not find any evidence of a Ca2+ current in target cells or in NK cells; therefore, our results cannot explain the Ca dependence of killing. Our findings show that there are K channels in NK cells and that these channels play a necessary role in the killing process. In contrast, the endogenous channel type in the target cell is probably not a factor in determining target cell

  6. Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins.

    PubMed

    Watanabe, Masaaki; Zemack, Helen; Johansson, Helene; Hagbard, Louise; Jorns, Carl; Li, Meng; Ellis, Ewa

    2016-01-01

    Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms -111, -211, -221, -332, -411, -421, -511, and -521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human

  7. Maintenance of Hepatic Functions in Primary Human Hepatocytes Cultured on Xeno-Free and Chemical Defined Human Recombinant Laminins

    PubMed Central

    Watanabe, Masaaki; Zemack, Helen; Johansson, Helene; Hagbard, Louise; Jorns, Carl; Li, Meng; Ellis, Ewa

    2016-01-01

    Refined methods for maintaining specific functions of isolated hepatocytes under xeno-free and chemical defined conditions is of great importance for the development of hepatocyte research and regenerative therapy. Laminins, a large family of heterotrimeric basement membrane adhesion proteins, are highly cell and tissue type specific components of the extracellular matrix and strongly influence the behavior and function of associated cells and/or tissues. However, detailed biological functions of many laminin isoforms are still to be evaluated. In this study, we determined the distribution of laminin isoforms in human liver tissue and isolated primary human hepatocytes by western blot analysis, and investigated the efficacy of different human recombinant laminin isoforms on hepatic functions during culture. Protein expressions of laminin-chain α2, α3, α4, β1, β3, γ1, and γ2 were detected in both isolated human hepatocytes and liver tissue. No α1 and α5 expression could be detected in liver tissue or hepatocytes. Hepatocytes were isolated from five different individual livers, and cultured on human recombinant laminin isoforms -111, -211, -221, -332, -411, -421, -511, and -521 (Biolamina AB), matrigel (extracted from Engelbreth-Holm-Swarm sarcoma), or collagen type IV (Collagen). Hepatocytes cultured on laminin showed characteristic hexagonal shape in a flat cell monolayer. Viability, double stranded DNA concentration, and Ki67 expression for hepatocytes cultured for six days on laminin were comparable to those cultured on EHS and Collagen. Hepatocytes cultured on laminin also displayed production of human albumin, alpha-1-antitrypsin, bile acids, and gene expression of liver-enriched factors, such as hepatocyte nuclear factor 4 alpha, glucose-6-phosphate, cytochrome P450 3A4, and multidrug resistance-associated protein 2. We conclude that all forms of human recombinant laminin tested maintain cell viability and liver-specific functions of primary human

  8. Greek Primary School Teachers' Understanding of Current Environmental Issues: An Exploration of Their Environmental Knowledge and Images of Nature

    ERIC Educational Resources Information Center

    Michail, Sirmo; Stamou, Anastasia G.; Stamou, George P.

    2007-01-01

    In this article, the Greek primary school teachers' understanding of three current environmental issues (acid rain, the ozone layer depletion, and the greenhouse effect) as well as the emerging images of nature were examined. The study revealed that teachers held several environmental knowledge gaps and misconceptions about the three phenomena.…

  9. 18 CFR 2.400 - Statement of interpretation of waste concerning natural gas as the primary energy source for...

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Statement of interpretation of waste concerning natural gas as the primary energy source for qualifying small power production facilities. 2.400 Section 2.400 Conservation of Power and Water Resources FEDERAL ENERGY...

  10. 18 CFR 2.400 - Statement of interpretation of waste concerning natural gas as the primary energy source for...

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Statement of interpretation of waste concerning natural gas as the primary energy source for qualifying small power production facilities. 2.400 Section 2.400 Conservation of Power and Water Resources FEDERAL ENERGY...

  11. 18 CFR 2.400 - Statement of interpretation of waste concerning natural gas as the primary energy source for...

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Statement of interpretation of waste concerning natural gas as the primary energy source for qualifying small power production facilities. 2.400 Section 2.400 Conservation of Power and Water Resources FEDERAL ENERGY...

  12. Oncogenic potential diverge among human papillomavirus type 16 natural variants

    SciTech Connect

    Sichero, Laura; Simao Sobrinho, Joao; Lina Villa, Luisa

    2012-10-10

    We compared E6/E7 protein properties of three different HPV-16 variants: AA, E-P and E-350G. Primary human foreskin keratinocytes (PHFK) were transduced with HPV-16 E6 and E7 and evaluated for proliferation and ability to grow in soft agar. E-P infected keratinocytes presented the lowest efficiency in colony formation. AA and E-350G keratinocytes attained higher capacity for in vitro transformation. We observed similar degradation of TP53 among HPV-16 variants. Furthermore, we accessed the expression profile in early (p5) and late passage (p30) transduced cells of 84 genes commonly involved in carcinogenesis. Most differences could be attributed to HPV-16 E6/E7 expression. In particular, we detected different expression of ITGA2 and CHEK2 in keratinocytes infected with AA and AA/E-350G late passage cells, respectively, and higher expression of MAP2K1 in E-350G transduced keratinocytes. Our results indicate differences among HPV-16 variants that could explain, at least in part, differences in oncogenic potential attributed to these variants.

  13. Thrombopoietin receptor expression in human cancer cell lines and primary tissues.

    PubMed

    Columbyova, L; Loda, M; Scadden, D T

    1995-08-15

    c-mpl is the receptor for the recently identified megakaryocyte growth and differentiation factor thrombopoietin. Thrombopoietin has been shown to be capable of raising platelet counts in animals and is about to enter clinical trials in humans. In anticipation of its likely use in the care of patients receiving cancer chemotherapy, we evaluated the expression of human c-mpl by reverse transcription PCR on 39 human cell lines and 20 primary human tissue samples derived from both normal and malignant sources. c-mpl transcripts were found in all megakaryocytic cell lines tested (CMK, CMK-2B, CMK-2D, SO, and DAMI), the CD34+ leukemia cell line KMT-2, and a hepatocellular carcinoma cell line (Hep3B). Among primary tissues, fetal liver cells and brain had detectable levels of c-mpl message, and among primary tumors, none were found to express c-mpl. These data support the conclusion that c-mpl has restricted expression that is primarily, but not exclusively, related to megakaryocytopoiesis. These observations suggest that thrombopoietin is unlikely to have direct effects on other malignant or normal tissue should it have a clinical role in the treatment of chemotherapy-induced thrombocytopenia. PMID:7627956

  14. Retroviral-mediated gene transfer and expression of human phenylalanine hydroxylase in primary mouse hepatocytes

    SciTech Connect

    Peng, H.; Armentano, D.; Mackenzie-Graham, L.; Shen, R.F.; Darlington, G.; Ledley, F.D.; Woo, S.L.C. )

    1988-11-01

    Genetic therapy for phenylketonuria (severe phenylalanine hydroxylase deficiency) may require introduction of a normal phenylalanine hydroxylase gene into hepatic cells of patients. The authors report development of a recombinant retrovirus based on the N2 vector for gene transfer and expression of human phenylalanine hydroxylase cDNA in primary mouse hepatocytes. This construct contains an internal promoter of the human {alpha}{sub 1}-antitrypsin gene driving transcription of the phenylalanine hydroxylase cDNA. Primary mouse hepatocytes were isolated from newborn mice, infected with the recombinant virus, and selected for expression of the neomycin-resistance gene. Hepatocytes transformed with the recombinant virus contained high levels of human phenylalanine hydroxylase mRNA transcripts originating from the retroviral and internal promoters. These results demonstrate that the transcriptional regulatory elements of the {alpha}{sub 1} antitrypsin gene retain their tissue-specific function in the recombinant provirus and establish a method for efficient transfer and high-level expression of human phenylalanine hydroxylase in primary hepatocytes.

  15. Modelling human decision-making in coupled human and natural systems

    NASA Astrophysics Data System (ADS)

    Feola, G.

    2012-12-01

    A solid understanding of human decision-making is essential to analyze the complexity of coupled human and natural systems (CHANS) and inform policies to promote resilience in the face of environmental change. Human decisions drive and/or mediate the interactions and feedbacks, and contribute to the heterogeneity and non-linearity that characterize CHANS. However, human decision-making is usually over-simplistically modeled, whereby human agents are represented deterministically either as dumb or clairvoyant decision-makers. Decision-making models fall short in the integration of both environmental and human behavioral drivers, and concerning the latter, tend to focus on only one category, e.g. economic, cultural, or psychological. Furthermore, these models render a linear decision-making process and therefore fail to account for the recursive co-evolutionary dynamics in CHANS. As a result, these models constitute only a weak basis for policy-making. There is therefore scope and an urgent need for better approaches to human decision-making, to produce the knowledge that can inform vulnerability reduction policies in the face of environmental change. This presentation synthesizes the current state-of-the-art of modelling human decision-making in CHANS, with particular reference to agricultural systems, and delineates how the above mentioned shortcomings can be overcome. Through examples from research on pesticide use and adaptation to climate change, both based on the integrative agent-centered framework (Feola and Binder, 2010), the approach for an improved understanding of human agents in CHANS are illustrated. This entails: integrative approach, focus on behavioral dynamics more than states, feedbacks between individual and system levels, and openness to heterogeneity.

  16. The Nature of Indexing: How Humans and Machines Analyze Messages and Texts for Retrieval. Part I: Research, and the Nature of Human Indexing.

    ERIC Educational Resources Information Center

    Anderson, James D.; Perez-Carballo, Jose

    2001-01-01

    Considers the role of human intellectual indexing in the face of increasingly sophisticated automatic indexing techniques. Critiques the comparative research and explores the nature of human analysis of messages or texts and efforts to formulate rules to make human practice more predictable. (Author/LRW)

  17. Effects of Human-Nature Interactions on Wildlife Habitat Dynamics: The Case of Wolong Nature Reserve for Giant Pandas

    NASA Astrophysics Data System (ADS)

    Vina, A.; Tuanmu, M.; Yang, W.; Liu, J.

    2012-12-01

    Human activities continue to induce the degradation of natural ecosystems, thus threatening not only the long-term survival of many wildlife species around the world, but also the resilience of natural ecosystems to global environmental changes. In response, many conservation efforts are emerging as adaptive strategies for coping with the degradation of natural ecosystems. Among them, the establishment of nature reserves is considered to be the most effective. However the effectiveness of nature reserves depends on the type and intensity of human activities occurring within their boundaries. But many of these activities constitute important livelihood systems for local human populations. Therefore, to enhance the effectiveness of conservation actions without significantly affecting local livelihood systems, it is essential to understand the complexity of human-nature interactions and their effects on the spatio-temporal dynamics of natural ecosystems. In this study, we evaluated the relation between giant panda habitat dynamics, conservation efforts and human activities in Wolong Nature Reserve for Giant Pandas, Sichuan Province, China. This reserve supports ca. 10% of the entire wild giant panda population but is also home to ca. 4,900 local residents. The spatio-temporal dynamics of giant panda habitat over the last four decades were analyzed using a time series of remotely sensed imagery acquired by different satellite sensor systems, including the Landsat Multi-Spectral Scanner, the Landsat Thematic Mapper and the Moderate Resolution Imaging Spectroradiometer (MODIS). Our assessment suggests that when local residents were actively involved in conservation efforts (through a payment for ecosystem services scheme established since around 2000) panda habitat started to recover, thus enhancing the resilience capacity of natural ecosystems in the Reserve. This reversed a long-term (> 30 years) trend of panda habitat degradation. The study not only has direct

  18. Effects of Humans on Behaviour of Wildlife Exceed Those of Natural Predators in a Landscape of Fear

    PubMed Central

    Ciuti, Simone; Northrup, Joseph M.; Muhly, Tyler B.; Simi, Silvia; Musiani, Marco; Pitt, Justin A.; Boyce, Mark S.

    2012-01-01

    Background Human disturbance can influence wildlife behaviour, which can have implications for wildlife populations. For example, wildlife may be more vigilant near human disturbance, resulting in decreased forage intake and reduced reproductive success. We measured the effects of human activities compared to predator and other environmental factors on the behaviour of elk (Cervus elaphus Linnaeus 1758) in a human-dominated landscape in Alberta, Canada. Methodology/Principal Findings We collected year-round behavioural data of elk across a range of human disturbances. We estimated linear mixed models of elk behaviour and found that human factors (land-use type, traffic and distance from roads) and elk herd size accounted for more than 80% of variability in elk vigilance. Elk decreased their feeding time when closer to roads, and road traffic volumes of at least 1 vehicle every 2 hours induced elk to switch into a more vigilant behavioural mode with a subsequent loss in feeding time. Other environmental factors, thought crucial in shaping vigilance behaviour in elk (natural predators, reproductive status of females), were not important. The highest levels of vigilance were recorded on public lands where hunting and motorized recreational activities were cumulative compared to the national park during summer, which had the lowest levels of vigilance. Conclusions/Significance In a human-dominated landscape, effects of human disturbance on elk behaviour exceed those of habitat and natural predators. Humans trigger increased vigilance and decreased foraging in elk. However, it is not just the number of people but also the type of human activity that influences elk behaviour (e.g. hiking vs. hunting). Quantifying the actual fitness costs of human disturbance remains a challenge in field studies but should be a primary focus for future researches. Some species are much more likely to be disturbed by humans than by non-human predators: for these species, quantifying human

  19. Pharmacologic inhibition of tpl2 blocks inflammatory responses in primary human monocytes, synoviocytes, and blood.

    PubMed

    Hall, J Perry; Kurdi, Yahya; Hsu, Sang; Cuozzo, John; Liu, Julie; Telliez, Jean-Baptiste; Seidl, Katherine J; Winkler, Aaron; Hu, Yonghan; Green, Neal; Askew, G Roger; Tam, Steve; Clark, James D; Lin, Lih-Ling

    2007-11-16

    Tumor necrosis factor alpha (TNFalpha) is a pro-inflammatory cytokine that controls the initiation and progression of inflammatory diseases such as rheumatoid arthritis. Tpl2 is a MAPKKK in the MAPK (i.e. ERK) pathway, and the Tpl2-MEK-ERK signaling pathway is activated by the pro-inflammatory mediators TNFalpha, interleukin (IL)-1beta, and bacterial endotoxin (lipopolysaccharide (LPS)). Moreover, Tpl2 is required for TNFalpha expression. Thus, pharmacologic inhibition of Tpl2 should be a valid approach to therapeutic intervention in the pathogenesis of rheumatoid arthritis and other inflammatory diseases in humans. We have developed a series of highly selective and potent Tpl2 inhibitors, and in the present study we have used these inhibitors to demonstrate that the catalytic activity of Tpl2 is required for the LPS-induced activation of MEK and ERK in primary human monocytes. These inhibitors selectively target Tpl2 in these cells, and they block LPS- and IL-1beta-induced TNFalpha production in both primary human monocytes and human blood. In rheumatoid arthritis fibroblast-like synoviocytes these inhibitors block ERK activation, cyclooxygenase-2 expression, and the production of IL-6, IL-8, and prostaglandin E(2), and the matrix metalloproteinases MMP-1 and MMP-3. Taken together, our results show that inhibition of Tpl2 in primary human cell types can decrease the production of TNFalpha and other pro-inflammatory mediators during inflammatory events, and they further support the notion that Tpl2 is an appropriate therapeutic target for rheumatoid arthritis and other human inflammatory diseases. PMID:17848581

  20. Telomerase-mediated life-span extension of human primary fibroblasts by human artificial chromosome (HAC) vector

    SciTech Connect

    Shitara, Shingo; Kakeda, Minoru; Nagata, Keiko; Hiratsuka, Masaharu; Sano, Akiko; Osawa, Kanako; Okazaki, Akiyo; Katoh, Motonobu; Kazuki, Yasuhiro; Oshimura, Mitsuo; Tomizuka, Kazuma

    2008-05-09

    Telomerase-mediated life-span extension enables the expansion of normal cells without malignant transformation, and thus has been thought to be useful in cell therapies. Currently, integrating vectors including the retrovirus are used for human telomerase reverse transcriptase (hTERT)-mediated expansion of normal cells; however, the use of these vectors potentially causes unexpected insertional mutagenesis and/or activation of oncogenes. Here, we established normal human fibroblast (hPF) clones retaining non-integrating human artificial chromosome (HAC) vectors harboring the hTERT expression cassette. In hTERT-HAC/hPF clones, we observed the telomerase activity and the suppression of senescent-associated SA-{beta}-galactosidase activity. Furthermore, the hTERT-HAC/hPF clones continued growing beyond 120 days after cloning, whereas the hPF clones retaining the silent hTERT-HAC senesced within 70 days. Thus, hTERT-HAC-mediated episomal expression of hTERT allows the extension of the life-span of human primary cells, implying that gene delivery by non-integrating HAC vectors can be used to control cellular proliferative capacity of primary cultured cells.

  1. Antiadipogenic properties of retinol in primary cultured differentiating human adipocyte precursor cells.

    PubMed

    Garcia, E; Lacasa, D; Agli, B; Giudicelli, Y; Castelli, D

    2000-04-01

    The aim of this study was to investigate the effect of retinol on the human adipose conversion process using primary cultured human adipocyte precursor cells. When these cells were seeded in a medium containing retinol (concentrations ranging from 3.5 nM to 3.5 muM), cell proliferation was slightly inhibited by high concentrations of retinol, as demonstrated by cell counting and [(3)H]-thymidine incorporation. Moreover, the differentiation capacities of these cells were markedly and dose-dependently inhibited by retinol, as shown by the reduced expression of the lipogenic enzyme glycerol-3-phosphate dehydrogenase and by microscopic morphological analysis. These results strongly suggest that retinol, by inhibiting the ability of human preadipocytes to convert into mature adipocytes, could be of potential interest in the prevention of human adipose tissue development in general and of cellulitis in particular. PMID:18503465

  2. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    SciTech Connect

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C. ); Grzeschik, K.H. )

    1988-02-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration.

  3. Production and Concentration of Lentivirus for Transduction of Primary Human T Cells.

    PubMed

    Kennedy, Alan; Cribbs, Adam P

    2016-01-01

    Lentiviral vectors have emerged as efficient tools for investigating T cell biology through their ability to efficiently deliver transgene expression into both dividing and nondividing cells. Such lentiviral vectors have the potential to infect a wide variety of cell types. However, despite this advantage, the ability to transduce primary human T cells remains challenging and methods to achieve efficient gene transfer are often time consuming and expensive. We describe a method for generating lentivirus that is simple to perform and does not require the purchase of non-standard equipment to transduce primary human T cells. Therefore, we provide an optimized protocol that is easy to implement and allow transduction with high efficiency and reproducibility. PMID:27317175

  4. Divergences of Two Coupled Human and Natural Systems on the Mongolian Plateau

    NASA Astrophysics Data System (ADS)

    Chen, J.

    2014-12-01

    Central to the concept of coupled natural and human (CNH) systems is that humans and nature are organized in interacting sub-systems that make a cohesive whole at multiple spatial and temporal scales. Following an overview of the challenges in implementing the CNH concept at the regional level, we used widely available measures of states in the social, economic, and ecological systems, including gross domestic product, population size, net primary productivity, and livestock and their ratios, to examine the CNH dynamics on the Mongolian Plateau during 1981-2010. Our cross-border analysis of the coupled dynamics over the past three decades demonstrated striking contrasts between Inner Mongolia (IM) and Mongolia (MG), with policies playing shifting roles on the above measures. For prioritizing future research on the CNH concept, we propose the hypothesis that while the divergence of IM and MG for 1981-2010 was largely driven by market economic reforms, the importance of socioeconomic forces relative to climate changes will gradually decrease in IM while they remain important in MG.

  5. Human T Follicular Helper Cells in Primary Immunodeficiency: Quality Just as Important as Quantity.

    PubMed

    Ma, Cindy S

    2016-05-01

    T follicular helper (Tfh) cells are a subset of effector CD4(+) T cells specialised to induce Ab production by B cells. This review highlights some of the recent advances in the field of human Tfh cells that have come from the study of primary immunodeficiencies. In particular it is increasingly evident that the quality of the Tfh cells that are generated, is just as important as the quantity.

  6. Human Immunodeficiency Virus Type 1 Coat Protein Neurotoxicity Mediated by Nitric Oxide in Primary Cortical Cultures

    NASA Astrophysics Data System (ADS)

    Dawson, Valina L.; Dawson, Ted M.; Uhl, George R.; Snyder, Solomon H.

    1993-04-01

    The human immunodeficiency virus type 1 coat protein, gp120, kills neurons in primary cortical cultures at low picomolar concentrations. The toxicity requires external glutamate and calcium and is blocked by glutamate receptor antagonists. Nitric oxide (NO) contributes to gp120 toxicity, since nitroarginine, an inhibitor of NO synthase, prevents toxicity as does deletion of arginine from the incubation medium and hemoglobin, which binds NO. Superoxide dismutase also attenuates toxicity, implying a role for superoxide anions.

  7. Constraint, natural selection, and the evolution of human body form.

    PubMed

    Savell, Kristen R R; Auerbach, Benjamin M; Roseman, Charles C

    2016-08-23

    Variation in body form among human groups is structured by a blend of natural selection driven by local climatic conditions and random genetic drift. However, attempts to test ecogeographic hypotheses have not distinguished between adaptive traits (i.e., those that evolved as a result of selection) and those that evolved as a correlated response to selection on other traits (i.e., nonadaptive traits), complicating our understanding of the relationship between climate and morphological distinctions among populations. Here, we use evolutionary quantitative methods to test if traits previously identified as supporting ecogeographic hypotheses were actually adaptive by estimating the force of selection on individual traits needed to drive among-group differentiation. Our results show that not all associations between trait means and latitude were caused by selection acting directly on each individual trait. Although radial and tibial length and biiliac and femoral head breadth show signs of responses to directional selection matching ecogeographic hypotheses, the femur was subject to little or no directional selection despite having shorter values by latitude. Additionally, in contradiction to ecogeographic hypotheses, the humerus was under directional selection for longer values by latitude. Responses to directional selection in the tibia and radius induced a nonadaptive correlated response in the humerus that overwhelmed its own trait-specific response to selection. This result emphasizes that mean differences between groups are not good indicators of which traits are adaptations in the absence of information about covariation among characteristics. PMID:27482101

  8. Harvesting energy from the natural vibration of human walking.

    PubMed

    Yang, Weiqing; Chen, Jun; Zhu, Guang; Yang, Jin; Bai, Peng; Su, Yuanjie; Jing, Qingsheng; Cao, Xia; Wang, Zhong Lin

    2013-12-23

    The triboelectric nanogenerator (TENG), a unique technology for harvesting ambient mechanical energy based on the triboelectric effect, has been proven to be a cost-effective, simple, and robust approach for self-powered systems. However, a general challenge is that the output current is usually low. Here, we demonstrated a rationally designed TENG with integrated rhombic gridding, which greatly improved the total current output owing to the structurally multiplied unit cells connected in parallel. With the hybridization of both the contact-separation mode and sliding electrification mode among nanowire arrays and nanopores fabricated onto the surfaces of two contact plates, the newly designed TENG produces an open-circuit voltage up to 428 V, and a short-circuit current of 1.395 mA with the peak power density of 30.7 W/m(2). Relying on the TENG, a self-powered backpack was developed with a vibration-to-electric energy conversion efficiency up to 10.62(±1.19) %. And it was also demonstrated as a direct power source for instantaneously lighting 40 commercial light-emitting diodes by harvesting the vibration energy from natural human walking. The newly designed TENG can be a mobile power source for field engineers, explorers, and disaster-relief workers. PMID:24180642

  9. The human chitotriosidase gene. Nature of inherited enzyme deficiency.

    PubMed

    Boot, R G; Renkema, G H; Verhoek, M; Strijland, A; Bliek, J; de Meulemeester, T M; Mannens, M M; Aerts, J M

    1998-10-01

    The human chitinase, named chitotriosidase, is a member of family 18 of glycosylhydrolases. Following the cloning of the chitotriosidase cDNA (Boot, R. G., Renkema, G. H., Strijland, A., van Zonneveld, A. J., and Aerts, J. M. F. G. (1995) J. Biol. Chem. 270, 26252-26256), the gene and mRNA have been investigated. The chitotriosidase gene is assigned to chromosome 1q31-q32. The gene consists of 12 exons and spans about 20 kilobases. The nature of the common deficiency in chitotriosidase activity is reported. A 24-base pair duplication in exon 10 results in activation of a cryptic 3' splice site, generating a mRNA with an in-frame deletion of 87 nucleotides. All chitotriosidase-deficient individuals tested were homozygous for the duplication. The observed carrier frequency of about 35% indicates that the duplication is the predominant cause of chitotriosidase deficiency. The presence of the duplication in individuals from various ethnic groups suggests that this mutation is relatively old.

  10. The DNA methylation profile of activated human natural killer cells.

    PubMed

    Wiencke, John K; Butler, Rondi; Hsuang, George; Eliot, Melissa; Kim, Stephanie; Sepulveda, Manuel A; Siegel, Derick; Houseman, E Andres; Kelsey, Karl T

    2016-05-01

    Natural killer (NK) cells are now recognized to exhibit characteristics akin to cells of the adaptive immune system. The generation of adaptive memory is linked to epigenetic reprogramming including alterations in DNA methylation. The study herein found reproducible genome wide DNA methylation changes associated with human NK cell activation. Activation led predominately to CpG hypomethylation (81% of significant loci). Bioinformatics analysis confirmed that non-coding and gene-associated differentially methylated sites (DMS) are enriched for immune related functions (i.e., immune cell activation). Known DNA methylation-regulated immune loci were also identified in activated NK cells (e.g., TNFA, LTA, IL13, CSF2). Twenty-one loci were designated high priority and further investigated as potential markers of NK activation. BHLHE40 was identified as a viable candidate for which a droplet digital PCR assay for demethylation was developed. The assay revealed high demethylation in activated NK cells and low demethylation in naïve NK, T- and B-cells. We conclude the NK cell methylome is plastic with potential for remodeling. The differentially methylated region signature of activated NKs revealed similarities with T cell activation, but also provided unique biomarker candidates of NK activation, which could be useful in epigenome-wide association studies to interrogate the role of NK subtypes in global methylation changes associated with exposures and/or disease states. PMID:26967308

  11. The natural product berberine is a human prolyl oligopeptidase inhibitor.

    PubMed

    Tarrago, Teresa; Kichik, Nessim; Seguí, Josep; Giralt, Ernest

    2007-03-01

    Prolyl oligopeptidase is a cytosolic serine peptidase that hydrolyzes proline-containing peptides at the carboxy terminus. This peptidase has been associated with schizophrenia, bipolar affective disorder, and related neuropsychiatric disorders, and therefore may have important clinical implications. Among the strategies used to find novel prolyl oligopeptidase inhibitors, traditional Chinese medicinal plants provide a rich source of unexplored compounds. We used (19)F NMR spectroscopy to search for new prolyl oligopeptidase inhibitors in a library of traditional Chinese medicine plant extracts. Several extracts were identified as powerful inhibitors of this peptidase. The alkaloid berberine was the prolyl oligopeptidase inhibitory molecule isolated from Rhizoma coptidis extract. Berberine inhibited prolyl oligopeptidase in a dose-dependent manner. As berberine is a natural compound that has been safely administered to humans, it opens up new perspectives for the treatment of neuropsychiatric diseases. The results described herein suggest that the initiation of clinical trials in patients with schizophrenia, bipolar affective disorder, or related diseases in which cognitive capabilities are affected should be undertaken with either the extract or pure BBR.

  12. Gene modification of primary tumor cells for active immunotherapy of human breast and ovarian cancer.

    PubMed

    Philip, R; Clary, B; Brunette, E; Kilinski, L; Murugesh, D; Sorich, M; Yau, J; Lebkowski, J; Lyerly, H K; Philip, M

    1996-01-01

    We have previously shown that cationic liposomes facilitate adeno-associated virus (AAV) plasmid transfections of primary and cultured cell types. To test the clinical feasibility of using genetically modified tumor vaccines for the treatment of breast and ovarian cancers, we have constructed an expression plasmid pMP6IL2 and investigated the use of liposome-mediated gene delivery into primary, uncultured human breast and ovarian tumor cells to produce interleukin 2 (IL-2)-secreting tumor cells. We have demonstrated significant levels of IL-2 expression in tumor cell lines and primary breast and ovarian tumor cells using this AAV-based expression plasmid complexed to cationic liposomes. Transfections with the non-AAV plasmid containing the identical expression cassette as the AAV plasmid induced IL-2 expression in the tumor cell line but failed to produce IL-2 in primary tumor cells. Significant levels of IL-2 were induced with the AAV plasmid regardless of liposome compositions used for transfection. The transfected breast cell line and primary tumor cells were able to express the transgene product for up to 28 days after lethal radiation. The transfection efficiency was comparable for both the tumor cell line and primary tumor cells and ranged from 20 to 50% for both cell types as assessed by intracellular IL-2 staining. Although the primary tumor cell preparations consist of mixed population of cells, at least 40% of the tumor cells expressed the transgene as assessed by immunostaining for IL-2. The ability to efficiently express transgenes in freshly isolated, nondividing tumor cells may potentiate active immunotherapy strategies for gene-based cancer treatment.

  13. Naturally occurring hepatitis B virus (HBV) variants with primary resistance to antiviral therapy and S-mutants with potential primary resistance to adefovir in Argentina.

    PubMed

    Cuestas, María L; Rivero, Cintia W; Minassian, María L; Castillo, Amalia I; Gentile, Emiliano A; Trinks, Julieta; León, Liliana; Daleoso, Graciela; Frider, Bernardo; Lezama, Carol; Galoppo, Marcela; Giacove, Gisela; Mathet, Verónica L; Oubiña, José R

    2010-07-01

    Hepatitis B virus (HBV) variants may either emerge in patients with chronic hepatitis B (CHB) as a result of positive selection pressure exerted by their own immune response, or during therapy with nucleos(t)ide analogues (NAs). Naturally occurring HBV variants with primary antiviral resistance are rarely observed. The aim of this study was to retrospectively analyze the (eventual) circulation of HBV variants with natural resistance to NAs currently used as therapy for CHB in Argentina. This study reports 13 cases of CHB-infected patients with natural antiviral resistance to at least one NA. Five of them were also carriers of S-variants that might escape the humoral immune system recognition with potential resistance to adefovir. In addition to the already reported A2 HBV subgenotype association to NAs natural resistance, E and F genotypes association to such resistance is described for the first time. These findings suggest that sequence analysis of the HBV reverse transcriptase might be an essential tool before starting antiviral therapy, in order to choose the proper NAs for optimizing the therapeutic management of chronically infected patients. Moreover, the circulation and transmission of S-mutants with resistance to such antiviral drugs should be of public health concern as they may represent an additional risk for the community.

  14. Naturally occurring hepatitis B virus (HBV) variants with primary resistance to antiviral therapy and S-mutants with potential primary resistance to adefovir in Argentina.

    PubMed

    Cuestas, María L; Rivero, Cintia W; Minassian, María L; Castillo, Amalia I; Gentile, Emiliano A; Trinks, Julieta; León, Liliana; Daleoso, Graciela; Frider, Bernardo; Lezama, Carol; Galoppo, Marcela; Giacove, Gisela; Mathet, Verónica L; Oubiña, José R

    2010-07-01

    Hepatitis B virus (HBV) variants may either emerge in patients with chronic hepatitis B (CHB) as a result of positive selection pressure exerted by their own immune response, or during therapy with nucleos(t)ide analogues (NAs). Naturally occurring HBV variants with primary antiviral resistance are rarely observed. The aim of this study was to retrospectively analyze the (eventual) circulation of HBV variants with natural resistance to NAs currently used as therapy for CHB in Argentina. This study reports 13 cases of CHB-infected patients with natural antiviral resistance to at least one NA. Five of them were also carriers of S-variants that might escape the humoral immune system recognition with potential resistance to adefovir. In addition to the already reported A2 HBV subgenotype association to NAs natural resistance, E and F genotypes association to such resistance is described for the first time. These findings suggest that sequence analysis of the HBV reverse transcriptase might be an essential tool before starting antiviral therapy, in order to choose the proper NAs for optimizing the therapeutic management of chronically infected patients. Moreover, the circulation and transmission of S-mutants with resistance to such antiviral drugs should be of public health concern as they may represent an additional risk for the community. PMID:20403388

  15. Bile Acid-Induced Necrosis in Primary Human Hepatocytes and in Patients with Obstructive Cholestasis

    PubMed Central

    Woolbright, Benjamin L.; Dorko, Kenneth; Antoine, Daniel J.; Clarke, Joanna I.; Gholami, Parviz; Li, Feng; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Fan, Fang; Jenkins, Rosalind E.; Park, B. Kevin; Hagenbuch, Bruno; Olyaee, Mojtaba; Jaeschke, Hartmut

    2015-01-01

    Accumulation of bile acids is a major mediator of cholestatic liver injury. Recent studies indicate bile acid composition between humans and rodents is dramatically different, as humans have a higher percent of glycine conjugated bile acids and increased chenodeoxycholate content, which increases the hydrophobicity index of bile acids. This increase may lead to direct toxicity that kills hepatocytes, and promotes inflammation. To address this issue, this study assessed how pathophysiological concentrations of bile acids measured in cholestatic patients affected primary human hepatocytes. Individual bile acid levels were determined in serum and bile by UPLC/QTOFMS in patients with extrahepatic cholestasis with, or without, concurrent increases in serum transaminases. Bile acid levels increased in serum of patients with liver injury, while biliary levels decreased, implicating infarction of the biliary tracts. To assess bile acid-induced toxicity in man, primary human hepatocytes were treated with relevant concentrations, derived from patient data, of the model bile acid glycochenodeoxycholic acid (GCDC). Treatment with GCDC resulted in necrosis with no increase in apoptotic parameters. This was recapitulated by treatment with biliary bile acid concentrations, but not serum concentrations. Marked elevations in serum full-length cytokeratin-18, high mobility group box1 protein (HMGB1), and acetylated HMGB1 confirmed inflammatory necrosis in injured patients; only modest elevations in caspase-cleaved cytokeratin-18 were observed. These data suggest human hepatocytes are more resistant to human-relevant bile acids than rodent hepatocytes, and die through necrosis when exposed to bile acids. These mechanisms of cholestasis in humans are fundamentally different to mechanisms observed in rodent models. PMID:25636263

  16. A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies

    PubMed Central

    Parikh, Mukti R.; Belch, Andrew R.; Pilarski, Linda M; Kirshner, Julia

    2014-01-01

    Tissue culture has been an invaluable tool to study many aspects of cell function, from normal development to disease. Conventional cell culture methods rely on the ability of cells either to attach to a solid substratum of a tissue culture dish or to grow in suspension in liquid medium. Multiple immortal cell lines have been created and grown using such approaches, however, these methods frequently fail when primary cells need to be grown ex vivo. Such failure has been attributed to the absence of the appropriate extracellular matrix components of the tissue microenvironment from the standard systems where tissue culture plastic is used as a surface for cell growth. Extracellular matrix is an integral component of the tissue microenvironment and its presence is crucial for the maintenance of physiological functions such as cell polarization, survival, and proliferation. Here we present a 3-dimensional tissue culture method where primary bone marrow cells are grown in extracellular matrix formulated to recapitulate the microenvironment of the human bone (rBM system). Embedded in the extracellular matrix, cells are supplied with nutrients through the medium supplemented with human plasma, thus providing a comprehensive system where cell survival and proliferation can be sustained for up to 30 days while maintaining the cellular composition of the primary tissue. Using the rBM system we have successfully grown primary bone marrow cells from normal donors and patients with amyloidosis, and various hematological malignancies. The rBM system allows for direct, in-matrix real time visualization of the cell behavior and evaluation of preclinical efficacy of novel therapeutics. Moreover, cells can be isolated from the rBM and subsequently used for in vivo transplantation, cell sorting, flow cytometry, and nucleic acid and protein analysis. Taken together, the rBM method provides a reliable system for the growth of primary bone marrow cells under physiological conditions

  17. Chemosensitivity of primary human fibroblasts with defective unhooking of DNA interstrand cross-links.

    PubMed

    Clingen, Peter H; Arlett, Colin F; Hartley, John A; Parris, Christopher N

    2007-02-15

    Xeroderma pigmentosum (XP) is characterised by defects in nucleotide excision repair, ultraviolet (UV) radiation sensitivity and increased skin carcinoma. Compared to other complementation groups, XP-F patients show relatively mild cutaneous symptoms. DNA interstrand cross-linking agents are a highly cytotoxic class of DNA damage induced by common cancer chemotherapeutics such as cisplatin and nitrogen mustards. Although the XPF-ERCC1 structure-specific endonuclease is required for the repair of ICLs cellular sensitivity of primary human XP-F cells has not been established. In clonogenic survival assays, primary fibroblasts from XP-F patients were moderately sensitive to both UVC and HN2 compared to normal cells (2- to 3-fold and 3- to 5-fold, respectively). XP-A fibroblasts were considerably more sensitive to UVC (10- to 12-fold) but not sensitive to HN2. The sensitivity of XP-F fibroblasts to HN2 correlated with the defective incision or 'unhooking' step of ICL repair. Using the comet assay, XP-F cells exhibited only 20% residual unhooking activity over 24 h. Over the same time, normal and XP-A cells unhooked greater than 95% and 62% of ICLs, respectively. After HN2 treatment, ICL-associated DNA double-strand breaks (DSBs) are detected by pulse field gel electrophoresis in dividing cells. Induction and repair of DNA DSBs was normal in XP-F fibroblasts. These findings demonstrate that in primary human fibroblasts, XPF is required for the unhooking of ICLs and not for the induction or repair of ICL-associated DNA DSBs induced by HN2. In terms of cancer chemotherapy, people with mild DNA repair defects affecting ICL repair may be more prevalent in the general population than expected. Since cellular sensitivity of primary human fibroblasts usually reflects clinical sensitivity such patients with cancer would be at risk of increased toxicity. PMID:17188678

  18. Chemosensitivity of primary human fibroblasts with defective unhooking of DNA interstrand cross-links

    SciTech Connect

    Clingen, Peter H. . E-mail: p.clingen@ucl.ac.uk; Arlett, Colin F.; Hartley, John A.; Parris, Christopher N.

    2007-02-15

    Xeroderma pigmentosum (XP) is characterised by defects in nucleotide excision repair, ultraviolet (UV) radiation sensitivity and increased skin carcinoma. Compared to other complementation groups, XP-F patients show relatively mild cutaneous symptoms. DNA interstrand cross-linking agents are a highly cytotoxic class of DNA damage induced by common cancer chemotherapeutics such as cisplatin and nitrogen mustards. Although the XPF-ERCC1 structure-specific endonuclease is required for the repair of ICLs cellular sensitivity of primary human XP-F cells has not been established. In clonogenic survival assays, primary fibroblasts from XP-F patients were moderately sensitive to both UVC and HN2 compared to normal cells (2- to 3-fold and 3- to 5-fold, respectively). XP-A fibroblasts were considerably more sensitive to UVC (10- to 12-fold) but not sensitive to HN2. The sensitivity of XP-F fibroblasts to HN2 correlated with the defective incision or 'unhooking' step of ICL repair. Using the comet assay, XP-F cells exhibited only 20% residual unhooking activity over 24 h. Over the same time, normal and XP-A cells unhooked greater than 95% and 62% of ICLs, respectively. After HN2 treatment, ICL-associated DNA double-strand breaks (DSBs) are detected by pulse field gel electrophoresis in dividing cells. Induction and repair of DNA DSBs was normal in XP-F fibroblasts. These findings demonstrate that in primary human fibroblasts, XPF is required for the unhooking of ICLs and not for the induction or repair of ICL-associated DNA DSBs induced by HN2. In terms of cancer chemotherapy, people with mild DNA repair defects affecting ICL repair may be more prevalent in the general population than expected. Since cellular sensitivity of primary human fibroblasts usually reflects clinical sensitivity such patients with cancer would be at risk of increased toxicity.

  19. Fibulin-5 is upregulated in decidualized human endometrial stromal cells and promotes primary human extravillous trophoblast outgrowth.

    PubMed

    Winship, Amy; Cuman, Carly; Rainczuk, Katarzyna; Dimitriadis, Evdokia

    2015-12-01

    Interactions between the highly invasive trophoblasts and the maternal uterine decidual extracellular matrix (ECM) are crucial in the determination of a successful pregnancy. Fibulin-5 (FBLN5) is a member of the fibulin family that alters cell adhesive and invasive properties and is expressed in human villous cytotrophoblasts. We aimed to determine the expression and immunolocalization of FBLN5 in human first trimester decidua and examine the effect of FBLN5 in trophoblast invasion in vitro using a first trimester placental villous outgrowth assay. We demonstrated that FBLN5 mRNA expression is upregulated in response to cAMP-mediated decidualization of primary human endometrial stromal cells, although FBLN5 itself does not enhance decidualization. We reported for the first time, FBLN5 protein production in first trimester decidual cells and also co-localization to HLAG-positive EVTs in first trimester decidua. Consequently, we investigated the effects of exogenous FBLN5 on placental villous outgrowth in vitro and demonstrated that FBLN5 promotes EVT migration/invasion. This is the first study to identify FBLN5 in decidualized human endometrial stromal cells, first trimester decidua and EVT and determine a functional role for FBLN5 in human EVTs, suggesting that decidual and or EVT-derived FBLN5 regulates EVT invasion and placentation in women. PMID:26506560

  20. Astrocytes As the Main Players in Primary Degenerative Disorders of the Human Central Nervous System.

    PubMed

    Capani, Francisco; Quarracino, Cecilia; Caccuri, Roberto; Sica, Roberto E P

    2016-01-01

    Along the last years it has been demonstrated that non-neural cells play a major role in the pathogenesis of the primary degenerative disorders (PDDs) of the human central nervous system. Among them, astrocytes coordinate and participate in many different and complex metabolic processes, in close interaction with neurons. Moreover, increasing experimental evidence hints an early astrocytic dysfunction in these diseases. In this mini review we summarize the astrocytic behavior in PDDs, with special consideration to the experimental observations where astrocytic pathology precedes the development of neuronal dysfunction. We also suggest a different approach that could be consider in human investigations in Alzheimer's and Parkinson's disease. We believe that the study of PDDs with human brain samples may hold the key of a paradigmatic physiopathological process in which astrocytes might be the main players. PMID:26973519

  1. Genotoxicity test of self-renovated ceramics in primary human peripheral lymphocytes.

    PubMed

    Hua, Nan; Zhu, Huifang; Zhuang, Jing; Chen, Liping

    2014-12-01

    Zirconia-based ceramics is widely used in dentistry. Different compositions of ceramics have different features. Our self-renovated ceramics become more machinable without scarifying its dental restoration properties after adjusting ratio of lanthanum phosphate (LaPO4)/yttrium oxide (Y2O3). In order to evaluate its safety, here, we tested its genotoxicity in primary human peripheral lymphocytes. The human lymphocytes cultured on three groups of different ratios of LaPO4/Y2O3 diphase ceramics for 6 days showed little effect of growth inhibition and similar effect of growth trend to the negative control. Furthermore, single-cell gel electrophoresis (comet assay) indicated that there was no significant difference of the value of tail moment between the tested ceramics and negative control, the IPS Empress II (P > 0.05). Our findings implicate that our self-renovated ceramics do not induce DNA damages in human peripheral lymphocytes and support their future clinic application.

  2. Integrated modeling of natural and human systems - problems and initiatives

    NASA Astrophysics Data System (ADS)

    Kessler, H.; Giles, J.; Gunnink, J.; Hughes, A.; Moore, R. V.; Peach, D.

    2009-12-01

    Governments and their executive agencies across the world are facing increasing pressure to make decisions about the management of resources in light of population growth and environmental change. In the UK and the Netherlands, for example, groundwater is becoming a scarce resource for large parts of its most densely populated areas. At the same time river and groundwater flooding resulting from high rainfall events are increasing in scale and frequency and sea level rise is threatening the defences of coastal cities. There is also a need for affordable housing, improved transport infrastructure and waste disposal as well as sources of renewable energy and sustainable food production. These challenges can only be resolved if solutions are based on sound scientific evidence. Although we have knowledge and understanding of many individual processes in the natural sciences it is clear that a single science discipline is unable to answer the questions and their inter-relationships. Modern science increasingly employs computer models to simulate the natural, economic and human system. Management and planning requires scenario modelling, forecasts and “predictions”. Although the outputs are often impressive in terms of apparent accuracy and visualisation, they are inherently not suited to simulate the response to feedbacks from other models of the earth system, such as the impact of human actions. Geological Survey Organisations (GSO) are increasingly employing advances in Information Technology to visualise and improve their understanding of geological systems. Instead of 2 dimensional paper maps and reports many GSOs now produce 3 dimensional geological framework models and groundwater flow models as their standard output. Additionally the British Geological Survey and the Geological Survey of the Netherlands have developed standard routines to link geological data to groundwater models, but these models are only aimed at solving one specific part of the earth

  3. Natural environmental associations in a 50-day human electrocardiogram.

    PubMed

    Delyukov, A; Gorgo, Y; Cornélissen, G; Otsuka, K; Halberg, F

    2001-07-01

    Meteorotropic associations of heart rate (HR) and HR variability (HRV) were investigated in a clinically healthy 48-year-old man in Kiev. His electrocardiogram (ECG) was determined over 50 days by fitting him with an ambulatorily wearable device; various natural physical environmental variables were also monitored. The mean inter-beat interval, the standard deviation of these intervals, the spectral power in several frequency ranges, the power ratio of the approx. 10.5-s/approx. 3.6-s spectral components and other aspects of HRV were computed over consecutive 14.4-min intervals. Together with ordinary meteorological variables, geomagnetic disturbances (GMD) and fluctuations of atmospheric pressure (FAP) in the range 0.01-0.10 Hz (10-100 s) were measured. The assessable infradian spectra (with frequencies lower than 1 cycle/28 hours) of all HRV parameters showed two major components with periods of about 3.5 and 10 days. Two environmental variables, FAP and wind speed (with which FAP is closely related), revealed both of these rhythms and showed the greatest cross-spectral coherence (0.70-0.98) with corresponding oscillations of HRV. Less specific but statistically significant product-moment correlations with major HRV indices were also found; most of these were with FAP, but correlations with air temperature, humidity, wind speed and geomagnetic disturbances were also found. Long-term ECG recording, essential in the detection of infradian rhythms, proved to be sensitive to physical environmental variables, notably meteorological ones. FAP, usually neglected since its role has not been considered in previous biometeorological studies, or some factor closely related to FAP is probably involved in synchronizing or influencing the approximately 3.5-day HR and HRV rhythms in humans.

  4. The effects of IL-17 upon human natural killer cells.

    PubMed

    Al Omar, Suliman; Flanagan, Brian F; Almehmadi, Mazen; Christmas, Stephen E

    2013-04-01

    These experiments were designed to investigate the effects of IL-17 upon the phenotype and function of human Natural Killer (NK) cells. Peripheral blood mononuclear cells from healthy subjects were cultured in the presence or absence of different combinations of IL-17s and changes in relative numbers and cell surface phenotype of NK cells and CD56+CD3+ cells measured by flow cytometry. Real time PCR was used to measure changes in expression of the cytotoxicity-related genes perforin A and granzymes A and B and IL-17 receptors. A chromium release assay was used to measure cytotoxic function against K562 tumour cells. IL-17D, IL-17A, IL-17F or the combination of both of the latter had little effect upon NK cell surface expression of Killer Immunoglobulin-like Receptors, although IL-17A modestly increased NK cell numbers. Slight but not significant increases in expression of perforin and granzymes were induced by IL-17A and/or IL-17F. Both IL-17A and D significantly increased cytotoxic function of NK cells at some E:T ratios. Similarly, numbers of NK cells induced to express CD107a after interaction with K562 cells were increased, but not significantly, by all combinations of IL-17s tested. IL-17RC was not found at the NK cell surface but was expressed at the message level and the protein detected intracellularly. NK cells are known to produce IL-17 but here we report that there is little response to this cytokine although some isoforms may moderately enhance cytotoxic function. There may therefore be some enhancement of NK cell function resulting from Th17 cell activation.

  5. Characterizing primary human microglia: A comparative study with myeloid subsets and culture models.

    PubMed

    Melief, J; Sneeboer, M A M; Litjens, M; Ormel, P R; Palmen, S J M C; Huitinga, I; Kahn, R S; Hol, E M; de Witte, L D

    2016-11-01

    The biology of microglia has become subject to intense study, as they are widely recognized as crucial determinants of normal and pathologic brain functioning. While they are well studied in animal models, it is still strongly debated what specifies most accurately the phenotype and functioning of microglia in the human brain. In this study, we therefore isolated microglia from postmortem human brain tissue of corpus callosum (CC) and frontal cortex (CTX). The cells were phenotyped for a panel of typical microglia markers and genes involved in myeloid cell biology. Furthermore, their response to pro- and anti-inflammatory stimuli was assessed. The microglia were compared to key human myeloid cell subsets, including monocytes, monocyte-derived macrophages and monocyte-derived dendritic cells, and several commonly used microglial cell models. Protein and mRNA expression profiles partly differed between microglia isolated from CC and frontal cortex and were clearly distinct from other myeloid subsets. Microglia responded to both pro- (LPS or poly I:C) and anti-inflammatory (IL-4 or dexamethasone) stimuli. Interestingly, pro-inflammatory responses differed between microglia and monocyte-derived macrophages, as the former responded more strongly to poly I:C and the latter more strongly to LPS. Furthermore, we defined a large phenotypic discrepancy between primary human microglia and currently used microglial cell models and cell lines. In conclusion, we further delineated the unique and specific features that discriminate human microglia from other myeloid subsets, and we show that currently used cellular models only partly reflect the phenotype of primary human microglia. GLIA 2016;64:1857-1868.

  6. Bisphenol S Induces Adipogenesis in Primary Human Preadipocytes From Female Donors.

    PubMed

    Boucher, Jonathan G; Ahmed, Shaimaa; Atlas, Ella

    2016-04-01

    Human exposure to bisphenol A has been associated with negative health outcomes in humans and its use is now regulated in a number of countries. Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A; however, its effects on cellular metabolism and potential role as an endocrine disruptor have not been fully characterized. In the current study, we evaluated the effect of BPS on adipogenesis in primary human preadipocytes. The effect of BPS on the differentiation of human preadipocytes was determined after treatment with BPS at concentrations ranging from 0.1 nM to 25 μM by quantifying lipid accumulation and mRNA and protein levels of key adipogenic markers. Treatment of preadipocytes with 25 μM BPS induced lipid accumulation and increased the mRNA and protein levels of several adipogenic markers including lipoprotein lipase and adipocyte protein 2 (aP2). Cotreatment of cells with the estrogen receptor antagonist ICI-182,780 significantly inhibited BPS-induced lipid accumulation and affected aP2 but not lipoprotein lipase protein levels. Cotreatment of cells with the glucocorticoid receptor antagonist RU486 had no effect on BPS-induced lipid accumulation or protein levels. Furthermore, reporter gene assays using a synthetic promoter containing peroxisome proliferator-activated receptor-γ (PPARG)-response elements and a PPARG-responsive human aP2 promoter region showed that BPS was able to activate PPARG. To our knowledge, this study is the first to show that BPS induces lipid accumulation and differentiation of primary human preadipocytes, and this effect may be mediated through a PPARG pathway.

  7. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

    SciTech Connect

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R.; Subramaniam, Meena; Gate, Rachel E.; Haliburton, Genevieve E.; Ye, Chun J.; Bluestone, Jeffrey A.; Doudna, Jennifer A.; Marson, Alexander

    2015-07-27

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4+ T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.

  8. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins.

    PubMed

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R; Subramaniam, Meena; Gate, Rachel E; Haliburton, Genevieve E; Ye, Chun J; Bluestone, Jeffrey A; Doudna, Jennifer A; Marson, Alexander

    2015-08-18

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently "knock out" genes and "knock in" targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4(+) T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9 RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ∼40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ∼20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.

  9. Generation of knock-in primary human T cells using Cas9 ribonucleoproteins

    DOE PAGESBeta

    Schumann, Kathrin; Lin, Steven; Boyer, Eric; Simeonov, Dimitre R.; Subramaniam, Meena; Gate, Rachel E.; Haliburton, Genevieve E.; Ye, Chun J.; Bluestone, Jeffrey A.; Doudna, Jennifer A.; et al

    2015-07-27

    T-cell genome engineering holds great promise for cell-based therapies for cancer, HIV, primary immune deficiencies, and autoimmune diseases, but genetic manipulation of human T cells has been challenging. Improved tools are needed to efficiently “knock out” genes and “knock in” targeted genome modifications to modulate T-cell function and correct disease-associated mutations. CRISPR/Cas9 technology is facilitating genome engineering in many cell types, but in human T cells its efficiency has been limited and it has not yet proven useful for targeted nucleotide replacements. Here we report efficient genome engineering in human CD4+ T cells using Cas9:single-guide RNA ribonucleoproteins (Cas9 RNPs). Cas9more » RNPs allowed ablation of CXCR4, a coreceptor for HIV entry. Cas9 RNP electroporation caused up to ~40% of cells to lose high-level cell-surface expression of CXCR4, and edited cells could be enriched by sorting based on low CXCR4 expression. Importantly, Cas9 RNPs paired with homology-directed repair template oligonucleotides generated a high frequency of targeted genome modifications in primary T cells. Targeted nucleotide replacement was achieved in CXCR4 and PD-1 (PDCD1), a regulator of T-cell exhaustion that is a validated target for tumor immunotherapy. Deep sequencing of a target site confirmed that Cas9 RNPs generated knock-in genome modifications with up to ~20% efficiency, which accounted for up to approximately one-third of total editing events. These results establish Cas9 RNP technology for diverse experimental and therapeutic genome engineering applications in primary human T cells.« less

  10. Effects of ultraviolet radiation on the primary production of natural phytoplankton assemblages in Lake Michigan.

    PubMed

    Gala, W R; Giesy, J P

    1991-12-01

    Inhibition of primary production of offshore Lake Michigan phytoplankton assemblages by solar ultraviolet radiation (SUVR) was observed from April to October in 1986 during in situ incubations in special Plexiglas chambers. Inhibition of primary production by SUVR was observed to a depth of 6 m and at intensities which were approximately 1% of the UV-B intensity at the lake surface. Significant inhibition of primary production by SUVR was restricted to the top third of the euphotic zone. The order of relative sensitivities of offshore Lake Michigan phytoplankton assemblages during different seasons to inhibition by SUVR were spring ED50 = 17.6 kJ/m2 UV-B) greater than fall (ED50 = 30.5 kJ/m2 UV-B) greater than summer (ED50 = 131.6 kJ/m2 UV-B). A hazard assessment model predicted a significant reduction (13%) in areal (total water column) primary production for offshore Lake Michigan due to current SUVR intensities. Concern about possible increased reduction of primary production in the North American Great Lakes due to depletion of the stratospheric ozone layer appears to be unwarranted.

  11. Houttuynia cordata Thunb extract inhibits cell growth and induces apoptosis in human primary colorectal cancer cells.

    PubMed

    Lai, Kuang-Chi; Chiu, Yu-Jen; Tang, Yih-Jing; Lin, Kuei-Li; Chiang, Jo-Hua; Jiang, Yi-Lin; Jen, Hsiu-Fang; Kuo, Yueh-Hsiung; Agamaya, Sakae; Chung, Jing-Gung; Yang, Jai-Sing

    2010-09-01

    It is reported that Houttuynia cordata Thunb. (HCT), a traditional Chinese herbal medicine, has many biological properties such as antiviral, antibacterial and antileukemic activities. However, the molecular mechanisms of cytotoxicity and apoptosis in human primary colorectal cancer cells are not clear. In this study, whether HCT induced cytotoxicity in primary colorectal cancer cells obtained from three patients was investigated. The results indicated that HCT inhibited growth of cancer cells in a dose-dependent manner. After treatment with HCT (250 μg/ml) for 24 h, cells exhibited chromatin condensation (an apoptotic characteristic). HCT increased reactive oxygen species (ROS) production and decreased the mitochondrial membrane potential (ΔΨ(m)) in examined cells. Mitochondria-dependent apoptotic signaling pathway was shown to be involved as determined by increase in the levels of cytochrome c, Apaf-1, and caspase-3 and -9. The decrease in the level of ΔΨ(m) was associated with an increase in the BAX/BCL-2 ratio which led to activation of caspase-9 and -3. Based on our results, HCT induced apoptotic cell death in human primary colorectal cancer cells through a mitochondria-dependent signaling pathway. PMID:20944136

  12. Gene expression profiling of dengue infected human primary cells identifies secreted mediators in vivo

    PubMed Central

    Becerra, Aniuska; Warke, Rajas V.; Martin, Katherine; Xhaja, Kris; de Bosch, Norma; Rothman, Alan L.; Bosch, Irene

    2009-01-01

    We used gene expression profiling of human primary cells infected in vitro with dengue virus (DENV) as a tool to identify secreted mediators induced in response to the acute infection. Affymetrix Genechip analysis of human primary monocytes, B cells and dendritic cells infected with DENV in vitro revealed a strong induction of monocyte chemotactic protein 2 (MCP-2/CCL8), interferon gamma-induced protein 10 (IP-10/CXCL10) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/TNFSF10). The expression of these genes was confirmed in dendritic cells infected with DENV in vitro at mRNA and protein levels. A prospectively enrolled cohort of DENV-infected Venezuelan patients was used to measure the levels of these proteins in serum during three different periods of the disease. Results showed significant increase of MCP-2, IP-10 and TRAIL levels in DENV-infected patients during the febrile period, when compared to healthy donors and patients with other febrile illnesses. MCP-2 and IP-10 levels were still elevated during the post-febrile period while TRAIL levels dropped close to normal after defervescense. Patients with primary infections had higher TRAIL levels than patients with secondary infections during the febrile period of the disease. Increased levels of IP-10, TRAIL and MCP-2 in acute DENV infections suggest a role for these mediators in the immune response to the infection. PMID:19551822

  13. Mindsets and Human Nature: Promoting Change in the Middle East, the Schoolyard, the Racial Divide, and Willpower

    ERIC Educational Resources Information Center

    Dweck, Carol S.

    2012-01-01

    Debates about human nature often revolve around what is built in. However, the hallmark of human nature is how much of a person's identity is not built in; rather, it is humans' great capacity to adapt, change, and grow. This nature versus nurture debate matters--not only to students of human nature--but to everyone. It matters whether people…

  14. Activation of Notch1 signaling is required for β-catenin–mediated human primary melanoma progression

    PubMed Central

    Balint, Klara; Xiao, Min; Pinnix, Chelsea C.; Soma, Akinobu; Veres, Imre; Juhasz, Istvan; Brown, Eric J.; Capobianco, Anthony J.; Herlyn, Meenhard; Liu, Zhao-Jun

    2005-01-01

    Notch is a highly conserved transmembrane receptor that determines cell fate. Notch signaling denotes cleavage of the Notch intracellular domain, its translocation to the nucleus, and subsequent activation of target gene transcription. Involvement of Notch signaling in several cancers is well known, but its role in melanoma remains poorly characterized. Here we show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed whereas constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth both in vitro and in vivo yet had little effect on metastatic melanoma cells. Activation of Notch1 signaling enabled primary melanoma cells to gain metastatic capability. Furthermore, the oncogenic effect of Notch1 on primary melanoma cells was mediated by β-catenin, which was upregulated following Notch1 activation. Inhibiting β-catenin expression reversed Notch1-enhanced tumor growth and metastasis. Our data therefore suggest a β-catenin–dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma. PMID:16239965

  15. Primary bone natural killer/T cell lymphoma, nasal type without EBV infection: a case report

    PubMed Central

    Tian, Chen; Wang, Yafei; Zhu, Lei; Yu, Yong; Zhang, Yizhuo

    2015-01-01

    Primary bone NK/T cell lymphoma is very rare. We report a case of 52-year-old man of primary bone NK/T cell lymphoma and then progressed to NK leukemia. The patient had low-grade fever for 4-month, and Ultrasonic B revealed a diffuse hepatosplenomegaly without lymphadenopathy. PET scanning showed increased FDG uptake in many bones of the whole body. The diagnosis was established by bone specimen. These neoplastic cells demonstrated a typical immunophenotype of CD56, CD3, CD2 and MPO positive, and CD5, CD20, CD30, PAX-5, CD4 and CD8 negative. Primary bone ENKTL is very rare; it should be made with the combination of clinical feature, PET-CT image, and pathological characteristics, and should be distinguished from other lymphomas or leukemia involved in bone. PMID:26823813

  16. A species of human alpha interferon that lacks the ability to boost human natural killer activity.

    PubMed Central

    Ortaldo, J R; Herberman, R B; Harvey, C; Osheroff, P; Pan, Y C; Kelder, B; Pestka, S

    1984-01-01

    Most species of recombinant leukocyte interferons (IFN-alpha A, -alpha B, -alpha C, -alpha D, -alpha F, -alpha I, and -alpha K) were capable of boosting human natural killer (NK) activity after a 2-hr treatment of cells at a concentration of 1-80 units/ml. In contrast, recombinant human IFN-alpha J was found to be incapable of augmenting NK activity after exposure of cells for 2 hr to concentrations as high as 10,000 units/ml. This inability of IFN-alpha J to boost NK activity was not complete because, after exposure of cells to a high concentration of IFN-alpha J (10,000 units/ml) for 18 hr, boosting of cytolysis was observed. IFN-alpha J appeared to interact with receptors for IFN on NK cells since it was found to interfere with the boosting of NK activity by other species of IFN-alpha. In contrast to its deficient ability to augment NK activity, IFN-alpha J has potent antiviral and antiproliferative activities. Such extensive dissociation of these biological activities has not been observed previously with any other natural or recombinant IFN species. Thus, this IFN species may be useful for evaluating the relative importance of various biological activities on the therapeutic effects of IFN, for understanding structure-function relationships, and for determining the biochemical pathways related to the various biological effects of IFN. PMID:6589637

  17. Contrast-dependent OFF-dominance in cat primary visual cortex facilitates discrimination of stimuli with natural contrast statistics.

    PubMed

    Liu, Kefei; Yao, Haishan

    2014-06-01

    Both theoretical and experimental studies suggest that response properties in the visual system are shaped by signals in the natural environment. Recent studies showed that, in the primary visual cortex (V1), neurons preferring light decrements (OFF stimuli) outnumber those preferring light increments (ON stimuli). However, it is not clear whether the OFF-dominance in V1 neurons is related to the contrast statistics in natural images. By analysing the distribution of negative and positive contrasts in natural images at several spatial scales, we showed that optimal coding of the natural contrast signals would lead to a contrast-dependent OFF-dominant response, with a stronger degree of OFF-dominance at a higher contrast. Using bright and dark stimuli at various contrast levels to measure the receptive fields of neurons in cat V1, we found an increasing degree of OFF-dominance of the neuronal population as the contrast was increased. By modeling receptive fields exhibiting OFF- and ON-dominance, we found that contrast-dependent OFF-dominance facilitated the discrimination of stimuli with natural contrast distribution. Thus, by matching contrast-dependent OFF-dominance to the statistics of contrast distribution in natural images, V1 neurons may better discriminate contrast information in natural scenes.

  18. Primary chronic angle-closure glaucoma in Chinese--a clinical exploration of its pathogenesis and natural course.

    PubMed

    Sun, X; Ji, X; Zheng, Y; Guo, B

    1994-09-01

    Forty-three cases (86 eyes) of primary chronic angle-closure glaucoma were randomly selected. An additional 44 cases (77 eyes) of primary acute angle-closure glaucoma and 30 normal subjects (34 eyes) were also randomly enrolled as control groups for comparison in the clinical study. Ultrasonic biometric measurements of the anterior chamber depth, lens thickness and axial length of the eyeball were performed. Using an potic microgauge attached to the slit-lamp, the entrance of anterior chamber angle was also calculated. The clinical manifestations and the natural course, including the characteristic appearance of anterior chamber angle, the form of peripheral anterior synechia as well as the facility of outflow, were carefully investigated. There were significant differences in the biometric parameters of the anterior segment of eye among above three groups. The facts reveal that the anatomic features of eyeball, especially in the anterior segment differentiate from those of primary acute angle-closure glaucoma. Follow-up study for the early stage cases showed that topical administration of miotics and/or peripheral iridectomy can effectively prevent iris from forming peripheral anterior synechia and thus halt its development. The criteria of diagnosis and the principles of prevention and treatment at the early stage cases were presented. The pathogenesis was discussed. We emphasized that the progressive stage after intermittent attacks of primary acute angle-closure glaucoma should not be confused with primary chronic angle-closure glaucoma.

  19. Natural mutagenesis of human genomes by endogenous retrotransposons

    PubMed Central

    Iskow, Rebecca C.; McCabe, Michael T.; Mills, Ryan E.; Torene, Spencer; Pittard, W. Stephen; Neuwald, Andrew F.; Van Meir, Erwin G.; Vertino, Paula M.; Devine, Scott E.

    2010-01-01

    SUMMARY Two abundant classes of mobile elements, namely Alu and L1 elements, continue to generate new retrotransposon insertions in human genomes. Estimates suggest that these elements have generated millions of new germline insertions in individual human genomes worldwide. Unfortunately, current technologies are not capable of detecting most of these young insertions, and the true extent of germline mutagenesis by endogenous human retrotransposons has been difficult to examine. Here, we describe new technologies for detecting these young retrotransposon insertions and demonstrate that such insertions indeed are abundant in human populations. We also found that new somatic L1 insertions occur at high frequencies in human lung cancer genomes. Genome-wide analysis suggests that altered DNA methylation may be responsible for the high levels of L1 mobilization observed in these tumors. Our data indicate that transposon-mediated mutagenesis is extensive in human genomes, and is likely to have a major impact on human biology and diseases. PMID:20603005

  20. Two methods for establishing primary human endometrial stromal cells from hysterectomy specimens.

    PubMed

    Jividen, Kasey; Movassagh, Mercedeh Javanbakht; Jazaeri, Amir; Li, Hui

    2014-01-01

    Many efforts have been devoted to establish in vitro cell culture systems. These systems are designed to model a vast number of in vivo processes. Cell culture systems arising from human endometrial samples are no exception. Applications range from normal cyclic physiological processes to endometrial pathologies such as gynecological cancers, infectious diseases, and reproductive deficiencies. Here, we provide two methods for establishing primary endometrial stromal cells from surgically resected endometrial hysterectomy specimens. The first method is referred to as "the scraping method" and incorporates mechanical scraping using surgical or razor blades whereas the second method is termed "the trypsin method." This latter method uses the enzymatic activity of trypsin to promote the separation of cells and primary cell outgrowth. We illustrate step-by-step methodology through digital images and microscopy. We also provide examples for validating endometrial stromal cell lines via quantitative real time polymerase chain reactions (qPCR) and immunofluorescence (IF). PMID:24894444

  1. Hyperoside protects human primary melanocytes against H2O2-induced oxidative damage

    PubMed Central

    YANG, BIN; YANG, QIN; YANG, XIN; YAN, HONG-BO; LU, QI-PING

    2016-01-01

    Cuscutae semen has been shown to have beneficial effects in the treatment of vitiligo, recorded in the Chinese Pharmacopoeia, whereas the effects of its constituent compounds remains to be elucidated. Using a tetrazolium bromide assay, the present study found that hyperoside (0.5–200 µg/ml) significantly increased the viability of human melanocytes in a time- and dose-dependent manner. The present study used a cell model of hydrogen peroxide (H2O2)-induced oxidative damage to examine the effect of hyperoside on human primary melanocytes. The results demonstrated that hyperoside pretreatment for 2 h decreased cell apoptosis from 54.03±9.11 to 17.46±3.10% in the H2O2-injured melanocytes. The levels of oxidative stress in the mitochondrial membrane potential of the melanocytes increased following hyperoside pretreatment. The mRNA and protein levels of B-cell lymphoma-2/Bcl-2-associated X protein and caspase 3 were regulated by hyperoside, and phosphoinositide 3-kinase/AKT and mitogen-activated protein kinase signaling were also mediated by hyperoside. In conclusion, the results of the present study demonstrated that hyperoside protected the human primary melanocytes against oxidative damage. PMID:27082158

  2. Electrotransfection and lipofection show comparable efficiency for in vitro gene delivery of primary human myoblasts.

    PubMed

    Mars, Tomaz; Strazisar, Marusa; Mis, Katarina; Kotnik, Nejc; Pegan, Katarina; Lojk, Jasna; Grubic, Zoran; Pavlin, Mojca

    2015-04-01

    Transfection of primary human myoblasts offers the possibility to study mechanisms that are important for muscle regeneration and gene therapy of muscle disease. Cultured human myoblasts were selected here because muscle cells still proliferate at this developmental stage, which might have several advantages in gene therapy. Gene therapy is one of the most sought-after tools in modern medicine. Its progress is, however, limited due to the lack of suitable gene transfer techniques. To obtain better insight into the transfection potential of the presently used techniques, two non-viral transfection methods--lipofection and electroporation--were compared. The parameters that can influence transfection efficiency and cell viability were systematically approached and compared. Cultured myoblasts were transfected with the pEGFP-N1 plasmid either using Lipofectamine 2000 or with electroporation. Various combinations for the preparation of the lipoplexes and the electroporation media, and for the pulsing protocols, were tested and compared. Transfection efficiency and cell viability were inversely proportional for both approaches. The appropriate ratio of Lipofectamine and plasmid DNA provides optimal conditions for lipofection, while for electroporation, RPMI medium and a pulsing protocol using eight pulses of 2 ms at E = 0.8 kV/cm proved to be the optimal combination. The transfection efficiencies for the optimal lipofection and optimal electrotransfection protocols were similar (32 vs. 32.5%, respectively). Both of these methods are effective for transfection of primary human myoblasts; however, electroporation might be advantageous for in vivo application to skeletal muscle.

  3. Oxidative Stress Kills Human Primary Oligodendrocytes Via Neutral Sphingomyelinase: Implications for Multiple Sclerosis

    PubMed Central

    Jana, Arundhati

    2007-01-01

    Multiple sclerosis (MS) is the most common human demyelinating disease of the central nervous system where oxidative stress has been proposed to play an important role in oligodendroglial death. However, molecular mechanisms that couple oxidative stress to the loss of oligodendrocytes are poorly understood. This study underlines the importance of neutral sphingomyelinase–ceramide pathway in mediating oxidative stress-induced apoptosis and cell death of human primary oligodendrocytes. Various oxidative stress-inducing agents, such as, superoxide radical produced by hypoxanthine and xanthine oxidase, hydrogen peroxide, aminotriazole capable of inhibiting catalase and increasing intracellular level of H2O2, or reduced glutathione-depleting diamide induced the activation of neutral sphingomyelinase and the production of ceramide. It is interesting to note that antisense knockdown of neutral but not acidic sphingomyelinase ablated oxidative stress-induced apoptosis and cell death in human primary oligodendrocytes. This study identifies neutral but not acidic sphingomyelinase as a target for possible therapeutic intervention in MS. PMID:18040843

  4. Human prion protein-induced autophagy flux governs neuron cell damage in primary neuron cells

    PubMed Central

    Moon, Ji-Hong; Lee, Ju-Hee; Nazim, Uddin MD; Lee, You-Jin; Seol, Jae-Won; Eo, Seong-Kug; Lee, John-hwa; Park, Sang-Youel

    2016-01-01

    An unusual molecular structure of the prion protein, PrPsc is found only in mammals with transmissible prion diseases. Prion protein stands for either the infectious pathogen itself or a main component of it. Recent studies suggest that autophagy is one of the major functions that keep cells alive and has a protective effect against the neurodegeneration. In this study, we investigated that the effect of human prion protein on autophagy-lysosomal system of primary neuronal cells. The treatment of human prion protein induced primary neuron cell death and decreased both LC3-II and p62 protein amount indicating autophagy flux activation. Electron microscope pictures confirmed the autophagic flux activation in neuron cells treated with prion protein. Inhibition of autophagy flux using pharmacological and genetic tools prevented neuron cell death induced by human prion protein. Autophagy flux induced by prion protein is more activated in prpc expressing cells than in prpc silencing cells. These data demonstrated that prion protein-induced autophagy flux is involved in neuron cell death in prion disease and suggest that autophagy flux might play a critical role in neurodegenerative diseases including prion disease. PMID:27102156

  5. Molecular cloning, primary structure, and expression of the human platelet/erythroleukemia cell 12-lipoxygenase

    SciTech Connect

    Funk, C.D.; Furci, L.; FitzGerald, G.A. )

    1990-08-01

    The major pathway of arachidonic acid metabolism in human platelets proceeds via a 12-lipoxygenase enzyme; however, the biological role of the product of this reaction, 12-hydro(pero)xyeicosatetraenoic acid (12-H(P)ETE), is unknown. Using a combination of the polymerase chain reaction and conventional screening procedures, the authors have isolated cDNA clones encoding the human platelet/human erythroleukemia (HEL) cell 12-lipoxygenase. From the deduced primary structure, human platelet/HEL 12-lipoxygenase would encode a M{sub r} 75,000 protein consisting of 663 amino acids. The cDNA encoding the full-length protein (pCDNA-12lx) under the control of the cytomegalovirus promoter was expressed in simian COS-M6 cells. Intact cells and lysed-cell supernatants were able to synthesize 12-H(P)ETE from arachidonic acid, whereas no 12-H(P)ETE synthesis was detected in mock-transfected cells. A single 2.4-kilobase mRNA was detected in erythroleukemia cells but not in several other tissues and cell lines evaluated by Northern blot analysis. Comparison of the human platelet/HEL 12-lipoxygenase sequence with that of porcine leukocyte 12-lipoxygenase and human reticulocyte 15-lipoxygenase revealed 65% amino acid identity to both enzymes. By contrast, the leukocyte 12-lipoxygenase is 86% identical to human reticulocyte 15-lipoxygenase. Sequence data and previously demonstrated immunochemical and biochemical evidence support the existence of distinct 12-lipoxygenase isoforms. The availability of cDNA probes for human platelet/HEL cell 12-lipoxygenase should facilitate elucidation of the biological role of this pathway.

  6. [A brief history of the natural causes of human disease].

    PubMed

    Lips-Castro, Walter

    2015-01-01

    In the study of the causes of disease that have arisen during the development of humankind, one can distinguish three major perspectives: the natural, the supernatural, and the artificial. In this paper we distinguish the rational natural causes of disease from the irrational natural causes. Within the natural and rational causal approaches of disease, we can highlight the Egyptian theory of putrid intestinal materials called "wechdu", the humoral theory, the atomistic theory, the contagious theory, the cellular theory, the molecular (genetic) theory, and the ecogenetic theory. Regarding the irrational, esoteric, and mystic causal approaches to disease, we highlight the astrological, the alchemical, the iatrochemical, the iatromechanical, and others (irritability, solidism, brownism, and mesmerism).

  7. Bisphenol A and Bisphenol S Induce Distinct Transcriptional Profiles in Differentiating Human Primary Preadipocytes

    PubMed Central

    Boucher, Jonathan G.; Gagné, Rémi; Rowan-Carroll, Andrea; Boudreau, Adèle; Yauk, Carole L.; Atlas, Ella

    2016-01-01

    Bisphenol S (BPS) is increasingly used as a replacement plasticizer for bisphenol A (BPA) but its effects on human health have not been thoroughly examined. Recent evidence indicates that both BPA and BPS induce adipogenesis, although the mechanisms leading to this effect are unclear. In an effort to identify common and distinct mechanisms of action in inducing adipogenesis, transcriptional profiles of differentiating human preadipocytes exposed to BPA or BPS were compared. Human subcutaneous primary preadipocytes were differentiated in the presence of either 25 μM BPA or BPS for 2 and 4 days. Poly-A RNA-sequencing was used to identify differentially expressed genes (DEGs). Functional analysis of DEGs was undertaken in Ingenuity Pathway Analysis. BPA-treatment resulted in 472 and 176 DEGs on days 2 and 4, respectively, affecting pathways such as liver X receptor (LXR)/retinoid X receptor (RXR) activation, hepatic fibrosis and cholestasis. BPS-treatment resulted in 195 and 51 DEGs on days 2 and 4, respectively, revealing enrichment of genes associated with adipogenesis and lipid metabolism including the adipogenesis pathway and cholesterol biosynthesis. Interestingly, the transcription repressor N-CoR was identified as a negative upstream regulator in both BPA- and BPS-treated cells. This study presents the first comparison of BPA- and BPS-induced transcriptional profiles in human differentiating preadipocytes. While we previously showed that BPA and BPS both induce adipogenesis, the results from this study show that BPS affects adipose specific transcriptional changes earlier than BPA, and alters the expression of genes specifically related to adipogenesis and lipid metabolism. The findings provide insight into potential BPS and BPA-mediated mechanisms of action in inducing adipogenesis in human primary preadipocytes. PMID:27685785

  8. The Extent and Nature of Bullying among Primary and Secondary Schoolchildren.

    ERIC Educational Resources Information Center

    Borg, Mark G.

    1999-01-01

    A study of 6,282 primary and secondary students in Malta found that one in three were involved in bullying either as victim or perpetrator. Most bullying takes place on the playground and in the classroom. There were gender differences in the occurrence and types of bullying. (SK)

  9. The Nature of Institutional Heteronormativity in Primary Schools and Practice-Based Responses

    ERIC Educational Resources Information Center

    DePalma, Renee; Atkinson, Elizabeth

    2010-01-01

    Concern for school-based homophobia is increasing, yet there is a tendency to focus on individual incidents of homophobic bullying rather than the cultural and institutional factors supporting them. We analyse ways in which institutional heteronormativity operates in primary schools and report results from our research in UK schools that…

  10. Improving Classroom Instruction: Understanding the Developmental Nature of Analyzing Primary Sources

    ERIC Educational Resources Information Center

    Dutt-Doner, Karen M.; Cook-Cottone, Catherine; Allen, Susan

    2007-01-01

    Authentic and constructive learning experiences that include analysis of primary source documents are necessary elements of effective social studies teaching (Bailyn, 1994; Leinhardt, Stainton, & Virji, 1994; Wineburg & Wilson, 1991; Young & Leinhardt, 1998). This study examines the abilities of 70 fifth and seventh grade students to complete…

  11. Computational study of human head response to primary blast waves of five levels from three directions.

    PubMed

    Wang, Chenzhi; Pahk, Jae Bum; Balaban, Carey D; Miller, Mark C; Wood, Adam R; Vipperman, Jeffrey S

    2014-01-01

    Human exposure to blast waves without any fragment impacts can still result in primary blast-induced traumatic brain injury (bTBI). To investigate the mechanical response of human brain to primary blast waves and to identify the injury mechanisms of bTBI, a three-dimensional finite element head model consisting of the scalp, skull, cerebrospinal fluid, nasal cavity, and brain was developed from the imaging data set of a human female. The finite element head model was partially validated and was subjected to the blast waves of five blast intensities from the anterior, right lateral, and posterior directions at a stand-off distance of one meter from the detonation center. Simulation results show that the blast wave directly transmits into the head and causes a pressure wave propagating through the brain tissue. Intracranial pressure (ICP) is predicted to have the highest magnitude from a posterior blast wave in comparison with a blast wave from any of the other two directions with same blast intensity. The brain model predicts higher positive pressure at the site proximal to blast wave than that at the distal site. The intracranial pressure wave invariably travels into the posterior fossa and vertebral column, causing high pressures in these regions. The severities of cerebral contusions at different cerebral locations are estimated using an ICP based injury criterion. Von Mises stress prevails in the cortex with a much higher magnitude than in the internal parenchyma. According to an axonal injury criterion based on von Mises stress, axonal injury is not predicted to be a cause of primary brain injury from blasts. PMID:25409326

  12. A transcriptional sketch of a primary human breast cancer by 454 deep sequencing

    PubMed Central

    Guffanti, Alessandro; Iacono, Michele; Pelucchi, Paride; Kim, Namshin; Soldà, Giulia; Croft, Larry J; Taft, Ryan J; Rizzi, Ermanno; Askarian-Amiri, Marjan; Bonnal, Raoul J; Callari, Maurizio; Mignone, Flavio; Pesole, Graziano; Bertalot, Giovanni; Bernardi, Luigi Rossi; Albertini, Alberto; Lee, Christopher; Mattick, John S; Zucchi, Ileana; De Bellis, Gianluca

    2009-01-01

    Background The cancer transcriptome is difficult to explore due to the heterogeneity of quantitative and qualitative changes in gene expression linked to the disease status. An increasing number of "unconventional" transcripts, such as novel isoforms, non-coding RNAs, somatic gene fusions and deletions have been associated with the tumoral state. Massively parallel sequencing techniques provide a framework for exploring the transcriptional complexity inherent to cancer with a limited laboratory and financial effort. We developed a deep sequencing and bioinformatics analysis protocol to investigate the molecular composition of a breast cancer poly(A)+ transcriptome. This method utilizes a cDNA library normalization step to diminish the representation of highly expressed transcripts and biology-oriented bioinformatic analyses to facilitate detection of rare and novel transcripts. Results We analyzed over 132,000 Roche 454 high-confidence deep sequencing reads from a primary human lobular breast cancer tissue specimen, and detected a range of unusual transcriptional events that were subsequently validated by RT-PCR in additional eight primary human breast cancer samples. We identified and validated one deletion, two novel ncRNAs (one intergenic and one intragenic), ten previously unknown or rare transcript isoforms and a novel gene fusion specific to a single primary tissue sample. We also explored the non-protein-coding portion of the breast cancer transcriptome, identifying thousands of novel non-coding transcripts and more than three hundred reads corresponding to the non-coding RNA MALAT1, which is highly expressed in many human carcinomas. Conclusion Our results demonstrate that combining 454 deep sequencing with a normalization step and careful bioinformatic analysis facilitates the discovery and quantification of rare transcripts or ncRNAs, and can be used as a qualitative tool to characterize transcriptome complexity, revealing many hitherto unknown

  13. Computational study of human head response to primary blast waves of five levels from three directions.

    PubMed

    Wang, Chenzhi; Pahk, Jae Bum; Balaban, Carey D; Miller, Mark C; Wood, Adam R; Vipperman, Jeffrey S

    2014-01-01

    Human exposure to blast waves without any fragment impacts can still result in primary blast-induced traumatic brain injury (bTBI). To investigate the mechanical response of human brain to primary blast waves and to identify the injury mechanisms of bTBI, a three-dimensional finite element head model consisting of the scalp, skull, cerebrospinal fluid, nasal cavity, and brain was developed from the imaging data set of a human female. The finite element head model was partially validated and was subjected to the blast waves of five blast intensities from the anterior, right lateral, and posterior directions at a stand-off distance of one meter from the detonation center. Simulation results show that the blast wave directly transmits into the head and causes a pressure wave propagating through the brain tissue. Intracranial pressure (ICP) is predicted to have the highest magnitude from a posterior blast wave in comparison with a blast wave from any of the other two directions with same blast intensity. The brain model predicts higher positive pressure at the site proximal to blast wave than that at the distal site. The intracranial pressure wave invariably travels into the posterior fossa and vertebral column, causing high pressures in these regions. The severities of cerebral contusions at different cerebral locations are estimated using an ICP based injury criterion. Von Mises stress prevails in the cortex with a much higher magnitude than in the internal parenchyma. According to an axonal injury criterion based on von Mises stress, axonal injury is not predicted to be a cause of primary brain injury from blasts.

  14. Computational Study of Human Head Response to Primary Blast Waves of Five Levels from Three Directions

    PubMed Central

    Wang, Chenzhi; Pahk, Jae Bum; Balaban, Carey D.; Miller, Mark C.; Wood, Adam R.; Vipperman, Jeffrey S.

    2014-01-01

    Human exposure to blast waves without any fragment impacts can still result in primary blast-induced traumatic brain injury (bTBI). To investigate the mechanical response of human brain to primary blast waves and to identify the injury mechanisms of bTBI, a three-dimensional finite element head model consisting of the scalp, skull, cerebrospinal fluid, nasal cavity, and brain was developed from the imaging data set of a human female. The finite element head model was partially validated and was subjected to the blast waves of five blast intensities from the anterior, right lateral, and posterior directions at a stand-off distance of one meter from the detonation center. Simulation results show that the blast wave directly transmits into the head and causes a pressure wave propagating through the brain tissue. Intracranial pressure (ICP) is predicted to have the highest magnitude from a posterior blast wave in comparison with a blast wave from any of the other two directions with same blast intensity. The brain model predicts higher positive pressure at the site proximal to blast wave than that at the distal site. The intracranial pressure wave invariably travels into the posterior fossa and vertebral column, causing high pressures in these regions. The severities of cerebral contusions at different cerebral locations are estimated using an ICP based injury criterion. Von Mises stress prevails in the cortex with a much higher magnitude than in the internal parenchyma. According to an axonal injury criterion based on von Mises stress, axonal injury is not predicted to be a cause of primary brain injury from blasts. PMID:25409326

  15. Use of primary high-risk human papillomavirus testing for cervical cancer screening: interim clinical guidance.

    PubMed

    Huh, Warner K; Ault, Kevin A; Chelmow, David; Davey, Diane D; Goulart, Robert A; Garcia, Francisco A R; Kinney, Walter K; Massad, L Stewart; Mayeaux, Edward J; Saslow, Debbie; Schiffman, Mark; Wentzensen, Nicolas; Lawson, Herschel W; Einstein, Mark H

    2015-02-01

    In 2011, the American Cancer Society, the American Society for Colposcopy and Cervical Pathology, and the American Society for Clinical Pathology updated screening guidelines for the early detection of cervical cancer and its precursors. Recommended screening strategies were cytology or cotesting (cytology in combination with high-risk human papillomavirus [hrHPV] testing). These guidelines also addressed the use of hrHPV testing alone as a primary screening approach, which was not recommended for use at that time. There is now a growing body of evidence for screening with primary hrHPV testing, including a prospective U.S.-based registration study. Thirteen experts, including representatives from the Society of Gynecologic Oncology, the American Society for Colposcopy and Cervical Pathology, the American College of Obstetricians and Gynecologists, the American Cancer Society, the American Society of Cytopathology, the College of American Pathologists, and the American Society for Clinical Pathology, convened to provide interim guidance for primary hrHPV screening. This guidance panel was specifically triggered by an application to the U.S. Food and Drug Administration (FDA) for a currently marketed HPV test to be labeled for the additional indication of primary cervical cancer screening. Guidance was based on literature review and review of data from the FDA registration study, supplemented by expert opinion. This document aims to provide information for health care providers who are interested in primary hrHPV testing and an overview of the potential advantages and disadvantages of this strategy for screening as well as to highlight areas in need of further investigation.

  16. Natural Disasters and Human Behavior: Explanation, Research and Models.

    ERIC Educational Resources Information Center

    Glenn, Christopher

    1979-01-01

    A survey of published research determined that individual and group reactions to natural disasters differ greatly and depend partially on the predisaster personality. Four models are examined to explain individual and group reactions to natural disasters. A conglomerate model and a possible structure to future disaster research are offered.…

  17. Counselors', Psychologists', and Homosexuals' Philosophies of Human Nature and Attitudes Toward Homosexual Behavior

    ERIC Educational Resources Information Center

    May, Eugene P.

    1974-01-01

    Using the Philosophies of Human Nature Scale (PHN), counselors, psychologists, and homosexuals were studied to determine their beliefs about human nature and homosexuals. The results suggest that counselors were significantly stronger than homosexuals and psychologists in the belief that people control their own outcomes. (Author/BW)

  18. A Philosophy of Man and Woman: Paul Goodman's Theory of Human Nature.

    ERIC Educational Resources Information Center

    Schwartz, Nadine Shanler

    Paul Goodman's criticisms of and proposals for institutions, including educational institutions, have as their foundation 1) a set of leading principles derived from experience and centered in a transactional view of experiences and 2) a concept of "self" which constitutes a theory of human nature. Human nature is viewed as process: tendencies or…

  19. Essentialism Regarding Human Nature in the Defence of Gender Equality in Education

    ERIC Educational Resources Information Center

    Holma, Katariina

    2007-01-01

    In this article I consider contemporary philosophical conceptions of human nature from the point of view of the ideal of gender equality. My main argument is that an essentialist account of human nature, unlike what I take to be its two main alternatives (the subjectivist account and the cultural account), is able coherently to justify the…

  20. Rabbit muscle creatine phosphokinase. CDNA cloning, primary structure and detection of human homologues.

    PubMed

    Putney, S; Herlihy, W; Royal, N; Pang, H; Aposhian, H V; Pickering, L; Belagaje, R; Biemann, K; Page, D; Kuby, S

    1984-12-10

    A cDNA library was constructed from rabbit muscle poly(A) RNA. Limited amino acid sequence information was obtained on rabbit muscle creatine phosphokinase and this was the basis for design and synthesis of two oligonucleotide probes complementary to a creatine kinase cDNA sequence which encodes a pentapeptide. Colony hybridizations with the probes and subsequent steps led to isolation of two clones, whose cDNA segments partially overlap and which together encode the entire protein. The primary structure was established from the sequence of two cDNA clones and from independently determined sequences of scattered portions of the polypeptide. The reactive cysteine has been located to position 282 within the 380 amino acid polypeptide. The rabbit cDNA hybridizes to digests of human chromosomal DNA. This reveals a restriction fragment length polymorphism associated with the human homologue(s) which hybridizes to the rabbit cDNA.

  1. Complexity of the primary genetic response to mitogenic activation of human T cells

    SciTech Connect

    Zipfel, P.F.; Siebenlist, U. ); Irving, S.G.; Kelly, K. )

    1989-03-01

    The authors describe the isolation and characterization of more than 60 novel cDNA clones that constitute part of the immediate genetic response to resting human peripheral blood T cells after mitogen activation. This primary response was highly complex, both in the absolute number of inducible genes and in the diversity of regulation. Although most of the genes expressed in activated T cells were shared with the activation response of normal human fibroblasts, a significant number were more restricted in tissue specificity and thus likely encode or effect the differentiated functions of activated T cells. The activatable genes could be further differentiated on the basis of kinetics of induction, response to cycloheximide, and sensitivity to the immunosuppressive drug cylcosporin A. It is of note that cyclosporin A inhibited the expression of more than 10 inducible genes, which suggests that this drug has a broad genetic mechanism of action.

  2. The Nature of Naming Errors in Primary Progressive Aphasia Versus Acute Post-Stroke Aphasia

    PubMed Central

    Budd, Maggi A.; Kortte, Kathleen; Cloutman, Lauren; Newhart, Melissa; Gottesman, Rebecca F.; Davis, Cameron; Heidler-Gary, Jennifer; Seay, Margaret W.; Hillis, Argye E.

    2011-01-01

    Objective To compare the distribution of error types across subgroups of primary progressive aphasia and poststroke aphasia in different vascular locations. Method We analyzed naming errors in 49 individuals with acute left hemisphere ischemic stroke and 55 individuals with three variants of primary progressive aphasia. Location of atrophy or ischemic stroke was characterized using MRI. Results We found that distribution of error types was very similar across all subgroups, irrespective of the site or etiology of the lesion. The only significant difference across groups was the percentage of circumlocutions (F(7, 96) = 3.02, p = .005). Circumlocution errors were highest among logopenic variant PPA (24%) and semantic variant PPA (24%). Semantic coordinate errors were common in all groups, probably because they can arise from disruption of different cognitive processes underlying naming and, therefore, from different locations of brain damage. Conclusions Semantic errors are common among all types of primary progressive aphasia and poststroke aphasia, and the type of error depends in part on the location of damage. PMID:20804246

  3. Occupancy rates of primary burrowing crayfish in natural and disturbed large river bottomlands

    USGS Publications Warehouse

    Loughman, Zachary J.; Welsh, Stuart; Simon, Thomas P.

    2012-01-01

    Among crayfish, primary burrowing species are the least understood ecologically. Many primary burrowing crayfish inhabit floodplains where forested landscapes have been fragmented by agricultural, industrial, or residential uses. In this study, site occupancy rates (ψ) were modeled for two primary burrowing crayfish, Fallicambarus fodiens (Cottle, 1863) and Cambarus thomai Jezerinac, 1993, from Ohio and Kanawha river floodplains in West Virginia, U.S.A. Fallicambarus fodiens is one of West Virginia’s rarest crayfish, while C. thomai is prevalent in most wetlands along both river floodplains. Occupancy rate modeling incorporated four environmental covariates (forest age, soil type, tree frequency, and land use). Based on presence/absence data, forests with tree ages >100 years (ΔQAICc = 0) and sites with loam soils (ΔQAICc = 1.80) were most likely to harbor F. fodiens populations. For C. thomai, several models were supported owing to model selection uncertainty, but those with the land use covariate had more total model weight (total w i = 0 . 54 ) than all other covariate models. Cambarus thomai rarely occupied industrial/agricultural sites, but were often present in forested and residential sites. Although the influence of covariates on site occupancy differed between species, both taxa readily utilized mature forested habitats when available. Conservation actions for F. fodiens and C. thomai should focus on preserving forested tracts along large river floodplains

  4. Landmarks in the Literature: Two Views of Human Nature.

    ERIC Educational Resources Information Center

    Bordin, Edward S.

    1981-01-01

    The author contrasts the psychological theories of Carl Rogers and B. F. Skinner as developed in their books, "Client-Centered Therapy" and "Science and Human Behavior," published in the early 1950s. He traces the continuing impact of these two theories on psychology, education, and the debate between humanism and science. (SJL)

  5. Viral symbiosis and the holobiontic nature of the human genome.

    PubMed

    Ryan, Francis Patrick

    2016-01-01

    The human genome is a holobiontic union of the mammalian nuclear genome, the mitochondrial genome and large numbers of endogenized retroviral genomes. This article defines and explores this symbiogenetic pattern of evolution, looking at the implications for human genetics, epigenetics, embryogenesis, physiology and the pathogenesis of inborn errors of metabolism and many other diseases.

  6. Neurotoxic potential and cellular uptake of T-2 toxin in human astrocytes in primary culture.

    PubMed

    Weidner, Maria; Lenczyk, Marlies; Schwerdt, Gerald; Gekle, Michael; Humpf, Hans-Ulrich

    2013-03-18

    The trichothecene mycotoxin T-2 toxin, which is produced by fungi of the Fusarium species, is a worldwide occurring contaminant of cereal based food and feed. The cytotoxic properties of T-2 toxin are already well described with apoptosis being a major mechanism of action in various cell lines as well as in primary cells of different origin. However, only few data on neurotoxic properties of T-2 toxin are reported so far, but in vivo studies showed different effects of T-2 toxin on behavior as well as on levels of brain amines in animals. To further investigate the cytotoxic properties of T-2 toxin on cells derived from brain tissue, normal human astrocytes in primary culture (NHA) were used in this study. Besides studies of cytotoxicity, apoptosis (caspase-3-activation, Annexin V) and necrosis (LDH-release), the cellular uptake and metabolism of T-2 toxin in NHA was analyzed and compared to the uptake in an established human cell line (HT-29). The results show that human astrocytes were highly sensitive to the cytotoxic properties of T-2 toxin, and apoptosis, induced at low concentrations, was identified for the first time as the mechanism of toxic action in NHA. Furthermore, a strong accumulation of T-2 toxin in NHA and HT-29 cells was detected, and T-2 toxin was subjected to metabolism leading to HT-2 toxin, a commonly found metabolite after T-2 toxin incubation in both cell types. This formation seems to occur within the cells since incubations of T-2 toxin with cell depleted culture medium did not lead to any degradation of the parent toxin. The results of this study emphasize the neurotoxic potential of T-2 toxin in human astrocytes at low concentrations after short incubation times. PMID:23363530

  7. 1,25 Dihydroxyvitamin D3 Inhibits TGFβ1-Mediated Primary Human Cardiac Myofibroblast Activation

    PubMed Central

    Meredith, Anna; Boroomand, Seti; Carthy, Jon; Luo, Zongshu; McManus, Bruce

    2015-01-01

    Aims Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D3) and cardiac fibrosis in human myocardial samples. Methods and Results Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)2D3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)2D3 treatment significantly inhibited TGFβ1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation. Conclusions Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis. PMID:26061181

  8. Isolation and genetic characterization of human coronavirus NL63 in primary human renal proximal tubular epithelial cells obtained from a commercial supplier, and confirmation of its replication in two different types of human primary kidney cells

    PubMed Central

    2013-01-01

    Background Cryopreserved primary human renal proximal tubule epithelial cells (RPTEC) were obtained from a commercial supplier for studies of Simian virus 40 (SV40). Within twelve hrs after cell cultures were initiated, cytoplasmic vacuoles appeared in many of the RPTEC. The RPTEC henceforth deteriorated rapidly. Since SV40 induces the formation of cytoplasmic vacuoles, this batch of RPTEC was rejected for the SV40 study. Nevertheless, we sought the likely cause(s) of the deterioration of the RPTEC as part of our technology development efforts. Methods Adventitious viruses in the RPTEC were isolated and/or detected and identified by isolation in various indicator cell lines, observation of cytopathology, an immunoflurorescence assay, electron microscopy, PCR, and sequencing. Results Cytomegalovirus (CMV) was detected in some RPTEC by cytology, an immunofluorescence assay, and PCR. Human Herpesvirus 6B was detected by PCR of DNA extracted from the RPTEC, but was not isolated. Human coronavirus NL63 was isolated and identified by RT-PCR and sequencing, and its replication in a fresh batch of RPTEC and another type of primary human kidney cells was confirmed. Conclusions At least 3 different adventitious viruses were present in the batch of contaminated RPTEC. Whereas we are unable to determine whether the original RPTEC were pre-infected prior to their separation from other kidney cells, or had gotten contaminated with HCoV-NL63 from an ill laboratory worker during their preparation for commercial sale, our findings are a reminder that human-derived biologicals should always be considered as potential sources of infectious agents. Importantly, HCoV-NL63 replicates to high titers in some primary human kidney cells. PMID:23805916

  9. Efficient Modification of the CCR5 Locus in Primary Human T Cells With megaTAL Nuclease Establishes HIV-1 Resistance

    PubMed Central

    Romano Ibarra, Guillermo S; Paul, Biswajit; Sather, Blythe D; Younan, Patrick M; Sommer, Karen; Kowalski, John P; Hale, Malika; Stoddard, Barry; Jarjour, Jordan; Astrakhan, Alexander; Kiem, Hans-Peter; Rawlings, David J

    2016-01-01

    A naturally occurring 32-base pair deletion of the HIV-1 co-receptor CCR5 has demonstrated protection against HIV infection of human CD4+ T cells. Recent genetic engineering approaches using engineered nucleases to disrupt the gene and mimic this mutation show promise for HIV therapy. We developed a megaTAL nuclease targeting the third extracellular loop of CCR5 that we delivered to primary human T cells by mRNA transfection. The CCR5 megaTAL nuclease established resistance to HIV in cell lines and disrupted the expression of CCR5 on primary human CD4+ T cells with a high efficiency, achieving up to 80% modification of the locus in primary cells as measured by molecular analysis. Gene-modified cells engrafted at levels equivalent to unmodified cells when transplanted into immunodeficient mice. Furthermore, genetically modified CD4+ cells were preferentially expanded during HIV-1 infection in vivo in an immunodeficient mouse model. Our results demonstrate the feasibility of targeting CCR5 in primary T cells using an engineered megaTAL nuclease, and the potential to use gene-modified cells to reconstitute a patient's immune system and provide protection from HIV infection.

  10. Efficient Modification of the CCR5 Locus in Primary Human T Cells With megaTAL Nuclease Establishes HIV-1 Resistance

    PubMed Central

    Romano Ibarra, Guillermo S; Paul, Biswajit; Sather, Blythe D; Younan, Patrick M; Sommer, Karen; Kowalski, John P; Hale, Malika; Stoddard, Barry; Jarjour, Jordan; Astrakhan, Alexander; Kiem, Hans-Peter; Rawlings, David J

    2016-01-01

    A naturally occurring 32-base pair deletion of the HIV-1 co-receptor CCR5 has demonstrated protection against HIV infection of human CD4+ T cells. Recent genetic engineering approaches using engineered nucleases to disrupt the gene and mimic this mutation show promise for HIV therapy. We developed a megaTAL nuclease targeting the third extracellular loop of CCR5 that we delivered to primary human T cells by mRNA transfection. The CCR5 megaTAL nuclease established resistance to HIV in cell lines and disrupted the expression of CCR5 on primary human CD4+ T cells with a high efficiency, achieving up to 80% modification of the locus in primary cells as measured by molecular analysis. Gene-modified cells engrafted at levels equivalent to unmodified cells when transplanted into immunodeficient mice. Furthermore, genetically modified CD4+ cells were preferentially expanded during HIV-1 infection in vivo in an immunodeficient mouse model. Our results demonstrate the feasibility of targeting CCR5 in primary T cells using an engineered megaTAL nuclease, and the potential to use gene-modified cells to reconstitute a patient's immune system and provide protection from HIV infection. PMID:27741222

  11. Four basic levels of the interactions between humanity and the imbalanced Nature

    NASA Astrophysics Data System (ADS)

    Kontar, V. A.

    2013-12-01

    There are the clearly distinguishable four basic levels of interaction the humanity with the imbalanced Nature: 1 Level - Naivety: Self-healing Nature in defiance of the humanity activities. 2 Level - Collaboration: Restoration of Nature in cooperation with humanity. 3 Level - Conflict: The resistance of Nature against the humanity's interference. 4 Level - Disappearance: Nature destroys humanity as the trouble maker. On the first level the people were afraid and respected Nature and are taking from Nature only what Nature gave willingly. Therefore Nature could easy regenerate itself. So it was thousands of years and people become under the false impression that it will be forever. The first signs the end of this period was visible in the era of industrialization. It turned out that resources are not infinite, and the waste of humanity grows much faster than Nature can utilize or dispose it. But in the world still had plenty of the untouched places and industrialization continued to develop rapidly. Thus problems with Nature were dislocated into the colonies rather far off from the prosperous metropolitan countries. The false impression about the man's victory over Nature has increased. Very soon the main untouched place was used, and the global circulations bring the pollutions from colonies to the metropolis. The second level was started as processes to creating the national parks, natural reservations, etc. It was some beginning of the cooperation humanity with Nature. The invasion into the Nature of the colonies was intensified. In addition start increasing the pollution in the metropolis from the waste of resources which have been imported from the colonies. The third level was started and Nature began to resist and revenge to the self-confident man. But man didn't stop and continued create more and more aggressive processes which provoked some avalanches-looks reactions of Nature. Now people can start these avalanches, but cannot stop it. One of these man

  12. Microstructured zirconia surfaces modulate osteogenic marker genes in human primary osteoblasts.

    PubMed

    Bergemann, Claudia; Duske, Kathrin; Nebe, J Barbara; Schöne, André; Bulnheim, Ulrike; Seitz, Hermann; Fischer, Jens

    2015-01-01

    In dentistry, zirconia has been used since the early 1990s for endodontic posts, more recently for implant abutments and frameworks for fixed dental prostheses. Zirconia is biocompatible and mechanically strong enough to serve as implant material for oral implants. Although several zirconia implant systems are available, currently the scientific and clinical data for zirconia implants are not sufficient to recommend them for routine clinical use. Here the influence of microstructured yttria-stabilized zirconia (YZ) on human primary osteoblast (HOB) behavior was determined. YZ surfaces were treated by sandblasting (YZ-S), acid etching (YZ-SE) and additionally heat treatment (YZ-SEH). Morphological changes of HOB were determined by scanning electron microscopy. Actin cytoskeleton was investigated by laser scanning microscopy and analyzed by novel actin quantification software. Differentiation of HOB was determined by real time RT-PCR. Improved mechanical interlocking of primary HOB into the porous microstructure of the acid etched and additionally heat treated YZ-surfaces correlates with drastically increased osteocalcin (OCN) gene expression. In particular, OCN was considerably elevated in primary HOB after 3 days on YZ-SE (13-fold) as well as YZ-SEH (12-fold) surfaces. Shorter actin filaments without any favored orientation on YZ-SE and YZ-SEH surfaces are associated with higher roughness (Ra) values. Topographically modified yttria-stabilized zirconia is a likely material for dental implants with cell stimulating properties achieving or actually exceeding those of titanium. PMID:25578704

  13. Phenotypic differentiation does not affect tumorigenicity of primary human colon cancer initiating cells.

    PubMed

    Dubash, Taronish D; Hoffmann, Christopher M; Oppel, Felix; Giessler, Klara M; Weber, Sarah; Dieter, Sebastian M; Hüllein, Jennifer; Zenz, Thorsten; Herbst, Friederike; Scholl, Claudia; Weichert, Wilko; Werft, Wiebke; Benner, Axel; Schmidt, Manfred; Schneider, Martin; Glimm, Hanno; Ball, Claudia R

    2016-02-28

    Within primary colorectal cancer (CRC) a subfraction of all tumor-initiating cells (TIC) drives long-term progression in serial xenotransplantation. It has been postulated that efficient maintenance of TIC activity in vitro requires serum-free spheroid culture conditions that support a stem-like state of CRC cells. To address whether tumorigenicity is indeed tightly linked to such a stem-like state in spheroids, we transferred TIC-enriched spheroid cultures to serum-containing adherent conditions that should favor their differentiation. Under these conditions, primary CRC cells did no longer grow as spheroids but formed an adherent cell layer, up-regulated colon epithelial differentiation markers, and down-regulated TIC-associated markers. Strikingly, upon xenotransplantation cells cultured under either condition equally efficient formed serially transplantable tumors. Clonal analyses of individual lentivirally marked TIC clones cultured under either culture condition revealed no systematic differences in contributing clone numbers, indicating that phenotypic differentiation does not select for few individual clones adapted to unfavorable culture conditions. Our results reveal that CRC TIC can be propagated under conditions previously thought to induce their elimination. This phenotypic plasticity allows addressing primary human CRC TIC properties in experimental settings based on adherent cell growth.

  14. Biomimetics: using nature as an inspiring model for human innovation

    NASA Technical Reports Server (NTRS)

    Bar-Cohen, Yoseph

    2006-01-01

    The evolution of nature over 3.8 billion years led to the highly effective and power efficient biological mechanisms. Imitating these mechanisms offers enormous potentials for the improvement of our life and the tools we use.

  15. [A brief history of the natural causes of human disease].

    PubMed

    Lips-Castro, Walter

    2015-01-01

    In the study of the causes of disease that have arisen during the development of humankind, one can distinguish three major perspectives: the natural, the supernatural, and the artificial. In this paper we distinguish the rational natural causes of disease from the irrational natural causes. Within the natural and rational causal approaches of disease, we can highlight the Egyptian theory of putrid intestinal materials called "wechdu", the humoral theory, the atomistic theory, the contagious theory, the cellular theory, the molecular (genetic) theory, and the ecogenetic theory. Regarding the irrational, esoteric, and mystic causal approaches to disease, we highlight the astrological, the alchemical, the iatrochemical, the iatromechanical, and others (irritability, solidism, brownism, and mesmerism). PMID:26581540

  16. Global Human Appropriation of Net Primary Production for Biomass Consumption in the European Union, 1986–2007

    PubMed Central

    Erb, Karl‐Heinz; Haberl, Helmut

    2015-01-01

    Summary The ongoing globalization process strengthens the connections between different geographic regions through trade. Biomass products, such as food, fiber, or bioenergy, are increasingly traded globally, thereby leading to telecouplings between distant, seemingly unrelated regions. For example, restrictions for agricultural production or changes in bioenergy demand in Europe or the United States might contribute to deforestation in Latin America or Sub‐Saharan Africa. One approach to analyze trade‐related land‐use effects of the global socioeconomic biomass metabolism is the “embodied human appropriation of net primary production” or eHANPP. eHANPP accounts allocate to any product the entire amount of the human appropriation of net primary production (HANPP) that emerges throughout its supply chain. This allows consumption‐based accounts to move beyond simple area‐demand approaches by taking differences in natural productivity as well as in land‐use intensity into account, both across land‐use types as well as across world regions. In this article, we discuss the eHANPP related to the European Union's (EU) consumption of biomass products in the period 1986–2007, based on a consistent global trade data set derived from bilateral data. We find a considerable dependency of the EU on the appropriation of biological productivity outside its own boundaries, with increasing reliance on Latin America as a main supplier. By using the EU as an illustrative example, we demonstrate the usefulness of eHANPP for assessing land‐use impacts caused by nations’ socioeconomic activities and conclude that the eHANPP approach can provide useful information to better manage ecosystems globally in the face of an increasingly interconnected world. PMID:27524879

  17. Origin and primary dispersal of the Mycobacterium tuberculosis Beijing genotype: Clues from human phylogeography

    PubMed Central

    Mokrousov, Igor; Ly, Ho Minh; Otten, Tatiana; Lan, Nguyen Ngoc; Vyshnevskyi, Boris; Hoffner, Sven; Narvskaya, Olga

    2005-01-01

    We suggest that the evolution of the population structure of microbial pathogens is influenced by that of modern humans. Consequently, the timing of hallmark changes in bacterial genomes within the last 100,000 yr may be attempted by comparison with relevant human migrations. Here, we used a lineage within Mycobacterium tuberculosis, a Beijing genotype, as a model and compared its phylogeography with human demography and Y chromosome-based phylogeography. We hypothesize that two key events shaped the early history of the Beijing genotype: (1) its Upper Palaeolithic origin in the Homo sapiens sapiens K-M9 cluster in Central Asia, and (2) primary Neolithic dispersal of the secondary Beijing NTF::IS6110 lineage by Proto-Sino-Tibetan farmers within east Asia (human O-M214/M122 haplogroup). The independent introductions of the Beijing strains from east Asia to northern Eurasia and South Africa were likely historically recent, whereas their differential dissemination within these areas has been influenced by demographic and climatic factors. PMID:16169923

  18. Spatiotemporal analysis of RhoA/B/C activation in primary human endothelial cells

    PubMed Central

    Reinhard, Nathalie R.; van Helden, Suzanne F.; Anthony, Eloise C.; Yin, Taofei; Wu, Yi I.; Goedhart, Joachim; Gadella, Theodorus W. J.; Hordijk, Peter L.

    2016-01-01

    Endothelial cells line the vasculature and are important for the regulation of blood pressure, vascular permeability, clotting and transendothelial migration of leukocytes and tumor cells. A group of proteins that that control the endothelial barrier function are the RhoGTPases. This study focuses on three homologous (>88%) RhoGTPases: RhoA, RhoB, RhoC of which RhoB and RhoC have been poorly characterized. Using a RhoGTPase mRNA expression analysis we identified RhoC as the highest expressed in primary human endothelial cells. Based on an existing RhoA FRET sensor we developed new RhoB/C FRET sensors to characterize their spatiotemporal activation properties. We found all these RhoGTPase sensors to respond to physiologically relevant agonists (e.g. Thrombin), reaching transient, localized FRET ratio changes up to 200%. These RhoA/B/C FRET sensors show localized GEF and GAP activity and reveal spatial activation differences between RhoA/C and RhoB. Finally, we used these sensors to monitor GEF-specific differential activation of RhoA/B/C. In summary, this study adds high-contrast RhoB/C FRET sensors to the currently available FRET sensor toolkit and uncover new insights in endothelial and RhoGTPase cell biology. This allows us to study activation and signaling by these closely related RhoGTPases with high spatiotemporal resolution in primary human cells. PMID:27147504

  19. Spatiotemporal analysis of RhoA/B/C activation in primary human endothelial cells.

    PubMed

    Reinhard, Nathalie R; van Helden, Suzanne F; Anthony, Eloise C; Yin, Taofei; Wu, Yi I; Goedhart, Joachim; Gadella, Theodorus W J; Hordijk, Peter L

    2016-01-01

    Endothelial cells line the vasculature and are important for the regulation of blood pressure, vascular permeability, clotting and transendothelial migration of leukocytes and tumor cells. A group of proteins that that control the endothelial barrier function are the RhoGTPases. This study focuses on three homologous (>88%) RhoGTPases: RhoA, RhoB, RhoC of which RhoB and RhoC have been poorly characterized. Using a RhoGTPase mRNA expression analysis we identified RhoC as the highest expressed in primary human endothelial cells. Based on an existing RhoA FRET sensor we developed new RhoB/C FRET sensors to characterize their spatiotemporal activation properties. We found all these RhoGTPase sensors to respond to physiologically relevant agonists (e.g. Thrombin), reaching transient, localized FRET ratio changes up to 200%. These RhoA/B/C FRET sensors show localized GEF and GAP activity and reveal spatial activation differences between RhoA/C and RhoB. Finally, we used these sensors to monitor GEF-specific differential activation of RhoA/B/C. In summary, this study adds high-contrast RhoB/C FRET sensors to the currently available FRET sensor toolkit and uncover new insights in endothelial and RhoGTPase cell biology. This allows us to study activation and signaling by these closely related RhoGTPases with high spatiotemporal resolution in primary human cells. PMID:27147504

  20. Rapid Reprogramming of Primary Human Astrocytes into Potent Tumor-Initiating Cells with Defined Genetic Factors.

    PubMed

    Li, Fang; Liu, Xinjian; Sampson, John H; Bigner, Darell D; Li, Chuan-Yuan

    2016-09-01

    Cancer stem-like cells (CSC) are thought to drive brain cancer, but their cellular and molecular origins remain uncertain. Here, we report the successful generation of induced CSC (iCSC) from primary human astrocytes through the expression of defined genetic factors. Combined transduction of four factors, Myc, Oct-4, p53DD, and Ras, induced efficient transformation of primary human astrocytes into malignant cells with powerful tumor-initiating capabilities. Notably, transplantation of 100 transduced cells into nude mice was sufficient for tumor formation. The cells showed unlimited self-renewal ability with robust telomerase activities. In addition, they expressed typical glioma stem-like cell markers, such as CD133, CD15, and CD90. Moreover, these cells could form spheres in culture and differentiate into neuron-like, astrocyte-like, and oligodendrocyte-like cells. Finally, they also displayed resistance to the widely used brain cancer drug temozolomide. These iCSCs could provide important tools for studies of glioma biology and therapeutics development. Cancer Res; 76(17); 5143-50. ©2016 AACR. PMID:27364552

  1. In vivo functional and myeloarchitectonic mapping of human primary auditory areas

    PubMed Central

    Dick, Frederic; Tierney, Adam Taylor; Lutti, Antoine; Josephs, Oliver; Sereno, Martin I.; Weiskopf, Nikolaus

    2012-01-01

    In contrast to vision, where retinotopic mapping alone can define areal borders, primary auditory areas such as A1 are best delineated by combining in vivo tonotopic mapping with post mortem cyto- or myelo-architectonics from the same individual. We combined high-resolution (800 μm) quantitative T1 mapping with phase-encoded tonotopic methods to map primary auditory areas (A1 and R) within the ‘auditory core’ of human volunteers. We first quantitatively characterize the highly myelinated auditory core in terms of shape, area, cortical depth profile, and position, with our data showing considerable correspondence to post-mortem myeloarchitectonic studies, both in cross-participant averages and in individuals. The core region contains two ‘mirror-image‘ tonotopic maps oriented along the same axis as observed in macaque and owl monkey. We suggest that thee two maps within the core are the human analogues of primate auditory areas A1 and R. The core occupies a much smaller portion of tonotopically organized cortex on the superior temporal plane and gyrus than is generally supposed. The multi-modal approach to defining the auditory core will facilitate investigations of structure-function relationships, comparative neuroanatomical studies, and promises new biomarkers for diagnosis and clinical studies. PMID:23152594

  2. On the relation between surface roughness of metallic substrates and adhesion of human primary bone cells.

    PubMed

    Anselme, K; Bigerelle, M

    2014-01-01

    Surface characteristics of materials, whether their topography, chemistry, or surface energy, play an essential part in osteoblast adhesion on biomaterials. Thus, the quality of cell adhesion will influence the cell's capacity to proliferate and differentiate in contact with a biomaterial. We have developed for more than ten years numerous studies on the influence of topography and chemistry of metallic substrates on the response of primary human bone cells. The originality of our approach is that contrary to most of other authors, we quantified the adhesion of primary human bone cells on metallic substrates with perfectly characterized surface topography after some hours but also over 21 days. Moreover, we have developed original statistical approaches for characterizing the relation between surface roughness and cell-adhesion parameters. In this article, we will illustrate different studies we did these last ten years concerning the development of a new adhesion parameter, the adhesion power; the correlation between short-term adhesion, long-term adhesion, and proliferation; the influence of roughness organization on cell adhesion and the development of the order parameter; our modeling approach of cell adhesion on surface topography; the relative influence of surface chemistry and topography on cell adhesion and contact angle; the relation between surface features dimensions and cell adhesion. Further, some considerations will be given on the methods for scanning surface topography for cell-adhesion studies. Finally, perspectives will be given to elucidate these intracellular mechanotransduction mechanisms induced by the deformation of cells on model sinusoidal peaks-or-valleys surfaces.

  3. Standardized 3D Bioprinting of Soft Tissue Models with Human Primary Cells.

    PubMed

    Rimann, Markus; Bono, Epifania; Annaheim, Helene; Bleisch, Matthias; Graf-Hausner, Ursula

    2016-08-01

    Cells grown in 3D are more physiologically relevant than cells cultured in 2D. To use 3D models in substance testing and regenerative medicine, reproducibility and standardization are important. Bioprinting offers not only automated standardizable processes but also the production of complex tissue-like structures in an additive manner. We developed an all-in-one bioprinting solution to produce soft tissue models. The holistic approach included (1) a bioprinter in a sterile environment, (2) a light-induced bioink polymerization unit, (3) a user-friendly software, (4) the capability to print in standard labware for high-throughput screening, (5) cell-compatible inkjet-based printheads, (6) a cell-compatible ready-to-use BioInk, and (7) standard operating procedures. In a proof-of-concept study, skin as a reference soft tissue model was printed. To produce dermal equivalents, primary human dermal fibroblasts were printed in alternating layers with BioInk and cultured for up to 7 weeks. During long-term cultures, the models were remodeled and fully populated with viable and spreaded fibroblasts. Primary human dermal keratinocytes were seeded on top of dermal equivalents, and epidermis-like structures were formed as verified with hematoxylin and eosin staining and immunostaining. However, a fully stratified epidermis was not achieved. Nevertheless, this is one of the first reports of an integrative bioprinting strategy for industrial routine application.

  4. Chemokine-Targeted Mouse Models of Human Primary and Metastatic Colorectal Cancer

    PubMed Central

    Chen, Huanhuan Joyce; Sun, Jian; Huang, Zhiliang; Hou, Harry; Arcilla, Myra; Rakhilin, Nikolai; Joe, Daniel J.; Choi, Jiahn; Gadamsetty, Poornima; Milsom, Jeff; Nandakumar, Govind; Longman, Randy; Zhou, Xi Kathy; Edwards, Robert; Chen, Jonlin; Chen, Kai Yuan; Bu, Pengcheng; Wang, Lihua; Xu, Yitian; Munroe, Robert; Abratte, Christian; Miller, Andrew D.; Gümüş, Zeynep H.; Shuler, Michael; Nishimura, Nozomi; Edelmann, Winfried; Shen, Xiling; Lipkin, Steven M.

    2015-01-01

    Current orthotopic xenograft models of human colorectal cancer (CRC) require surgery and do not robustly form metastases in the liver, the most common site clinically. CCR9 traffics lymphocytes to intestine and colorectum. We engineered use of the chemokine receptor CCR9 in CRC cell lines and patient-derived cells to create primary gastrointestinal (GI) tumors in immunodeficient mice by tail-vein injection rather than surgery. The tumors metastasize inducibly and robustly to the liver. Metastases have higher DKK4 and NOTCH signaling levels and are more chemoresistant than paired sub-cutaneous xenografts. Using this approach, we generated 17 chemokine-targeted mouse models (CTMMs) that recapitulate the majority of common human somatic CRC mutations. We also show that primary tumors can be modeled in immunocompetent mice by microinjecting CCR9-expressing cancer cell lines into early-stage mouse blastocysts, which induces central immune tolerance. We expect that CTMMs will facilitate investigation of the biology of CRC metastasis and drug screening. PMID:26006007

  5. Role of primary human alveolar epithelial cells in host defense against Francisella tularensis infection.

    PubMed

    Gentry, Megan; Taormina, Joanna; Pyles, Richard B; Yeager, Linsey; Kirtley, Michelle; Popov, Vsevolod L; Klimpel, Gary; Eaves-Pyles, Tonyia

    2007-08-01

    Francisella tularensis, an intracellular pathogen, is highly virulent when inhaled. Alveolar epithelial type I (ATI) and type II (ATII) cells line the majority of the alveolar surface and respond to inhaled pathogenic bacteria via cytokine secretion. We hypothesized that these cells contribute to the lung innate immune response to F. tularensis. Results demonstrated that the live vaccine strain (LVS) contacted ATI and ATII cells by 2 h following intranasal inoculation of mice. In culture, primary human ATI or ATII cells, grown on transwell filters, were stimulated on the apical (AP) surface with virulent F. tularensis Schu 4 or LVS. Basolateral (BL) conditioned medium (CM), collected 6 and 24 h later, was added to the BL surfaces of transwell cultures of primary human pulmonary microvasculature endothelial cells (HPMEC) prior to the addition of polymorphonuclear leukocytes (PMNs) or dendritic cells (DCs) to the AP surface. HPMEC responded to S4- or LVS-stimulated ATII, but not ATI, CM as evidenced by PMN and DC migration. Analysis of the AP and BL ATII CM revealed that both F. tularensis strains induced various levels of a variety of cytokines via NF-kappaB activation. ATII cells pretreated with an NF-kappaB inhibitor prior to F. tularensis stimulation substantially decreased interleukin-8 secretion, which did not occur through Toll-like receptor 2, 2/6, 4, or 5 stimulation. These data indicate a crucial role for ATII cells in the innate immune response to F. tularensis. PMID:17502386

  6. Role of Primary Human Alveolar Epithelial Cells in Host Defense against Francisella tularensis Infection▿

    PubMed Central

    Gentry, Megan; Taormina, Joanna; Pyles, Richard B.; Yeager, Linsey; Kirtley, Michelle; Popov, Vsevolod L.; Klimpel, Gary; Eaves-Pyles, Tonyia

    2007-01-01

    Francisella tularensis, an intracellular pathogen, is highly virulent when inhaled. Alveolar epithelial type I (ATI) and type II (ATII) cells line the majority of the alveolar surface and respond to inhaled pathogenic bacteria via cytokine secretion. We hypothesized that these cells contribute to the lung innate immune response to F. tularensis. Results demonstrated that the live vaccine strain (LVS) contacted ATI and ATII cells by 2 h following intranasal inoculation of mice. In culture, primary human ATI or ATII cells, grown on transwell filters, were stimulated on the apical (AP) surface with virulent F. tularensis Schu 4 or LVS. Basolateral (BL) conditioned medium (CM), collected 6 and 24 h later, was added to the BL surfaces of transwell cultures of primary human pulmonary microvasculature endothelial cells (HPMEC) prior to the addition of polymorphonuclear leukocytes (PMNs) or dendritic cells (DCs) to the AP surface. HPMEC responded to S4- or LVS-stimulated ATII, but not ATI, CM as evidenced by PMN and DC migration. Analysis of the AP and BL ATII CM revealed that both F. tularensis strains induced various levels of a variety of cytokines via NF-κB activation. ATII cells pretreated with an NF-κB inhibitor prior to F. tularensis stimulation substantially decreased interleukin-8 secretion, which did not occur through Toll-like receptor 2, 2/6, 4, or 5 stimulation. These data indicate a crucial role for ATII cells in the innate immune response to F. tularensis. PMID:17502386

  7. In Vitro Model for Hepatotoxicity Studies Based on Primary Human Hepatocyte Cultivation in a Perfused 3D Bioreactor System

    PubMed Central

    Knöspel, Fanny; Jacobs, Frank; Freyer, Nora; Damm, Georg; De Bondt, An; van den Wyngaert, Ilse; Snoeys, Jan; Monshouwer, Mario; Richter, Marco; Strahl, Nadja; Seehofer, Daniel; Zeilinger, Katrin

    2016-01-01

    Accurate prediction of the potential hepatotoxic nature of new pharmaceuticals remains highly challenging. Therefore, novel in vitro models with improved external validity are needed to investigate hepatic metabolism and timely identify any toxicity of drugs in humans. In this study, we examined the effects of diclofenac, as a model substance with a known risk of hepatotoxicity in vivo, in a dynamic multi-compartment bioreactor using primary human liver cells. Biotransformation pathways of the drug and possible effects on metabolic activities, morphology and cell transcriptome were evaluated. Formation rates of diclofenac metabolites were relatively stable over the application period of seven days in bioreactors exposed to 300 µM diclofenac (300 µM bioreactors (300 µM BR)), while in bioreactors exposed to 1000 µM diclofenac (1000 µM BR) metabolite concentrations declined drastically. The biochemical data showed a significant decrease in lactate production and for the higher dose a significant increase in ammonia secretion, indicating a dose-dependent effect of diclofenac application. The microarray analyses performed revealed a stable hepatic phenotype of the cells over time and the observed transcriptional changes were in line with functional readouts of the system. In conclusion, the data highlight the suitability of the bioreactor technology for studying the hepatotoxicity of drugs in vitro. PMID:27092500

  8. Efficient nanoparticle mediated sustained RNA interference in human primary endothelial cells.

    PubMed

    Mukerjee, Anindita; Shankardas, Jwalitha; Ranjan, Amalendu P; Vishwanatha, Jamboor K

    2011-11-01

    Endothelium forms an important target for drug and/or gene therapy since endothelial cells play critical roles in angiogenesis and vascular functions and are associated with various pathophysiological conditions. RNA mediated gene silencing presents a new therapeutic approach to overcome many such diseases, but the major challenge of such an approach is to ensure minimal toxicity and effective transfection efficiency of short hairpin RNA (shRNA) to primary endothelial cells. In the present study, we formulated shAnnexin A2 loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles which produced intracellular small interfering RNA (siRNA) against Annexin A2 and brought about the downregulation of Annexin A2. The per cent encapsulation of the plasmid within the nanoparticle was found to be 57.65%. We compared our nanoparticle based transfections with Lipofectamine mediated transfection, and our studies show that nanoparticle based transfection efficiency is very high (~97%) and is more sustained compared to conventional Lipofectamine mediated transfections in primary retinal microvascular endothelial cells and human cancer cell lines. Our findings also show that the shAnnexin A2 loaded PLGA nanoparticles had minimal toxicity with almost 95% of cells being viable 24 h post-transfection while Lipofectamine based transfections resulted in only 30% viable cells. Therefore, PLGA nanoparticle based transfection may be used for efficient siRNA transfection to human primary endothelial and cancer cells. This may serve as a potential adjuvant treatment option for diseases such as diabetic retinopathy, retinopathy of prematurity and age related macular degeneration besides various cancers.

  9. Efficient nanoparticle mediated sustained RNA interference in human primary endothelial cells

    NASA Astrophysics Data System (ADS)

    Mukerjee, Anindita; Shankardas, Jwalitha; Ranjan, Amalendu P.; Vishwanatha, Jamboor K.

    2011-11-01

    Endothelium forms an important target for drug and/or gene therapy since endothelial cells play critical roles in angiogenesis and vascular functions and are associated with various pathophysiological conditions. RNA mediated gene silencing presents a new therapeutic approach to overcome many such diseases, but the major challenge of such an approach is to ensure minimal toxicity and effective transfection efficiency of short hairpin RNA (shRNA) to primary endothelial cells. In the present study, we formulated shAnnexin A2 loaded poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles which produced intracellular small interfering RNA (siRNA) against Annexin A2 and brought about the downregulation of Annexin A2. The per cent encapsulation of the plasmid within the nanoparticle was found to be 57.65%. We compared our nanoparticle based transfections with Lipofectamine mediated transfection, and our studies show that nanoparticle based transfection efficiency is very high (~97%) and is more sustained compared to conventional Lipofectamine mediated transfections in primary retinal microvascular endothelial cells and human cancer cell lines. Our findings also show that the shAnnexin A2 loaded PLGA nanoparticles had minimal toxicity with almost 95% of cells being viable 24 h post-transfection while Lipofectamine based transfections resulted in only 30% viable cells. Therefore, PLGA nanoparticle based transfection may be used for efficient siRNA transfection to human primary endothelial and cancer cells. This may serve as a potential adjuvant treatment option for diseases such as diabetic retinopathy, retinopathy of prematurity and age related macular degeneration besides various cancers.

  10. Human norovirus in untreated sewage and effluents from primary, secondary and tertiary treatment processes.

    PubMed

    Campos, Carlos J A; Avant, Justin; Lowther, James; Till, Dale; Lees, David N

    2016-10-15

    Wastewater treatments are considered important means to control the environmental transmission of human norovirus (NoV). Information about NoV concentrations in untreated and treated effluents, their seasonality and typical removal rates achieved by different treatment processes is required to assess the effectiveness of sewage treatment processes in reducing human exposure to NoV. This paper reports on a characterisation of concentrations of NoV (genogroups I and II) in untreated sewage (screened influent) and treated effluents from five full scale wastewater treatment works (WwTW) in England. Results are shown for effluent samples characteristic of primary- (primary settlement, storm tank overflows), secondary- (activated sludge, trickling filters, humus tanks) and tertiary (UV disinfection) treatments. NoV occurrence in untreated sewage varied between years. This variation was consistent with the annual variation of the virus in the community as indicated by outbreak laboratory reports. Significant differences were found between mean NoV concentrations in effluents subject to different levels of treatment. Primary settlement achieved approximately 1 log10 removal for both genogroups. Concentrations of NoV and Escherichia coli in untreated sewage were of the same order of magnitude of those in storm tank overflows. Of the secondary treatments studied, activated sludge was the most effective in removing NoV with mean log10 removals of 3.11 and 2.34 for GI and GII, respectively. The results of this study provide evidence that monitoring of NoV in raw sewage or treated effluents could provide early warning of an elevated risk for NoV and potentially help prevent outbreaks through environmental exposure. They also provide evidence that elimination of stormwater discharges and improvement of the efficiency of activated sludge for NoV removal would be effective for reducing the risk of environmental transmission. PMID:27470292

  11. SORBS2 and TLR3 induce premature senescence in primary human fibroblasts and keratinocytes

    PubMed Central

    2013-01-01

    Background Genetic aberrations are required for the progression of HPV-induced cervical precancers. A prerequisite for clonal expansion of cancer cells is unlimited proliferative capacity. In a cell culture model for cervical carcinogenesis loss of genes located on chromosome 4q35→qter and chromosome 10p14-p15 were found to be associated with escape from senescence. Moreover, by LOH and I-FISH analyses a higher frequency of allele loss of these regions was also observed in cervical carcinomas as compared to CIN3. The aim of this study was to identify candidate senescence-related genes located on chromosome 4q35→qter and chromosome 10p14-p15 which may contribute to clonal expansion at the transition of CIN3 to cancer. Methods Microarray expression analyses were used to identify candidate genes down-regulated in cervical carcinomas as compared to CIN3. In order to relate these genes with the process of senescence their respective cDNAs were overexpressed in HPV16-immortalized keratinocytes as well as in primary human fibroblasts and keratinocytes using lentivirus mediated gene transduction. Results Overall fifteen genes located on chromosome 4q35→qter and chromosome 10p14-p15 were identified. Ten of these genes could be validated in biopsies by RT-PCR. Of interest is the novel finding that SORBS2 and TLR3 can induce senescence in primary human fibroblasts and keratinocytes but not in HPV-immortalized cell lines. Intriguingly, the endogenous expression of both genes increases during finite passaging of primary keratinocytes in vitro. Conclusions The relevance of the genes SORBS2 and TLR3 in the process of cellular senescence warrants further investigation. In ongoing experiments we are investigating whether this increase in gene expression is also characteristic of replicative senescence. PMID:24165198

  12. Additional survey on genotoxicity of natural anthraquinones in the hepatocyte primary culture/DNA repair assay.

    PubMed

    Mori, H; Yoshimi, N; Iwata, H; Tanaka, T; Kawai, K; Sankawa, U

    1988-08-01

    Genotoxicity of fungal anthraquinones of islandicin, iridoskyrin and (-) rubroskyrin, and a colorant of insect origin, cochineal and its component, carminic acid, an anthraquinone, was examined in the hepatocyte primary culture/DNA repair test. The results were compared with that of versicolorin A, an anthraquinone with bisfuran ring, which had been proved to be genotoxic on this assay. All of these anthraquinones, differently from versicolorin A did not show clear response of DNA repair. The results suggest that these agents are not genotoxic carcinogens. PMID:3193483

  13. Natural soil reservoirs for human pathogenic and fecal indicator bacteria

    USGS Publications Warehouse

    Boschiroli, Maria L; Falkinham, Joseph; Favre-Bonte, Sabine; Nazaret, Sylvie; Piveteau, Pascal; Sadowsky, Michael J.; Byappanahalli, Muruleedhara; Delaquis, Pascal; Hartmann, Alain

    2016-01-01

    Soils receive inputs of human pathogenic and indicator bacteria through land application of animal manures or sewage sludge, and inputs by wildlife. Soil is an extremely heterogeneous substrate and contains meso- and macrofauna that may be reservoirs for bacteria of human health concern. The ability to detect and quantify bacteria of human health concern is important in risk assessments and in evaluating the efficacy of agricultural soil management practices that are protective of crop quality and protective of adjacent water resources. The present chapter describes the distribution of selected Gram-positive and Gram-negative bacteria in soils. Methods for detecting and quantifying soilborne bacteria including extraction, enrichment using immunomagnetic capture, culturing, molecular detection and deep sequencing of metagenomic DNA to detect pathogens are overviewed. Methods for strain phenotypic and genotypic characterization are presented, as well as how comparison with clinical isolates can inform the potential for human health risk.

  14. Human Longevity : nature vs nurture-fact or fiction.

    SciTech Connect

    Carnes, B. A.; Jay Olshansky, S.; Gavrilov, L.; Gavrilova, N.; Grahn, D.; Center for Mechanistic Biology and Biotechnology; Univ. of Chicago

    1999-04-01

    Genetic effects may have a greater influence on human longevity than biomedical intervention. An alternative perspective examines the heritability effects of genetic damage caused by free radicals within somatic cells, or genetic damage that accumulates over a lifetime.

  15. Gene–culture coevolution and the nature of human sociality

    PubMed Central

    Gintis, Herbert

    2011-01-01

    Human characteristics are the product of gene–culture coevolution, which is an evolutionary dynamic involving the interaction of genes and culture over long time periods. Gene–culture coevolution is a special case of niche construction. Gene–culture coevolution is responsible for human other-regarding preferences, a taste for fairness, the capacity to empathize and salience of morality and character virtues. PMID:21320901

  16. THE ANTICORRELATED NATURE OF THE PRIMARY AND SECONDARY ECLIPSE TIMING VARIATIONS FOR THE KEPLER CONTACT BINARIES

    SciTech Connect

    Tran, K.; Rappaport, S.; Levine, A.; Borkovits, T.; Csizmadia, Sz.; Kalomeni, B. E-mail: aml@space.mit.edu E-mail: szilard.csizmadia@dlr.de

    2013-09-01

    We report a study of the eclipse timing variations in contact binary systems, using long-cadence lightcurves from the Kepler archive. As a first step, observed minus calculated (O - C) curves were produced for both the primary and secondary eclipses of some 2000 Kepler binaries. We find {approx}390 short-period binaries with O - C curves that exhibit (1) random walk-like variations or quasi-periodicities, with typical amplitudes of {+-}200-300 s, and (2) anticorrelations between the primary and secondary eclipse timing variations. We present a detailed analysis and results for 32 of these binaries with orbital periods in the range of 0.35 {+-} 0.05 days. The anticorrelations observed in their O - C curves cannot be explained by a model involving mass transfer, which, among other things, requires implausibly high rates of {approx}0.01 M{sub Sun} yr{sup -1}. We show that the anticorrelated behavior, the amplitude of the O - C delays, and the overall random walk-like behavior can be explained by the presence of a starspot that is continuously visible around the orbit and slowly changes its longitude on timescales of weeks to months. The quasi-periods of {approx}50-200 days observed in the O - C curves suggest values for k, the coefficient of the latitude dependence of the stellar differential rotation, of {approx}0.003-0.013.

  17. Differential effects of antidepressants on glucocorticoid receptors in human primary blood cells and human monocytic U-937 cells.

    PubMed

    Heiske, Andreas; Jesberg, Jutta; Krieg, Jürgen-Christian; Vedder, Helmut

    2003-04-01

    A number of data support the assumption that antidepressants (ADs) normalize the altered function of the hypothalamic-pituitary-adrenocortical (HPA) system involved in the pathophysiology of depressive disorder via direct effects on glucocorticoid receptors (GRs). In the present study, we examined the tricyclic ADs desipramine (DESI) and imipramine (IMI), the noradrenaline reuptake inhibitor maprotiline (MAPRO), and the noradrenergic and specific serotonergic AD (NaSSA) mirtazapine (MIR) for their effects on GR expression in primary human leukocytes and in monocytic U-937 cells. Semiquantitative RT-PCR indicated that the ADs exert differential effects on GR-mRNA levels in both primary human leukocytes and U-937 cells: whereas MAPRO and IMI did not induce pronounced changes in GR-mRNA levels, DESI and MIR significantly decreased the amounts of GR-mRNA in both cell systems. Further characterization of the effects of MIR revealed a time dependency of the regulation with an initial increase of GR-mRNA levels above control levels after 2.5 h of treatment and a decrease after 4, 24, and 48 h of incubation. A dose-response analysis demonstrated maximal effects of MIR at a concentration of 10(-7) M. Immunohistochemical studies showed that MIR increased the GR protein levels in a time-dependent manner and that this upregulation appeared earlier by additional treatment with dexamethasone (DEX). A translocation of the GR protein from the cytoplasm to the nucleus was induced between 24 and 48 h of treatment with MIR and MIR/DEX, respectively. Taken together, our data further support the assumption that ADs influence the neuroendocrine and immune system via effects on cellular GRs. PMID:12655328

  18. Two compartment model of diazepam biotransformation in an organotypical culture of primary human hepatocytes

    SciTech Connect

    Acikgoez, Ali; Karim, Najibulla; Giri, Shibashish; Schmidt-Heck, Wolfgang; Bader, Augustinus

    2009-01-15

    Drug biotransformation is one of the most important parameters of preclinical screening tests for the registration of new drug candidates. Conventional existing tests rely on nonhuman models which deliver an incomplete metabolic profile of drugs due to the lack of proper CYP450 expression as seen in human liver in vivo. In order to overcome this limitation, we used an organotypical model of human primary hepatocytes for the biotransformation of the drug diazepam with special reference to metabolites in both the cell matrix phase and supernatant and its interaction of three inducers (phenobarbital, dexamethasone, aroclor 1254) in different time responses (1, 2, 4, 8, 24 h). Phenobarbital showed the strongest inducing effect in generating desmethyldiazepam and induced up to a 150 fold increase in oxazepam-content which correlates with the increased availability of the precursor metabolites (temazepam and desmethyldiazepam). Aroclor 1254 and dexamethasone had the strongest inducing effect on temazepam and the second strongest on oxazepam. The strong and overlapping inductive role of phenobarbital strengthens the participation of CYP2B6 and CYP3A in diazepam N-demethylation and CYP3A in temazepam formation. Aroclor 1254 preferentially generated temazepam due to the interaction with CYP3A and potentially CYP2C19. In parallel we represented these data in the form of a mathematical model with two compartments explaining the dynamics of diazepam metabolism with the effect of these other inducers in human primary hepatocytes. The model consists of ten differential equations, with one for each concentration c{sub i,j} (i = diazepam, temazepam, desmethyldiazepam, oxazepam, other metabolites) and one for each compartment (j = cell matrix phase, supernatant), respectively. The parameters p{sub k} (k = 1, 2, 3, 4, 13) are rate constants describing the biotransformation of diazepam and its metabolites and the other parameters (k = 5, 6, 7, 8, 9, 10, 11, 12, 14, 15) explain the

  19. The effect of ethidium bromide and chloramphenicol on mitochondrial biogenesis in primary human fibroblasts

    SciTech Connect

    Kao, Li-Pin; Ovchinnikov, Dmitry; Wolvetang, Ernst

    2012-05-15

    The expression of mitochondrial components is controlled by an intricate interplay between nuclear transcription factors and retrograde signaling from mitochondria. The role of mitochondrial DNA (mtDNA) and mtDNA-encoded proteins in mitochondrial biogenesis is, however, poorly understood and thus far has mainly been studied in transformed cell lines. We treated primary human fibroblasts with ethidium bromide (EtBr) or chloramphenicol for six weeks to inhibit mtDNA replication or mitochondrial protein synthesis, respectively, and investigated how the cells recovered from these insults two weeks after removal of the drugs. Although cellular growth and mitochondrial gene expression were severely impaired after both inhibitor treatments we observed marked differences in mitochondrial structure, membrane potential, glycolysis, gene expression, and redox status between fibroblasts treated with EtBr and chloramphenicol. Following removal of the drugs we further detected clear differences in expression of both mtDNA-encoded genes and nuclear transcription factors that control mitochondrial biogenesis, suggesting that the cells possess different compensatory mechanisms to recover from drug-induced mitochondrial dysfunction. Our data reveal new aspects of the interplay between mitochondrial retrograde signaling and the expression of nuclear regulators of mitochondrial biogenesis, a process with direct relevance to mitochondrial diseases and chloramphenicol toxicity in humans. -- Highlights: ► Cells respond to certain environmental toxins by increasing mitochondrial biogenesis. ► We investigated the effect of Chloramphenicol and EtBr in primary human fibroblasts. ► Inhibiting mitochondrial protein synthesis or DNA replication elicit different effects. ► We provide novel insights into the cellular responses toxins and antibiotics.

  20. UVA and UVB Irradiation Differentially Regulate microRNA Expression in Human Primary Keratinocytes

    PubMed Central

    Kraemer, Anne; Chen, I-Peng; Henning, Stefan; Faust, Alexandra; Volkmer, Beate; Atkinson, Michael J.; Moertl, Simone; Greinert, Ruediger

    2013-01-01

    MicroRNA (miRNA)-mediated regulation of the cellular transcriptome is an important epigenetic mechanism for fine-tuning regulatory pathways. These include processes related to skin cancer development, progression and metastasis. However, little is known about the role of microRNA as an intermediary in the carcinogenic processes following exposure to UV-radiation. We now show that UV irradiation of human primary keratinocytes modulates the expression of several cellular miRNAs. A common set of miRNAs was influenced by exposure to both UVA and UVB. However, each wavelength band also activated a distinct subset of miRNAs. Common sets of UVA- and UVB-regulated miRNAs harbor the regulatory elements GLYCA-nTRE, GATA-1-undefined-site-13 or Hox-2.3-undefined-site-2 in their promoters. In silico analysis indicates that the differentially expressed miRNAs responding to UV have potential functions in the cellular pathways of cell growth and proliferation. Interestingly, the expression of miR-23b, which is a differentiation marker of human keratinocytes, is remarkably up-regulated after UVA irradiation. Studying the interaction between miR-23b and its putative skin-relevant targets using a Luciferase reporter assay revealed that RRAS2 (related RAS viral oncogene homolog 2), which is strongly expressed in highly aggressive malignant skin cancer, to be a direct target of miR-23b. This study demonstrates for the first time a differential miRNA response to UVA and UVB in human primary keratinocytes. This suggests that selective regulation of signaling pathways occurs in response to different UV energies. This may shed new light on miRNA-regulated carcinogenic processes involved in UV-induced skin carcinogenesis. PMID:24391759

  1. Automatic analysis of the micronucleus test in primary human lymphocytes using image analysis.

    PubMed

    Frieauff, W; Martus, H J; Suter, W; Elhajouji, A

    2013-01-01

    The in vitro micronucleus test (MNT) is a well-established test for early screening of new chemical entities in industrial toxicology. For assessing the clastogenic or aneugenic potential of a test compound, micronucleus induction in cells has been shown repeatedly to be a sensitive and a specific parameter. Various automated systems to replace the tedious and time-consuming visual slide analysis procedure as well as flow cytometric approaches have been discussed. The ROBIAS (Robotic Image Analysis System) for both automatic cytotoxicity assessment and micronucleus detection in human lymphocytes was developed at Novartis where the assay has been used to validate positive results obtained in the MNT in TK6 cells, which serves as the primary screening system for genotoxicity profiling in early drug development. In addition, the in vitro MNT has become an accepted alternative to support clinical studies and will be used for regulatory purposes as well. The comparison of visual with automatic analysis results showed a high degree of concordance for 25 independent experiments conducted for the profiling of 12 compounds. For concentration series of cyclophosphamide and carbendazim, a very good correlation between automatic and visual analysis by two examiners could be established, both for the relative division index used as cytotoxicity parameter, as well as for micronuclei scoring in mono- and binucleated cells. Generally, false-positive micronucleus decisions could be controlled by fast and simple relocation of the automatically detected patterns. The possibility to analyse 24 slides within 65h by automatic analysis over the weekend and the high reproducibility of the results make automatic image processing a powerful tool for the micronucleus analysis in primary human lymphocytes. The automated slide analysis for the MNT in human lymphocytes complements the portfolio of image analysis applications on ROBIAS which is supporting various assays at Novartis.

  2. Activity, inhibition, and induction of cytochrome P450 2J2 in adult human primary cardiomyocytes.

    PubMed

    Evangelista, Eric A; Kaspera, Rüdiger; Mokadam, Nahush A; Jones, J P; Totah, Rheem A

    2013-12-01

    Cytochrome P450 2J2 plays a significant role in the epoxidation of arachidonic acid to signaling molecules important in cardiovascular events. CYP2J2 also contributes to drug metabolism and is responsible for the intestinal clearance of ebastine. However, the interaction between arachidonic acid metabolism and drug metabolism in cardiac tissue, the main expression site of CYP2J2, has not been examined. Here we investigate an adult-derived human primary cardiac cell line as a suitable model to study metabolic drug interactions (inhibition and induction) of CYP2J2 in cardiac tissue. The primary human cardiomyocyte cell line demonstrated similar mRNA-expression profiles of P450 enzymes to adult human ventricular tissue. CYP2J2 was the dominant isozyme with minor contributions from CYP2D6 and CYP2E1. Both terfenadine and astemizole oxidation were observed in this cell line, whereas midazolam was not metabolized suggesting lack of CYP3A activity. Compared with recombinant CYP2J2, terfenadine was hydroxylated in cardiomyocytes at a similar K(m) value of 1.5 μM. The V(max) of terfenadine hydroxylation in recombinant enzyme was found to be 29.4 pmol/pmol P450 per minute and in the cells 6.0 pmol/pmol P450 per minute. CYP2J2 activity in the cell line was inhibited by danazol, astemizole, and ketoconazole in submicromolar range, but also by xenobiotics known to cause cardiac adverse effects. Of the 14 compounds tested for CYP2J2 induction, only rosiglitazone increased mRNA expression, by 1.8-fold. This cell model can be a useful in vitro model to investigate the role of CYP2J2-mediated drug metabolism, arachidonic acid metabolism, and their association to drug induced cardiotoxicity. PMID:24021950

  3. Serotyping of primary human immunodeficiency virus type 1 isolates from diverse geographic locations by flow cytometry.

    PubMed Central

    Zolla-Pazner, S; O'Leary, J; Burda, S; Gorny, M K; Kim, M; Mascola, J; McCutchan, F

    1995-01-01

    The immunologic relatedness of the various human immunodeficiency virus type 1 (HIV-1) clades was determined with 13 human anti-HIV-1 monoclonal antibodies (MAbs) to six immunogenic regions of the HIV-1 structural proteins. The immunoreactivity of the native, oligomeric viral envelope glycoproteins expressed on the surfaces of human peripheral blood mononuclear cells infected in vitro with primary isolates from clades A through E was determined by flow cytometry. Some epitopes in the immunodominant region of gp41 and the C terminus of gp120 appear to be HIV-1 group specific in that they are expressed on the surfaces of cells in cultures infected with the majority of viruses tested from clades A to E. Epitopes within the V3 region appear to be clade restricted. Surprisingly, one MAb to an epitope in the C terminus of gp120 was entirely clade B specific. Staining with anti-V2 and anti-CD4 binding domain (CD4bd) reagents was infrequently detected. Anti-CD4bd MAbs stained only CD4-negative T cells because the CD4bd of gp120 appeared to be complexed with membrane CD4. When present, the epitopes of V2 and the CD4bd appeared to be expressed on cells infected with various clades. Thus, the results suggest that MAbs to gp41, the C terminus, and the V3 loop of gp120 are most useful in serotyping primary isolates of HIV-1, providing group-specific, clade-restricted, and clade-specific reagents. The use of the immunofluorescent method with the reagents described herein distinguishes infection with clade B from that with all other HIV-1 clades. With additional MAbs, this technique will allow a broadly applicable, reproducible, and practical method for serotyping HIV-1. PMID:7745728

  4. Temporary management of permanent central incisors loss caused by trauma in primary dentition with natural crowns: a case report.

    PubMed

    Tüzüner, Tamer; Kuşgöz, Adem; Nur, Bilge Gülsüm

    2009-10-01

    Primary teeth injuries may cause developmental disturbances in the permanent dentition and loss of permanent incisors could be treated with different options. In this case report, an 11-year-old boy, with a history of trauma at the age of 4 years, is presented. Premature loss of permanent upper right central and upper left central teeth because of the mobility and arrest in root development were treated using patient's own natural crowns on a removable appliance. This treatment option could be considered as an esthetic and functional temporary management of permanent central incisors loss until the definitive treatment will be completed in the future.

  5. Independent component filters of natural images compared with simple cells in primary visual cortex.

    PubMed Central

    van Hateren, J H; van der Schaaf, A

    1998-01-01

    Properties of the receptive fields of simple cells in macaque cortex were compared with properties of independent component filters generated by independent component analysis (ICA) on a large set of natural images. Histograms of spatial frequency bandwidth, orientation tuning bandwidth, aspect ratio and length of the receptive fields match well. This indicates that simple cells are well tuned to the expected statistics of natural stimuli. There is no match, however, in calculated and measured distributions for the peak of the spatial frequency response: the filters produced by ICA do not vary their spatial scale as much as simple cells do, but are fixed to scales close to the finest ones allowed by the sampling lattice. Possible ways to resolve this discrepancy are discussed. PMID:9523437

  6. Climate-relevant properties of primary particulate emissions from oil and natural gas combustion

    NASA Astrophysics Data System (ADS)

    Bond, Tami C.; Wehner, Birgit; Plewka, Antje; Wiedensohler, Alfred; Heintzenberg, Jost; Charlson, Robert J.

    We report emissions of mass, light absorption, particle number, chemical composition and size-resolved organic species from an industrial boiler that burned natural gas and residual oil. Organic compounds detected from oil combustion are mainly alkanes; it is not a major source of identifiable polyaromatic hydrocarbons. Elemental carbon (EC) and organic carbon (OC) make up approximately 38% and 15% of the particles from oil burning, respectively. Mass emissions from natural gas were below detection limits. A number peak of ultrafine aerosol (diameters lower than 10 nm) was always associated with oil burning. Burning at full power produced the greatest number of particles in the accumulation mode. Natural gas also produced fine particles, but at a much lower rate. The emission rate of light-absorbing particles from this relatively new boiler is lower than that in current emission inventories. However, real-time measurements show a large contribution to emitted light absorption from boiler warm-up and transients, even those with very short durations. The measured absorption is best explained with a constant absorption cross-section for EC, rather than predictions based on size distribution or mixed aerosol; this finding is consistent with EC in fractal-aggregate form. We compare the emissions with those of a lignite stoker, which this boiler replaced during environmental cleanup in the mid-1990s. Emissions of mass, light absorption and particles are lowest from natural gas, but the oil boiler is also a substantial improvement: emissions of particulate matter are 100 times lower, and emitted absorption is three times lower. However, the oil-burning emissions have a greater net warming effect per mass than those of the lignite plant.

  7. Riverine threat indices to assess watershed condition and identify primary management capacity of agriculture natural resource management agencies.

    PubMed

    Fore, Jeffrey D; Sowa, Scott P; Galat, David L; Annis, Gust M; Diamond, David D; Rewa, Charles

    2014-03-01

    Managers can improve conservation of lotic systems over large geographies if they have tools to assess total watershed conditions for individual stream segments and can identify segments where conservation practices are most likely to be successful (i.e., primary management capacity). The goal of this research was to develop a suite of threat indices to help agriculture resource management agencies select and prioritize watersheds across Missouri River basin in which to implement agriculture conservation practices. We quantified watershed percentages or densities of 17 threat metrics that represent major sources of ecological stress to stream communities into five threat indices: agriculture, urban, point-source pollution, infrastructure, and all non-agriculture threats. We identified stream segments where agriculture management agencies had primary management capacity. Agriculture watershed condition differed by ecoregion and considerable local variation was observed among stream segments in ecoregions of high agriculture threats. Stream segments with high non-agriculture threats were most concentrated near urban areas, but showed high local variability. 60 % of stream segments in the basin were classified as under U.S. Department of Agriculture's Natural Resources Conservation Service (NRCS) primary management capacity and most segments were in regions of high agricultural threats. NRCS primary management capacity was locally variable which highlights the importance of assessing total watershed condition for multiple threats. Our threat indices can be used by agriculture resource management agencies to prioritize conservation actions and investments based on: (a) relative severity of all threats, (b) relative severity of agricultural threats, and (c) and degree of primary management capacity.

  8. Human liver alcohol dehydrogenase. 2. The primary structure of the gamma 1 protein chain.

    PubMed

    Bühler, R; Hempel, J; Kaiser, R; de Zalenski, C; von Wartburg, J P; Jörnvall, H

    1984-12-17

    The primary structure of the gamma 1 subunit of human liver alcohol dehydrogenase isoenzyme gamma 1 gamma 1 was deduced by characterization of 36 tryptic and 2 CNBr peptides. The polypeptide chain is composed of 373 amino acid residues. gamma 1 differs from the beta 1 subunit of human liver alcohol dehydrogenase at 21 positions, and from the E subunit of horse liver alcohol dehydrogenase at 43 positions including a gap at position 128 as in the beta 1 subunit. All zinc-liganding residues from the E subunit of the horse protein and the beta 1 subunit of the human enzyme are conserved, but like beta 1, gamma 1 also has an additional cysteine residue at position 286 (in the positional numbering system of the horse enzyme) due to a Tyr----Cys exchange. Most amino acid exchanges preserve the properties of the residues affected and are largely located on the surface of the molecules, away from the active site and the coenzyme binding region. However, eight positions with charge differences in relation to the E subunit of the horse enzyme are noticed. These result in a net positive charge increase of one in gamma 1 versus E, explaining the electrophoretic mobilities on starch gels. Of functional significance is the conservation of Ser-48 in gamma 1 relative to E. The residue is close to the active site but different (Thr-48) in the beta 1 subunit of the human enzyme. Thus, the closer structural relationship between human gamma 1 and horse E enzyme subunit than between beta 1 and E is also reflected in functionally important residues, explaining a greater similarity between gamma 1 gamma 1 and EE than between beta 1 beta 1 and EE. PMID:6391921

  9. Development of Functional Microfold (M) Cells from Intestinal Stem Cells in Primary Human Enteroids

    PubMed Central

    Rouch, Joshua D.; Scott, Andrew; Lei, Nan Ye; Solorzano-Vargas, R. Sergio; Wang, Jiafang; Hanson, Elaine M.; Kobayashi, Masae; Lewis, Michael; Stelzner, Matthias G.; Dunn, James C. Y.; Eckmann, Lars; Martín, Martín G.

    2016-01-01

    Background & Aims Intestinal microfold (M) cells are specialized epithelial cells that act as gatekeepers of luminal antigens in the intestinal tract. They play a critical role in the intestinal mucosal immune response through transport of viruses, bacteria and other particles and antigens across the epithelium to immune cells within Peyer’s patch regions and other mucosal sites. Recent studies in mice have demonstrated that M cells are generated from Lgr5+ intestinal stem cells (ISCs), and that infection with Salmonella enterica serovar Typhimurium increases M cell formation. However, it is not known whether and how these findings apply to primary human small intestinal epithelium propagated in an in vitro setting. Methods Human intestinal crypts were grown as monolayers with growth factors and treated with recombinant RANKL, and assessed for mRNA transcripts, immunofluorescence and uptake of microparticles and S. Typhimurium. Results Functional M cells were generated by short-term culture of freshly isolated human intestinal crypts in a dose- and time-dependent fashion. RANKL stimulation of the monolayer cultures caused dramatic induction of the M cell-specific markers, SPIB, and Glycoprotein-2 (GP2) in a process primed by canonical WNT signaling. Confocal microscopy demonstrated a pseudopod phenotype of GP2-positive M cells that preferentially take up microparticles. Furthermore, infection of the M cell-enriched cultures with the M cell-tropic enteric pathogen, S. Typhimurium, led to preferential association of the bacteria with M cells, particularly at lower inoculum sizes. Larger inocula caused rapid induction of M cells. Conclusions Human intestinal crypts containing ISCs can be cultured and differentiate into an epithelial layer with functional M cells with characteristic morphological and functional properties. This study is the first to demonstrate that M cells can be induced to form from primary human intestinal epithelium, and that S. Typhimurium

  10. Mechanisms of acetaminophen-induced cell death in primary human hepatocytes

    SciTech Connect

    Xie, Yuchao; McGill, Mitchell R.; Dorko, Kenneth; Kumer, Sean C.; Schmitt, Timothy M.; Forster, Jameson; Jaeschke, Hartmut

    2014-09-15

    Acetaminophen (APAP) overdose is the most prevalent cause of drug-induced liver injury in western countries. Numerous studies have been conducted to investigate the mechanisms of injury after APAP overdose in various animal models; however, the importance of these mechanisms for humans remains unclear. Here we investigated APAP hepatotoxicity using freshly isolated primary human hepatocytes (PHH) from either donor livers or liver resections. PHH were exposed to 5 mM, 10 mM or 20 mM APAP over a period of 48 h and multiple parameters were assessed. APAP dose-dependently induced significant hepatocyte necrosis starting from 24 h, which correlated with the clinical onset of human liver injury after APAP overdose. Interestingly, cellular glutathione was depleted rapidly during the first 3 h. APAP also resulted in early formation of APAP-protein adducts (measured in whole cell lysate and in mitochondria) and mitochondrial dysfunction, indicated by the loss of mitochondrial membrane potential after 12 h. Furthermore, APAP time-dependently triggered c-Jun N-terminal kinase (JNK) activation in the cytosol and translocation of phospho-JNK to the mitochondria. Both co-treatment and post-treatment (3 h) with the JNK inhibitor SP600125 reduced JNK activation and significantly attenuated cell death at 24 h and 48 h after APAP. The clinical antidote N-acetylcysteine offered almost complete protection even if administered 6 h after APAP and a partial protection when given at 15 h. Conclusion: These data highlight important mechanistic events in APAP toxicity in PHH and indicate a critical role of JNK in the progression of injury after APAP in humans. The JNK pathway may represent a therapeutic target in the clinic. - Highlights: • APAP reproducibly causes cell death in freshly isolated primary human hepatocytes. • APAP induces adduct formation, JNK activation and mitochondrial dysfunction in PHH. • Mitochondrial adducts and JNK translocation are delayed in PHH compared to

  11. Origin of germ cells and formation of new primary follicles in adult human ovaries

    PubMed Central

    Bukovsky, Antonin; Caudle, Michael R; Svetlikova, Marta; Upadhyaya, Nirmala B

    2004-01-01

    sophisticated adaptive mechanism created during the evolution of female reproduction. Our data indicate that the pool of primary follicles in adult human ovaries does not represent a static but a dynamic population of differentiating and regressing structures. An essential mission of such follicular turnover might be elimination of spontaneous or environmentally induced genetic alterations of oocytes in resting primary follicles. PMID:15115550

  12. Variation in the population structure between a natural and a human-modified forest for a pioneer tropical tree species not restricted to large gaps.

    PubMed

    Silvestrini, Milene; Dos Santos, Flavio Antonio Maës

    2015-06-01

    The distribution of tree species in tropical forests is generally related to the occurrence of disturbances and shifts in the local environmental conditions such as light, temperature, and biotic factors. Thus, the distribution of pioneer tree species is expected to vary according to the gap characteristics and with human disturbances. We asked whether there was variation in the distribution of a pioneer species under different environmental conditions generated by natural disturbances, and between two forests with contrasting levels of human disturbance. To answer this question, we studied the distribution patterns and population persistence of the pioneer tree species Croton floribundus in the size and age gap range of a primary Brazilian forest. Additionally, we compared the plant density of two size-classes between a primary and an early successional human-disturbed forest. Croton floribundus was found to be widespread and equally distributed along the gap-size gradient in the primary forest. Overall density did not vary with gap size or age (F-ratio = 0.062, P = 0.941), and while juveniles were found to have a higher density in the early successional forest (P = 0.021), tree density was found to be similar between forests (P = 0.058). Our results indicate that the population structure of a pioneer tree species with long life span and a broad gap-size niche preference varied between natural and human-disturbed forests, but not with the level of natural disturbance. We believe this can be explained by the extreme environmental changes that occur after human disturbance. The ecological processes that affect the distribution of pioneer species in natural and human-modified forests may be similar, but our results suggest they act differently under the contrasting environmental conditions generated by natural and human disturbances.

  13. Variation in the population structure between a natural and a human-modified forest for a pioneer tropical tree species not restricted to large gaps

    PubMed Central

    Silvestrini, Milene; dos Santos, Flavio Antonio Maës

    2015-01-01

    The distribution of tree species in tropical forests is generally related to the occurrence of disturbances and shifts in the local environmental conditions such as light, temperature, and biotic factors. Thus, the distribution of pioneer tree species is expected to vary according to the gap characteristics and with human disturbances. We asked whether there was variation in the distribution of a pioneer species under different environmental conditions generated by natural disturbances, and between two forests with contrasting levels of human disturbance. To answer this question, we studied the distribution patterns and population persistence of the pioneer tree species Croton floribundus in the size and age gap range of a primary Brazilian forest. Additionally, we compared the plant density of two size-classes between a primary and an early successional human-disturbed forest. Croton floribundus was found to be widespread and equally distributed along the gap-size gradient in the primary forest. Overall density did not vary with gap size or age (F-ratio = 0.062, P = 0.941), and while juveniles were found to have a higher density in the early successional forest (P = 0.021), tree density was found to be similar between forests (P = 0.058). Our results indicate that the population structure of a pioneer tree species with long life span and a broad gap-size niche preference varied between natural and human-disturbed forests, but not with the level of natural disturbance. We believe this can be explained by the extreme environmental changes that occur after human disturbance. The ecological processes that affect the distribution of pioneer species in natural and human-modified forests may be similar, but our results suggest they act differently under the contrasting environmental conditions generated by natural and human disturbances. PMID:26120431

  14. Xenobiotic-Metabolizing Enzyme and Transporter Gene Expression in Primary Cultures of Human Hepatocytes Modulated by Toxcast Chemicals

    EPA Science Inventory

    Primary human hepatocyte cultures are useful in vitro model systems of human liver because when cultured under appropriate conditions the hepatocytes retain liver-like functionality such as metabolism, transport, and cell signaling. This model system was used to characterize the ...

  15. Profiling Bioactivity of the ToxCast Chemical Library Using BioMAP Primary Human Cell Systems

    EPA Science Inventory

    The complexity of human biology has made prediction of health effects as a consequence of exposure to environmental chemicals especially challenging. Complex cell systems, such as the Biologically Multiplexed Activity Profiling (BioMAP) primary, human, cell-based disease models, ...

  16. Neuro-impressions: interpreting the nature of human creativity

    PubMed Central

    Siler, Todd Lael

    2012-01-01

    Understanding the creative process is essential for realizing human potential. Over the past four decades, the author has explored this subject through his brain-inspired drawings, paintings, symbolic sculptures, and experimental art installations that present myriad impressions of human creativity. These impressionistic artworks interpret rather than illustrate the complexities of the creative process. They draw insights from empirical studies that correlate how human beings create, learn, remember, innovate, and communicate. In addition to offering fresh aesthetic experiences, this metaphorical art raises fundamental questions concerning the deep connections between the brain and its creations. The author describes his artworks as embodiments of everyday observations about the neuropsychology of creativity, and its all-purpose applications for stimulating and accelerating innovation. PMID:23091455

  17. Rangeland Ecosystem Services: Nature's Supply and Human's Demands

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Ecosystem services are the benefits that society receives from nature and they include the regulation of climate, the pollination of crops, the provisioning of intellectual inspiration and recreational environment, as well as many essential goods such as food, fiber, and wood. Rangeland ecosystem se...

  18. Children's Understanding of Human and Super-Natural Mind

    ERIC Educational Resources Information Center

    Makris, Nikos; Pnevmatikos, Dimitris

    2007-01-01

    Barrett, Richert, and Driesenga [Barrett, J. L., Richert, R. A., & Driesenga, A. (2001). "God's beliefs versus mother's: The development of nonhuman agents concepts." "Child Development," 72(1), 50-65] have suggested that children are able to conceptualize the representational properties held by certain super-natural entities, such as God, before…

  19. Assessing the primary nature of the Ediacaran δ13C record

    NASA Astrophysics Data System (ADS)

    Bergmann, K.; Osburn, M. R.; Grotzinger, J. P.; Eiler, J. M.; Fischer, W. W.

    2014-12-01

    Neoproterozoic large negative carbon isotope excursions remain an enigmatic feature of the long-term carbon isotopic record yet their temporal distribution predating the appearance and diversification of complex animals in the fossil record demands an improved understanding of their origin. There is considerable uncertainty on whether these extreme excursions reflect primary perturbations in marine DIC, or whether they are post-depositional features. A variety of diagenetic processes have been proposed to generate the observed record including mechanisms relating to sea level drawdown, burial diagenesis in the presence of hydrocarbons and precipitation of authigenic carbonates. We examine perplexing aspects of the largest negative excursion on record—the Ediacaran Shuram Excursion—including: (1) co-variation in δ13C and δ18O carbonate, (2) elevated trace metal signatures, and (3) its global distribution. We combine bulk and micro-scale analysis of isotopic composition using carbonate clumped isotope thermometry and SIMS, and trace metal enrichments using ICP-OES, XANES and electron microprobe measurements. We find there is little evidence for large-scale isotopic re-ordering associated with open system diagenesis. Instead the bulk of the δ18Omin trend can be explained by a two-step change caused by 1) a temperature increase and fluid composition change from enriched evaporative fluids to open marine fluids and 2) a mineralogical shift from dolomite to calcite. The excursion is correlated with an increase in fine-grained, poorly-weathered detrital sediment that accounts for the majority of the increase in bulk trace metal enrichment. Additionally, SIMS analysis indicates there is no difference in the δ13C of authigenic phases versus primary carbonate phases suggesting the δ13C of the fluid was not modified during burial. These results suggest the combined influences of pH, temperature and carbonate mineralogy (calcite vs. aragonite) on the isotopic

  20. Natural course of pain and disability following primary lumbar discectomy: protocol for a systematic review and meta-analysis

    PubMed Central

    Rushton, A; Heneghan, N; Heijmans, M W; Staal, J B; Goodwin, P

    2016-01-01

    Introduction Knowledge about the natural clinical course is needed to improve understanding of recovery postsurgery as outcome is poor for some patients. Knowledge of the natural clinical course of symptoms and disability will inform optimal timing and the nature of rehabilitation intervention. The objective of this study is to provide first evidence synthesis investigating the natural clinical course of disability and pain in patients aged >16 years post primary lumbar discectomy. Methods and analysis A systematic review and data synthesis will be conducted. Prospective cohorts that include a well-defined inception cohort (point of surgery) of adult participants who have undergone primary lumbar discectomy/microdiscectomy will be included. Outcomes will include measurements reported on 1 or more outcomes of disability and pain, with a baseline presurgery measurement. Following development of the search strategy, 2 reviewers will independently search information sources, assess identified studies for inclusion, extract data and assess risk of bias. A third reviewer will mediate on any disagreement at each stage. The search will employ sensitive topic-based strategies designed for each database from inception to 31 January 2016. There will be no language or geographical restrictions. Risk of bias will be assessed using a modified QUality In Prognostic Studies (QUIPS) tool . Data will be extracted for time points where follow-up was at least 80%. Means and 95% CIs will be plotted over time for pain and disability. All results will be reported in the context of study quality. Ethics and dissemination This review will provide the first rigorous summary of the course of pain and disability across all published prospective cohorts. The findings will inform our understanding of when to offer and how to optimise rehabilitation following surgery. Results will be published in an open access journal. The study raises no ethical issues. PROSPERO registration number CRD

  1. DGEM--a microarray gene expression database for primary human disease tissues.

    PubMed

    Xia, Yuni; Campen, Andrew; Rigsby, Dan; Guo, Ying; Feng, Xingdong; Su, Eric W; Palakal, Mathew; Li, Shuyu

    2007-01-01

    Gene expression patterns can reflect gene regulations in human tissues under normal or pathologic conditions. Gene expression profiling data from studies of primary human disease samples are particularly valuable since these studies often span many years in order to collect patient clinical information and achieve a large sample size. Disease-to-Gene Expression Mapper (DGEM) provides a beneficial community resource to access and analyze these data; it currently includes Affymetrix oligonucleotide array datasets for more than 40 human diseases and 1400 samples. The data are normalized to the same scale and stored in a relational database. A statistical-analysis pipeline was implemented to identify genes abnormally expressed in disease tissues or genes whose expressions are associated with clinical parameters such as cancer patient survival. Data-mining results can be queried through a web-based interface at http://dgem.dhcp.iupui.edu/. The query tool enables dynamic generation of graphs and tables that are further linked to major gene and pathway resources that connect the data to relevant biology, including Entrez Gene and Kyoto Encyclopedia of Genes and Genomes (KEGG). In summary, DGEM provides scientists and physicians a valuable tool to study disease mechanisms, to discover potential disease biomarkers for diagnosis and prognosis, and to identify novel gene targets for drug discovery. The source code is freely available for non-profit use, on request to the authors. PMID:17570735

  2. Electrically Activated Primary Human Fibroblasts Improve In Vitro and In Vivo Skin Regeneration.

    PubMed

    Rouabhia, Mahmoud; Park, Hyun Jin; Zhang, Ze

    2016-08-01

    Electrical stimulation (ES) changes cellular behaviors and thus constitutes a potential strategy to promote wound healing. However, well-controlled in vitro findings have yet to be translated to in vivo trials. This study was to demonstrate the feasibility and advantages of transplanting electrically activated cells (E-Cells) to help wound healing. Primary human skin fibroblasts were activated through well defined ES and cultured with keratinocytes to generate engineered human skin (EHS), which were transplanted to nu/nu mice. The electrically activated EHS grafts were analyzed at 20 and 30 days post-grafting, showing faster wound closure, thick epidermis, vasculature, and functional basement membrane containing laminin and type IV collagen that were totally produced by the implanted human cells. Because a variety of cells can be electrically activated, E-Cells may become a new cell source and the transplantation of E-Cells may represent a new strategy in wound healing and tissue engineering. J. Cell. Physiol. 231: 1814-1821, 2016. © 2015 Wiley Periodicals, Inc. PMID:26661681

  3. RTTN Mutations Link Primary Cilia Function to Organization of the Human Cerebral Cortex

    PubMed Central

    Kheradmand Kia, Sima; Verbeek, Elly; Engelen, Erik; Schot, Rachel; Poot, Raymond A.; de Coo, Irenaeus F.M.; Lequin, Maarten H.; Poulton, Cathryn J.; Pourfarzad, Farzin; Grosveld, Frank G.; Brehm, António; de Wit, Marie Claire Y.; Oegema, Renske; Dobyns, William B.; Verheijen, Frans W.; Mancini, Grazia M.S.

    2012-01-01

    Polymicrogyria is a malformation of the developing cerebral cortex caused by abnormal organization and characterized by many small gyri and fusion of the outer molecular layer. We have identified autosomal-recessive mutations in RTTN, encoding Rotatin, in individuals with bilateral diffuse polymicrogyria from two separate families. Rotatin determines early embryonic axial rotation, as well as anteroposterior and dorsoventral patterning in the mouse. Human Rotatin has recently been identified as a centrosome-associated protein. The Drosophila melanogaster homolog of Rotatin, Ana3, is needed for structural integrity of centrioles and basal bodies and maintenance of sensory neurons. We show that Rotatin colocalizes with the basal bodies at the primary cilium. Cultured fibroblasts from affected individuals have structural abnormalities of the cilia and exhibit downregulation of BMP4, WNT5A, and WNT2B, which are key regulators of cortical patterning and are expressed at the cortical hem, the cortex-organizing center that gives rise to Cajal-Retzius (CR) neurons. Interestingly, we have shown that in mouse embryos, Rotatin colocalizes with CR neurons at the subpial marginal zone. Knockdown experiments in human fibroblasts and neural stem cells confirm a role for RTTN in cilia structure and function. RTTN mutations therefore link aberrant ciliary function to abnormal development and organization of the cortex in human individuals. PMID:22939636

  4. Electrically Activated Primary Human Fibroblasts Improve In Vitro and In Vivo Skin Regeneration.

    PubMed

    Rouabhia, Mahmoud; Park, Hyun Jin; Zhang, Ze

    2016-08-01

    Electrical stimulation (ES) changes cellular behaviors and thus constitutes a potential strategy to promote wound healing. However, well-controlled in vitro findings have yet to be translated to in vivo trials. This study was to demonstrate the feasibility and advantages of transplanting electrically activated cells (E-Cells) to help wound healing. Primary human skin fibroblasts were activated through well defined ES and cultured with keratinocytes to generate engineered human skin (EHS), which were transplanted to nu/nu mice. The electrically activated EHS grafts were analyzed at 20 and 30 days post-grafting, showing faster wound closure, thick epidermis, vasculature, and functional basement membrane containing laminin and type IV collagen that were totally produced by the implanted human cells. Because a variety of cells can be electrically activated, E-Cells may become a new cell source and the transplantation of E-Cells may represent a new strategy in wound healing and tissue engineering. J. Cell. Physiol. 231: 1814-1821, 2016. © 2015 Wiley Periodicals, Inc.

  5. Foxp3-dependent transformation of human primary CD4+ T lymphocytes by the retroviral protein tax.

    PubMed

    Chen, Li; Liu, Dan; Zhang, Yang; Zhang, Huan; Cheng, Hua

    2015-10-23

    The retroviral Tax proteins of human T cell leukemia virus type 1 and 2 (HTLV-1 and -2) are highly homologous viral transactivators. Both viral proteins can immortalize human primary CD4+ memory T cells, but when expressed alone they rarely transform T cells. In the present study, we found that the Tax proteins displayed a differential ability to immortalize human CD4+Foxp3+ T cells with characteristic expression of CTLA-4 and GITR. Because epidermal growth factor receptor (EGFR) was reportedly expressed and activated in a subset of CD4+Foxp3+ T cells, we introduced an activated EGFR into Tax-immortalized CD4+Foxp3+ T cells. We observed that these modified cells were grown independently of exogenous IL-2, correlating with a T cell transformation phenotype. In Tax-immortalized CD4+Foxp3- T cells, ectopic expression of Foxp3 was a prerequisite for Tax transformation of T cells. Accordingly, treatment of the transformed T cells with erlotinib, a selective inhibitor of EGFR, induced degradation of EGFR in lysosome, consequently causing T cell growth inhibition. Further, we identified autophagy as a crucial cellular survival pathway for the transformed T cells. Silencing key autophagy molecules including Beclin1, Atg5 and PI3 kinase class III (PI3KC3) resulted in drastic impairment of T cell growth. Our data, therefore, unveiled a previously unidentified role of Foxp3 in T cell transformation, providing a molecular basis for HTLV-1 transformation of CD4+Foxp3+ T cells.

  6. Impact of Environmental Chemicals on the Transcriptome of Primary Human Hepatocytes: Potential for Health Effects.

    PubMed

    Mitchell, Robert D; Dhammi, Anirudh; Wallace, Andrew; Hodgson, Ernest; Roe, R Michael

    2016-08-01

    New paradigms for human health risk assessment of environmental chemicals emphasize the use of molecular methods and human-derived cell lines. In this study, we examined the effects of the insect repellent DEET (N,N-diethyl-m-toluamide) and the phenylpyrazole insecticide fipronil (fluocyanobenpyrazole) on transcript levels in primary human hepatocytes. These chemicals were tested individually and as a mixture. RNA-Seq showed that 100 μM DEET significantly increased transcript levels (α = 0.05) for 108 genes and lowered transcript levels for 64 genes and fipronil at 10 μM increased the levels of 2246 transcripts and decreased the levels for 1428 transcripts. Fipronil was 21-times more effective than DEET in eliciting changes, even though the treatment concentration was 10-fold lower for fipronil versus DEET. The mixture of DEET and fipronil produced a more than additive effect (levels increased for 3017 transcripts and decreased for 2087 transcripts). The transcripts affected for all chemical treatments were classified by GO analysis and mapped to chromosomes. The overall treatment responses, specific pathways, and individual transcripts affected were discussed at different levels of fold-change. Changes found in transcript levels in response to treatments will require further research to understand their importance in overall cellular, organ, and organismic function. PMID:27091632

  7. Dexamethasone-Mediated Activation of Fibronectin Matrix Assembly Reduces Dispersal of Primary Human Glioblastoma Cells

    PubMed Central

    Shannon, Stephen; Vaca, Connan; Jia, Dongxuan; Entersz, Ildiko; Schaer, Andrew; Carcione, Jonathan; Weaver, Michael; Avidar, Yoav; Pettit, Ryan; Nair, Mohan; Khan, Atif; Foty, Ramsey A.

    2015-01-01

    Despite resection and adjuvant therapy, the 5-year survival for patients with Glioblastoma multiforme (GBM) is less than 10%. This poor outcome is largely attributed to rapid tumor growth and early dispersal of cells, factors that contribute to a high recurrence rate and poor prognosis. An understanding of the cellular and molecular machinery that drive growth and dispersal is essential if we are to impact long-term survival. Our previous studies utilizing a series of immortalized GBM cell lines established a functional causation between activation of fibronectin matrix assembly (FNMA), increased tumor cohesion, and decreased dispersal. Activation of FNMA was accomplished by treatment with Dexamethasone (Dex), a drug routinely used to treat brain tumor related edema. Here, we utilize a broad range of qualitative and quantitative assays and the use of a human GBM tissue microarray and freshly-isolated primary human GBM cells grown both as conventional 2D cultures and as 3D spheroids to explore the role of Dex and FNMA in modulating various parameters that can significantly influence tumor cell dispersal. We show that the expression and processing of fibronectin in a human GBM tissue-microarray is variable, with 90% of tumors displaying some abnormality or lack in capacity to secrete fibronectin or assemble it into a matrix. We also show that low-passage primary GBM cells vary in their capacity for FNMA and that Dex treatment reactivates this process. Activation of FNMA effectively “glues” cells together and prevents cells from detaching from the primary mass. Dex treatment also significantly increases the strength of cell-ECM adhesion and decreases motility. The combination of increased cohesion and decreased motility discourages in vitro and ex vivo dispersal. By increasing cell-cell cohesion, Dex also decreases growth rate of 3D spheroids. These effects could all be reversed by an inhibitor of FNMA and by the glucocorticoid receptor antagonist, RU-486. Our

  8. Enhanced uptake of multiple sclerosis-derived myelin by THP-1 macrophages and primary human microglia

    PubMed Central

    2014-01-01

    Background The pathological hallmark of multiple sclerosis (MS) is myelin phagocytosis. It remains unclear why microglia and macrophages demyelinate axons in MS, but previously found or yet-unknown changes in the myelin of MS patients could contribute to this process. We therefore studied whether myelin from normal-appearing white matter (NAWM) of MS donors is phagocytosed more efficiently than myelin from control donors. Methods Myelin was isolated from 11 MS and 12 control brain donors and labeled with the pH-sensitive fluorescent dye pHrodo to quantify uptake in lysosomes. Phagocytosis by differentiated THP-1 macrophages and by primary human microglia was quantified with flow cytometry. Whereas myelin uptake by THP-1 macrophages reached a plateau after approximately 24 hours, uptake by primary human microglia showed an almost linear increase over a 72–hour period. Data were statistically analyzed with the Mann–Whitney U test. Results MS-derived myelin was phagocytosed more efficiently by THP-1 macrophages after 6-hour incubation (P = 0.001 for the percentage of myelin-phagocytosing cells and P = 0.0005 for total myelin uptake) and after 24-hour incubation (P = 0.0006 and P = 0.0001, respectively), and by microglia after 24-hour incubation (P = 0.0106 for total myelin uptake). This enhanced uptake was not due to differences in the oxidation status of the myelin. Interestingly, myelin phagocytosis correlated negatively with the age of myelin donors, whereas the age of microglia donors showed a positive trend with myelin phagocytosis. Conclusions Myelin isolated from normal-appearing white matter of MS donors was phagocytosed more efficiently than was myelin isolated from control brain donors by both THP-1 macrophages and primary human microglia. These data indicate that changes in MS myelin might precede phagocyte activation and subsequent demyelination in MS. Identifying these myelin changes responsible for enhancing phagocytic ability

  9. Genotoxic and clastogenic effects of monohaloacetic acid drinking water disinfection by-products in primary human lymphocytes.

    PubMed

    Escobar-Hoyos, Luisa F; Hoyos-Giraldo, Luz Stella; Londoño-Velasco, Elizabeth; Reyes-Carvajal, Ingrid; Saavedra-Trujillo, Diana; Carvajal-Varona, Silvio; Sánchez-Gómez, Adalberto; Wagner, Elizabeth D; Plewa, Michael J

    2013-06-15

    The haloacetic acids (HAAs) are the second-most prevalent class of drinking water disinfection by-products formed by chemical disinfectants. Previous studies have determined DNA damage and repair of HAA-induced lesions in mammalian and human cell lines; however, little is known of the genomic DNA and chromosome damage induced by these compounds in primary human cells. The aim of this study was to evaluate the genotoxic and clastogenic effects of the monoHAA disinfection by-products in primary human lymphocytes. All monoHAAs were genotoxic in primary human lymphocytes, the rank order of genotoxicity and cytotoxicity was IAA > BAA > CAA. After 6 h of repair time, only 50% of the DNA damage (maximum decrease in DNA damage) was repaired compared to the control. This demonstrates that primary human lymphocytes are less efficient in repairing the induced damage by monoHAAs than previous studies with mammalian cell lines. In addition, the monoHAAs induced an increase in the chromosome aberration frequency as a measurement of the clastogenic effect of these compounds. These results coupled with genomic technologies in primary human cells and other mammalian non-cancerous cell lines may lead to the identification of biomarkers that may be employed in feedback loops to aid water chemists and engineers in the overall goal of producing safer drinking water.

  10. The optical nature of methylsuccinic acid in human urine

    NASA Technical Reports Server (NTRS)

    Zeitman, B.; Lawless, J. G.

    1975-01-01

    Methylsuccinic acid was isolated from human urine, derivatized as the di-S-(+)-2-butyl ester, and analyzed using a gas chromatographic system capable of separating the enantiomers of the derivative. The R-(+)-isomer was found to be present. Methylsuccinic acid is potentially important as a criterion for abiogenicity, having been obtained as a racemic mixture from sources known to be abiotic.

  11. Gradient Shifts with Naturally Occurring Human Face Stimuli

    ERIC Educational Resources Information Center

    Derenne, Adam; Breitstein, R. Michael

    2006-01-01

    The present research examined stimulus generalization and gradient shifts on a dimension involving human faces. Twenty undergraduates were instructed to examine the proportion of the total face length that lay between the tip of the nose and the end of the chin. The face stimuli were images of actual people shown on a computer screen; no face was…

  12. Natural selection on genes that underlie human disease susceptibility

    PubMed Central

    Blekhman, Ran; Man, Orna; Herrmann, Leslie; Boyko, Adam R.; Indap, Amit; Kosiol, Carolin; Bustamante, Carlos D.; Teshima, Kosuke M.; Przeworski, Molly

    2008-01-01

    What evolutionary forces shape genes that contribute to the risk of human disease? Do similar selective pressures act on alleles that underlie simple vs. complex disorders? [1-3]. Answers to these questions will shed light on the origin of human disorders (e.g., [4]), and help to predict the population frequencies of alleles that contribute to disease risk, with important implications for the efficient design of mapping studies [5-7]. As a first step towards addressing them, we created a hand-curated version of the Mendelian Inheritance in Man database (OMIM). We then examined selective pressures on Mendelian disease genes, genes that contribute to complex disease risk and genes known to be essential in mouse, by analyzing patterns of human polymorphism and of divergence between human and rhesus macaque. We find that Mendelian disease genes appear to be under widespread purifying selection, especially when the disease mutations are dominant (rather than recessive). In contrast, the class of genes that influence complex disease risk shows little signs of evolutionary conservation, possibly because this category includes both targets of purifying and positive selection. PMID:18571414

  13. Continuous mucociliary transport by primary human airway epithelial cells in vitro

    PubMed Central

    Sears, Patrick R.; Yin, Wei-Ning

    2015-01-01

    Mucociliary clearance (MCC) is an important innate defense mechanism that continuously removes inhaled pathogens and particulates from the airways. Normal MCC is essential for maintaining a healthy respiratory system, and impaired MCC is a feature of many airway diseases, including both genetic (cystic fibrosis, primary ciliary dyskinesia) and acquired (chronic obstructive pulmonary disease, bronchiectasis) disorders. Research into the fundamental processes controlling MCC, therefore, has direct clinical application, but has been limited in part due to the difficulty of studying this complex multicomponent system in vitro. In this study, we have characterized a novel method that allows human airway epithelial cells to differentiate into a mucociliary epithelium that transports mucus in a continuous circular track. The mucociliary transport device allows the measurement and manipulation of all features of mucociliary transport in a controlled in vitro system. In this initial study, the effect of ciliary beat frequency and mucus concentration on the speed of mucociliary transport was investigated. PMID:25979076

  14. Frequency preference and attention effects across cortical depths in the human primary auditory cortex

    PubMed Central

    De Martino, Federico; Moerel, Michelle; Ugurbil, Kamil; Goebel, Rainer; Yacoub, Essa; Formisano, Elia

    2015-01-01

    Columnar arrangements of neurons with similar preference have been suggested as the fundamental processing units of the cerebral cortex. Within these columnar arrangements, feed-forward information enters at middle cortical layers whereas feedback information arrives at superficial and deep layers. This interplay of feed-forward and feedback processing is at the core of perception and behavior. Here we provide in vivo evidence consistent with a columnar organization of the processing of sound frequency in the human auditory cortex. We measure submillimeter functional responses to sound frequency sweeps at high magnetic fields (7 tesla) and show that frequency preference is stable through cortical depth in primary auditory cortex. Furthermore, we demonstrate that—in this highly columnar cortex—task demands sharpen the frequency tuning in superficial cortical layers more than in middle or deep layers. These findings are pivotal to understanding mechanisms of neural information processing and flow during the active perception of sounds. PMID:26668397

  15. Chemotherapy-induced Dkk-1 expression by primary human mesenchymal stem cells is p53 dependent.

    PubMed

    Hare, Ian; Evans, Rebecca; Fortney, James; Moses, Blake; Piktel, Debbie; Slone, William; Gibson, Laura F

    2016-10-01

    Mesenchymal stem cells (MSCs) are abundant throughout the body and regulate signaling within tumor microenvironments. Wnt signaling is an extrinsically regulated pathway that has been shown to regulate tumorigenesis in many types of cancer. After evaluating a panel of Wnt activating and inhibiting molecules, we show that primary human MSCs increase the expression of Dkk-1, an inhibitor of Wnt signaling, into the extracellular environment following chemotherapy exposure in a p53-dependent manner. Dkk-1 has been shown to promote tumor growth in several models of malignancy, suggesting that MSC-derived Dkk-1 could counteract the intent of cytotoxic chemotherapy, and that pharmacologic inhibition of Dkk-1 in patients receiving chemotherapy treatment for certain malignancies may be warranted. PMID:27586146

  16. Nanoparticle-mediated conversion of primary human astrocytes into neurons and oligodendrocytes.

    PubMed

    Li, Xiaowei; Kozielski, Kristen; Cheng, Yu-Hao; Liu, Huanhuan; Zamboni, Camila Gadens; Green, Jordan; Mao, Hai-Quan

    2016-06-21

    Central nervous system (CNS) diseases and injuries are accompanied by reactive gliosis and scarring involving the activation and proliferation of astrocytes to form hypertrophic and dense structures, which present a significant barrier to neural regeneration. Engineering astrocytes to functional neurons or oligodendrocytes may constitute a novel therapeutic strategy for CNS diseases and injuries. Such direct cellular programming has been successfully demonstrated using viral vectors via the transduction of transcriptional factors, such as Sox2, which could program resident astrocytes into neurons in the adult brain and spinal cord, albeit the efficiency was low. Here we report a non-viral nanoparticle-based transfection method to deliver Sox2 or Olig2 into primary human astrocytes and demonstrate the effective conversion of the astrocytes into neurons and oligodendrocyte progenitors following the transgene expression of Sox2 and Olig2, respectively. This approach is highly translatable for engineering astrocytes to repair injured CNS tissues. PMID:27328202

  17. The Degradation Interface of Magnesium Based Alloys in Direct Contact with Human Primary Osteoblast Cells

    PubMed Central

    Willumeit-Römer, Regine; Laipple, Daniel; Luthringer, Bérengère; Feyerabend, Frank

    2016-01-01

    Magnesium alloys have been identified as a new generation material of orthopaedic implants. In vitro setups mimicking physiological conditions are promising for material / degradation analysis prior to in vivo studies however the direct influence of cell on the degradation mechanism has never been investigated. For the first time, the direct, active, influence of human primary osteoblasts on magnesium-based materials (pure magnesium, Mg-2Ag and Mg-10Gd alloys) is studied for up to 14 days. Several parameters such as composition of the degradation interface (directly beneath the cells) are analysed with a scanning electron microscope equipped with energy dispersive X-ray and focused ion beam. Furthermore, influence of the materials on cell metabolism is examined via different parameters like active mineralisation process. The results are highlighting the influences of the selected alloying element on the initial cells metabolic activity. PMID:27327435

  18. Primary human adult lung epithelial cells in vitro: response to interferon-gamma and cytomegalovirus.

    PubMed Central

    Ibrahim, L; Dominguez, M; Yacoub, M

    1993-01-01

    Primary human adult lung epithelial cells (ALEC) were established in culture using the most distal parts of the lung to avoid the airways. Immunocytochemical peroxidase staining and semiquantitative flow cytometry were used to characterize the cells in conjunction with a panel of monoclonal antibodies (mAb). The cells showed a constitutive expression of major histocompatibility complex (MHC) class I antigens, patchy expression of intercellular adhesion molecule-1 (ICAM-1) and a weak patchy expression of MHC class II antigens (detected using immunocytochemical staining). Incubation of the primary ALEC with interferon-gamma (IFN-gamma) (250 U/ml) stimulated an up-regulation of the expression of these three antigens to varying degrees; expression of MHC class I antigens and ICAM-1 molecules showed an up-regulation at 10 hr after the start of the treatment, reaching a peak at 48 hr, maintaining it for the next 24 hr and then, steadily and progressively, losing it towards the end of the experiment at 96 hr. Expression of HLA-DR showed an up-regulation at 17 hr after the start of the treatment, reaching a peak at 72 hr and maintaining it for the next 24 hr. Cytomegalovirus (CMV) infection of ALEC in culture caused an up-regulation of expression of class I antigens and ICAM-1, but not DR. However, when the infected cells were incubated with IFN-gamma, an up-regulation in the expression of DR took place. Therefore, within the micro-environment of the transplanted lung the presence of cytokines (IFN-gamma) produced by infiltrating activated mononuclear cells, may render the lung epithelial cells capable of acting as antigen-presenting cells, expressing high levels of class I antigens, ICAM-1 and class II antigens, activating CD8 and CD4 cells thus playing a major part in the process of rejection of the lung allograft; themselves becoming a primary target in the process. Images Figure 1 Figure 2 PMID:8099565

  19. A five-primary photostimulator suitable for studying intrinsically photosensitive retinal ganglion cell functions in humans.

    PubMed

    Cao, Dingcai; Nicandro, Nathaniel; Barrionuevo, Pablo A

    2015-01-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) can respond to light directly through self-contained photopigment, melanopsin. IpRGCs also receive synaptic inputs from rods and cones. Thus, studying ipRGC functions requires a novel photostimulating method that can account for all of the photoreceptor inputs. Here, we introduced an inexpensive LED-based five-primary photostimulator that can control the excitations of rods, S-, M-, L-cones, and melanopsin-containing ipRGCs in humans at constant background photoreceptor excitation levels, a critical requirement for studying the adaptation behavior of ipRGCs with rod, cone, or melanopsin input. We described the theory and technical aspects (including optics, electronics, software, and calibration) of the five-primary photostimulator. Then we presented two preliminary studies using the photostimulator we have implemented to measure melanopsin-mediated pupil responses and temporal contrast sensitivity function (TCSF). The results showed that the S-cone input to pupil responses was antagonistic to the L-, M- or melanopsin inputs, consistent with an S-OFF and (L + M)-ON response property of primate ipRGCs (Dacey et al., 2005). In addition, the melanopsin-mediated TCSF had a distinctive pattern compared with L + M or S-cone mediated TCSF. Other than controlling individual photoreceptor excitation independently, the five-primary photostimulator has the flexibility in presenting stimuli modulating any combination of photoreceptor excitations, which allows researchers to study the mechanisms by which ipRGCs combine various photoreceptor inputs. PMID:25624466

  20. A five-primary photostimulator suitable for studying intrinsically photosensitive retinal ganglion cell functions in humans

    PubMed Central

    Cao, Dingcai; Nicandro, Nathaniel; Barrionuevo, Pablo A.

    2015-01-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) can respond to light directly through self-contained photopigment, melanopsin. IpRGCs also receive synaptic inputs from rods and cones. Thus, studying ipRGC functions requires a novel photostimulating method that can account for all of the photoreceptor inputs. Here, we introduced an inexpensive LED-based five-primary photostimulator that can control the excitations of rods, S-, M-, L-cones, and melanopsin-containing ipRGCs in humans at constant background photoreceptor excitation levels, a critical requirement for studying the adaptation behavior of ipRGCs with rod, cone, or melanopsin input. We described the theory and technical aspects (including optics, electronics, software, and calibration) of the five-primary photostimulator. Then we presented two preliminary studies using the photostimulator we have implemented to measure melanopsin-mediated pupil responses and temporal contrast sensitivity function (TCSF). The results showed that the S-cone input to pupil responses was antagonistic to the L-, M- or melanopsin inputs, consistent with an S-OFF and (L + M)-ON response property of primate ipRGCs (Dacey et al., 2005). In addition, the melanopsin-mediated TCSF had a distinctive pattern compared with L + M or S-cone mediated TCSF. Other than controlling individual photoreceptor excitation independently, the five-primary photostimulator has the flexibility in presenting stimuli modulating any combination of photoreceptor excitations, which allows researchers to study the mechanisms by which ipRGCs combine various photoreceptor inputs. PMID:25624466

  1. Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission.

    PubMed

    Tabata, Takako; Petitt, Matthew; Puerta-Guardo, Henry; Michlmayr, Daniela; Wang, Chunling; Fang-Hoover, June; Harris, Eva; Pereira, Lenore

    2016-08-10

    Zika virus (ZIKV) infection during pregnancy is linked to severe birth defects, but mother-to-fetus transmission routes are unknown. We infected different primary cell types from mid- and late-gestation placentas and explants from first-trimester chorionic villi with the prototype Ugandan and a recently isolated Nicaraguan ZIKV strain. ZIKV infects primary human placental cells and explants-cytotrophoblasts, endothelial cells, fibroblasts, and Hofbauer cells in chorionic villi and amniotic epithelial cells and trophoblast progenitors in amniochorionic membranes-that express Axl, Tyro3, and/or TIM1 viral entry cofactors. ZIKV produced NS3 and E proteins and generated higher viral titers in amniotic epithelial cells from mid-gestation compared to late-gestation placentas. Duramycin, a peptide that binds phosphatidylethanolamine in enveloped virions and precludes TIM1 binding, reduced ZIKV infection in placental cells and explants. Our results suggest that ZIKV spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes and that targeting TIM1 could suppress infection at the uterine-placental interface. PMID:27443522

  2. Human umbilical mesenchymal stem cells conditioned medium promote primary wound healing regeneration

    PubMed Central

    Kusindarta, Dwi Liliek; Wihadmadyatami, Hevi; Fibrianto, Yuda Heru; Nugroho, Widagdo Sri; Susetya, Heru; Musana, Dewi Kania; Wijayanto, Hery; Prihatna, Surya Agus; Wahyuni, A. E. T. H.

    2016-01-01

    Aim: This research was conducted to clarify the capability of human umbilical mesenchymal stem cells conditioned medium (HU-MSCM) to promote regenerations of primary wound healing on the incision skin injury. Materials and Methods: In this study, two approaches in vitro and in vivo already done. On in vitro analysis, tube formation was performed using HU vein endothelial cells in the presence of HU-MSCM, in some experiments cells line was incubated prior the presence of lipopolysaccharide and HU-MSCM then apoptosis assay was performed. Furthermore, in vivo experiments 12 female rats (Rattus norvegicus) were used after rats anesthetized, 7 mm wound was made by incision on the left side of the body. The wound was treated with HU-MSCM containing cream, povidone iodine was run as a control. Wound healing regenerations on the skin samples were visualized by hematoxylin-eosin staining. Results: In vitro models elucidate HU-MSCM may decreasing inflammation at the beginning of wound healing, promote cell migration and angiogenesis. In addition in vivo models show that the incision length on the skin is decreasing and more smaller, HE staining describe decreasing of inflammation phase, increasing of angiogenesis, accelerate fibroplasia, and maturation phase. Conclusions: Taken together our observation indicates that HU-MSCM could promote the acceleration of skin tissue regenerations in primary wound healing process. PMID:27397984

  3. Replication of human immunodeficiency virus type 1 in primary dendritic cell cultures.

    PubMed Central

    Langhoff, E; Terwilliger, E F; Bos, H J; Kalland, K H; Poznansky, M C; Bacon, O M; Haseltine, W A

    1991-01-01

    The ability of the human immunodeficiency virus type 1 (HIV-1) to replicate in primary blood dendritic cells was investigated. Dendritic cells compose less than 1% of the circulating leukocytes and are nondividing cells. Highly purified preparations of dendritic cells were obtained using recent advances in cell fractionation. The results of these experiments show that dendritic cells, in contrast to monocytes and T cells, support the active replication of all strains of HIV-1 tested, including T-cell tropic and monocyte/macrophage tropic isolates. The dendritic cell cultures supported much more virus production than did cultures of primary unseparated T cells, CD4+ T cells, and adherent as well as nonadherent monocytes. Replication of HIV-1 in dendritic cells produces no noticeable cytopathic effect nor does it decrease total cell number. The ability of the nonreplicating dendritic cells to support high levels of replication of HIV-1 suggests that this antigen-presenting cell population, which is also capable of supporting clonal T-cell growth, may play a central role in HIV pathogenesis, serving as a source of continued infection of CD4+ T cells and as a reservoir of virus infection. Images PMID:1910172

  4. Response of Primary Human Airway Epithelial Cells to Influenza Infection: A Quantitative Proteomic Study

    PubMed Central

    2012-01-01

    Influenza A virus exerts a large health burden during both yearly epidemics and global pandemics. However, designing effective vaccine and treatment options has proven difficult since the virus evolves rapidly. Therefore, it may be beneficial to identify host proteins associated with viral infection and replication to establish potential new antiviral targets. We have previously measured host protein responses in continuously cultured A549 cells infected with mouse-adapted virus strain A/PR/8/34(H1N1; PR8). We here identify and measure host proteins differentially regulated in more relevant primary human bronchial airway epithelial (HBAE) cells. A total of 3740 cytosolic HBAE proteins were identified by 2D LC–MS/MS, of which 52 were up-regulated ≥2-fold and 41 were down-regulated ≥2-fold after PR8 infection. Up-regulated HBAE proteins clustered primarily into interferon signaling, other host defense processes, and molecular transport, whereas down-regulated proteins were associated with cell death signaling pathways, cell adhesion and motility, and lipid metabolism. Comparison to influenza-infected A549 cells indicated some common influenza-induced host cell alterations, including defense response, molecular transport proteins, and cell adhesion. However, HBAE-specific alterations consisted of interferon and cell death signaling. These data point to important differences between influenza replication in continuous and primary cell lines and/or alveolar and bronchial epithelial cells. PMID:22694362

  5. Zika Virus Targets Different Primary Human Placental Cells, Suggesting Two Routes for Vertical Transmission.

    PubMed

    Tabata, Takako; Petitt, Matthew; Puerta-Guardo, Henry; Michlmayr, Daniela; Wang, Chunling; Fang-Hoover, June; Harris, Eva; Pereira, Lenore

    2016-08-10

    Zika virus (ZIKV) infection during pregnancy is linked to severe birth defects, but mother-to-fetus transmission routes are unknown. We infected different primary cell types from mid- and late-gestation placentas and explants from first-trimester chorionic villi with the prototype Ugandan and a recently isolated Nicaraguan ZIKV strain. ZIKV infects primary human placental cells and explants-cytotrophoblasts, endothelial cells, fibroblasts, and Hofbauer cells in chorionic villi and amniotic epithelial cells and trophoblast progenitors in amniochorionic membranes-that express Axl, Tyro3, and/or TIM1 viral entry cofactors. ZIKV produced NS3 and E proteins and generated higher viral titers in amniotic epithelial cells from mid-gestation compared to late-gestation placentas. Duramycin, a peptide that binds phosphatidylethanolamine in enveloped virions and precludes TIM1 binding, reduced ZIKV infection in placental cells and explants. Our results suggest that ZIKV spreads from basal and parietal decidua to chorionic villi and amniochorionic membranes and that targeting TIM1 could suppress infection at the uterine-placental interface.

  6. Radiological trace of mandibular primary growth center in postnatal human mandibles.

    PubMed

    Lee, Young Joon; Lee, Sang Shin; Park, Byoung Geol; Woo, Sang Doo; Kim, Eun Cheol; Kim, Yeon Sook; Lee, Suk Keun; Chi, Je Geun

    2006-12-01

    The mandibular primary growth center (MdPGC) of human fetus was conspicuously defined in the soft X-ray view of fetal mandibles. As the peripheral adaptive growth of mandible advances during the postnatal period, the MdPGC image became overshadowed by condensed cortical bones in soft X-ray view. In this study, we traced a sclerotic sequela of MdPGC during the postnatal period. Panoramic radiograms of 200 adults and soft X-ray views of 30 dried adult mandibles were analyzed by statistical methods. The former clearly showed an MdPGC below the middle portion of apices of canine and first premolar, which was distinguishable from mental foramen, and the latter also showed the MdPGC at the same area as a radiating and condensed radiopaque image, measuring 0.5-1.0 cm in diameter. This MdPGC position was seldom changed in the elderly people, even in the edentulous mandibles. Additionally, in the radiological examination, the benign tumors including odontogenic cysts hardly involved the MdPGC, while the malignant tumors of both primary and metastatic cancer frequently destroyed the MdPGC.

  7. CIT, a gene involved in neurogenic cytokinesis, is mutated in human primary microcephaly.

    PubMed

    Basit, Sulman; Al-Harbi, Khalid M; Alhijji, Sabri A M; Albalawi, Alia M; Alharby, Essa; Eldardear, Amr; Samman, Mohammed I

    2016-10-01

    Autosomal recessive primary microcephaly (MCPH) is a static neurodevelopmental disorder characterized by congenital small head circumference and non-progressive intellectual disability without additional severe brain malformations. MCPH is a genetically heterogeneous disorder. Sixteen genes (MCPH1-MCPH16) have been discovered so far, mutations thereof lead to autosomal recessive primary microcephaly. In a family, segregating MCPH in an autosomal recessive manner, genome-wide homozygosity mapping mapped a disease locus to 16.9-Mb region on chromosome 12q24.11-q24.32. Following this, exome sequencing in three affected individuals of the family discovered a splice site variant (c.753+3A>T) in citron kinase (CIT) gene, segregating with the disorder in the family. CIT co-localizes to the midbody ring during cytokinesis, and its loss of expression results in defects in neurogenic cytokinesis in both humans and mice. Splice site variant in CIT, identified in this study, is predicted to abolish splice donor site. cDNA sequence of an affected individual showed retention of an intron next to the splice donor site. The study, presented here, revealed the first variant in the CIT causing MCPH in the family. PMID:27519304

  8. Learning and Recognition of a Non-conscious Sequence of Events in Human Primary Visual Cortex

    PubMed Central

    Rosenthal, Clive R.; Andrews, Samantha K.; Antoniades, Chrystalina A.; Kennard, Christopher; Soto, David

    2016-01-01

    Summary Human primary visual cortex (V1) has long been associated with learning simple low-level visual discriminations [1] and is classically considered outside of neural systems that support high-level cognitive behavior in contexts that differ from the original conditions of learning, such as recognition memory [2, 3]. Here, we used a novel fMRI-based dichoptic masking protocol—designed to induce activity in V1, without modulation from visual awareness—to test whether human V1 is implicated in human observers rapidly learning and then later (15–20 min) recognizing a non-conscious and complex (second-order) visuospatial sequence. Learning was associated with a change in V1 activity, as part of a temporo-occipital and basal ganglia network, which is at variance with the cortico-cerebellar network identified in prior studies of “implicit” sequence learning that involved motor responses and visible stimuli (e.g., [4]). Recognition memory was associated with V1 activity, as part of a temporo-occipital network involving the hippocampus, under conditions that were not imputable to mechanisms associated with conscious retrieval. Notably, the V1 responses during learning and recognition separately predicted non-conscious recognition memory, and functional coupling between V1 and the hippocampus was enhanced for old retrieval cues. The results provide a basis for novel hypotheses about the signals that can drive recognition memory, because these data (1) identify human V1 with a memory network that can code complex associative serial visuospatial information and support later non-conscious recognition memory-guided behavior (cf. [5]) and (2) align with mouse models of experience-dependent V1 plasticity in learning and memory [6]. PMID:26948883

  9. Proangiogenic effects of environmentally relevant levels of bisphenol A in human primary endothelial cells.

    PubMed

    Andersson, Helén; Brittebo, Eva

    2012-03-01

    Bisphenol A (BPA) is widely used in the manufacturing of consumer products such as plastic food containers and food cans. Experimental studies suggest a relationship between exposure to BPA and changes in metabolic processes and reproductive organs. Also, epidemiological studies report an association between elevated exposure to BPA and cardiovascular disease and diabetes. Although alterations in the vascular endothelium are implicated in pathological conditions associated with BPA, little is known about the effects of BPA in the human endothelium. This study aimed to investigate the effects of 0.1 nM-1 μM of BPA on selected biomarkers of endothelial dysfunction, inflammation, and angiogenesis in human umbilical vein endothelial cells (HUVEC). The mRNA expression of biomarkers was assayed using qRT-PCR, and the production of nitric oxide and reactive oxygen species was measured using the H(2)DCFDA and the DAF-FM assays. The effect of BPA on phosphorylated eNOS was examined using Western blot and immunofluorescence, and the endothelial tube formation assay was used to investigate in vitro angiogenesis. BPA (≤1 μM) increased the mRNA expression of the proangiogenic genes VEGFR-2, VEGF-A, eNOS, and Cx43 and increased the production of nitric oxide in HUVEC. Furthermore, BPA increased the expression of phosphorylated eNOS and endothelial tube formation in HUVEC. These studies demonstrate that environmentally relevant levels of BPA have direct proangiogenic effects on human primary endothelial cells in vitro suggesting that the human endothelium may be an important target for BPA.

  10. Learning and Recognition of a Non-conscious Sequence of Events in Human Primary Visual Cortex.

    PubMed

    Rosenthal, Clive R; Andrews, Samantha K; Antoniades, Chrystalina A; Kennard, Christopher; Soto, David

    2016-03-21

    Human primary visual cortex (V1) has long been associated with learning simple low-level visual discriminations [1] and is classically considered outside of neural systems that support high-level cognitive behavior in contexts that differ from the original conditions of learning, such as recognition memory [2, 3]. Here, we used a novel fMRI-based dichoptic masking protocol-designed to induce activity in V1, without modulation from visual awareness-to test whether human V1 is implicated in human observers rapidly learning and then later (15-20 min) recognizing a non-conscious and complex (second-order) visuospatial sequence. Learning was associated with a change in V1 activity, as part of a temporo-occipital and basal ganglia network, which is at variance with the cortico-cerebellar network identified in prior studies of "implicit" sequence learning that involved motor responses and visible stimuli (e.g., [4]). Recognition memory was associated with V1 activity, as part of a temporo-occipital network involving the hippocampus, under conditions that were not imputable to mechanisms associated with conscious retrieval. Notably, the V1 responses during learning and recognition separately predicted non-conscious recognition memory, and functional coupling between V1 and the hippocampus was enhanced for old retrieval cues. The results provide a basis for novel hypotheses about the signals that can drive recognition memory, because these data (1) identify human V1 with a memory network that can code complex associative serial visuospatial information and support later non-conscious recognition memory-guided behavior (cf. [5]) and (2) align with mouse models of experience-dependent V1 plasticity in learning and memory [6]. PMID:26948883

  11. IFNL3 genotype is associated with differential induction of IFNL3 in primary human hepatocytes

    PubMed Central

    Kurbanov, Fuat; Kim, Yonghak; Latanich, Rachel; Chaudhari, Pooja; El-Diwany, Ramy; Knabel, Matt; Kandathil, Abraham J; Cameron, Andrew; Cox, Andrea; Jang, Yoon-Young; Thomas, David L; Balagopal, Ashwin

    2016-01-01

    Background Lambda interferons (IFNLs) have potent antiviral activity against HCV, and polymorphisms within the IFNL gene cluster near the IFNL3 gene strongly predict spontaneous- and treatment-related HCV infection outcomes. The mechanism(s) linking IFNL polymorphisms and HCV control is currently elusive. Methods IFNL induction was studied in primary human hepatocytes (PHH) from 18 human donors, peripheral blood mononuclear cells (PBMCs) from 18 human donors, multiple cell lines and induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-hepatocytes) from 7 human donors. After stimulation with intracellular RNA and infectious HCV, quantitative PCR (qPCR) primers and probes were designed to distinguish and quantify closely related IFNL messenger (m)RNAs from IFNL1, IFNL2 and IFNL3. Results PHH demonstrated the most potent induction of IFNLs, although had lower pre-stimulation levels compared to PBMCs, monocytes and cell lines. PHH stimulation with cytoplasmic poly I:C induced >1,000-fold expression of IFNL1, IFNL2 and IFNL3. PHH from donors who were homozygous for the favourable IFNL3 allele (IFNL3-CC) had higher IFNL3 induction compared to PHH from IFNL3-TT donors (P=0.03). Baseline IFNL mRNA expression and induction was also tested in iPSC-hepatocytes: iPSC-hepatocytes had significantly higher baseline expression of IFNLs compared to PHH (P<0.0001), and IFNL3 induction was marginally different in iPSC-hepatocytes by IFNL genotype (P=0.07). Conclusions Hepatocytes express IFNLs when stimulated by a synthetic viral RNA that signals the cell through the cytoplasm. IFNL induction may be greater in persons with the favourable IFNL3 allele. These data provide insight into the strong linkage between IFNL3 genetics and control of HCV infection. PMID:26109548

  12. Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells.

    PubMed

    Brun, Paola; Pathak, Surajit; Castagliuolo, Ignazio; Palù, Giorgio; Brun, Paola; Zuin, Matteo; Cavazzana, Roberto; Martines, Emilio

    2014-01-01

    Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS) in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR)-γ, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine) cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-γ anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and can be considered a

  13. Clinically used selective oestrogen receptor modulators increase LDL receptor activity in primary human lymphocytes

    PubMed Central

    Cerrato, F; Fernández-Suárez, M E; Alonso, R; Alonso, M; Vázquez, C; Pastor, O; Mata, P; Lasunción, M A; Gómez-Coronado, D

    2015-01-01

    Background and Purpose Treatment with selective oestrogen receptor modulators (SERMs) reduces low-density lipoprotein (LDL) cholesterol levels. We assessed the effect of tamoxifen, raloxifene and toremifene and their combinations with lovastatin on LDL receptor activity in lymphocytes from normolipidaemic and familial hypercholesterolaemic (FH) subjects, and human HepG2 hepatocytes and MOLT-4 lymphoblasts. Experimental Approach Lymphocytes were isolated from peripheral blood, treated with different compounds, and 1,1′-dioctadecyl-3,3,3,3′-tetramethylindocarbocyanine perchlorate (DiI)-labelled LDL uptake was analysed by flow cytometry. Key Results Tamoxifen, toremifene and raloxifene, in this order, stimulated DiI-LDL uptake by lymphocytes by inhibiting LDL-derived cholesterol trafficking and subsequent down-regulation of LDL receptor expression. Differently to what occurred in HepG2 and MOLT-4 cells, only tamoxifen consistently displayed a potentiating effect with lovastatin in primary lymphocytes. The SERM-mediated increase in LDL receptor activity was not altered by the anti-oestrogen ICI 182 780 nor was it reproduced by 17β-oestradiol. However, the tamoxifen-active metabolite endoxifen was equally effective as tamoxifen. The SERMs produced similar effects on LDL receptor activity in heterozygous FH lymphocytes as in normal lymphocytes, although none of them had a potentiating effect with lovastatin in heterozygous FH lymphocytes. The SERMs had no effect in homozygous FH lymphocytes. Conclusions and Implications Clinically used SERMs up-regulate LDL receptors in primary human lymphocytes. There is a mild enhancement between SERMs and lovastatin of lymphocyte LDLR activity, the potentiation being greater in HepG2 and MOLT-4 cells. The effect of SERMs is independent of oestrogen receptors but is preserved in the tamoxifen-active metabolite endoxifen. This mechanism may contribute to the cholesterol-lowering action of SERMs. PMID:25395200

  14. Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

    PubMed

    Jones, Christina B; Lulic, Tea; Bailey, Aaron Z; Mackenzie, Tanner N; Mi, Yi Qun; Tommerdahl, Mark; Nelson, Aimee J

    2016-05-01

    Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively.

  15. Biocompatibility of Polypyrrole with Human Primary Osteoblasts and the Effect of Dopants

    PubMed Central

    Fahlgren, Anna; Bratengeier, Cornelia; Gelmi, Amy; Semeins, Cornelis M.; Klein-Nulend, Jenneke; Jager, Edwin W. H.; Bakker, Astrid D.

    2015-01-01

    Polypyrrole (PPy) is a conducting polymer that enables controlled drug release upon electrical stimulation. We characterized the biocompatibility of PPy with human primary osteoblasts, and the effect of dopants. We investigated the biocompatibility of PPy comprising various dopants, i.e. p-toluene sulfonate (PPy-pTS), chondroitin sulfate (PPy-CS), or dodecylbenzenesulfonate (PPy-DBS), with human primary osteoblasts. PPy-DBS showed the roughest appearance of all surfaces tested, and its wettability was similar to the gold-coated control. The average number of attached cells was 45% higher on PPy-DBS than on PPy-CS or PPy-pTS, although gene expression of the proliferation marker Ki-67 was similar in osteoblasts on all surfaces tested. Osteoblasts seeded on PPy-DBS or gold showed similar vinculin attachment points, vinculin area per cell area, actin filament structure, and Feret’s diameter, while cells seeded on PPY-CS or PPY-pTS showed disturbed focal adhesions and were enlarged with disorganized actin filaments. Osteoblasts grown on PPy-DBS or gold showed enhanced alkaline phosphatase activity and osteocalcin gene expression, but reduced osteopontin gene expression compared to cells grown on PPy-pTS and PPy-CS. In conclusion, PPy doped with DBS showed excellent biocompatibility, which resulted in maintaining focal adhesions, cell morphology, cell number, alkaline phosphatase activity, and osteocalcin gene expression. Taken together, conducting polymers doped with DBS are well tolerated by osteoblasts. Our results could provide a basis for the development of novel orthopedic or dental implants with controlled release of antibiotics and pharmaceutics that fight infections or focally enhance bone formation in a tightly controlled manner. PMID:26225862

  16. Oxidative Stress Markers Induced by Hyperosmolarity in Primary Human Corneal Epithelial Cells

    PubMed Central

    Deng, Ruzhi; Hua, Xia; Li, Jin; Chi, Wei; Zhang, Zongduan; Lu, Fan; Zhang, Lili; Pflugfelder, Stephen C.; Li, De-Quan

    2015-01-01

    Oxidative stress has been known to be involved in pathogenesis of dry eye disease. However, few studies have comprehensively investigated the relationship between hyperosmolarity and oxidative damage in human ocular surface. This study was to explore whether and how hyperosmolarity induces oxidative stress markers in primary human corneal epithelial cells (HCECs). Primary HCECs were established from donor limbal explants. The hyperosmolarity model was made in HCECs cultured in isosmolar (312 mOsM) or hyperosmotic (350, 400, 450 mOsM) media. Production of reactive oxygen species (ROS), oxidative damage markers, oxygenases and anti-oxidative enzymes were analyzed by DCFDA kit, RT-qPCR, immunofluorescent and immunohistochemical staining and Western blotting. Compared to isosmolar medium, ROS production significantly increased at time- and osmolarity-dependent manner in HCECs exposed to media with increasing osmolarities (350–450 mOsM). Hyperosmolarity significantly induced oxidative damage markers in cell membrane with increased toxic products of lipid peroxidation, 4–hydroxynonenal (4-HNE) and malondialdehyde (MDA), and in nuclear and mitochondria DNA with increased aconitase-2 and 8-OHdG. Hyperosmotic stress also increased the mRNA expression and protein production of heme oxygenase-1 (HMOX1) and cyclooxygenase-2 (COX2), but reduced the levels of antioxidant enzymes, superoxide dismutase-1 (SOD1), and glutathione peroxidase-1 (GPX1). In conclusion, our comprehensive findings demonstrate that hyperosmolarity induces oxidative stress in HCECs by stimulating ROS production and disrupting the balance of oxygenases and antioxidant enzymes, which in turn cause cell damage with increased oxidative markers in membrane lipid peroxidation and mitochondrial DNA damage. PMID:26024535

  17. Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes

    PubMed Central

    Grosse, Susann; Stenvik, Jørgen; Nilsen, Asbjørn M

    2016-01-01

    Co-stimulation of the immune system to more than one agent concomitantly is very common in real life, and considering the increasing use of engineered nanoparticles and nanomaterials, it is highly relevant to assess the ability of these materials to modulate key innate immune responses, which has not yet been studied in detail. We investigated the immunomodulatory effects of 10 nm and 30 nm iron oxide nanoparticles (IONPs) on primary human monocytes in the presence and absence of Toll-like receptor 4 agonist lipopolysaccharide (LPS). Prior to the cell studies, we characterized the physicochemical properties of the nanoparticles in cell culture medium and ensured that the nanoparticles were free from biological contamination. Cellular uptake of the IONPs in monocytes was assessed using transmission electron microscopy. Using enzyme-linked immunosorbent assay, we found that the IONPs per se did not induce the production of proinflammatory cytokines tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, the IONPs had the ability to suppress LPS-induced nuclear factor kappa B activation and production of proinflammatory cytokines in primary human monocytes in an LPS and a particle dose-dependent manner. Using confocal microscopy and fluorescently labeled LPS, we showed that the effects correlated with impaired LPS internalization by monocytes in the presence of IONPs, which could be partly explained by LPS adsorption onto the nanoparticle surface. Additionally, the results from particle pretreatment experiments indicate that other cellular mechanisms might also play a role in the observed effects, which warrants further studies to elucidate the additional mechanisms underlying the capacity of IONPs to alter the reactivity of monocytes to LPS and to mount an appropriate cellular response. PMID:27695322

  18. Discovering Molecules That Regulate Efferocytosis Using Primary Human Macrophages and High Content Imaging

    PubMed Central

    Santulli-Marotto, Sandra; Gervais, Alexis; Fisher, Jamie; Strake, Brandy; Ogden, Carol Anne; Riveley, Chelsea; Giles-Komar, Jill

    2015-01-01

    Defective clearance of apoptotic cells can result in sustained inflammation and subsequent autoimmunity. Macrophages, the “professional phagocyte” of the body, are responsible for efficient, non-phlogistic, apoptotic cell clearance. Controlling phagocytosis of apoptotic cells by macrophages is an attractive therapeutic opportunity to ameliorate inflammation. Using high content imaging, we have developed a system for evaluating the effects of antibody treatment on apoptotic cell uptake in primary human macrophages by comparing the Phagocytic Index (PI) for each antibody. Herein we demonstrate the feasibility of evaluating a panel of antibodies of unknown specificities obtained by immunization of mice with primary human macrophages and show that they can be distinguished based on individual PI measurements. In this study ~50% of antibodies obtained enhance phagocytosis of apoptotic cells while approximately 5% of the antibodies in the panel exhibit some inhibition. Though the specificities of the majority of antibodies are unknown, two of the antibodies that improved apoptotic cell uptake recognize recombinant MerTK; a receptor known to function in this capacity in vivo. The agonistic impact of these antibodies on efferocytosis could be demonstrated without addition of either of the MerTK ligands, Gas6 or ProS. These results validate applying the mechanism of this fundamental biological process as a means for identification of modulators that could potentially serve as therapeutics. This strategy for interrogating macrophages to discover molecules regulating apoptotic cell uptake is not limited by access to purified protein thereby increasing the possibility of finding novel apoptotic cell uptake pathways. PMID:26674639

  19. Augmented Inhibition of CYP3A4 in Human Primary Hepatocytes by Ritonavir Solid Drug Nanoparticles.

    PubMed

    Martin, Philip; Giardiello, Marco; McDonald, Tom O; Smith, Darren; Siccardi, Marco; Rannard, Steven P; Owen, Andrew

    2015-10-01

    Ritonavir is a protease inhibitor utilized primarily as a pharmaco-enhancer with concomitantly administered antiviral drugs including other protease inhibitors. However, poor tolerance, serious side effects, and toxicities associated with drug-drug interactions are common during exposure to ritonavir. The aim of this work was to investigate the impact of nanoformulation on ritonavir pharmacological properties. Emulsion-templated freeze-drying techniques were used to generate ritonavir (10 wt %) solid drug nanoparticle formulations. A total of 68 ritonavir formulations containing various mixtures of excipients were assessed for inhibition of CYP3A4 in baculosomes and primary human hepatocytes. Accumulation and cytotoxicity were assessed in HepG2 (hepatocytes), Caco-2 (intestinal), THP-1 (monocytes), A-THP-1 (macrophage), and CEM (lymphocytes). Transcellular permeation across Caco-2 cells was also assessed. From 68 solid drug nanoparticle formulations tested, 50 (73.5%) for baculosome and 44 (64.7%) for human primary hepatocytes exhibited enhanced CYP3A4 inhibition relative to an aqueous ritonavir solution. Sixty-one (89.7%) and 49 (72%) solid drug nanoformulations had higher apical to basal permeation across Caco-2 cells than aqueous solution of ritonavir after 60 and 120 min, respectively. No significant difference in cellular accumulation was observed for any solid drug nanoparticle for any cell type compared to aqueous ritonavir. However, incubation with the vast majority of solid drug nanoparticle formulations resulted in lower cytotoxicity of ritonavir than detected with an aqueous solution. These data provide in vitro proof of concept for improved inhibition of CYP3A4 by ritonavir through formation of solid drug nanoparticles. Nanodispersions also showed enhanced permeability across Caco-2 cells lower cytotoxicity across hepatic, intestinal, and immune cell types compared to an aqueous solution of ritonavir.

  20. Iron oxide nanoparticles modulate lipopolysaccharide-induced inflammatory responses in primary human monocytes

    PubMed Central

    Grosse, Susann; Stenvik, Jørgen; Nilsen, Asbjørn M

    2016-01-01

    Co-stimulation of the immune system to more than one agent concomitantly is very common in real life, and considering the increasing use of engineered nanoparticles and nanomaterials, it is highly relevant to assess the ability of these materials to modulate key innate immune responses, which has not yet been studied in detail. We investigated the immunomodulatory effects of 10 nm and 30 nm iron oxide nanoparticles (IONPs) on primary human monocytes in the presence and absence of Toll-like receptor 4 agonist lipopolysaccharide (LPS). Prior to the cell studies, we characterized the physicochemical properties of the nanoparticles in cell culture medium and ensured that the nanoparticles were free from biological contamination. Cellular uptake of the IONPs in monocytes was assessed using transmission electron microscopy. Using enzyme-linked immunosorbent assay, we found that the IONPs per se did not induce the production of proinflammatory cytokines tumor necrosis factor-α, interleukin-6, and interleukin-1β. However, the IONPs had the ability to suppress LPS-induced nuclear factor kappa B activation and production of proinflammatory cytokines in primary human monocytes in an LPS and a particle dose-dependent manner. Using confocal microscopy and fluorescently labeled LPS, we showed that the effects correlated with impaired LPS internalization by monocytes in the presence of IONPs, which could be partly explained by LPS adsorption onto the nanoparticle surface. Additionally, the results from particle pretreatment experiments indicate that other cellular mechanisms might also play a role in the observed effects, which warrants further studies to elucidate the additional mechanisms underlying the capacity of IONPs to alter the reactivity of monocytes to LPS and to mount an appropriate cellular response.

  1. Brincidofovir (CMX001) inhibits BK polyomavirus replication in primary human urothelial cells.

    PubMed

    Tylden, Garth D; Hirsch, Hans H; Rinaldo, Christine Hanssen

    2015-01-01

    BK polyomavirus (BKPyV)-associated hemorrhagic cystitis (PyVHC) complicates 5 to 15% of allogeneic hematopoietic stem cell transplantations. Targeted antivirals are still unavailable. Brincidofovir (BCV; previously CMX001) has shown inhibitory activity against diverse viruses, including BKPyV in a primary human renal tubule cell culture model of polyomavirus-associated nephropathy. We investigated the effects of BCV in BKPyV-infected and uninfected primary human urothelial cells (HUCs), the target cells of BKPyV in PyVHC. The BCV concentrations causing 50 and 90% reductions (EC50 and EC90) in the number of intracellular BKPyV genome equivalents per cell (icBKPyV) were 0.27 μM and 0.59 μM, respectively. At 0.63 μM, BCV reduced viral late gene expression by 90% and halted progeny release. Preinfection treatment for only 24 h reduced icBKPyV similarly to treatment from 2 to 72 h postinfection, while combined pre- and postinfection treatment suppressed icBKPyV completely. After investigating BCV's effects on HUC viability, mean selectivity indices at 50 and 90% inhibition (SI50 and SI90) calculated for cellular DNA replication were 2.7 and 2.9, respectively, those for mitochondrial activity were 8.9 and 10.4, those for total ATP were 8.6 and 8.2, and those for membrane integrity were 25.9 and 16.7. The antiviral and cytostatic effects, but less so the cytotoxic effects, were inversely related to cell density. The cytotoxic effects at concentrations of ≥10 μM were rapid and likely related to BCV's lipid moiety. After carefully defining the antiviral, cytostatic, and cytotoxic properties of BCV in HUCs, we conclude that a preemptive or prophylactic approach in PyVHC is likely to give the best results.

  2. Metaplasticity in human primary somatosensory cortex: effects on physiology and tactile perception.

    PubMed

    Jones, Christina B; Lulic, Tea; Bailey, Aaron Z; Mackenzie, Tanner N; Mi, Yi Qun; Tommerdahl, Mark; Nelson, Aimee J

    2016-05-01

    Theta-burst stimulation (TBS) over human primary motor cortex evokes plasticity and metaplasticity, the latter contributing to the homeostatic balance of excitation and inhibition. Our knowledge of TBS-induced effects on primary somatosensory cortex (SI) is limited, and it is unknown whether TBS induces metaplasticity within human SI. Sixteen right-handed participants (6 females, mean age 23 yr) received two TBS protocols [continuous TBS (cTBS) and intermittent TBS (iTBS)] delivered in six different combinations over SI in separate sessions. TBS protocols were delivered at 30 Hz and were as follows: a single cTBS protocol, a single iTBS protocol, cTBS followed by cTBS, iTBS followed by iTBS, cTBS followed by iTBS, and iTBS followed by cTBS. Measures included the amplitudes of the first and second somatosensory evoked potentials (SEPs) via median nerve stimulation, their paired-pulse ratio (PPR), and temporal order judgment (TOJ). Dependent measures were obtained before TBS and at 5, 25, 50, and 90 min following stimulation. Results indicate similar effects following cTBS and iTBS; increased amplitudes of the second SEP and PPR without amplitude changes to SEP 1, and impairments in TOJ. Metaplasticity was observed such that TOJ impairments following a single cTBS protocol were abolished following consecutive cTBS protocols. Additionally, consecutive iTBS protocols altered the time course of effects when compared with a single iTBS protocol. In conclusion, 30-Hz cTBS and iTBS protocols delivered in isolation induce effects consistent with a TBS-induced reduction in intracortical inhibition within SI. Furthermore, cTBS- and iTBS-induced metaplasticity appear to follow homeostatic and nonhomeostatic rules, respectively. PMID:26984422

  3. Helium generated cold plasma finely regulates activation of human fibroblast-like primary cells.

    PubMed

    Brun, Paola; Pathak, Surajit; Castagliuolo, Ignazio; Palù, Giorgio; Brun, Paola; Zuin, Matteo; Cavazzana, Roberto; Martines, Emilio

    2014-01-01

    Non-thermal atmospheric pressure plasmas are being developed for a wide range of health care applications, including wound healing. However in order to exploit the potential of plasma for clinical applications, the understanding of the mechanisms involved in plasma-induced activation of fibroblasts, the cells active in the healing process, is mandatory. In this study, the role of helium generated plasma in the tissue repairing process was investigated in cultured human fibroblast-like primary cells, and specifically in hepatic stellate cells and intestinal subepithelial myofibroblasts. Five minutes after treatment, plasma induced formation of reactive oxygen species (ROS) in cultured cells, as assessed by flow cytometric analysis of fluorescence-activated 2',7'-dichlorofluorescein diacetate probe. Plasma-induced intracellular ROS were characterized by lower concentrations and shorter half-lives with respect to hydrogen peroxide-induced ROS. Moreover ROS generated by plasma treatment increased the expression of peroxisome proliferator activated receptor (PPAR)-γ, nuclear receptor that modulates the inflammatory responses. Plasma exposure promoted wound healing in an in vitro model and induced fibroblast migration and proliferation, as demonstrated, respectively, by trans-well assay and partitioning between daughter cells of carboxyfluorescein diacetate succinimidyl ester fluorescent dye. Plasma-induced fibroblast migration and proliferation were found to be ROS-dependent as cellular incubation with antioxidant agents (e.g. N-acetyl L-cysteine) cancelled the biological effects. This study provides evidence that helium generated plasma promotes proliferation and migration in liver and intestinal fibroblast-like primary cells mainly by increasing intracellular ROS levels. Since plasma-evoked ROS are time-restricted and elicit the PPAR-γ anti-inflammatory molecular pathway, this strategy ensures precise regulation of human fibroblast activation and can be considered a

  4. Humans make efficient use of natural image statistics when performing spatial interpolation

    PubMed Central

    D'Antona, Anthony D.; Perry, Jeffrey S.; Geisler, Wilson S.

    2013-01-01

    Visual systems learn through evolution and experience over the lifespan to exploit the statistical structure of natural images when performing visual tasks. Understanding which aspects of this statistical structure are incorporated into the human nervous system is a fundamental goal in vision science. To address this goal, we measured human ability to estimate the intensity of missing image pixels in natural images. Human estimation accuracy is compared with various simple heuristics (e.g., local mean) and with optimal observers that have nearly complete knowledge of the local statistical structure of natural images. Human estimates are more accurate than those of simple heuristics, and they match the performance of an optimal observer that knows the local statistical structure of relative intensities (contrasts). This optimal observer predicts the detailed pattern of human estimation errors and hence the results place strong constraints on the underlying neural mechanisms. However, humans do not reach the performance of an optimal observer that knows the local statistical structure of the absolute intensities, which reflect both local relative intensities and local mean intensity. As predicted from a statistical analysis of natural images, human estimation accuracy is negligibly improved by expanding the context from a local patch to the whole image. Our results demonstrate that the human visual system exploits efficiently the statistical structure of natural images. PMID:24344054

  5. Estimating net primary production of natural grassland and its spatio-temporal distribution in China.

    PubMed

    Zhang, Meiling; Lal, Rattan; Zhao, Youyi; Jiang, Wenlan; Chen, Quangong

    2016-05-15

    The net primary production (NPP) of grassland largely determines terrestrial carbon (C) sinks, and thus plays an important role in the global C cycle. Comprehensive and sequential classification system of grasslands (CSCS) is a unique vegetation classification system (mainly for grassland) that is dependent on quantitative measurement indices [>0°C annual cumulative temperature (Σθ) and moisture index (K-value)]. Based on the relationship of the quantitative classification of CSCS and grassland NPP, a modified model of Carnegie-Ames-Stanford Approach (CASA) was used to predict the grassland NPP and its temporal and spatial distribution in China from 2004 to 2008. The scatter plot of the estimated NPP and the observed NPP showed that the estimated data can be accepted with correlation coefficient of 0.896 (P<0.05). The average annual NPP of grassland from 2004 to 2008 in China ranged from 443.23 to 554.40 g Cm(-2)yr.(-)(1). The NPP also showed spatial-temporal variations. There existed an increasing trend of NPP from the northwest to southeast due to the zonal distribution of vegetation. From the trend of monthly variations, it can be drawn that the NPP accumulation primarily occurred between April and October. The average NPP over seven months from April to October was 482.19 g Cm(-2), or about 88.78% of the annual total. The spatial-temporal trend suggests the importance of water and thermal regimes in determining the grassland NPP (i.e. water and thermal are key limited factors for the grassland production), which is also confirmed by a cluster analysis. The mean annual NPP and the total annual NPP differed significantly among grassland classes corresponding with different Σθ and K-value. The results demonstrate that the grassland NPP and the classes/super-classes in CSCS achieve the optimum coupling.

  6. The Nature and Influence of Teacher Beliefs and Knowledge on the Science Teaching Practice of Three Generalist New Zealand Primary Teachers

    ERIC Educational Resources Information Center

    Anderson, Dayle

    2015-01-01

    Students' negative experiences of science in the primary sector have commonly been blamed on poor teacher content knowledge. Yet, teacher beliefs have long been identified as strong influences on classroom practice. Understanding the nature of teacher beliefs and their influence on primary science teaching practice could usefully inform teacher…

  7. Characterization of Primary Isolate-Like Variants of Simian-Human Immunodeficiency Virus

    PubMed Central

    Crawford, John M.; Earl, Patricia L.; Moss, Bernard; Reimann, Keith A.; Wyand, Michael S.; Manson, Kelledy H.; Bilska, Miroslawa; Zhou, Jin Tao; Pauza, C. David; Parren, Paul W. H. I.; Burton, Dennis R.; Sodroski, Joseph G.; Letvin, Norman L.; Montefiori, David C.

    1999-01-01

    Several different strains of simian-human immunodeficiency virus (SHIV) that contain the envelope glycoproteins of either T-cell-line-adapted (TCLA) strains or primary isolates of human immunodeficiency virus type 1 (HIV-1) are now available. One of the advantages of these chimeric viruses is their application to studies of HIV-1-specific neutralizing antibodies in preclinical AIDS vaccine studies in nonhuman primates. In this regard, an important consideration is the spectrum of antigenic properties exhibited by the different envelope glycoproteins used for SHIV construction. The antigenic properties of six SHIV variants were characterized here in neutralization assays with recombinant soluble CD4 (rsCD4), monoclonal antibodies, and serum samples from SHIV-infected macaques and HIV-1-infected individuals. Neutralization of SHIV variants HXBc2, KU2, 89.6, and 89.6P by autologous and heterologous sera from SHIV-infected macaques was restricted to an extent that these viruses may be considered heterologous to one another in their major neutralization determinants. Little or no variation was seen in the neutralization determinants on SHIV variants 89.6P, 89.6PD, and SHIV-KB9. Neutralization of SHIV HXBc2 by sera from HXBc2-infected macaques could be blocked with autologous V3-loop peptide; this was less true in the case of SHIV 89.6 and sera from SHIV 89.6-infected macaques. The poorly immunogenic but highly conserved epitope for monoclonal antibody IgG1b12 was a target for neutralization on SHIV variants HXBc2, KU2, and 89.6 but not on 89.6P and KB9. The 2G12 epitope was a target for neutralization on all five SHIV variants. SHIV variants KU2, 89.6, 89.6P, 89.6PD, and KB9 exhibited antigenic properties characteristic of primary isolates by being relatively insensitive to neutralization in peripheral blood mononuclear cells with serum samples from HIV-1-infected individuals and 12-fold to 38-fold less sensitive to inhibition with recombinant soluble CD4 than TCLA

  8. Interference between the agents of Lyme disease and human granulocytic ehrlichiosis in a natural reservoir host.

    PubMed

    Levin, M L; Fish, D

    2001-01-01

    Agents of Lyme disease (Borrelia burgdorferi) and human granulocytic ehrlichiosis (Ehrlichia phagocytophila) are perpetuated in a natural cycle involving the black-legged tick (Ixodes scapularis) and its vertebrate hosts. Using I. scapularis nymphs as the mode of infectious challenge, we studied how infection with one pathogen in white-footed mice (Peromyscus leucopus) affects their ability to acquire the other agent and subsequently to infect larvae, which these agents would do in nature. Two groups of mice were infected with either B. burgdorferi or E. phagocytophila. One week later, B. burgdorferi-infected mice were challenged with E. phagocytophila, and E. phagocytophila-infected mice were challenged with B. burgdorferi. Simultaneously, two control groups of uninfected mice were infected with each agent from the same tick cohorts used on the first groups of mice. Uninfected I. scapularis larvae were fed on all mice for xenodiagnosis at weekly intervals lasting 2 months. For the B. burgdorferi challenge, all control and E. phagocytophila-infected mice acquired B. burgdorferi. However, fewer xenodiagnostic larvae acquired B. burgdorferi from mice with mixed infections compared with mice infected with B. burgdorferi only. For the E. phagocytophila challenge, all five control mice acquired E. phagocytophila, but only two of five mice infected with B. burgdorferi subsequently acquired E. phagocytophila. Consequently, mice with both infections produced fewer xenodiagnostic ticks infected with E. phagocytophila than mice infected with E. phagocytophila only. Thus, a primary infection with either B. burgdorferi or E. phagocytophila in mice inhibited transmission of a second agent, suggesting interference between these two agents.

  9. Visuomotor Control of Human Adaptive Locomotion: Understanding the Anticipatory Nature

    PubMed Central

    Higuchi, Takahiro

    2013-01-01

    To maintain balance during locomotion, the central nervous system (CNS) accommodates changes in the constraints of spatial environment (e.g., existence of an obstacle or changes in the surface properties). Locomotion while modifying the basic movement patterns in response to such constraints is referred to as adaptive locomotion. The most powerful means of ensuring balance during adaptive locomotion is to visually perceive the environmental properties at a distance and modify the movement patterns in an anticipatory manner to avoid perturbation altogether. For this reason, visuomotor control of adaptive locomotion is characterized, at least in part, by its anticipatory nature. The purpose of the present article is to review the relevant studies which revealed the anticipatory nature of the visuomotor control of adaptive locomotion. The anticipatory locomotor adjustments for stationary and changeable environment, as well as the spatio-temporal patterns of gaze behavior to support the anticipatory locomotor adjustments are described. Such description will clearly show that anticipatory locomotor adjustments are initiated when an object of interest (e.g., a goal or obstacle) still exists in far space. This review also show that, as a prerequisite of anticipatory locomotor adjustments, environmental properties are accurately perceived from a distance in relation to individual’s action capabilities. PMID:23720647

  10. Testing primary-school children's understanding of the nature of science.

    PubMed

    Koerber, Susanne; Osterhaus, Christopher; Sodian, Beate

    2015-03-01

    Understanding the nature of science (NOS) is a critical aspect of scientific reasoning, yet few studies have investigated its developmental beginnings and initial structure. One contributing reason is the lack of an adequate instrument. Two studies assessed NOS understanding among third graders using a multiple-select (MS) paper-and-pencil test. Study 1 investigated the validity of the MS test by presenting the items to 68 third graders (9-year-olds) and subsequently interviewing them on their underlying NOS conception of the items. All items were significantly related between formats, indicating that the test was valid. Study 2 applied the same instrument to a larger sample of 243 third graders, and their performance was compared to a multiple-choice (MC) version of the test. Although the MC format inflated the guessing probability, there was a significant relation between the two formats. In summary, the MS format was a valid method revealing third graders' NOS understanding, thereby representing an economical test instrument. A latent class analysis identified three groups of children with expertise in qualitatively different aspects of NOS, suggesting that there is not a single common starting point for the development of NOS understanding; instead, multiple developmental pathways may exist.

  11. Effects of primary metabolites of organophosphate flame retardants on transcriptional activity via human nuclear receptors.

    PubMed

    Kojima, Hiroyuki; Takeuchi, Shinji; Van den Eede, Nele; Covaci, Adrian

    2016-03-14

    Organophosphate flame retardants (OPFRs) have been used in a wide variety of applications and detected in several environmental matrices, including indoor air and dust. Continuous human exposure to these chemicals is of growing concern. In this study, the agonistic and/or antagonistic activities of 12 primary OPFR-metabolites against ten human nuclear receptors were examined using cell-based transcriptional assays, and compared to those of their parent compounds. As a result, 3-hydroxylphenyl diphenyl phosphate and 4-hydroxylphenyl diphenyl phosphate showed more potent estrogen receptor α (ERα) and ERβ agonistic activity than did their parent, triphenyl phosphate (TPHP). In addition, these hydroxylated TPHP-metabolites also showed ERβ antagonistic activity at higher concentrations and exhibited pregnane X receptor (PXR) agonistic activity as well as androgen receptor (AR) and glucocorticoid receptor (GR) antagonistic activities at similar levels to those of TPHP. Bis(2-butoxyethyl) 3'-hydroxy-2-butoxyethyl phosphate and 2-hydroxyethyl bis(2-butoxyethyl) phosphate act as PXR agonists at similar levels to their parent, tris(2-butoxyethyl) phosphate. On the other hand, seven diester OPFR-metabolites and 1-hydroxy-2-propyl bis(1-chloro-2-propyl) phosphate did not show any receptor activity. Taken together, these results suggest that hydroxylated TPHP-metabolites show increased estrogenicity compared to the parent compound, whereas the diester OPFR-metabolites may have limited nuclear receptor activity compared to their parent triester OPFRs.

  12. Electrical Stimulation Modulates the Expression of Multiple Wound Healing Genes in Primary Human Dermal Fibroblasts.

    PubMed

    Park, Hyun Jin; Rouabhia, Mahmoud; Lavertu, Denis; Zhang, Ze

    2015-07-01

    This study profiled multiple human dermal fibroblast wound-healing genes in response to electrical stimulation (ES) by using an RT(2) profiler PCR-Array system. Primary human skin fibroblasts were seeded on heparin (HE)-bioactivated polypyrrole (PPy)/poly(l-lactic acid) (PLLA) conductive membranes, cultured, and subsequently exposed to ES of 50 or 200 mV/mm for 6 h. Following ES, the cells were used to extract RNA for gene profiling, and culture supernatants were used to measure the level of the different wound healing mediators. A total of 57 genes were affected (activated/repressed) by ES; among these, 49 were upregulated and 8 were downregulated. ES intensities at 50 and 200 mV/mm activated/repressed different genes. The ES-modulated genes are involved in cell adhesion, remodeling and spreading, cytoskeletal activity, extracellular matrix metabolism, production of inflammatory cytokines/chemokines and growth factors, as well as signal transduction. The expression of several genes was supported by protein production. Protein analyses showed that ES increased CCL7, KGF, and TIMP2, but reduced MMP2. This study demonstrated that ES modulates the expression of a variety of genes involved in the wound healing process, confirming that ES is a useful tool in regenerative medicine. PMID:25873313

  13. Synergistic toxicity of gentamicin- and nanosilver-doped polymethylmethacrylate bone cement on primary human osteoclasts.

    PubMed

    Pauksch, Linda; Franke, Jörg; Schnettler, Reinhard; Lips, Katrin S

    2014-01-01

    Bacterial colonization of implant surfaces is a feared complication in surgery and orthopedics. Due to the increasing number of periprosthetic infections caused by multidrug-resistant microorganisms, new antibacterial coatings for biomaterials must be developed. The excellent antibacterial properties of silver nanoparticles (AgNPs) against multidrug-resistant bacteria, for example, have been repeatedly described. For this reason, we tested a nanosilver-doped polymethylmethacrylate (PMMA) bone cement and a nanosilver-coated titanium alloy regarding their influence on osteoclastogenesis of primary human peripheral blood mononuclear cells. Both implant variants did not inhibit osteoclast differentiation. Excellent cell attachment and unaltered podosomal structures were confirmed. Additionally, no induction of oxidative or endoplasmic reticulum stress could be observed. However, PMMA loaded with gentamicin and nanosilver inhibited preosteoclast fusion and further osteoclastogenesis. The material also led to decreased clathrin-dependent endocytosis as well as decreased levels of endoplasmic reticulum stress. Therefore, biomaterial functionalization with AgNPs did not disturb osteoclastogenesis, while addition of gentamicin reduced the cytocompatibility of nanosilver-doped materials towards human osteoclasts.

  14. Cholesteryl ester transfer protein gene expression during differentiation of human preadipocytes to adipocytes in primary culture.

    PubMed

    Gauthier, B; Robb, M; McPherson, R

    1999-02-01

    The expression pattern of the CETP gene in relationship to that of LPL, adipsin, PPARgamma, C/EBPalpha, ADD1/SREBPI and actin was examined by RT-PCR during differentiation of human fibroblastic preadipocytes to adipocytes in primary culture. Preadipocytes were isolated from subcutaneous fat obtained from healthy female subjects undergoing mammary reduction procedures, and induced to differentiate in culture. Morphologically, adipogenesis was confirmed by the accumulation of lipid droplets in cells. We show that the gene encoding CETP is expressed in preadipocytes and is present throughout differentiation as compared to LPL and adipsin which were detected in the majority of samples by day 2 or 3 of adipogenesis. The transcription factors, PPARgamma, ADD1/SREBP1 and C/EBPalpha were expressed by day 2, concomitant with the appearance of LPL and adipsin but subsequent to the appearance of CETP. CETP mRNA was not detectable in human skin fibroblasts. These studies demonstrate that CETP. expression is induced at an early stage of commitment to the adipocyte lineage and may be activated by transcription factor(s), which are not members of the PPAR, ADD1/SREBP1 or C/EBP families. PMID:10030381

  15. Membrane damage and repair in primary monocytes exposed to human β-defensin-3

    PubMed Central

    Lioi, Anthony B.; Reyes Rodriguez, Angel L.; Funderburg, Nicholas T.; Feng, Zhimin; Weinberg, Aaron; Sieg, Scott F.

    2012-01-01

    Interactions of AMPs with plasma membranes of primary human immune cells are poorly characterized. Analysis of PI exclusion as a measure of membrane integrity indicated that hBD-3 caused membrane perturbations in monocytes but not T or B cells at concentrations typically used to kill bacteria or to induce activation of APCs. Bleb-like structures were observed in monocytes exposed to hBD-3. These cells also increased surface expression of LAMP1, a membrane repair marker after exposure to hBD-3. Furthermore, cell death was enhanced by adding an inhibitor of membrane repair. Removal of cholesterol from membranes resulted in greater susceptibility of cells to hBD-3, but cholesterol content was not different between the cell types, as assessed by filipin staining. Freshly isolated monocytes expressed higher levels of the negatively charged phospholipid, PS, on their outer leaflet compared with B or T cells. Preincubation of monocytes with molecules that bind PS protected these cells from hBD-3-induced membrane damage, suggesting that outer-membrane PS expression can at least partially explain monocyte susceptibility to hBD-3. The potential for membrane disruption caused by AMPs should be evaluated in various cell types when considering these molecules for therapeutic applications in humans. PMID:22837529

  16. Chemical proteomic map of dimethyl fumarate-sensitive cysteines in primary human T cells.

    PubMed

    Blewett, Megan M; Xie, Jiji; Zaro, Balyn W; Backus, Keriann M; Altman, Amnon; Teijaro, John R; Cravatt, Benjamin F

    2016-01-01

    Dimethyl fumarate (DMF) is an electrophilic drug that is used to treat autoimmune conditions, including multiple sclerosis and psoriasis. The mechanism of action of DMF is unclear but may involve the covalent modification of proteins or DMF serving as a prodrug that is converted to monomethyl fumarate (MMF). We found that DMF, but not MMF, blocked the activation of primary human and mouse T cells. Using a quantitative, site-specific chemical proteomic platform, we determined the DMF sensitivity of >2400 cysteine residues in human T cells. Cysteines sensitive to DMF, but not MMF, were identified in several proteins with established biochemical or genetic links to T cell function, including protein kinase Cθ (PKCθ). DMF blocked the association of PKCθ with the costimulatory receptor CD28 by perturbing a CXXC motif in the C2 domain of this kinase. Mutation of these DMF-sensitive cysteines also impaired PKCθ-CD28 interactions and T cell activation, designating the C2 domain of PKCθ as a key functional, electrophile-sensing module important for T cell biology. PMID:27625306

  17. [Propagation of the HTV in primary human embryonic kidney and lung cell culture].

    PubMed

    Liu, B; Dai, J; Wang, X; Wang, X; Shen, G

    1994-08-01

    2 strains of Hantaan virus (HTV, 76-118, Hubei-114) have been propagated successfully in cultured primary human embryonic kidney (HEK) and lung (HEL) cells. Cytopathic effect (CPE) was observed in the two kind of cells on day 5 to 7 postinoculation which showed the cell became round and clustered, then detached. The replicating peak of the Hubei-114 in two kinds of cell cultures appeared on the 11th day and another strain on the 14th or 17th day after infection. The ultrastructure changes were observed with EM and IEM, which stained by ICGT before embedding. It was discovered that the mitochondia atrophied and decreased, and inclusion bodies in the cytoplasma of HEK and KEL cells. A large amount of gold granulae were found in the inclusion bodies and the virions were seen occasionally. Contamination with other agents have been ruled out. Our data suggest that the replicating characters of HTV in these cell systems might be possible for the pathogenicity of HFRS for human. PMID:7801638

  18. Dengue-2 infection and the induction of apoptosis in human primary monocytes.

    PubMed

    Torrentes-Carvalho, Amanda; Azeredo, Elzinandes L; Reis, Sonia R I; Miranda, Alessandro S; Gandini, Mariana; Barbosa, Luciana S; Kubelka, Claire F

    2009-12-01

    Monocytes/macrophages are important targets for dengue virus (DENV) replication; they induce inflammatory mediators and are sources of viral dissemination in the initial phase of the disease. Apoptosis is an active process of cellular destruction genetically regulated, in which a complex enzymatic pathway is activated and may be trigged by many viral infections. Since the mechanisms of apoptotic induction in DENV-infected target cells are not yet defined, we investigated the virus-cell interaction using a model of primary human monocyte infection with DENV-2 with the aim of identifying apoptotic markers. Cultures analyzed by flow cytometry and confocal microscopy yielded DENV antigen positive cells with rates that peaked at the second day post infection (p.i.), decayed afterwards and produced the apoptosis-related cytokines TNF-alpha and IL-10. Phosphatidylserine, an early marker for apoptosis, was increased at the cell surface and the Fas death receptor was upregulated at the second day p.i. at significantly higher rates in DENV infected cell cultures than controls. However, no detectable changes were observed in the expression of the anti-apoptotic protein Bcl-2 in infected cultures. Our data support virus modulation of extrinsic apoptotic factors in the in vitro model of human monocyte DENV-2 infection. DENV may be interfering in activation and death mechanisms by inducing apoptosis in target cells.

  19. Reduced DPP4 activity improves insulin signaling in primary human adipocytes.

    PubMed

    Röhrborn, Diana; Brückner, Julia; Sell, Henrike; Eckel, Jürgen

    2016-03-11

    DPP4 is a ubiquitously expressed cell surface protease which is also released to the circulation as soluble DPP4 (sDPP4). Recently, we identified DPP4 as a novel adipokine oversecreted in obesity and thus potentially linking obesity to the metabolic syndrome. Furthermore, sDPP4 impairs insulin signaling in an autocrine and paracrine fashion in different cell types. However, it is still unknown which functional role DPP4 might play in adipocytes. Therefore, primary human adipocytes were treated with a specific DPP4 siRNA. Adipocyte differentiation was not affected by DPP4 silencing. Interestingly, DPP4 reduction improved insulin responsiveness of adipocytes at the level of insulin receptor, proteinkinase B (Akt) and Akt substrate of 160 kDa. To investigate whether the observed effects could be attributed to the enzymatic activity of DPP4, human adipocytes were treated with the DPP4 inhibitors sitagliptin and saxagliptin. Our data show that insulin-stimulated activation of Akt is augmented by DPP4 inhibitor treatment. Based on our previous observation that sDPP4 induces insulin resistance in adipocytes, and that adipose DPP4 levels are higher in obese insulin-resistant patients, we now suggest that the abundance of DPP4 might be a regulator of adipocyte insulin signaling. PMID:26872429

  20. Chemical proteomic map of dimethyl fumarate-sensitive cysteines in primary human T cells.

    PubMed

    Blewett, Megan M; Xie, Jiji; Zaro, Balyn W; Backus, Keriann M; Altman, Amnon; Teijaro, John R; Cravatt, Benjamin F

    2016-09-13

    Dimethyl fumarate (DMF) is an electrophilic drug that is used to treat autoimmune conditions, including multiple sclerosis and psoriasis. The mechanism of action of DMF is unclear but may involve the covalent modification of proteins or DMF serving as a prodrug that is converted to monomethyl fumarate (MMF). We found that DMF, but not MMF, blocked the activation of primary human and mouse T cells. Using a quantitative, site-specific chemical proteomic platform, we determined the DMF sensitivity of >2400 cysteine residues in human T cells. Cysteines sensitive to DMF, but not MMF, were identified in several proteins with established biochemical or genetic links to T cell function, including protein kinase Cθ (PKCθ). DMF blocked the association of PKCθ with the costimulatory receptor CD28 by perturbing a CXXC motif in the C2 domain of this kinase. Mutation of these DMF-sensitive cysteines also impaired PKCθ-CD28 interactions and T cell activation, designating the C2 domain of PKCθ as a key functional, electrophile-sensing module important for T cell biology.

  1. Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells

    PubMed Central

    Blewett, Megan M.; Xie, Jiji; Zaro, Balyn W.; Backus, Keriann M.; Altman, Amnon; Teijaro, John R.; Cravatt, Benjamin F.

    2016-01-01

    Dimethyl fumarate (DMF) is an electrophilic drug that is used to treat autoimmune conditions, including multiple sclerosis and psoriasis. The mechanism of action of DMF is unclear, but may involve the covalent modification of proteins or DMF serving as a pro-drug that is converted to monomethyl fumarate (MMF). Here, we found that DMF, but not MMF, blocked the activation of primary human and mouse T cells. Using a quantitative, site-specific chemical proteomic platform, we determined the DMF-sensitivity of > 2400 cysteine residues in human T cells. Cysteines sensitive to DMF, but not MMF, were identified in several proteins with established biochemical or genetic links to T cell function, including protein kinase C θ (PKCθ). Furthermore, DMF blocked the association of PKCθ with the costimulatory receptor CD28 by perturbing a CXXC motif in the C2 domain of this kinase. Mutation of these DMF-sensitive cysteines also impaired PKCθ-CD28 interactions and T cell activation, designating the C2 domain of PKCθ as a key functional, electrophile-sensing module important for T cell biology. PMID:27625306

  2. Analysis of long-range interactions in primary human cells identifies cooperative CFTR regulatory elements

    PubMed Central

    Moisan, Stéphanie; Berlivet, Soizik; Ka, Chandran; Gac, Gérald Le; Dostie, Josée; Férec, Claude

    2016-01-01

    A mechanism by which control DNA elements regulate transcription over large linear genomic distances is by achieving close physical proximity with genes, and looping of the intervening chromatin paths. Alterations of such regulatory ‘chromatin looping’ systems are likely to play a critical role in human genetic disease at large. Here, we studied the spatial organization of a ≈790 kb locus encompassing the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Dysregulation of CFTR is responsible for cystic fibrosis, which is the most common lethal genetic disorder in Caucasian populations. CFTR is a relatively large gene of 189 kb with a rather complex tissue-specific and temporal expression profile. We used chromatin conformation at the CFTR locus to identify new DNA sequences that regulate its transcription. By comparing 5C chromatin interaction maps of the CFTR locus in expressing and non-expressing human primary cells, we identified several new contact points between the CFTR promoter and its surroundings, in addition to regions featuring previously described regulatory elements. We demonstrate that two of these novel interacting regions cooperatively increase CFTR expression, and suggest that the new enhancer elements located on either side of the gene are brought together through chromatin looping via CTCF. PMID:26615198

  3. MicroRNA Response of Primary Human Macrophages to Arcobacter Butzleri Infection

    PubMed Central

    zur Bruegge, Jennifer; Backes, Christina; Gölz, Greta; Hemmrich-Stanisak, Georg; Scharek-Tedin, Lydia; Franke, Andre; Alter, Thomas; Einspanier, Ralf; Keller, Andreas; Sharbati, Soroush

    2016-01-01

    The role of microRNAs (miRNAs) in infectious diseases is becoming more and more apparent, and the use of miRNAs as a diagnostic tool and their therapeutic application has become the major focus of investigation. The aim of this study was to identify miRNAs involved in the immune signaling of macrophages in response to Arcobacter (A.) butzleri infection, an emerging foodborne pathogen causing gastroenteritis. Therefore, primary human macrophages were isolated and infected, and miRNA expression was studied by means of RNAseq. Analysis of the data revealed the expression of several miRNAs, which were previously associated with bacterial infections such as miR-155, miR-125, and miR-212. They were shown to play a key role in Toll-like receptor signaling where they act as fine-tuners to establish a balanced immune response. In addition, miRNAs which have yet not been identified during bacterial infections such as miR-3613, miR-2116, miR-671, miR-30d, and miR-629 were differentially regulated in A. butzleri-infected cells. Targets of these miRNAs accumulated in pathways such as apoptosis and endocytosis – processes that might be involved in A. butzleri pathogenesis. Our study contributes new findings about the interaction of A. butzleri with human innate immune cells helping to understand underlying regulatory mechanisms in macrophages during infection. PMID:27429792

  4. Postnatal accumulation of intermediate filaments in the cat and human primary visual cortex.

    PubMed

    Song, Seoho; Mitchell, Donald E; Crowder, Nathan A; Duffy, Kevin R

    2015-10-01

    A principal characteristic of the mammalian visual system is its high capacity for plasticity in early postnatal development during a time commonly referred to as the critical period. The progressive diminution of plasticity with age is linked to the emergence of a collection of molecules called molecular brakes that reduce plasticity and stabilize neural circuits modified by earlier visual experiences. Manipulation of braking molecules either pharmacologically or though experiential alteration enhances plasticity and promotes recovery from visual impairment. The stability of neural circuitry is increased by intermediate filamentous proteins of the cytoskeleton such as neurofilaments and α-internexin. We examined levels of these intermediate filaments within cat and human primary visual cortex (V1) across development to determine whether they accumulate following a time course consistent with a molecular brake. In both species, levels of intermediate filaments increased considerably throughout early postnatal life beginning shortly after the peak of the critical period, with the highest levels measured in adults. Neurofilament phosphorylation was also observed to increase throughout development, raising the possibility that posttranslational modification by phosphorylation reduces plasticity due to increased protein stability. Finally, an approach to scale developmental time points between species is presented that compares the developmental profiles of intermediate filaments between cats and humans. Although causality between intermediate filaments and plasticity was not directly tested in this study, their accumulation relative to the critical period indicates that they may contribute to the decline in plasticity with age, and may also constrain the success of treatments for visual disorders applied in adulthood.

  5. Human Primary Keratinocytes as a Tool for the Analysis of Caspase-1-Dependent Unconventional Protein Secretion.

    PubMed

    Strittmatter, Gerhard E; Garstkiewicz, Martha; Sand, Jennifer; Grossi, Serena; Beer, Hans-Dietmar

    2016-01-01

    Inflammasomes comprise a group of protein complexes, which activate the protease caspase-1 upon sensing a variety of stress factors. Active caspase-1 in turn cleaves and thereby activates the pro-inflammatory cytokines prointerleukin (IL)-1β and -18, and induces unconventional protein secretion (UPS) of mature IL-1β, IL-18, as well as of many other proteins involved in and required for induction of inflammation. Human primary keratinocytes (HPKs) represent epithelial cells able to activate caspase-1 in an inflammasome-dependent manner upon irradiation with a physiological dose of ultraviolet B (UVB) light. Here, we describe the isolation of keratinocytes from human skin, their cultivation, and induction of caspase-1-dependent UPS upon UVB irradiation as well as its siRNA- and chemical-mediated inhibition. In contrast to inflammasome activation of professional immune cells, UVB-irradiated HPKs represent a robust and physiological cell culture system for the analysis of UPS induced by active caspase-1. PMID:27665556

  6. Human liver alcohol dehydrogenase. 1. The primary structure of the beta 1 beta 1 isoenzyme.

    PubMed

    Hempel, J; Bühler, R; Kaiser, R; Holmquist, B; de Zalenski, C; von Wartburg, J P; Vallee, B; Jörnvall, H

    1984-12-17

    Determination of the amino acid sequence of the beta 1 subunit from the class I (pyrazole-sensitive) human liver alcohol dehydrogenase isoenzyme beta 1 beta 1 revealed a 373-residue structure differing at 48 positions (including a gap) from that of the subunit of the well studied horse liver alcohol dehydrogenase EE isoenzyme. The structure deduced is compatible with known differences in composition, ultraviolet absorbance, electrophoretic mobility and catalytic properties between the horse and human enzymes. All zinc-liganding residues of the horse E subunit are strictly conserved in the human beta 1 subunit, despite an earlier report of a mutation involving Cys-46. This residue therefore remains conserved in all known alcohol dehydrogenase structures. However, the total cysteine content of the beta 1 structure is raised from 14 in the subunit of the horse enzyme to 15 by a Tyr----Cys exchange. Most exchanges are on the surface of the molecule and of a well conserved nature. Substitutions close to the catalytic centre are of interest to explain the altered substrate specificity and different catalytic activity of the beta 1 homodimer. Functionally, a Ser----Thr exchange at position 48 appears to be of special importance, since Thr-48 in beta 1 instead of Ser-48 in the horse enzyme can restrict available space. Four other substitutions also line the active-site pocket, and appear to constitute partly compensated exchanges. PMID:6391920

  7. In Vitro Modeling of RSV Infection and Cytopathogenesis in Well-Differentiated Human Primary Airway Epithelial Cells (WD-PAECs).

    PubMed

    Broadbent, Lindsay; Villenave, Remi; Guo-Parke, Hong; Douglas, Isobel; Shields, Michael D; Power, Ultan F

    2016-01-01

    The choice of model used to study human respiratory syncytial virus (RSV) infection is extremely important. RSV is a human pathogen that is exquisitely adapted to infection of human hosts. Rodent models, such as mice and cotton rats, are semi-permissive to RSV infection and do not faithfully reproduce hallmarks of RSV disease in humans. Furthermore, immortalized airway-derived cell lines, such as HEp-2, BEAS-2B, and A549 cells, are poorly representative of the complexity of the respiratory epithelium. The development of a well-differentiated primary pediatric airway epithelial cell models (WD-PAECs) allows us to simulate several hallmarks of RSV infection of infant airways. They therefore represent important additions to RSV pathogenesis modeling in human-relevant tissues. The following protocols describe how to culture and differentiate both bronchial and nasal primary pediatric airway epithelial cells and how to use these cultures to study RSV cytopathogenesis. PMID:27464691

  8. Distancing Students from Nature: Science Camp and the Representation of the Human-Nature Relationship

    ERIC Educational Resources Information Center

    Terrill, Laura Anne

    2015-01-01

    This study investigated the curricular representations of the environment and the human-environment relationship at one residential school sponsored science camp. Data gathered included field notes from observational time at the camp, interviews with staff and classroom teachers, and documents from the site's website, guides, manuals, and…

  9. Population response to natural images in the primary visual cortex encodes local stimulus attributes and perceptual processing.

    PubMed

    Ayzenshtat, Inbal; Gilad, Ariel; Zurawel, Guy; Slovin, Hamutal

    2012-10-01

    The primary visual cortex (V1) is extensively studied with a large repertoire of stimuli, yet little is known about its encoding of natural images. Using voltage-sensitive dye imaging in behaving monkeys, we measured neural population response evoked in V1 by natural images presented during a face/scramble discrimination task. The population response showed two distinct phases of activity: an early phase that was spread over most of the imaged area, and a late phase that was spatially confined. To study the detailed relation between the stimulus and the population response, we used a simple encoding model to compute a continuous map of the expected neural response based on local attributes of the stimulus (luminance and contrast), followed by an analytical retinotopic transformation. Then, we computed the spatial correlation between the maps of the expected and observed response. We found that the early response was highly correlated with the local luminance of the stimulus and was sufficient to effectively discriminate between stimuli at the single trial level. The late response, on the other hand, showed a much lower correlation to the local luminance, was confined to central parts of the face images, and was highly correlated with the animal's perceptual report. Our study reveals a continuous spatial encoding of low- and high-level features of natural images in V1. The low level is directly linked to the stimulus basic local attributes and the high level is correlated with the perceptual outcome of the stimulus processing.