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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. 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

  4. 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

  5. Natural History of Primary Epstein-Barr Virus Infection in Children of Mothers Infected with Human Immunodeficiency Virus Type 1

    PubMed Central

    Jenson, Hal; McIntosh, Kenneth; Pitt, Jane; Husak, Scott; Tan, Ming; Bryson, Yvonne; Easley, Kirk

    2015-01-01

    The natural history of Epstein-Barr virus (EBV) infection in 556 infants born to 517 human immunodeficiency virus (HIV) type 1–infected mothers was studied in a prospective, multicenter, cohort study. HIV-1–infected children had a cumulative EBV infection rate similar to HIV-1–uninfected children at age 3 years (77.8% vs. 84.9%) but had more frequent oropharyngeal EBV shedding (50.4% vs. 28.2%; P < .001). The probability of shedding decreased with longer time from EBV seroconversion and was similar to that of HIV-1–uninfected children 3 years after seroconversion. HIV-1–infected children identified as rapid progressors shed EBV more frequently than nonrapid progressors (69.4% vs.41.0%; P = .01). HIV-1–infected children with EBV infection had higher mean CD8 cell counts. EBV infection did not have an independent effect on mean CD4 cell counts, percent CD4, IgG levels, HIV-1 RNA levels, lymphadenopathy, hepatomegaly, or splenomegaly. Early EBV infection is common in children born to HIV-1–infected mothers. Children with rapidly progressive HIV-1 disease have more frequent EBV shedding. PMID:10228060

  6. 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

  7. 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

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

    PubMed

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

    2012-12-01

    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

  9. The Natural Human IgM Antibody PAT-SM6 Induces Apoptosis in Primary Human Multiple Myeloma Cells by Targeting Heat Shock Protein GRP78

    PubMed Central

    Rasche, Leo; Duell, Johannes; Morgner, Charlotte; Chatterjee, Manik; Hensel, Frank; Rosenwald, Andreas; Einsele, Hermann

    2013-01-01

    In contrast to other haematological malignancies, targeted immunotherapy has not entered standard treatment regimens for de novo or relapsed multiple myeloma (MM) yet. While a number of IgG-formatted monoclonal antibodies are currently being evaluated in clinical trials in MM, our study aimed to investigate whether the fully human IgM monoclonal antibody PAT-SM6 that targets a tumour-specific variant of the heat shock protein GRP78 might be an attractive candidate for future immunotherapeutic approaches. We here show that GRP78 is stably and consistently expressed on the surface on tumour cells from patients with de novo, but also relapsed MM and that binding of PAT-SM6 to MM cells can specifically exert cytotoxic effects on malignant plasma cells, whereas non-malignant cells are not targeted. We demonstrate that the induction of apoptosis and, to a lesser extent, complement dependent cytotoxicity is the main mode of action of PAT-SM6, whereas antibody dependent cellular cytotoxicity does not appear to contribute to the cytotoxic properties of this antibody. Given the favourable safety profile of PAT-SM6 in monkeys, but also in a recent phase I trial in patients with malignant melanoma, our results form the basis for a planned phase I study in patients with relapsed MM. PMID:23667612

  10. The natural human IgM antibody PAT-SM6 induces apoptosis in primary human multiple myeloma cells by targeting heat shock protein GRP78.

    PubMed

    Rasche, Leo; Duell, Johannes; Morgner, Charlotte; Chatterjee, Manik; Hensel, Frank; Rosenwald, Andreas; Einsele, Hermann; Topp, Max S; Brändlein, Stephanie

    2013-01-01

    In contrast to other haematological malignancies, targeted immunotherapy has not entered standard treatment regimens for de novo or relapsed multiple myeloma (MM) yet. While a number of IgG-formatted monoclonal antibodies are currently being evaluated in clinical trials in MM, our study aimed to investigate whether the fully human IgM monoclonal antibody PAT-SM6 that targets a tumour-specific variant of the heat shock protein GRP78 might be an attractive candidate for future immunotherapeutic approaches. We here show that GRP78 is stably and consistently expressed on the surface on tumour cells from patients with de novo, but also relapsed MM and that binding of PAT-SM6 to MM cells can specifically exert cytotoxic effects on malignant plasma cells, whereas non-malignant cells are not targeted. We demonstrate that the induction of apoptosis and, to a lesser extent, complement dependent cytotoxicity is the main mode of action of PAT-SM6, whereas antibody dependent cellular cytotoxicity does not appear to contribute to the cytotoxic properties of this antibody. Given the favourable safety profile of PAT-SM6 in monkeys, but also in a recent phase I trial in patients with malignant melanoma, our results form the basis for a planned phase I study in patients with relapsed MM. PMID:23667612

  11. 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. PMID:23593771

  12. 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 ( ...

  13. 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 Central

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

    2008-01-01

    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

  14. 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…

  15. Human Nature, Sociobiology and Counselling.

    ERIC Educational Resources Information Center

    Lang, William A.; West, Lloyd W.

    1980-01-01

    Sociobiology suggests that our basic pyschological makeup is genetically determined and has evolved by means of natural selection. Biologically based human predispositions often conflict with legal and moral requirements of modern life. Sociobiology provides support for the direct teaching of moral values and social skills. (Author)

  16. [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

  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. 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.

  19. Detection of primary cilia in human glioblastoma

    PubMed Central

    Sarkisian, Matthew R.; Siebzehnrubl, Dorit; Hoang-Minh, Lan; Deleyrolle, Loic; Silver, Daniel J.; Siebzehnrubl, Florian A.; Guadiana, Sarah M.; Srivinasan, Gayathri; Semple-Rowland, Susan; Harrison, Jeffrey K.; Steindler, Dennis A.; Reynolds, Brent A.

    2015-01-01

    Glioblastoma (GBM) is the most common malignant adult brain tumor and carries a poor prognosis due to primary and acquired resistance. While many cellular features of GBM have been documented, it is unclear if cells within these tumors extend a primary cilium, an organelle whose associated signaling pathways may regulate proliferation, migration, and survival of neural precursor and tumor cells. Using immunohistochemical and electron microscopy (EM) techniques, we screened human GBM tumor biopsies and primary cell lines for cilia. Immunocytochemical staining of five primary GBM cell lines revealed that between 8 and 25 % of the cells in each line possessed gamma tubulin-positive basal bodies from which extended acetylated, alpha-tubulin-positive axonemes. EM analyses confirmed the presence of cilia at the cell surface and revealed that their axonemes contained organized networks of microtubules, a structural feature consistent with our detection of IFT88 and Arl13b, two trafficked cilia proteins, along the lengths of the axonemes. Notably, cilia were detected in each of 23 tumor biopsies (22 primary and 1 recurrent) examined. These cilia were distributed across the tumor landscape including regions proximal to the vasculature and within necrotic areas. Moreover, ciliated cells within these tumors co-stained with Ki67, a marker for actively dividing cells, and ZEB1, a transcription factor that is upregulated in GBM and linked to tumor initiation, invasion, and chemoresistance. Collectively, our data show that subpopulations of cells within human GBM tumors are ciliated. In view of mounting evidence supporting roles of primary cilia in tumor initiation and propagation, it is likely that further study of the effects of cilia on GBM tumor cell function will improve our understanding of GBM pathogenesis and may provide new directions for GBM treatment strategies. PMID:24510433

  20. Gene targeting in primary human trophoblasts

    PubMed Central

    Rosario, Fredrick J; Sadovsky, Yoel; Jansson, Thomas

    2012-01-01

    Studies in primary human trophoblasts provide critical insights into placental function in normal and complicated pregnancies. Mechanistic studies in these cells require experimental tools to modulate gene expression. Lipid-based methods to transfect primary trophoblasts are fairly simple to use and allow for the efficient delivery of nucleic acids, but potential toxic effects limit these methods. Viral vectors are versatile transfection tools of native trophoblastic or foreign cDNAs, providing high transfection efficiency, low toxicity and stable DNA integration into the trophoblast genome. RNA interference (RNAi), using small interfering RNA (siRNA) or microRNA, constitutes a powerful approach to silence trophoblast genes. However, off-target effects, such as regulation of unintended complementary transcripts, inflammatory responses and saturation of the endogenous RNAi machinery, are significant concerns. Strategies to minimize off-target effects include using multiple individual siRNAs, elimination of pro-inflammatory sequences in the siRNA construct and chemical modification of a nucleotide in the guide strand or of the ribose moiety. Tools for efficient gene targeting in primary human trophoblasts are currently available, albeit not yet extensively validated. These methods are critical for exploring the function of human trophoblast genes and may provide a foundation for the future application of gene therapy that targets placental trophoblasts. PMID:22831880

  1. 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

  2. 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

  3. 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…

  4. 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…

  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. 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…

  7. Natural Helpers: A Study of Primary Caregivers among Migrant Women.

    ERIC Educational Resources Information Center

    Greenfield, Wilma L.

    Natural helpers exist even among the most oppressed populations in this country, particularly migrant women, and recognition of their helping networks can give professional caregivers access to a resource that is often more adaptive, more efficient, and more humane than many static, impersonal, and obsolete human service bureaucracies. Migrant…

  8. 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…

  9. The Nature of Referred Subtypes of Primary Speech Disability

    ERIC Educational Resources Information Center

    Broomfield, J.; Dodd, B.

    2004-01-01

    Of 1100 children referred to a mainstream paediatric speech and language therapy service in a 15-month period (January 1999 to April 2000), 320 had primary speech impairment. No referred child had significant hearing impairment, learning disability or physical disability. This paper describes the nature of the subtypes of speech disability…

  10. 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.

  11. 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

  12. The Human Nature of Professionalism.

    ERIC Educational Resources Information Center

    Ong, Walter J.

    The issue of professional identity is of special concern to academicians in the humanities, especially those involved in the study of modern languages and literature. There is the problem of self-definition. Even reviewing the past of modern language and literature study affords no simple definition, as English as an academic subject has no clear…

  13. 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)

  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. 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

  16. The nature of human aggression.

    PubMed

    Archer, John

    2009-01-01

    Human aggression is viewed from four explanatory perspectives, derived from the ethological tradition. The first consists of its adaptive value, which can be seen throughout the animal kingdom, involving resource competition and protection of the self and offspring, which has been viewed from a cost-benefit perspective. The second concerns the phylogenetic origin of aggression, which in humans involves brain mechanisms that are associated with anger and inhibition, the emotional expression of anger, and how aggressive actions are manifest. The third concerns the origin of aggression in development and its subsequent modification through experience. An evolutionary approach to development yields conclusions that are contrary to the influential social learning perspective, notably that physical aggression occurs early in life, and its subsequent development is characterized by learned inhibition. The fourth explanation concerns the motivational mechanisms controlling aggression: approached from an evolutionary background, these mechanisms range from the inflexible reflex-like responses to those incorporating rational decision-making. PMID:19411108

  17. HIV binding, penetration, and primary infection in human cervicovaginal tissue

    PubMed Central

    Maher, Diane; Wu, Xiaoyun; Schacker, Timothy; Horbul, Julie; Southern, Peter

    2005-01-01

    We have developed human cervicovaginal organ culture systems to examine the initiating events in HIV transmission after exposure to various sources of HIV infectivity, including semen. Newly infected cells were detected in the cervical submucosa 3–4 days after exposure to a primary HIV isolate. At earlier times, extensive and stable binding occurred when cervical surfaces were exposed to virions or seminal cells. Cervical mucus provided some protection for the endocervical surface, by physically trapping virions and seminal cells. Confocal microscopy combined with 3D surface reconstruction revealed that virions could both bind to the external surface of the cervical epithelium and actually penetrate beneath the epithelial surface. In quantitative assays, pretreatment with a blocking antibody directed against β1 integrin reduced HIV virion binding. Collectively, these results highlight a continuum of complex interactions that occurs when natural sources of HIV infectivity are deposited onto mucosal surfaces in the female reproductive tract. PMID:16061810

  18. 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…

  19. 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

  20. Sociobiology, Anti-Sociobiology, and Human Nature

    ERIC Educational Resources Information Center

    Leeds, Anthony

    1977-01-01

    Summarizes arguments on both sides of the nature nurture controversy and relates the arguments to the new discipline of sociobiology. Concludes that both camps avoid consideration of postulation and reflexivity, which are described as central human capacities. For journal availability, see SO 505 653. (Author/DB)

  1. 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.

  2. The human genome and the human control of natural evolution.

    PubMed

    Sakamoto, H

    2001-10-01

    Recent advances in research on the Human Genome are provoking many critical problems in the global policy regarding the future status of human beings as well as in that of the whole life system on the earth, and consequently, these advances provoke the serious bioethical and philosophical questions. Firstly, how can we comprehend that we are going to have the complete technology to manipulate the system of the human genome and other non-human genomes? Though no science and technology can be complete, we will, I believe, take possession of an almost complete gene technology in the early stage of the next Century. Gene technology will soon fall into the hands of human beings instead of rendering in the province of God. Secondly, which gene technologies will we actually realize and utilize in the early stages of the 21st Century? Most probably, we will adopt these technologies to health care to treat some apparent bodily diseases, for instance, cancer, hemophilia, ADA deficiency, and so forth, and sooner or later we will adopt gene therapy to germ lines, which, in the long run, suggests the possibility of a future "artificial evolution" instead of the "natural evolution" of the past. Thirdly, how is the new concept of "artificial evolution" justified ethically? I believe this kind of manmade evolution is the only way for human beings to survive into the future global environment. There cannot be any serious ethical objection against the idea of artificial evolution. Fourthly, what is the background philosophy for the concept of "artificial evolution"? I will discuss the nature of modern European humanism with individual dignity and fundamental human rights which has led the philosophy of modern culture and modern society, and I will conclude by suggesting that we should abolish an essential part of modern humanism and newly devise some alternative philosophy to fit the new Millennium. PMID:15011660

  3. Natural history of pruritus in primary biliary cirrhosis.

    PubMed

    Talwalkar, Jayant A; Souto, Enrico; Jorgensen, Roberta A; Lindor, Keith D

    2003-07-01

    The natural history of pruritus in primary biliary cirrhosis (PBC) remains poorly defined. The aim of this investigation was to evaluate outcomes of pruritus in clinical trials for ursodeoxycholic acid (UDCA). In a UDCA-placebo trial begun in 1988 (n = 180), a 55% prevalence rate for pruritus was observed. Serum alkaline phosphatase level and Mayo risk score were independent risk factors for pruritus (P < 0.0001). Among placebo-treated patients (n = 91), the annual risks for development or improvement/resolution of pruritus were 27% and 23%, respectively. For UDCA-treated patients (n = 89), a trend toward improvement in pruritus was observed after 1 year compared to placebo (30% vs. 23%, P = 0.08) but not at 2 or 3 years. In a 3-dose UDCA trial begun in 1995 (n = 155), the overall prevalence of pruritus was significantly lower at 37% when compared to UDCA-placebo participants (P < 0.001). Baseline serum alkaline phosphatase level and Mayo risk score were again independent risk factors for pruritus (P < 0.0001). Among 13 (3.9%) patients with refractory pruritus, symptom resolution (n = 5) or improvement (n = 8) was associated with the use of oral rifampin (300 or 600 mg daily). Two patients treated with rifampin developed biochemical evidence for hepatotoxicity necessitating drug withdrawal. Although less prevalent among recently diagnosed individuals, more than one third of PBC patients develop pruritus. No significant risk reduction in developing pruritus with UDCA therapy was observed compared to placebo-treated patients. The long-term administration of rifampin for refractory pruritus is associated with occasional hepatotoxicity. PMID:15017671

  4. Natural history of human rotavirus infection.

    PubMed

    Bishop, R F

    1996-01-01

    Rotavirus infections occur repeatedly in humans from birth to old age. Most are asymptomatic or are associated with mild enteric symptoms. Infection in young children can be accompanied by severe life-threatening diarrhea, most commonly after primary infection. Annual childhood morbidity rates for severe diarrhea are similar worldwide. Mortality rates are low in developed countries but approach 1,000,000 annually in young children in developing countries. Rotaviruses can be classified into Groups A-E according to antigenic groups on VP6, the major capsid antigen. Only Group A,B and C rotaviruses have been shown to infect humans, and most human rotavirus disease is caused by Group A viruses. These are further classified into G and P types based on identification of antigens on the outer capsid proteins VP7 and VP4 respectively. Most severe infections in young children are caused by serotypes G1-4, and during the last two decades, G1 infections appear to have predominated worldwide. In general the more densely populated countries show the most complex patterns of occurrence of serotypes. Clinical rotavirus disease can be accompanied by shedding of > 10(12) rotavirus particles/gm feces. The virus is highly infectious and appears to retain infectivity over many months. In temperate climates, disease is most common during the colder months, when it is likely that rapid spread within families and communities occurs. Nosocomial infections are frequent, and rotaviruses can become endemic within obstetric hospital nurseries for the newborn. Few (if any) human rotavirus infections appear to be zoonoses, even though Group A rotaviruses are widespread in the young of all mammalian species. However infection of humans with reassortant rotavirus strains derived from human-animal sources can occur. The extent to which this contributes to new epidemic strains within particular countries (or worldwide) remains to be determined. PMID:9015109

  5. 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.

  6. 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

  7. DNA methylation contributes to natural human variation

    PubMed Central

    Heyn, Holger; Moran, Sebastian; Hernando-Herraez, Irene; Sayols, Sergi; Gomez, Antonio; Sandoval, Juan; Monk, Dave; Hata, Kenichiro; Marques-Bonet, Tomas; Wang, Liewei; Esteller, Manel

    2013-01-01

    DNA methylation patterns are important for establishing cell, tissue, and organism phenotypes, but little is known about their contribution to natural human variation. To determine their contribution to variability, we have generated genome-scale DNA methylation profiles of three human populations (Caucasian-American, African-American, and Han Chinese-American) and examined the differentially methylated CpG sites. The distinctly methylated genes identified suggest an influence of DNA methylation on phenotype differences, such as susceptibility to certain diseases and pathogens, and response to drugs and environmental agents. DNA methylation differences can be partially traced back to genetic variation, suggesting that differentially methylated CpG sites serve as evolutionarily established mediators between the genetic code and phenotypic variability. Notably, one-third of the DNA methylation differences were not associated with any genetic variation, suggesting that variation in population-specific sites takes place at the genetic and epigenetic levels, highlighting the contribution of epigenetic modification to natural human variation. PMID:23908385

  8. 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

  9. 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.

  10. Anthropologia transscendentalis. Kant's theory of human nature.

    PubMed

    Battaglia, F

    2012-01-01

    In recent years mankind has greatly extended its knowledge of living things, in general, and itself, in particular. Such a wide-ranging body of knowledge has consequently led to the need for a theory to encompass it, that is, a coherent framework in which to systematically arrange mankind's understanding of itself, not only with regard to its physical nature, but to its individuality and sociality as well. Such a theory would moreover provide the means to mediate between the various domains of scientific and technological enquiry, on the one hand, and the cultural dimensions of human society, on the other. Already in the 18th century, Immanuel Kant strove to establish a discipline that was systematic, yet at the same time accessible. It was due to his efforts that philosophical anthropology was introduced into university curricula, to the benefit not only of philosophers, but of physicians and jurists as well. Kant's position is by no means prejudicial towards science. To the contrary, he was quite careful to appraise the impact of the sciences on the overall cognitive horizons of mankind and therefore on their potential to influence humankind's idea of itself. Clearly such a perspective is relevant to today's strongly felt need to reconcile modern neuroscience's revolutionary findings on the biological bases of the mind - of man's experience and behaviour - with the idea man needs of himself in order to orient his actions not only as individual but also as "citizen of the world" as well - something on which Kant worked with unremitting commitment throughout his entire research career. This article traces Kant's anthropological conception with regard to four specific issues: (1) its relation to science; (2) the relationship between empirical and transcendental in the speculative use and in practical use of reason; (3) the dialectic between what nature does and what human beings does, in the construction of humanity itself; (4) and finally about the character of the

  11. 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.

  12. 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…

  13. 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)

  14. 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

  15. Human alveolar epithelial type II cells in primary culture.

    PubMed

    Mao, Pu; Wu, Songling; Li, Jianchun; Fu, Wei; He, Weiqun; Liu, Xiaoqing; Slutsky, Arthur S; Zhang, Haibo; Li, Yimin

    2015-02-01

    Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator-induced lung injury, and pulmonary fibrosis. We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels. Adult human peripheral normal lung tissues of oncologic patients undergoing lung resection were collected. The AEII cells were isolated and identified by the expression of pro-surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)-8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy. The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP-A, SP-B, SP-C, SP-D), CK-8, KL-6, αENaC, and aquaporin (AQP)-3, which was maintained over 20 days. The biological activity of the primary human AEII cells producing SP-C, cytokines, and intercellular adhesion molecule-1 was vigorous in response to stimulation with tumor necrosis factor-α. We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture. This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells. PMID:25677546

  16. Human alveolar epithelial type II cells in primary culture

    PubMed Central

    Mao, Pu; Wu, Songling; Li, Jianchun; Fu, Wei; He, Weiqun; Liu, Xiaoqing; Slutsky, Arthur S; Zhang, Haibo; Li, Yimin

    2015-01-01

    Alveolar epithelial type II (AEII) cells are a key structure and defender in the lung but also are the targets in many lung diseases, including acute respiratory distress syndrome, ventilator-induced lung injury, and pulmonary fibrosis. We sought to establish an optimized method for high yielding and long maintenance of characteristics of primary human AEII cells to facilitate the investigation of the mechanisms of lung diseases at the cellular and molecular levels. Adult human peripheral normal lung tissues of oncologic patients undergoing lung resection were collected. The AEII cells were isolated and identified by the expression of pro-surfactant protein (SP)C, epithelial sodium channel (αENaC) and cytokeratin (CK)-8, the lamellar bodies specific for AEII cells, and confirmed by the histology using electron microscopy. The phenotype of AEII cells was characterized by the expression of surfactant proteins (SP-A, SP-B, SP-C, SP-D), CK-8, KL-6, αENaC, and aquaporin (AQP)-3, which was maintained over 20 days. The biological activity of the primary human AEII cells producing SP-C, cytokines, and intercellular adhesion molecule-1 was vigorous in response to stimulation with tumor necrosis factor-α. We have modified previous methods and optimized a method for isolation of high purity and long maintenance of the human AEII cell phenotype in primary culture. This method provides an important tool for studies aiming at elucidating the molecular mechanisms of lung diseases exclusively in AEII cells. PMID:25677546

  17. 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

  18. 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

  19. 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…

  20. 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

  1. Ferritin-mediated siRNA delivery and gene silencing in human tumor and primary cells.

    PubMed

    Li, Le; Muñoz-Culla, Maider; Carmona, Unai; Lopez, Maria Paz; Yang, Fan; Trigueros, Cesar; Otaegui, David; Zhang, Lianbing; Knez, Mato

    2016-08-01

    We demonstrate a straightforward method to encapsulate siRNA into naturally available and unmodified human apoferritin. The encapsulation into apoferritin is independent of the sequence of the siRNA and provides superior protection for those sensitive molecules. High efficiency in transfection can be achieved in human tumorigenic cells, human primary mesenchymal stem cells (hMSC) and peripheral blood mononuclear cells (PBMCs). In contrast to Lipofectamine, highly effective gene silencing can be achieved with ferritin as the delivery agent in both tumor cells and PBMCs at low siRNA concentrations (10 nM). As an endogenous delivery agent, apoferritin does not induce immune activation of T- and B-cells in human PBMCs. Apoferritin shows intrinsic anti-inflammatory effects and apoferritin-mediated delivery shows a preference for immune-activated T- and B-cells, a natural selectivity which may turn useful for drug delivery in case of infections or inflammatory diseases. PMID:27187278

  2. REPLICATIVE POTENTIAL OF HUMAN NATURAL KILLER CELLS

    PubMed Central

    Fujisaki, Hiroyuki; Kakuda, Harumi; Imai, Chihaya; Mullighan, Charles G.; Campana, Dario

    2009-01-01

    The replicative potential of human CD56+ CD3− natural killer (NK) cells is unknown. We found that by exposing NK cells to the leukemic cell line K562 genetically modified to express 4-1BB ligand and interleukin 15 (K562-mb15-41BBL), they expanded for up to 30 population doublings, achieving numbers that ranged from 1.6 × 105 to 1.2 × 1011 percent (median, 5.9 × 106 percent; n = 7) of those originally seeded. However, NK cells eventually became unresponsive to stimulation and died. Their demise could be suppressed by enforcing the expression of the human telomerase reverse transcriptase (TERT) gene. TERT-overexpressing NK cells continued to proliferate in response to K562-mb15-41BBL stimulation for more than 1 year of culture, while maintaining a normal karyotype and genotype. Long-lived NK cells had high cytotoxicity against myeloid and T-lineage leukemic cells. They remained susceptible to genetic manipulation, becoming highly cytotoxic to B-lineage leukemic cells after expression of anti-CD19 signaling receptors. Thus, human NK cells have a replicative potential similar to that of T lymphocytes and their lifespan can be significantly prolonged by an increase in TERT activity. We suggest that the methods described here should have many applications in studies of NK cell biology and NK cell-based therapies. PMID:19344420

  3. 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.

  4. Serum-free primary human fibroblast and keratinocyte coculture.

    PubMed

    Mujaj, Sally; Manton, Kerry; Upton, Zee; Richards, Sean

    2010-04-01

    Research has shown that the inclusion of a fibroblast cell support layer is required for the isolation and expansion of primary keratinocytes. Recent advances have provided keratinocyte culture with fibroblast-free alternatives. However, these technologies are often undefined and rely on the incorporation of purified proteins/components. To address this problem we developed a medium that used recombinant proteins to support the serum-free isolation and expansion of human dermal fibroblasts and keratinocytes. The human dermal fibroblasts were able to be isolated serum free by adding recombinant human albumin to a collagenase solution. These fibroblasts were then expanded using a serum-free medium containing recombinant proteins: epidermal growth factor, basic fibroblast growth factor, chimeric vitronectin:insulin-like growth factor-I protein, and recombinant human albumin. These fibroblasts maintained a typical morphology and expressed fibroblast markers during their serum-free isolation, expansion, and freezing. Moreover, these fibroblasts were able to support the serum-free isolation and expansion of primary keratinocytes using these recombinant proteins. Real-time polymerase chain reaction and immunofluorescence analysis confirmed that there were no differences in expression levels of p63 or keratins 1, 6, and 10 when keratinocytes were grown in either serum-supplemented or serum-free medium. Using a three-dimensional human skin equivalent model we demonstrated that these keratinocytes also maintained their ability to reform an epidermal layer. In summary, the techniques described provide a valuable alternative for culturing fibroblasts and keratinocytes using recombinant proteins. PMID:19929322

  5. 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…

  6. Ultrastructural analysis of primary human urethral epithelial cell cultures infected with Neisseria gonorrhoeae.

    PubMed

    Harvey, H A; Ketterer, M R; Preston, A; Lubaroff, D; Williams, R; Apicella, M A

    1997-06-01

    In men with gonococcal urethritis, the urethral epithelial cell is a site of infection. To study the pathogenesis of gonorrhea in this cell type, we have developed a method to culture primary human urethral epithelial cells obtained at the time of urologic surgery. Fluorescent analysis demonstrated that 100% of the cells stained for keratin. Microscopic analyses indicated that these epithelial cells arrayed in a pattern similar to that seen in urethral epithelium. Using immunoelectron and confocal microscopy, we compared the infection process seen in primary cells with events occurring during natural infection of the same cell type in men with gonococcal urethritis. Immunoelectron microscopy studies of cells infected with Neisseria gonorrhoeae 1291 Opa+ P+ showed adherence of organisms to the epithelial cell membrane, pedestal formation with evidence of intimate association between the gonococcal and the epithelial cell membranes, and intracellular gonococci present in vacuoles. Confocal studies of primary urethral epithelial cells showed actin polymerization upon infection. Polyclonal antibodies to the asialoglycoprotein receptor (ASGP-R) demonstrated the presence of this receptor on infected cells in the primary urethral cell culture. In situ hybridization using a fluorescent-labeled probe specific to the ASGP-R mRNA demonstrated this message in uninfected and infected cells. These features were identical to those seen in urethral epithelial cells in exudates from males with gonorrhea. Infection of primary urethral cells in culture mimics events seen in natural infection and will allow detailed molecular analysis of gonococcal pathogenesis in a human epithelial cell which is commonly infected. PMID:9169783

  7. "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…

  8. 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

  9. 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.

  10. 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

  11. 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

  12. 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

  13. Axonal Degeneration in Dental Pulp Precedes Human Primary Teeth Exfoliation.

    PubMed

    Suzuki, K; Lovera, M; Schmachtenberg, O; Couve, E

    2015-10-01

    The dental pulp in human primary teeth is densely innervated by a plethora of nerve endings at the coronal pulp-dentin interface. This study analyzed how the physiological root resorption (PRR) process affects dental pulp innervation before exfoliation of primary teeth. Forty-four primary canine teeth, classified into 3 defined PRR stages (early, middle, and advanced) were fixed and demineralized. Longitudinal cryosections of each tooth were stained for immunohistochemical and quantitative analysis of dental pulp nerve fibers and associated components with confocal and electron microscopy. During PRR, axonal degeneration was prominent and progressive in a Wallerian-like scheme, comprising nerve fiber bundles and nerve endings within the coronal and root pulp. Neurofilament fragmentation increased significantly during PRR progression and was accompanied by myelin degradation and a progressive loss of myelinated axons. Myelin sheath degradation involved activation of autophagic activity by Schwann cells to remove myelin debris. These cells expressed a sequence of responses comprising dedifferentiation, proliferative activity, GAP-43 overexpression, and Büngner band formation. During the advanced PRR stage, increased immune cell recruitment within the dental pulp and major histocompatibility complex (MHC) class II upregulation by Schwann cells characterized an inflammatory condition associated with the denervation process in preexfoliative primary teeth. The ensuing loss of dental pulp axons is likely to be responsible for the progressive reduction of sensory function of the dental pulp during preexfoliative stages. PMID:26149320

  14. "Nature" and the "Environment" in Jamaica's Primary School Curriculum Guides

    ERIC Educational Resources Information Center

    Ferguson, Therese

    2008-01-01

    In cases where environmental education is institutionalised within schools, the curriculum can affect what and how students learn about "nature" and the "environment". In Jamaica, schools are considered important settings for environmental education; the curriculum therefore includes environmental issues. Using content analysis, representations of…

  15. Burkholderia pseudomallei induces IL-23 production in primary human monocytes.

    PubMed

    Kulsantiwong, Panthong; Pudla, Matsayapan; Boondit, Jitrada; Wikraiphat, Chanthiwa; Dunachie, Susanna J; Chantratita, Narisara; Utaisincharoen, Pongsak

    2016-06-01

    Burkholderia pseudomallei, a gram-negative intracellular bacterium, is a causative agent of melioidosis. The bacterium has been shown to induce the innate immune response, particularly pro-inflammatory cytokine production in several of both mouse and human cell types. In the present study, we investigate host immune response in B. pseudomallei-infected primary human monocytes. We discover that wild-type B. pseudomallei is able to survive and multiply inside the primary human monocytes. In contrast, B. pseudomallei LPS mutant, a less virulent strain, is susceptible to host killing during bacterial infection. Moreover, microarray result showed that wild-type B. pseudomallei but not B. pseudomallei LPS mutant is able to activate gene expression of IL-23 as demonstrated by the up-regulation of p19 and p40 subunit expression. Consistent with gene expression analysis, the secretion of IL-23 analyzed by ELISA also showed that wild-type B. pseudomallei induces a significantly higher level of IL-23 secretion than that of B. pseudomallei LPS mutant. These results implied that IL-23 may be an important cytokine for the innate immune response during B. pseudomallei infection. The regulation of IL-23 production may drive the different host innate immune responses between patients and may relate to the severity of melioidosis. PMID:26563410

  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. On the pulpal nerve supply in primary human teeth: evidence for the innervation of primary dentine.

    PubMed

    Egan, C A; Hector, M P; Bishop, M A

    1999-03-01

    The presence of nerves in human tooth pulp has been recognized for over a hundred years, and the innervation of dentine for about 40 years. These observations have been made in permanent teeth. Very few studies have reported on the innervation of the primary pulp and dentine. The purpose of this study was to describe the innervation of the primary tooth pulp-dentine complex. Ten mature primary teeth (one incisor, six canines and three molars) were used. Immediately following extraction they were divided into three sections using a diamond disc and saline coolant. They were then immersion fixed in a solution of formaldehyde and picric acid dissolved in a phosphate buffer pH 7.4). The teeth were then demineralized for 1-3 weeks in formic acid. Following complete demineralization, 30 microns sections were cut on a freezing microtome. Neural tissue was stained using a specific antibody to calcitonin gene related peptide (CGRP). Sections were mounted on glass slides and examined using light microscopy. No individual nerve fibres were seen in the control sections, suggesting that the method used was specific for CGRP-containing nerve fibres. The primary teeth appeared to be well innervated. Myelinated and unmyelinated nerves were seen. There was a dense but variable subodontoblastic plexus of nerves (plexus of Raschkow) and nerve fibres were seen to leave this to travel towards the odontoblast layer. Most terminated here, but a few penetrated the odontoblast layer to enter predentine and the dentine tubules. The maximum penetration was 125 microns but most terminated within 30 microns of the dentinopulpal junction. The coronal region was more densely innervated than the root. Within the crown the cervical third was the most densely innervated region, followed by the pulp horn and the middle third. In conclusion, this study has demonstrated that mature primary tooth contains a pulp which is well innervated and has many nerve endings terminating in or near the odontoblast

  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 Immunodeficiency Syndromes Affecting Human Natural Killer Cell Cytolytic Activity

    PubMed Central

    Ham, Hyoungjun; Billadeau, Daniel D.

    2013-01-01

    Natural killer (NK) cells are lymphocytes of the innate immune system that secrete cytokines upon activation and mediate the killing of tumor cells and virus-infected cells, especially those that escape the adaptive T cell response caused by the down regulation of MHC-I. The induction of cytotoxicity requires that NK cells contact target cells through adhesion receptors, and initiate activation signaling leading to increased adhesion and accumulation of F-actin at the NK cell cytotoxic synapse. Concurrently, lytic granules undergo minus-end directed movement and accumulate at the microtubule-organizing center through the interaction with microtubule motor proteins, followed by polarization of the lethal cargo toward the target cell. Ultimately, myosin-dependent movement of the lytic granules toward the NK cell plasma membrane through F-actin channels, along with soluble N-ethylmaleimide-sensitive factor attachment protein receptor-dependent fusion, promotes the release of the lytic granule contents into the cleft between the NK cell and target cell resulting in target cell killing. Herein, we will discuss several disease-causing mutations in primary immunodeficiency syndromes and how they impact NK cell-mediated killing by disrupting distinct steps of this tightly regulated process. PMID:24478771

  1. 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.

  2. Isolation of highly enriched primary human microglia for functional studies.

    PubMed

    Rustenhoven, Justin; Park, Thomas I-H; Schweder, Patrick; Scotter, John; Correia, Jason; Smith, Amy M; Gibbons, Hannah M; Oldfield, Robyn L; Bergin, Peter S; Mee, Edward W; Faull, Richard L M; Curtis, Maurice A; Scott Graham, E; Dragunow, Mike

    2016-01-01

    Microglia, the resident macrophages of the central nervous system play vital roles in brain homeostasis through clearance of pathogenic material. Microglia are also implicated in neurological disorders through uncontrolled activation and inflammatory responses. To date, the vast majority of microglial studies have been performed using rodent models. Human microglia differ from rodent counterparts in several aspects including their response to pharmacological substances and their inflammatory secretions. Such differences highlight the need for studies on primary adult human brain microglia and methods to isolate them are therefore required. Our procedure generates microglial cultures of >95% purity from both biopsy and autopsy human brain tissue using a very simple media-based culture procedure that takes advantage of the adherent properties of these cells. Microglia obtained in this manner can be utilised for research within a week. Isolated microglia demonstrate phagocytic ability and respond to inflammatory stimuli and their purity makes them suitable for numerous other forms of in vitro studies, including secretome and transcriptome analysis. Furthermore, this protocol allows for the simultaneous isolation of neural precursor cells during the microglial isolation procedure. As human brain tissue is such a precious and valuable resource the simultaneous isolation of multiple cell types is highly beneficial. PMID:26778406

  3. Telomerase Contributes to Fludarabine Resistance in Primary Human Leukemic Lymphocytes

    PubMed Central

    Shawi, May; Chu, Tsz Wai; Martinez-Marignac, Veronica; Yu, Y.; Gryaznov, Sergei M.; Johnston, James B.; Lees-Miller, Susan P.; Assouline, Sarit E.; Autexier, Chantal; Aloyz, Raquel

    2013-01-01

    We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR), can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1) if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2) the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo) on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku) to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells. PMID:23922990

  4. Telomerase contributes to fludarabine resistance in primary human leukemic lymphocytes.

    PubMed

    Shawi, May; Chu, Tsz Wai; Martinez-Marignac, Veronica; Yu, Y; Gryaznov, Sergei M; Johnston, James B; Lees-Miller, Susan P; Assouline, Sarit E; Autexier, Chantal; Aloyz, Raquel

    2013-01-01

    We report that Imetelstat, a telomerase inhibitor that binds to the RNA component of telomerase (hTR), can sensitize primary CLL lymphocytes to fludarabine in vitro. This effect was observed in lymphocytes from clinically resistant cases and with cytogenetic abnormalities associated with bad prognosis. Imetelstat mediated-sensitization to fludarabine was not associated with telomerase activity, but with the basal expression of Ku80. Since both Imetelstat and Ku80 bind hTR, we assessed 1) if Ku80 and Imetelstat alter each other's binding to hTR in vitro and 2) the effect of an oligonucleotide complementary to the Ku binding site in hTR (Ku oligo) on the survival of primary CLL lymphocytes exposed to fludarabine. We show that Imetelstat interferes with the binding of Ku70/80 (Ku) to hTR and that the Ku oligo can sensitize CLL lymphocytes to FLU. Our results suggest that Ku binding to hTR may contribute to fludarabine resistance in CLL lmphocytes. This is the first report highlighting the potentially broad effectiveness of Imetelstat in CLL, and the potential biological and clinical implications of a functional interaction between Ku and hTR in primary human cancer cells. PMID:23922990

  5. Natural Organic Matter as Global Antennae for Primary Production

    PubMed Central

    Van Trump, J. Ian; Rivera Vega, Fransheska J.

    2013-01-01

    Abstract 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. Key Words: Deep subsurface biosphere—Chemolithotrophic microorganisms—Organic matter—Geochemistry—Iron-oxidizing bacteria. Astrobiology 13, 476–482. PMID:23683047

  6. 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. PMID:23683047

  7. FFTF primary system transition to natural circulation from low reactor power

    SciTech Connect

    Bouchey, G.D.; Additon, S.L.; Nutt, W.T.

    1980-01-01

    Plans for reactor and primary loop natural circulation testing in the Fast Flux Test Facility (FFTF) are summarized. Detailed pretest planning with an emphasis on understanding the implications of process noise and model uncertainties for model verification and test acceptance are discussed for a transition to natural circulation in the reactor core and primary heat transport loops from initial conditions of 5% of rated reactor power and 75% of full flow.

  8. Cellular Proteome Dynamics during Differentiation of Human Primary Myoblasts.

    PubMed

    Le Bihan, Marie-Catherine; Barrio-Hernandez, Inigo; Mortensen, Tenna Pavia; Henningsen, Jeanette; Jensen, Søren Skov; Bigot, Anne; Blagoev, Blagoy; Butler-Browne, Gillian; Kratchmarova, Irina

    2015-08-01

    Muscle stem cells, or satellite cells, play an important role in the maintenance and repair of muscle tissue and have the capacity to proliferate and differentiate in response to physiological or environmental changes. Although they have been extensively studied, the key regulatory steps and the complex temporal protein dynamics accompanying the differentiation of primary human muscle cells remain poorly understood. Here, we demonstrate the advantages of applying a MS-based quantitative approach, stable isotope labeling by amino acids in cell culture (SILAC), for studying human myogenesis in vitro and characterize the fine-tuned changes in protein expression underlying the dramatic phenotypic conversion of primary mononucleated human muscle cells during in vitro differentiation to form multinucleated myotubes. Using an exclusively optimized triple encoding SILAC procedure, we generated dynamic expression profiles during the course of myogenic differentiation and quantified 2240 proteins, 243 of which were regulated. These changes in protein expression occurred in sequential waves and underlined vast reprogramming in key processes governing cell fate decisions, i.e., cell cycle withdrawal, RNA metabolism, cell adhesion, proteolysis, and cytoskeletal organization. In silico transcription factor target analysis demonstrated that the observed dynamic changes in the proteome could be attributed to a cascade of transcriptional events involving key myogenic regulatory factors as well as additional regulators not yet known to act on muscle differentiation. In addition, we created of a dynamic map of the developing myofibril, providing valuable insights into the formation and maturation of the contractile apparatus in vitro. Finally, our SILAC-based quantitative approach offered the possibility to follow the expression profiles of several muscle disease-associated proteins simultaneously and therefore could be a valuable resource for future studies investigating

  9. 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

  10. 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.…

  11. 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)

  12. 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

    ... 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...

  13. 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

    ... 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...

  14. 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

    ... 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. Face representation in the human primary somatosensory cortex.

    PubMed

    Nguyen, Binh T; Tran, Tuan D; Hoshiyama, Minoru; Inui, Koji; Kakigi, Ryusuke

    2004-10-01

    To investigate the representation of facial skin areas in the primary somatosensory cortex (SI), we recorded magnetic fields evoked by air pressure-induced tactile stimulation applied to six points on the face, lower lip and thumb. The thumb area in the SI was located more medial and superior to the lip area, which was consistent with Penfield's homunculus. However, the representations of all skin-covered areas including forehead, cheek, nose and chin in the SI were located between the thumb and lower lip area. There was no significant difference in location among the six facial points. Our results imply that lips occupy a large area of the face representation in the SI, whereas only a small area located between the thumb and lip areas is devoted to skin-covered surfaces. This is the first study showing that the facial skin areas in the human SI are located between the thumb and lower lip areas and close together. PMID:15380330

  16. 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. PMID:27595140

  17. Testing gene therapy vectors in human primary nasal epithelial cultures

    PubMed Central

    Cao, Huibi; Ouyang, Hong; Ip, Wan; Du, Kai; Duan, Wenming; Avolio, Julie; Wu, Jing; Duan, Cathleen; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Hu, Jim; Moraes, Theo J

    2015-01-01

    Cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which codes for a chloride/bicarbonate channel in the apical epithelial membranes. CFTR dysfunction results in a multisystem disease including the development of life limiting lung disease. The possibility of a cure for CF by replacing defective CFTR has led to different approaches for CF gene therapy; all of which ultimately have to be tested in preclinical model systems. Primary human nasal epithelial cultures (HNECs) derived from nasal turbinate brushing were used to test the efficiency of a helper-dependent adenoviral (HD-Ad) vector expressing CFTR. HD-Ad-CFTR transduction resulted in functional expression of CFTR at the apical membrane in nasal epithelial cells obtained from CF patients. These results suggest that HNECs can be used for preclinical testing of gene therapy vectors in CF. PMID:26730394

  18. Testing gene therapy vectors in human primary nasal epithelial cultures.

    PubMed

    Cao, Huibi; Ouyang, Hong; Ip, Wan; Du, Kai; Duan, Wenming; Avolio, Julie; Wu, Jing; Duan, Cathleen; Yeger, Herman; Bear, Christine E; Gonska, Tanja; Hu, Jim; Moraes, Theo J

    2015-01-01

    Cystic fibrosis (CF) results from mutations in the CF transmembrane conductance regulator (CFTR) gene, which codes for a chloride/bicarbonate channel in the apical epithelial membranes. CFTR dysfunction results in a multisystem disease including the development of life limiting lung disease. The possibility of a cure for CF by replacing defective CFTR has led to different approaches for CF gene therapy; all of which ultimately have to be tested in preclinical model systems. Primary human nasal epithelial cultures (HNECs) derived from nasal turbinate brushing were used to test the efficiency of a helper-dependent adenoviral (HD-Ad) vector expressing CFTR. HD-Ad-CFTR transduction resulted in functional expression of CFTR at the apical membrane in nasal epithelial cells obtained from CF patients. These results suggest that HNECs can be used for preclinical testing of gene therapy vectors in CF. PMID:26730394

  19. 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…

  20. 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)

  1. Dopamine Receptor Activation Increases HIV Entry into Primary Human Macrophages

    PubMed Central

    Gaskill, Peter J.; Yano, Hideaki H.; Kalpana, Ganjam V.; Javitch, Jonathan A.; Berman, Joan W.

    2014-01-01

    Macrophages are the primary cell type infected with HIV in the central nervous system, and infection of these cells is a major component in the development of neuropathogenesis and HIV-associated neurocognitive disorders. Within the brains of drug abusers, macrophages are exposed to increased levels of dopamine, a neurotransmitter that mediates the addictive and reinforcing effects of drugs of abuse such as cocaine and methamphetamine. In this study we examined the effects of dopamine on HIV entry into primary human macrophages. Exposure to dopamine during infection increased the entry of R5 tropic HIV into macrophages, irrespective of the concentration of the viral inoculum. The entry pathway affected was CCR5 dependent, as antagonizing CCR5 with the small molecule inhibitor TAK779 completely blocked entry. The effect was dose-dependent and had a steep threshold, only occurring above 108 M dopamine. The dopamine-mediated increase in entry required dopamine receptor activation, as it was abrogated by the pan-dopamine receptor antagonist flupenthixol, and could be mediated through both subtypes of dopamine receptors. These findings indicate that the effects of dopamine on macrophages may have a significant impact on HIV pathogenesis. They also suggest that drug-induced increases in CNS dopamine may be a common mechanism by which drugs of abuse with distinct modes of action exacerbate neuroinflammation and contribute to HIV-associated neurocognitive disorders in infected drug abusers. PMID:25268786

  2. `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.

  3. 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

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

    PubMed

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

    2013-06-18

    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

  5. 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

  6. 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

  7. 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…

  8. Helicobacter hepaticus Induces an Inflammatory Response in Primary Human Hepatocytes

    PubMed Central

    Kleine, Moritz; Worbs, Tim; Schrem, Harald; Vondran, Florian W. R.; Kaltenborn, Alexander; Klempnauer, Jürgen; Förster, Reinhold; Josenhans, Christine; Suerbaum, Sebastian; Bektas, Hüseyin

    2014-01-01

    Helicobacter hepaticus can lead to chronic hepatitis and hepatocellular carcinoma in certain strains of mice. Until now the pathogenic role of Helicobacter species on human liver tissue is still not clarified though Helicobacter species identification in human liver cancer was successful in case controlled studies. Therefore we established an in vitro model to investigate the interaction of primary human hepatocytes (PHH) with Helicobacter hepaticus. Successful co-culturing of PHH with Helicobacter hepaticus was confirmed by visualization of motile bacteria by two-photon-microscopy. Isolated human monocytes were stimulated with PHH conditioned media. Changes in mRNA expression of acute phase cytokines and proteins in PHH and stimulated monocytes were determined by Real-time PCR. Furthermore, cytokines and proteins were analyzed in PHH culture supernatants by ELISA. Co-cultivation with Helicobacter hepaticus induced mRNA expression of Interleukin-1 beta (IL-1β), Tumor necrosis factor-alpha, Interleukin-8 (IL-8) and Monocyte chemotactic protein-1 (MCP-1) in PHH (p<0.05) resulting in a corresponding increase of IL-8 and MCP-1 concentrations in PHH supernatants (p<0.05). IL-8 and IL-1β mRNA expression was induced in monocytes stimulated with Helicobacter hepaticus infected PHH conditioned media (p<0.05). An increase of Cyclooxygenase-2 mRNA expression was observed, with a concomitant increase of prostaglandin E2 concentration in PHH supernatants at 24 and 48 h (p<0.05). In contrast, at day 7 of co-culture, no persistent elevation of cytokine mRNA could be detected. High expression of intercellular adhesion molecule-1 on PHH cell membranes after co-culture was shown by two-photon-microscopy and confirmed by flow-cytomety. Finally, expression of Cytochrome P450 3A4 and albumin mRNA were downregulated, indicating an impairment of hepatocyte synthesis function by Helicobacter hepaticus presence. This is the first in vitro model demonstrating a pathogenic effect of a

  9. Dynamics and distribution of natural and human-caused hypoxia

    NASA Astrophysics Data System (ADS)

    Rabalais, N. N.; Díaz, R. J.; Levin, L. A.; Turner, R. E.; Gilbert, D.; Zhang, J.

    2010-02-01

    Water masses can become undersaturated with oxygen when natural processes alone or in combination with anthropogenic processes produce enough organic carbon that is aerobically decomposed faster than the rate of oxygen re-aeration. The dominant natural processes usually involved are photosynthetic carbon production and microbial respiration. The re-supply rate is indirectly related to its isolation from the surface layer. Hypoxic water masses (<2 mg L-1, or approximately 30% saturation) can form, therefore, under "natural" conditions, and are more likely to occur in marine systems when the water residence time is extended, water exchange and ventilation are minimal, stratification occurs, and where carbon production and export to the bottom layer are relatively high. Hypoxia has occurred through geological time and naturally occurs in oxygen minimum zones, deep basins, eastern boundary upwelling systems, and fjords. Hypoxia development and continuation in many areas of the world's coastal ocean is accelerated by human activities, especially where nutrient loading increased in the Anthropocene. This higher loading set in motion a cascading set of events related to eutrophication. The formation of hypoxic areas has been exacerbated by any combination of interactions that increase primary production and accumulation of organic carbon leading to increased respiratory demand for oxygen below a seasonal or permanent pycnocline. Nutrient loading is likely to increase further as population growth and resource intensification rises, especially with increased dependency on crops using fertilizers, burning of fossil fuels, urbanization, and waste water generation. It is likely that the occurrence and persistence of hypoxia will be even more widespread and have more impacts than presently observed. Global climate change will further complicate the causative factors in both natural and human-caused hypoxia. The likelihood of strengthened stratification alone, from increased

  10. Greek primary school teachers' understanding of current environmental issues: An exploration of their environmental knowledge and images of nature

    NASA Astrophysics Data System (ADS)

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

    2007-03-01

    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. Using the media as major environmental information sources, in which environmental issues are constructed as environmental risks, teachers are being environmentally educated in lay and not in scientific terms. Moreover, the image of nature emerging from their ideas about the three environmental issues is that of the romantic archetype, which prevails in postindustrial societies. Such a view, though, gives a conceptualization of nature as balance, under which the greenhouse effect and acid rain are seen as exclusively human-induced disturbances.

  11. Microbiota and the human nature: know thyself.

    PubMed

    Brüssow, Harald

    2015-01-01

    Biology has been driven by the human desire for self-knowledge. The discovery of our intimate symbiosis with microbes raises the question about our identity. A central issue is whether the microbiome associated with humans changes our phenotype in an observable way. As we deal with a great multitude of colonizing microbes and as even monozygotic twins differ substantially for their microbiome, we might deal with a dynamic system that is highly sensitive to initial conditions for which long-term prediction are impossible according to chaos theory. The overall colonization of the human alimentary tract can be teleological rationalized by a strong antimicrobial activity in the proximal and a mutualistic but controlled relationship with the microbiome in the distal gut segments. Yet the association of a specific microbiome with physiological traits turned out to be complicated and became frequently only clear after microbiota transfer experiments into gnotobiotic mice as a reductionist approach. As pathogenic bacteria create human phenotypes by their presence, mutualistic bacteria create symptoms (phenotypes) by their absence as exemplified by lactobacilli in bacterial vaginosis. PMID:25521462

  12. Long non-coding RNA expression in primary human monocytes.

    PubMed

    Mirsafian, Hoda; Manda, Srinivas Srikanth; Mitchell, Christopher J; Sreenivasamurthy, Sreelakshmi; Ripen, Adiratna Mat; Mohamad, Saharuddin Bin; Merican, Amir Feisal; Pandey, Akhilesh

    2016-07-01

    Long non-coding RNAs (lncRNAs) have been shown to possess a wide range of functions in both cellular and developmental processes including cancers. Although some of the lncRNAs have been implicated in the regulation of the immune response, the exact function of the large majority of lncRNAs still remains unknown. In this study, we characterized the lncRNAs in human primary monocytes, an essential component of the innate immune system. We performed RNA sequencing of monocytes from four individuals and combined our data with eleven other publicly available datasets. Our analysis led to identification of ~8000 lncRNAs of which >1000 have not been previously reported in monocytes. PCR-based validation of a subset of the identified novel long intergenic noncoding RNAs (lincRNAs) revealed distinct expression patterns. Our study provides a landscape of lncRNAs in monocytes, which could facilitate future experimental studies to characterize the functions of these molecules in the innate immune system. PMID:26778813

  13. 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

  14. 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

  15. 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.

  16. 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.

  17. 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

  18. 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. PMID:21133975

  19. Human vision is attuned to the diffuseness of natural light

    PubMed Central

    Morgenstern, Yaniv; Geisler, Wilson S.; Murray, Richard F.

    2014-01-01

    All images are highly ambiguous, and to perceive 3-D scenes, the human visual system relies on assumptions about what lighting conditions are most probable. Here we show that human observers' assumptions about lighting diffuseness are well matched to the diffuseness of lighting in real-world scenes. We use a novel multidirectional photometer to measure lighting in hundreds of environments, and we find that the diffuseness of natural lighting falls in the same range as previous psychophysical estimates of the visual system's assumptions about diffuseness. We also find that natural lighting is typically directional enough to override human observers' assumption that light comes from above. Furthermore, we find that, although human performance on some tasks is worse in diffuse light, this can be largely accounted for by intrinsic task difficulty. These findings suggest that human vision is attuned to the diffuseness levels of natural lighting conditions. PMID:25139864

  20. 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.

  1. Discriminating man-made and natural objects in sidescan sonar imagery: human versus computer recognition performance

    NASA Astrophysics Data System (ADS)

    Kessel, Ronald T.; Myers, Vincent L.

    2005-05-01

    Sidescan sonar is increasingly accepted as the sensor of choice for sea minehunting over large areas in shallow water. Automatic Target Recognition (ATR) algorithms are therefore being developed to assist and, in the case of autonomous vehicles, even replace the human operator as the primary recognition agent deciding whether an object in the sonar imagery is a mine or simply benign seafloor clutter. Whether ATR aids or replaces a human operator, a natural benchmark for judging the quality of ATR is the unaided human performance when ATR is not used. The benchmark can help when estimating the performance benefit (or cost) of switching from human to automatic recognition for instance, or when planning how human and machine should best interact in cooperative search operations. This paper reports a human performance study using a large library of real sonar images collected for the development and testing of ATR algorithms. The library features 234 mine-like man-made objects deployed for the purpose, as well as 105 instances of naturally occurring clutter. The human benchmark in this case is the average of ten human subjects expressed in terms of a receiver operating characteristic (ROC) curve. An ATR algorithm for man-made/natural object discrimination is also tested and compared with the human benchmark . The implications of its relative performance for the integration of ATR are considered.

  2. 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…

  3. 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…

  4. 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…

  5. 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. PMID:26662791

  6. Natural convection around the human head.

    PubMed

    Clark, R P; Toy, N

    1975-01-01

    1. Factors determining the convective flow patterns around the human head in 'still' conditions are discussed in relation to body posture. 2. The flow patterns have been visualized using a schlieren optical system which reveals that the head has a thicker 'insulating' layer of convecting air in the erect posture than in the supine position. 3. Local convective and radiative heat transfer measurements from the head have been using surface calorimeters. These results are seen to be closely related to the thickness of the convective boundary layer flows. 4. The total convective and radiative heat loss from the head of a subject in the erect and supine position has been evaluated from the local measurements. For the head of the supine subject the heat loss was found to be 30% more than when the subject was standing. PMID:1142118

  7. 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.

  8. 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

  9. Natural auditory scene statistics shapes human spatial hearing.

    PubMed

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

    2014-04-22

    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

  10. 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

  11. 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

  12. 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

  13. 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…

  14. 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

  15. 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. PMID:17847946

  16. 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

  17. 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)

  18. 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

  19. 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

  20. Robotics and nature: from primitive creatures to human intelligence

    NASA Astrophysics Data System (ADS)

    Ghaffari, Masoud; Hall, Ernest L.

    2004-10-01

    For thousands of years, humans have looked to nature to find solutions for their problems. This trend has affected the robotics field as well as artificial intelligence, manufacturing, biomechanics, vision and many others. In the robotics field, there are many unsolved problems which amazingly have been solved in nature. These problems vary from basic motion control to high level intelligence problems. Insects' motion, human's walking, driving, exploring an unstructured environment, and object recognition are examples of these problems. Robotics researchers have looked to nature to find solutions to these problems. However, what is missing is human-like computation ability. The presumption is that if we want to create a human like robot, we should implement systems which perceive and operate similar to humans. This paper is a survey on how robotics has been inspired by mimicking nature. It introduces different trends and reviews the modern biologically inspired technology. It also focuses on human perception and potentials for perception based robotics. The significance of this work is that it provides an understanding of the importance of perception in the design of a robot controller.

  1. 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.

  2. 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

  3. [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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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 facilities. 2.400 Section 2.400 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... concerning natural gas as the primary energy source for qualifying small power production facilities....

  9. 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 facilities. 2.400 Section 2.400 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY... concerning natural gas as the primary energy source for qualifying small power production facilities....

  10. 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. PMID:26891694

  11. 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

  12. 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…

  13. Natural human gene correction by small extracellular genomic DNA fragments.

    PubMed

    Yakubov, Leonid A; Rogachev, Vladimir A; Likhacheva, Anastasia C; Bogachev, Sergei S; Sebeleva, Tamara E; Shilov, Alexander G; Baiborodin, Sergei I; Petrova, Natalia A; Mechetina, Ludmila V; Shurdov, Mikhail A; Wickstrom, Eric

    2007-09-15

    Classical gene targeting employs natural homologous recombination for a gene correction using a specially designed and artificially delivered DNA construct but the method is very inefficient. On the other hand, small DNA fragments in the form of tiny chromatin-like particles naturally present in blood plasma can spontaneously penetrate into human cells and cell nuclei. We hypothesized that these natural DNA nanoparticles with recombinagenic free ends might be effective agents for gene replacement therapy. We demonstrate that a mixture of small fragments of total human chromatin from non-mutant cells added to a culture medium without transfection agents efficiently repaired a 47 base pair deletion in the CASP3 gene in 30% of treated human MCF7 breast cancer cells, as shown by restoration of caspase-3 apoptotic function and CASP3 DNA and mRNA structure. Such an innate gene replacement mechanism might function naturally in an organism using its own apoptotic DNA fragments. This mechanism might enable human cancer cell phenotype normalization in the presence of excess normal cells. PMID:17703110

  14. Human efficiency for classifying natural versus random text

    PubMed Central

    Neri, Peter; Liu, Alicia; Levi, Dennis M.

    2010-01-01

    Humans are remarkably efficient at processing natural text. We quantified efficiency for discriminating a sample of meaningful text from a sample of random text by disrupting the meaningful sample, and measuring how much disruption human readers can tolerate before the two samples become indistinguishable. We performed these measurements for a wide range of conditions, involving samples of different lengths and containing letters, words or Chinese characters. We then compared human performance to the best possible performance achieved by a Bayesian estimator under the conditions in which we tested our participants, and in so doing we determined their absolute efficiency. Values were mostly in the range 5–40%, in agreement with reported efficiencies for many visual tasks. Although not intended as a veridical model of human processing, we found that the Bayesian model captured some (but not all) aspects of how humans classified text in our tasks and conditions. PMID:20079757

  15. Gene expression profiling and differentiation assessment in primary human hepatocyte cultures, established hepatoma cell lines, and human liver tissues

    SciTech Connect

    Olsavsky, Katy M.; Page, Jeanine L.; Johnson, Mary C.; Zarbl, Helmut; Strom, Stephen C.; Omiecinski, Curtis J. . E-mail: cjo10@psu.edu

    2007-07-01

    Frequently, primary hepatocytes are used as an in vitro model for the liver in vivo. However, the culture conditions reported vary considerably, with associated variability in performance. In this study, we characterized the differentiation character of primary human hepatocytes cultured using a highly defined, serum-free two-dimensional sandwich system, one that configures hepatocytes with collagen I as the substratum together with a dilute extracellular matrix (Matrigel{sup TM}) overlay combined with a defined serum-free medium containing nanomolar levels of dexamethasone. Gap junctional communication, indicated by immunochemical detection of connexin 32 protein, was markedly enhanced in hepatocytes cultured in the Matrigel sandwich configuration. Whole genome expression profiling enabled direct comparison of liver tissues to hepatocytes and to the hepatoma-derived cell lines, HepG2 and Huh7. PANTHER database analyses were used to identify biological processes that were comparatively over-represented among probe sets expressed in the in vitro systems. The robustness of the primary hepatocyte cultures was reflected by the extent of unchanged expression character when compared directly to liver, with more than 77% of the probe sets unchanged in each of the over-represented categories, representing such genes as C/EBP{alpha}, HNF4{alpha}, CYP2D6, and ABCB1. In contrast, HepG2 and Huh7 cells were unchanged from the liver tissues for fewer than 48% and 55% of these probe sets, respectively. Further, hierarchical clustering of the hepatocytes, but not the cell lines, shifted from donor-specific to treatment-specific when the probe sets were filtered to focus on phenobarbital-inducible genes, indicative of the highly differentiated nature of the hepatocytes when cultured in a highly defined two-dimensional sandwich system.

  16. An Unusual Natural Product Primary Sulfonamide: Synthesis, Carbonic Anhydrase Inhibition, and Protein X-ray Structures of Psammaplin C.

    PubMed

    Mujumdar, Prashant; Teruya, Kanae; Tonissen, Kathryn F; Vullo, Daniela; Supuran, Claudiu T; Peat, Thomas S; Poulsen, Sally-Ann

    2016-06-01

    Psammaplin C is one of only two described natural product primary sulfonamides. Here we report the synthesis of psammaplin C and evaluate the inhibition profile against therapeutically relevant carbonic anhydrase (CA) zinc metalloenzymes. The compound exhibited unprecedented inhibition of an important cancer-associated isozyme, hCA XII, with a Ki of 0.79 nM. The compound also displayed good isoform selectivity for hCA XII over other CAs. We present the first reported protein X-ray crystal structures of psammaplin C in complex with human CAs. We engineered the easily crystallized hCA II enzyme to mimic both the hCA IX and hCA XII binding sites and then utilized protein X-ray crystallography to determine the binding pose of psammaplin C within the hCA II, hCA IX, and hCA XII mimic active sites, all to high resolution. This is the first time a natural product primary sulfonamide inhibitor has been assessed for inhibition and binding to CAs. PMID:27172398

  17. Adherence of Helicobacter pylori to primary human gastrointestinal cells.

    PubMed Central

    Clyne, M; Drumm, B

    1993-01-01

    Helicobacter pylori adheres only to gastric cells in vivo. However, the organism adheres to a wide variety of nongastric cells in vitro. In this study, we have used flow cytometry to assess the adherence of H. pylori to primary epithelial cells isolated from gastric, duodenal, and colonic biopsy specimens by collagenase digestion. After incubation of bacteria and cells together and subsequent staining with a two-stage fluorescein isothiocyanate-labelled H. pylori antibody method, cells with adherent bacteria could be easily distinguished from cells without bacteria. Binding to Kato III cells (a gastric adenocarcinoma cell line) was saturable when bacteria and cells were mixed at a ratio of 250:1. Adherence to cells isolated from gastric biopsy specimens was significantly better than adherence to cells isolated from duodenal or colonic biopsy specimens. Almost 70% of gastric cells had bacteria bound, in contrast to 30% of duodenal cells and 32% of colonic cells (P < 0.0001). There was no correlation between expression of hemagglutinins by the bacteria and ability to bind to either Kato III cells or primary epithelial cells isolated from gastric biopsy specimens. In view of the strict tropism that the organism exhibits in vivo for gastric cells, the results of this study indicate that primary cells are ideal for assessing the factors that might play a role in the pathogenesis of disease caused by the organism. Images PMID:8406792

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

    PubMed

    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

  19. 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

  20. Genome-wide analysis of high risk human papillomavirus E2 proteins in human primary keratinocytes.

    PubMed

    Sunthamala, Nuchsupha; Pang, Chai Ling; Thierry, Francoise; Teissier, Sebastien; Pientong, Chamsai; Ekalaksananan, Tipaya

    2014-12-01

    The E2 protein is expressed in the early stage of human papillomavirus (HPV) infection that is associated with cervical lesions. This protein plays important roles in regulation of viral replication and transcription. To characterize the role of E2 protein in modulation of cellular gene expression in HPV infected cells, genome-wide expression profiling of human primary keratinocytes (HPK) harboring HPV16 E2 and HPV18 E2 was investigated using microarray. The Principle Components Analysis (PCA) revealed that the expression data of HPV16 E2 and HPV18 E2-transduced HPKs were rather closely clustered. The Venn diagram of modulated genes showed an overlap of 10 common genes in HPV16 E2 expressing HPK and HPV18 E2 expressing HPK. These genes were expressed with significant difference by comparison with control cells. In addition, the distinct sets of modulated genes were detected 14 and 34 genes in HPV16 E2 and HPV18 E2 expressing HPKs, respectively. PMID:26484085

  1. 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

  2. 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…

  3. An aggressive primary orbital natural killer/T-cell lymphoma case: poor response to chemotherapy.

    PubMed

    Marchino, Tizana; Ibáñez, Núria; Prieto, Sebastián; Novelli, Silvana; Szafranska, Justyna; Mozos, Anna; Graell, Xavier; Buil, José A

    2014-01-01

    Natural killer/T-cell lymphoma (NKTCL) and its presentation with extranodal orbital involvement as a single lesion are extremely rare. The aim of this article was to describe the presentation, diagnosis, and systemic treatment of a primary orbital NKTCL. A 67-year-old Caucasian woman presented with left exophthalmos, pain, periorbital swelling, and limited extrinsic ocular motility. Orbital cellulitis was suspected, but finally orbital biopsy was performed due to no response to initial antibiotic and anti-inflammatory standard treatment. The pathologic diagnosis was NKTCL. Systemic evaluations were negative. CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) chemotherapy was initiated, but after 2 cycles of treatment, tumoral progression was observed. SMILE (dexamethasone, methotrexate, ifosfamide, L-asparaginase, etoposide) rescue chemotherapy was then administered. Lymphoma progression was inevitable. She died 10 months later. Although more nasal NKTCL cases have been described, the nonnasal primary orbital NKTCL is an uncommon neoplasm with high mortality rate, despite the recent use of more potent chemotherapy regimens. PMID:24317101

  4. 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.

  5. 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

  6. 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.

  7. Induction of apoptosis of human primary osteoclasts treated with extracts from the medicinal plant Emblica officinalis

    PubMed Central

    Penolazzi, Letizia; Lampronti, Ilaria; Borgatti, Monica; Khan, Mahmud Tareq Hassan; Zennaro, Margherita; Piva, Roberta; Gambari, Roberto

    2008-01-01

    Background Osteoclasts (OCs) are involved in rheumatoid arthritis and in several pathologies associated with bone loss. Recent results support the concept that some medicinal plants and derived natural products are of great interest for developing therapeutic strategies against bone disorders, including rheumatoid arthritis and osteoporosis. In this study we determined whether extracts of Emblica officinalis fruits display activity of possible interest for the treatment of rheumatoid arthritis and osteoporosis by activating programmed cell death of human primary osteoclasts. Methods The effects of extracts from Emblica officinalis on differentiation and survival of human primary OCs cultures obtained from peripheral blood were determined by tartrate-acid resistant acid phosphatase (TRAP)-positivity and colorimetric MTT assay. The effects of Emblica officinalis extracts on induction of OCs apoptosis were studied using TUNEL and immunocytochemical analysis of FAS receptor expression. Finally, in vitro effects of Emblica officinalis extracts on NF-kB transcription factor activity were determined by gel shift experiments. Results Extracts of Emblica officinalis were able to induce programmed cell death of mature OCs, without altering, at the concentrations employed in our study, the process of osteoclastogenesis. Emblica officinalis increased the expression levels of Fas, a critical member of the apoptotic pathway. Gel shift experiments demonstrated that Emblica officinalis extracts act by interfering with NF-kB activity, a transcription factor involved in osteoclast biology. The data obtained demonstrate that Emblica officinalis extracts selectively compete with the binding of transcription factor NF-kB to its specific target DNA sequences. This effect might explain the observed effects of Emblica officinalis on the expression levels of interleukin-6, a NF-kB specific target gene. Conclusion Induction of apoptosis of osteoclasts could be an important strategy both in

  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. 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.

  10. 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…

  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. Neuronal responses in cat primary auditory cortex to natural and altered species-specific calls.

    PubMed

    Gehr, D D; Komiya, H; Eggermont, J J

    2000-12-01

    We investigated how natural and morphed cat vocalizations are represented in primary auditory cortex (AI). About 40% of the neurons showed time-locked responses to major peaks in the vocalization envelope, 60% only responded at the onset. Simultaneously recorded multi-unit (MU) activity of these peak-tracking neurons on separate electrodes was significantly more synchronous during stimulation than under silence. Thus, the representation of the vocalizations is likely synchronously distributed across the cortex. The sum of the responses to the low and high frequency part of the meow, with the boundary at 2.5 kHz, was larger than the neuronal response to the natural meow itself, suggesting that strong lateral inhibition is shaping the response to the natural meow. In this sense, the neurons are combination-sensitive. The frequency-tuning properties and the response to amplitude-modulated tones of the MU recordings can explain the responses to natural, and temporally and spectrally altered vocalizations. Analysis of the mutual information in the firing rate suggests that the activity of at least 95 recording sites in AI would be needed to reliably distinguish between the nine different vocalizations. This suggests that a distributed representation based on temporal stimulus aspects may be more efficient than one based on firing rate. PMID:11077191

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

    PubMed Central

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

    2012-01-01

    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. PMID:22547810

  14. 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

  15. Pericellular oxygen concentration of cultured primary human trophoblasts

    PubMed Central

    Chen, Baosheng; Longtine, Mark S.; Nelson, D. Michael

    2012-01-01

    Introduction Oxygen is pivotal in placental development and function. In vitro culture of human trophoblasts provides a useful model to study this phenomenon, but a hotly debated issue is whether or not the oxygen tension of the culture conditions mimics in vivo conditions. We tested the hypothesis that ambient oxygen tensions in culture reflect the pericellular oxygen levels. Methods We used a microelectrode oxygen sensor to measure the concentration of dissolved oxygen in the culture medium equilibrated with 21%, 8% or <0.5% oxygen. Results The concentration of oxygen in medium without cells resembled that in the ambient atmosphere. The oxygen concentration present in medium bathing trophoblasts was remarkably dependent on the depth within the medium where sampling occurred, and the oxygen concentration within the overlying atmosphere was not reflected in medium immediately adjacent to the cells. Indeed, the pericellular oxygen concentration was in a range that most would consider severe hypoxia, at ≤ 0.6% oxygen or about 4.6 mm Hg, when the overlying atmosphere was 21% oxygen. Conclusions We conclude that culture conditions of 21% oxygen are unable to replicate the pO2 of 40–60 mm Hg commonly attributed to the maternal blood in the intervillous space in the second and third trimesters of pregnancy. We further surmise that oxygen atmospheres in culture conditions between 0.5% and 21% provide different oxygen fluxes in the immediate pericellular environment yet can still yield insights into the responses of human trophoblast to different oxygen conditions. PMID:23211472

  16. The impact of natural odors on affective states in humans.

    PubMed

    Weber, Sandra T; Heuberger, Eva

    2008-06-01

    Laboratory studies have shown a significant influence of certain fragrances on affective as well as cognitive states in humans. The aim of the current study was to measure the relationship between complex, natural odors and affective states, that is, calmness, alertness, and mood, in the field. In 4 experiments, the emotional impact, intensity, and hedonics of complex, natural plant odors were assessed in 32 healthy human subjects and compared with control conditions involving a similar outdoor environment without the tested fragrant plants. In all experiments, the selected fragrances were evaluated as more intense than the odors in the control conditions but pleasantness ratings differed only in 2 of the 4 experiments. The fragrances improved subjective ratings of calmness, alertness, and mood depending on the sequence of the conditions but independent of visual features of the environment. In contrast, a fifth experiment which tested the influence of natural and artificial pleasant odors and an artificial unpleasant odor on calmness, alertness, and mood in 22 subjects showed that the unpleasant odor impaired these affective states in humans independent of the order of presentation. On the other hand, no effects of the pleasant odors on mood and calmness were observed in this experiment. PMID:18353767

  17. 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. PMID:24446150

  18. Molecular genetics of human primary microcephaly: an overview

    PubMed Central

    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

  19. 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

  20. [The comprehensive nature of primary health care: evaluation from the user standpoint].

    PubMed

    Silva, Carla Silvana de Oliveira e; Fonseca, Adélia Dayane Guimarães; Souza, Luís Paulo Souza e; Siqueira, Leila das Graças; Belasco, Angélica Gonçalves Silva; Barbosa, Dulce Aparecida

    2014-11-01

    This study sought to evaluate the comprehensive nature of Primary Health Care (PHC), from the standpoint of the users of the Family Health Strategy (FHS) and users of others services of PHC. It involved a cross-sectional, analytical and quantitative study conducted in Montes Claros in the Brazilian state of Minas Gerais. For data collection, the adult version of a validated Primary Care Assessment Tool questionnaire was applied to 373 adult service users, of which 124 (33.6%) reported attendance by the FHS and 249 (66.4%) reported attendance by other services. Scores were assigned for the eight dimensions of the instrument, though only three were used for this study, namely first contact, accessibility, and longitudinality. The results showed that in relation to the comprehensive nature of PHC, there was a better evaluation by the population that uses the FHS compared to those who use other services. The first contact, accessibility and longitudinality attributes obtained higher scores in the FHS care provided in comparison with other services, with statistical significance for all attributes. The conclusion drawn is that it is of fundamental importance to assess the attributes of PHC in order to improve the quality of services provided. PMID:25351307

  1. Productive Lytic Replication of a Recombinant Kaposi's Sarcoma-Associated Herpesvirus in Efficient Primary Infection of Primary Human Endothelial Cells

    PubMed Central

    Gao, Shou-Jiang; Deng, Jian-Hong; Zhou, Fu-Chun

    2003-01-01

    Kaposi's sarcoma-associated herpesvirus (KSHV) is linked to the development of Kaposi's sarcoma (KS), a vascular spindle cell tumor primarily consisting of proliferating endothelial cells. Although KSHV has been shown to infect primary human endothelial cells and convert them into spindle shapes, KSHV infection is largely latent, and efforts to establish a highly efficient and sustainable infection system have been unsuccessful. A recombinant KSHV, BAC36, that has high primary-infection efficiency in 293 cells has been obtained (F. C. Zhou, Y. J. Zhang, J. H. Deng, X. P. Wang, H. Y. Pan, E. Hettler, and S. J. Gao, J. Virol. 76:6185-6196, 2002). BAC36 contains a green fluorescent protein cassette which can be used to conveniently monitor viral infection. Here, we describe the establishment of a KSHV lytic-replication-permissive infection cell model using BAC36 virions to infect primary human umbilical vein endothelial cell (HUVEC) cultures. BAC36 infection of HUVEC cultures has as high as 90% primary-infection efficiency and consists of two phases: a permissive phase, in which the cultures undergo active viral lytic replication, producing a large number of virions and concomitantly resulting in large-scale cell death, and a latent phase, in which the surviving cells from the permissive phase switch into latent infection, with a small number of cells undergoing spontaneous viral lytic replication, and proliferate into bundles of spindle cells with KS slit-like spaces. An assay for determining the KSHV titer in a virus preparation has also been developed. The cell model should be useful for examining KSHV infection and replication, as well as for understanding the development of KS. PMID:12941882

  2. 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

  3. The primary inhibitor of plasmin in human plasma.

    PubMed Central

    Müllertz, S; Clemmensen, I

    1976-01-01

    A complex between plasmin and an inhibitor was isolated by affinity chromatography from urokinase-activated human plasma. The complex did not react with antibodies against any of the known proteinase inhibitors in plasma. A rabbit antiserum against the complex was produced. It contained antibodies agianst plasminogen+plasmin and an alpha2 protein. By crossed immunoelectrophoresis the alpha2 protein was shown to form a complex with plasmin, when generated by urokinase in plasma, and with purified plasmin. The alpha2 protein was eluted by Sephadex G-200 gel filtration with KD approx. 0.35, different from the other inhibitors of plasmin in plasma, and corresponding to an apparent relative molecular mass (Mr) of about 75000. By sodium dodecyl sulphate/polyacrylamide-gel electrophoresis, the Mr of the complex was found to be approx. 130000. After reduction of the complex two main bands of protein were observed, with Mr, about 72000 and 66000, probably representing an acyl-enzyme complex of plasmin-light chain and inhibitor-heavy chain, and a plasmin-heavy chain. A weak band with Mr 9000 was possibly an inhibitor-light chain. The inhibitor was partially purified and used to titrate purified plasmin of known active-site concentration. The inhibitor bound plasmin rapidly and strongly. Assuming an equimolar combining ratio, the concentration of active inhibitor in normal human plasma was estimated to be 1.1 mumol/1. A fraction about 0.3 of the antigenic inhibitor protein appeared to be functionally inactive. In plasma, plasmin is primarily bound to the inhibitor. Only after its saturation does lysis of fibrinogen and fibrin occur and a complex between plasmin and alpha2 macroglobulin appear. Images PLATE 1 PLATE 2 PLATE 3 PLATE 4 PMID:137718

  4. 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

  5. Macaques exhibit a naturally-occurring depression similar to humans.

    PubMed

    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

  6. 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

  7. Primary porcine proximal tubular cells as an alternative to human primary renal cells in vitro: an initial characterization

    PubMed Central

    2013-01-01

    Background A good in vitro model should approximate an in vivo-like behavior as closely as possible in order to reflect most likely the in vivo situation. Regarding renal physiology of different species, humans are more closely related to pigs than to rodents, therefore primary porcine kidney cells (PKC) and their subsequent cell strain could be a valid alternative to primary human cells for renal in vitro toxicology. For this PKC must display inherent characteristics (e.g. structural organization) and functions (e.g. transepithelial transport) as observed under in vivo conditions within the respective part of the kidney. Results We carried out a comprehensive characterization of PKC and their subsequent cell strain, including morphology and growth as well as transporter expression and functionality. The data presented here demonstrate that PKC express various transporters including pMrp1 (abcc1), pMrp2 (abcc2), pOat1 (slc22a6) and pOat3 (slc22a8), whereas pMdr1 (abcb1) and pOatp1a2 (slco1a2) mRNA could not be detected in either the PKCs or in the porcine cortical tissue. Functionality of the transporters was demonstrated by determining the specific PAH transport kinetics. Conclusions On the basis of the presented results it can be concluded that PKC and to some extent their subsequent cell strain represent a valuable model for in vitro toxicology, which might be used as an alternative to human primary cells. PMID:24308307

  8. 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.

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

    PubMed

    Stefanon, Bruno; Pomari, Elena; Colitti, Monica

    2015-07-01

    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

  10. Micropatterned coculture of primary human hepatocytes and supportive cells for the study of hepatotropic pathogens.

    PubMed

    March, Sandra; Ramanan, Vyas; Trehan, Kartik; Ng, Shengyong; Galstian, Ani; Gural, Nil; Scull, Margaret A; Shlomai, Amir; Mota, Maria M; Fleming, Heather E; Khetani, Salman R; Rice, Charles M; Bhatia, Sangeeta N

    2015-12-01

    The development of therapies and vaccines for human hepatropic pathogens requires robust model systems that enable the study of host-pathogen interactions. However, in vitro liver models of infection typically use either hepatoma cell lines that exhibit aberrant physiology or primary human hepatocytes in culture conditions in which they rapidly lose their hepatic phenotype. To achieve stable and robust in vitro primary human hepatocyte models, we developed micropatterned cocultures (MPCCs), which consist of primary human hepatocytes organized into 2D islands that are surrounded by supportive fibroblast cells. By using this system, which can be established over a period of days, and maintained over multiple weeks, we demonstrate how to recapitulate in vitro hepatic life cycles for the hepatitis B and C viruses and the Plasmodium pathogens P. falciparum and P. vivax. The MPCC platform can be used to uncover aspects of host-pathogen interactions, and it has the potential to be used for drug and vaccine development. PMID:26584444

  11. 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

  12. Expression of natural antimicrobials by human placenta and fetal membranes.

    PubMed

    King, A E; Paltoo, A; Kelly, R W; Sallenave, J-M; Bocking, A D; Challis, J R G

    2007-01-01

    Preterm birth associated with infection is a major clinical problem. We hypothesized that this condition is associated with altered expression of natural antimicrobial molecules (beta-defensins (HBD), elafin). Therefore, we examined expression of these molecules and their regulation by proinflammatory cytokines in placentae and fetal membranes from term pregnancy. HBD1-3 and elafin were localized by immunohistochemistry in fetal membranes and placenta. Real-time quantitative PCR was used to examine mRNA expression in primary trophoblast cells treated with inflammatory molecules. HBD1-3 and elafin were immunolocalized to placental and chorion trophoblast layers of fetal membranes and placenta. Immunoreactivity was also observed in amnion epithelium and decidua. No differences were noted between samples from women who were not in labour compared to those in active labour. In in vitro cultures of primary trophoblast cells, HBD2 and elafin mRNA expression was upregulated by the proinflammatory cytokine, IL-1beta. These results suggest that the chorion and placental trophoblast layers may be key barriers to the progression of infection in the pregnant uterus. Natural antimicrobial expression may be altered in response to inflammatory mediator expression associated with the onset of labour and/or uterine infection, providing increased protection when the uterus may be particularly susceptible to infection. PMID:16513165

  13. 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…

  14. 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

  15. Natural human interferon-alpha 2 is O-glycosylated.

    PubMed Central

    Adolf, G R; Kalsner, I; Ahorn, H; Maurer-Fogy, I; Cantell, K

    1991-01-01

    Natural human interferon alpha 2 (IFN-alpha 2) was isolated from a preparation of partially purified human leucocyte IFN by monoclonal-antibody immunoaffinity chromatography. The purified protein had a specific activity of 1.5 x 10(8) i.u./mg; it was estimated to constitute 10-20% of the total antiviral activity of leucocyte IFN. N-Terminal amino-acid-sequence analysis identified the subspecies IFN-alpha 2b and/or IFN-alpha 2c, whereas IFN-alpha 2a was not detectable. The structure of natural IFN-alpha 2 was found to differ from that of its recombinant (Escherichia coli-derived) equivalent. First, reverse-phase h.p.l.c. showed that natural IFN-alpha 2 was significantly more hydrophilic then expected. Secondly, the apparent molecular mass of the natural protein determined by SDS/PAGE was higher than that of recombinant IFN-alpha 2; incubation under mild alkaline conditions known to eliminate O-linked carbohydrates resulted in a reduction of the apparent molecular mass to that of the recombinant protein. On sequence analysis of proteolytic peptides, Thr-106 was found to be modified. These results suggested that Thr-106 of natural IFN-alpha 2 carries O-linked carbohydrates. Reverse-phase h.p.l.c. as well as SDS/PAGE of natural IFN-alpha 2 showed that glycosylation is heterogeneous. For characterization of the carbohydrate moieties, the protein was treated with neuraminidase and/or O-glycanase and analysed by gel electrophoresis; in addition, glycopeptides obtained by proteinase digestion and separated by h.p.l.c. were characterized by sequence analysis and m.s. Further information on the composition of the glycans was obtained by monosaccharide analysis. The results indicate that natural IFN-alpha 2 contains the disaccharide galactosyl-N-acetylgalactosamine (Gal-GalNAc) linked to Thr-106. In part of the molecules, this core carbohydrate carries (alpha-)N-acetylneuraminic acid, whereas a disaccharide, probably N-acetyl-lactosamine, is bound to Gal-GalNAc in another

  16. HIV-1 increases TLR responses in human primary astrocytes

    PubMed Central

    Serramía, M Jesús; Muñoz-Fernández, M Ángeles; Álvarez, Susana

    2015-01-01

    Astrocytes are the major glial cell within the central nervous system and have a number of important physiological properties related to brain homeostasis. They provide trophic support to neurons and are immune cells with key roles during states-of-inflammation. The potential for production of proinflammatory cytokines and its consequences has been studied in the context of HIV-1 infection of normal human astrocytes (NHA). NHA express TLR3, TLR4, and TLR5. TLR3 ligation induced the strongest proinflammatory polarizing response, characterized by generation of high levels of TNF-α, IL-6, and IL-8. HIV-1 increased the transient production of key inflammatory mediators, and exposure to LPS of HIV-1-infected cells increased significantly the cytokine secretion. We confirmed that it is necessary viral gene expression from the moment of pretreatment with antiretrovirals inhibited totally HIV-1-induced TLR response. The higher response to LPS from HIV-1-infected cells did not correlate with TLR4 or MyD88 increased expression. LPS responsiveness of infected cells parallels MHC class II expression, but not CD14. HIV-1-infected NHA present increased sensitivity to the proinflammatory effects of LPS. If this phenomenon occurs in vivo, it will contribute to the immunopathogenesis of this disease and may ultimately offer novel targets for immunomodulatory therapy. PMID:26671458

  17. 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

  18. 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

  19. From nature-dominated to human-dominated environmental changes

    NASA Astrophysics Data System (ADS)

    Messerli, Bruno; Grosjean, Martin; Hofer, Thomas; Núñez, Lautaro; Pfister, Christian

    2000-01-01

    To what extent is it realistic and useful to view human history as a sequence of changes from highly vulnerable societies of hunters and gatherers through periods with less vulnerable, well buffered and highly productive agrarian-urban societies to a world with regions of extreme overpopulation and overuse of life support systems, so that vulnerability to climatic-environmental changes and extreme events is again increasing? This question cannot be fully answered in our present state of knowledge, but at least we can try to illustrate, with three case studies from different continents, time periods and ecosystems, some fundamental changes in the relationship between natural processes and human activities that occur, as we pass from a nature-dominated to a human dominated environment. 1. Early-mid Holocene: Nature dominated environment — human adaptation, mitigation, and migration. In the central Andes, the Holocene climate changed from humid (10,800-8000 BP) to extreme arid (8000-3600 BP) conditions. Over the same period, prehistoric hunting communities adopted a more sedentary pattern of resource use by settling close to the few perennial water bodies, where they began the process of domesticating camelids around 5000 BP and irrigation from about 3100 BP. 2. Historical period: An agrarian society in transition from an "enduring" to an innovative human response. Detailed documentary evidence from Western Europe may be used to reconstruct quite precisely the impacts of climatic variations on agrarian societies. The period considered spans a major transition from an apparently passive response to the vagaries of the environment during the 16th century to an active and innovative attitude from the onset of the agrarian revolution in the late 18th century through to the present day. The associated changes in technology and in agricultural practices helped to create a society better able to survive the impact of climatic extremes. 3. The present day: A human dominated

  20. 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. PMID:26411425

  1. [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

  2. 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.

  3. 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

  4. Relaxed natural selection in human populations during the Pleistocene.

    PubMed

    Takahata, N

    1993-12-01

    Available genetic data reveals that the human population is more variable than the chimpanzee population at the protein level, whereas the opposite is the case at the DNA level. The lower level of silent polymorphism in the human population suggests that its long-term breeding size is smaller than the chimpanzee's. The neutral theory suggests that natural selection has been relaxed in the human population under the improved environment. The possibility that the relaxation began with the emergence of Homo sapiens is examined, because it is known that H. habilis underwent for the first time dramatic changes in brain size, way of life, and culture, and that the childhood of H. erectus was already twice as long as that of chimpanzee. The relaxation hypothesis predicts that, relative to chimpanzee, some 20% of deleterious mutations became harmless under the changed environment throughout the Pleistocene. More extensive study of genetic variation in non-human primates is necessary not only to confirm the hypothesis, but also to better understand the human genome itself. PMID:8031575

  5. Primary human osteoblast culture on 3D porous collagen-hydroxyapatite scaffolds.

    PubMed

    Jones, Gemma L; Walton, Robin; Czernuszka, Jan; Griffiths, Sarah L; El Haj, Alicia J; Cartmell, Sarah H

    2010-09-15

    There is a need in tissue-engineering for 3D scaffolds that mimic the natural extracellular matrix of bone to enhance cell adhesion, proliferation, and differentiation. The scaffold is also required to be degradable. A highly porous scaffold has been developed to incorporate two of the extracellular components found in bone-collagen and hydroxyapatite (HA). The scaffold's collagen component is an afibrillar monomeric type I atelocollagen extracted from foetal calf's skin. This provided a novel environment for the inclusion of HA powder. Five hundred thousand primary human osteoblasts were seeded onto 4 mm cubed scaffolds that varied in ratio of HA to collagen. Weight ratios of 1:99, 25:75, 50:50, and 75:25 hydroxyapatite:collagen (HA:Collagen) were analysed. The scaffolds plus cells were cultured for 21 days. DNA assays and live/dead viability staining demonstrated that all of the scaffolds supported cell proliferation and viability. An alkaline phosphatase assay showed similar osteoblast phenotype maintenance on all of the 3D scaffolds analysed at 21 days. MicroCT analysis demonstrated an increase in total sample volume (correlating to increase in unmineralised matrix production). An even distribution of HA throughout the collagen matrix was observed using this technique. Also at 3 weeks, reductions in the percentage of the mineralised phase of the constructs were seen. These results indicate that each of the ratios of HA/collagen scaffolds have great potential for bone tissue engineering. PMID:20694991

  6. 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

  7. 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

  8. '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.

  9. 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).

  10. 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.

  11. Establishment and characterization of OS 99-1, a cell line derived from a highly aggressive primary human osteosarcoma.

    PubMed

    Gillette, Jennifer M; Gibbs, C Parker; Nielsen-Preiss, Sheila M

    2008-01-01

    Osteosarcoma is the most common form of primary bone cancer. In this study, we established a human osteosarcoma cell line (OS 99-1) from a highly aggressive primary tumor. G-banding karyotype analysis demonstrated a large number of clonal abnormalities, as well as extensive intercellular heterogeneity. Through the use of immunologic, molecular, and biochemical analyses, we characterized protein and gene expression profiles confirming the osteogenic nature of the cells. Further evaluation indicated that OS 99-1 cells maintain the capacity to differentiate in an in vitro mineralization assay as well as form tumors in the in vivo chicken embryo model. This cell line provides a useful tool to investigate the molecular mechanisms contributing to osteosarcoma and may have the potential to serve as a culture system for studies involving bone physiology. PMID:18247100

  12. 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

  13. Molecular cloning of an activated human oncogene, homologous to v-raf, from primary stomach cancer.

    PubMed Central

    Shimizu, K; Nakatsu, Y; Sekiguchi, M; Hokamura, K; Tanaka, K; Terada, M; Sugimura, T

    1985-01-01

    Transfection with high molecular weight DNA from a primary stomach cancer induced foci of transformed NIH 3T3 cells, and the transformed cells were tumorigenic in nude mice. By screening with a human Alu-family probe, we isolated the human DNA sequence from the secondary transformant cells. This transforming sequence encompasses about 60 kilobase pairs and is unrelated to known human transforming genes. Examination of homologies between this sequence and retroviral oncogenes revealed that the human transforming sequence is closely related to the v-raf oncogene of murine transforming retrovirus 3611-MSV. Images PMID:3862088

  14. The importance of being we: human nature and intergroup relations.

    PubMed

    Brewer, Marilynn B

    2007-11-01

    The author discusses the nature of in-group bias and the social motives that underlie ethnocentric attachment to one's own membership groups. Two common assumptions about in-group bias are challenged: that in-group positivity necessitates out-group derogation and that in-group bias is motivated by self-enhancement. A review of relevant theory and research on intergroup relations provides evidence for 3 alternative principles: (a) in-group attachment and positivity are primary and independent of out-groups, (b) security motives (belonging and distinctiveness) underlie universal in-group favoritism, and (c) attitudes toward out-groups vary as a function of intergroup relationships and associated threats to belonging and distinctiveness PMID:18020737

  15. 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

  16. 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

  17. 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

  18. 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

  19. [Natural history of the infection for human papillomavirus: an actualization].

    PubMed

    Martínez, Gerardo González; Troconis, José Núñez

    2014-03-01

    In recent years, there have been major advances in our understanding of the biology and natural history of Human Papilloma Virus (HPV). Most papillomavirus infections are transmitted by close contact of either skin to skin or mucosa to mucosa. Sexual intercourse is not a requirement for genital HPV infection. Digital-oral infections occur and there is evidence that digital-genital and oral-genital contacts can result in the transmission of HPV, although in a relatively low percentage. Vertical transmission from mother to fetus is a common route of infection; in fact, it is recognized that more than 80% of infants born from mothers infected with genital HPV will be positive for HPV DNA determination in the nasal-pharyngeal region and oral mucosa. Women with transient infections often develop cytological abnormalities that take place while there is active HPV replication. This occurs because productive HPV infections result in cytological abnormalities in infected epithelial cells. The strong association between the risk of HPV infection and increased immune suppression, supports a direct biological effect of Human Immunodeficiency Virus (HIV) infection on the natural history of HPV. PMID:24758104

  20. 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

  1. Updating the Natural History of Human Papillomavirus and Anogenital Cancers

    PubMed Central

    Moscicki, Anna-Barbara; Schiffman, Mark; Burchell, Ann; Albero, Ginesa; Giuliano, Anna; Goodman, Marc T.; Kjaer, Susanne K.; Palefsky, Joel

    2013-01-01

    This chapter addresses the natural history of anogenital human papillomavirus (HPV) infection. Cervical infections are the best understood HPV infection. Cervical HPV persistence is the known necessary event for the development of cervical cancer. New infections appearing at any age are benign unless they persist. Several long-term natural history studies have now shed light on the very low risk of cervical intraepithelial neoplasia (CIN) 3+ in women past the peak of HPV acquisition (e.g., 30 or older) who are HPV-negative or clear their HPV. Although data on transmission of HPV are finally emerging, rates of transmission between heterosexual couples vary widely among studies. Factors that affect the calculations of these rates include a) intervals between testing points, b) rates of concordance or discordance at baseline, and c) difficulty in defining established infections versus contamination. Both cervix to anus and anus to cervix autoinoculation in the same woman appears to be quite common. Whether either site serves as a long-term reservoir is unknown. Studies show that anal infections in women and in men who have sex with men are quite common with cumulative rates up to 70–90%. Similarly, clearance of anal HPV is also common, with few individuals showing persistence unless they are human immunodeficiency virus (HIV)-infected. HIV strongly influences the development of anal intraepithelial neoplasia (AIN). The few studies on the natural history of AIN in HIV-infected men suggest that high-grade AIN is a precursor to invasive anal cancer. Although no natural history studies of AIN are available in women, women with other HPV-associated lesions, including CIN3+ and vulvar cancer, have higher rates of anal cancer. Data on the natural history of HPV of the male genitalia are also emerging, although penile intraepithelial neoplasia is poorly understood. Cumulative rates of HPV are extremely high in men and risks are associated with sexual behavior. Unlike women

  2. 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

  3. 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.

  4. 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

  5. Natural polymorphism S119R of HIV-1 integrase enhances primary INSTI resistance.

    PubMed

    Hachiya, Atsuko; Ode, Hirotaka; Matsuda, Masakazu; Kito, Yumiko; Shigemi, Urara; Matsuoka, Kazuhiro; Imamura, Junji; Yokomaku, Yoshiyuki; Iwatani, Yasumasa; Sugiura, Wataru

    2015-07-01

    Integrase strand transfer inhibitors (INSTIs), which block proviral DNA integration into the host chromosome, are clinically effective against HIV-1 isolates exhibiting resistance to other classes of antiretroviral agents. Although naturally occurring amino acid variation has been less frequently observed in the integrase region, the functional constraints of this variation on primary INSTI resistance-associated mutations are not fully understood. In the present study, we focused on the S119G/R/P/T (S119X) polymorphisms, which are frequently observed in HIV-1 sequences derived from clinical specimens (naïve, n=458, 26%). The frequency of the S119X polymorphism together with Q148H/R (n=8, 63%) or N155H (n=12, 83%) was relatively high compared with that of naïve group. Our in vitro assays revealed that S119G/P/T alone exerted no effect on the susceptibility to INSTIs, whereas S119R enhanced the level of INSTI resistance induced by well-known INSTI resistance-associated mutations (Y143C, Q148H or N155H). Notably, the S119R polymorphism contributed to a significant (5.9-fold) increase in dolutegravir resistance caused by G140S/Q148H. Analysis of two cases of virological failure during raltegravir-based therapy showed that the accumulation and the rapid evolution of primary INSTI resistance-associated mutations coincided with the S119R mutation. These data highlight the role of the S119X polymorphism in INSTI resistance, and this polymorphism might be linked to the potential treatment outcome with INSTI-based therapy. PMID:25956162

  6. 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

  7. 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

  8. Arctigenin from Arctium lappa inhibits interleukin-2 and interferon gene expression in primary human T lymphocytes

    PubMed Central

    2011-01-01

    Background Arctium lappa (Niubang), a Chinese herbal medicine, is used to treat tissue inflammation. This study investigates the effects of arctigenin (AC), isolated from A. lappa, on anti-CD3/CD28 Ab-stimulated cell proliferation and cytokine gene expression in primary human T lymphocytes. Methods Cell proliferation was determined with enzyme immunoassays and the tritiated thymidine uptake method. Cytokine production and gene expression were analyzed with reverse transcription-polymerase chain reaction. Results AC inhibited primary human T lymphocytes proliferation activated by anti-CD3/CD28 Ab. Cell viability test indicated that the inhibitory effects of AC on primary human T lymphocyte proliferation were not due to direct cytotoxicity. AC suppressed interleukin-2 (IL-2) and interferon-γ (IFN-γ) production in a concentration-dependent manner. Furthermore, AC decreased the IL-2 and IFN-γ gene expression in primary human T lymphocytes induced by anti-CD3/CD28 Ab. Reporter gene analyses revealed that AC decreased NF-AT-mediated reporter gene expression. Conclusion AC inhibited T lymphocyte proliferation and decreased the gene expression of IL-2, IFN-γ and NF-AT. PMID:21435270

  9. 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…

  10. Recombinant Adeno-Associated Virus Serotype 6 Efficiently Transduces Primary Human Melanocytes

    PubMed Central

    Verdon, Daniel; Chen, Jennifer; Taylor, John A.; Dunbar, P. Rod

    2013-01-01

    The study of melanocyte biology is important to understand their role in health and disease. However, current methods of gene transfer into melanocytes are limited by safety or efficacy. Recombinant adeno-associated virus (rAAV) has been extensively investigated as a gene therapy vector, is safe and is associated with persistent transgene expression without genome integration. There are twelve serotypes and many capsid variants of rAAV. However, a comparative study to determine which rAAV is most efficient at transducing primary human melanocytes has not been conducted. We therefore sought to determine the optimum rAAV variant for use in the in vitro transduction of primary human melanocytes, which could also be informative to future in vivo studies. We have screened eight variants of rAAV for their ability to transduce primary human melanocytes and identified rAAV6 as the optimal serotype, transducing 7–78% of cells. No increase in transduction was seen with rAAV6 tyrosine capsid mutants. The number of cells expressing the transgene peaked at 6–12 days post-infection, and transduced cells were still detectable at day 28. Therefore rAAV6 should be considered as a non-integrating vector for the transduction of primary human melanocytes. PMID:23646140

  11. 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

  12. Human Amplified Natural Change: An approach for vulnerability assessment and mitigation planning

    NASA Astrophysics Data System (ADS)

    Wilcock, P.; Belmont, P.; Gran, K. B.

    2011-12-01

    Addressing the environmental impacts of agricultural development is made difficult by the scale and complexity of the natural system, the pervasive human alteration of that system, the contingent and nonlinear nature of system response, and the web of natural-human interactions driving social, economic, and regulatory decisions over periods of decades to centuries. One of the most difficult challenges is determining those locations within the landscape that are most sensitive to change. One approach is the concept of human-amplified natural change (HANC), a hypothesis that states that areas of the landscape that are most susceptible to human, climatic, and other external changes are those that are undergoing the highest rates of natural change. High variability in system response implies that there are locations and moments that are especially vulnerable to changes in climate and human actions. These 'critical areas' are not only essential to understand for mitigation purposes, but also serve as targeted locations in which to monitor change in an accelerated environment. Under the HANC hypothesis, it is these locations that should be the focus for both research and management. We explore the HANC hypothesis using the case of sediment delivery to the Upper Mississippi River. Work on Lake Pepin, a natural lake on the Mississippi River, has shown that sediment supply has increased ten-fold over the past 150 years. This period corresponds with widespread implementation of drainage and row cropping in the Minnesota River Basin, the primary contributor of sediment to the Upper Mississippi. Although this development is clearly important, the watershed was geologically primed to produce large amounts of sediment as it incises through soft glacial sediments in response to a base level fall associated with the carving of the Minnesota River valley over 13,000 years before present. The nearly complete transformation of the land surface, vegetation, and hydrology over the past

  13. 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. PMID:11390041

  14. 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

  15. Oregonin reduces lipid accumulation and proinflammatory responses in primary human macrophages.

    PubMed

    Lundqvist, Annika; Magnusson, Lisa U; Ullström, Christina; Krasilnikova, Jelena; Telysheva, Galina; Dizhbite, Tatjana; Hultén, Lillemor Mattsson

    2015-03-13

    Inflammation in the vascular wall is important for the development of atherosclerosis. We have previously shown that inflammatory macrophages are more abundant in human atherosclerotic lesions than in healthy arteries. Activated macrophages produce reactive oxygen species (ROS) that promote local inflammation in atherosclerotic lesions. Here, we investigated the role of oregonin, a diarylheptanoid, on proinflammatory responses in primary human macrophages and found that oregonin decreased cellular lipid accumulation and proinflammatory cytokine secretion. We also found that oregonin decreased ROS production in macrophages. Additionally, we observed that treatment of lipopolysaccharide-exposed macrophages with oregonin significantly induced the expression of antioxidant-related genes, including Heme oxygenase-1 and NADPH dehydrogenase quinone 1. In summary, we have shown that oregonin reduces lipid accumulation, inflammation and ROS production in primary human macrophages, indicating that oregonin has anti-inflammatory bioactivities. PMID:25686497

  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. PMID:26957449

  17. 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.

  18. Early activation of natural killer and B cells in response to primary dengue virus infection in A/J mice.

    PubMed

    Shresta, Sujan; Kyle, Jennifer L; Robert Beatty, P; Harris, Eva

    2004-02-20

    Dengue virus (DEN) causes the most prevalent arthropod-borne viral illness in humans worldwide. Immune mechanisms that are involved in protection and pathogenesis of DEN infection have not been fully elucidated due largely to the lack of an adequate animal model. Therefore, as a first step, we characterized the primary immune response in immunocompetent inbred A/J mice that were infected intravenously with a non-mouse-adapted DEN type 2 (DEN2) strain. A subset (55%) of infected mice developed paralysis by 14 days post-infection (p.i.), harbored infectious DEN in the central nervous system (CNS), and had an elevated hematocrit and a decreased white blood cell (WBC) count. Immunologic studies detected (i). increased numbers of CD69(+) splenic natural killer (NK) and B cells at day 3 p.i., (ii). DEN-specific IgM and IgG responses by days 3 and 7 p.i., respectively, and (iii). splenocyte production of IFNgamma at day 14 p.i. We conclude that the early activities of NK cells, B cells and IgM, and later actions of IFNgamma and IgG likely play a role in the defense against DEN infection. PMID:14980486

  19. Natural history of primary sclerosing cholangitis and prognostic value of cholangiography in a Dutch population

    PubMed Central

    Ponsioen, C Y; Vrouenraets, S M E; Prawirodirdjo, W; Rajaram, R; Rauws, E A J; Mulder, C J J; Reitsma, J B; Heisterkamp, S H; Tytgat, G N J

    2002-01-01

    Background: Median survival of patients with primary sclerosing cholangitis (PSC) has been estimated to be 12 years. Cholangiography is the gold standard for diagnosis but is rarely used in estimating prognosis. Aims: To assess the natural history of Dutch PSC patients and to evaluate the prognostic value of a cholangiographic classification system. Patients: A total of 174 patients with established PSC attending a university hospital and three teaching hospitals from 1970 to 1999. Methods: Charts were reviewed for validity and time of diagnosis, concurrent inflammatory bowel disease, interventions, liver transplantation, occurrence of cholangiocarcinoma, and death. Follow up data were obtained from the charts and from the attending clinician or family physician. Median follow up was 76 months (range 1–300). The earliest available cholangiography was scored using a radiological classification system for the severity of sclerosis, developed in our institution. Survival curves were computed by the Kaplan-Meier method. Cholangiographic staging was used to construct a prognostic model, applying Cox proportional hazards analysis. Results: The estimated median survival from time of diagnosis to death from liver disease or liver transplantation was 18 years. Cholangiocarcinoma was found in 18 (10%) patients. Fourteen patients (8%) underwent liver transplantation. Cholangiographic scoring was inversely correlated with survival. A combination of intrahepatic and extrahepatic scoring, together with age at endoscopic retrograde cholangiopancreatography, proved strongly predictive of survival. Conclusions: The observed survival was considerably better than reported in earlier series from Sweden, the UK, and the USA. Classification and staging of cholangiographic abnormalities has prognostic value. PMID:12235081

  20. 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

  1. 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

  2. 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

  3. Using natural disasters to study prenatal maternal stress in humans.

    PubMed

    King, Suzanne; Laplante, David P

    2015-01-01

    Animal studies of prenatal maternal stress permit random assignment of pregnant animals to stress and no-stress groups, and allow total control of the type, severity, and timing of the stressor in utero. Human studies have obvious constraints that make the use of experimental methods nearly impossible. Studying pregnant women who experience natural disasters during pregnancy, however, approximates the random assignment to groups enjoyed by animal studies, and can characterize the timing of the stressor in utero with great precision. In this chapter, we briefly describe our three ongoing prospective longitudinal studies of children exposed to prenatal maternal stress from natural disasters. We present results from Project Ice Storm in detail, showing effects of prenatal maternal stress on cognitive and neurodevelopment. We contrast these results with preliminary findings from the Iowa Flood Study and introduce the QF2011 Queensland Flood Project. In the "Discussion" section, we present conclusions to date and discuss the relative effects of the severity of maternal objective disaster exposure and maternal subjective distress levels, the moderating effects of fetal sex and the timing of the stressor in utero, and the longevity of the effects. Finally, we discuss some possible mechanisms that may mediate the effects of prenatal maternal stress on the neurodevelopment of children. PMID:25287546

  4. Insect natural products and processes: new treatments for human disease.

    PubMed

    Ratcliffe, Norman A; Mello, Cicero B; Garcia, Eloi S; Butt, Tariq M; Azambuja, Patricia

    2011-10-01

    In this overview, some of the more significant recent developments in bioengineering natural products from insects with use or potential use in modern medicine are described, as well as in utilisation of insects as models for studying essential mammalian processes such as immune responses to pathogens. To date, insects have been relatively neglected as sources of modern drugs although they have provided valuable natural products, including honey and silk, for at least 4-7000 years, and have featured in folklore medicine for thousands of years. Particular examples of Insect Folk Medicines will briefly be described which have subsequently led through the application of molecular and bioengineering techniques to the development of bioactive compounds with great potential as pharmaceuticals in modern medicine. Insect products reviewed have been derived from honey, venom, silk, cantharidin, whole insect extracts, maggots, and blood-sucking arthropods. Drug activities detected include powerful antimicrobials against antibiotic-resistant bacteria and HIV, as well as anti-cancer, anti-angiogenesis and anti-coagulant factors and wound healing agents. Finally, the many problems in developing these insect products as human therapeutic drugs are considered and the possible solutions emerging to these problems are described. PMID:21658450

  5. Vascular status in human primary and permanent teeth in health and disease.

    PubMed

    Rodd, Helen D; Boissonade, Fiona M

    2005-04-01

    The present study sought to compare the vascular status of human primary teeth with that of human permanent teeth, and to determine whether caries or painful pulpitis was associated with changes in vascularity. Coronal pulps were removed from 62 primary and 62 permanent mandibular molars with a known pain history. Teeth were categorized as intact, moderately carious or grossly carious. Pulp sections were labelled with Ulex europaeus I lectin (UEIL), which is a marker of human vascular endothelium. Image analysis was then used to quantify the percentage area of UEIL-labelled tissue (vascularity) and the number of blood vessels present within three regions: the pulp horn, the subodontoblastic region, and the mid-coronal pulp. Only the mid-coronal region of the primary tooth pulp was found to be significantly more vascular than the corresponding area of the permanent tooth pulp. Both dentitions showed a significant increase in vascularity within the pulp horn region with caries progression, but this was not accompanied by an increase in vessel number. There was no correlation between vascularity and pain symptoms. These findings suggest that the primary tooth pulp is more vascular than its successor within the mid-coronal region. However, the functional and clinical significance of this finding remains speculative. PMID:15819818

  6. [Biologic and molecular genetic properties of a transplantable human primary gastric cancer in nude mice].

    PubMed

    Chen, S S

    1989-05-01

    A human primary gastric cancer tissue (adenocarcinoma II-III) was transplanted into nude mice (SWISS/DF. nu/nu). It has been transferred for 8 generations at 56 sites in 28 nude mice with transplantable rate of 100%. The transplanted tumor is designated as transplantable human primary gastric cancer-1 in nude mice (THPGC-1). The growth of THPGC-1 is rather rapid and the size of transplanted tumor reaches 1 cm2, 4-5 weeks after transfer. The morphology and histochemistry of the original tumor were retained well in the initial and serial transplanted tumors. THPGC-1 could secret carcinoembryonic antigen (CEA). After intravenous or intraperitoneal injection of 131I-antiCEA monoclonal antibody into the THPGC-1 bearing nude mice, the radiolabeled antibody was concentrated and localized in the tumor as shown by gamma-camera analysis. Similar pattern of lactate dehydrogenase isoenzyme was observed both in primary gastric cancer tissue and THPGC-1 tissue. Chromosomal examination revealed that THPGC-1 was human aneuploid ones. Southern blot analysis showed that the pattern of repetitive DNA bands and the structures of 28s, rDNA, c-H-ras and c-myc genes in THPGC-1 were identical to the original primary gastric cancer DNA. The results suggest that THPGC-1 be a reliable model for the research of the molecular biology of cancer cells and experimental gastric cancer diagnosis and treatment. PMID:2693024

  7. 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

  8. 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

  9. 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

  10. 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