Sample records for cell type emigrating

  1. Endothelial domes encapsulate adherent neutrophils and minimize increases in vascular permeability in paracellular and transcellular emigration.

    Directory of Open Access Journals (Sweden)

    Mia Phillipson

    Full Text Available Local edema, a cardinal sign of inflammation associates closely with neutrophil emigration. Neutrophil emigration has been described to occur primarily through endothelial junctions (paracellular and more rarely directly through endothelial cells (transcellular. Recently, we reported that unlike in wild-type (wt mice, Mac-1-/- (CD11b neutrophils predominantly emigrated transcellularly and was significantly delayed taking 20-30 min longer than the paracellular emigration (wt. In the present study we noted significant anatomical disruption of the endothelium and hypothesized that transcellular emigration would greatly increase vascular permeability. Surprisingly, despite profound disruption of the endothelial barrier as the neutrophils moved through the cells, the changes in vascular permeability during transcellular emigration (Mac-1-/- were not increased more than in wt mice. Instead increased vascular permeability completely tracked the number of emigrated cells and as such, permeability changes were delayed in Mac-1-/- mice. However, by 60 min neutrophils from both sets of mice were emigrating in large numbers. Electron-microscopy and spinning disk multichannel fluorescence confocal microscopy revealed endothelial docking structures that progressed to dome-like structures completely covering wt and Mac-1-/- neutrophils. These domes completely enveloped the emigrating neutrophils in both wt and Mac-1-/- mice making the mode of emigration underneath these structures extraneous to barrier function. In conclusion, predominantly paracellular versus predominantly transcellular emigration does not affect vascular barrier integrity as endothelial dome-like structures retain barrier function.

  2. Endothelial domes encapsulate adherent neutrophils and minimize increases in vascular permeability in paracellular and transcellular emigration. (United States)

    Phillipson, Mia; Kaur, Jaswinder; Colarusso, Pina; Ballantyne, Christie M; Kubes, Paul


    Local edema, a cardinal sign of inflammation associates closely with neutrophil emigration. Neutrophil emigration has been described to occur primarily through endothelial junctions (paracellular) and more rarely directly through endothelial cells (transcellular). Recently, we reported that unlike in wild-type (wt) mice, Mac-1-/- (CD11b) neutrophils predominantly emigrated transcellularly and was significantly delayed taking 20-30 min longer than the paracellular emigration (wt). In the present study we noted significant anatomical disruption of the endothelium and hypothesized that transcellular emigration would greatly increase vascular permeability. Surprisingly, despite profound disruption of the endothelial barrier as the neutrophils moved through the cells, the changes in vascular permeability during transcellular emigration (Mac-1-/-) were not increased more than in wt mice. Instead increased vascular permeability completely tracked the number of emigrated cells and as such, permeability changes were delayed in Mac-1-/- mice. However, by 60 min neutrophils from both sets of mice were emigrating in large numbers. Electron-microscopy and spinning disk multichannel fluorescence confocal microscopy revealed endothelial docking structures that progressed to dome-like structures completely covering wt and Mac-1-/- neutrophils. These domes completely enveloped the emigrating neutrophils in both wt and Mac-1-/- mice making the mode of emigration underneath these structures extraneous to barrier function. In conclusion, predominantly paracellular versus predominantly transcellular emigration does not affect vascular barrier integrity as endothelial dome-like structures retain barrier function.

  3. CCR7 Controls Thymus Recirculation, but Not Production and Emigration, of Foxp3(+) T Cells. (United States)

    Cowan, Jennifer E; McCarthy, Nicholas I; Anderson, Graham


    Current models of Foxp3(+) regulatory T cell (Treg) development involve CCR7-mediated migration of thymocytes into the thymus medulla to enable essential interactions with medullary epithelium. However, increased Foxp3(+) thymic Treg numbers in Ccr7(-/-) mice challenge this view, and the role of CCR7 in Treg development, emigration, and/or recirculation is unknown. Here, we have examined CCR7 and Rag2pGFP levels during Treg development and generated Rag2pGFPCcr7(-/-) mice to study its impact on the intrathymic Treg pool. We reveal surprising developmental heterogeneity in thymocytes described as Treg precursors, showing that they contain recirculating CCR6(+)CCR7(-)Rag2pGFP(-) T cells. Although CCR7 defines bona fide Rag2GFP(+) Treg precursors, it is not required for Treg production and emigration. Rather, we show that lack of CCR7 renders the thymus more receptive to Treg thymus homing. Our study reveals a role for CCR7 in limiting Treg recirculation back to the thymus and enables separation of the mechanisms controlling Treg production and thymic recirculation.

  4. Emigrants and Emigration States in Historical Perspective


    Waldinger, Roger


    International migration from poorer to richer states gives emigrants resources that they can use to exercise leverage over home states, but also leaves them vulnerable to exploitation and discrimination in host states, conditions that activate interventions by emigration states seeking to influence and protect nationals abroad.  This paper traces the changing patterns of interaction between emigrants and emigration states over the past century and a half.  Many of the underlying incentives fo...

  5. Emigrants and Emigration in Historical Perspective


    Waldinger, Roger


    International migration from poorer to richer states gives emigrants resources that they can use to exercise leverage over home states, but also leaves them vulnerable to exploitation and discrimination in host states, conditions that activate interventions by emigration states seeking to influence and protect nationals abroad.  This paper traces the changing patterns of interaction between emigrants and emigration states over the past century and a half.  Many of the underlying incentives fo...

  6. Detection of a novel population of fetal thymocytes characterized by preferential emigration and a TCRgammadelta+ T cell fate after dioxin exposure. (United States)

    Majora, Marc; Frericks, Markus; Temchura, Vladimir; Reichmann, Gaby; Esser, Charlotte


    T cell maturation into TCRalphabeta(+) or TCRgammadelta(+) cells from common immature CD4(-)CD8(-)(DN) precursors occurs in the thymus, and is controlled through ordered regulation of genes. The aryl hydrocarbon receptor (AHR), a latent cytoplasmic transcription factor, affects thymocyte maturation and differentiation at several stages, also including DN cells. We analyzed in murine fetal thymus organ cultures (FTOC) the outcome of AHR-signaling and found a higher frequency of DN TCRgammadelta(+) cells in the presence of the AHR-activating ligand TCDD. We detected a novel population of CD25(int/lo)CD44(hi) cells associated with preferential emigration and a TCRgammadelta(+) T cell fate of thymocytes. Sorted DN TCRgammadelta(+) emigrants could proliferate if IL-2 was available. Moreover, they suppressed the proliferation of co-cultivated, activated CD4(+) T cells. Gene expression profiles of purified DN emigrants from TCDD*FTOC revealed 295 modulated genes, 10% of which are genes of the immune system. For instance, RAG-1, TdT, and Gfi-1 were downregulated, yet genes indicative of mature thymocytes were upregulated. In conclusion, we have detected changes in the differentiation programme of fetal DN thymocytes after ligand-activation of the AHR. In particular, we observed a higher frequency of DN TCRgammadelta(+) cells with high emigration potential, and possible regulatory functions.

  7. Emigration of mature T cells from the thymus is inhibited by the imidazole-based compound 2-acetyl-4-tetrahydroxybutylimidazole. (United States)

    Gugasyan, R; Coward, A; O'Connor, L; Shortman, K; Scollay, R


    The primary role of the thymus is to provide mature T cells for the peripheral immune system. The mechanisms involved in the cellular export processes are as yet unknown. In this study, we examined the ability of 2-acetyl-4-tetrahydroxybutylimidazole (THI), an agent widely used as a component of ammonia caramel food colouring, to inhibit T-cell export from the thymus. BALB/c mice were maintained on drinking water containing THI for 5 days. The mice showed a twofold increase in the total number of mature medullary thymocytes (CD4+CD8- and CD4-CD8+) as well as a slight decrease in the total number of immature double-positive cells (CD4+CD8+). The mature single-positive thymocytes were found to express high levels of the homing molecule L-selectin, suggesting that these potential emigrants were prevented from leaving the thymus. To confirm this, THI-treated mice were injected intrathymically with fluorescein isothiocyanate and the number of labelled T cells appearing in the lymph nodes and spleen was determined 16 hr later. A 10-fold decrease in the number of CD4+ and CD8+ recent thymic emigrants in the lymph nodes and spleen of THI-treated mice was observed. Previous studies have shown that THI does not affect other aspects of thymocyte development, such as proliferation and differentiation. Taken together, these results suggest that the immunosuppressive effects of THI may be due, in part, to preventing of the final step of T-cell export out of the thymus.

  8. Emigration for Development?

    DEFF Research Database (Denmark)

    Careja, Romana


    is necessary if resources from emigration are to become seeds for development. By analysing the case of Romania, one of the largest labour sending countries in Eastern Europe, it argues that its laissez-faire approach is likely not enough to capitalize on emigrants' resources for development. International...

  9. Emigration from the Sahel. (United States)

    Findley, S; Traore, S; Ouedraogo, D; Diarra, S


    This report on international migration from the Sahel (the band of countries which lies just south of the Sahara and extends to the Atlantic) opens with a historical overview of the region which includes a description of the response of its people to periodic droughts (including gradual migration to the south), a look at commercial expansion which led to the growth of urban centers, and the destabilizing effects of Atlantic trade and subsequent colonization. The report continues by examining 1) the ethnic and political factors which influenced migration, 2) emigration trends from the region, 3) economic factors, and 4) the effect of the agricultural system on male migration. It is noted that the agricultural sector is unlikely to meet the region's needs for food or cash and that the mining sector can generate cash but not food or sufficient jobs. Industrial growth has been limited, and only the public sector has shown consistent growth. After examining the macro-economic context formed by foreign aid and foreign debt, the current international migration situation is described. The recent phenomenon of female migrants is analyzed as a response to economic crisis. A case study is then presented of emigration from Mali with an emphasis on emigration from the Senegal River Valley which has been plagued by drought. Finally, it is projected that migration trends will continue as long as the propelling economic, environmental, and political crises continue. A need exists for programs to help migrants channel their funds for their return. In addition, collaborative development projects should incorporate the emigration process by 1) strengthening the financial contribution of emigrants, 2) incorporating return migrants, and 3) strengthening the underlying economic insecurity which exacerbates migration.

  10. T-cell Receptor Excision Circles (TREC) in CD4+ and CD8+ T-cell Subpopulations in Atopic Dermatitis and Psoriasis Show Major Differences in the Emission of Recent Thymic Emigrants

    DEFF Research Database (Denmark)

    Just, Helle; Deleuran, Mette; Vestergaard, Christian;


    We used T-cell receptor excision circles (TREC) to evaluate thymic function in adult patients with atopic dermatitis and psoriasis. We observed that men, but not women, with atopic dermatitis had a significantly faster decline in TREC content with increasing age compared with healthy men. In cont......-cells, this indicates that atopic dermatitis patients can have compensatory emissions of thymic emigrants, whereas psoriatic patients do not, thus supporting different thymic function in these two diseases....

  11. iNKT Cell Emigration out of the Lung Vasculature Requires Neutrophils and Monocyte-Derived Dendritic Cells in Inflammation (United States)

    Thanabalasuriar, A; Neupane, A.S; Wang, J; Krummel, M.F; Kubes, P


    iNKT cells are a subset of innate T cells that recognize glycolipids presented on CD1d molecules and protect against a variety of bacterial infections including S. pneumoniae. Using lung intravital imaging, we examined the behavior and mechanism of pulmonary iNKT cell activation in response to the potent iNKT cell ligand α-galactosylceramide or during S. pneumoniae infection. In untreated mice the major fraction of iNKT cells resided in the vasculature, but a small critical population resided in the extravascular space in proximity to monocyte-derived DCs. Administration of either α-GalCer or S. pneumoniae, induced CD1d dependent rapid recruitment of neutrophils out of the vasculature. This neutrophil exodus paved the way for extravasation of iNKT cells from the lung vasculature via CCL17. Depletion of monocyte-derived DCs abrogated both the neutrophil and subsequent iNKT cell extravasation. Moreover, impairing iNKT cell migration out of the lung vasculature by blocking CCL17 greatly increased susceptibility to S. pneumoniae infection, suggesting a critical role for the secondary wave of iNKT cells in host defense. PMID:27653688

  12. Progressive activation of CD127+132- recent thymic emigrants into terminally differentiated CD127-132+ T-cells in HIV-1 infection.

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    Sarah C Sasson

    Full Text Available AIM: HIV infection is associated with distortion of T-cell homeostasis and the IL-7/IL7R axis. Progressive infection results in loss of CD127+132- and gains in CD127-132+ CD4+ and CD8+ T-cells. We investigated the correlates of loss of CD127 from the T-cell surface to understand mechanisms underlying this homeostatic dysregulation. METHODS: Peripheral and cord blood mononuclear cells (PBMCs; CBMC from healthy volunteers and PBMC from patients with HIV infection were studied. CD127+132-, CD127+132+ and CD127-132+ T-cells were phenotyped by activation, differentiation, proliferation and survival markers. Cellular HIV-DNA content and signal-joint T-cell receptor excision circles (sjTRECs were measured. RESULTS: CD127+132- T-cells were enriched for naïve cells while CD127-132+ T-cells were enriched for activated/terminally differentiated T-cells in CD4+ and CD8+ subsets in health and HIV infection. HIV was associated with increased proportions of activated/terminally differentiated CD127-132+ T-cells. In contrast to CD127+132- T-cells, CD127-132+ T-cells were Ki-67+Bcl-2(low and contained increased levels of HIV-DNA. Naïve CD127+132- T-cells contained a higher proportion of sjTRECs. CONCLUSION: The loss of CD127 from the T-cell surface in HIV infection is driven by activation of CD127+132- recent thymic emigrants into CD127-132+ activated/terminally differentiated cells. This process likely results in an irreversible loss of CD127 and permanent distortion of T-cell homeostasis.

  13. Types of Stem Cells (United States)

    ... Stem Cell Glossary Search Toggle Nav Types of Stem Cells Stem cells are the foundation from which all ... Learn About Stem Cells > Types of Stem Cells Stem cells Stem cells are the foundation for every organ ...

  14. Emigration dynamics: the Indian context. (United States)

    Premi, M K; Mathur, M D


    This report on emigration dynamics in India opens by providing background on short- and long-distance migration to and from India in response to such events as the formation of Pakistan as well as to the policies of the British Empire and Commonwealth. Section 2 discusses India's demographic and sociocultural setting in terms of population growth, urbanization, patterns of internal migration, growth of the labor force, economic growth, poverty alleviation, health, and education. The third section describes the lack of data on international migration. Some data are available on emigrants, but the only information on return migration is that gleaned from surveys in Kerala. Section 4 considers emigration to industrialized countries and notes that it is almost exclusively permanent and largely composed of individuals with professional, technical, or managerial skills. The resulting brain drain is described as is the incidence of illegal migration. India does not create conditions from which citizens must seek asylum, rather the country has absorbed flows of refugees from Pakistan, Tibet, Bangladesh, Afghanistan, and Sri Lanka. Available data on the characteristics of emigrants and return migrants are reviewed in the next two sections, and section 7 looks at the data on financial flows gathered from macro-level estimates of remittances. Section 8 is devoted to the community, family, and individual factors which influence emigration including the networks that facilitate migration and means of meeting migration costs. The ninth section summarizes the political setting with an emphasis on the adverse reaction of Nepal to population movement from India. The final section of the report projects future population movements. It is noted that if there were no restrictions on migration, millions of Indians would emigrate to the Americas, Africa, and Australia. Whereas poverty, unemployment, and population growth will likely erode living conditions in India, the government has

  15. Estimating temporary emigration and breeding proportions using capture-recapture data with Pollock's robust design (United States)

    Kendall, W.L.; Nichols, J.D.; Hines, J.E.


    Statistical inference for capture-recapture studies of open animal populations typically relies on the assumption that all emigration from the studied population is permanent. However, there are many instances in which this assumption is unlikely to be met. We define two general models for the process of temporary emigration, completely random and Markovian. We then consider effects of these two types of temporary emigration on Jolly-Seber (Seber 1982) estimators and on estimators arising from the full-likelihood approach of Kendall et al. (1995) to robust design data. Capture-recapture data arising from Pollock's (1982) robust design provide the basis for obtaining unbiased estimates of demographic parameters in the presence of temporary emigration and for estimating the probability of temporary emigration. We present a likelihood-based approach to dealing with temporary emigration that permits estimation under different models of temporary emigration and yields tests for completely random and Markovian emigration. In addition, we use the relationship between capture probability estimates based on closed and open models under completely random temporary emigration to derive three ad hoc estimators for the probability of temporary emigration, two of which should be especially useful in situations where capture probabilities are heterogeneous among individual animals. Ad hoc and full-likelihood estimators are illustrated for small mammal capture-recapture data sets. We believe that these models and estimators will be useful for testing hypotheses about the process of temporary emigration, for estimating demographic parameters in the presence of temporary emigration, and for estimating probabilities of temporary emigration. These latter estimates are frequently of ecological interest as indicators of animal movement and, in some sampling situations, as direct estimates of breeding probabilities and proportions.

  16. Bulgarian Turkish emigration and return. (United States)

    Vasileva, D


    The main factors which determined the 1989 migration of Turks in Bulgaria back to Turkey are discussed. Background history is provided. After World War I, Turks in bulgaria comprised 10% of the total population. Bulgarian policy had been, up to the 1980s to send Rumelian Turks back, but the policy after 1980 was one of a national revival process to integrate Turks into the developed socialist society. Muslim traditions, customs, and Turkish language were interfered with. International disfavor resulted. In May 1989, the Communist Party declared, in an effort to show democratic ideals, open borders. Thus began the new emigration wave. 369,839 people fled to the Turkish border. 43% of the 9.47 ethnic Turks in bulgaria went to Turkey within 4 months. The numbers decreased in November, and soon after the communist regime ended. New laws were adopted allowing Turks to assume their original Turkish names. The huge migration was clearly political, and as such, the emigrant Turks should be determined as refugees and asylum seekers. The provocation of ethnic Turks was used by the communist regime to solve potential social conflicts. Not only did Turks flee to escape from violence or for religious, cultural, and moral reasons but also due to free market initiatives begun in Turkey in the early 1980s which improved Turkish quality of life. Food and consumer goods were cheaper and economic advantages were perceived. Emigrants were primarily peasants with lower levels of education, professional qualifications, and labor skills. 154,937 (42%) returned to bulgaria and 58% stayed in Turkey to comprise 25% of the former Turkish population. During this period, tensions between countries was high.l Bulgarians actively encouraged emigration and Turkey welcomed it. The emigrants to Turkey were seen as foreigners (muhacir or gocmen) but were received with good will and were readily accepted into menial positions. Emigrants were confronted with political, linguistic, and cultural

  17. Differentiation of ICOS+ and ICOS- recent thymic emigrant regulatory T cells (RTE T regs) during normal pregnancy, pre-eclampsia and HELLP syndrome. (United States)

    Wagner, M I; Jöst, M; Spratte, J; Schaier, M; Mahnke, K; Meuer, S; Zeier, M; Steinborn, A


    Two different subsets of naturally occurring regulatory T cells (nTregs), defined by their expression of the inducible co-stimulatory (ICOS) molecule, are produced by the human thymus. To examine the differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) recent thymic emigrant (RTE) T regs during normal pregnancy and in the presence of pre-eclampsia or haemolysis elevated liver enzymes low platelet (HELLP)-syndrome, we used six-colour flow cytometric analysis to determine the changes in the composition of the ICOS(+) and ICOS(-) T reg pools with CD45RA(+) CD31(+) RTE T regs, CD45RA(+) CD31(-) mature naive (MN) T regs, CD45RA(-) CD31(+) and CD45RA(-) CD31(-) memory Tregs. With the beginning of pregnancy until term, we observed a strong differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE, but not CD45RA(+) CD31(-) MN T regs, into CD45RA(-) CD31(-) memory T regs. At the end of pregnancy, the onset of spontaneous term labour was associated with a significant breakdown of ICOS(+) CD45RA(-) CD31(-) memory T regs. However, in the presence of pre-eclampsia, there was a significantly increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs into CD45RA(-) CD31(+) memory T regs, wherein the lacking differentiation into CD45RA(-) CD31(-) memory T regs was partially replaced by the increased differentiation of ICOS(+) and ICOS(-) CD45RA(+) CD31(-) MN Tregs into CD45RA(-) CD31(-) memory T regs. In patients with HELLP syndrome, this alternatively increased differentiation of CD45RA(-) CD31(-) MN T regs seemed to be exaggerated, and presumably restored the suppressive activity of magnetically isolated ICOS(+) and ICOS(-) T regs, which were shown to be significantly less suppressive in pre-eclampsia patients, but not in HELLP syndrome patients. Hence, our findings propose that the regular differentiation of both ICOS(+) and ICOS(-) CD45RA(+) CD31(+) RTE T regs ensures a healthy pregnancy course, while their disturbed differentiation is

  18. Reducing bias in survival under non-random temporary emigration (United States)

    Peñaloza, Claudia L.; Kendall, William L.; Langtimm, Catherine Ann


    Despite intensive monitoring, temporary emigration from the sampling area can induce bias severe enough for managers to discard life-history parameter estimates toward the terminus of the times series (terminal bias). Under random temporary emigration unbiased parameters can be estimated with CJS models. However, unmodeled Markovian temporary emigration causes bias in parameter estimates and an unobservable state is required to model this type of emigration. The robust design is most flexible when modeling temporary emigration, and partial solutions to mitigate bias have been identified, nonetheless there are conditions were terminal bias prevails. Long-lived species with high adult survival and highly variable non-random temporary emigration present terminal bias in survival estimates, despite being modeled with the robust design and suggested constraints. Because this bias is due to uncertainty about the fate of individuals that are undetected toward the end of the time series, solutions should involve using additional information on survival status or location of these individuals at that time. Using simulation, we evaluated the performance of models that jointly analyze robust design data and an additional source of ancillary data (predictive covariate on temporary emigration, telemetry, dead recovery, or auxiliary resightings) in reducing terminal bias in survival estimates. The auxiliary resighting and predictive covariate models reduced terminal bias the most. Additional telemetry data was effective at reducing terminal bias only when individuals were tracked for a minimum of two years. High adult survival of long-lived species made the joint model with recovery data ineffective at reducing terminal bias because of small-sample bias. The naïve constraint model (last and penultimate temporary emigration parameters made equal), was the least efficient, though still able to reduce terminal bias when compared to an unconstrained model. Joint analysis of several

  19. Determinants of Soviet emigration policies. (United States)

    Friedgut, T H


    "The object of this paper is the presentation and analysis of the political values that are expressed in Soviet emigration policy. Underlying this is an attempt to discern points of change in these values, in particular through the post-World War II history of the USSR. Our concluding point will be the new law on entry and exit from the USSR, pending before the Supreme Soviet [in 1991] with its passage promised in the nearest future." The study covers the period from the 1920s to the present.

  20. The Export Promoting Effect of Emigration

    DEFF Research Database (Denmark)

    Hiller, Sanne

    . This paper provides a first attempt to identify the export-promoting effect of emigration on the firm level. Using detailed Danish firm-level data, we can parsimoniously control for export determinants other than emigration, unobserved heterogeneity at the firm level, as well as for self-selection of firms...

  1. Attitudes of Israeli Students Toward Emigration (United States)

    Shapira, Rina; Etzioni, Eva


    Students in Israel, whether of Jewish or Oriental origin, tend to form their attitudes on the subject of emigration according to the amount of emphasis they place on career advancement and patriotism. Because of the vital need of Israel for all of its best brains, emigrants are often viewed as quasi-traitors. (CK)

  2. Emigration from Russia: New Trends and Forms

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    Vladimir Alekseyevich Iontsev


    Full Text Available The subject-matter of this article is migration from Russia. The study deals with current aspects and new forms of emigration. The goal of this paper is to identify new patterns determining the emigration from Russia. The article views the emigration in a broad sense, including, in addition to classic emigration (i.e. leaving the home country for permanent residence in another country, various categories of return migration (labor migration, shuttle traders, seasonal migration, episodic migration, economic tourism, business migration, education abroad, etc.. With the emergence of these new forms and categories, there is a need to clarify the migration concepts. This analysis is built on a broad historical perspective on emigration, which has been a typical phenomenon for Russia over the last three centuries. The article is based on such economic theories, as the human capital theory, new economic theory of migration, Todaro’s economic theory of migration and other. In this article, a variety of methods are used, including historical analogy, statistical and mathematical approaches, sociological and econometric models. The article analyzes the patterns of modern emigration from Russia. It also considers certain aspects in the legal regulation of migration processes, with a focus on emigrants, including potential emigrants. In conclusion, the article notes the need for the state control of emigration processes. This means not so much the improvement of statistical records for this group of migrants, but rather specific government measures aimed at providing the state support to these categories of migrants in order to prevent the nonreturn migration. In other words, it is not aimed at banning the emigration (a measure, the adverse effects of which were noted as long ago as by Mikhail Lomonosov, but at providing the state support to these categories of migrants in order to prevent the non-return migration. The findings of this research can be

  3. Enteroendocrine cell types revisited

    DEFF Research Database (Denmark)

    Engelstoft, Maja S; Egerod, Kristoffer Lihme; Lund, Mari L


    The GI-tract is profoundly involved in the control of metabolism through peptide hormones secreted from enteroendocrine cells scattered throughout the gut mucosa. A large number of recently generated transgenic reporter mice have allowed for direct characterization of biochemical and cell...... biological properties of these previously highly elusive enteroendocrine cells. In particular the surprisingly broad co-expression of six functionally related hormones in the intestinal enteroendocrine cells indicates that it should be possible to control not only the hormone secretion but also the type...... and number of enteroendocrine cells. However, this will require a more deep understanding of the factors controlling differentiation, gene expression and specification of the enteroendocrine cells during their weekly renewal from progenitor cells in the crypts of the mucosa....

  4. Emigration trajectories of former Portuguese emigrants: the construction of family integrity

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    Filipa Daniela Marques


    Full Text Available Constructing family integrity is a normative developmental challenge for older people, which is influenced by the family and social systems. This exploratory study examines the emigration trajectories of former Portuguese emigrants, now in old age, who returned to their home country (Portugal. And aims to contribute to a better understand of the influence of emigration experiences in the construction of family integrity versus disconnection and alienation.

  5. Emigration dynamics in southern Africa. (United States)

    Milazi, D


    This review of the dynamics of international migration in Southern Africa focuses on four aspects of labor migration: 1) while migrant workers suffer from discrimination and lack of protection, there are few alternatives for them; 2) the regulations imposed by the Chamber of Mines in South Africa favor the mining industry at the expense of the workers; 3) worker supplier states have few options for negotiating a commercialized migration policy to achieve economic benefits; and 4) foreign mine workers must unionize in order to escape perpetual subordination. The review opens with a consideration of how migrant mine workers from Botswana, Lesotho, and Swaziland have provided a source of cheap labor which has enhanced the economic prosperity of South Africa. The role of the Chamber of Mines in regulating the supply of labor and employment policy for its members is described. Attention is then turned to Lesotho where land pressure has exacerbated poverty levels. Large-scale migration has led the citizens of Lesotho to consider it a place to live or retire to, not a place to work. Labor migration from Lesotho is organized, is supported by the government, is recurrent, and remains a viable alternative despite faltering demand. The discussion of Lesotho includes a consideration of its political, economic, and demographic situation as well as of ecological factors. Briefer analyses are then provided for Botswana, Swaziland, and Mozambique. The receiving country, South Africa, is shown to be suffering a decline in economic growth which is marked by widespread unemployment. More than 250,000 Whites are prospective emigrants from South Africa. After considering the issues surrounding refugees, regional concerns created by changing economic and political scenarios, and labor strategies which could be adopted by supplier states, the report reiterates a series of recommendations which arose from two major conferences on the problem of unemployment. It is concluded that the

  6. Emerging Issues in Migration, Emigration, and Immigration. (United States)

    Journal of Intergroup Relations, 1984


    Reports on findings presented at three workshops on immigration and emigration at a 1982 conference on human rights. Addresses topics ranging from rights of refugees and migrants to philosophies of cultural pluralism. (KH)

  7. THE COSSACK EMIGRE IN 1945 – 1960

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    Full Text Available This article deals with the problem of formation and development of the Cossack émigré after World War II. The Cossack émigré is being examined as integral part of the Russian emigre. Most reasons which resulted that some part of the Cossacks to stay abroad were of an objective nature. However it is rarely possible to pick out the only reason of reluctance of return. The structure of the Cossack emigre had changed. It was increased with former Soviet citizens and at the same time some part of former white émigré was delivered to the USSR. Cossacks who were situated both in camps for displaced persons and generally in Europe and China tried to leave for countries placed outside the Eurasian continent. In this respect the most attractive were the USA, Canada, Australia and states of the South America. In some degree decision of migration was caused by the immigration policy of some states. After World War II the most part of Russian and Cossack associations, organizations and communities had mainly socio-cultural nature. There were socio-political and psychological contradictions between the members of the first and the second emigration waves. Sometimes they encouraged mistrust, opposition and in many cases open enmity and struggle inside the emigre. At once the Cossack emigre was affected be factors which by contrast contributed to rapprochement of the members of two emigration waves. Being an integral part of the Russian emigre the Cossacks after World War II went down the same road as the other Russian emigrants but having some special aspects caused by different factors of both objective and subjective origins.

  8. Estimation of temporary emigration in male toads (United States)

    Muths, E.; Scherer, R. D.; Corn, P.S.; Lambert, B.A.


    Male boreal toads (Bufo boreas) are thought to return to the breeding site every year but, if absent in a particular year, will be more likely to return the following year. Using Pollock's robust design we estimated temporary emigration (the probability a male toad is absent from a breeding site in a given year) at three locations in Colorado, USA: two in Rocky Mountain National Park and one in Chaffee County. We present data that suggest that not all male toads return to the breeding site every year. Our analyses indicate that temporary emigration varies by site and time (for example, from 1992 to 1998, the probability of temporary emigration ranged from 10% to 29% and from 3% to 95% at Lost Lake and Kettle Tarn, respectively). Although the results provide weak evidence that males are more likely to return after a year's hiatus, a general pattern of state-dependent temporary emigration was not supported. We also hypothesized relationships between temporary emigration and a number of weather variables. While some competitive models included weather covariates, imprecise and variable estimates of the effects of these covariates precluded fully defining their impact on temporary emigration. ?? 2006 by the Ecological Society of America.

  9. Emigration dynamics from and within South Asia. (United States)

    Shah, N M


    This review of current knowledge about emigration dynamics from and within South Asia (Bangladesh, India, Pakistan, and Sri Lanka) opens with a brief history of the three phases of emigration from the area since the 1830s (plantation labor; postindependence to the UK, US, Canada, and Australia; and labor migration to the oil-exporting countries). The influence of the creation of Pakistan and Bangladesh is also covered as are British colonial and commonwealth policies. It is noted that migration data are incomplete and that India exhibits an ambivalence about collecting such information. The discussion then turns to emigration since 1970 and considers permanent migration from South Asia to the traditional receivers; South Asian asylum seekers in Europe; South Asian refugees, illegal migrants, migrant workers (flows and destinations), the stock of contract migrant workers (and their characteristics); returnee migrant workers; and skill levels. Analysis is provided of macro level determinants of emigrations such as gross national product (level and growth), the general demographic and social situation, labor force growth and structure, poverty and inequality, and internal and international migration. Environmental factors causing displacement in Southern Asia include floods, cyclones, river bank erosion, drought, and desertification. Global warming could displace millions of people in the region, and development projects have contributed to displacement. The remainder of the report covers political and ethnic factors, micro-factors influencing migration decision-making, the policies of sending and receiving countries, the consequences of emigration, and the potential for migration in the future.

  10. Insect food aiming at Mars emigration (United States)

    Katayama, Naomi; Yamashita, Masamichi; Hashimoto, Hirofumi; Nagasaka, Sanako; Kuwayama, Akemi; Sofue, Megumi


    We study insect food aiming at Mars emigration.In space agriculture, insect is the important creature which we cannot miss.It is necessary for the pollination of the plant, and it is rich to protein and lipid as food.I reported that silkworm is an insect necessary for astroponics in particular last time.We make clothes using silk thread, and the pupa becomes the food.In addition, the clothes can make food as protein when we need not to use it. The bee is a very important insect in the space agriculture,too.We examined nutrition of silkworm, bee, grasshopper, snail and the white ant which are necessary for Mars emigration.We will introduce of good balance space foods.We will report many meal menu for Mars emigration.

  11. Pakistani labour emigration: new destinations in Europe

    Directory of Open Access Journals (Sweden)

    Nasra M. Shah


    Full Text Available In the first part of this paper a historical overview is made of Pakistani labour emigration to the countries of the Persian Gulf, and to Anglo-Saxon countries in general and to the United Kingdom in particular. In the second part of the paper the new European labourmarkets which Pakistani emigrants have been increasingly discovering is analyzed. In this sense, Spain has become one of the new destinations. The author goes on to point out the specific nature of this new situation and at the same time details some of the future implications for Spain.

  12. Emigration, wage differentials and brain drain: The case of Suriname

    NARCIS (Netherlands)

    T.W. Dulam (Tina); Ph.H.B.F. Franses (Philip Hans)


    textabstractIn this paper we examine two hypotheses concerning emigration. The first hypothesis is that emigration is positively correlated with wage differentials. The second hypothesis concerns a positive correlation between emigration and higher education in the sending country (the so-called bra

  13. Motivations and Earnings of Emigrants from a Rich Welfare State

    DEFF Research Database (Denmark)

    Poutvaara, Panu; Munk, Martin D.


    little is known about individual motivations to emigrate. To bridge this gap, we organized the first-ever survey of emigrants from a welfare state. We find that migration decisions are rarely driven by taxes. For men, the main reason to emigrate is own work, for women partner and family....

  14. The Impacts of Emigration on the Mexican Economy. (United States)

    Newman, Allen R.


    The assumption that Mexican emigration to the United States provides benefits to Mexico in the form of jobs for unemployed Mexicans and wage remittances has kept Mexican officials from discouraging illegal emigration. In fact, emigration drains the Mexican economy and should be a cause for Mexican government concern. (Author/MJL)


    Directory of Open Access Journals (Sweden)

    Dorel AILENEI


    Full Text Available Migration is one of the oldest phenomena that accompanied the development of human society, sometimes causing clashes between peoples, cultures and civilizations. Recent events or from a not too distant past of Europe show that tensions created by migratory movements often have an impact on political and economic relations between countries, cultures and religions. The Romanian reality shows that after 1989 the resident population experienced a decline. According to the National Institute of Statistics, in the period 1989-2012, Romania's population decreased by about 3.1 million, this reduction being due to both migration phenomenon and negative natural increase of population. Some statistic records also show that the extremes are usually among those who decide to emigrate. On the one hand those who are choosing this path are individuals with low income and a low or medium level of education; on the other hand, we can find the phenomenon of brain drain. It is alarming that among those who choose to emigrate are registered young people able to work, this generating the problem of funding on medium and long term the social services. Starting from such aspects, this paper aims to highlight key issues regarding the intention of emigration of highly educated young people. Using quantitative and qualitative methods the authors of this paper aim to identify some possible causes that may determine the highly educated youth to emigrate, evaluate some possible effects due to this phenomenon and to find proposals to limit the negative effects of demographic decline.

  16. The Impact of Emigration on Jamaican Employment. (United States)

    Dixon, Heriberto


    Massive emigration from Jamaica of professionals, technicians, managers and administrators, and skilled workers has resulted in a critical shortage of a well-educated work force. If present political and economic trends continue, this problem is likely to remain for some time to come. (ST)

  17. Materialism as a Social Value and Impetus for Intentions to Emigrate from Croatia

    Directory of Open Access Journals (Sweden)

    Krešimir Peračković


    unemployed and unskilled has negative demographic consequences, the emigration of highly educated (and already employed experts (brain drain is harmful to an even greater extent, because the socio-economic damage is twofold: first, it lowers developmental potential and quality of life in local communities, and second, investment in the education of those who left becomes futile. Besides these objective circumstances and ”traditional” motives, current emigration may be encouraged by materialism (materialistic values as a latent motive. The aim of this paper was to empirically determine if this is the case. Data for analysis were collected in 2014 by face-to-face survey on a representative sample of adult population of Croatia (N = 1000. Results showed that materialism was relatively low prominent but it had become an evenly distributed (universal value among the population, which means that to a greater extent it varies individually rather than between relevant socio-demographic and status groups. Younger generations are the exception: they are slightly more materialistic and their intentions to emigrate are much more prominent than among older (40 years and over segments of population. Likewise, in the cohorts younger than 40 materialism is a significant and independent predictor of intentions to leave, in comparison with other more or less relevant objective (education level, employment, income, type of dwelling, relatives abroad, marital status, number of children and subjective predictors (satisfaction with one’s own personal standard and general situation in Croatia. Finally, it is concluded (with regard to the relevance of both phenomena in today's Croatian society that relationship between materialism and (intended and actual emigration should be further examined.

  18. Health emigration: a challenge in paediatric oncology. (United States)

    Massimo, Luisa M; Wiley, Thomas J; Caprino, Daniela


    For the past 10 years European states have experienced an increasing flow of emigrating families from developing countries seeking better medical care for their sick children. For Italian paediatricians this has become a new challenge, considering the cultural differences in customs regarding the illness. The onset of a life-threatening disease has a strong impact on the family. The natural bond between the patient and the family must be preserved and strengthened; parents should be encouraged to entertain their child during hospitalization. The inclusion of art therapy may facilitate communication, especially for children of a different language and culture. This approach can help medical staff to understand better both the child's and the parents' anxieties and feelings. This article discusses facets of the now well-known phenomenon of ;health emigration', that is, when a family searches abroad in the hope of finding the most advanced medical treatment possible for their sick child.

  19. Periodical Archaeology: Digital Production, Critical Discourse and Textual Communities in Emigre

    NARCIS (Netherlands)

    McVarish, Emily


    abstractPublished in 1989, Emigre magazine’s eleventh issue, Ambition/Fear: Graphic Designers and the Macintosh Computer, contains vivid artifacts of a discipline’s first encounter with digital tools. From the aesthetics of bitmaps to the expressive interventions made possible by new access to types

  20. Non-random temporary emigration and the robust design: Conditions for bias at the end of a time series: Section VIII (United States)

    Langtimm, Catherine A.


    Deviations from model assumptions in the application of capture–recapture models to real life situations can introduce unknown bias. Understanding the type and magnitude of bias under these conditions is important to interpreting model results. In a robust design analysis of long-term photo-documented sighting histories of the endangered Florida manatee, I found high survival rates, high rates of non-random temporary emigration, significant time-dependence, and a diversity of factors affecting temporary emigration that made it difficult to model emigration in any meaningful fashion. Examination of the time-dependent survival estimates indicated a suspicious drop in survival rates near the end of the time series that persisted when the original capture histories were truncated and reanalyzed under a shorter time frame. Given the wide swings in manatee emigration estimates from year to year, a likely source of bias in survival was the convention to resolve confounding of the last survival probability in a time-dependent model with the last emigration probabilities by setting the last unmeasurable emigration probability equal to the previous year’s probability when the equality was actually false. Results of a series of simulations demonstrated that if the unmeasurable temporary emigration probabilities in the last time period were not accurately modeled, an estimation model with significant annual variation in survival probabilities and emigration probabilities produced bias in survival estimates at the end of the study or time series being explored. Furthermore, the bias propagated back in time beyond the last two time periods and the number of years affected varied positively with survival and emigration probabilities. Truncating the data to a shorter time frame and reanalyzing demonstrated that with additional years of data surviving temporary emigrants eventually return and are detected, thus in subsequent analysis unbiased estimates are eventually realized.

  1. Emigration flows from North Africa to Europe. (United States)

    Kassar, Hassène; Marzouk, Diaa; Anwar, Wagida A; Lakhoua, Chérifa; Hemminki, Kari; Khyatti, Meriem


    The region of North Africa (NA) represents a striking locality regarding migration with several migration patterns, namely emigration in the form of labour export to Europe and North America and, to a lesser extent, to the Arab Gulf area. The latter has increased enormously in the last decade because of the political instability in most of the NA countries. The aim of the present chapter was to explore the patterns of migration stocks and flows in NA countries, based on several websites, systematic review of journals, comparable data available by the United Nations and by the International Organization of Migration. The NA region has become an area of transit migration and labour migration. Emigrant flows from NA countries towards Europe and North America are increasing this decade more than towards the Arab Gulf countries after being replaced by Asian labour. The recent increase in the proportion of women among the migrant population is remarkable. Remittances sent by African migrants have become an important source of external finance for countries of origin. Transient and irregular migration to Egypt originates at the borders with Sudan, Palestine and Libya with destination to the Euro Mediterranean countries. In Tunisia and Morocco, irregular migrants originate from Sub-Saharan Africa to the northern borders. The NA countries serve as departure rather than destination countries, and migration flows to the Euro-Mediterranean countries through legal or illegal routes.

  2. When the Quality of a Nation Triggers Emigration

    NARCIS (Netherlands)

    H.P. van Dalen (Hendrik); K. Henkens


    textabstractWhy do people leave high-income countries with extensive welfare states? This article will examine what underlies the emigration intentions of native-born inhabitants of one industrialized country in particular: the Netherlands. To understand emigration from high-income countries we focu

  3. Applying Organizational Commitment and Human Capital Theories to Emigration Research (United States)

    Verkhohlyad, Olga; McLean, Gary N.


    Purpose: This study aims to bring some additional insight into the issue of emigration by establishing a relationship between emigration and psychic return of citizens to their human capital investment in the country. Design/methodology/approach: The article adopts a quantitative research strategy. It applies organizational commitment and human…

  4. Order on programmes of assistance favouring emigrants, 15 January 1988. (United States)


    This Order sets forth programs of assistance containing the following categories of aid: 1) aid for elderly emigrants who are Spanish or in the process of recovering Spanish citizenship and are ill and incapable of working; 2) aid to cover the extraordinary costs related to emigration or the return of Spanish emigrant workers and their families who are in a state of need; 3) aid to facilitate the integration into the workplace of returned Spanish emigrants who are unemployed; 4) aid for emigrant centers, associations, and federations helping Spanish emigrants; 5) aid to organizations to improve the assistance and hospital and cultural activities that they provide to Spanish emigrants; 6) aid to organizations that promote professional and occupational orientation and training to facilitate the professional promotion and insertion in the workplace of Spanish emigrant workers; 7) aid to Spanish emigrants and their families resident abroad who have special abilities and wish to pursue higher education and lack the means to do so in Spain; 8) aid to young Spanish emigrants resident abroad to promote their participation in cultural, sociocultural, artistic, and youth activities; 9) aid to promote the social integration of foreign workers in Spain; and 10) aid to programs involving the exchange of young workers within the European Economic Community. Further provisions of the Order deal with beneficiaries of aid, documentation required, and applications, among other things. This Order repeals provisions of an Order of 30 January 1987 (Boletin Oficial del Estado, No. 42, 18 February 1987, pp. 4952-4964) on the same topic in so far as those provisions are in conflict with the provisions of this Order.

  5. Does Emigration Affects Wages? A Case Study on Romania

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    Costin-Alexandru Ciupureanu


    Full Text Available The migration phenomenon in Romania is characterized by emigration; the number of Romanian migrants skyrocketed after the Romanian accession to the European Union in 2007. With the economic and financial crisis outlook and with the labour market liberalization across the whole European Union for the Romanian workers starting this year the number of Romanian migrants is expected to increase further. Against this background this paper analyses the effects of emigration on wages in Romania. It is found that emigration has a positive impact on wages in Romania.

  6. Emigration dynamics in Sub-Saharan Africa. (United States)

    Adepoju, A


    The introduction to this description of emigration dynamics in sub-Saharan Africa notes that the region is characterized by intensive migration caused by such factors as population growth, negative economic growth, ethnic conflict, and human rights abuses. The second section of the report discusses the fragmentary and incomplete nature of data on international migration in the region, especially data on conventional migration. Section 3 looks at demographic factors such as high population growth, illiteracy levels, HIV seroprevalence, and urbanization which lead to high unemployment and emigration. The fourth section considers the effects of the rapid expansion of education which is outstripping the absorptive capacity of the economies of many countries. Unemployment is a serious problem which is projected to become worse as increases in employment opportunities continue to lag behind increases in output. Sections five, six, and seven of the report describe relevant economic factors such as per capita income, income distribution, the economic resource base, and economic development; poverty; and the effects of economic adjustment programs, especially on employment opportunities and wages in the public and private sectors. The next section is devoted to sociocultural factors influencing migration both on the micro- and the macro-levels, including the influence of ethnicity and ethnic conflicts as well as the domination of leadership positions by members of minority groups. The political factors discussed in section 9 include women's status, repressive regimes, political instability which leads to underdevelopment, and the policies of the Organization of African Unity which broadened the definition of refugees and set inviolable borders of member states identical to those inherited upon independence. Section 10 outlines ecological factors contributing to migration, including the decline in acreage of arable land, soil deterioration, poor land management, and the

  7. Demographic and Related Determinants of Recent Cuban Emigration. (United States)

    Briquets, Sergio Diaz


    Examines principal demographic determinants of recent Cuban emigration and discusses how these demographic variables interact with other social, economic, and political determinants. Suggests that Cuban labor migration is more responsive to demographic factors than some theorists assume. (Author/MJL)

  8. Emigration as an Aspect of the Barbadian Social Environment. (United States)

    Marshall, Dawn I.


    Demonstrates how since emancipation, emigration has always been viewed as a positive experience among Barbadians. Presents demographic data and data on cash value of remittances to the island from Barbadians living abroad. (GC)

  9. [Cell therapy for type I diabete]. (United States)

    Sokolova, I B


    Cell therapy is a modern and promising approach to type I diabetes mellitus treatment. Nowadays a wide range of cells is used in laboratory experiments and clinical studies, including allogeneic and xenogeneic cells of Langergance islets, bone marrow cells, haematopoietic stem cells, mesenchymal stem cells, and cord blood stem cells. Any type of the cells named could correct the status of the patients to a certain extent. However, full recovery after cell therapy has not been achieved yet.

  10. Gender, Power, and Emigration From Mexico. (United States)

    Nobles, Jenna; McKelvey, Christopher


    The prevailing model of migration in developing countries conceives of a risk-diversifying household in which members act as a single entity when making migration decisions. Ethnographic studies challenge this model by documenting gender hierarchy in family decisions and arguing that, in many contexts, men and women have differing views on the value of migration. We assess these perspectives using longitudinal survey data from Mexico. We show that Mexican households are heterogeneous in terms of women's decision-making authority and control over resources, and this variation predicts the subsequent emigration of their male partners to the United States. We then use data from a policy experiment to demonstrate that an exogenous increase in a woman's control over household resources decreases the probability that her spouse migrates. Our findings support the presence of important gender differences in how migration is valued. They also suggest that women's role in these decisions is inadvertently underrepresented in studies of migrant families. Staying is also a migration decision, and it is more likely in homes in which women have greater authority. From a policy perspective, the results suggest that Mexican migration is influenced not only by increases in household resources but also by which members of the household control them.

  11. Gender, Power, and Emigration From Mexico (United States)

    Nobles, Jenna; McKelvey, Christopher


    The prevailing model of migration in developing countries conceives of a risk-diversifying household in which members act as a single entity when making migration decisions. Ethnographic studies challenge this model by documenting gender hierarchy in family decisions and arguing that, in many contexts, men and women have differing views on the value of migration. We assess these perspectives using longitudinal survey data from Mexico. We show that Mexican households are heterogeneous in terms of women's decision-making authority and control over resources, and this variation predicts the subsequent emigration of their male partners to the United States. We then use data from a policy experiment to demonstrate that an exogenous increase in a woman's control over household resources decreases the probability that her spouse migrates. Our findings support the presence of important gender differences in how migration is valued. They also suggest that women's role in these decisions is inadvertently underrepresented in studies of migrant families. Staying is also a migration decision, and it is more likely in homes in which women have greater authority. From a policy perspective, the results suggest that Mexican migration is influenced not only by increases in household resources but also by which members of the household control them. PMID:26100982

  12. [Emigration and immigration in Italy. (1861-2011)]. (United States)

    Pasini, Walter


    The creation of the Italian Kingdom was characterized by the mass emigration of Italian people, mainly peasants towards European and American destinations. Poverty, unemployment, diseases, like pellagra, malaria and tubercolosis forced millions of Italians to leave the Country. The phenomenon of emigration is usually divided in three periods: the mass emigration from 1976 to 1914, the second one between the two world wars, the third one from 1946 to 1976. In the last quarter of the 20th century the number of repatriations overcome expatriations and the number of immigrants from Albania, Romania, Senegal, Tunisia, China, Philippines grew up becoming more and more important. Italy was a country of emigrants, now is a country of immigrants. It is difficult to compare the work conditions of the Italian emigrants with the new immigrants. At the end of the 19th Century or in the first decades of the 20th Century there were no consideration for human rights, no legislations to protect workers. Immigration from North Africa and from all the low and middle income countries should be studied in all its aspects because it will characterize our future. In the new era of economical globalization, Universities should prepare the new medical doctors to extend their professional culture to a international dimension to be able to cope with the new challenges of our time.

  13. Linguistic identity and the study of emigrant letters: Irish English in the making


    Amador Moreno, Carolina P; McCafferty, Kevin


    This paper builds on the findings from a larger research project that analyses written data extracted from a corpus of emigrant letters. This preliminary study is an exploration of the Irish Emigration Database (IED), an electronic word-searchable collection of primary source documents on Irish emigration to North America (USA and Canada) in the 18th and 19th centuries. The IED contains a variety of original material including emigrant letters, newspaper articles, shippin...

  14. Longing for the good life: understanding emigration from a high-income country

    NARCIS (Netherlands)

    van Dalen, H.P.; Henkens, C.J.I.M.


    The outline of this article is as follows. First, we provide information on trends in emigration from highly developed countries. We review salient aspects of Dutch emigration history to provide a broader context for the extraordinary nature of today’s upsurge in emigration. We describe the theoreti

  15. Explaining emigration intentions and behaviour in the Netherlands, 2005-10

    NARCIS (Netherlands)

    van Dalen, H.P.; Henkens, K.


    We examined the emigration intentions of native-born Dutch residents and their subsequent emigration behaviour from 2005 to 2010. Data were collected from two surveys on emigration intentions, one conducted locally and one nationally. A number of novel results stand out. First, intentions were good

  16. Just One of the 'PIIGS' or a European Outlier? Studying Irish Emigration from a Comparative Perspective

    NARCIS (Netherlands)

    Glynn, I.A.


    The return of high levels of emigration has become one of the most debated and sensitive social topics in Ireland in recent years. But Irish emigration continues to be discussed in the singular rather than the plural. This paper compares Irish emigration to other Eurozone states that also encountere

  17. Colombian Emigration: A Research Note on Its Probable Quantitative Extent. (United States)

    Diaz-Briquets, Sergio; Frederick, Melinda J.


    Provides a brief overview of quantitative estimates of Colombian emigration including a discussion of how estimates were prepared. Concludes that estimates of international migration from Colombia are inflated and that such migration is not as significant as some observers claim. (CMG)

  18. Attachment styles, personality, and Dutch emigrants ' intercultural adjustment

    NARCIS (Netherlands)

    Bakker, W; Van Oudenhoven, JP; Van Der Zee, KI


    The present study examines the relationship of adult attachment styles with personality and psychological and sociocultural adjustment. A sample of 847 first-generation Dutch emigrants filled out measures for attachment styles, the Big Five, and indicators of psychological and sociocultural adjustme

  19. Prague as the Centre of Russian Educational Emigration: Czechoslovakia's Educational Policy for Russian Emigrants (1918-1938) (United States)

    Mchitarjan, Irina


    This article looks at the role played by the Czechoslovakian Republic in the establishment and maintenance of the "Russian education system in exile" in Europe during the 1920s and 1930s. No other country supported the educational activities of the Russian emigrants as generously as Czechoslovakia. Thanks to this extensive and targeted support, a…

  20. Cell-Type-Specific Optogenetics in Monkeys. (United States)

    Namboodiri, Vijay Mohan K; Stuber, Garret D


    The recent advent of technologies enabling cell-type-specific recording and manipulation of neuronal activity spurred tremendous progress in neuroscience. However, they have been largely limited to mice, which lack the richness in behavior of primates. Stauffer et al. now present a generalizable method for achieving cell-type specificity in monkeys.

  1. Patterning of cell assemblies regulated by adhesion receptors of the cadherin superfamily.



    During morphogenesis, cell-cell association patterns are dynamically altered. We are interested in how cell adhesion molecules can regulate the patterning of cellular assemblies. Cadherins, a group of cell-cell adhesion receptors, are crucial for the organized assembly of many cell types, but they also regulate dynamic aspects of cell association. For example, during neural crest emigration from the neural tube, the cadherin subtypes expressed by crest cells are switched from one subtype to a...

  2. Explaining emigration intentions and behaviour in the Netherlands, 2005-10. (United States)

    van Dalen, Hendrik P; Henkens, Kène


    We examined the emigration intentions of native-born Dutch residents and their subsequent emigration behaviour from 2005 to 2010. Data were collected from two surveys on emigration intentions, one conducted locally and one nationally. A number of novel results stand out. First, intentions were good predictors of future emigration: 34 per cent of those who had stated an intention to emigrate actually emigrated within the 5-year follow-up period. Second, the personality of potential migrants and their discontent with the quality of the public domain in the Netherlands (e.g., crowded space and inadequate access to unspoilt nature, pollution, crime level, mentality of people) were the strongest contributors to the motivation to move abroad. Third, the main difference between movers and those who stated intentions to emigrate but had not (yet) followed through was their state of health: healthy people were more likely to follow through with their migration intentions than those in poorer health.

  3. Space Insect-Food Aiming at Mars Emigration (United States)

    Katayama, Naomi; Hashimoto, Hirofumi; Yamashita, Masamichi; Takase, Yoshimi; Kawai, Mika; Space Agriculture Task Force

    We study space insect-food during 10 years. We are aiming at Mars emigration. In space agriculture, insect is the important creature which we cannot miss. It is necessary for the pollination of the plant, and it is rich to protein and lipid as food. We reported that silkworm, bee, grasshopper, snail, fly and termite (white ant) are insects necessary for astroponics in particular last time. We make clothes using silk thread, and the pupa becomes the food. In addition, the clothes can make food as protein when we need not to use it. The bee is a very important insect in the space agriculture, too. We calculated the nourishment ingredient of those insects and thought about ideal space foods which ara necessary for Mars emigration. We will introduce good balance space foods.


    Directory of Open Access Journals (Sweden)

    Мария Игоревна Шкредова


    Full Text Available In this article the author analyzes the features of functioning of the Soviet ideologeme in the literature of emigrants in details. Much attention is given to the term "ideologeme", its characteristics and features. Criteria of differentiation of the terms "Sovietism" and "ideologeme" are considered. There is the analysis of changes in perception of ideological expressions into space and time by examples of passages from the literature of the emigrant writers.The received results of research will spark the interest of the authors of dictionaries and teachers in development of programs for studying lexicon, stylistics and the culture of speech.DOI:

  5. Psychoanalysis and the Emigration of Central and Eastern European Intellectuals(). (United States)

    Erős, Ferenc


    One of the most important phenomena in the intellectual history of the 20th century was the exodus of the European mind, the emigration of persons, ideas, techniques, and institutions in the vast areas of social, human, and natural sciences, as well as in literature and the visual arts. Among these exiled intellectuals, psychoanalysts formed a special group. This paper examines the major lines of the emigration of psychoanalysts from the countries of issue to the countries of reception. It focuses, in particular on Hungarian analysts and analytic candidates who left their country of birth in two waves, first after the failure of revolutions in 1918/19 for Berlin, and then after 1938, to escape the Nazis. The paper comments on the existential situation of émigré psychoanalysts in light of Hannah Arendt's writings on refugees.

  6. "Should I Stay or Should I Go? - The Emigrating Immigrants"

    DEFF Research Database (Denmark)

    Rezaei, Shahamak; Goli, Marco


    in keeping those immigrants who contribute to the development of the universal welfare state, while reducing the burden of the others. Thus, the controversial question arises: whom among the immigrants from non-western countries will chose to stay in their new country and who will emigrate again......? The following is an empirical clarification of this issue, the state of the art and the attitudes and future trends, based on two sets of comprehensive quantitative data collection....

  7. Modeling the effects of physician emigration on human development.



    We analyzed the effects of physician emigration on human development indicators in developing countries. First, the geographical distribution of physician brain drain was documented for the period 1991–2004. Second, random and fixed effects models were employed to investigate the effects of physicians in the home countries and abroad on child mortality and vaccination rates. Third, models were estimated to investigate migration-induced incentives in the medical sector that would increase the ...

  8. Emigration preferences and plans among medical students in Poland

    Directory of Open Access Journals (Sweden)

    Krajewski-Siuda Krzysztof


    Full Text Available Abstract Background Migration and ethical recruitment of health care workers is receiving increased attention worldwide. Europe’s aging population is creating new opportunities for medical doctors for finding employment in other countries, particularly those of a better standard of living. Methods We conducted a survey among 1214 medical students in five out of eleven universities in Poland with medical schools in October 2008. A series of statistical tests was applied to analyse the characteristics of potential migrants. Projections were obtained using statistical analyses: descriptive, multifactorial logistic regression and other statistical methods . Results We can forecast that 26–36% of Polish medical students will emigrate over the next few years; 62% of respondents estimated the likelihood of emigration at 50%. Students in their penultimate year of study declared a stronger desire to migrate than those in the final year. At the same time, many students were optimistic about career opportunities in Poland. Also noted among students were: the decline in interest in leaving among final year students, their moderate elaboration of departure plans, and their generally optimistic views about the opportunities for professional development in Poland. Conclusions The majority of Polish students see the emigration as a serious alternative to the continuation of their professional training. This trend can pose a serious threat to the Polish health care system, however the observed decline of the interest in leaving among final year students, the moderate involvement in concrete departure plans and the optimistic views about the opportunities for professional development in Poland suggest that the actual scale of brain drain of young Polish doctors due to emigration will be more limited than previously feared.

  9. The Russian musical emigration in Yugoslavia after 1917

    Directory of Open Access Journals (Sweden)

    Melita Milin


    Full Text Available Around forty thousand Russian emigrants settled in Yugoslavia running away from the terror of the 1917 Revolution. A high percentage of them were writers, artists, musicians and ballet dancers. Their greatest contribution to Yugoslav musical culture consists in the important acceleration they brought to the development of the domestic scene. Especially valuable were the activities of opera singers and directors, ballet dancers and choreographers, scenery designers, conductors of church choirs and music pedagogues.


    Directory of Open Access Journals (Sweden)

    Matsievsky German Olegovitch


    Full Text Available Purpose: To consider the main tendencies and features of political life of the Cossack emigration in the XX century. Methodology: Methodological basis of research are the standard principles of a historicism and the objectivity, assuming the concrete historical approach to the analysis of events in their dialectic development. Results: It is revealed that the Cossack emigration lost the political positions. Separation from sociocultural and geographical space of formation and development of traditional culture; foreign culture environment; refusal of the Cossack ideas of a collectivism and military brotherhood; destruction of the main institute of preservation and transfer of historical and cultural experience – a family; the constant feeling of «temporariness», despair and loss of belief in the future – all this generated the phenomenon called in cross-cultural psychology «cultural shock». Also crisis of ethnic and sociocultural consciousness and self-identification increased. Practical implications: Results of research can be interesting to the experts who are taking up the problems stories of the Cossacks in emigration.

  11. Inference about density and temporary emigration in unmarked populations (United States)

    Chandler, Richard B.; Royle, J. Andrew; King, David I.


    Few species are distributed uniformly in space, and populations of mobile organisms are rarely closed with respect to movement, yet many models of density rely upon these assumptions. We present a hierarchical model allowing inference about the density of unmarked populations subject to temporary emigration and imperfect detection. The model can be fit to data collected using a variety of standard survey methods such as repeated point counts in which removal sampling, double-observer sampling, or distance sampling is used during each count. Simulation studies demonstrated that parameter estimators are unbiased when temporary emigration is either "completely random" or is determined by the size and location of home ranges relative to survey points. We also applied the model to repeated removal sampling data collected on Chestnut-sided Warblers (Dendroica pensylvancia) in the White Mountain National Forest, USA. The density estimate from our model, 1.09 birds/ha, was similar to an estimate of 1.11 birds/ha produced by an intensive spot-mapping effort. Our model is also applicable when processes other than temporary emigration affect the probability of being available for detection, such as in studies using cue counts. Functions to implement the model have been added to the R package unmarked.

  12. [Preventive health control of U. S. emigrants at the beginning of 20th century on the example of hotel "Emigrants" in Rijeka]. (United States)

    Rotim Malvić, Jasna


    Rijeka inscribed herself on the list of great European emigration ports like Hamburg, Bremen, Liverpool in the end of the year 1903 when a ship of the British Cunard Line established a travel line from Rijeka to New York. Up to the year 1914, 317639 passengers - emigrants travelled to America from the port of Rijeka. The large flow of people caused problems for the city, for that reason, already in 1906 did the Hungarian ministry of home affairs started the construction of a grandiose building intended for the emigrants. When it was opened in 1908 it was named Hotel Emigrants and had a capacity of 2500 guests. The name Hotel was given to him because of the highest construction and sanitary standards applied during his construction, but also because of comfort provided for the emigrants, large bright dormitories, living rooms, one big and spacious terrace and a number of smaller ones indicated more to a touristic hotel than to a house for emigrants. Health surveillance of emigrants was performed by Dr. David Friedman, Dr. Arturo Jellouscheg and Dr. Emil Tauffer. They were in charge in front of the Maritime Gubernia in Rijeka, the U.S. consulate in Rijeka and the Adria Maritime Society. Although the city authorities and the Hungarian authorities boasted of the hotel and the rigid medical control over immigrants which was done there, American authorities have still often returned some emigrants, at the expense of the company, after inspection at Ellis Island revealing that before landing some individuals are sick.

  13. Effects of hatchery fish density on emigration, growth, survival, and predation risk of natural steelhead parr in an experimental stream channel (United States)

    Tatara, Christopher P.; Riley, Stephen C.; Berejikian, Barry A.


    Hatchery supplementation of steelhead Oncorhynchus mykiss raises concerns about the impacts on natural populations, including reduced growth and survival, displacement, and increased predation. The potential risks may be density dependent.We examined how hatchery stocking density and the opportunity to emigrate affect the responses of natural steelhead parr in an experimental stream channel and after 15 d found no density-dependent effects on growth, emigration, or survival at densities ranging from 1-6 hatchery parr/m2. The opportunity for steelhead parr to emigrate reduced predation by coastal cutthroat trout O. clarkii clarkii on both hatchery and natural steelhead parr. The cutthroat trout exhibited a type-I functional response (constant predation rate with increased prey density) for the hatchery and composite populations. In contrast, the predation rate on natural parr decreased as hatchery stocking density increased. Supplementation with hatchery parr at any experimental stocking density reduced the final natural parr density. This decline was explained by increased emigration fromthe supplemented groups. Natural parr had higher mean instantaneous growth rates than hatchery parr. The proportion of parr emigrating decreased as parr size increased over successive experimental trials. Smaller parr had lower survival and suffered higher predation. The final density of the composite population, a measure of supplementation effectiveness, increased with the hatchery steelhead stocking rate. Our results indicate that stocking larger hatchery parr (over 50 d postemergence) at densities within the carrying capacity would have low short-term impact on the growth, survival, and emigration of natural parr while increasing the density of the composite population; in addition, a stocking density greater than 3 fish/m2 might be a good starting point for the evaluation of parr stocking in natural streams.

  14. Industrial n-type solar cells with >20% cell efficiency

    Energy Technology Data Exchange (ETDEWEB)

    Romijn, I.G.; Anker, J.; Burgers, A.R.; Gutjahr, A.; Koppes, M.; Kossen, E.J.; Lamers, M.W.P.E.; Heurtault, Benoit; Saynova-Oosterling, D.S.; Tool, C.J.J. [ECN Solar Energy, Petten (Netherlands)


    To realize high efficiencies at low costs, ECN has developed the n-Pasha solar cell concept. The n-Pasha cell concept is a bifacial solar cell concept on n-Cz base material, with which average efficiencies of above 20% have been demonstrated. In this paper recent developments at ECN to improve the cost of ownership (lower Euro/Wp) of the n-Pasha cell concept are discussed. Two main drivers for the manufacturing costs of n-type solar cells are addressed: the n-type Cz silicon material and the silver consumption. We show that a large resistivity range between 2 and 8 cm can be tolerated for high cell efficiency, and that the costs due to the silver metallization can be significantly reduced while increasing the solar cell efficiency. Combining the improved efficiency and cost reduction makes the n-Pasha cell concept a very cost effective solution to manufacture high efficient solar cells and modules.

  15. Emigration and the Processes of Globalization: Challenges, Contemporary Trends, Issues, Solutions

    Directory of Open Access Journals (Sweden)

    Indrė Naulickaitė


    Full Text Available The article complexly investigates the processes of emigration from Lithuania and other European Union countries in Central and Eastern Europe which appear under contemporary conditions of economic globalization. The main attention is given to those determinants of emigration which are caused by the processes taking place in the global economy, social and economic circumstances occuring globally. The theoretical study for the processes of migration and emigration in contemporary environment of globalization has been made. The original theoretical conception intended to analyze migration flows, motives and reasons of emigration, allowing to complexly assess the impact of various economic determinants has been suggested: on the basis of this conception researches of emigration from Lithuania and other European Union countries in Central and Eastern Europe have been carried out and peculiarities of the processes of emigration reflecting the impact of circumstances determined by economic globalization have been highlighted. Carrying out empirical researches the instrumentation of economic mathematical modeling has been used.

  16. Moving to the Welfare Countries: Emigrants from Serbia 1961-2002

    Directory of Open Access Journals (Sweden)

    Milka Bubalo-Živković


    Full Text Available The main characteristic of Balkan region in history is permanent migration. The character of this migration is changed from period to period. After WWII in Serbia migrations had economical character. These migrations are dominated till the last decade of XX century. According to the 2002 census, in foreign countries lives more than 400,000 citizens of Serbia. About 50 percent of citizens emigrated in decades before 1990, and the next 50 percent emigrated in period between 1990 and 2002. About 80 percent of emigrations are from central Serbia, and rest are from Vojvodina Province. Major emigration from Serbia has been directed towards Austria, Germany and Switzerland. The number of emigrants from Serbia is also high in France, Italy and Sweden. Outside of Europe most of the emigrants went in the United States of America.

  17. Emigration of a colony of the leaf-cutting ant Acromyrmex heyeri Forel (Hymenoptera, Formicidae

    Directory of Open Access Journals (Sweden)

    Mariane Aparecida Nickele


    Full Text Available Emigration of a colony of the leaf-cutting ant Acromyrmex heyeri Forel (Hymenoptera, Formicidae. Colony migration is a poorly studied phenomenon in leaf-cutting ants. Here we report on the emigration of a colony of the leaf-cutting ant A. heyeri in Brazil. The colony emigrated to a new location 47.4 m away from the original nest site, possibly because it had undergone considerable stress due to competitive interactions with a colony of Acromyrmex crassispinus.

  18. A model for estimating passive integrated transponder (PIT) tag antenna efficiencies for interval-specific emigration rates (United States)

    Horton, G.E.; Dubreuil, T.L.; Letcher, B.H.


    Our goal was to understand movement and its interaction with survival for populations of stream salmonids at long-term study sites in the northeastern United States by employing passive integrated transponder (PIT) tags and associated technology. Although our PIT tag antenna arrays spanned the stream channel (at most flows) and were continuously operated, we are aware that aspects of fish behavior, environmental characteristics, and electronic limitations influenced our ability to detect 100% of the emigration from our stream site. Therefore, we required antenna efficiency estimates to adjust observed emigration rates. We obtained such estimates by testing a full-scale physical model of our PIT tag antenna array in a laboratory setting. From the physical model, we developed a statistical model that we used to predict efficiency in the field. The factors most important for predicting efficiency were external radio frequency signal and tag type. For most sampling intervals, there was concordance between the predicted and observed efficiencies, which allowed us to estimate the true emigration rate for our field populations of tagged salmonids. One caveat is that the model's utility may depend on its ability to characterize external radio frequency signals accurately. Another important consideration is the trade-off between the volume of data necessary to model efficiency accurately and the difficulty of storing and manipulating large amounts of data.

  19. A field test of the extent of bias in selection estimates after accounting for emigration (United States)

    Letcher, B.H.; Horton, G.E.; Dubreuil, T.L.; O'Donnell, M. J.


    Question: To what extent does trait-dependent emigration bias selection estimates in a natural system? Organisms: Two freshwater cohorts of Atlantic salmon (Salmo salar) juveniles. Field site: A 1 km stretch of a small stream (West Brook) in western Massachusetts. USA from which emigration could be detected continuously. Methods: Estimated viability selection differentials for body size either including or ignoring emigration (include = emigrants survived interval, ignore = emigrants did not survive interval) for 12 intervals. Results: Seasonally variable size-related emigration from our study site generated variable levels of bias in selection estimates for body size. The magnitude of this bias was closely related with the extent of size-dependent emigration during each interval. Including or ignoring the effects of emigration changed the significance of selection estimates in 5 of the 12 intervals, and changed the estimated direction of selection in 4 of the 12 intervals. These results indicate the extent to which inferences about selection in a natural system can be biased by failing to account for trait-dependent emigration. ?? 2005 Benjamin H. Letcher.

  20. Environmental emigration stress of slope farmland in the Three Gorges area

    Institute of Scientific and Technical Information of China (English)


    The project of 'grain for green', to restore woodland and grass by retreating from slopefarmland, as a fundamental measure of eeo-environmental rehabilitation, is being conducted in thereservoir area of the Three Gorges gradually. However, the de-farming of slope farmland will reducethe amount of farmland in de-farmed areas, especially in the areas with concentrated slope farmland,which would cause the problems of environmental emigration. The people who cannot regain enoughfarmland by relocating farmlands within village after de-farming and have to emigrate to other placesare called environmental emigrants or ecological emigrants. In the research, a de-farming stress indexmodel and an environmental emigration model are developed based on GRID data, and the potentialamount of environmental emigration caused by de-farming of slope farmland in the reservoir area issimulated aided with GIS. The simulation indicates that the potential emigration amount caused byde-farming is quite large. When the de-farming stress index reaches 40%, the amount is as large as890,000 people, which is equivalent to the emigrants caused by the submergence of the ThreeGorges reservoir. So it should be considered as a big problem during the eco-environmentalrehabilitation in this area. Some suggestions are raised to tackle the problem. Firstly, the emigrationplan should be included in the de-farming plan. Secondly, some provinces, especially those located inthe lower reaches of the Yangtze River, should accommodate part of the environmental emigrants.

  1. Fuel cells - Fundamentals and types: Unique features (United States)

    Selman, J. R.

    An overview of the working principles, thermodynamic efficiencies, types, and engineering aspects of fuel cells is presented. It is noted that fuel cells are distinguished from other direct energy conversion devices by the existence of charge separation at the electrodes involving ions in an electrolyte. The electrical energy produced by a fuel cell is shown to be equal to the change in the free energy of the reactants, and thermodynamic balances of reactions in different fuel cells are provided. The production of electricity in the discharge mode involves a spontaneous reaction of overproduction of electrons at the anode and consumption of the electrons at the cathode, with the total ionic current being equal to the electronic current in the external circuit. Attention is given to the operations and problems of acid, alkaline, molten carbonate, and solid oxide fuel cells, in addition to applications of electro-organic fuel cells.

  2. Migrating neural crest cells in the trunk of the avian embryo are multipotent


    Fraser, Scott E.; Bronner-Fraser, Marianne


    Trunk neural crest cells migrate extensively and give rise to diverse cell types, including cells of the sensory and autonomic nervous systems. Previously, we demonstrated that many premigratory trunk neural crest cells give rise to descendants with distinct phenotypes in multiple neural crest derivatives. The results are consistent with the idea that neural crest cells are multipotent prior to their emigration from the neural tube and become restricted in phenotype after leaving the neural t...

  3. RNA cell typing and DNA profiling of mixed samples: can cell types and donors be associated? (United States)

    Harteveld, Joyce; Lindenbergh, Alexander; Sijen, Titia


    Forensic samples regularly involve mixtures, which are readily recognised in forensic analyses. Combined DNA and mRNA profiling is an upcoming forensic practice to examine donors and cell types from the exact same sample. From DNA profiles individual genotypes may be deconvoluted, but to date no studies have established whether the cell types identified in corresponding RNA profiles can be associated with individual donors. Although RNA expression levels hold many variables from which an association may not be expected, proof of concept is important to forensic experts who may be cross examined about this possible correlation in court settings. Clearly, the gender-specificity of certain body fluids (semen, vaginal mucosa, menstrual secretion) can be instructive. However, when donors of the same gender or gender-neutral cell types are involved, alternatives are needed. Here we analyse basic two-component mixtures (two cell types provided by different donors) composed of six different cell types, and assess whether the heights of DNA and RNA peaks may guide association of donor and cell type. Divergent results were obtained; for some mixtures RNA peak heights followed the DNA results, but for others the major DNA component did not present higher RNA peaks. Also, variation in mixture ratios was observed for RNA profiling replicates and when different donor couples gave the same two body fluids. As sample degradation may affect the two nucleic acids and/or distinct cell types differently (and thus influence donor and cell type association), mixtures were subjected to elevated temperature or UV-light. Variation in DNA and RNA stability was observed both between and within cell types and depended on the method inducing degradation. Taken together, we discourage to associate cell types and donors from peak heights when performing RNA and DNA profiling.

  4. Emigrating Beyond Earth Human Adaptation and Space Colonization

    CERN Document Server

    Smith, Cameron M


    For four million years humankind has been actively expanding geographically and in doing so has adapted to a wide variety of hostile environments. Now we are looking towards the ultimate adaptation - the colonization of space. Emigrating Beyond Earth illustrates that this is not a technocratic endeavor, but a natural continuation of human evolution; a journey not just for the engineer and rocket scientist, but for everyman. Based on the most current understanding of our universe, human adaptation and evolution, the authors explain why space colonization must be planned as an adaptation to, rather than the conquest of, space. Emigrating Beyond Earth argues that space colonization is an insurance policy for our species, and that it isn't about rockets and robots, it's about humans doing what we've been doing for four million years: finding new places and new ways to live. Applying a unique anthropological approach, the authors outline a framework for continued human space exploration and offer a glimpse of a po...

  5. Dispersal Timing: Emigration of Insects Living in Patchy Environments.

    Directory of Open Access Journals (Sweden)

    Milica Lakovic

    Full Text Available Dispersal is a life-history trait affecting dynamics and persistence of populations; it evolves under various known selective pressures. Theoretical studies on dispersal typically assume 'natal dispersal', where individuals emigrate right after birth. But emigration may also occur during a later moment within a reproductive season ('breeding dispersal'. For example, some female butterflies first deposit eggs in their natal patch before migrating to other site(s to continue egg-laying there. How breeding compared to natal dispersal influences the evolution of dispersal has not been explored. To close this gap we used an individual-based simulation approach to analyze (i the evolution of timing of breeding dispersal in annual organisms, (ii its influence on dispersal (compared to natal dispersal. Furthermore, we tested (iii its performance in direct evolutionary contest with individuals following a natal dispersal strategy. Our results show that evolution should typically result in lower dispersal under breeding dispersal, especially when costs of dispersal are low and population size is small. By distributing offspring evenly across two patches, breeding dispersal allows reducing direct sibling competition in the next generation whereas natal dispersal can only reduce trans-generational kin competition by producing highly dispersive offspring in each generation. The added benefit of breeding dispersal is most prominent in patches with small population sizes. Finally, the evolutionary contests show that a breeding dispersal strategy would universally out-compete natal dispersal.

  6. The Fatal Panacea: The Emigrant Experience in the Novels of Ferreira de Castro. (United States)

    Silva, John de Oliveira E

    The twin emigration sagas of Ferreira de Castro (1898-1974), "Emigrantes" (1928) and "A Selva" (1930) embody what has been described as the primary driving forces of emigration: hunger and injustice. The main protagonists of "Emigrantes" and "A Selva," Manuel and Alberto, illustrate these forces. Manuel, a middle-aged Portuguese farmer decides to…

  7. Emigration Intentions : Mere Words or True Plans? Explaining International Migration Intentions and Behavior

    NARCIS (Netherlands)

    van Dalen, H.P.; Henkens, K.


    Do people follow up on their intentions? In this paper we confront the emigration intentions formed by inhabitants of the Netherlands during the year 2004-2005 and the emigration steps they took in the subsequent two years. Three results stand out. First, it appears that intentions are good predicto

  8. Development and the Urban and Rural Geography of Mexican Emigration to the United States (United States)

    Hamilton, Erin R.; Villarreal, Andres


    Past research on international migration from Mexico to the United States uses geographically-limited data and analyzes emigrant-sending communities in isolation. Theories supported by this research may not explain urban emigration, and this research does not consider connections between rural and urban Mexico. In this study we use national data…

  9. The Fatal Panacea: The Emigrant Experience in the Novels of Ferreira de Castro. (United States)

    Silva, John de Oliveira E

    The twin emigration sagas of Ferreira de Castro (1898-1974), "Emigrantes" (1928) and "A Selva" (1930) embody what has been described as the primary driving forces of emigration: hunger and injustice. The main protagonists of "Emigrantes" and "A Selva," Manuel and Alberto, illustrate these forces. Manuel, a…

  10. Threat of Emigration for the Socio-Economic Development of Lithuania

    Directory of Open Access Journals (Sweden)

    Olga Ranceva


    Full Text Available The phenomenon of international migration is among the most prominent global demographic processes currently taking place and influencing both the economic and social situation worldwide. An intensive emigration is a matter of serious concern for such a small country as Lithuania. Firstly, emigration further exacerbates the current negative demographic indicators (low birth rate, high mortality rate, stagnant average lifespan, which, on the whole, leads to a decrease in the absolute number of the population. Secondly, emigration of persons of working age, leaving behind the population that lacks the capacity for work, reduces the state budget and social security budget revenues. Thirdly, departure of well-educated and competent citizens from the country results in the shrinking of the country’s intellectual potential and diminishing of possibilities of mastering and development of high technologies, innovations and modernisation of the economy. The authors of the article point out the threat posed by emigration to Lithuania’s socioeconomic development and present a comprehensive analysis of the demographic structure of the population: by sex and age, the population ageing tendency, the causes and consequences of emigration. The goal of the article is to raise the issue of emigration from Lithuania and to manifest its impact on the socio-economic development of the country. The object of the article is the extent, dynamics, structure, causes and economic effects of emigration and the problems arising for the economy in the context of emigration.

  11. Dependence of herpes simplex virus type 1-induced cell fusion on cell type

    Energy Technology Data Exchange (ETDEWEB)

    Bzik, D.J.; Person, S.


    Syncytial mutants of herpes simplex virus type 1 (HSV-1), such as syn20, cause extensive fusion of human embryonic lung (HEL) cells but only a small amount of fusion of human epidermoid carcinoma No. 2 (HEp-2) cells. In order to determine the cellular basis of this difference in fusion, sparse cultures of syn20-infected HEL or HEp-2 cells, previously labeled with (/sup 3/H)thymidine, were surrounded with uninfected, unlabeled HEL or HEp-2 cells. The fusion of radioactive with nonradioactive cells was determined at different times after infection using radioautography. The major difference in the fusion capacity of HEL and HEp-2 cells was not due to a difference in cell-surface receptors for a fusion factor in the two cell types. The process of infection of HEp-2 cells did not cause the plasma membranes of the cells to become refractory to fusion, because syn20-infected HEL cells fused equally well with either uninfected or infected HEp-2 cells. In a mixed infection with equal numbers of MP and its nonsyncytial parent, mP, extensive fusion was observed for infected HEL cells and significantly less fusion was observed for infected African green monkey (CV-1), baby hamster kidney (BHK-21), and HEp-2 cells.

  12. Immigration and Emigration of Professional and Skilled Manpower During the Post-War Period. Special Study No. 1. (United States)

    Parai, Louis

    The impact of immigration and emigration on Canada's stock of professional and skilled manpower was analyzed for the period 1946-1963. Although the number of immigrants is recorded by Canadian authorities there is no complete record of emigration from Canada; however, a reasonably reliable picture was obtained from emigration data of other…

  13. CD4+ Recent Thymic Emigrants Are Recruited into Granulomas during Leishmania donovani Infection but Have Limited Capacity for Cytokine Production (United States)

    Moore, John W. J.; Beattie, Lynette; Osman, Mohamed; Owens, Benjamin M. J.; Brown, Najmeeyah; Dalton, Jane E.; Maroof, Asher


    Recent thymic emigrants (RTEs) represent a source of antigen-naïve T cells that enter the periphery throughout life. However, whether RTEs contribute to the control of chronic parasitic infection and how their potential might be harnessed by therapeutic intervention is currently unclear. Here, we show that CD4+ recent thymic emigrants emerging into the periphery of mice with ongoing Leishmania donovani infection undergo partial activation and are recruited to sites of granulomatous inflammation. However, CD4+ RTEs displayed severely restricted differentiation either into IFNγ+ or IFNγ+TNFα+ effectors, or into IL-10-producing regulatory T cells. Effector cell differentiation in the chronically infected host was not promoted by adoptive transfer of activated dendritic cells or by allowing extended periods of post-thymic differentiation in the periphery. Nevertheless, CD4+ RTEs from infected mice retained the capacity to transfer protection into lymphopenic RAG2-/- mice. Taken together, our data indicate that RTEs emerging into a chronically inflamed environment are not recruited into the effector pool, but retain the capacity for subsequent differentiation into host protective T cells when placed in a disease-free environment. PMID:27658046

  14. Cell type-specific bipolar cell input to ganglion cells in the mouse retina. (United States)

    Neumann, S; Hüser, L; Ondreka, K; Auler, N; Haverkamp, S


    Many distinct ganglion cell types, which are the output elements of the retina, were found to encode for specific features of a visual scene such as contrast, color information or movement. The detailed composition of retinal circuits leading to this tuning of retinal ganglion cells, however, is apart from some prominent examples, largely unknown. Here we aimed to investigate if ganglion cell types in the mouse retina receive selective input from specific bipolar cell types or if they sample their synaptic input non-selectively from all bipolar cell types stratifying within their dendritic tree. To address this question we took an anatomical approach and immunolabeled retinae of two transgenic mouse lines (GFP-O and JAM-B) with markers for ribbon synapses and type 2 bipolar cells. We morphologically identified all green fluorescent protein (GFP)-expressing ganglion cell types, which co-stratified with type 2 bipolar cells and assessed the total number of bipolar input synapses and the proportion of synapses deriving from type 2 bipolar cells. Only JAM-B ganglion cells received synaptic input preferentially from bipolar cell types other than type 2 bipolar cells whereas the other analyzed ganglion cell types sampled their bipolar input most likely from all bipolar cell terminals within their dendritic arbor.

  15. [The effects of manpower emigration on income distribution and consumption models in the Egyptian economy]. (United States)

    Abdel Fadil, M


    This work analyzes the effects of emigration from Egypt on the distribution of income and the consumption model of the Egyptian economy. The increasing role of remittances as a principal source of household income has disturbed the old division of income among socioeconomic groups. It is difficult to estimate the volume of remittances with any precision because of the variety of ways in which they can be made. Official statistics tend to underestimate their value by ignoring black market transactions, remittances of merchandise, and other forms. An estimate was made of the value of remittances in 1980 taking account of wage levels of 5 different types of workers in the principal employing countries, their average propensities to save, and the employment structure of migrants by socioprofessional groups. The average educational level of emigrants appears to have declined somewhat between 1972-78. Average monthly income for emigrants was estimated to range from 792 Egyptian pounds for technical and professional workers to 252 for unskilled workers and the propensity to save was estimated to range from 40% for technical and scientific workers to 15% for unskilled workers. The total income remitted in 1980 in millions of Egyptian pounds was estimated at 912 for 240,000 technical and scienfific workers, 739 for 360,000 intermediate level workers, 415 for 300,000 artisans and workers, 60 for 60,000 chauffeurs, and 109 for 240,000 unskilled workers. Although remittances have elevated the per capita income of the low income groups, their impact has been diminished by severe inflationary pressures which have led to a decline in living levels and a less complete satisfaction of basic needs. Salary levels of construction workers were 7-9 times higher in Egyptian pounds in 1977 in 3 countries of immigration than in Egypt, while they were 7-10 times higher in 4 countries for university professors. Remittances are used by families receiving them for subsistence or investment

  16. Queen movement during colony emigration in the facultatively polygynous ant Pachycondyla obscuricornis (United States)

    Pezon, Antoine; Denis, Damien; Cerdan, Philippe; Valenzuela, Jorge; Fresneau, Dominique


    In ants, nest relocations are frequent but nevertheless perilous, especially for the reproductive caste. During emigrations, queens are exposed to predation and face the risk of becoming lost. Therefore the optimal strategy should be to move the queen(s) swiftly to a better location, while maintaining maximum worker protection at all times in the new and old nests. The timing of that event is a crucial strategic issue for the colony and may depend on queen number. In monogynous colonies, the queen is vital for colony survival, whereas in polygynous colonies a queen is less essential, if not dispensable. We tested the null hypothesis that queen movement occurs at random within the sequence of emigration events in both monogynous and polygynous colonies of the ponerine ant Pachycondyla obscuricornis. Our study, based on 16 monogynous and 16 polygynous colony emigrations, demonstrates for the first time that regardless of the number of queens per colony, the emigration serial number of a queen occurs in the middle of all emigration events and adult ant emigration events, but not during brood transport events. It therefore appears that the number of workers in both nests plays an essential role in the timing of queen movement. Our results correspond to a robust colony-level strategy since queen emigration is related neither to colony size nor to queen number. Such an optimal strategy is characteristic of ant societies working as highly integrated units and represents a new instance of group-level adaptive behaviors in social insect colonies.

  17. Migrations in Vojvodina during the 1990s: More immigrants, less emigrants

    Directory of Open Access Journals (Sweden)

    Penev Goran


    Full Text Available The results of the 2002 census deepened our insights into a very intensive immigration of the population into Vojvodina, primarily refugees. At the same time, there also occurred significant emigration movements which still had a much weaker intensity than the immigrational ones. The census statistics only partly included emigration, so the paper used indirect methods to acquire as comprehensive estimate as possible about the scope and character of the emigration of the Vojvodina population in the inter-census period 1991-2002. The results of the estimates indicate that in the period the total net emigration was 73 thousand inhabitants, which is 4 thousand persons less than in the preceding inter-census period. At the same time the net immigration was increased for about 3,5 times (from 62 thousand to 213 thousand. The paper points out to the basic characteristics of the emigration (local, inter-municipal, external. Special attention was paid to the regional aspect of migrations (net immigration, net emigration and migration score in order to determine if there was a close interdependence between the number of the immigrated and emigrated persons in the municipalities. The paper also analyzed the influence of migrations on the process of demographic ageing and change in the national structure of the population.

  18. Act No. 29/1989 on emigration and immigration, 19 October 1989. (United States)


    Hungary Act 29/1989 on emigration and immigration, October 19, 1989 includes fundamental rules which allow the free choice of domicile and specify that emigration from and immigration to Hungary are fundamental rights that may restricted rarely when specified by law. The desire to emigrate shall be declared in person by presenting a document to the authorized body and meeting specified requirements, i.e., being free of public liabilities. The right of emigration is to be registered in the passport with other specified documents. The refusal of registration of the right of emigration or withdrawal of said registered right must be stated in the decision. Specified groups may not emigrate, i.e., persons not properly providing care for their incapable child; no emigration right exists for persons possessing State secrets until 3 years have passed since they possessed State secrets. Repatriation i permitted for all Hungarian subjects living at any time abroad and may not be restricted. Immigration documents must be presented in person to the foreign representation of Hungary. Foreigners staying in Hungary with a valid residence permit may present their application to the police office of their future permanent residence. Specified foreigners may not immigrate: persons having committed a serious crime, or living evilly; those offending state security, public order, health, morals, or the rights and freedoms of others; and those expelled from Hungary. Where emigration and immigration requests have been denied, the party may appeal the decision. The Minister for Home Affairs is authorized to regulate matters of emigration, repatriation, and immigration, in accordance with the Minister for Foreign Affairs.

  19. Emigration from Croatia from 1900 to 2001: Demographic Consequences of the Centuries-Old Process

    Directory of Open Access Journals (Sweden)

    Ivo Nejašmić


    Full Text Available In the period between 1900 and 2001, about 2.3 million people emigrated from the present-day territory of the Republic of Croatia. Immigration mitigated the outflow of “human capital”; it replaced almost a half of the total emigrated contingent. The migration “balance deficit” took 33.4% of the average population number, or 52% of the total natural change (increase. Only a few countries have had such a significant population loss due to emigration. Total Croatian population losses in the observed period amount to about 1.89 million people, and some categories have the following share: negative emigration balance 63.3%, war losses 32.7% and epidemics 4.0%. If there were no emigration (i.e. in a hypothetical “closed population”, Croatia would have at least 6.22 million people in 2001 or 40.1% more than the registered number. The long-term (delayed effects of emigration have also come to the fore. The emigration of the most vital age groups has led to the narrowing of fertile cohorts, and consequently to a decrease in birth rates and increased mortality. In the early 1990s, negative natural change was recorded. Several factors affected biological (natural depopulation, but emigration took the first place. Continuous and strong emigration, and negative net migration respectively, is one of the main reasons underlying the fact that Croatia belongs to the group of ten European countries with the oldest population. After the 19th century, in which the population of Croatia doubled, and the 20th century, when the country saw weak growth (40.4%, the 21st century will be marked by depopulation. A highly negative migration balance from the analyzed centennial period has an important role among many factors having impact on such Croatian demographic perspective.

  20. Genomic Typing of Red Cell Antigens (United States)


    Antigen‐Matched  Red  Cells  for  Sickle  Cell  Anemia   Patients  Using  Molecular Typing to Augment Testing: Meghan Delaney, Prashant Gaur, Askale...Storry JR &  Delaney, M. CASE  REPORT OF TESTING AND MANAGEMENT OF BOMBAY  (OH)  PREGNANCY . XXXIst  International  Congress of the ISBT, Berlin, Germany...JK null Phenotype (Manuscript in preparation).  5. Delaney M et al: A Genetic Impossibility? Case report of Bombay (Oh)  pregnancy  with Group AB

  1. Moving hot cell for LMFBR type reactor

    Energy Technology Data Exchange (ETDEWEB)

    Kanbe, Mitsuru


    A moving hot cell for an LMFBR type reactor is made movable on a reactor operation floor between a position just above the reactor container and a position retreated therefrom. Further, it comprises an overhung portion which can incorporate a spent fuel just thereunder, and a crane for moving a fuel assembly between a spent fuel cask and a reactor container. Further, an opening/closing means having a shielding structure is disposed to the bottom portion and the overhung portion thereof, to provide a sealing structure, in which only the receiving port for the spent fuel cask faces to the inner side, and the cask itself is disposed at the outside. Upon exchange of fuels, the movable hot cell is placed just above the reactor to take out the spent fuels, so that a region contaminated with primary sodium is limited within the hot cell. On the other hand, upon maintenance and repair for equipments, the hot cell is moved, thereby enabling to provide a not contaminated reactor operation floor. (N.H.).

  2. Homeostatic properties and phenotypic maturation of murine CD4+ pre-thymic emigrants in the thymus.

    Directory of Open Access Journals (Sweden)

    Jie Dong

    Full Text Available After a tightly regulated developmental program in the thymus, "mature" single positive (SP thymocytes leave the thymus and enter the periphery. These newly arrived recent thymic emigrants (RTEs are phenotypically and functionally immature, and will complete a dynamic maturation in the peripheral lymphoid organs before being licensed to be resident naïve T cells. To study the early events occurring in the RTE maturation process, we identified the phenotype of CD4(+ pre-RTEs, a population of CD4(+ SP thymocytes that have acquired the thymus egress capability. Compared to peripheral naïve T cells, CD4(+ pre-RTEs displayed superior survival capability in lymphoreplete mice and faster proliferation under lymphopenic condition. The differences in Bcl2/Bim expression and/or heightened IL-7 signaling pathway may account for the pre-RTEs' better responsiveness to homeostatic signals. Qa2, the expression of which indicates the phenotypic maturation of SPs and RTEs, was found to be upregulated in CD4(+ pre-RTEs in thymic perivascular space. Migratory dendritic cells that surround this region contribute to Qa2 expression in pre-RTEs. The dendritic cell-driven Qa2 induction of CD4(+ pre-RTEs is independent of MHC class II and Aire molecules.

  3. Socio-Psychological Capital, Values And Emigration Intentions Of Russian Youth


    Sergey V. Chuvashov


    This research defines the relatively new concept of socio-psychological capital and examines the interrelation between socio-psychological capital and emigration intentions of Russian youth. Socio-psychological capital is seen as a resource of psychological relations, available to individuals belonging to a group. Socio-psychological capital includes trust, national identity, ethnic tolerance. The research also deals with the theory of planned behaviour, applied to emigration intentions. The ...

  4. Those easily forgotten: the impact of emigration on those left behind. (United States)

    Marchetti-Mercer, Maria C


    Much has been written about the experiences and stresses of those who emigrate. By contrast, little attention has been paid to the experiences of those who stay behind-family members and friends who for various reasons do not to join their loved ones in the destination country. In this article, I describe the experiences of some South Africans whose families and friends have emigrated. This study forms part of a larger research project focusing on the impact of emigration on South African family life. Twenty-one participants were interviewed by means of a semistructured interview at least 6 months after one or more family member(s) and/or friend(s) left South Africa, to explore participants' experiences around their loved ones' emigration. A thematic analysis of the data reveals that those left behind experience various emotions, ranging from emotional ambivalence to anger and distress. Emigration is mostly experienced as a vast loss, almost akin to a "death," bringing about significant changes in social networks and relationships. The therapeutic significance of the findings for those working with emigrant families is also explored.

  5. An emigration versus a globalization perspective of the Lebanese physician workforce: a qualitative study

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    Akl Elie A


    Full Text Available Abstract Background Lebanon is witnessing an increased emigration of physicians. The objective of this study was to understand the perceptions of Lebanese policymakers of this emigration, and elicit their proposals for future policies and strategies to deal with this emigration. Methods We conducted semi-structured individual interviews with the deans of Lebanon’s seven medical schools, the presidents of the two physicians professional associations, and governmental officials. We analyzed the results qualitatively. Results Participants differed in the assessment of the extent and gravity of emigration. Lebanon has a surplus of physicians, driven largely by the over-production of graduates by a growing number of medical schools. Participants cited advantages and disadvantages of the emigration on the personal, financial, medical education system, healthcare system, and national levels. Proposed strategies included limiting the number of students entering medical schools, creating job opportunities for graduating students, and implementing quality standards. Most participants acknowledged the globalization of the Lebanese physician workforce, including exchanges with the Gulf region, exchanges with developed countries, and the involvement of North American medical education institutions in the region. Conclusion Many Lebanese policy makers, particularly deans of medical schools, perceive the emigration of the physician workforce as an opportunity in the context of the globalization of the profession.

  6. Emigration and Economic Crisis: Recent Evidence from Uruguay

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    Adela Pellegrino


    Full Text Available Uruguay es uno de los países sudamericanos con una proporción significativa de su población viviendo en el exterior. Desde los años setenta, el país ha tenido una emigración neta. Aunque esta tendencia se debilitó a principios de los noventa, recobró fuerza con la llegada de una severa crisis económica en 1999. En este artículo se discuten las características de la migración reciente de uruguayos y se pone en evidencia la relación entre crisis económica y emigración. El volumen del flujo poblacional en 2002 es comparable con las olas de migración que tuvieron lugar en los setenta. Los emigrantes con educación universitaria están sobrerrepresentados en comparación con la población general. Existe una correlación entre el acceso a redes de emigrantes uruguayos en los países de destino y la probabilidad de que un hogar haya tenido un miembro que emigró en 2002.

  7. Re-emigration Capacity of the Brown Planthopper, Nilaparvata lugens%褐飞虱的再迁飞能力

    Institute of Scientific and Technical Information of China (English)

    封传红; 翟保平; 张孝羲


    Re-emigration potential of the brown planthopper (BPH),Nilaparvata lugens after an emigration and feeding different resistant varieties was simulated. Tethered flight of brown planthopper on a set of computerized flight mill revealed that the natural population of BPH in the rice cropping areas of the lower reaches of Yangtze River consisted of individuals with different flight characteristics, i.e., deposited type (flying less than 20 min), migratory type (flying more than 20 min, MT), strong migratory type (flying more than 160 min, SMT) and re-emigration type (2nd flying more than 20 min, RET). The flight capability and the differentiation of the MT of BPH was influenced significantly by the nutritive conditions. The individuals feeding on the sensitive varieties at heading stage would show a lower ratio of MT, but a stronger ability of migration and re-emigration among their MT individuals. The RET rate would be increased markedly by keeping apart the females, and the SMT individuals would display higher performance of re-emigration. There would only be 0.84 and 4.9 percent of the RET BPH among the natural populations and MT individuals respectively.%通过室内模拟试验研究了褐飞虱经过一次远迁降落、取食不同食料后的再迁飞能力。根据吊飞试验测得的飞行能力可将褐飞虱种群分为居留型(小于20min)、迁飞型(20min以上)、强迁飞型(160min以上)和再迁飞型(二次吊飞飞行20min以上)。不同营养条件对褐飞虱的飞行能力和迁飞型的分化有显著影响,早期营养条件好(取食穗期感性水稻品种)的迁飞型比率较低,但迁飞型个体的飞行能力和再迁飞能力均较强。未交配能显著提高再迁飞型比率。自然种群中褐飞虱再迁飞型比率仅占0.84%,吊飞一次后的迁飞型个体再次吊飞时的再迁飞型比率为4.9%,且强迁飞型个体具有较强的再迁飞能力。

  8. Emigration, mutations sociales et changements culinaires en pays mixtèque (Oaxaca, Mexique

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    Esther Katz


    Full Text Available Comme dans d’autres régions du Mexique, les paysans du haut pays mixtèque (Etat d’Oaxaca ne vivent pratiquement plus de l’agriculture, sinon des revenus de leurs parents émigrés aux États-Unis. Dans la région, le phénomène de la migration a énormément augmenté au cours des dix dernières années. Comme la majorité des jeunes adultes émigrent, de nombreux foyers ne sont plus composés que de la mère et des enfants ou des grands-parents et des petits-enfants. Avec des ressources monétaires plus importantes, l’équipement des cuisines se modernise, impliquant des bouleversements techniques dans les préparations culinaires ; la consommation de viande et d’aliments industriels augmente tandis que celle de légumes spontanés diminue. Simultanément, divers programmes de développement, impulsés par le gouvernement, provoquent des changements profonds au niveau de l’économie familiale, de l’organisation sociale et du rôle des femmes. Actuellement le statut économique des familles ne dépend plus de l’étendue de leurs terres, mais du nombre de leurs membres qui travaillent « au Nord ». Néanmoins, le riche patrimoine culinaire de cette population est préservé, en particulier à l’occasion des repas festifs.Emigration, Social Mutations And Food Changes In The Mixtec Highlands (Oaxaca, MexicoLike in many regions of Mexico, farmers of the Mixtec Highlands, for the most part, no longer make a living from agriculture, but rather rely on money sent home by migrant family members. People from this region have been migrating for several decades, but this phenomenon, now mainly to the United States, has tremendously increased in the past ten years. Since most young adults have migrated, many households are composed of mothers and children or grandparents and grandchildren. As more monetary resources are available, the kitchen equipment is more modern, resulting in technical changes in culinary preparations. Meat and

  9. Activation of Type II Cells into Regenerative Stem Cell Antigen-1+ Cells during Alveolar Repair (United States)

    Kumar, Varsha Suresh; Zhang, Wei; Rehman, Jalees; Malik, Asrar B.


    The alveolar epithelium is composed of two cell types: type I cells comprise 95% of the gas exchange surface area, whereas type II cells secrete surfactant, while retaining the ability to convert into type I cells to induce alveolar repair. Using lineage-tracing analyses in the mouse model of Pseudomonas aeruginosa–induced lung injury, we identified a population of stem cell antigen (Sca)-1–expressing type II cells with progenitor cell properties that mediate alveolar repair. These cells were shown to be distinct from previously reported Sca-1–expressing bronchioalveolar stem cells. Microarray and Wnt reporter studies showed that surfactant protein (Sp)-C+Sca-1+ cells expressed Wnt signaling pathway genes, and inhibiting Wnt/β-catenin signaling prevented the regenerative function of Sp-C+Sca-1+ cells in vitro. Thus, P. aeruginosa–mediated lung injury induces the generation of a Sca-1+ subset of type II cells. The progenitor phenotype of the Sp-C+Sca-1+ cells that mediates alveolar epithelial repair might involve Wnt signaling. PMID:25474582

  10. Lung ICAM-1 and ICAM-2 support spontaneous intravascular effector lymphocyte entrapment but are not required for neutrophil entrapment or emigration inside endotoxin-inflamed lungs. (United States)

    Petrovich, Ekaterina; Feigelson, Sara W; Stoler-Barak, Liat; Hatzav, Miki; Solomon, Adam; Bar-Shai, Amir; Ilan, Neta; Li, Jin-Ping; Engelhardt, Britta; Vlodavsky, Israel; Alon, Ronen


    The pulmonary vasculature constitutively expresses the integrin lymphocyte function-associated antigen-1 ligands intercellular adhesion molecule (ICAM)-1 and -2. In this study, effector T cells were temporarily entrapped by the lung vasculature on their way to inflamed lymph nodes, and this entrapment was strongly reduced in ICAM-1 and -2 double-deficient mice (79 and 86% reduction for CD8(+) and CD4(+) effectors, respectively, compared with wild-type mice). Although the pulmonary vasculature has been suggested to be masked by the heparan sulfate-containing glycocalyx, which is susceptible to heparanase-mediated shedding, lung and lymphocyte heparanase have been found to be unnecessary for this entrapment. Systemic LPS induced rapid neutrophil entrapment in the lung vasculature, but in contrast to T-cell entrapment, this sequestration was ICAM-1, ICAM-2, and heparanase independent. Furthermore, neutrophil migration into the bronchoalveolar space induced by LPS inhalation and LPS-induced leakage of red blood cells into this space were not dependent on lung ICAMs or heparanase activity. Nevertheless, heparanase was critical for neutrophil accumulation in smoke-exposed lungs. Our results indicate that, whereas T cells use ICAM-1 and -2 for temporary pulmonary entrapment, neutrophils get sequestered and extravasate into inflamed lungs independent of ICAMs. This is the first demonstration that the pulmonary vasculature is differentially recognized by T cells and neutrophils.-Petrovich, E., Feigelson, S. W., Stoler-Barak, L., Hatzav, M., Solomon, A., Bar-Shai, A., Ilan, N., Li, J.-P., Engelhardt, B., Vlodavsky, I., Alon, R. Lung ICAM-1 and ICAM-2 support spontaneous intravascular effector lymphocyte entrapment but are not required for neutrophil entrapment or emigration inside endotoxin-inflamed lungs.

  11. A Web-Server of Cell Type Discrimination System

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    Anyou Wang


    Full Text Available Discriminating cell types is a daily request for stem cell biologists. However, there is not a user-friendly system available to date for public users to discriminate the common cell types, embryonic stem cells (ESCs, induced pluripotent stem cells (iPSCs, and somatic cells (SCs. Here, we develop WCTDS, a web-server of cell type discrimination system, to discriminate the three cell types and their subtypes like fetal versus adult SCs. WCTDS is developed as a top layer application of our recent publication regarding cell type discriminations, which employs DNA-methylation as biomarkers and machine learning models to discriminate cell types. Implemented by Django, Python, R, and Linux shell programming, run under Linux-Apache web server, and communicated through MySQL, WCTDS provides a friendly framework to efficiently receive the user input and to run mathematical models for analyzing data and then to present results to users. This framework is flexible and easy to be expended for other applications. Therefore, WCTDS works as a user-friendly framework to discriminate cell types and subtypes and it can also be expended to detect other cell types like cancer cells.

  12. Localized Castleman disease of plasma cell type in the abdomen

    Institute of Scientific and Technical Information of China (English)

    LU Zhi-hua; WU Mei


    Castleman disease is a relatively rare entity,with the hyaline-vascular type the predominant form.Although the plasma cell type is uncommon,it still comprises approximately 10% of cases of localized diseases.In addition,the abdomen is a rare site for involvement and localized Castleman disease of the plasma cell type in the abdomen is rare.The radiologic features of localized plasma cell type in the abdomen are mostly limited to case reports.In addition to the conventional imaging findings,we present some new imaging findings of localized plasma cell type in the abdomen.

  13. The selection and function of cell type-specific enhancers. (United States)

    Heinz, Sven; Romanoski, Casey E; Benner, Christopher; Glass, Christopher K


    The human body contains several hundred cell types, all of which share the same genome. In metazoans, much of the regulatory code that drives cell type-specific gene expression is located in distal elements called enhancers. Although mammalian genomes contain millions of potential enhancers, only a small subset of them is active in a given cell type. Cell type-specific enhancer selection involves the binding of lineage-determining transcription factors that prime enhancers. Signal-dependent transcription factors bind to primed enhancers, which enables these broadly expressed factors to regulate gene expression in a cell type-specific manner. The expression of genes that specify cell type identity and function is associated with densely spaced clusters of active enhancers known as super-enhancers. The functions of enhancers and super-enhancers are influenced by, and affect, higher-order genomic organization.

  14. Functional identification of islet cell types by electrophysiological fingerprinting (United States)

    Zhang, Quan; Vergari, Elisa; Kellard, Joely A.; Rodriguez, Blanca; Ashcroft, Frances M.; Rorsman, Patrik


    The α-, β- and δ-cells of the pancreatic islet exhibit different electrophysiological features. We used a large dataset of whole-cell patch-clamp recordings from cells in intact mouse islets (N = 288 recordings) to investigate whether it is possible to reliably identify cell type (α, β or δ) based on their electrophysiological characteristics. We quantified 15 electrophysiological variables in each recorded cell. Individually, none of the variables could reliably distinguish the cell types. We therefore constructed a logistic regression model that included all quantified variables, to determine whether they could together identify cell type. The model identified cell type with 94% accuracy. This model was applied to a dataset of cells recorded from hyperglycaemic βV59M mice; it correctly identified cell type in all cells and was able to distinguish cells that co-expressed insulin and glucagon. Based on this revised functional identification, we were able to improve conductance-based models of the electrical activity in α-cells and generate a model of δ-cell electrical activity. These new models could faithfully emulate α- and δ-cell electrical activity recorded experimentally. PMID:28275121

  15. GABAergic cell types in the lizard hippocampus. (United States)

    Guirado, S; Dávila, J C


    The neurochemical classification of GABAergic cells in the lizard hippocampus resulted in a further division into four major, non-overlapping subtypes. Each GABAergic cell subtype displays specific targets on the principal hippocampal neurons. The synaptic targets of the GABA/neuropeptide subtype are the distal apical dendrites of principal neurons. Calretinin- and parvalbumin-containing GABAergic cells synapse on the cell body and proximal dendrites of principal cells. Calbindin is expressed in a distinct group of interneurons, the synapses of which are directed to the dendrites of principal neurons. Finally, another subtype displays NADPH-diaphorase activity, but its synaptic target has not been established.

  16. Gene expression profile of renal cell carcinoma clear cell type

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    Marcos F. Dall’Oglio


    Full Text Available PURPOSE: The determination of prognosis in patients with renal cell carcinoma (RCC is based, classically, on stage and histopathological aspects. The metastatic disease develops in one third of patients after surgery, even in localized tumors. There are few options for treating those patients, and even the new target designed drugs have shown low rates of success in controlling disease progression. Few studies used high throughput genomic analysis in renal cell carcinoma for determination of prognosis. This study is focused on the identification of gene expression signatures in tissues of low-risk, high-risk and metastatic RCC clear cell type (RCC-CCT. MATERIALS AND METHODS: We analyzed the expression of approximately 55,000 distinct transcripts using the Whole Genome microarray platform hybridized with RNA extracted from 19 patients submitted to surgery to treat RCC-CCT with different clinical outcomes. They were divided into three groups (1 low risk, characterized by pT1, Fuhrman grade 1 or 2, no microvascular invasion RCC; (2 high risk, pT2-3, Fuhrman grade 3 or 4 with, necrosis and microvascular invasion present and (3 metastatic RCC-CCT. Normal renal tissue was used as control. RESULTS: After comparison of differentially expressed genes among low-risk, high-risk and metastatic groups, we identified a group of common genes characterizing metastatic disease. Among them Interleukin-8 and Heat shock protein 70 were over-expressed in metastasis and validated by real-time polymerase chain reaction. CONCLUSION: These findings can be used as a starting point to generate molecular markers of RCC-CCT as well as a target for the development of innovative therapies.

  17. Freedom of expression: cell-type-specific gene profiling. (United States)

    Otsuki, Leo; Cheetham, Seth W; Brand, Andrea H


    Cell fate and behavior are results of differential gene regulation, making techniques to profile gene expression in specific cell types highly desirable. Many methods now enable investigation at the DNA, RNA and protein level. This review introduces the most recent and popular techniques, and discusses key issues influencing the choice between these such as ease, cost and applicability of information gained. Interdisciplinary collaborations will no doubt contribute further advances, including not just in single cell type but single-cell expression profiling.

  18. Private sector contributions and their effect on physician emigration in the developing world. (United States)

    Loh, Lawrence C; Ugarte-Gil, Cesar; Darko, Kwame


    The contribution made by the private sector to health care in a low- or middle-income country may affect levels of physician emigration from that country. The increasing importance of the private sector in health care in the developing world has resulted in newfound academic interest in that sector's influences on many aspects of national health systems. The growth in physician emigration from the developing world has led to several attempts to identify both the factors that cause physicians to emigrate and the effects of physician emigration on primary care and population health in the countries that the physicians leave. When the relevant data on the emerging economies of Ghana, India and Peru were investigated, it appeared that the proportion of physicians participating in private health-care delivery, the percentage of health-care costs financed publicly and the amount of private health-care financing per capita were each inversely related to the level of physician expatriation. It therefore appears that private health-care delivery and financing may decrease physician emigration. There is clearly a need for similar research in other low- and middle-income countries, and for studies to see if, at the country level, temporal trends in the contribution made to health care by the private sector can be related to the corresponding trends in physician emigration. The ways in which private health care may be associated with access problems for the poor and therefore reduced equity also merit further investigation. The results should be of interest to policy-makers who aim to improve health systems worldwide.

  19. Effect of Climate-Induced Change in Crop Yields on Emigration: The Case of Mexico (United States)

    Oppenheimer, M.; Krueger, A. B.; Feng, S.


    Researchers have suggested several channels through which future global warming could trigger mass migration across country borders. This paper examines one of them by focusing on the effect of climate- induced crop failures on out-migration. Using data from Mexico, we identify and estimate elasticity of emigration with respect to changes in crop yield, which sheds light on the possible magnitudes of migrant flows for other areas of the world under different climate change scenarios. We choose Mexico as the study object as it is by far the largest migrant-sending country, with an estimated number of emigrants living in the United States to be well over 10 million. In addition, over 20% of Mexico population directly relies on the agricultural sector, which is heavily dependent on climate. For example, the prolonged drought from 1996 to 1998 in northern Mexico resulted in mass crop failures and the death of livestock. Historically, farmers have been using emigration as an adaptation strategy to cope with crop yield reductions. We first examine the relationship between corn yields and climate variables for the period of 1980-2000, using state-level data. We find significant positive effects of annual precipitation and annual average temperature, but a negative effect of summer temperature on corn yields. The effects of both annual and summer temperatures are also nonlinear. Our analyses of other crops such as wheat yield very similar results. Using Mexico Census micro data, we calculate the number of emigrants from each state for the periods of 1990-1995 and 1995-2000. We then regress changes in the number of emigrants on changes in crop yields, instrumented by changes in temperatures and precipitation. Our preferred specification gives an elasticity of -4, which suggests that a 25% reduction in crop yields would double the number of emigrants. The null hypothesis of no effect is rejected at the 5% significance level.

  20. Private sector contributions and their effect on physician emigration in the developing world (United States)

    Ugarte-Gil, Cesar; Darko, Kwame


    Abstract The contribution made by the private sector to health care in a low- or middle-income country may affect levels of physician emigration from that country. The increasing importance of the private sector in health care in the developing world has resulted in newfound academic interest in that sector’s influences on many aspects of national health systems. The growth in physician emigration from the developing world has led to several attempts to identify both the factors that cause physicians to emigrate and the effects of physician emigration on primary care and population health in the countries that the physicians leave. When the relevant data on the emerging economies of Ghana, India and Peru were investigated, it appeared that the proportion of physicians participating in private health-care delivery, the percentage of health-care costs financed publicly and the amount of private health-care financing per capita were each inversely related to the level of physician expatriation. It therefore appears that private health-care delivery and financing may decrease physician emigration. There is clearly a need for similar research in other low- and middle-income countries, and for studies to see if, at the country level, temporal trends in the contribution made to health care by the private sector can be related to the corresponding trends in physician emigration. The ways in which private health care may be associated with access problems for the poor and therefore reduced equity also merit further investigation. The results should be of interest to policy-makers who aim to improve health systems worldwide. PMID:23476095

  1. Cui-ui reproductive success from potential egg deposition to larval emigration (United States)

    Scoppettone, G. Gary; Rissler, Peter H.


    From 1985 to 2006, we tracked cui-ui, Chasmistes cujus, survival from potential egg deposition of migrating spawners to emigrating larvae. Tahoe sucker larvae emigrated to Pyramid Lake the same time as cui-ui larvae, but cui-ui was the predominant catostomid larvae we captured. Survival of cui-ui larvae ranged from 0.46% to 21.17%, declining significantly with decreased flow and increased number of spawners (P cui-ui spawners, along with sufficient stream flows, may enhance early life-stage survival.

  2. Pathogenic memory type Th2 cells in allergic inflammation. (United States)

    Endo, Yusuke; Hirahara, Kiyoshi; Yagi, Ryoji; Tumes, Damon J; Nakayama, Toshinori


    Immunological memory is a hallmark of adaptive immunity. Memory CD4 T helper (Th) cells are central to acquired immunity, and vaccines for infectious diseases are developed based on this concept. However, memory Th cells also play a critical role in the pathogenesis of various chronic inflammatory diseases, including asthma. We refer to these populations as 'pathogenic memory Th cells.' Here, we review recent developments highlighting the functions and characteristics of several pathogenic memory type Th2 cell subsets in allergic inflammation. Also discussed are the similarities and differences between pathogenic memory Th2 cells and recently identified type 2 innate lymphoid cells (ILC2), focusing on cytokine production and phenotypic profiles.

  3. Observations on Forced Colony Emigration in Parachartergus fraternus (Hymenoptera: Vespidae: Epiponini: New Nest Site Marked with Sprayed Venom

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    Sidnei Mateus


    Full Text Available Five cases of colony emigration induced by removal of nest envelope and combs and a single one by manipulation are described. The disturbance was followed by defensive patterns, buzz running, and adult dispersion. An odor trail created by abdomen dragging, probably depositing venom or Dufour's gland secretions, connected the original nest to the newly selected nesting place and guided the emigration. The substrate of the selected nesting place is intensely sprayed with venom prior to emigration, and this chemical cue marked the emigration end point. The colony moves to the new site in a diffuse cloud with no temporary clusters formed along the odor trail. At the original nest, scouts performed rapid gaster dragging and intense mouth contacts stimulating inactive individuals to depart. Males were unable to follow the swarm. Individual scouts switched between different behavioral tasks before and after colony emigration. Pulp collected from the old nest was reused at the new nest site.

  4. Characterization of cloned cells from an immortalized fetal pulmonary type II cell line

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, R.F.; Waide, J.J.; Lechner, J.F.


    A cultured cell line that maintained expression of pulmonary type II cell markers of differentiation would be advantageous to generate a large number of homogenous cells in which to study the biochemical functions of type II cells. Type II epithelial cells are the source of pulmonary surfactant and a cell of origin for pulmonary adenomas. Last year our laboratory reported the induction of expression of two phenotypic markers of pulmonary type II cells (alkaline phosphatase activity and surfactant lipid synthesis) in cultured fetal rat lung epithelial (FRLE) cells, a spontaneously immortalized cell line of fetal rat lung type II cell origin. Subsequently, the induction of the ability to synthesize surfactant lipid became difficult to repeat. We hypothesized that the cell line was heterogenuous and some cells were more like type II cells than others. The purpose of this study was to test this hypothesis and to obtain a cultured cell line with type II cell phenotypic markers by cloning several FRLE cells and characterizing them for phenotypic markers of type II cells (alkaline phosphatase activity and presence of surfactant lipids). Thirty cloned cell lines were analyzed for induced alkaline phosphatase activity (on x-axis) and for percent of phospholipids that were disaturated (i.e., surfactant).

  5. Functional cell types in taste buds have distinct longevities.

    Directory of Open Access Journals (Sweden)

    Isabel Perea-Martinez

    Full Text Available Taste buds are clusters of polarized sensory cells embedded in stratified oral epithelium. In adult mammals, taste buds turn over continuously and are replenished through the birth of new cells in the basal layer of the surrounding non-sensory epithelium. The half-life of cells in mammalian taste buds has been estimated as 8-12 days on average. Yet, earlier studies did not address whether the now well-defined functional taste bud cell types all exhibit the same lifetime. We employed a recently developed thymidine analog, 5-ethynil-2'-deoxyuridine (EdU to re-evaluate the incorporation of newly born cells into circumvallate taste buds of adult mice. By combining EdU-labeling with immunostaining for selected markers, we tracked the differentiation and lifespan of the constituent cell types of taste buds. EdU was primarily incorporated into basal extragemmal cells, the principal source for replenishing taste bud cells. Undifferentiated EdU-labeled cells began migrating into circumvallate taste buds within 1 day of their birth. Type II (Receptor taste cells began to differentiate from EdU-labeled precursors beginning 2 days after birth and then were eliminated with a half-life of 8 days. Type III (Presynaptic taste cells began differentiating after a delay of 3 days after EdU-labeling, and they survived much longer, with a half-life of 22 days. We also scored taste bud cells that belong to neither Type II nor Type III, a heterogeneous group that includes mostly Type I cells, and also undifferentiated or immature cells. A non-linear decay fit described these cells as two sub-populations with half-lives of 8 and 24 days respectively. Our data suggest that many post-mitotic cells may remain quiescent within taste buds before differentiating into mature taste cells. A small number of slow-cycling cells may also exist within the perimeter of the taste bud. Based on their incidence, we hypothesize that these may be progenitors for Type III cells.

  6. Majority Children's Evaluation of Acculturation Preferences of Immigrant and Emigrant Peers (United States)

    Verkuyten, Maykel; Thijs, Jochem; Sierksma, Jellie


    Using an experimental design, native majority group children (8-13 years, N = 842) evaluated acculturation strategies (assimilation, integration, and separation) adopted by immigrant and emigrant peers. There were medium to large effects of the perceived acculturation strategies on children's peer evaluations. Overall, assimilation was valued…

  7. From Emigration to Immigration: New Dawn for an Intercultural 21st Century Ireland (United States)

    Mutwarasibo, Fidele


    Within the course of a decade Ireland has emerged from being a country of emigration to a country of immigration. Since the mid-1990s, Ireland has undergone rapid economic expansion with the recent economic growth resulting in approximately 252,000 migrants entering Ireland over the last 6 years, according to the Irish Times (2003). While a large…

  8. Cyclically-Determined Homeward Flows of Migrant Workers and the Effects of Emigration. (United States)

    Kayser, Bernard

    This study of the effects of emigrant labor in Europe is focused on the statistics of the homeward flows of migrant labor. The 1966-67 economic recession led to a steep decline in the employment of foreigners and a corresponding increase in the number of returnees home. Cyclicall-determined homeward flows were substantial and numerous and…

  9. Type I Interferons and Natural Killer Cell Regulation in Cancer (United States)

    Müller, Lena; Aigner, Petra; Stoiber, Dagmar


    Type I interferons (IFNs) are known to mediate antitumor effects against several tumor types and have therefore been commonly used in clinical anticancer treatment. However, how IFN signaling exerts its beneficial effects is only partially understood. The clinically relevant activity of type I IFNs has been mainly attributed to their role in tumor immune surveillance. Different mechanisms have been postulated to explain how type I IFNs stimulate the immune system. On the one hand, they modulate innate immune cell subsets such as natural killer (NK) cells. On the other hand, type I IFNs also influence adaptive immune responses. Here, we review evidence for the impact of type I IFNs on immune surveillance against cancer and highlight the role of NK cells therein.

  10. Ovarian Small Cell Carcinoma Hypercalcemic Type: A Case Report

    LENUS (Irish Health Repository)

    Rahma, M B.


    A 31-year-old female was diagnosed with small cell carcinoma of the ovary hypercalcaemic type (OSCCHT) post left oophorectomy. This is a rare aggressive ovarian tumour of which less than 300 cases were reported.

  11. IL-10-Producing Type 1 Regulatory T Cells and Allergy

    Institute of Scientific and Technical Information of China (English)

    Kui Wu; Yutian Bi; Kun Sun; Changzheng Wang


    As an important subset of regulatory T (Treg) cells, IL-10-producing type 1 regulatory T cells (Tr1), have some different features to thymic-derived naturally occurring CD4+CD25+Foxp3+ Treg cells(nTreg cells). Similar to nTreg cells, Tr1 also play important roles in the control of allergic inflammation in several ways. There is a fine balance between Tr1 and Th2 responses in healthy subjects. Skewing of allergic-specific effctor T cells to a Tr1 phenotype appears to be a critical event in successful allergen-specific immunotherapy and glucocorticoids and β2-agonists treatment. Tr1 suppress Th2 cells and effector cells of allergic inflammation, such as eosinophils, mast cells, basophils, through producing IL-10, and perhaps TGF-β. Understanding of Tr1 may be helpful in developing new strategies for treatment of allergic diseases.

  12. Gene pair signatures in cell type transcriptomes reveal lineage control (United States)

    Heinäniemi, Merja; Nykter, Matti; Kramer, Roger; Wienecke-Baldacchino, Anke; Sinkkonen, Lasse; Zhou, Joseph Xu; Kreisberg, Richard; Kauffman, Stuart A.; Huang, Sui; Shmulevich, Ilya


    The distinct cell types of multicellular organisms arise due to constraints imposed by gene regulatory networks on the collective change of gene expression across the genome, creating self-stabilizing expression states, or attractors. We compiled a resource of curated human expression data comprising 166 cell types and 2,602 transcription regulating genes and developed a data driven method built around the concept of expression reversal defined at the level of gene pairs, such as those participating in toggle switch circuits. This approach allows us to organize the cell types into their ontogenetic lineage-relationships and to reflect regulatory relationships among genes that explain their ability to function as determinants of cell fate. We show that this method identifies genes belonging to regulatory circuits that control neuronal fate, pluripotency and blood cell differentiation, thus offering a novel large-scale perspective on lineage specification. PMID:23603899

  13. Reactivity of alveolar epithelial cells in primary culture with type I cell monoclonal antibodies. (United States)

    Danto, S I; Zabski, S M; Crandall, E D


    An understanding of the process of alveolar epithelial cell growth and differentiation requires the ability to trace and analyze the phenotypic transitions that the cells undergo. This analysis demands specific phenotypic probes to type II and, especially, type I pneumocytes. To this end, monoclonal antibodies have been generated to type I alveolar epithelial cells using an approach designed to enhance production of lung-specific clones from a crude lung membrane preparation. The monoclonal antibodies were screened by a combination of enzyme-linked immunosorbent assay and immunohistochemical techniques, with the determination of type I cell specificity resting primarily on immunoelectron microscopic localization. Two of these new markers of the type I pneumocyte phenotype (II F1 and VIII B2) were used to analyze primary cultures of type II cells growing on standard tissue culture plastic and on a variety of substrata reported to affect the morphology of these cells in culture. On tissue culture plastic, the antibodies fail to react with early (days 1 to 3) type II cell cultures. The cells become progressively more reactive with time in culture to a plateau of approximately 6 times background by day 8, with a maximum rate of increase between days 3 and 5. This finding is consistent with the hypothesis that type II cells in primary culture undergo at least partial differentiation into type I cells. Type II cells grown on laminin, which reportedly delays the loss of type II cell appearance, and on fibronectin, which has been reported to facilitate cell spreading and loss of type II cell features, develop the type I cell markers during cultivation in vitro with kinetics similar to those on uncoated tissue culture plastic. Cells on type I collagen and on tissue culture-treated Nuclepore filters, which have been reported to support monolayers with type I cell-like morphology, also increase their expression of the II F1 and VIII B2 epitopes around days 3 to 5. Taken

  14. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin



    Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34+ hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex...

  15. Nanomaterial cytotoxicity is composition, size, and cell type dependent

    Directory of Open Access Journals (Sweden)

    Sohaebuddin Syed K


    Full Text Available Abstract Background Despite intensive research efforts, reports of cellular responses to nanomaterials are often inconsistent and even contradictory. Additionally, relationships between the responding cell type and nanomaterial properties are not well understood. Using three model cell lines representing different physiological compartments and nanomaterials of different compositions and sizes, we have systematically investigated the influence of nanomaterial properties on the degrees and pathways of cytotoxicity. In this study, we selected nanomaterials of different compositions (TiO2 and SiO2 nanoparticles, and multi-wall carbon nanotubes [MWCNTs] with differing size (MWCNTs of different diameters 50 nm; but same length 0.5-2 μm to analyze the effects of composition and size on toxicity to 3T3 fibroblasts, RAW 264.7 macrophages, and telomerase-immortalized (hT bronchiolar epithelial cells. Results Following characterization of nanomaterial properties in PBS and serum containing solutions, cells were exposed to nanomaterials of differing compositions and sizes, with cytotoxicity monitored through reduction in mitochondrial activity. In addition to cytotoxicity, the cellular response to nanomaterials was characterized by quantifying generation of reactive oxygen species, lysosomal membrane destabilization and mitochondrial permeability. The effect of these responses on cellular fate - apoptosis or necrosis - was then analyzed. Nanomaterial toxicity was variable based on exposed cell type and dependent on nanomaterial composition and size. In addition, nanomaterial exposure led to cell type dependent intracellular responses resulting in unique breakdown of cellular functions for each nanomaterial: cell combination. Conclusions Nanomaterials induce cell specific responses resulting in variable toxicity and subsequent cell fate based on the type of exposed cell. Our results indicate that the composition and size of nanomaterials as well as the

  16. Towards Optimal Diagnosis of Type II Germ Cell Tumors

    NARCIS (Netherlands)

    J.A. Stoop (Hans)


    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies pr

  17. Generation of diverse neural cell types through direct conversion

    Institute of Scientific and Technical Information of China (English)

    Gayle; F; Petersen; Padraig; M; Strappe


    A characteristic of neurological disorders is the loss of critical populations of cells that the body is unable to replace,thus there has been much interest in identifying methods of generating clinically relevant numbers of cells to replace those that have been damaged or lost.The process of neural direct conversion,in which cells of one lineage are converted into cells of a neural lineage without first inducing pluripotency,shows great potential,with evidence of the generation of a range of functional neural cell types both in vitro and in vivo,through viral and non-viral delivery of exogenous factors,as well as chemical induction methods.Induced neural cells have been proposed as an attractive alternative to neural cells derived from embryonic or induced pluripotent stem cells,with prospective roles in the investigation of neurological disorders,including neurodegenerative disease modelling,drug screening,and cellular replacement for regenerative medicine applications,however further investigations into improving the efficacy and safety of these methods need to be performed before neural direct conversion becomes a clinically viable option.In this review,we describe the generation of diverse neural cell types via direct conversion of somatic cells,with comparison against stem cell-based approaches,as well as discussion of their potential research and clinical applications.

  18. Cytocompatibility of Three Corneal Cell Types with Amniotic Membrane

    Institute of Scientific and Technical Information of China (English)

    CHENJian-su; CHENRui; XUJin-tang; DINGYong; ZHAOSong-bin; LISui-lian


    Rabbit limbal corneal epithelial cells, corneal endothelial cells and keratocytes were cultured on amniotic membrane. Phase contrast microscope examination was performed daily. Histological and scan electron microscopic examinations were carried out to observe the growth, arrangement and adhesion of cultivated cells. Results showed that three corneal cell types seeded on amniotic membrane grew well and had normal cell morphology. Cultured cells attached firmly on the surface of amniotic membrane. Corneal epithelial cells showed singular layer or stratification. Cell boundaries were formed and tightly opposed. Corneal endothelial cells showed cobblestone or polygonal morphologic characteristics that appeared uniform in size. The cellular arrangement was compact. Keratocytes elongated and showed triangle or dendritic morphology with many intercellular joints which could form networks. In conclusion, amniotic membrane has good scaffold property, diffusion effect and compatibility with corneal cells. The basement membrane side of amniotic membrane facilitated the growth of corneal epithelial cells and endothelial cells and cell junctions were tightly developed. The spongy layer of amniotic membrane facilitated the growth of keratocytes and intercellular joints were rich. Amniotic membrane is an ideal biomaterial for layering tissue engineered cornea.

  19. Asturians in America. Photography, Identity and Traditional Costume in Emigration (1880-1900

    Directory of Open Access Journals (Sweden)

    Fe Santoveña Zapatero


    Full Text Available In the mid-nineteenth century, a sector of Asturian society related to the intellectual elites that espoused romantic regionalism, established clothing stereotypes of that would become known as regional or Asturian costume. These would later be identified with folklore and popular traditions, conveying a territorial and identity unity inherited from a heroic past. Emigrants to Latin America reformulated the aesthetic expression of these outfits in line with local customs, creating a hybrid costume which combined customs remembered from distant Asturias and the cultural expressions of the host countries. Thus clad, Asturian emigrants posed for the picture, leaving graphic testimony of the new mixed identities that emerged in the aftermath of Spanish colonialism overseas.

  20. The production of diaspora: Algerian emigration from colonialism to neo-colonialism (1840-1970). (United States)

    Samers, M


    "This paper is part of a larger project investigating the production and regulation of North African immigrants in the greater Paris automobile industry. Its aims are twofold. First, to reverse the emphasis placed on immigrants in the receiving countries and to (re-)explore the historical production of Algerian emigration into metropolitan industry, more specifically within the automobile industry....Second, in adopting an ¿articulation of modes of production' (AMOP) narrative as an alternative to other Eurocentric approaches, the first part of this paper emphasizes the contradictory layering of various modes which have produced an Algerian colonial diaspora. The latter half of the paper argues that the history of post-independence Algeria confirms that emigration was reinforced through a complex neocolonial relationship during a period of rapid acceleration of Algerian migration to France."

  1. Stochastic differential equation model for linear growth birth and death processes with immigration and emigration (United States)

    Granita, Bahar, A.


    This paper discusses on linear birth and death with immigration and emigration (BIDE) process to stochastic differential equation (SDE) model. Forward Kolmogorov equation in continuous time Markov chain (CTMC) with a central-difference approximation was used to find Fokker-Planckequation corresponding to a diffusion process having the stochastic differential equation of BIDE process. The exact solution, mean and variance function of BIDE process was found.

  2. Stochastic differential equation model for linear growth birth and death processes with immigration and emigration

    Energy Technology Data Exchange (ETDEWEB)

    Granita, E-mail: [Dept. Mathematical Education, State Islamic University of Sultan Syarif Kasim Riau, 28293 Indonesia and Dept. of Mathematical Science, Universiti Teknologi Malaysia, 81310,Johor (Malaysia); Bahar, A. [Dept. of Mathematical Science, Universiti Teknologi Malaysia, 81310,Johor Malaysia and UTM Center for Industrial and Applied Mathematics (UTM-CIAM) (Malaysia)


    This paper discusses on linear birth and death with immigration and emigration (BIDE) process to stochastic differential equation (SDE) model. Forward Kolmogorov equation in continuous time Markov chain (CTMC) with a central-difference approximation was used to find Fokker-Planckequation corresponding to a diffusion process having the stochastic differential equation of BIDE process. The exact solution, mean and variance function of BIDE process was found.

  3. Surgical treatment of unicentric plasma cell histological type Castleman's disease

    Directory of Open Access Journals (Sweden)

    Marić Nebojša


    Full Text Available Introduction. Castleman’s disease or angiofollicular lymph hyperplasia is a rare disease with two identified clinical forms. Unicentric or localized form is characterized by isolated growth of lymph nodes, most often in mediastinum, and multicentric form is expressed as systemic disease with spread lymphadenopathy, organomegaly and presence of general symptoms of the disease. Histological types are hyalovascular, plasma-cell and transitive (mixed cell. Case report. This case report shows a woman, 59 years old, with unicentric form of plasma-cell type of Castleman’s disease. Unicentric form is usually shown as hyalovascular histological type, extremely rare as plasma-cell type, and transitive (mixed cell type was never described in literature as localized clinical form. The disease was manifested with chest pain, loss of body weight, exhaustion and weakness of legs. Further diagnostic procedures found the presence of enlarged lymph nodes paratracheally right, in a close contact with vena cava superior. The disease was confirmed by histopathological analysis of bioptated mediastinal lymph node after mediastinoscopy. Surgical treatment included extirpation of enlarged lymph nodes. After the regular postoperative condition, a full therapy effect was confirmed. Conclusion. Unicentric form of Castleman’s disease is expressed with enlarged lymph nodes on predilected places, usually in mediastinum. Surgical treatment is best method for the management of the disease and brings a full recovery of patient.


    Directory of Open Access Journals (Sweden)

    Mikko Karjalainen,


    Full Text Available Agricultural residues are receiving increasing interest when studying renewable raw materials for industrial use. Residues, generally referred to as nonwood materials, are usually complex materials. Wheat straw is one of the most abundant agricultural residues around the world and is therefore available for extensive industrial use. However, more information of its cell types is needed to utilize wheat straw efficiently in pulp and papermaking. The pulp cell types and particle dimensions of wheat straw were studied, using an optical microscope and an automatic optical fibre analyzer. The role of various cell types in wheat straw pulp and papermaking is discussed. Wheat straw pulp components were categorized according to particle morphology and categorization with an automatic optical analyzer was used to determine wheat straw pulp cell types. The results from automatic optical analysis were compared to those with microscopic analysis and a good correlation was found. Automatic optical analysis was found to be a promising tool for the in-depth analysis of wheat straw pulp cell types.

  5. Alveolar epithelial type II cell: defender of the alveolus revisited

    Directory of Open Access Journals (Sweden)

    Fehrenbach Heinz


    Full Text Available Abstract In 1977, Mason and Williams developed the concept of the alveolar epithelial type II (AE2 cell as a defender of the alveolus. It is well known that AE2 cells synthesise, secrete, and recycle all components of the surfactant that regulates alveolar surface tension in mammalian lungs. AE2 cells influence extracellular surfactant transformation by regulating, for example, pH and [Ca2+] of the hypophase. AE2 cells play various roles in alveolar fluid balance, coagulation/fibrinolysis, and host defence. AE2 cells proliferate, differentiate into AE1 cells, and remove apoptotic AE2 cells by phagocytosis, thus contributing to epithelial repair. AE2 cells may act as immunoregulatory cells. AE2 cells interact with resident and mobile cells, either directly by membrane contact or indirectly via cytokines/growth factors and their receptors, thus representing an integrative unit within the alveolus. Although most data support the concept, the controversy about the character of hyperplastic AE2 cells, reported to synthesise profibrotic factors, proscribes drawing a definite conclusion today.

  6. Demographic Development of the Island of Brač and the Islanders’ Tendency to Emigrate

    Directory of Open Access Journals (Sweden)

    Jelena Nakićen


    Full Text Available The paper analyses the basic demographic indicators of the Island of Brač and its settlements. Particular focus is on emigration from the island and its effect on demographic development of the island. The paper also presents the results of the survey conducted on the island in 2014. The aim of the survey was to investigate the level of satisfaction related to life on the island, and the respondents’ attitude toward emigration. Since the survey encompassed 151 permanent residents of the Island of Brač, the sample cannot be regarded as representative, so the survey results were not analysed separately, but rather incorporated in the demographic analysis. Throughout most of the 20th century, the Croatian insular area was characterised by intensive depopulation. Peak population on the islands was recorded in 1921, and it was followed by a long period of population decline, which lasted until 1991. However, the peak population on the Island of Brač was recorded in 1900, and it was also followed by a long period of depopulation, which ended in 1981. Official census data indicate that from 1981 until the present day Brač has recorded population increase, but that increase is actually fictitious (it was actually caused by “administrative immigration” – people increasingly registered their residence on the island in order to gain certain benefits regardless of their actual place of living or residence. Analysis of the population trends on the Island of Brač shows that in the period from 1857 to 1900, all the settlements on the island had population increase due to very favourable economic situation on the island brought by the vine-growing expansion. Economic prosperity of the island and high birth rates in the first phase of demographic transition resulted in rapid population growth. However, after the Wine Clause had been signed in 1891, and particularly after 1910, when phylloxera devastated the local vineyards, the insular economy

  7. Connectivity between the OFF bipolar type DB3a and six types of ganglion cell in the marmoset retina. (United States)

    Masri, Rania A; Percival, Kumiko A; Koizumi, Amane; Martin, Paul R; Grünert, Ulrike


    Parallel visual pathways originate at the first synapse in the retina, where cones make connections with cone bipolar cells that in turn contact ganglion cells. There are more ganglion cell types than bipolar types, suggesting that there must be divergence from bipolar to ganglion cells. Here we analyze the contacts between an OFF bipolar type (DB3a) and six ganglion cell types in the retina of the marmoset monkey (Callithrix jacchus). Ganglion cells were transfected via particle-mediated gene transfer of an expression plasmid for the postsynaptic density 95-green fluorescent protein (PSD95-GFP), and DB3a cells were labeled via immunohistochemistry. Ganglion cell types that fully or partially costratified with DB3a cells included OFF parasol, OFF midget, broad thorny, recursive bistratified, small bistratified, and large bistratified cells. On average, the number of DB3a contacts to parasol cells (18 contacts per axon terminal) is higher than that to other ganglion cell types (between four and seven contacts). We estimate that the DB3a output to OFF parasol cells accounts for at least 30% of the total DB3a output. Furthermore, we found that OFF parasol cells receive approximately 20% of their total bipolar input from DB3a cells, suggesting that other diffuse bipolar types also provide input to OFF parasol cells. We conclude that DB3a cells preferentially contact OFF parasol cells but also provide input to other ganglion cell types.

  8. Is Transforming Stem Cells to Pancreatic Beta Cells Still the Holy Grail for Type 2 Diabetes? (United States)

    Kahraman, Sevim; Okawa, Erin R; Kulkarni, Rohit N


    Diabetes is a progressive disease affecting millions of people worldwide. There are several medications and treatment options to improve the life quality of people with diabetes. One of the strategies for the treatment of diabetes could be the use of human pluripotent stem cells or induced pluripotent stem cells. The recent advances in differentiation of stem cells into insulin-secreting beta-like cells in vitro make the transplantation of the stem cell-derived beta-like cells an attractive approach for treatment of type 1 and type 2 diabetes. While stem cell-derived beta-like cells provide an unlimited cell source for beta cell replacement therapies, these cells can also be used as a platform for drug screening or modeling diseases.

  9. Single-cell transcriptome analysis of fish immune cells provides insight into the evolution of vertebrate immune cell types (United States)

    Ferreira, Lauren; Macaulay, Iain C.; Stubbington, Michael J.T.


    The immune system of vertebrate species consists of many different cell types that have distinct functional roles and are subject to different evolutionary pressures. Here, we first analyzed conservation of genes specific for all major immune cell types in human and mouse. Our results revealed higher gene turnover and faster evolution of trans-membrane proteins in NK cells compared with other immune cell types, and especially T cells, but similar conservation of nuclear and cytoplasmic protein coding genes. To validate these findings in a distant vertebrate species, we used single-cell RNA sequencing of lck:GFP cells in zebrafish and obtained the first transcriptome of specific immune cell types in a nonmammalian species. Unsupervised clustering and single-cell TCR locus reconstruction identified three cell populations, T cells, a novel type of NK-like cells, and a smaller population of myeloid-like cells. Differential expression analysis uncovered new immune-cell–specific genes, including novel immunoglobulin-like receptors, and neofunctionalization of recently duplicated paralogs. Evolutionary analyses confirmed the higher gene turnover of trans-membrane proteins in NK cells compared with T cells in fish species, suggesting that this is a general property of immune cell types across all vertebrates. PMID:28087841

  10. Cell-type specific four-component hydrogel.

    Directory of Open Access Journals (Sweden)

    Timo Aberle

    Full Text Available In the field of regenerative medicine we aim to develop implant matrices for specific tissue needs. By combining two per se, cell-permissive gel systems with enzymatic crosslinkers (gelatin/transglutaminase and fibrinogen/thrombin to generate a blend (technical term: quattroGel, an unexpected cell-selectivity evolved. QuattroGels were porous and formed cavities in the cell diameter range, possessed gelation kinetics in the minute range, viscoelastic properties and a mechanical strength appropriate for general cell adhesion, and restricted diffusion. Cell proliferation of endothelial cells, chondrocytes and fibroblasts was essentially unaffected. In contrast, on quattroGels neither endothelial cells formed vascular tubes nor did primary neurons extend neurites in significant amounts. Only chondrocytes differentiated properly as judged by collagen isoform expression. The biophysical quattroGel characteristics appeared to leave distinct cell processes such as mitosis unaffected and favored differentiation of sessile cells, but hampered differentiation of migratory cells. This cell-type selectivity is of interest e.g. during articular cartilage or invertebral disc repair, where pathological innervation and angiogenesis represent adverse events in tissue engineering.

  11. Role of T Cells in Type 2 Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Chia-Chao Wu


    Full Text Available Type 2 diabetic nephropathy (DN is the most common cause of end-stage renal disease and is increasingly considered as an inflammatory disease characterized by leukocyte infiltration at every stage of renal involvement. Inflammation and activation of the immune system are closely involved in the pathogenesis of diabetes and its microvascular complications. Macrophage has been well recognized to play an important role in type 2 DN, leukocyte infiltration, and participated in process of DN, as was proposed recently. Th1, Th2, Th17, T reg, and cytotoxic T cells are involved in the development and progression of DN. The purpose of this review is to assemble current information concerning the role of T cells in the development and progression of type 2 DN. Specific emphasis is placed on the potential interaction and contribution of the T cells to renal damage. The therapeutic strategies involving T cells in the treatment of type 2 DN are also reviewed. Improving knowledge of the recognition of T cells as significant pathogenic mediators in DN reinforces the possibility of new potential therapeutic targets translated into future clinical treatments.

  12. Towards Optimal Diagnosis of Type II Germ Cell Tumors


    Stoop, Hans


    textabstractThe aim of the work described in this thesis is to improve the understanding of the pathobiology of testicular cancer (type II Germ Cell Tumors) to create possibilities for optimalization of diagnosis for this type of malignancy in routine pathology laboratories. The different studies presented here show valuable additional information on the microscopic diagnostics in daily practice. This enables proper and complete diagnosis of this relative rare variant of cancer ensuring the b...

  13. Cell type specific DNA methylation in cord blood: A 450K-reference data set and cell count-based validation of estimated cell type composition. (United States)

    Gervin, Kristina; Page, Christian Magnus; Aass, Hans Christian D; Jansen, Michelle A; Fjeldstad, Heidi Elisabeth; Andreassen, Bettina Kulle; Duijts, Liesbeth; van Meurs, Joyce B; van Zelm, Menno C; Jaddoe, Vincent W; Nordeng, Hedvig; Knudsen, Gunn Peggy; Magnus, Per; Nystad, Wenche; Staff, Anne Cathrine; Felix, Janine F; Lyle, Robert


    Epigenome-wide association studies of prenatal exposure to different environmental factors are becoming increasingly common. These studies are usually performed in umbilical cord blood. Since blood comprises multiple cell types with specific DNA methylation patterns, confounding caused by cellular heterogeneity is a major concern. This can be adjusted for using reference data consisting of DNA methylation signatures in cell types isolated from blood. However, the most commonly used reference data set is based on blood samples from adult males and is not representative of the cell type composition in neonatal cord blood. The aim of this study was to generate a reference data set from cord blood to enable correct adjustment of the cell type composition in samples collected at birth. The purity of the isolated cell types was very high for all samples (>97.1%), and clustering analyses showed distinct grouping of the cell types according to hematopoietic lineage. We explored whether this cord blood and the adult peripheral blood reference data sets impact the estimation of cell type composition in cord blood samples from an independent birth cohort (MoBa, n = 1092). This revealed significant differences for all cell types. Importantly, comparison of the cell type estimates against matched cell counts both in the cord blood reference samples (n = 11) and in another independent birth cohort (Generation R, n = 195), demonstrated moderate to high correlation of the data. This is the first cord blood reference data set with a comprehensive examination of the downstream application of the data through validation of estimated cell types against matched cell counts.

  14. Erythroid differentiation of human induced pluripotent stem cells is independent of donor cell type of origin. (United States)

    Dorn, Isabel; Klich, Katharina; Arauzo-Bravo, Marcos J; Radstaak, Martina; Santourlidis, Simeon; Ghanjati, Foued; Radke, Teja F; Psathaki, Olympia E; Hargus, Gunnar; Kramer, Jan; Einhaus, Martin; Kim, Jeong Beom; Kögler, Gesine; Wernet, Peter; Schöler, Hans R; Schlenke, Peter; Zaehres, Holm


    Epigenetic memory in induced pluripotent stem cells, which is related to the somatic cell type of origin of the stem cells, might lead to variations in the differentiation capacities of the pluripotent stem cells. In this context, induced pluripotent stem cells from human CD34(+) hematopoietic stem cells might be more suitable for hematopoietic differentiation than the commonly used fibroblast-derived induced pluripotent stem cells. To investigate the influence of an epigenetic memory on the ex vivo expansion of induced pluripotent stem cells into erythroid cells, we compared induced pluripotent stem cells from human neural stem cells and human cord blood-derived CD34(+) hematopoietic stem cells and evaluated their potential for differentiation into hematopoietic progenitor and mature red blood cells. Although genome-wide DNA methylation profiling at all promoter regions demonstrates that the epigenetic memory of induced pluripotent stem cells is influenced by the somatic cell type of origin of the stem cells, we found a similar hematopoietic induction potential and erythroid differentiation pattern of induced pluripotent stem cells of different somatic cell origin. All human induced pluripotent stem cell lines showed terminal maturation into normoblasts and enucleated reticulocytes, producing predominantly fetal hemoglobin. Differences were only observed in the growth rate of erythroid cells, which was slightly higher in the induced pluripotent stem cells derived from CD34(+) hematopoietic stem cells. More detailed methylation analysis of the hematopoietic and erythroid promoters identified similar CpG methylation levels in the induced pluripotent stem cell lines derived from CD34(+) cells and those derived from neural stem cells, which confirms their comparable erythroid differentiation potential.

  15. Engineering controlled mammalian type O-Glycosylation in plant cells

    DEFF Research Database (Denmark)

    Yang, Zhang; Drew, Damian Paul; Jørgensen, Bodil


    Human mucins are large heavily O-glycosylated glycoproteins (>200 kDa), which account for the majority of proteins in mucus layers that e.g. hydrate, lubricate and protect cells from proteases as well as from pathogens. O-linked mucin glycans are truncated in many cancers, yielding truncated cancer...... specific glyco-peptide epitopes, such as the Tn epitope (GalNAc sugar attached to either Serine or Threonine), which are antigenic to the immune system. In the present study, we have identified plant cells as the only eukaryotic cells without mammalian type O-glycosylation or competing (for sites) O...

  16. Type I collagen gel protects murine fibrosarcoma L929 cells from TNFα-induced cell death

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hong-Ju; He, Wen-Qi; Chen, Ling; Liu, Wei-Wei; Xu, Qian; Xia, Ming-Yu; Hayashi, Toshihiko [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China); Fujisaki, Hitomi; Hattori, Shunji [Nippi Research Institute of Biomatrix, Toride, Ibaraki 302-0017 (Japan); Tashiro, Shin-ichi [Institute for Clinical and Biomedical Sciences, Kyoto 603-8072 (Japan); Onodera, Satoshi [Department of Clinical and Pharmaceutical Sciences, Showa Pharmaceutical University, Tokyo 194-8543 (Japan); Ikejima, Takashi, E-mail: [China-Japan Research Institute of Medical and Pharmaceutical Sciences, Shenyang Pharmaceutical University, Shenyang 110016 (China)


    Murine fibrosarcoma L929 cells have been used to test efficacy of proinflammatory cytokine TNFα. In the present study, we reported on protective effect of type I collagen gel used as L929 cell culture. L929 cell grew and proliferated well on collagen gel. However, the L929 cells exhibited cobblestone-like morphology which was much different from the spread fusiform shape when cultured on conventional cell dishes as well as the cells tended to aggregate. On conventional cell culture dishes, the cells treated with TNFα became round in shape and eventually died in a necroptotic manner. The cells cultured on collagen gel, however, were completely unaffected. TNFα treatment was reported to induce autophagy in L929 cells on the plastic dish, and therefore we investigated the effect of collagen gel on induction of autophagy. The results indicated that autophagy induced by TNFα treatment was much reduced when the cells were cultured on collagen gel. In conclusion, type I collagen gel protected L929 cell from TNFα-induced cell death. - Highlights: • Collagen gel culture changed the morphology of L929 cells. • L929 cell cultured on collagen gel were resistant to TNFα-induced cell death. • Collagen gel culture inhibited TNFα-induced autophagy in L929 cells.

  17. Single-cell LEP-type cavity on measurement stand

    CERN Multimedia


    A single-cell cavity, made of copper, with tapered connectors for impedance measurements. It was used as a model of LEP-type superconducting cavities, to investigate impedance and higher-order modes and operated at around 600 MHz (the LEP acceleration frequency was 352.2 MHz). See 8202500.

  18. Susceptibility of different leukocyte cell types to Vaccinia virus infection

    Directory of Open Access Journals (Sweden)

    Sánchez-Puig Juana M


    Full Text Available Abstract Background Vaccinia virus, the prototype member of the family Poxviridae, was used extensively in the past as the Smallpox vaccine, and is currently considered as a candidate vector for new recombinant vaccines. Vaccinia virus has a wide host range, and is known to infect cultures of a variety of cell lines of mammalian origin. However, little is known about the virus tropism in human leukocyte populations. We report here that various cell types within leukocyte populations have widely different susceptibility to infection with vaccinia virus. Results We have investigated the ability of vaccinia virus to infect human PBLs by using virus recombinants expressing green fluorescent protein (GFP, and monoclonal antibodies specific for PBL subpopulations. Flow cytometry allowed the identification of infected cells within the PBL mixture 1–5 hours after infection. Antibody labeling revealed that different cell populations had very different infection rates. Monocytes showed the highest percentage of infected cells, followed by B lymphocytes and NK cells. In contrast to those cell types, the rate of infection of T lymphocytes was low. Comparison of vaccinia virus strains WR and MVA showed that both strains infected efficiently the monocyte population, although producing different expression levels. Our results suggest that MVA was less efficient than WR in infecting NK cells and B lymphocytes. Overall, both WR and MVA consistently showed a strong preference for the infection of non-T cells. Conclusions When infecting fresh human PBL preparations, vaccinia virus showed a strong bias towards the infection of monocytes, followed by B lymphocytes and NK cells. In contrast, very poor infection of T lymphocytes was detected. These finding may have important implications both in our understanding of poxvirus pathogenesis and in the development of improved smallpox vaccines.

  19. A Stromal Cell Niche for Human and Mouse Type 3 Innate Lymphoid Cells. (United States)

    Hoorweg, Kerim; Narang, Priyanka; Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R; Coles, Mark C; Cupedo, Tom


    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation, and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells. Moreover, both cell types are conserved from mice to humans and colocalize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult marginal reticular cells and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs.

  20. Single-cell RNA sequencing identifies distinct mouse medial ganglionic eminence cell types (United States)

    Chen, Ying-Jiun J.; Friedman, Brad A.; Ha, Connie; Durinck, Steffen; Liu, Jinfeng; Rubenstein, John L.; Seshagiri, Somasekar; Modrusan, Zora


    Many subtypes of cortical interneurons (CINs) are found in adult mouse cortices, but the mechanism generating their diversity remains elusive. We performed single-cell RNA sequencing on the mouse embryonic medial ganglionic eminence (MGE), the major birthplace for CINs, and on MGE-like cells differentiated from embryonic stem cells. Two distinct cell types were identified as proliferating neural progenitors and immature neurons, both of which comprised sub-populations. Although lineage development of MGE progenitors was reconstructed and immature neurons were characterized as GABAergic, cells that might correspond to precursors of different CINs were not identified. A few non-neuronal cell types were detected, including microglia. In vitro MGE-like cells resembled bona fide MGE cells but expressed lower levels of Foxg1 and Epha4. Together, our data provide detailed understanding of the embryonic MGE developmental program and suggest how CINs are specified. PMID:28361918

  1. Genes affecting β-cell function in type 1 diabetes

    DEFF Research Database (Denmark)

    Fløyel, Tina; Kaur, Simranjeet; Pociot, Flemming


    Type 1 diabetes (T1D) is a multifactorial disease resulting from an immune-mediated destruction of the insulin-producing pancreatic β cells. Several environmental and genetic risk factors predispose to the disease. Genome-wide association studies (GWAS) have identified around 50 genetic regions...... that affect the risk of developing T1D, but the disease-causing variants and genes are still largely unknown. In this review, we discuss the current status of T1D susceptibility loci and candidate genes with focus on the β cell. At least 40 % of the genes in the T1D susceptibility loci are expressed in human...... islets and β cells, where they according to recent studies modulate the β-cell response to the immune system. As most of the risk variants map to noncoding regions of the genome, i.e., promoters, enhancers, intergenic regions, and noncoding genes, their possible involvement in T1D pathogenesis as gene...

  2. [Pakistan: emigration in the Gulf and its effects on the home economy]. (United States)

    Imdad, N


    Pakistani emigration since the early 1970s has been primarily directed toward the oil-rich Gulf states. Over 2 million Pakistanis, 10% of the adult male workforce, now live outside their home country, 3/4 of them in the Gulf states. The emigration has shortterm advantages for Pakistan, which has a high unemployment rate and few other exports. 2 government bureaus and over 300 recruiting agencies encourage Pakistani emigration to the Gulf, and because of the foreign exchange earnings generated, such emigration has become an important concern of the government. Emigration has a long history in Pakistan as part of the migratory movements of the Indian subcontinent in general. Emigration in the 1960s was prompted by mechanization of agriculture and disturbances of traditional agrarian labor arrangements brought on by the Green Revolution. Concentrations of lands among the successful middle-sized producers led to a rural proletariat and exodus towards the cities, where possibilities of employment were scarce. Regions of declining income around the new capital of Islamabad were the 1st to take advantage of new employment opportunities in the Gulf states. Pakistani migration to the Gulf countries is temporary for individual workers, who stay an average of 3-6 years, but the effect is of chain migration as returning workers are replaced by other family members. Workers are not accompanied by family members and have almost no contact with the local Arab populations. They send most of their earnings to their families in Pakistan. 3/4 are under 30 years old, most are of rural origin, and the majority are from the northern provinces. Although 70% are married, only 4% of migrants, the most highly qualified, are accompanied by their families. About 41% are unskilled workers and 42.6% are semiskilled or skilled manual workers. In 1981, the average annual salary repatriated by a Pakistani working in the Gulf was $3000. The Pakistani government has not defined a migration policy

  3. On emergencies and emigration: how (not) to justify compulsory medical service. (United States)

    Blake, Michael


    I have argued that the best way to understand the supposed right to restrict emigration is with reference to the concept of an emergency; restrictions on emigration are permitted, if at all, only as responses to an emergency situation, and must be judged with reference to the ethics of responding to such an emergency. Eszter Kollar argues, against this, that the concept of 'emergency' fails to describe the actual situation in low/middle-income countries, in which shortages of medical personnel are long-standing problems; she also argues that there is no need to invoke the concept of an emergency, when we might simply discuss these restrictions with reference to the relative importance of the human goods and interests involved. I argue, against Kollar, that we have no reason to think that an emergency must involve novelty; if the moral stakes are significant enough, we have reason to think of a situation as an emergency, regardless of when that situation began. I argue, too, that we have reason to differentiate between restrictions of liberties undertaken as part of the process of specifying liberal freedoms and emergency restrictions of those liberties defended by liberalism itself. The latter, I suggest, ought to be recognised and defended as a distinct moral category, if only to recognise the continuing moral remainder when a liberal right is temporarily suspended under emergency circumstances. I conclude that a permission to restrict emigration is, if at all, only justifiable as an emergency response to unfavourable circumstances, and ought not to be analysed in the more conventional liberal terms Kollar deploys.

  4. Partitioning detectability components in populations subject to within-season temporary emigration using binomial mixture models.

    Directory of Open Access Journals (Sweden)

    Katherine M O'Donnell

    Full Text Available Detectability of individual animals is highly variable and nearly always < 1; imperfect detection must be accounted for to reliably estimate population sizes and trends. Hierarchical models can simultaneously estimate abundance and effective detection probability, but there are several different mechanisms that cause variation in detectability. Neglecting temporary emigration can lead to biased population estimates because availability and conditional detection probability are confounded. In this study, we extend previous hierarchical binomial mixture models to account for multiple sources of variation in detectability. The state process of the hierarchical model describes ecological mechanisms that generate spatial and temporal patterns in abundance, while the observation model accounts for the imperfect nature of counting individuals due to temporary emigration and false absences. We illustrate our model's potential advantages, including the allowance of temporary emigration between sampling periods, with a case study of southern red-backed salamanders Plethodon serratus. We fit our model and a standard binomial mixture model to counts of terrestrial salamanders surveyed at 40 sites during 3-5 surveys each spring and fall 2010-2012. Our models generated similar parameter estimates to standard binomial mixture models. Aspect was the best predictor of salamander abundance in our case study; abundance increased as aspect became more northeasterly. Increased time-since-rainfall strongly decreased salamander surface activity (i.e. availability for sampling, while higher amounts of woody cover objects and rocks increased conditional detection probability (i.e. probability of capture, given an animal is exposed to sampling. By explicitly accounting for both components of detectability, we increased congruence between our statistical modeling and our ecological understanding of the system. We stress the importance of choosing survey locations and

  5. Generation of cloned calves from different types of somatic cells

    Institute of Scientific and Technical Information of China (English)


    Six types of bovine somatic cell lines,including a granulosa cell line of Chinese red-breed yellow cattle(YGR),a granulosa cell line of Holstein cow(HGR),two skin fibroblast cell lines of two adult Holstein cows respectively(AFB1 and AFB2),a skin fibroblast cell line(FFB)and an oviduct epithelial cell line(FOV)of a Holstein fetus,were established.Somatic cell nuclear transfer(SCNT)was carried out using these cells as nuclei donor,and a total of 12 healthy calves were cloned.The effects of different types of donor cells on developmental potential of bovine SCNT embryos were investigated.(i)There was no significant difference in development rates to the blastocyst stage for SCNT embryos from YGR and HGR(33.2% and 35.1%,respectively).Pregnancy rates of them were 33.3% and 30.2%,respectively; and birth rates were 16.7%and 11.6%,respectively.(ii)Development rates to the blastocyst stage for SCNT embryos from diffetent individuals(AFB1 and AFB2)differed significantly(27.9% and 39.4%,respectively,P <0.05).Pregnancy rates of them were 36.2% and 36.4%,respectively; and birth rates were 14.9% and 27.3%,respectively.(iii)There was significant difference in development rates to the blastocyst stage for SCNT embryos from FFB and FOV of the same fetus(37.9% and 41.5%,respectively,P < 0.05).Pregnancy rates of them were 45.7% and 24.1%,respectively; and birth rates were 22.9 % and 10.3%,respectively.Finally,developmental potential of bovine SCNT embryos from all four types of somatic cells from Holstein cows(HGR,AFB,FFB and FOV)were compared.For in vitro development stage,development rates to the blastocyst stage for SCNT embryos from HGR,AFB,FFB and FOV were 35.1%A,29.4%B,37.9%A and 41.5%C,respectively(pABC<0.05); for in vivo development stage,pregnancy rates of them were 30.2%,36.2%,45.7%and 24.1%,respectively; and birth rates of them were 11.6%,17.2%,22.9% and 10.3% respectively.

  6. The STATs in cell stress-type responses

    Directory of Open Access Journals (Sweden)

    Best James


    Full Text Available Abstract In the early 1990's, a new cell signaling pathway was described. This new paradigm, now known as the JAK/STAT pathway, has been extensively investigated in immune-type cells in response to interferons and interleukins. However, recent evidence suggests that the JAK/STAT pathway also mediates diverse cellular responses to various forms of biological stress including hypoxia/reperfusion, endotoxin, ultraviolet light, and hyperosmolarity. The current literature describing the JAK/STAT pathway's role in cellular stress responses has been reviewed herein, but it is clear that our knowledge in this area is far from complete.

  7. Asymptotic regimes for the partition into colonies of a branching process with emigration

    CERN Document Server

    Bertoin, Jean


    We consider a spatial branching process with emigration in which children either remain at the same site as their parents or migrate to new locations and then found their own colonies. We are interested in asymptotics of the partition of the total population into colonies for large populations with rare migrations. Under appropriate regimes, we establish weak convergence of the rescaled partition to some random measure that is constructed from the restriction of a Poisson point measure to a certain random region, and whose cumulant solves a simple integral equation.

  8. [Ernst von der Porten : looking for facts before and after forced emigration]. (United States)

    Goerig, M; Bruijn, L


    The Ernst von der Porten medal has been awarded for many years to exceptional personalities by the Alliance of German Anesthesiologists to honor the outstanding achievements of the physician Ernst von der Porten from Hamburg in the development of anesthesiology as an autonomous discipline Only recent access to hitherto inaccessible documents enabled the reconstruction of his final years. He was persecuted and excluded by the National Socialist (NS) regime due to his Jewish roots and finally forced to emigrate. Records revealed that even in the so-called safe exile, degrading treatment and humiliation continued for Ernst von der Porten and his family. He eventually evaded this situation by committing suicide.

  9. Effects of food limitation and emigration on self-thinning in experimental minnow cohorts (United States)

    Dunham, J.B.; Dickerson, B. R.; Beever, E.; Duncan, R. D.; Vinyard, G.L.


    1. The theory of food-regulated self-thinning (FST) for mobile animals predicts population density (N) to be an inverse function of mean body mass (W) scaled to an exponent (b), such that N = k W−b, where k is a constant. FST also predicts energy requirements (or energy flow) to remain constant over time (termed energetic equivalence) as losses to cohorts (e.g. emigration and mortality) are balanced by increased growth of surviving individuals.

  10. Emigration, immigration and return: Mexican immigrant’s cycle in Calexico, California, USA

    Directory of Open Access Journals (Sweden)

    Norma Fimbres Durazo


    Full Text Available This article describes a community of Mexican immigrants legally residing in the city of Calexico, California. Firstly, a brief review on the history of migration from Mexico to the United States, chiefly to Imperial County, is presented. Afterwards, the traits of the immigrant group is described according to the data coming from a survey that was applied to 407 Mexican immigrants. To conclude, the results provided by the survey on the causes for such emigration, the motives for immigrating, as well as the bearing existing between the immigrant and his/her country of origin, through the return migration, are all presented.

  11. Student Mobility or Emigration Flow? The Case of Students Commuting from Serbia to Hungary

    Directory of Open Access Journals (Sweden)

    Zoltan Takac


    Full Text Available Student mobility between two European countries in transition, Hungary and Serbia, was considered for the period 2001-2010. The high motivation and number of Hungarian-speaking students emigrating/commuting to Hungary began in 1990, with the beginning of the Yugoslav Wars. In 2010, 1,385 Hungarian-speaking students (from Vojvodina, Serbia studied in Hungary and 3,152 in Serbia. Student mobility between Hungary and Serbia is highly concentrated and causes a very low returning rate of educated young elite (approximately 30%. For this reason, the future of the Hungarian minority has begun to be put into question in Serbia, in the Autonomous Province of Vojvodina, where their percentage within whole population is noticeably decreasing (1991: 16.9%, 2001: 14.3%. The research has been focused on answering the following questions: Are there integration conflicts in the autochthon minority within the state borders of Serbia? What can higher education offer to these students? Does the region offer enough to provide perspectives for young members of the elite? Will early student mobility end with continuous emigration? Empirical background: Interviews with young adult migrants from Serbia to Hungary; Location: Serbia. Objective: To examine the motives and willingness to emigrate among the Hungarian young adults/students from Vojvodina. Interview subjects: 18 university/college students or young adults with a diploma (from Vojvodina. It is important to note that only those young adults were interviewed who have returned to Serbia having finished their educational career or who are likely to come back later. Conclusions in brief: The Yugoslav Wars, worsening economic conditions, and low living standards have significantly influenced the willingness of the youth to migrate. The motives of migration among the Hungarian youth in Vojvodina are gaining professional experience, broadening knowledge, and improving language. Hungary is the first target country of

  12. Absence of C-type virus production in human leukemic B cell, T cell and null cell lines.

    Directory of Open Access Journals (Sweden)



    Full Text Available Electron microscope observation of cultured human leukemic B cell, T cell and null cell lines and reverse transcriptase assay of the culture supernatants were all negative for the presence of C-type virus. Bat cell line, which propagates primate C-type viruses well, was cocultivated with the human leukemic cell lines, in the hope of amplification of virus if present. Three weeks after mixed culture, the culture supernatants were again examined for reverse transcriptase activity and the cells were tested for syncytia formation by cocultivation with rat XC, human KC and RSb cell lines. All these tests, except for the positive control using a simian sarcoma virus, were negative, suggesting that no C-type was produced from these human leukemic cell lines.

  13. Preimplantation HLA typing for stem cell transplantation treatment of hemoglobinopathies

    Directory of Open Access Journals (Sweden)

    Anver Kuliev


    Full Text Available Preimplantation genetic diagnosis (PGD for HLA typing is steadily becoming an option for at risk couples with thalassemic children, requiring HLA matched bone marrow transplantation treatment. The paper presents the world’s largest PGD experience of 475 cases for over 2 dozens thalassemia mutations, resulting in birth of 132 unaffected children. A total of 146 cases were performed together with preimplantation HLA typing, resulting in detection and transfer of HLA matched unaffected embryos in 83 of them, yielding the birth of 16 HLA matched children, potential donors for their affected siblings. The presented experience of HLA matched stem cell transplantation for thalassemia, following PGD demonstrated a successful hematopoietic reconstitution both for younger and older patients. The data show that PGD is an efficient approach for HLA matched stem cell transplantation treatment for thalassemia.

  14. Interleukin 18 stimulates HIV type 1 in monocytic cells. (United States)

    Shapiro, L; Puren, A J; Barton, H A; Novick, D; Peskind, R L; Shenkar, R; Gu, Y; Su, M S; Dinarello, C A


    The cytokine interleukin (IL) 18 (formerly interferon gamma-inducing factor) induces the T helper type 1 response. In the present studies, IL-18 increased HIV type 1 (HIV-1) production from 5- to 30-fold in the chronically infected U1 monocytic cell line. Inhibition of tumor necrosis factor (TNF) activity by the addition of TNF-binding protein reduced IL-18-stimulated HIV-1 production by 48%. In the same cultures, IL-18-induced IL-8 was inhibited by 96%. Also, a neutralizing anti-IL-6 mAb reduced IL-18-induced HIV-1 by 63%. Stimulation of U1 cells with IL-18 resulted in increased production of IL-6, and exogenous IL-6 added to U1 cells increased HIV-1 production 4-fold over control. A specific inhibitor of the p38 mitogen-activated protein kinase reduced IL-18-induced HIV-1 by 73%, and a 50% inhibition was observed at 0.05 microM. In the same cultures, IL-8 was inhibited by 87%. By gel-shift and supershift analyses, increased binding activity of the transcription factor NF-kappaB was measured in nuclear extracts from U1 cells 1 h after exposure to IL-18. These results demonstrate induction of HIV-1 by IL-18 in a monocyte target associated with an intermediate role for TNF and IL-6, activation of p38 mitogen-activated protein kinase, and nuclear translocation of NF-kappaB.

  15. Different Types of Cell Death Induced by Enterotoxins

    Directory of Open Access Journals (Sweden)

    Ming-Yuan Hong


    Full Text Available The infection of bacterial organisms generally causes cell death to facilitate microbial invasion and immune escape, both of which are involved in the pathogenesis of infectious diseases. In addition to the intercellular infectious processes, pathogen-produced/secreted enterotoxins (mostly exotoxins are the major weapons that kill host cells and cause diseases by inducing different types of cell death, particularly apoptosis and necrosis. Blocking these enterotoxins with synthetic drugs and vaccines is important for treating patients with infectious diseases. Studies of enterotoxin-induced apoptotic and necrotic mechanisms have helped us to create efficient strategies to use against these well-characterized cytopathic toxins. In this article, we review the induction of the different types of cell death from various bacterial enterotoxins, such as staphylococcal enterotoxin B, staphylococcal alpha-toxin, Panton-Valentine leukocidin, alpha-hemolysin of Escherichia coli, Shiga toxins, cytotoxic necrotizing factor 1, heat-labile enterotoxins, and the cholera toxin, Vibrio cholerae. In addition, necrosis caused by pore-forming toxins, apoptotic signaling through cross-talk pathways involving mitochondrial damage, endoplasmic reticulum stress, and lysosomal injury is discussed.

  16. Different types of cell death induced by enterotoxins. (United States)

    Lin, Chiou-Feng; Chen, Chia-Ling; Huang, Wei-Ching; Cheng, Yi-Lin; Hsieh, Chia-Yuan; Wang, Chi-Yun; Hong, Ming-Yuan


    The infection of bacterial organisms generally causes cell death to facilitate microbial invasion and immune escape, both of which are involved in the pathogenesis of infectious diseases. In addition to the intercellular infectious processes, pathogen-produced/secreted enterotoxins (mostly exotoxins) are the major weapons that kill host cells and cause diseases by inducing different types of cell death, particularly apoptosis and necrosis. Blocking these enterotoxins with synthetic drugs and vaccines is important for treating patients with infectious diseases. Studies of enterotoxin-induced apoptotic and necrotic mechanisms have helped us to create efficient strategies to use against these well-characterized cytopathic toxins. In this article, we review the induction of the different types of cell death from various bacterial enterotoxins, such as staphylococcal enterotoxin B, staphylococcal alpha-toxin, Panton-Valentine leukocidin, alpha-hemolysin of Escherichia coli, Shiga toxins, cytotoxic necrotizing factor 1, heat-labile enterotoxins, and the cholera toxin, Vibrio cholerae. In addition, necrosis caused by pore-forming toxins, apoptotic signaling through cross-talk pathways involving mitochondrial damage, endoplasmic reticulum stress, and lysosomal injury is discussed.

  17. Induction of Human Squamous Cell-Type Carcinomas by Arsenic

    Directory of Open Access Journals (Sweden)

    Victor D. Martinez


    Full Text Available Arsenic is a potent human carcinogen. Around one hundred million people worldwide have potentially been exposed to this metalloid at concentrations considered unsafe. Exposure occurs generally through drinking water from natural geological sources, making it difficult to control this contamination. Arsenic biotransformation is suspected to have a role in arsenic-related health effects ranging from acute toxicities to development of malignancies associated with chronic exposure. It has been demonstrated that arsenic exhibits preference for induction of squamous cell carcinomas in the human, especially skin and lung cancer. Interestingly, keratins emerge as a relevant factor in this arsenic-related squamous cell-type preference. Additionally, both genomic and epigenomic alterations have been associated with arsenic-driven neoplastic process. Some of these aberrations, as well as changes in other factors such as keratins, could explain the association between arsenic and squamous cell carcinomas in humans.

  18. Development and Testing of Shingle-type Solar Cell Modules (United States)

    Shepard, N. F., Jr.


    The design, development, fabrication and testing of a shingle-type terrestrial solar cell module which produces 98 watts/sq m of exposed module area at 1 kW/sq m insolation and 61 C are reported. These modules make it possible to easily incorporate photovoltaic power generation into the sloping roofs of residential or commercial buildings by simply nailing the modules to the plywood roof sheathing. This design consists of nineteen series-connected 53 mm diameter solar cells arranged in a closely packed hexagon configuration. These cells are individually bonded to the embossed surface of a 3 mm thick thermally tempered hexagon-shaped piece of glass. Polyvinyl butyral is used as the laminating adhesive.

  19. New type of cells with multiple chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail:


    A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

  20. Lamella formation and emigration from the water by a laboratory colony of Biomphalaria glabrata (SAY in flow-through system

    Directory of Open Access Journals (Sweden)

    Ricardo D. A. Dannemann


    Full Text Available Lamella formation and emigration from the water were investigated in juvenile Biomphalaria glabrata reared at two temperatures in aquaria with a constant water flow. Most snails (97.4% reared at the lower temperature (21- C formed lamella at the shell aperture and emigrated from the water, whereas only 10.1% did so at 25- C. Eighty percent of emigrations at 21- C occurred within a period of 15 days, 70-85 days after hatching. A comparison of the studies done so far indicates that the phenomenon may be affected by the ageing of snail colonies kept in the laboratory and their geographic origin, rather than the rearing conditions. This hypothesis, however, requires experimental confirmation.

  1. Emigration dynamics in South Asia, IOM / UNFPA workshop, 2-3 September 1996, IOM headquarters, Geneva, Switzerland. (United States)

    Appleyard, R


    This paper describes the six research monographs that were presented at the Emigration Dynamic Workshops in South Asia in September 1996. Research reports were presented by Associate Professor Nasra Shah on an overview of emigration dynamics, Dr. Godfrey Gunatilleke on the role of networks and community structures in migration from Sri Lanka, Dr. Raisul Awal Mahmood on illegal migration from Bangladesh to Singapore, Kuala Lumpur, Bangkok, and Delhi due to desperate poverty, Dr. Farooq-i-Azam on high and low labor-sending migration districts in Pakistan, Dr. Mahendra K. Premi on the impact of internal Indian migration on international migration, and Dr. P.R. Gopinathan Nair on emigration from Kerala, India, to the Middle East. Representatives of South Asian governments discussed the implications of the research findings. Pakistan's representative urged cooperation and joint strategies among labor-sending countries. He cautioned that income and remittance estimates were unstable and unrealistic for inclusion in economic development plans. The Indian representative noted that, although Indian emigration is low, it is highly visible in the press. He agreed with the suggestion for greater cooperation between sending countries. The Bangladesh representative stated that the country needed to locate new markets for Bangladeshi emigrants, to guarantee the rights of emigrant workers, and to prevent trafficking in illegal migrant workers. Three major topics were discussed in the workshop session on the implementation of programs based on research findings. Workshop participants recommended updated information on migration trends, updated information on labor markets in receiving countries, formal and regular policy dialogue between sending countries, and promotion of continuing research by the International Organization on Migration.

  2. Emigration Gothic: A Scotswoman’s Contribution to the New World

    Directory of Open Access Journals (Sweden)

    Michelle Gadpaille


    Full Text Available Ellen Ross (1816?–1892 emigrated from Scotland to Montreal at mid-century and wrote two Gothic novels, in one of which – Violet Keith, An Autobiography (1868 – she used the Canadian setting as a fantastic Gothic locale in which to explore areas of social and sexual transgression. Drawing on earlier traditions of European Gothic, including Sir Walter Scott’s mythologized Scottish landscape, and on an emerging North American genre of convent exposes, Ross’s writing accommodates female protest, distances it from reality and allows its dissipation in conventional denouements. If female Gothic can be read as an analogue of realistic women’s problems, then perhaps this analogy can be extended to encompass emigration and immigrant life. The paper analyzes Ross’s motifs of loss, imprisonment, solitude, surveillance and deliverance and considers the possibility that Gothic motifs in her work both conceal and express features of the immigrant’s psychic battle with the transition to the New World.

  3. Esmeralda Energy Company, Final Scientific Technical Report, January 2008. Emigrant Slimhole Drilling Project, DOE GRED III

    Energy Technology Data Exchange (ETDEWEB)

    Deymonaz, John [Fish Lake Green Power Co. (United States); Hulen, Jeffrey B. [Univ. of Utah, Salt Lake City, UT (United States). Energy and Geosciences Inst.; Nash, Gregory D. [Univ. of Utah, Salt Lake City, UT (United States). Energy and Geosciences Inst.; Schriener, Alex [Earth Systems Southwest (United States)


    The Emigrant Slimhole Drilling Project (ESDP) was a highly successful, phased resource evaluation program designed to evaluate the commercial geothermal potential of the eastern margin of the northern Fish Lake Valley pull-apart basin in west-central Nevada. The program involved three phases: (1) Resource evaluation; (2) Drilling and resource characterization; and (3) Resource testing and assessment. Efforts included detailed geologic mapping; 3-D modeling; compilation of a GIS database; and production of a conceptual geologic model followed by the successful drilling of the 2,938 foot deep 17-31 slimhole (core hole), which encountered commercial geothermal temperatures (327⁰ F) and exhibits an increasing, conductive, temperature gradient to total depth; completion of a short injection test; and compilation of a detailed geologic core log and revised geologic cross-sections. Results of the project greatly increased the understanding of the geologic model controlling the Emigrant geothermal resource. Information gained from the 17-31 core hole revealed the existence of commercial temperatures beneath the area in the Silver Peak Core Complex which is composed of formations that exhibit excellent reservoir characteristics. Knowledge gained from the ESDP may lead to the development of a new commercial geothermal field in Nevada. Completion of the 17-31 core hole also demonstrated the cost-effectiveness of deep core drilling as an exploration tool and the unequaled value of core in understanding the geology, mineralogy, evolutional history and structural aspects of a geothermal resource.

  4. Species richness and occupancy estimation in communities subject to temporary emigration (United States)

    Kery, M.; Royle, J. Andrew; Plattner, M.; Dorazio, R.M.


    Species richness is the most common biodiversity metric, although typically some species remain unobserved. Therefore, estimates of species richness and related quantities should account for imperfect detectability. Community dynamics can often be represented as superposition of species-specific phenologies (e. g., in taxa with well-defined flight [insects], activity [rodents], or vegetation periods [plants]). We develop a model for such predictably open communities wherein species richness is expressed as the sum over observed and unobserved species of estimated species-specific and site-specific occurrence indicators and where seasonal occurrence is modeled as a species-specific function of time. Our model is a multispecies extension of a multistate model with one unobservable state and represents a parsimonious way of dealing with a widespread form of 'temporary emigration.'' For illustration we use Swiss butterfly monitoring data collected under a robust design (RD); species were recorded on 13 transects during two secondary periods within emigration where rigorous estimation of community metrics has proved challenging so far.

  5. Use of olfactory cues by newly metamorphosed wood frogs (Lithobates sylvaticus) during emigration (United States)

    Zydlewski, Joseph; Popescu, Viorel D.; Brodie, Bekka S.; Hunter, Malcom L.


    Juvenile amphibians are capable of long-distance upland movements, yet cues used for orientation during upland movements are poorly understood. We used newly metamorphosed Wood Frogs (Lithobates sylvaticus) to investigate: (1) the existence of innate (i.e., inherited) directionality, and (2) the use of olfactory cues, specifically forested wetland and natal pond cues during emigration. In a circular arena experiment, animals with assumed innate directionality did not orient in the expected direction (suggested by previous studies) when deprived of visual and olfactory cues. This suggests that juvenile Wood Frogs most likely rely on proximate cues for orientation. Animals reared in semi-natural conditions (1500 l cattle tanks) showed a strong avoidance of forested wetland cues in two different experimental settings, although they had not been previously exposed to such cues. This finding is contrary to known habitat use by adult Wood Frogs during summer. Juvenile Wood Frogs were indifferent to the chemical signature of natal pond (cattle tank) water. Our findings suggest that management strategies for forest amphibians should consider key habitat features that potentially influence the orientation of juveniles during emigration movements, as well as adult behavior.

  6. Cross-reactivity of cell-mediated immunity between interstitial (type I) and basement membrane (type IV) collagens



    In the present study, we demonstrate delayed-type hypersensitivity (DTH) to homologous type I collagen that cross-reacts with type IV collagen. Mice immunized with native or denatured type I collagens and challenged with these same antigens or native type IV collagen develop a peak DTH response on day 7. Challenge with denatured type IV collagen or collagenase-treated type IV collagen failed to elicit DTH in type I collagen-sensitized mice. Type I collagen-sensitized spleen cells adoptively t...

  7. Emigration of Natural and Hatchery Chinook Salmon and Steelhead Smolts from the Imnaha River, Oregon, 1998-1999 Annual Report.

    Energy Technology Data Exchange (ETDEWEB)

    Cleary, Peter J.; Blenden, Michael L.; Kucera, Paul A.


    This report summarizes the results of the Lower Snake River Compensation Plan Hatchery Evaluation Studies (LSRCP) and the Imnaha Smolt Monitoring Program (SMP) for the 1999 smolt migration from the Imnaha River, Oregon. These studies were designed and closely coordinated to provide information about juvenile natural and hatchery chinook salmon (Oncorhynchus tshawytscha) and steelhead (Oncorhynchus mykiss) biological characteristics, behavior and emigrant timing, survival, arrival timing and travel time to the Snake River dams and McNary Dam on the Columbia River. Data collected from these studies are shared with the Fish Passage Center (FPC). These data are essential to quantify smolt survival rates under the current passage conditions and to evaluate the future recovery strategies that seek to optimize smolt survival through the hydroelectric system. Information shared with the FPC assists with in-season shaping of flow and spill management requests in the Snake River reservoirs. The Bonneville Power Administration and the United States Fish and Wildlife Service contracted the Nez Perce Tribe (NPT) to monitor emigration timing and tag 21,200 emigrating natural and hatchery chinook salmon and steelhead smolts from the Imnaha River during the spring emigration period (March 1-June 15) with passive integrated transponder (PIT) tags. The completion of trapping in the spring of 1999 marked the eighth year of emigration studies on the Imnaha River and the sixth year of participating in the FPC smolt monitoring program. Monitoring and evaluation objectives were to: (1) Determine spring emigration timing of chinook salmon and steelhead smolts collected at the Imnaha River trap. (2) Evaluate effects of flow, temperature and other environmental factors on emigration timing. (3) Monitor the daily catch and biological characteristics of juvenile chinook salmon and steelhead smolts collected at the Imnaha River screw trap. (4) Determine emigration timing, travel time, and in

  8. Activated Type 2 Innate Lymphoid Cells regulate Beige Fat Biogenesis (United States)

    Lee, Min-Woo; Odegaard, Justin I.; Mukundan, Lata; Qiu, Yifu; Molofsky, Ari B.; Nussbaum, Jesse C.; Yun, Karen; Locksley, Richard M.; Chawla, Ajay


    SUMMARY Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2-and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα+ APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PMID:25543153

  9. Establishment of human cell type-specific iPS cells with enhanced chondrogenic potential. (United States)

    Guzzo, Rosa M; Scanlon, Vanessa; Sanjay, Archana; Xu, Ren-He; Drissi, Hicham


    The propensity of induced pluripotent stem (iPS) cells to differentiate into specific lineages may be influenced by a number of factors, including the selection of the somatic cell type used for reprogramming. Herein we report the generation of new iPS cells, which we derived from human articular chondrocytes and from cord blood mononucleocytes via lentiviral-mediated delivery of Oct4, Klf4, Sox2, and cMyc. Molecular, cytochemical, and cytogenic analyses confirmed the acquisition of hallmark features of pluripotency, as well as the retention of normal karyotypes following reprogramming of both the human articular chondrocytes (AC) and the cord blood (CB) cells. In vitro and in vivo functional analyses formally established the pluripotent differentiation capacity of all cell lines. Chondrogenic differentiation assays comparing iPS cells derived from AC, CB, and a well established dermal fibroblast cell line (HDFa-Yk26) identified enhanced proteoglycan-rich matrix formation and cartilage-associated gene expression from AC-derived iPS cells. These findings suggest that the tissue of origin may impact the fate potential of iPS cells for differentiating into specialized cell types, such as chondrocytes. Thus, we generated new cellular tools for the identification of inherent features driving high chondrogenic potential of reprogrammed cells.

  10. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Directory of Open Access Journals (Sweden)

    Elena Restelli

    Full Text Available BACKGROUND: A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions. PRINCIPAL FINDINGS: Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells. SIGNIFICANCE: These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  11. Liver stem cell-derived β-cell surrogates for treatment of type 1 diabetes☆ (United States)

    Yang, Li-Jun


    Consistent with the common embryonic origin of liver and pancreas as well the similar glucose-sensing systems in hepatocytes and pancreatic β-cells, it should not be surprising that liver stem cells/hepatocytes can transdifferentiate into insulin-producing cells under high-glucose culture conditions or by genetic reprogramming. Persistent expression of the pancreatic duodenal homeobox-1 (Pdx1) transcription factor or its super-active form Pdx1-VP16 fusion protein in hepatic cells reprograms these cells into pancreatic β-cell precursors. In vitro culture at elevated glucose concentrations or in vivo exposure to a hyperglycemia are required for further differentiation and maturation of liver-derived pancreatic β-cell precursor into functional insulin-producing pancreatic β-like cells. Under appropriate conditions, multiple pancreatic transcription factors can work in concert to reprogram liver stem/adult liver cells into functional insulin-producing cells. If such autologous liver-derived insulin-producing cells can be made to escape the type 1 diabetes-associated autoimmunity, they may serve as a valuable cell source for future cell replacement therapy without the need for life-long immunosuppression. PMID:16890895

  12. Muse Cells, a New Type of Pluripotent Stem Cell Derived from Human Fibroblasts. (United States)

    Liu, Qi; Zhang, Ru-zhi; Li, Di; Cheng, Sai; Yang, Yu-hua; Tian, Ting; Pan, Xiao-ru


    A new type of mesenchymal stem cells (MSCs) that expresses stage-specific embryonic antigen 3 (SSEA-3) and the mesenchymal cell marker CD105 are known as multilineage-differentiating stress-enduring (Muse) cells. Studies have shown that stem cells in suspension cultures are more likely to generate embryoid body-like stem cell spheres and maintain an undifferentiated phenotype and pluripotency. We separated Muse cells derived from human dermal fibroblasts by long-term trypsin incubation (LTT) through suspension cultures in methylcellulose. The Muse cells obtained expressed several pluripotency markers, including Nanog, Oct4, Sox2, and SSEA-3, and could differentiate in vitro into cells of the three germ layers, such as hepatocytes (endodermal), neural cells (ectodermal) and adipocytes, and osteocytes (mesodermal cells). These cells showed a low level of DNA methylation and a high nucleo-cytoplasmic ratio. Our study provides an innovative and exciting platform for exploring the potential cell-based therapy of various human diseases using Muse cells as well as their great possibility for regenerative medicine.

  13. Concise review: alchemy of biology: generating desired cell types from abundant and accessible cells. (United States)

    Pournasr, Behshad; Khaloughi, Keynoush; Salekdeh, Ghasem Hosseini; Totonchi, Mehdi; Shahbazi, Ebrahim; Baharvand, Hossein


    A major goal of regenerative medicine is to produce cells to participate in the generation, maintenance, and repair of tissues that are damaged by disease, aging, or trauma, such that function is restored. The establishment of induced pluripotent stem cells, followed by directed differentiation, offers a powerful strategy for producing patient-specific therapies. Given how laborious and lengthy this process can be, the conversion of somatic cells into lineage-specific stem/progenitor cells in one step, without going back to, or through, a pluripotent stage, has opened up tremendous opportunities for regenerative medicine. However, there are a number of obstacles to overcome before these cells can be widely considered for clinical applications. Here, we focus on induced transdifferentiation strategies to convert mature somatic cells to other mature cell types or progenitors, and we summarize the challenges that need to be met if the potential applications of transdifferentiation technology are to be achieved.

  14. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease

    Directory of Open Access Journals (Sweden)

    Lynne Robertson


    Full Text Available Background. Darier's disease (DD, also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002. Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  15. Target cell cyclophilins facilitate human papillomavirus type 16 infection.

    Directory of Open Access Journals (Sweden)

    Malgorzata Bienkowska-Haba


    Full Text Available Following attachment to primary receptor heparan sulfate proteoglycans (HSPG, human papillomavirus type 16 (HPV16 particles undergo conformational changes affecting the major and minor capsid proteins, L1 and L2, respectively. This results in exposure of the L2 N-terminus, transfer to uptake receptors, and infectious internalization. Here, we report that target cell cyclophilins, peptidyl-prolyl cis/trans isomerases, are required for efficient HPV16 infection. Cell surface cyclophilin B (CyPB facilitates conformational changes in capsid proteins, resulting in exposure of the L2 N-terminus. Inhibition of CyPB blocked HPV16 infection by inducing noninfectious internalization. Mutation of a putative CyP binding site present in HPV16 L2 yielded exposed L2 N-terminus in the absence of active CyP and bypassed the need for cell surface CyPB. However, this mutant was still sensitive to CyP inhibition and required CyP for completion of infection, probably after internalization. Taken together, these data suggest that CyP is required during two distinct steps of HPV16 infection. Identification of cell surface CyPB will facilitate the study of the complex events preceding internalization and adds a putative drug target for prevention of HPV-induced diseases.

  16. The role of family networks and migration culture in the continuation of Moroccan emigration : A gender perspective

    NARCIS (Netherlands)

    Heering, L; van der Erf, R; van Wissen, L


    About 1.5 million people of Moroccan origin live as legal migrants in the countries of the European Union. For several decades, emigration has affected various provinces of Morocco. In some regions, the process started more than 40 years ago; in others the migration experience is much more recent. T

  17. Historical invasions of the intertidal zone of Atlantic North America associated with distinctive patterns of trade and emigration

    NARCIS (Netherlands)

    Brawley, S.H.; Coyer, J.A.; Blakeslee, A.M.H.; Hoarau, G.G.; Johnson, L.E.; Byers, J.E.; Stam, W.T.; Olsen, J.L.


    Early invasions of the North American shore occurred mainly via deposition of ballast rock, which effectively transported pieces of the intertidal zone across the Atlantic. From 1773- 1861, > 880 European ships entered Pictou Harbor, Nova Scotia, as a result of emigration and trade from Europe. The

  18. 22 CFR 99.2 - Reporting requirements for adoption cases involving children emigrating from the United States. (United States)


    ... 22 Foreign Relations 1 2010-04-01 2010-04-01 false Reporting requirements for adoption cases involving children emigrating from the United States. 99.2 Section 99.2 Foreign Relations DEPARTMENT OF... Convention case, or in a non-Convention case, the reporting provider is the agency, person, public...

  19. LFA-1 and Mac-1 define characteristically different intralumenal crawling and emigration patterns for monocytes and neutrophils in situ. (United States)

    Sumagin, Ronen; Prizant, Hen; Lomakina, Elena; Waugh, Richard E; Sarelius, Ingrid H


    To exit blood vessels, most (∼80%) of the lumenally adhered monocytes and neutrophils crawl toward locations that support transmigration. Using intravital confocal microscopy of anesthetized mouse cremaster muscle, we separately examined the crawling and emigration patterns of monocytes and neutrophils in blood-perfused unstimulated or TNF-α-activated venules. Most of the interacting cells in microvessels are neutrophils; however, in unstimulated venules, a greater percentage of the total monocyte population is adherent compared with neutrophils (58.2 ± 6.1% versus 13.6 ± 0.9%, adhered/total interacting), and they crawl for significantly longer distances (147.3 ± 13.4 versus 61.8 ± 5.4 μm). Intriguingly, after TNF-α activation, monocytes crawled for significantly shorter distances (67.4 ± 9.6 μm), resembling neutrophil crawling. Using function-blocking Abs, we show that these different crawling patterns were due to CD11a/CD18 (LFA-1)- versus CD11b/CD18 (Mac-1)-mediated crawling. Blockade of either Mac-1 or LFA-1 revealed that both LFA-1 and Mac-1 contribute to monocyte crawling; however, the LFA-1-dependent crawling in unstimulated venules becomes Mac-1 dependent upon inflammation, likely due to increased expression of Mac-1. Mac-1 alone was responsible for neutrophil crawling in both unstimulated and TNF-α-activated venules. Consistent with the role of Mac-1 in crawling, Mac-1 block (compared with LFA-1) was also significantly more efficient in blocking TNF-α-induced extravasation of both monocytes and neutrophils in cremaster tissue and the peritoneal cavity. Thus, mechanisms underlying leukocyte crawling are important in regulating the inflammatory responses by regulating the numbers of leukocytes that transmigrate.

  20. Emigration and wages in an open economy: some evidence from Pakistan. (United States)

    Mahmood, Z


    "This paper examines the impact of labour emigration on the wages of both the skilled and unskilled workers....Using... Pakistani data, it is found that unskilled labour is used extremely intensively in the agriculture sector (exportable), skilled labour is used extremely intensively in the manufacturing sector (importable), and capital is used as the middle factor in both the traded goods sectors. Moreover, capital is used significantly less intensively in the construction (non-traded) sector relative to both the traded sectors.... The results suggest that the higher wages to both the skilled and unskilled workers must be compensated by a reduction in the rate of returns to capital if export-oriented and import-competing sectors in Pakistan are to remain internationally competitive."

  1. The Macrophage Galactose-Type C-Type Lectin (MGL Modulates Regulatory T Cell Functions.

    Directory of Open Access Journals (Sweden)

    Ilaria Grazia Zizzari

    Full Text Available Regulatory T cells (Tregs are physiologically designed to prevent autoimmune disease and maintain self-tolerance. In tumour microenvironments, their presence is related to a poor prognosis, and they influence the therapeutic outcome due to their capacity to suppress the immune response by cell-cell contact and to release immunosuppressive cytokines. In this study, we demonstrate that Treg immunosuppressive activity can be modulated by the cross-linking between the CD45RA expressed by Tregs and the C-type lectin MGL. This specific interaction strongly decreases the immunosuppressive activity of Tregs, restoring the proliferative capacity of co-cultured T lymphocytes. This effect can be attributed to changes in CD45RA and TCR signalling through the inhibition of Lck and inactivation of Zap-70, an increase in the Foxp3 methylation status and, ultimately, the reduced production of suppressive cytokines. These results indicate a role of MGL as an immunomodulator within the tumour microenvironment interfering with Treg functions, suggesting its possible use in the design of anticancer vaccines.

  2. The literature of Slovenian political emigrants in Argentina after the Second World War

    Directory of Open Access Journals (Sweden)

    Marija Uršula Geršak


    Full Text Available After the Second World War many political emigrants escaped from Slovenia to Argentina, among them leaders and soldiers of the home guard (belogardisti, sympathizers of the fascist forces, opponents of communism and their families, who were persecuted by the Yugoslav socialist regime. Among them were many intellectuals and artists, typically of right-wing political conviction and of Christian faith. In Argentina, they founded a hermetic community that kept the Slovenian language and traditional values, and hoped that one day they could return. People in the former Yugoslavia knew nothing about them or their activities or indeed about events after the war from the point of view of the Other. This paper reviews the historical circumstances that led to the emigration, the organization of the émigré community and their cultural life in Argentina, their literature, mainly novels and their ensconcement in another time and space, which is the time and space of memory and an idealized homeland. They were culturally very active and wrote mostly in Slovenian. It was not until the second generation and after Slovenia‘s independence when they published several works in Spanish. Mostly they wrote historical novels, memoirs, dealing with unhealed wounds years after the Second World War, exile, life in refugee camps, post-war killings. Many of the works are ideologically laden, moralistic and idealizing life in Slovenia before the War. Due to their close community, literary works are often subject to some kind of ‚(self censorship‘. Nevertheless, after Slovenia‘s independence, albeit with a delay, some of their works, because of their aesthetic and cultural values have become part of the national literatary canon and school textbooks.

  3. Carryover aquatic effects on survival of metamorphic frogs during pond emigration (United States)

    Chelgren, N.D.; Rosenberg, D.K.; Heppell, S.S.; Gitelman, A.I.


    In organisms with complex life cycles, physiological stressors during early life stages may have fitness-level impacts that are delayed into later stages or habitats. We tested the hypothesis that body size and date of metamorphosis, which are highly responsive to aquatic stressors, influence post-metamorphic survival and movement patterns in the terrestrial phase of an ephemeral pond-breeding frog by examining these traits in two populations of northern red-legged frogs (Rana aurora aurora). To increase variation of body size at metamorphosis, we manipulated food availability for 314 of 1045 uniquely marked tadpoles and estimated the probability that frogs survived and emigrated using concentric rings of drift fencing surrounding ponds and Bayesian capture-recapture modeling. The odds of surviving and emigrating from the ponds to the innermost drift fences, ???12 m, increased by factors of 2.20 (95% credibility intervals 1.39-4.23) and 2.54 (0.94-4.91) with each millimeter increase in snout-vent length and decreased by factors of 0.91 (0.85-0.96) and 0.89 (0.80-1.00) with each day's delay in metamorphosis for the two ponds. The odds of surviving and moving to the next ring of fencing, 12 m to ???40 m from the ponds, increased by a factor of 1.20 (0.45-4.06) with each millimeter increase in size. Our results demonstrated that body size and timing of metamorphosis relate strongly to the performance of newly metamorphosed frogs during their initial transition into terrestrial habitat. Carryover effects of aquatic stressors that reduce size and delay metamorphosis may have population-level impacts that are not expressed until terrestrial stages. Since changes in both aquatic and terrestrial systems are implicated in many amphibian declines, quantifying both immediate and delayed effects of stressors on demographic rates is critical to sound management. ?? 2006 by the Ecological Society of America.

  4. Escape from Socialist Yugoslavia ‒ Illegal Emigration from Croatia from 1945 to the Beginning of the 1960s

    Directory of Open Access Journals (Sweden)

    Tatjana Šarić


    Full Text Available In the post-war socialist Yugoslavia political and/or economic situation has become unacceptable for part of the population. Since legal emigration from Croatia was not allowed, the number of illegal immigrants increased since the end of World War II. The article deals with this group of migrants using the comparative analysis of original archival materials and available literature in the period from 1945 to 1961 when the state began to gradually open the border. Mostly young people, under 25 years of age, immigrated illegally, mainly for economic reasons, and this was associated with a tradition of emigration, especially in the coastal region. In addition to the poor economic situation, people also emigrated for political reasons, then for adventure, to avoid serving in the Yugoslav People’s Army or to escape from the law for committing criminal offenses. They were fleeing by land or by sea, which was much more successful. Usually the first destinations of the immigrants were Italy, Austria and Germany, from where the majority of them moved to overseas countries. Most people fled the districts of Rijeka, Pula, Zagreb, Zadar, Šibenik and Split that existed at that time so that 74% of all illegal immigrants came from them. The runaways were mostly workers, followed by farmers, vocational school students, public servants, pupils and students, sailors and craftsmen. According to gender, there were many more men than women among the runaways, most of whom were unmarried. The authorities were trying to prevent the escape abroad by methods of controlling the border and prison sentences, but also by the attempts to ensure better living conditions in the affected areas. As these measures had not yielded the desired results, but also due to the beginning of the economic crisis and the appearance of unemployment, the authorities liberalized emigration procedures and opened the borders to immigrants which resulted in a new wave of economic emigration.

  5. Casein gene expression in mouse mammary epithelial cell lines: Dependence upon extracellular matrix and cell type

    Energy Technology Data Exchange (ETDEWEB)

    Medina, D.; Oborn, C.J. (Baylor College of Medicine, Houston, TX (USA)); Li, M.L.; Bissell, M.J. (Univ. of California, Berkeley (USA))


    The COMMA-D mammary cell line exhibits mammary-specific functional differentiation under appropriate conditions in cell culture. The cytologically heterogeneous COMMA-D parental line and the clonal lines DB-1, TA-5, and FA-1 derived from the COMMA-D parent were examined for similar properties of functional differentiation. In monolayer cell culture, the cell lines DB-1, TA-5, FA-1, and MA-4 were examined for expression of mammary-specific and epithelial-specific proteins by an indirect immunofluorescence assay. The clonal cell lines were relatively homogeneous in their respective staining properties and seemed to represent three subpopulations found in the heterogeneous parental COMMA-D lines. None of the four clonal lines appeared to represent myoepithelial cells. The cell lines were examined for expression of {beta}-casein mRNA in the presence or absence of prolactin. The inducibility of {beta}-casein in the COMMA-D cell line was further enhanced by a reconstituted basement membrane preparation enriched in laminin, collagen IV, and proteoglycans. These results support the hypothesis that the functional response of inducible mammary cell populations is a result of interaction among hormones, multiple extracellular matrix components, and specific cell types.

  6. β-cell replacement sources for type 1 diabetes: a focus on pancreatic ductal cells. (United States)

    Corritore, Elisa; Lee, Yong-Syu; Sokal, Etienne M; Lysy, Philippe A


    Thorough research on the capacity of human islet transplantation to cure type 1 diabetes led to the achievement of 3- to 5-year-long insulin independence in nearly half of transplanted patients. Yet, translation of this technique to clinical routine is limited by organ shortage and the need for long-term immunosuppression, restricting its use to adults with unstable disease. The production of new bona fide β cells in vitro was thus investigated and finally achieved with human pluripotent stem cells (PSCs). Besides ethical concerns about the use of human embryos, studies are now evaluating the possibility of circumventing the spontaneous tumor formation associated with transplantation of PSCs. These issues fueled the search for cell candidates for β-cell engineering with safe profiles for clinical translation. In vivo studies revealed the regeneration capacity of the exocrine pancreas after injury that depends at least partially on facultative progenitors in the ductal compartment. These stimulated subpopulations of pancreatic ductal cells (PDCs) underwent β-cell transdifferentiation through reactivation of embryonic signaling pathways. In vitro models for expansion and differentiation of purified PDCs toward insulin-producing cells were described using cocktails of growth factors, extracellular-matrix proteins and transcription factor overexpression. In this review, we will describe the latest findings in pancreatic β-cell mass regeneration due to adult ductal progenitor cells. We will further describe recent advances in human PDC transdifferentiation to insulin-producing cells with potential for clinical translational studies.

  7. Regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 in cultured rat Sertoli and Leydig cells

    Institute of Scientific and Technical Information of China (English)

    刘以训; 杜群; 周红明; 刘奎; 胡召元


    New data are provided to show that (i) rat Sertoli cells produce two types of plasminogen activators, tissue type (tPA) and urokinase type (uPA), and a plasminogen activator inhibitor type-1 (PAI-1); (ii) both tPA (but not uPA) and PAI-1 secretion in the culture are modified by FSH, forskolin, dbcAMP, GnRH, PMA and growth factors (EGF and FGF), but not by hCG and androstenedione (△4); (iii) in vitro secretion of tPA and PA-PAI-1 complexes of Sertoli cells are greatly enhanced by presence of Leydig cells which produce negligible tPA but measurable PAI-1 activity;(iv) combination culture of Sertoli and Leydig cells remarkably increases FSH-induced PAI-1 activity and decreases hCG- and forskolin-induced inhibitor activity as compared with that of two cell types cultured alone. These data suggest that rat Sertoli cells, similar to ovarian granulosa cells, are capable of secreting both tPA and uPA, as well as PAI-1. The interaction of Sertoli cells and Leydig cells is essential for the cells to response to

  8. Detection of gene expression in an individual cell type within a cell mixture using microarray analysis.

    Directory of Open Access Journals (Sweden)

    Penelope A Bryant

    Full Text Available BACKGROUND: A central issue in the design of microarray-based analysis of global gene expression is the choice between using cells of single type and a mixture of cells. This study quantified the proportion of lipopolysaccharide (LPS induced differentially expressed monocyte genes that could be measured in peripheral blood mononuclear cells (PBMC, and determined the extent to which gene expression in the non-monocyte cell fraction diluted or obscured fold changes that could be detected in the cell mixture. METHODOLOGY/PRINCIPAL FINDINGS: Human PBMC were stimulated with LPS, and monocytes were then isolated by positive (Mono+ or negative (Mono- selection. The non-monocyte cell fraction (MonoD remaining after positive selection of monocytes was used to determine the effect of non-monocyte cells on overall expression. RNA from LPS-stimulated PBMC, Mono+, Mono- and MonoD samples was co-hybridised with unstimulated RNA for each cell type on oligonucleotide microarrays. There was a positive correlation in gene expression between PBMC and both Mono+ (0.77 and Mono- (0.61-0.67 samples. Analysis of individual genes that were differentially expressed in Mono+ and Mono- samples showed that the ability to detect expression of some genes was similar when analysing PBMC, but for others, differential expression was either not detected or changed in the opposite direction. As a result of the dilutional or obscuring effect of gene expression in non-monocyte cells, overall about half of the statistically significant LPS-induced changes in gene expression in monocytes were not detected in PBMC. However, 97% of genes with a four fold or greater change in expression in monocytes after LPS stimulation, and almost all (96-100% of the top 100 most differentially expressed monocyte genes were detected in PBMC. CONCLUSIONS/SIGNIFICANCE: The effect of non-responding cells in a mixture dilutes or obscures the detection of subtle changes in gene expression in an individual

  9. Stem cell approaches for the treatment of type 1 diabetes mellitus. (United States)

    Wagner, Ryan T; Lewis, Jennifer; Cooney, Austin; Chan, Lawrence


    Type 1 diabetes is characterized by near total absence of pancreatic b cells. Current treatments consisting of insulin injections and islet transplantation are clinically unsatisfactory. In order to develop a cure for type 1 diabetes, we must find a way to reverse autoimmunity, which underlies b cell destruction, as well as an effective strategy to generate new b cells. This article reviews the different approaches that are being taken to produce new b cells. Much emphasis has been placed on selecting the right non-b cell population, either in vivo or in vitro, as the starting material. Different cell types, including adult stem cells, other types of progenitor cells in situ, and even differentiated cell populations, as well as embryonic stem cells and induced pluripotent stem cells, will require different methods for islet and b cell induction. We discussed the pros and cons of the different strategies that are being used to re-invent the pancreatic b cell.

  10. Singling out Drosophila tendon cells: a dialogue between two distinct cell types. (United States)

    Volk, T


    The precise match between somatic muscles and their epidermal attachment cells is achieved through a continuous dialogue between these two cell types. Whereas tendon cells direct myotube migration and final patterning, the muscles are essential for the maintenance of the fate of tendon cells. The Drosophila neuregulin-like ligand, Vein, and its receptor, the epidermal growth factor receptor (Egfr), are critical components in the inductive signaling process that takes place between muscles and tendon cells. Additional gene products that relay the Vein-Egfr effect in Drosophila are conserved in the vertebrate neuregulin-mediated cascade. This review describes genetic and molecular aspects of the muscle-tendon inductive processes in Drosophila, and compares them with the relevant mechanisms in the vertebrate embryo.

  11. The statistical geometry of transcriptome divergence in cell-type evolution and cancer

    NARCIS (Netherlands)

    Liang, Cong; Forrest, Alistair R R; Wagner, Günter P; Clevers, J.C.


    In evolution, body plan complexity increases due to an increase in the number of individualized cell types. Yet, there is very little understanding of the mechanisms that produce this form of organismal complexity. One model for the origin of novel cell types is the sister cell-type model. According

  12. Demonstration of different modes of cell death upon herpes simplex virus 1 infection in different types of oral cells. (United States)

    Huang, C R; Lin, S S; Chou, M Y; Ho, C C; Wang, L; Lee, Y L; Chen, C S; Yang, C C


    The effects of Herpes simplex virus 1 (HSV-1) infection on five different types of oral cancerous cells (neck metastasis of gingival carcinoma (GNM) cells and tongue squamous cells of carcinoma (TSCCa) and non-cancerous cells (buccal mucosal fibroblasts (BF), gingival fibroblasts (GF), oral submucosal fibrosis cells (OSF)) and one type of non-oral cancerous cells (KB cells) were investigated. In HSV-1-infected cells the cell viability, CPE, viral antigens accumulation, caspase-3 activity, annexin V binding and DNA fragmentation were estimated. Three different forms or pathways of cell death were considered: apoptosis (the presence or rise of caspase-3 activity, DNA fragmentation and annexin V binding), slow cell death (the presence or rise of DNA fragmentation, the absence or decline of caspase-3 activity and annexin V binding), and necrosis (the absence of decline of caspase-3 activity, DNA fragmentation and annexin V binding). The viability of all cell types, except for KB cells, was reduced by the infection. CPE and viral antigens data demonstrated that all six types of cells could be infected with HSV-1. Upon HSV-1 infection there occurred (i) a classical apoptosis in GF cells, (ii) apoptosis in the early phase of infection and necrosis in the late phase of infection in GNM and TSCCa cells, (iii) slow cell death followed by necrosis in BF and OSF cells (however, these cells showed a different type of CPE), (iv) a classical slow cell death in KB cells. It is hypothesized that HSV-1 infection has a potential to induce several distinct pathways leading to cell death or several forms of cell death. Moreover, more than one pathway may be involved in the death of particular cell type. As HSV-1 was demonstrated to infect different oral and non-oral cells and cause different pathways or forms of cell death, the safety of using HSV-1 as a vector for gene therapy should be re-considered.

  13. IL-4 increases type 2, but not type 1, cytokine production in CD8+ T cells from mild atopic asthmatics

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    Coyle Anthony J


    Full Text Available Abstract Background Virus infections are the major cause of asthma exacerbations. CD8+ T cells have an important role in antiviral immune responses and animal studies suggest a role for CD8+ T cells in the pathogenesis of virus-induced asthma exacerbations. We have previously shown that the presence of IL-4 during stimulation increases the frequency of IL-5-positive cells and CD30 surface staining in CD8+ T cells from healthy, normal subjects. In this study, we investigated whether excess IL-4 during repeated TCR/CD3 stimulation of CD8+ T cells from atopic asthmatic subjects alters the balance of type 1/type 2 cytokine production in favour of the latter. Methods Peripheral blood CD8+ T cells from mild atopic asthmatic subjects were stimulated in vitro with anti-CD3 and IL-2 ± excess IL-4 and the expression of activation and adhesion molecules and type 1 and type 2 cytokine production were assessed. Results Surface expression of very late antigen-4 [VLA-4] and LFA-1 was decreased and the production of the type 2 cytokines IL-5 and IL-13 was augmented by the presence of IL-4 during stimulation of CD8+ T cells from mild atopic asthmatics. Conclusion These data suggest that during a respiratory virus infection activated CD8+ T cells from asthmatic subjects may produce excess type 2 cytokines and may contribute to asthma exacerbation by augmenting allergic inflammation.

  14. Metal-sulfur type cell having improved positive electrode (United States)

    Dejonghe, Lutgard C.; Visco, Steven J.; Mailhe, Catherine C.; Armand, Michel B.


    A novel metal-sulfur type cell operable at a temperature of 200 C or less with an energy density of 150 Whrs/Kg or better is disclosed characterized by an organo-sulfur cathode formed from an organic-sulfur compound having the general formula, in its charged state, of (R(S) sub y) n wherein y = 1 to 6; n = 2 to 20; and R is one or more different aliphatic or aromatic organic moieties having 1 to 20 carbon atoms, which may include one or more oxygen, sulfur, or nitrogen heteroatoms when R comprises one or more aromatic rings, or one or more oxygen, sulfur, nitrogen, or fluorine atoms associated with the chain when R comprises an aliphatic chain, wherein the aliphatic group may be linear or branched, saturated or unsaturated, and wherein either the aliphatic chain or the aromatic ring may have substituted groups thereon.

  15. Galvanic Cell Type Sensor for Soil Moisture Analysis. (United States)

    Gaikwad, Pramod; Devendrachari, Mruthyunjayachari Chattanahalli; Thimmappa, Ravikumar; Paswan, Bhuneshwar; Raja Kottaichamy, Alagar; Makri Nimbegondi Kotresh, Harish; Thotiyl, Musthafa Ottakam


    Here we report the first potentiometric sensor for soil moisture analysis by bringing in the concept of Galvanic cells wherein the redox energies of Al and conducting polyaniline are exploited to design a battery type sensor. The sensor consists of only simple architectural components, and as such they are inexpensive and lightweight, making it suitable for on-site analysis. The sensing mechanism is proved to be identical to a battery type discharge reaction wherein polyaniline redox energy changes from the conducting to the nonconducting state with a resulting voltage shift in the presence of soil moisture. Unlike the state of the art soil moisture sensors, a signal derived from the proposed moisture sensor is probe size independent, as it is potentiometric in nature and, hence, can be fabricated in any shape or size and can provide a consistent output signal under the strong aberration conditions often encountered in soil moisture analysis. The sensor is regenerable by treating with 1 M HCl and can be used for multiple analysis with little read out hysteresis. Further, a portable sensor is fabricated which can provide warning signals to the end user when the moisture levels in the soil go below critically low levels, thereby functioning as a smart device. As the sensor is inexpensive, portable, and potentiometric, it opens up avenues for developing effective and energy efficient irrigation strategies, understanding the heat and water transfer at the atmosphere-land interface, understanding soil mechanics, forecasting the risk of natural calamities, and so on.

  16. Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration. (United States)

    Lachmann, Sylvie; Jevons, Amy; De Rycker, Manu; Casamassima, Adele; Radtke, Simone; Collazos, Alejandra; Parker, Peter J


    The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

  17. Regulatory domain selectivity in the cell-type specific PKN-dependence of cell migration.

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    Sylvie Lachmann

    Full Text Available The mammalian protein kinase N (PKN family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relatively highly expressed, to assess the potential redundancy of these isoforms in migratory responses. It is established that PKN2 has a critical role in the migration and invasion of these cells. Furthermore, using a PKN wild-type and chimera rescue strategy, it is shown that PKN isoforms are not simply redundant in supporting migration, but appear to be linked through isoform specific regulatory domain properties to selective upstream signals. It is concluded that intervention in PKNs may need to be directed at multiple isoforms to be effective in different cell types.

  18. Stem cell sources for clinical islet transplantation in type 1 diabetes: embryonic and adult stem cells. (United States)

    Miszta-Lane, Helena; Mirbolooki, Mohammadreza; James Shapiro, A M; Lakey, Jonathan R T


    Lifelong immunosuppressive therapy and inadequate sources of transplantable islets have led the islet transplantation benefits to less than 0.5% of type 1 diabetics. Whereas the potential risk of infection by animal endogenous viruses limits the uses of islet xeno-transplantation, deriving islets from stem cells seems to be able to overcome the current problems of islet shortages and immune compatibility. Both embryonic (derived from the inner cell mass of blastocysts) and adult stem cells (derived from adult tissues) have shown controversial results in secreting insulin in vitro and normalizing hyperglycemia in vivo. ESCs research is thought to have much greater developmental potential than adult stem cells; however it is still in the basic research phase. Existing ESC lines are not believed to be identical or ideal for generating islets or beta-cells and additional ESC lines have to be established. Research with ESCs derived from humans is controversial because it requires the destruction of a human embryo and/or therapeutic cloning, which some believe is a slippery slope to reproductive cloning. On the other hand, adult stem cells are already in some degree specialized, recipients may receive their own stem cells. They are flexible but they have shown mixed degree of availability. Adult stem cells are not pluripotent. They may not exist for all organs. They are difficult to purify and they cannot be maintained well outside the body. In order to draw the future avenues in this field, existent discrepancies between the results need to be clarified. In this study, we will review the different aspects and challenges of using embryonic or adult stem cells in clinical islet transplantation for the treatment of type 1 diabetes.

  19. Red cell distribution width in type 2 diabetic patients

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    Nada AM


    Full Text Available Aml Mohamed Nada Department of Internal Medicine, Unit of Endocrinology, Diabetes and Metabolism, Faculty of Medicine, Mansoura University, Mansoura, Egypt Objective: To study the indices of some elements of the complete blood count, in type 2 diabetic patients, in comparison with nondiabetic healthy controls; and to find out the effects of glycemic control and different medications on these indices. To the best of our knowledge, this study is novel in our environment and will serve as a foundation for other researchers in this field. Methods: This retrospective study included 260 type 2 diabetic patients on treatment and 44 healthy control subjects. Sex, age, weight, height, blood pressure, complete blood count, fasting plasma glucose, hemoglobin A1c (HbA1c, and lipid profile data, were available for all of the study population. For diabetic patients, data on duration of diabetes and all medications were also available. Results: Red cell distribution width (RDW was significantly higher in diabetic patients than in control subjects (P=0.008. It was also higher in patients with uncontrolled glycemia (HbA1c >7% than those with good control (HbA1c ≤7%; P=0.035. Mean platelet volume (MPV was comparable in both diabetic patients and healthy controls (P=0.238. RDW and MPV did not significantly correlate with fasting plasma glucose, HbA1c, or duration of diabetes. Both aspirin and clopidogrel did not show a significant effect on MPV. Both insulin and oral hypoglycemic agents did not show a significant effect on RDW, mean corpuscular volume, MPV, platelet count, or white blood cell count. Diabetic patients treated with indapamide or the combined thiazides and angiotensin receptor blockers showed no significant difference in RDW when compared with the control subjects. Conclusion: RDW, which is recently considered as an inflammatory marker with a significant predictive value of mortality in diseased and healthy populations, is significantly higher in

  20. When is an Alveolar Type 2 Cell an Alveolar Type 2 Cell? A Conundrum for Lung Stem Cell Biology and Regenerative Medicine. (United States)

    Beers, Michael F; Moodley, Yuben


    Generating mature, differentiated, adult lung cells from pluripotent cells such as induced pluripotent cells (iPS) and embryonic stem cells (ES) offers the hope of both generating disease specific in vitro models and creating definitive and personalized therapies for a host of debilitating lung parenchymal and airway diseases. With the goal of advancing lung regenerative medicine, several groups have developed and reported on protocols utilizing either defined media, co-culture with mesenchymal components, or sequential treatments mimicking lung development, to obtain distal lung epithelial cells from stem cell precursors. However, there remains significant controversy about the degree of differentiation of these cells compared to their primary counterparts coupled with a lack of consistency or uniformity in assessing the resultant phenotypes. Given the inevitable, exponential expansion of these approaches and the probable but yet to emerge 2nd and higher generation techniques to create such assets, we were prompted to pose the question: "What makes a lung epithelial cell a lung epithelial cell?" and more specifically for this Perspective "What are the minimum features that constitute an alveolar type II epithelial cell (AT2)". In addressing this, we summarize a body of work spanning nearly five decades amassed by a series of "lung epithelial cell biology pioneers" which carefully describes well characterized molecular, functional, and morphological features critical for discriminate assessment of an AT2 phenotype. Armed with this we propose a series of core criteria to assist the field in confirming that cells obtained following a differentiating protocol are indeed mature and functional AT2 epithelial cells.

  1. Clostridium botulinum Type E Toxins Bind to Caco-2 Cells by a Different Mechanism from That of Type A Toxins

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    Full Text Available Cultured Clostridium botulinum strains produce progenitor toxins designated as 12S, 16S, and 19S toxins. The 12S toxin consists of a neurotoxin (NTX, 7S and a non-toxic non-hemagglutinin (NTNH. The 16S and 19S toxins are formed by conjugation of the 12S toxin with hemagglutinin (HA, and the 19S toxin is a dimer of the 16S toxin. Type A cultures produce all 3 of these progenitor toxins, while type E produces only the 12S toxin. The 7S toxin is cleaved into heavy (H and light (L chains by a protease(s in some strains, and the H chain has 2 domains, the N-terminus (Hn and C-terminus (Hc. It has been reported that type A toxins bind to the intestinal cells or cultured cells via either HA or Hc. In this study, we investigated the binding of type A and E toxins to Caco-2 cells using Western blot analysis. Both the type E 7S and 12S toxins bound to the cells, with the 7S toxin binding more strongly, whereas, in the type A strain, only the 16S/19S toxins showed obvious binding. Pre-incubation of the type E 7S toxin with IgG against recombinant type E Hc significantly inhibited the 7S toxin binding, indicating that Hc might be a main binding domain of the type E toxin.

  2. Lineage relationship of prostate cancer cell types based on gene expression

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    Ware Carol B


    Full Text Available Abstract Background Prostate tumor heterogeneity is a major factor in disease management. Heterogeneity could be due to multiple cancer cell types with distinct gene expression. Of clinical importance is the so-called cancer stem cell type. Cell type-specific transcriptomes are used to examine lineage relationship among cancer cell types and their expression similarity to normal cell types including stem/progenitor cells. Methods Transcriptomes were determined by Affymetrix DNA array analysis for the following cell types. Putative prostate progenitor cell populations were characterized and isolated by expression of the membrane transporter ABCG2. Stem cells were represented by embryonic stem and embryonal carcinoma cells. The cancer cell types were Gleason pattern 3 (glandular histomorphology and pattern 4 (aglandular sorted from primary tumors, cultured prostate cancer cell lines originally established from metastatic lesions, xenografts LuCaP 35 (adenocarcinoma phenotype and LuCaP 49 (neuroendocrine/small cell carcinoma grown in mice. No detectable gene expression differences were detected among serial passages of the LuCaP xenografts. Results Based on transcriptomes, the different cancer cell types could be clustered into a luminal-like grouping and a non-luminal-like (also not basal-like grouping. The non-luminal-like types showed expression more similar to that of stem/progenitor cells than the luminal-like types. However, none showed expression of stem cell genes known to maintain stemness. Conclusions Non-luminal-like types are all representatives of aggressive disease, and this could be attributed to the similarity in overall gene expression to stem and progenitor cell types.

  3. Amiloride-sensitive channels in type I fungiform taste cells in mouse

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    Clapp Tod R


    Full Text Available Abstract Background Taste buds are the sensory organs of taste perception. Three types of taste cells have been described. Type I cells have voltage-gated outward currents, but lack voltage-gated inward currents. These cells have been presumed to play only a support role in the taste bud. Type II cells have voltage-gated Na+ and K+ current, and the receptors and transduction machinery for bitter, sweet, and umami taste stimuli. Type III cells have voltage-gated Na+, K+, and Ca2+ currents, and make prominent synapses with afferent nerve fibers. Na+ salt transduction in part involves amiloride-sensitive epithelial sodium channels (ENaCs. In rodents, these channels are located in taste cells of fungiform papillae on the anterior part of the tongue innervated by the chorda tympani nerve. However, the taste cell type that expresses ENaCs is not known. This study used whole cell recordings of single fungiform taste cells of transgenic mice expressing GFP in Type II taste cells to identify the taste cells responding to amiloride. We also used immunocytochemistry to further define and compare cell types in fungiform and circumvallate taste buds of these mice. Results Taste cell types were identified by their response to depolarizing voltage steps and their presence or absence of GFP fluorescence. TRPM5-GFP taste cells expressed large voltage-gated Na+ and K+ currents, but lacked voltage-gated Ca2+ currents, as expected from previous studies. Approximately half of the unlabeled cells had similar membrane properties, suggesting they comprise a separate population of Type II cells. The other half expressed voltage-gated outward currents only, typical of Type I cells. A single taste cell had voltage-gated Ca2+ current characteristic of Type III cells. Responses to amiloride occurred only in cells that lacked voltage-gated inward currents. Immunocytochemistry showed that fungiform taste buds have significantly fewer Type II cells expressing PLC signalling

  4. Effects of Cell Type and Culture Media on Interleukin-6 Secretion in Response to Environmental Particles


    Veranth, John M; Cutler, N. Shane; Kaser, Erin G.; Reilly, Christopher A.; Yost, Garold S.


    Cultured lung cells provide an alternative to animal exposures for comparing the effects of different types of air pollution particles. Studies of particulate matter in vitro have reported proinflammatory cytokine signaling in response to many types of environmental particles, but there have been few studies comparing identical treatments in multiple cell types or identical cells with alternative cell culture protocols. We compared soil-derived, diesel, coal fly ash, titanium dioxide, and kao...

  5. Chronic lymphocytic lymphoma and concomitant renal cell carcinoma (Clear Cell Type: Review of the literature

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    Burak Uz


    Full Text Available In the present report, a 73 years-old male patient who developed clear cell type renal cell carcinoma (RCC 5 years after the diagnosis of chronic lymphocytic lymphoma (CLL and plausible explanations for this association were discussed by the authors. The incidence of CLL and RCC occurring in the same patient is higher than that expected in the general population. Various explicative hypotheses of this concurrence include treatment-related development of a second malignancy, immunomodulatory mechanisms, viral aetiology, cytokine (interleukin 6 release from a tumor, and common genetic mutations. Further investigations are warranted.

  6. LagC is required for cell-cell interactions that are essential for cell-type differentiation in Dictyostelium. (United States)

    Dynes, J L; Clark, A M; Shaulsky, G; Kuspa, A; Loomis, W F; Firtel, R A


    Strain AK127 is a developmental mutant of Dictyostelium discoideum that was isolated by restriction enzyme-mediated integration (REMI). Mutant cells aggregate normally but are unable to proceed past the loose aggregate stage. The cloned gene, lagC (loose aggregate C), encodes a novel protein of 98 kD that contains an amino-terminal signal sequence and a putative carboxy-terminal transmembrane domain. The mutant strain AK127 shows no detectable lagC transcript upon Northern analysis, indicating that the observed phenotype is that of a null allele. Expression of the lagC cDNA in AK127 cells complements the arrest at the loose aggregate stage, indicating that the mutant phenotype results from disruption of the lagC gene. In wild-type cells, lagC mRNA is induced at the loose aggregate stage and is expressed through the remainder of development. lagC- null cells aggregate but then disaggregate and reaggregate to form small granular mounds. Mature spores are produced at an extremely low efficiency (rasD and CP2 and do not express the DIF-induced prestalk-specific gene ecmA or the cAMP-induced prespore-specific gene SP60 to significant levels. In chimeric organisms resulting from the coaggregation of lagC- null and wild-type cells, cell-type-specific gene expression is rescued in the lagC- null cells; however, lagC- prespore cells are localized to the posterior of the prespore region and do not form mature spores, suggesting that LagC protein has both no cell-autonomous and cell-autonomous functions. Overexpression of lagC from an actin promoter in both wild-type and lagC- cells causes a delay at the tight aggregate stage, the first stage requiring LagC activity. These results suggest that the LagC protein functions as a nondiffusible cell-cell signaling molecule that is required for multicellular development.

  7. Internationally recruited nurses from India and the Philippines in the United Kingdom: the decision to emigrate

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    Maben Jill


    Full Text Available Abstract Background The United Kingdom has recruited nurses from countries with a reported surplus in their nursing workforce, such as India and the Philippines. However, little is known about the decision to emigrate made by nurses from these countries. One theory suggests that individuals weigh the benefits and costs of migration: the push and pull factors. This paper challenges the restricted economic focus of this predominant theory and compares the diverse motivations of nurses from different countries as well as those of nurses with previous migratory experience and first-time migrants. Methods This research was undertaken in a National Health Service acute trust in London by means of a qualitative interpretative approach. Data were collected through face-to-face longitudinal and cross-sectional interviews with internationally recruited nurses from India (n = 6 and the Philippines (n = 15; and analysis of their narratives was used to generate data about their expectations and experiences. Data were analysed by means of a framework approach that allowed for intra-case and cross-case analysis. Results From an individual perspective, nurses in this study reported economic reasons as the main trigger for migration in the first instance. Yet this doesn't entirely explain the decision to move from previous migratory destinations (e.g. Saudi Arabia where economic needs are already fulfilled. In these cases migration is influenced by professional and social aspirations that highlight the influence of the cultural environment – specifically some religious and gender-related issues. Family support and support from migratory networks in the country of origin and destination were also important elements conducive to and supportive of migration. Nurses from India report coming to the United Kingdom to stay, while Filipina nurses come as temporary migrants sending remittances to support their families in the Philippines. Conclusion This study shows

  8. Environmental correlates of temporary emigration for female Weddell seals and consequences for recruitment (United States)

    Stauffer, Glenn E.; Rotella, Jay J.; Garrott, Robert A.; Kendall, William


    In colonial-breeding species, prebreeders often emigrate temporarily from natal reproductive colonies then subsequently return for one or more years before producing young. Variation in attendance–nonattendance patterns can have implications for subsequent recruitment. We used open robust-design multistate models and 28 years of encounter data for prebreeding female Weddell seals (Leptonychotes weddellii [Lesson]) to evaluate hypotheses about (1) the relationships of temporary emigration (TE) probabilities to environmental and population size covariates and (2) motivations for attendance and consequences of nonattendance for subsequent probability of recruitment to the breeding population. TE probabilities were density dependent (βˆBPOP = 0.66,  = 0.17; estimated effects [β] and standard errors of population size in the previous year) and increased when the fast-ice edge was distant from the breeding colonies (βˆDIST = 0.75,  = 0.04; estimated effects and standard errors of distance to the sea-ice edge in the current year on TE probability in the current year) and were strongly age and state dependent. These results suggest that trade-offs between potential benefits and costs of colony attendance vary annually and might influence motivation to attend colonies. Recruitment probabilities were greatest for seals that consistently attended colonies in two or more years (e.g.,  = 0.56, SD = 0.17) and lowest for seals that never or inconsistently attended prior to recruitment (e.g.,  = 0.32, SD = 0.15), where denotes the mean recruitment probability (over all years) for 10-year-old seals for the specified prebreeder state. In colonial-breeding seabirds, repeated colony attendance increases subsequent probability of recruitment to the adult breeding population; our results suggest similar implications for a marine mammal and are consistent with the hypothesis that prebreeders were motivated to attend reproductive colonies to gain reproductive skills or

  9. Emigration, Education, and Social Change among Eastern and Southern Europeans in Their Homelands and in the United States, 1890 - 1940. Final Report. (United States)

    Smith, Timothy L.

    This report is a summary of research already completed which concerns emigration, education, and social change among Eastern and Southern Europeans in their homelands and in the United States from 1890 to 1940. (Author/EK)

  10. Cell type-specific and common characteristics of exosomes derived from mouse cell lines: Yield, physicochemical properties, and pharmacokinetics. (United States)

    Charoenviriyakul, Chonlada; Takahashi, Yuki; Morishita, Masaki; Matsumoto, Akihiro; Nishikawa, Makiya; Takakura, Yoshinobu


    Exosomes are small membrane vesicles secreted from cells and are expected to be used as drug delivery systems. Important characteristics of exosomes, such as yield, physicochemical properties, and pharmacokinetics, may be different among different cell types. However, there is limited information about the effect of cell type on these characteristics. In the present study, we evaluated these characteristics of exosomes derived from five different types of mouse cell lines: B16BL6 murine melanoma cells, C2C12 murine myoblast cells, NIH3T3 murine fibroblasts cells, MAEC murine aortic endothelial cells, and RAW264.7 murine macrophage-like cells. Exosomes were collected using a differential ultracentrifugation method. The exosomes collected from all the cell types were negatively charged globular vesicles with a diameter of approximately 100nm. C2C12 and RAW264.7 cells produced more exosomes than the other types of cells. The exosomes were labeled with a fusion protein of Gaussia luciferase and lactadherin to evaluate their pharmacokinetics. After intravenous injection into mice, all the exosomes rapidly disappeared from the systemic circulation and mainly distributed to the liver. In conclusion, the exosome yield was significantly different among the cell types, and all the exosomes evaluated in this study showed comparable physicochemical and pharmacokinetic properties.

  11. Cell type-specific responses of peripheral blood mononuclear cells to silver nanoparticles. (United States)

    Greulich, C; Diendorf, J; Gessmann, J; Simon, T; Habijan, T; Eggeler, G; Schildhauer, T A; Epple, M; Köller, M


    Silver nanoparticles (Ag-NP) are increasingly used in biomedical applications because of their remarkable antimicrobial activity. In biomedicine, Ag-NP are coated onto or embedded in wound dressings, surgical instruments and bone substitute biomaterials, such as silver-containing calcium phosphate cements. Free Ag-NP and silver ions are released from these coatings or after the degradation of a biomaterial, and may come into close contact with blood cells. Despite the widespread use of Ag-NP as an antimicrobial agent, there is a serious lack of information on the biological effects of Ag-NP on human blood cells. In this study, the uptake of Ag-NP by peripheral monocytes and lymphocytes (T-cells) was analyzed, and the influence of nanosilver on cell biological functions (proliferation, the expression of adhesion molecules, cytokine release and the generation of reactive oxygen species) was studied. After cell culture in the presence of monodispersed Ag-NP (5-30μgml(-1) silver concentration), agglomerates of nanoparticles were detected within monocytes (CD14+) but not in T-cells (CD3+) by light microscopy, flow cytometry and combined focused ion beam/scanning electron microscopy. The uptake rate of nanoparticles was concentration dependent, and the silver agglomerates were typically found in the cytoplasm. Furthermore, a concentration-dependent activation (e.g. an increased expression of adhesion molecule CD54) of monocytes at Ag-NP concentrations of 10-15μgml(-1) was observed, and cytotoxicity of Ag-NP-treated monocytes was observed at Ag-NP levels of 25μgml(-1) and higher. However, no modulation of T-cell proliferation was observed in the presence of Ag-NP. Taken together, our results provide the first evidence for a cell-type-specific uptake of Ag-NP by peripheral blood mononuclear cells (PBMC) and the resultant cellular responses after exposure.

  12. Types of HLA in the bladder transitional cell carcinoma (TCC). (United States)

    Yılmaz, Erkan; Uğur Özalp, Ali; Cekmen, Arman; Eren, Bülent; Onal, Bülent; Akkuş, Emre; Erdoğan, Ergun


    HLA plays a complementary role in the interaction between tumor and body immunology. The aim of this study was to determine the existence of the association between the HLA system and transitional cell carcinoma (TCC). Using standard micro-lymphocytotoxic method of Terasaki, HLA-A, B, DR and DQ antigen types of 30 patients with TCC of the bladder were compared with the control group (30 healthy people). In the TCC patient group, HLA -DQ6(1) and HLA -DQ7(3) antigens were detected with a significantly higher frequency than in the control group (p=0.018 and p=0.038, respectively), whereas HLA-A10, B4, DR53 and DQ1 antigens were detected with significantly higher frequency in the control group (p less 0.05 in all). It suggests that patients who had the antigens detected were at higher risk of TCC, and the ones who had the antigens displaying protective features as were detected in the control group, were at lesser risk.

  13. Steviol Glycosides Modulate Glucose Transport in Different Cell Types

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    Benedetta Rizzo


    Full Text Available Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway.

  14. Steviol glycosides modulate glucose transport in different cell types. (United States)

    Rizzo, Benedetta; Zambonin, Laura; Angeloni, Cristina; Leoncini, Emanuela; Dalla Sega, Francesco Vieceli; Prata, Cecilia; Fiorentini, Diana; Hrelia, Silvana


    Extracts from Stevia rebaudiana Bertoni, a plant native to Central and South America, have been used as a sweetener since ancient times. Currently, Stevia extracts are largely used as a noncaloric high-potency biosweetener alternative to sugar, due to the growing incidence of type 2 diabetes mellitus, obesity, and metabolic disorders worldwide. Despite the large number of studies on Stevia and steviol glycosides in vivo, little is reported concerning the cellular and molecular mechanisms underpinning the beneficial effects on human health. The effect of four commercial Stevia extracts on glucose transport activity was evaluated in HL-60 human leukaemia and in SH-SY5Y human neuroblastoma cells. The extracts were able to enhance glucose uptake in both cellular lines, as efficiently as insulin. Our data suggest that steviol glycosides could act by modulating GLUT translocation through the PI3K/Akt pathway since treatments with both insulin and Stevia extracts increased the phosphorylation of PI3K and Akt. Furthermore, Stevia extracts were able to revert the effect of the reduction of glucose uptake caused by methylglyoxal, an inhibitor of the insulin receptor/PI3K/Akt pathway. These results corroborate the hypothesis that Stevia extracts could mimic insulin effects modulating PI3K/Akt pathway.

  15. Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis (United States)

    Størling, Joachim; Pociot, Flemming


    Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established. A significant part of the genes located in the T1D susceptibility loci are expressed in human islets and β cells and mounting evidence suggests that some of these genes modulate the β-cell response to the immune system and viral infection and regulate apoptotic β-cell death. Here, we discuss the current status of T1D susceptibility loci and candidate genes with focus on pancreatic islet cell inflammation and β-cell apoptosis. PMID:28212332

  16. Type 1 Diabetes Candidate Genes Linked to Pancreatic Islet Cell Inflammation and Beta-Cell Apoptosis. (United States)

    Størling, Joachim; Pociot, Flemming


    Type 1 diabetes (T1D) is a chronic immune-mediated disease resulting from the selective destruction of the insulin-producing pancreatic islet β-cells. Susceptibility to the disease is the result of complex interactions between environmental and genetic risk factors. Genome-wide association studies (GWAS) have identified more than 50 genetic regions that affect the risk of developing T1D. Most of these susceptibility loci, however, harbor several genes, and the causal variant(s) and gene(s) for most of the loci remain to be established. A significant part of the genes located in the T1D susceptibility loci are expressed in human islets and β cells and mounting evidence suggests that some of these genes modulate the β-cell response to the immune system and viral infection and regulate apoptotic β-cell death. Here, we discuss the current status of T1D susceptibility loci and candidate genes with focus on pancreatic islet cell inflammation and β-cell apoptosis.

  17. The Optimal Emigration out of Population of Bisexual Branching Processes by a Barrier Strategy%边界策略下的最优移出移民

    Institute of Scientific and Technical Information of China (English)

    张学清; 邢永胜


    The way to maximize the emigration out of population is studied.It's shown that a band strategy will be the best strategy,and the total emigration by a barrier strategy is obtained.%考虑了最多移民数量策略,证明了边界策略为最优移民策略,并且给出了边界策略下最优的移民数量.

  18. General approach for in vivo recovery of cell type-specific effector gene sets. (United States)

    Barsi, Julius C; Tu, Qiang; Davidson, Eric H


    Differentially expressed, cell type-specific effector gene sets hold the key to multiple important problems in biology, from theoretical aspects of developmental gene regulatory networks (GRNs) to various practical applications. Although individual cell types of interest have been recovered by various methods and analyzed, systematic recovery of multiple cell type-specific gene sets from whole developing organisms has remained problematic. Here we describe a general methodology using the sea urchin embryo, a material of choice because of the large-scale GRNs already solved for this model system. This method utilizes the regulatory states expressed by given cells of the embryo to define cell type and includes a fluorescence activated cell sorting (FACS) procedure that results in no perturbation of transcript representation. We have extensively validated the method by spatial and qualitative analyses of the transcriptome expressed in isolated embryonic skeletogenic cells and as a consequence, generated a prototypical cell type-specific transcriptome database.

  19. Expression weighted cell type enrichments reveal genetic and cellular nature of major brain disorders

    Directory of Open Access Journals (Sweden)

    Nathan Gerald Skene


    Full Text Available The cell types that trigger the primary pathology in many brain diseases remain largely unknown. One route to understanding the primary pathological cell type for a particular disease is to identify the cells expressing susceptibility genes. Although this is straightforward for monogenic conditions where the causative mutation may alter expression of a cell type specific marker, methods are required for the common polygenic disorders. We developed the Expression Weighted Cell Type Enrichment (EWCE method that uses single cell transcriptomes to generate the probability distribution associated with a gene list having an average level of expression within a cell type. Following validation, we applied EWCE to human genetic data from cases of epilepsy, Schizophrenia, Autism, Intellectual Disability, Alzheimer’s disease, Multiple Sclerosis and anxiety disorders. Genetic susceptibility primarily affected microglia in Alzheimer’s and Multiple Sclerosis; was shared between interneurons and pyramidal neurons in Autism and Schizophrenia; while intellectual disabilities and epilepsy were attributable to a range of cell-types, with the strongest enrichment in interneurons. We hypothesised that the primary cell type pathology could trigger secondary changes in other cell types and these could be detected by applying EWCE to transcriptome data from diseased tissue. In Autism, Schizophrenia and Alzheimer’s disease we find evidence of pathological changes in all of the major brain cell types. These findings give novel insight into the cellular origins and progression in common brain disorders. The methods can be applied to any tissue and disorder and have applications in validating mouse models.

  20. Concise Review: Methods and Cell Types Used to Generate Down Syndrome Induced Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Youssef Hibaoui


    Full Text Available Down syndrome (DS, trisomy 21, is the most common viable chromosomal disorder, with an incidence of 1 in 800 live births. Its phenotypic characteristics include intellectual impairment and several other developmental abnormalities, for the majority of which the pathogenetic mechanisms remain unknown. Several models have been used to investigate the mechanisms by which the extra copy of chromosome 21 leads to the DS phenotype. In the last five years, several laboratories have been successful in reprogramming patient cells carrying the trisomy 21 anomaly into induced pluripotent stem cells, i.e., T21-iPSCs. In this review, we summarize the different T21-iPSCs that have been generated with a particular interest in the technical procedures and the somatic cell types used for the reprogramming.

  1. Identification of intermediate cell types by keratin expression in the developing human prostate

    NARCIS (Netherlands)

    Xue, Y; Smedts, F; Debruyne, FMJ; de la Rosette, JJMCH; Schalken, JA


    BACKGROUND. The secretory acini of the adult human prostate contain basal, luminal, and intermediate types of exocrine cells. Intermediate cells are thought to play an important role in normal growth and neoplastic transformation. In this study we investigated whether this cell type is present in ea

  2. Delayed Workforce Entry and High Emigration Rates for Recent Canadian Radiation Oncology Graduates

    Energy Technology Data Exchange (ETDEWEB)

    Loewen, Shaun K., E-mail: [CancerCare Manitoba, Winnipeg, MB (Canada); Halperin, Ross; Lefresne, Shilo [BC Cancer Agency, Vancouver, BC (Canada); Trotter, Theresa [Tom Baker Cancer Centre, Calgary, AB (Canada); Stuckless, Teri [Dr H. Bliss Murphy Cancer Centre, St. John' s, NL (Canada); Brundage, Michael [Cancer Centre of Southeastern Ontario, Kingston, ON (Canada)


    Purpose: To determine the employment status and location of recent Canadian radiation oncology (RO) graduates and to identify current workforce entry trends. Methods and Materials: A fill-in-the-blank spreadsheet was distributed to all RO program directors in December 2013 and June 2014, requesting the employment status and location of their graduates over the last 3 years. Visa trainee graduates were excluded. Results: Response rate from program directors was 100% for both survey administrations. Of 101 graduates identified, 99 (98%) had known employment status and location. In the December survey, 5 2013 graduates (16%), 17 2012 graduates (59%), and 18 2011 graduates (75%) had permanent staff employment. Six months later, 5 2014 graduates (29%), 15 2013 graduates (48%), 24 2012 graduates (83%), and 21 2011 graduates (88%) had secured staff positions. Fellowships and temporary locums were common for those without staff employment. The proportion of graduates with staff positions abroad increased from 22% to 26% 6 months later. Conclusions: Workforce entry for most RO graduates was delayed but showed steady improvement with longer time after graduation. High emigration rates for jobs abroad signify domestic employment challenges for newly certified, Canadian-trained radiation oncologists. Coordination on a national level is required to address and regulate radiation oncologist supply and demand disequilibrium in Canada.

  3. p-Type MWT. Integrated cell and module technology

    Energy Technology Data Exchange (ETDEWEB)

    Tool, C.J.J.; Kossen, E.J.; Bennett, I.J.


    A major issue of concern in MWT solar cells is the increased leakage current at reversed bias voltage through the vias compared. At ECN we have been working on reducing this leakage current to levels comparable to H-pattern cells. In this study we present the results of this work. We further show the benefit of a combined cell and module design for MWT solar cells. At the cell level, MWT production costs per wafer are comparable with H-pattern while the cell output increases. At the module level this design results in a further increase of the power output.

  4. p-type MWT. Integrated Cell and Module Technology

    Energy Technology Data Exchange (ETDEWEB)

    Tool, C.J.J.; Kossen, E.J.; Bennett, I.J. [ECN Solar Energy, Petten (Netherlands)


    A major issue of concern in MWT (metal wrap-through) solar cells is the increased leakage current at reversed bias voltage through the vias compared. At ECN we have been working on reducing this leakage current to levels comparable to H-pattern cells. In this study we present the results of this work. We further show the benefit of a combined cell and module design for MWT solar cells. At the cell level, MWT production costs per wafer are comparable with H-pattern while the cell output increases. At the module level this design results in a further increase of the power output.

  5. Effects of Radiofrequency Ablation on Lymphocyte Subsets and Type 1/Type 2 T Cell Subpopulations in Patients with Hepatocellular Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Yan-bin Wang; Wei-Guo Xu; He-liang Liu; Kun Yan; Lin Ma; Wan-hou Guo


    Objective: To evaluate whether radiofrequency ablation (RFA) might have an influence on immune status in hepatocellular carcinoma (HCC) patients. Methods: We measured the T lymphocytes, B lymphocyte and NK cells, and determined the population of Th1, Th2, Tc1 and Tc2 of peripheral blood samples taken from 26 HCC patients before and after RFA. Results: The proportion of Type1 cells (Th1 and Tc1) and NK cells were significantly increased after RFA, especially in patients of the following subgroups: male, age>55 years, pathological grade I-II tumor, clinical stage I-II or Child-Pugh A and B. Conclusion: Type1 cells and NK cells in HCC patients were increased in a short period after RFA.

  6. Beta-cell function and mass in type 2 diabetes. (United States)

    Larsen, Marianne O


    The aim of the work described here was to improve our understanding of beta-cell function (BCF) and beta-cell mass (BCM) and their relationship in vivo using the minipig as a model for some of the aspects of human type 2 diabetes (T2DM). More specifically, the aim was to evaluate the following questions: How is BCF, especially high frequency pulsatile insulin secretion, affected by a primary reduction in BCM or by primary obesity or a combination of the two in the minipig? Can evaluation of BCF in vivo be used as a surrogate measure to predict BCM in minipigs over a range of BCM and body weight? We first developed a minipig model of reduced BCM and mild diabetes using administration of a combination of streptozotocin (STZ) and nicotinamide (NIA) as a tool to study effects of a primary reduction of BCM on BCF. The model was characterized using a mixed-meal oral glucose tolerance test and intravenous stimulation with glucose and arginine as well as by histology of the pancreas after euthanasia. It was shown that stable, moderate diabetes can be induced and that the model is characterized by fasting and postprandial hyperglycemia, reduced insulin secretion and reduced BCM. Several defects in insulin secretion are well documented in human T2DM; however, the role in the pathogenesis and the possible clinical relevance of high frequency (rapid) pulsatile insulin secretion is still debated. We therefore investigated this phenomenon in normal minipigs and found easily detectable pulses in peripheral vein plasma samples that were shown to be correlated with pulses found in portal vein plasma. Furthermore, the rapid kinetics of insulin in the minipig strongly facilitates pulse detection. These characteristics make the minipig particularly suitable for studying the occurrence of disturbed pulsatility in relation to T2DM. Disturbances of rapid pulsatile insulin secretion have been reported to be a very early event in the development of T2DM and include disorderliness of pulses

  7. Tumor Budding Cells, Cancer Stem Cells and Epithelial-Mesenchymal Transition-type Cells in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Eva eKaramitopoulou


    Full Text Available Pancreatic ductal adenocarcinoma (PDAC is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4 and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with WNT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT. Emerging evidence has demonstrated that cancer stem cells (CSCs, small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5 of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric and ampullary carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs and EMT-type cells in PDAC.

  8. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage. (United States)

    Aparicio-Domingo, Patricia; Romera-Hernandez, Monica; Karrich, Julien J; Cornelissen, Ferry; Papazian, Natalie; Lindenbergh-Kortleve, Dicky J; Butler, James A; Boon, Louis; Coles, Mark C; Samsom, Janneke N; Cupedo, Tom


    Disruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence of this high mitotic activity, mucosal surfaces are frequently targeted by anticancer therapies, leading to dose-limiting side effects. The cellular mechanisms that control tissue protection and mucosal healing in response to intestinal damage remain poorly understood. Type 3 innate lymphoid cells (ILC3s) are regulators of homeostasis and tissue responses to infection at mucosal surfaces. We now demonstrate that ILC3s are required for epithelial activation and proliferation in response to small intestinal tissue damage induced by the chemotherapeutic agent methotrexate. Multiple subsets of ILC3s are activated after intestinal tissue damage, and in the absence of ILC3s, epithelial activation is lost, correlating with increased pathology and severe damage to the intestinal crypts. Using ILC3-deficient Lgr5 reporter mice, we show that maintenance of intestinal stem cells after damage is severely impaired in the absence of ILC3s or the ILC3 signature cytokine IL-22. These data unveil a novel function of ILC3s in limiting tissue damage by preserving tissue-specific stem cells.


    Institute of Scientific and Technical Information of China (English)

    Li Jian; Xia Yongjing; Jiang Lei; Li Hongxia; Hu Yajun; Yi Lin; Hu Shixue; Xu Hongji


    Objective: To study the growth suppression of lung adenocarcinoma cell by the introduction of wild-type P53gene and explore a gene therapy approach for lung adenocarcinoma. Methods: A replication-deficient adenovirus vector encoding a wild-type P53 was constructed and transfected into the cultured human lung adenocarcinoma cell line GLC-82. The efficiency of gene transfection and expression was detected by immunochemical staining and polymerase chain reaction. The cell growth rate and cell cycle were analysed by cell-counting and flow cytometry. Results: Wild-type P53 gene could be quickly and effectively transfected into the cells by adenovirus vector. Wild-type P53 expression could inhibit GLC-82 cell proliferation and induce apoptosis.Conclusion: The results indicated that recombinant adenovirus expressing wild-type P53 might be useful vector for gene therapy of human lung adenocarcinoma.

  10. Estimation of Cell-Type Composition Including T and B Cell Subtypes for Whole Blood Methylation Microarray Data. (United States)

    Waite, Lindsay L; Weaver, Benjamin; Day, Kenneth; Li, Xinrui; Roberts, Kevin; Gibson, Andrew W; Edberg, Jeffrey C; Kimberly, Robert P; Absher, Devin M; Tiwari, Hemant K


    DNA methylation levels vary markedly by cell-type makeup of a sample. Understanding these differences and estimating the cell-type makeup of a sample is an important aspect of studying DNA methylation. DNA from leukocytes in whole blood is simple to obtain and pervasive in research. However, leukocytes contain many distinct cell types and subtypes. We propose a two-stage model that estimates the proportions of six main cell types in whole blood (CD4+ T cells, CD8+ T cells, monocytes, B cells, granulocytes, and natural killer cells) as well as subtypes of T and B cells. Unlike previous methods that only estimate overall proportions of CD4+ T cell, CD8+ T cells, and B cells, our model is able to estimate proportions of naïve, memory, and regulatory CD4+ T cells as well as naïve and memory CD8+ T cells and naïve and memory B cells. Using real and simulated data, we are able to demonstrate that our model is able to reliably estimate proportions of these cell types and subtypes. In studies with DNA methylation data from Illumina's HumanMethylation450k arrays, our estimates will be useful both for testing for associations of cell type and subtype composition with phenotypes of interest as well as for adjustment purposes to prevent confounding in epigenetic association studies. Additionally, our method can be easily adapted for use with whole genome bisulfite sequencing (WGBS) data or any other genome-wide methylation data platform.

  11. Advances in understanding the cell types and approaches used for generating induced pluripotent stem cells. (United States)

    Li, Jun; Song, Wei; Pan, Guangjin; Zhou, Jun


    Successfully reprogramming somatic cells to a pluripotent state generates induced pluripotent stem (iPS) cells (or iPSCs), which have extensive self-renewal capacity like embryonic stem cells (ESCs). iPSCs can also generate daughter cells that can further undergo differentiation into various lineages or terminally differentiate to reach their final functional state. The discovery of how to produce iPSCs opened a new field of stem cell research with both intellectual and therapeutic benefits. The huge potential implications of disease-specific or patient-specific iPSCs have impelled scientists to solve problems hindering their applications in clinical medicine, especially the issues of convenience and safety. To determine the range of tissue types amenable to reprogramming as well as their particular characteristics, cells from three embryonic germ layers have been assessed, and the advantages that some tissue origins have over fibroblast origins concerning efficiency and accessibility have been elucidated. To provide safe iPSCs in an efficient and convenient way, the delivery systems and combinations of inducing factors as well as the chemicals used to generate iPSCs have also been significantly improved in addition to the efforts on finding better donor cells. Currently, iPSCs can be generated without c-Myc and Klf4 oncogenes, and non-viral delivery integration-free chemically mediated reprogramming methods have been successfully employed with relatively satisfactory efficiency. This paper will review recent advances in iPS technology by highlighting tissue origin and generation of iPSCs. The obstacles that need to be overcome for clinical applications of iPSCs are also discussed.

  12. Goblet Cell Carcinoid in a Patient with Neurofibromatosis Type 1: A Rare Combination

    Directory of Open Access Journals (Sweden)

    Tine Gregersen


    Full Text Available Neuroendocrine tumors are rare tumors primarily located in the gastrointestinal tract. Goblet cell carcinoid is a rare subgroup of neuroendocrine tumors located in the appendix. Neurofibromatosis type 1 is an autosomal dominant disorder caused by a mutation in the NF1 gene. Patients with neurofibromatosis type 1 have an increased incidence of typical neuroendocrine tumors, but it is unknown if this is the case with goblet cell carcinoids. We describe a patient with both neurofibromatosis type 1 and goblet cell carcinoid, that according to literature would occur in 0.00017 per million per year. This may suggest a previously unknown association between neurofibromatosis type 1 and goblet cell carcinoids.

  13. Ryanodine Receptors Selectively Interact with L Type Calcium Channels in Mouse Taste Cells.

    Directory of Open Access Journals (Sweden)

    Michelle R Rebello

    Full Text Available WE REPORTED THAT RYANODINE RECEPTORS ARE EXPRESSED IN TWO DIFFERENT TYPES OF MAMMALIAN PERIPHERAL TASTE RECEPTOR CELLS: Type II and Type III cells. Type II cells lack voltage-gated calcium channels (VGCCs and chemical synapses. In these cells, ryanodine receptors contribute to the taste-evoked calcium signals that are initiated by opening inositol trisphosphate receptors located on internal calcium stores. In Type III cells that do have VGCCs and chemical synapses, ryanodine receptors contribute to the depolarization-dependent calcium influx.The goal of this study was to establish if there was selectivity in the type of VGCC that is associated with the ryanodine receptor in the Type III taste cells or if the ryanodine receptor opens irrespective of the calcium channels involved. We also wished to determine if the ryanodine receptors and VGCCs require a physical linkage to interact or are simply functionally associated with each other. Using calcium imaging and pharmacological inhibitors, we found that ryanodine receptors are selectively associated with L type VGCCs but likely not through a physical linkage.Taste cells are able to undergo calcium induced calcium release through ryanodine receptors to increase the initial calcium influx signal and provide a larger calcium response than would otherwise occur when L type channels are activated in Type III taste cells.

  14. Stimulation of DNA synthesis in cultured rat alveolar type II cells

    Energy Technology Data Exchange (ETDEWEB)

    Leslie, C.C.; McCormick-Shannon, K.; Robinson, P.C.; Mason, R.J.


    Restoration of the alveolar epithelium after injury is thought to be dependent on the proliferation of alveolar type II cells. To understand the factors that may be involved in promoting type II cell proliferation in vivo, we determined the effect of potential mitogens and culture substrata on DNA synthesis in rat alveolar type II cells in primary culture. Type II cells cultured in basal medium containing 10% fetal bovine serum (FBS) exhibited essentially no DNA synthesis. Factors that stimulated /sup 3/H-thymidine incorporation included cholera toxin, epidermal growth factor, and rat serum. The greatest degree of stimulation was achieved by plating type II cells on an extracellular matrix prepared from bovine corneal endothelial cells and then by culturing the pneumocytes in medium containing rat serum, cholera toxin, insulin, and epidermal growth factor. Under conditions of stimulation of /sup 3/H-thymidine incorporation there was an increased DNA content per culture dish but no increase in cell number. The ability of various culture conditions to promote DNA synthesis in type II cells was verified by autoradiography. Type II cells were identified by the presence of cytoplasmic inclusions, which were visualized by tannic acid staining before autoradiography. These results demonstrate the importance of soluble factors and culture substratum in stimulating DNA synthesis in rat alveolar type II cells in primary culture.

  15. Late appearance of a type I alveolar epithelial cell marker during fetal rat lung development. (United States)

    Danto, S I; Zabski, S M; Crandall, E D


    Recent studies in fetal lung using immunological and molecular probes have revealed type I and type II cell phenotypic markers in primordial lung epithelial cells prior to the morphogenesis of these cell types. We have recently developed monoclonal antibodies specific for adult type I cells. To evaluate further the temporal appearance of the type I cell phenotype during alveolar epithelial cell ontogeny, we analyzed fetal lung development using one of our monoclonal antibodies (mAb VIII B2). The epitope recognized by mAb VIII B2 first appears in the canalicular stage of fetal lung development, at approx. embryonic day 19 (E19), in occasional, faintly stained tubules. Staining with this type I cell probe becomes more intense and more widespread with increasing gestational age, during which time the pattern of staining changes. Initially, all cells of the distal epithelial tubules are uniformly labelled along their apical and basolateral surfaces. As morphological differentiation of the alveolar epithelium proceeds, type I cell immunoreactivity appears to become restricted to the apical surface of the primitive type I cells in a pattern approaching that seen in the mature lung. We concurrently analyzed developing fetal lung with an antiserum to surfactant apoprotein-A (alpha-SP-A). Consistent with the findings of others, labeling of SP-A was first detectable in scattered cuboidal cells at E18. Careful examination of the double-labeled specimens suggested that some cells were reactive with both the VIII B2 and SP-A antibodies, particularly at E20. Confocal microscopic analysis of such sections from E20 lung confirmed this impression. Three populations of cells were detected: cells labeled only with alpha-SP-A, cells labeled only with mAb VIII B2, and a smaller subset of cells labeled by both.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. Calcium signaling and T-type calcium channels in cancer cell cycling

    Institute of Scientific and Technical Information of China (English)

    James T Taylor; Xiang-Bin Zeng; Jonathan E Pottle; Kevin Lee; Alun R Wang; Stephenie G Yi; Jennifer A S Scruggs; Suresh S Sikka; Ming Li


    Regulation of intracellular calcium is an important signaling mechanism for cell proliferation in both normal and cancerous cells. In normal epithelial cells,free calcium concentration is essential for cells to enter and accomplish the S phase and the M phase of the cell cycle. In contrast, cancerous cells can pass these phases of the cell cycle with much lower cytoplasmic free calcium concentrations, indicating an alternative mechanism has developed for fulfilling the intracellular calcium requirement for an increased rate of DNA synthesis and mitosis of fast replicating cancerous cells. The detailed mechanism underlying the altered calcium loading pathway remains unclear;however, there is a growing body of evidence that suggests the T-type Ca2+ channel is abnormally expressed in cancerous cells and that blockade of these channels may reduce cell proliferation in addition to inducing apoptosis. Recent studies also show that the expression of T-type Ca2+ channels in breast cancer cells is proliferation state dependent, i.e. the channels are expressed at higher levels during the fast-replication period, and once the cells are in a non-proliferation state, expression of this channel isminimal. Therefore, selectively blocking calcium entry into cancerous cells may be a valuable approach for preventing tumor growth. Since T-type Ca2+ channels are not expressed in epithelial cells, selective T-type Ca2+ channel blockers may be useful in the treatment of certain types of cancers.

  17. Inactivation of the transforming growth factor beta type II receptor in human small cell lung cancer cell lines

    DEFF Research Database (Denmark)

    Hougaard, S; Nørgaard, P; Abrahamsen, N;


    Transforming growth factor beta (TGF-beta) exerts a growth inhibitory effect on many cell types through binding to two types of receptors, the type I and II receptors. Resistance to TGF-beta due to lack of type II receptor (RII) has been described in some cancer types including small cell lung...... cancer (SCLC). The purpose of this study was to examine the cause of absent RII expression in SCLC cell lines. Northern blot analysis showed that RII RNA expression was very weak in 16 of 21 cell lines. To investigate if the absence of RII transcript was due to mutations, we screened the poly-A tract...... for mutations, but no mutations were detected. Additional screening for mutations of the RII gene revealed a GG to TT base substitution in one cell line, which did not express RII. This mutation generates a stop codon resulting in predicted synthesis of a truncated RII of 219 amino acids. The nature...

  18. Enrichment of putative human epidermal stem cells based on cell size and collagen type IV adhesiveness

    Institute of Scientific and Technical Information of China (English)

    Juxue Li; Enkui Duan; Chenglin Miao; Weixiang Guo; Liwei Jia; Jiaxi Zhou; Baohua Ma; Sha Peng; Shuang Liu; Yujing Cao


    The enrichment and identification of human epidermal stem cells (EpSCs) are of paramount importance for both basic research and clinical application. Although several approaches for the enrichment of EpSCs have been established, enriching a pure population of viable EpSCs is still a challenging task. An improved approach is worth developing to enhance the purity and viability of EpSCs. Here we report that cell size combined with collagen type IV adhesiveness can be used in an improved approach to enrich pure and viable human EpSCs. We separated the rapidly adherent keratinocytes into three populations that range in size from 5-7 μm (population A), to 7-9 μm (population B), to >9 μm (population C) in diameter, and found that human putative EpSCs could be further enriched in population A with the smallest size. Among the three populations, population A displayed the highest density of βl-integrin receptor, contained the highest percentage of cells in G0/G1 phase, showed the highest nucleus to cytoplasm ratio, and possessed the highest colony formation efficiency (CFE). When injected into murine blastocysts, these cells participated in multi-tissue formation. More significantly, compared with a previous approach that sorted putative EpSCs according to pl-integrin antibody staining, the viability of the EpSCs enriched by the improved approach was significantly enhanced. Our results provide a putative strategy for the enrichment of human EpSCs, and encourage further study into the role of cell size in stem cell biology.

  19. Effect of donor cell type on nuclear remodelling in rabbit somatic cell nuclear transfer embryos. (United States)

    Tian, J; Song, J; Li, H; Yang, D; Li, X; Ouyang, H; Lai, L


    Cloned rabbits have been produced for many years by somatic cell nuclear transfer (SCNT). The efficiency of cloning by SCNT, however, has remained extremely low. Most cloned embryos degenerate in utero, and the few that develop to term show a high incidence of post-natal death and abnormalities. The cell type used for donor nuclei is an important factor in nuclear transfer (NT). As reported previously, NT embryos reconstructed with fresh cumulus cells (CC-embryos) have better developmental potential than those reconstructed with foetal fibroblasts (FF-embryos) in vivo and in vitro. The reason for this disparity in developmental capacity is still unknown. In this study, we compared active demethylation levels and morphological changes between the nuclei of CC-embryos and FF-embryos shortly after activation. Anti-5-methylcytosine immunofluorescence of in vivo-fertilized and cloned rabbit embryos revealed that there was no detectable active demethylation in rabbit zygotes or NT-embryos derived from either fibroblasts or CC. In the process of nuclear remodelling, however, the proportion of nuclei with abnormal appearance in FF-embryos was significantly higher than that in CC-embryos during the first cell cycle. Our study demonstrates that the nuclear remodelling abnormality of cloned rabbit embryos may be one important factor for the disparity in developmental success between CC-embryos and FF-embryos.

  20. Transdifferentiation between Luminal- and Basal-Type Cancer Cells (United States)


    growth factor receptor 3; EREG, epiregulin (a member of EGF family); ITGA6; Integrin alpha 6; ITGB4, Integrin beta 4; Cox2, Cyclooxygenase 2; IL 1B...targets E-cadherin in LNCaP, an E-cadherin positive prostate cancer cell line, can reduce PKD1 activation as judged by S910 autophosphorylation (Fig 1C...purchased from Open Biosystems/Thermo Scientific. Cell culture and immunofluorescence staining. Prostate LNCaP and lung cancer cell lines were

  1. Genome-Derived Cytosolic DNA Mediates Type I Interferon-Dependent Rejection of B Cell Lymphoma Cells

    Directory of Open Access Journals (Sweden)

    Yu J. Shen


    Full Text Available The DNA damage response (DDR induces the expression of type I interferons (IFNs, but the underlying mechanisms are poorly understood. Here, we show the presence of cytosolic DNA in different mouse and human tumor cells. Treatment of cells with genotoxic agents increased the levels of cytosolic DNA in a DDR-dependent manner. Cloning of cytosolic DNA molecules from mouse lymphoma cells suggests that cytosolic DNA is derived from unique genomic loci and has the potential to form non-B DNA structures, including R-loops. Overexpression of Rnaseh1, which resolves R-loops, reduced the levels of cytosolic DNA, type I Ifn transcripts, and type I IFN-dependent rejection of lymphoma cells. Live-cell imaging showed a dynamic contact of cytosolic DNA with mitochondria, an important organelle for innate immune recognition of cytosolic nucleotides. In summary, we found that cytosolic DNA is present in many tumor cells and contributes to the immunogenicity of tumor cells.

  2. Effects of cell type and culture media on Interleukin-6 secretion in response to environmental particles. (United States)

    Veranth, John M; Cutler, N Shane; Kaser, Erin G; Reilly, Christopher A; Yost, Garold S


    Cultured lung cells provide an alternative to animal exposures for comparing the effects of different types of air pollution particles. Studies of particulate matter in vitro have reported proinflammatory cytokine signaling in response to many types of environmental particles, but there have been few studies comparing identical treatments in multiple cell types or identical cells with alternative cell culture protocols. We compared soil-derived, diesel, coal fly ash, titanium dioxide, and kaolin particles along with soluble vanadium and lipopolysaccharide, applied to airway-derived cells grown in submerged culture. Cell types included A549, BEAS-2B, RAW 264.7, and primary macrophages. The cell culture models (specific combinations of cell types and culture conditions) were reproducibly different in the cytokine signaling responses to the suite of treatments. Further, Interleukin-6 (IL-6) response to the treatments changed when the same cells, BEAS-2B, were grown in KGM versus LHC-9 media or in media containing bovine serum. The effect of changing media composition was reversible over multiple changes of media type. Other variables tested included culture well size and degree of confluence. The observation that sensitivity of a cell type to environmental agonists can be manipulated by modifying culture conditions suggests a novel approach for studying biochemical mechanisms of particle toxicity.

  3. Effects of cell type and culture media on Interleukin-6 secretion in response to environmental particles

    Energy Technology Data Exchange (ETDEWEB)

    Veranth, J.M.; Cutler, N.S.; Kaser, E.G.; Reilly, C.A.; Yost, G.S. [University of Utah, Salt Lake City, UT (United States)


    Cultured lung cells provide an alternative to animal exposures for comparing the effects of different types of air pollution particles. Studies of particulate matter in vitro have reported proinflammatory cytokine signaling in response to many types of environmental particles, but there have been few studies comparing identical treatments in multiple cell types or identical cells with alternative cell culture protocols. We compared soil-derived, diesel, coal fly ash, titanium dioxide, and kaolin particles along with soluble vanadium and lipopolysaccharide, applied to airway-derived cells grown in submerged culture. Cell types included A549, BEAS-2B, RAW 264.7, and primary macrophages. The cell culture models (specific combinations of cell types and culture conditions) were reproducibly different in the cytokine signaling responses to the suite of treatments. Further, Interleukin-6 (IL-6) response to the treatments changed when the same cells, BEAS-2B, were grown in KGM versus LHC-9 media or in media containing bovine serum. The effect of changing media composition was reversible over multiple changes of media type. Other variables tested included culture well size and degree of confluence. The observation that sensitivity of a cell type to environmental agonists can be manipulated by modifying culture conditions suggests a novel approach for studying biochemical mechanisms of particle toxicity.

  4. Red cell alloimmunisation in patients with different types of infections

    NARCIS (Netherlands)

    Evers, Dorothea; van der Bom, Johanna G; Tijmensen, Janneke; Middelburg, Rutger A; de Haas, Masja; Zalpuri, Saurabh; de Vooght, Karen M K; van de Kerkhof, Daan; Visser, Otto; Péquériaux, Nathalie C V; Hudig, Francisca; Zwaginga, Jaap Jan


    Red cell alloantigen exposure can cause alloantibody-associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case-control study within a sou

  5. Red cell alloimmunisation in patients with different types of infections.

    NARCIS (Netherlands)

    Evers, D.; Bom, J.G. Van Der; Tijmensen, J.; Middelburg, R.A.; Haas, M. de; Zalpuri, S.; Vooght, K.M. De; Kerkhof, D. van de; Visser, O; Pequeriaux, N.C.V.; Hudig, F.; Zwaginga, J.J.


    Red cell alloantigen exposure can cause alloantibody-associated morbidity. Murine models have suggested that inflammation modulates red cell alloimmunisation. This study quantifies alloimmunisation risks during infectious episodes in humans. We performed a multicentre case-control study within a sou

  6. A Primary Study of the Network Development of Emigrant Mail Business in Fujian%闽帮侨批业网络发展初探

    Institute of Scientific and Technical Information of China (English)



    "Emigrant Mail files" is a collection of records of human interactions in a specific historical era. Taking the Emigrant network development of Remittance House as a main line and according to the records of Emigrant Mail, we observed the development from the individuals to the entire Emigrant Mail network and thought that the Fujian Emigrant Mail was international and financial as a business organization which promoted the business of Emigrant Mail in accordance with the time and the place. Finally, an example of Wu Daosheng, who served his apprenticeship at Remittance House at the beginning and then opened a Jiannan Remittance House and then established a Jiannan Bank, illustrated how the Fujian Emigrant Mail developed by opening new business from these activities.%“侨批档案”是特定历史时代人类的记忆遗产。以信局网络发展为主线,以侨批实物上记载的信息为依据,考察水客个人、信局网络到侨批行业网络整个侨批业发展过程,认为闽帮侨批局作为企业组织,有其网络经营的国际化视野和金融属性,能够因时因地而变,从而促进和适应不同时期侨批的业务发展。最后以吴道盛从当信局学徒,到开办建南信局,进而创办建南银行为例,说明闽帮侨批业最终归宿是获得新生,得到了进化。

  7. Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites. (United States)

    Gerbe, François; Sidot, Emmanuelle; Smyth, Danielle J; Ohmoto, Makoto; Matsumoto, Ichiro; Dardalhon, Valérie; Cesses, Pierre; Garnier, Laure; Pouzolles, Marie; Brulin, Bénédicte; Bruschi, Marco; Harcus, Yvonne; Zimmermann, Valérie S; Taylor, Naomi; Maizels, Rick M; Jay, Philippe


    Helminth parasitic infections are a major global health and social burden. The host defence against helminths such as Nippostrongylus brasiliensis is orchestrated by type 2 cell-mediated immunity. Induction of type 2 cytokines, including interleukins (IL) IL-4 and IL-13, induce goblet cell hyperplasia with mucus production, ultimately resulting in worm expulsion. However, the mechanisms underlying the initiation of type 2 responses remain incompletely understood. Here we show that tuft cells, a rare epithelial cell type in the steady-state intestinal epithelium, are responsible for initiating type 2 responses to parasites by a cytokine-mediated cellular relay. Tuft cells have a Th2-related gene expression signature and we demonstrate that they undergo a rapid and extensive IL-4Rα-dependent amplification following infection with helminth parasites, owing to direct differentiation of epithelial crypt progenitor cells. We find that the Pou2f3 gene is essential for tuft cell specification. Pou2f3(-/-) mice lack intestinal tuft cells and have defective mucosal type 2 responses to helminth infection; goblet cell hyperplasia is abrogated and worm expulsion is compromised. Notably, IL-4Rα signalling is sufficient to induce expansion of the tuft cell lineage, and ectopic stimulation of this signalling cascade obviates the need for tuft cells in the epithelial cell remodelling of the intestine. Moreover, tuft cells secrete IL-25, thereby regulating type 2 immune responses. Our data reveal a novel function of intestinal epithelial tuft cells and demonstrate a cellular relay required for initiating mucosal type 2 immunity to helminth infection.

  8. Single cell-type comparative metabolomics of epidermal bladder cells from the halophyte Mesembryanthemum crystallinum.

    Directory of Open Access Journals (Sweden)

    Bronwyn Jane Barkla


    Full Text Available One of the remarkable adaptive features of the halophyte and facultative CAM plant Mesembryathemum crystallinum are the specialized modified trichomes called epidermal bladder cells (EBC which cover the leaves, stems, and peduncle of the plant. They are present from an early developmental stage but upon salt stress rapidly expand due to the accumulation of water and sodium. This particular plant feature makes it an attractive system for single cell type studies, with recent proteomics and transcriptomics studies of the EBC establishing that these cells are metabolically active and have roles other than sodium sequestration. To continue our investigation into the function of these unusual cells we carried out a comprehensive global analysis of the metabolites present in the EBC extract by gas chromatography Time-of-Flight mass spectrometry (GC-TOF and identified 194 known and 722 total molecular features. Statistical analysis of the metabolic changes between control and salt-treated samples was used to identify 352 significantly differing metabolites (268 after correction for FDR. Principal components analysis provided an unbiased evaluation of the data variance structure. Biochemical pathway enrichment analysis suggested significant perturbations in 13 biochemical pathways as defined in KEGG. More than 50% of the metabolites that show significant changes in the EBC, can be classified as compatible solutes and include sugars, sugar alcohols, protein and non-protein amino acids, and organic acids, highlighting the need to maintain osmotic homeostasis to balance the accumulation of Na and Cl ions. Overall, the comparison of metabolic changes in salt treated relative to control samples suggest large alterations in Mesembryanthemum crystallinum epidermal bladder cells.

  9. Transcriptome atlas of eight liver cell types uncovers effects of histidine catabolites on rat liver regeneration

    Indian Academy of Sciences (India)

    C. F. Chang; J. Y. Fan; F. C. Zhang; J. Ma; C. S. Xu


    Eight liver cell types were isolated using the methods of Percoll density gradient centrifugation and immunomagnetic beads to explore effects of histidine catabolites on rat liver regeneration. Rat Genome 230 2.0 Array was used to detect the expression profiles of genes associated with metabolism of histidine and its catabolites for the above-mentioned eight liver cell types, and bioinformatic and systems biology approaches were employed to analyse the relationship between above genes and rat liver regeneration. The results showed that the urocanic acid (UA) was degraded from histidine in Kupffer cells, acts on Kupffer cells itself and dendritic cells to generate immune suppression by autocrine and paracrine modes. Hepatocytes, biliary epithelia cells, oval cells and dendritic cells can convert histidine to histamine, which can promote sinusoidal endothelial cells proliferation by GsM pathway, and promote the proliferation of hepatocytes and biliary epithelia cells by GqM pathway.

  10. A host-parasite model for a two-type cell population

    CERN Document Server

    Alsmeyer, Gerold


    A host-parasite model is considered for a population of cells that can be of two types, A or B, and exhibits unilateral reproduction: while a B-cell always splits into two cells of the same type, the two daughter cells of an A-cell can be of any type. The random mechanism that describes how parasites within a cell multiply and are then shared into the daughter cells is allowed to depend on the hosting mother cell as well as its daughter cells. Focusing on the subpopulation of A-cells and its parasites, the model differs from the single-type model recently studied by Bansaye (2008) in that the sharing mechanism may be biased towards one of the two types. Main results are concerned with the nonextinctive case and provide information on the behavior, as $n\\to\\infty$, of the number A-parasites in generation n and the relative proportion of A- and B-cells in this generation which host a given number of parasites. As in (Bansaye,2008), proofs will make use of a so-called random cell line which, when conditioned to ...

  11. Human amniotic membrane-derived stromal cells (hAMSC) interact depending on breast cancer cell type through secreted molecules. (United States)

    Kim, Sun-Hee; Bang, So Hee; Kang, So Yeong; Park, Ki Dae; Eom, Jun Ho; Oh, Il Ung; Yoo, Si Hyung; Kim, Chan-Wha; Baek, Sun Young


    Human amniotic membrane-derived stromal cells (hAMSC) are candidates for cell-based therapies. We examined the characteristics of hAMSC including the interaction between hAMSC and breast cancer cells, MCF-7, and MDA-MB-231. Human amniotic membrane-derived stromal cells showed typical MSC properties, including fibroblast-like morphology, surface antigen expression, and mesodermal differentiation. To investigate cell-cell interaction via secreted molecules, we cultured breast cancer cells in hAMSC-conditioned medium (hAMSC-CM) and analyzed their proliferation, migration, and secretome profiles. MCF-7 and MDA-MB-231 cells exposed to hAMSC-CM showed increased proliferation and migration. However, in hAMSC-CM, MCF-7 cells proliferated significantly faster than MDA-MB-231 cells. When cultured in hAMSC-CM, MCF-7 cells migrated faster than MDA-MB-231 cells. Two cell types showed different profiles of secreted factors. MCF-7 cells expressed much amounts of IL-8, GRO, and MCP-1 in hAMSC-CM. Human amniotic membrane-derived stromal cells interact with breast cancer cells through secreted molecules. Factors secreted by hAMSCs promote the proliferation and migration of MCF-7 breast cancer cells. For much safe cell-based therapies using hAMSC, it is necessary to study carefully about interaction between hAMSC and cancer cells.

  12. Magnetically modified microbial cells: A new type of magnetic adsorbents

    Institute of Scientific and Technical Information of China (English)

    Ivo; Safarik; Mirka; Safarikova


    Microbial cells, either in free or immobilized form, can be used for the preconcentration or removal of metal ions, organic and inorganic xenobiotics or biologically active compounds. Magnetic modification of these cells enables to prepare magnetic adsorbents that can be easily manipulated in difficult-to-handle samples, such as suspensions, in the presence of external magnetic field. In this review, typical examples of magnetic modifications of microbial cells are presented, as well as their possible applications for the separation of organic xenobiotics and heavy metal ions.

  13. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

    DEFF Research Database (Denmark)

    Barnathan, E S; Kuo, A; Karikó, K


    Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...

  14. Recycling of p-type mc-si Top Cuts into p-type mono c-Si Solar Cells

    Energy Technology Data Exchange (ETDEWEB)

    Bronsveld, P.C.P.; Manshanden, P.; Lenzmann, F.O. [ECN Solar Energy, Westerduinweg 3, P.O. Box 1, NL-1755 ZG Petten (Netherlands); Gjerstad, O. [Si Pro Holding AS, Ornesveien 3, P.O. Box 37, 8161, Glomfjord (Norway); Oevrelid, E.J. [SINTEF, Alfred Getz Vei 2, 7465, Trondheim (Norway)


    Solar cell results and material analysis are presented of 2 p-type Czochralski (Cz) ingots pulled from a charge consisting of 100% and 50% recycled multicrystalline silicon top cuts. The top cuts were pre-cleaned with a dedicated low energy consuming technology. No structure loss was observed in the bodies of the ingots. The performance of solar cells made from the 100% recycled Si ingot decreases towards the seed end of the ingot, which could be related to a non-optimal pulling process. Solar cells from the tail end of this ingot and from the 50% recycled Si ingot demonstrated an average solar cell efficiency of 18.6%. This is only 0.1% absolute lower than the efficiency of higher resistivity reference solar cells from commercially available wafers that were co-processed.

  15. Effects of peripheral-type benzodiazepine receptor ligands on Ehrlich tumor cell proliferation. (United States)

    Sakai, Mônica; Fonseca, Evelise Souza Monteiro; Oloris, Silvia Catarina Salgado; Matsuzaki, Patrícia; Otake, Andréia Hanada; Leite, Kátia Ramos Moura; Massoco, Cristina Oliveira; Dagli, Maria Lúcia Zaidan; Palermo-Neto, João


    Peripheral-type benzodiazepine receptors have been found throughout the body, and particularly, in high numbers, in neoplastic tissues such as the ovary, liver, colon, breast, prostate and brain cancer. Peripheral-type benzodiazepine receptor expression has been associated with tumor malignity, and its subcellular localization is important to define its function in tumor cells. We investigated the presence of peripheral-type benzodiazepine receptors in Ehrlich tumor cells, and the in vitro effects of peripheral-type benzodiazepine receptors ligands on tumor cell proliferation. Our results demonstrate the presence of peripheral-type benzodiazepine receptor in the nucleus of Ehrlich tumor cells (85.53+/-12.60%). They also show that diazepam and Ro5-4864 (peripheral-type benzodiazepine receptor agonists) but not clonazepam (a molecule with low affinity for the peripheral-type benzodiazepine receptor) decreased the percentage of tumor cells in G0-G1 phases and increased that of cells in S-G2-M phases. The effects of those agonists were prevented by PK11195 (a peripheral-type benzodiazepine receptor antagonist) that did not produce effects by itself. Altogether, these data suggest that the presence of peripheral-type benzodiazepine receptor within the nucleus of Ehrlich tumor cells is associated with tumor malignity and proliferation capacity.

  16. Production of transgenic blastocyst by nuclear transfer from different types of somatic cells in cattle

    Institute of Scientific and Technical Information of China (English)

    GONG Guochun; LI Rong; LI Ning; DAI Yunping; FAN Baoliang; ZHU Huabing; WANG Haiping; WANG Lili; FANG Changge; WAN Rong; LIU Ying


    The present study examined the effects of genetic manipulation to the donor cell and different types of transgenic donor cells on developmental potential of bovine nuclear transfer (NT) embryos. Four types of bovine somatic cells, including granulosa cells, fetal fibroblasts, fetal oviduct epithelial cells and fetal ovary epithelial cells, were transfected with a plasmid (pCE-EGFP-Ires-Neo-dNdB) containing the enhanced green fluorescent protein (EGFP) and neomycin-resistant (Neor) genes by electroporation. After 14 days selection with 800 μg/mL G418, transgenic cell lines from each type of somatic cells were obtained. Nontransgenic granulosa cells and all 4 types of transgenic somatic cells were used as nuclear donor to produce transgenic embryos by NT. There was no significant difference in development rates to the blastocyst stage for NT embryos from transgenic and nontransgenic granulosa cells (44.6% and 42.8%, respectively), and transfer of NT embryos derived from transgenic and nontransgenic granulosa cells to recipients resulted in similar pregnancy rates on day 90 (19% and 25%, respectively). The development rates to the blastocyst stage of NT embryos were significantly different among different types of transgenic donor cells (P<0.05). Blastocyst rates from fetal oviduct epithelial cell and granulosa cell (49.1% and 44.6%, respectively) were higher than those from fetal fibroblast (32.7%) and fetal ovary epithelial cell (22.5%). These results suggest that (i) genetic manipulation to donor cells has no negative effect on in vitro and early in vivo developmental competence of bovine NT embryos and (ii) granulosa and fetal oviduct epithelial cells can be used to produce transgenic bovine NT embryos more efficiently. In addition, GFP can be used to select transgenic NT embryos as a non-invasive selective marker.

  17. Separation of spermatogenic cell types using STA-PUT velocity sedimentation. (United States)

    Bryant, Jessica M; Meyer-Ficca, Mirella L; Dang, Vanessa M; Berger, Shelley L; Meyer, Ralph G


    Mammalian spermatogenesis is a complex differentiation process that occurs in several stages in the seminiferous tubules of the testes. Currently, there is no reliable cell culture system allowing for spermatogenic differentiation in vitro, and most biological studies of spermatogenic cells require tissue harvest from animal models like the mouse and rat. Because the testis contains numerous cell types--both non-spermatogenic (Leydig, Sertoli, myeloid, and epithelial cells) and spermatogenic (spermatogonia, spermatocytes, round spermatids, condensing spermatids and spermatozoa)--studies of the biological mechanisms involved in spermatogenesis require the isolation and enrichment of these different cell types. The STA-PUT method allows for the separation of a heterogeneous population of cells--in this case, from the testes--through a linear BSA gradient. Individual cell types sediment with different sedimentation velocity according to cell size, and fractions enriched for different cell types can be collected and utilized in further analyses. While the STA-PUT method does not result in highly pure fractions of cell types, e.g. as can be obtained with certain cell sorting methods, it does provide a much higher yield of total cells in each fraction (~1 x 10(8) cells/spermatogenic cell type from a starting population of 7-8 x 10(8) cells). This high yield method requires only specialized glassware and can be performed in any cold room or large refrigerator, making it an ideal method for labs that have limited access to specialized equipment like a fluorescence activated cell sorter (FACS) or elutriator.

  18. Secondary prevention of type 1 diabetes mellitus: stopping immune destruction and promoting ß-cell regeneration

    Directory of Open Access Journals (Sweden)

    C.E.B. Couri


    Full Text Available Type 1 diabetes mellitus results from a cell-mediated autoimmune attack against pancreatic ß-cells. Traditional treatments involve numerous daily insulin dosages/injections and rigorous glucose control. Many efforts toward the identification of ß-cell precursors have been made not only with the aim of understanding the physiology of islet regeneration, but also as an alternative way to produce ß-cells to be used in protocols of islet transplantation. In this review, we summarize the most recent studies related to precursor cells implicated in the regeneration process. These include embryonic stem cells, pancreas-derived multipotent precursors, pancreatic ductal cells, hematopoietic stem cells, mesenchymal stem cells, hepatic oval cells, and mature ß-cells. There is controversial evidence of the potential of these cell sources to regenerate ß-cell mass in diabetic patients. However, clinical trials using embryonic stem cells, umbilical cord blood or adult bone marrow stem cells are under way. The results of various immunosuppressive regimens aiming at blocking autoimmunity against pancreatic ß-cells and promoting ß-cell preservation are also analyzed. Most of these regimens provide transient and partial effect on insulin requirements, but new regimens are beginning to be tested. Our own clinical trial combines a high dose immunosuppression with mobilized peripheral blood hematopoietic stem cell transplantation in early-onset type 1 diabetes mellitus.

  19. [Xenogeneic cell therapeutics: Treatment of type 1 diabetes using porcine pancreatic islets and islet cells]. (United States)

    Godehardt, Antonia W; Schilling-Leiß, Dagmar; Sanzenbacher, Ralf; Tönjes, Ralf R


    In view of the existing shortage of human donor organs and tissues, xenogeneic cell therapeutics (xCT) offer an alternative for adequate treatment. In particular, porcine pancreatic islets and islet cells have already entered the field of experimental therapy for type-1 diabetes mellitus (T1DM) patients. Thereby, xCT depict challenging products with a glance on medical, ethical, and regulatory questions. With cross-species transplantation (xenotransplantation), the risk of immunological graft rejection as well as the risk of infectious transmission of microbial and viral pathogens must be considered. This includes the bidirectional transmission of microorganisms from graft to host as well as from host to graft. Crossing the border of species requires a critical risk-benefit evaluation as well as a thorough longtime surveillance of transplant recipients after treatment. The international legal and regulatory requirements for xCT are inter alia based on the World Health Organization criteria summarized in the Changsha Communiqué (2008). In the European Union, they were reflected by the European Medicines Agency (EMA) Guideline on Xenogeneic Cell-based Medicinal Products following the implementation of the Regulation on Advanced Therapies (ATMP). On the basis of this regulation, the first non-clinical and clinical experiences were obtained for porcine islets. The results suggest that supportive treatment of T1DM risk patients with xCT may be an alternative to established allogeneic organ transplantation in the future.

  20. Dynamics of dye release from nanocarriers of different types in model cell membranes and living cells

    Directory of Open Access Journals (Sweden)

    Tkacheva T. N.


    Full Text Available Aim. To study the dynamics of lipophilic content release from nanocarriers of different types, organic molecular ensembles and inorganic nanoparticles (NPs in vitro experiments. Methods. Two-channel ratiometric fluorescence detection method based on Forster Resonance Energy Transfer, fluorescent spectroscopy and micro-spectroscopy have been used. Results. It has been found that the profiles of lipophilic dyes release from organic nanocarriers (PC liposomes and SDS micelles and inorganic ones (GdYVO4:Eu3+ and CeO2 NPs are well fitted by the first-order reaction kinetics in both model cell membranes and living cells (rat hepatocytes. The dye release constants (K and half-lives (t1/2 were analyzed. Conclusions. GdYVO4:Eu3+ and CeO2 NPs have been shown to provide faster lipophilic content release in model cell membranes as compared to PC liposomes. Negatively charged or lipophilic compounds added into nanocarriers can decrease the rate of lipophilic dyes release. Specific interaction of GdYVO4:Eu3+ NPs with rat hepatocytes has been observed.

  1. Type 2 innate lymphoid cells-new members of the "type 2 franchise" that mediate allergic airway inflammation. (United States)

    Mjösberg, Jenny; Spits, Hergen


    Type 2 innate lymphoid cells (ILC2s) are members of an ILC family, which contains NK cells and Rorγt(+) ILCs, the latter including lymphoid tissue inducer (LTi) cells and ILCs producing IL-17 and IL-22. ILC2s are dedicated to the production of IL-5 and IL-13 and, as such, ILC2s provide an early and important source of type 2 cytokines critical for helminth expulsion in the gut. Several studies have also demonstrated a role for ILC2s in airway inflammation. In this issue of the European Journal of Immunology, Klein Wolterink et al. [Eur. J. Immunol. 2012. 42: 1106-1116] show that ILC2s are instrumental in several models of experimental asthma where they significantly contribute to production of IL-5 and IL-13, key cytokines in airway inflammation. This study sheds light over the relative contribution of ILC2s versus T helper type 2 cells (Th2) in type 2 mediated allergen-specific inflammation in the airways as discussed in this commentary.

  2. Polypeptide composition and gag gene-coded products of type-D oncovirus from HEp-2 cells. (United States)

    Morozov, V A


    The protein composition of type-D oncovirus HEp-2, isolated from cell-free medium of continuous human HEp-2 cell line, has been investigated using electrophoresis on gradient polyacrylamide gels with sodium dodecyl sulfate (SDS). Labeling with 14C-amino acids revealed five viral polypeptides with molecular weights of 70 000 (gp70), 27 000 (p27), 19 000 (p19), 15 000 (p15), 12 000-10 000 (p12-10). The 70 000 dalton protein was shown to be the only glycoprotein by incorporation of radioactive glucosamine. A polypeptide with molecular weight of 78 000 has been specifically precipitated from pulse-labeled type-D oncovirus producing HEp-2 cells with goat anti Mason-Pfizer p27 serum. This protein was shown to be gag gene-coded polyprotein precursor (Pr78gag) of the major virus polypeptide p27. Pulse-labeled HEp-2 and Mason-Pfizer infected Tu 197 cells were rinsed, lysed, clarified and precipitated with goat anti Mason-Pfizer p27 serum. In both cases Pr78gag was detected.

  3. Theoretical and experimental investigation of 'grating' type photovoltaic cells (United States)

    Loferski, J. J.; Crisman, E. E.; Armitage, W.; Chen, L. Y.


    The fabrication procedure and properties of 'grating' cells made by forming a fine grating pattern of aluminum alloyed into n-silicon wafers are described. The finest grating lines achieved in the cells described were 5 microns; the smallest spacing was about 15 microns. The best temperature for alloying was found to be about 600 C, a bit above the Si-Al eutectic temperature (576 C). The short-circuit current obtained from the best of these cells exposed to 100 mW/sq cm of (simulated air mass zero) illumination was at least equal to that obtained from conventional diffused cells, but their open-circuit voltage was lower. Their quantum yield was strongly blue-shifted; it was flat from 4000 to 8500 A.

  4. Attachment of cells to basement membrane collagen type IV



    Of ten different cell lines examined, three showed distinct attachment and spreading on collagen IV substrates, and neither attachment nor spreading was enhanced by adding soluble laminin or fibronectin. This reaction was not inhibited by cycloheximide or antibodies to laminin, indicating a direct attachment to collagen IV without the need of mediator proteins. Cell-binding sites were localized to the major triple-helical domain of collagen IV and required an intact triple helical conformatio...

  5. [Red Blood Cells Raman Spectroscopy Comparison of Type Two Diabetes Patients and Rats]. (United States)

    Wang, Lei; Liu, Gui-dong; Mu, Xin; Xiao, Hong-bin; Qi, Chao; Zhang, Si-qi; Niu Wen-ying; Jiang, Guang-kun; Feng, Yue-nan; Bian, Jing-qi


    By using confocal Raman spectroscopy, Raman spectra were measured in normal rat red blood cells, normal human red blood cells, STZ induced diabetetic rats red blood cells, Alloxan induced diabetetic rats red blood cells and human type 2 diabetes red blood cells. Then principal component analysis (PCA) with support vector machine (SVM) classifier was used for data analysis, and then the distance between classes was used to judge the degree of close to two kinds of rat model with type 2 diabetes. The results found significant differences in the Raman spectra of red blood cell in diabetic and normal red blood cells. To diabetic red blood cells, the peak in the amide VI C=O deformation vibration band is obvious, and amide V N-H deformation vibration band spectral lines appear deviation. Belong to phospholipid fatty acyl C-C skeleton, the 1 130 cm(-1) spectral line is enhanced and the 1 088 cm(-1) spectral line is abated, which show diabetes red cell membrane permeability increased. Raman spectra of PCA combined with SVM can well separate 5 types of red blood cells. Classifier test results show that the classification accuracy is up to 100%. Through the class distance between the two induced method and human type 2 diabetes, it is found that STZ induced model is more close to human type 2 diabetes. In conclusion, Raman spectroscopy can be used for diagnosis of diabetes and rats STZ induced diabetes method is closer to human type 2 diabetes.

  6. Proteolysis of synaptobrevin, syntaxin, and SNAP-25 in alveolar epithelial type II cells. (United States)

    Zimmerman, U J; Malek, S K; Liu, L; Li, H L


    Synaptobrevin-2, syntaxin-1, and SNAP-25 were identified in rat alveolar epithelial type II cells by Western blot analysis. Synaptobrevin-2 was localized in the lamellar bodies, and syntaxin-1 and SNAP-25 were found in 0.4% Nonidet P40-soluble and -insoluble fractions, respectively, of the type II cells. When the isolated type II cells were stimulated for secretion with calcium ionophore A23187 or with phorbol 12-myristate 13-acetate, these proteins were found to have been proteolyzed. Preincubation of cells with calpain inhibitor II (N-acetylleucylleucylmethionine), however, prevented the proteolysis. Treatment of the cell lysate with exogenous calpain resulted in a time-dependent decrease of these proteins. The data suggest that synaptobrevin, syntaxin, and SNAP-25 are subject to proteolytic modification by activated calpain in intact type II cells stimulated for secretion.

  7. Recognition of lysophosphatidylcholine by type II NKT cells and protection from an inflammatory liver disease (United States)

    Maricic, Igor; Girardi, Enrico; Zajonc, Dirk M.; Kumar, Vipin


    Summary Lipids presented by the major histocompatibility complex (MHC) class I-like molecule, CD1d, are recognized by natural killer T (NKT) cells, which can be broadly categorized into two subsets. The well-characterized type I NKT cells, express a semi-invariant T cell receptor (TCR) and can recognize both α- and β-linked glycolipids, whereas type II NKT cells are less well studied, express a relatively diverse TCR repertoire, and recognize β-linked lipids. Recent structural studies have shown a distinct mode of recognition of a self-glycolipid sulfatide bound to CD1d by a type II NKT TCR. To further characterize antigen recognition by these cells we have used the structural data and screened other small molecules able to bind to CD1d and activate type II NKT cells. Using plate-bound CD1d and APC-based antigen presentation assay we found that phospholipids such as lysophosphatidylcholine (LPC) can stimulate the sulfatide-reactive type II NKT hybridoma Hy19.3 in a CD1d-dependent manner. Using plasmon resonance studies we found that this type II NKT TCR binds with CD1d-bound LPC with micromolar affinities similar to that for sulfatide. Furthermore LPC-mediated activation of type II NKT cells leads to anergy induction in type I NKT cells and affords protection from ConA-induced hepatitis. These data indicate that, in addition to self-glycolipids, self-lysophospholipids are also recognized by type II NKT cells. Since lysophospholipids are involved during inflammation our findings have implications for not only understanding activation of type II NKT cells in physiological settings but also for the development of immune intervention in inflammatory diseases. PMID:25261475

  8. Isolation (from a basal cell carcinoma) of a functionally distinct fibroblast-like cell type that overexpresses Ptch. (United States)

    Dicker, Anthony J; Serewko, Magdalena M; Russell, Terry; Rothnagel, Joseph A; Strutton, Geoff M; Dahler, Alison L; Saunders, Nicholas A


    In this study we report on the isolation and characterization of a nonepithelial, nontumorigenic cell type (BCC1) derived from a basal cell carcinoma from a patient. The BCC1 cells share many characteristics with dermal fibroblasts, such as the expression of vimentin, lack of expression of cytokeratins, and insensitivity to agents that cause growth inhibition and differentiation of epithelial cells; however, significant differences between BCC1 cells and fibroblasts also exist. For example, BCC1 cells are stimulated to undergo DNA synthesis in response to interferon-gamma, whereas dermal fibroblasts are not. More over, BCC1 cells overexpress the basal cell carcinoma-specific genes ptch and ptch2. These data indicate that basal cell carcinomas are associated with a functionally distinct population of fibroblast-like cells that overexpress known tumor-specific markers (ptch and ptch2).

  9. Emigrants’ Resources, Rights, Poverty and Settlement Area Development-The Survey Based on the Emigrants Settlement in Wuqiangxi Reservoir by Settling the Emigrants Backwardly and Locally%移民资源、权利、贫困与安置区发展*--基于五强溪库区就地后靠安置移民的调查

    Institute of Scientific and Technical Information of China (English)

    许源源; 张艳


    就地后靠安置模式下的水库移民是特殊的贫困人群。对五强溪库区就地后靠安置移民的实地调研表明,其生存空间狭小,可资利用的资源窘迫,权利难以伸张。目前,我国大部分移民资源的贫乏导致其权利无法伸张,进而产生普遍的移民贫困;因此,必须由政府介入,通过政策手段来推动移民权利的实现及其能力的提升,帮助其摆脱资源贫乏状态,进而促进安置区经济发展、消除移民贫困。具体来说,需要发展市场经济以促进公平交易和自主发展,加强教育培训以提升移民能力,创造良好环境以利于移民权利实现。%The emigrants who were settled backwardly and locally in the construction of the reservoir are a special group of poverty emigrants, the spot survey on the emigrants settled backwardly and locally in Wuqiangxi Reservoir shows that the emigrants have small living space, embarrassed available resources and un-promoted rights. Currently, the lacking of resources in the majority of Chinese emigrants causes the rights of the emigrants to be difficult to be protected, further to produce ubiquitous emigration poverty. As a result, the right protection and capacity improvement of the emigrants must be implemented by government participation and policy regulation in order to help the emigrants to get rid of resources insufficiency and to boost the economic development in their settlement areas so as to eliminate emigration poverty. In practice, China needs to develop market-oriented economy to promote fair trade and autonomous development, consolidate education and training to improve the capacity of the emigrants, and create good environment to help the realization of the emigrants’ rights.

  10. Single-cell transcriptomes identify human islet cell signatures and reveal cell-type–specific expression changes in type 2 diabetes (United States)

    Bolisetty, Mohan; Kursawe, Romy; Sun, Lili; Sivakamasundari, V.; Kycia, Ina


    Blood glucose levels are tightly controlled by the coordinated action of at least four cell types constituting pancreatic islets. Changes in the proportion and/or function of these cells are associated with genetic and molecular pathophysiology of monogenic, type 1, and type 2 (T2D) diabetes. Cellular heterogeneity impedes precise understanding of the molecular components of each islet cell type that govern islet (dys)function, particularly the less abundant delta and gamma/pancreatic polypeptide (PP) cells. Here, we report single-cell transcriptomes for 638 cells from nondiabetic (ND) and T2D human islet samples. Analyses of ND single-cell transcriptomes identified distinct alpha, beta, delta, and PP/gamma cell-type signatures. Genes linked to rare and common forms of islet dysfunction and diabetes were expressed in the delta and PP/gamma cell types. Moreover, this study revealed that delta cells specifically express receptors that receive and coordinate systemic cues from the leptin, ghrelin, and dopamine signaling pathways implicating them as integrators of central and peripheral metabolic signals into the pancreatic islet. Finally, single-cell transcriptome profiling revealed genes differentially regulated between T2D and ND alpha, beta, and delta cells that were undetectable in paired whole islet analyses. This study thus identifies fundamental cell-type–specific features of pancreatic islet (dys)function and provides a critical resource for comprehensive understanding of islet biology and diabetes pathogenesis. PMID:27864352

  11. Type I (CD64) and type II (CD32) Fc gamma receptor-mediated phagocytosis by human blood dendritic cells. (United States)

    Fanger, N A; Wardwell, K; Shen, L; Tedder, T F; Guyre, P M


    Three classes of Fc receptors for IgG, Fc gamma RI (CD64), Fc gamma RII (CD32), and Fc gamma RIII (CD16), are expressed on blood leukocytes. Although Fc gamma R are important phagocytic receptors on phagocytes, most reports suggest that dendritic cells lack Fc gamma R-mediated phagocytosis and express significant levels of only CD32. We now report that phagocytically active forms of both CD64 and CD32 are expressed significantly on at least one subset of human blood dendritic cells. Countercurrent elutriation and magnetic bead selection were used to rapidly enrich subsets of blood dendritic cells (CD33brightCD14-HLA-DRbrightCD83-) and monocytes (CD33brightCD14brightHLA-DRdimCD83-). Upon culture for 2 days, dendritic cells became CD83-positive and markedly increased HLA-DR expression, whereas monocytes did not express CD83 and exhibited reduced levels of HLA-DR. Constitutive CD64 expression was identified on this circulating dendritic cell population, but at a lower level than on monocytes. CD64 expression by dendritic cells and monocytes did not decrease during 2 days in culture, and was up-regulated on both cell types following incubation with IFN-gamma. Freshly isolated blood dendritic cells performed CD64- and CD32-mediated phagocytosis, although at a lower level than monocytes. Dendritic cells generated by culture of adherent mononuclear cells in granulocyte-macrophage CSF and IL-4 also up-regulated CD64 following IFN-gamma stimulation, and mediated CD64-dependent phagocytosis. These results indicate that both CD64 and CD32 expressed on blood dendritic cells may play a role in uptake of foreign particles and macromolecules through a phagocytic mechanism before trafficking to T cell-reactive areas.

  12. Mouse B-Type Lamins Are Required for Proper Organogenesis But Not by Embryonic Stem Cells


    Kim, Youngjo; Sharov, Alexei A; McDole, Katie; Cheng, Melody; Hao, Haiping; Fan, Chen-Ming; Gaiano, Nicholas; Minoru S.H. Ko; Zheng, Yixian


    B-type lamins, the major components of the nuclear lamina, are believed to be essential for cell proliferation and survival. We found that mouse embryonic stem cells (ESCs) do not need any lamins for self-renewal and pluripotency. Although genome-wide lamin-B binding profiles correlate with reduced gene expression, such binding is not directly required for gene silencing in ESCs or trophectoderm cells. However, B-type lamins are required for proper organogenesis. Defects in spindle orientatio...

  13. The immunoglobulin superfamily member CD200R identifies cells involved in type 2 immune responses

    DEFF Research Database (Denmark)

    Blom, Lars H; Martel, Britta C; Larsen, Lau F


    BACKGROUND: The pathology of allergic diseases involves type 2 immune cells, such as Th2, ILC2, and basophils exerting their effect by production of IL-4, IL-5, and IL-13. However, surface receptors that are specifically expressed on type 2 immune cells are less well documented. The aim...... and ILC2 cells and basophils. In peanut-allergic subjects the peanut-specific Th2 (CD154(+) CRTh2(+) ) cells expressed more CD200R than the non-allergen specific Th2 (CD154(-) CRTh2(+) ) cells. Moreover, co-staining of CD161 and CD200R identified peanut-specific highly differentiated IL-4(+) IL-5(+) Th2...

  14. The GalNAc-type O-Glycoproteome of CHO Cells Characterized by the SimpleCell Strategy

    DEFF Research Database (Denmark)

    Zhang, Yang; Halim, Adnan; Narimatsu, Yoshiki;


    of glycan structures (glycostructures) on glycoproteins are well established, our knowledge of the capacity of CHO cells for attaching GalNAc-type O-glycans to proteins (glycosites) is minimal. This type of O-glycosylation is one of the most abundant forms of glycosylation, and it is differentially...... regulated in cells by expression of a subset of homologous polypeptide GalNAc-transferases. Here, we have genetically engineered CHO cells to produce homogeneous truncated O-glycans, so-called SimpleCells, which enabled lectin enrichment of O-glycoproteins and characterization of the O-glycoproteome. We...

  15. Patch Type Granuloma Annulare Imitating Cutaneous T-Cell Lymphoma

    Directory of Open Access Journals (Sweden)

    Seval Doğruk Kaçar


    Full Text Available Granuloma annulare (GA is a benign inflammatory skin disease with distinct clinical and histopathological findings. Patch type GA is described with erythematous patches beyond the classical clinical appearance and an interstitial pattern is observed without histopathologically granulomas with disseminated histiocytes among collagen bundles and vessels. Here we report 46 year old woman diagnosed as patch type GA after a punch biopsy performed from the annular bordered patches in belly area, which is a classical area for mycosis fungoides (MF evolution, and lesions increasingly spreading out within a 2 year period.

  16. List of gene variants developed for cancer cells from nine tissue types (United States)

    NCI scientists have developed a comprehensive list of genetic variants for each of the types of cells that comprise what is known as the NCI-60 cell line collection. This new list adds depth to the most frequently studied human tumor cell lines in cancer

  17. Neurosecretory Cell Types and Distribution in Unfed Female Hyalomma Dromedari (Acari: Ixodoidea: Ixodidae) Synganglion (United States)


    of the cell in subtype VIh (Fig. 2). Type IX : In these oval celo, 2 subtypes are distinguished according to cell size and NSG distribution. The NSG...1977) : Neurosecretion in Ornithodoros savignyi (Audouin) (Ixodoidea : Arga- sidae ). The distribution of neurosecretory cells in the brain. J. Vet. Res

  18. Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes

    Directory of Open Access Journals (Sweden)

    Jue Lin


    Full Text Available Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL in CD4+, CD8+CD28+, and CD8+CD28− T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28− cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation.

  19. Systematic and Cell Type-Specific Telomere Length Changes in Subsets of Lymphocytes. (United States)

    Lin, Jue; Cheon, Joshua; Brown, Rashida; Coccia, Michael; Puterman, Eli; Aschbacher, Kirstin; Sinclair, Elizabeth; Epel, Elissa; Blackburn, Elizabeth H


    Telomeres, the protective DNA-protein complexes at the ends of linear chromosomes, are important for genome stability. Leukocyte or peripheral blood mononuclear cell (PBMC) telomere length is a potential biomarker for human aging that integrates genetic, environmental, and lifestyle factors and is associated with mortality and risks for major diseases. However, only a limited number of studies have examined longitudinal changes of telomere length and few have reported data on sorted circulating immune cells. We examined the average telomere length (TL) in CD4+, CD8+CD28+, and CD8+CD28- T cells, B cells, and PBMCs, cross-sectionally and longitudinally, in a cohort of premenopausal women. We report that TL changes over 18 months were correlated among these three T cell types within the same participant. Additionally, PBMC TL change was also correlated with those of all three T cell types, and B cells. The rate of shortening for B cells was significantly greater than for the three T cell types. CD8+CD28- cells, despite having the shortest TL, showed significantly more rapid attrition when compared to CD8+CD28+ T cells. These results suggest systematically coordinated, yet cell type-specific responses to factors and pathways contribute to telomere length regulation.

  20. Common themes and cell type specific variations of higher order chromatin arrangements in the mouse

    Directory of Open Access Journals (Sweden)

    Cremer Thomas


    Full Text Available Abstract Background Similarities as well as differences in higher order chromatin arrangements of human cell types were previously reported. For an evolutionary comparison, we now studied the arrangements of chromosome territories and centromere regions in six mouse cell types (lymphocytes, embryonic stem cells, macrophages, fibroblasts, myoblasts and myotubes with fluorescence in situ hybridization and confocal laser scanning microscopy. Both species evolved pronounced differences in karyotypes after their last common ancestors lived about 87 million years ago and thus seem particularly suited to elucidate common and cell type specific themes of higher order chromatin arrangements in mammals. Results All mouse cell types showed non-random correlations of radial chromosome territory positions with gene density as well as with chromosome size. The distribution of chromosome territories and pericentromeric heterochromatin changed during differentiation, leading to distinct cell type specific distribution patterns. We exclude a strict dependence of these differences on nuclear shape. Positional differences in mouse cell nuclei were less pronounced compared to human cell nuclei in agreement with smaller differences in chromosome size and gene density. Notably, the position of chromosome territories relative to each other was very variable. Conclusion Chromosome territory arrangements according to chromosome size and gene density provide common, evolutionary conserved themes in both, human and mouse cell types. Our findings are incompatible with a previously reported model of parental genome separation.

  1. Divergent responses of different endothelial cell types to infection with Candida albicans and Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    Kati Seidl

    Full Text Available Endothelial cells are important in the pathogenesis of bloodstream infections caused by Candida albicans and Staphylococcus aureus. Numerous investigations have used human umbilical vein endothelial cells (HUVECs to study microbial-endothelial cell interactions in vitro. However, the use of HUVECs requires a constant supply of umbilical cords, and there are significant donor-to-donor variations in these endothelial cells. The use of an immortalized endothelial cell line would obviate such difficulties. One candidate in this regard is HMEC-1, an immortalized human dermal microvascular endothelial cell line. To determine if HMEC-1 cells are suitable for studying the interactions of C. albicans and S. aureus with endothelial cells in vitro, we compared the interactions of these organisms with HMEC-1 cells and HUVECs. We found that wild-type C. albicans had significantly reduced adherence to and invasion of HMEC-1 cells as compared to HUVECs. Although wild-type S. aureus adhered to and invaded HMEC-1 cells similarly to HUVECs, an agr mutant strain had significantly reduced invasion of HMEC-1 cells, but not HUVECs. Furthermore, HMEC-1 cells were less susceptible to damage induced by C. albicans, but more susceptible to damage caused by S. aureus. In addition, HMEC-1 cells secreted very little IL-8 in response to infection with either organism, whereas infection of HUVECs induced substantial IL-8 secretion. This weak IL-8 response was likely due to the anatomic site from which HMEC-1 cells were obtained because infection of primary human dermal microvascular endothelial cells with C. albicans and S. aureus also induced little increase in IL-8 production above basal levels. Thus, C. albicans and S. aureus interact with HMEC-1 cells in a substantially different manner than with HUVECs, and data obtained with one type of endothelial cell cannot necessarily be extrapolated to other types.

  2. Hematologically and genetically distinct forms of sickle cell anemia in Africa. The Senegal type and the Benin type. (United States)

    Nagel, R L; Fabry, M E; Pagnier, J; Zohoun, I; Wajcman, H; Baudin, V; Labie, D


    Patients with sickle cell anemia vary in the hematologic and clinical features of their disease, in part because of variability in the presence of linked and unlinked genes that modify the expression of the disease. The hemoglobin S gene is strongly linked to three different haplotypes of polymorphic endonuclease-restriction sites of the beta-like gene cluster (genes in the vicinity of the beta-globin gene)--one prevalent in Atlantic West Africa, another in central West Africa, and yet another in Bantu-speaking Africa (equatorial, East, and southern Africa). We have studied the differences in the hematologic characteristics of patients with sickle cell anemia from the first two geographical areas. We find that the Senegalese (Atlantic West Africa) patients have higher levels of hemoglobin F, a preponderance of G gamma chains in hemoglobin F, a lower proportion of very dense red cells, and a lower percentage of irreversibly sickled cells than those from Benin (central West Africa). We interpret these data to mean that the gamma-chain composition and the hemoglobin F level are haplotype linked and that the decrease in the percentage of dense cells and irreversibly sickled cells is secondary to the elevation in the hemoglobin F level. Patients with sickle cell anemia in the New World probably correspond to various combinations of these types, in addition to the still hematologically undefined haplotype associated with sickle cell anemia in the Bantu-speaking areas of Africa.

  3. 侨州郡县判断标准探析——兼议侨州郡县发端时间%Inquiry about the Criterion of Emigrant State and County——And Discussing When Emerged the Emigrant State and County

    Institute of Scientific and Technical Information of China (English)

    田志馥; 张淑兰


    目前学界对侨州郡县发端于何时,尚存不同看法。究其根源,不难发现,侨州郡县滥觞之争在于侨州郡县判断标准不同。侨州郡县判断标准至关重要,是讨论侨州郡县发端及相关问题的先决条件。本文在前人关于侨州郡县判定的三条标准,即侨人、旧壤之名、设置侨置机构基础之上,增补一条判断标准,即无实土、不役不税。并据此提出侨州郡县产生于东晋南朝时期。%There are arguments in academic community at present about when the Emigrant State and County originated.To fully resolve this problem,it is necessary to understand the criterion of judging Emigrant state and county.Predecessors have pointed three criterions——emigrant,the original place name,the agency of Emigrant State and County.This article will present the fourth: the emigrant have no any plough and have no tax or service,and argue that the emigrant state and county come into being during the Eastern Jin Dynasty.

  4. Curt Teichert - Dokumente zu einer Emigration (Dänemark - Australien - USA) (United States)

    Seibold, Eugen; Seibold, Ilse


    Curt Teichert (Königsberg 1905—Arlington, Virginia 1996) provides in his life story examples of the many hardships and difficulties encountered by emigrants who were fortunate to escape Hitleŕs regime. He was a great paleontologist and stratigrapher whose fieldwork on four continents involved nearly every fossil group; his interests were focussed mainly on the Paleozoic and the Triassic. His results and critical remarks on many general topics filled numerous publications. Remarkably, he accomplished all this under partly very unfavorable working conditions. He donated his scientific correspondence from his times in Germany, Denmark and Australia to the Geological Archive in Freiburg. The following article makes use of these documents. Teichert’s professional career started in Germany in the scientifically exciting nineteen-twenties; he worked at the universities in Königsberg, Munich and Freiburg/Breisgau. In Freiburg, however, he had serious disagreements with the Director of the Geological Institute there—this in spite of his investigations having produced some excellent results. The times around 1930 were a period of a global economic crisis, and, like many others, he could only survive financially by getting fellowships from different institutions and payments for publications. In 1933, his situation in Germany became even more critical: this was because he had married a “Non-Aryan”. However, he was able to work in Copenhagen from the end of 1933; this was largely a result of his having participated in 1931 1932 in an expedition to Greenland led by the Dane Lauge Koch. Unfortunately, he could not get a permanent position in Copenhagen because the relations between him and the influential Koch became very unpleasant. Noting Hitleŕs war preparation, Teichert tried to escape from Europe. He wrote many touching letters to correspondents around the globe, receiving mostly disappointing answers. Finally, in 1937, he succeeded in getting the post of a

  5. T-helper Cell Type-1 Transcription Factor T-Bet Is Down-regulated in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Hajar Vaseghi


    Full Text Available T cells have been identified as key players in the pathogenesis of type 1 diabetes. However, the exact role of T-cell subpopulations in this pathway is presently unknown. The purpose of this study was to assess the expression pattern of two lineage-specifying transcription factors GATA-3 and T-bet, which are important in T helper type 1 (Th1 and Th2 cell development, respectively. Gene expression analysis of peripheral blood mononuclear cells (PBMCs was performed using reverse transcription-quantitative polymerase chain reaction (RT-qPCR. Plasma levels of IFN-γ and IL-4 were also determined by ELISA. T-bet and IFN-γ gene expression was significantly lower in patients group compared with healthy controls (p<0.05. The expression of GATA-3 was relatively similar in patients and controls; however, IL-4 mRNAs were significantly increased in the PBMCs from patients as compared with normal controls (p<0.05. In addition, a marked increase in plasma IL-4 levels were observed in patient group compared with controls (p<0.001. To the contrary, IFN-γ protein levels were decreased in patients in comparison with controls (p<0.001. These data suggest additional implications of the role of Th1/Th2 imbalance for the immunopathogenesis of type 1 diabetes. 

  6. Cell proliferation in human epiretinal membranes: characterization of cell types and correlation with disease condition and duration

    NARCIS (Netherlands)

    Lesnik Oberstein, S.Y.; Byun, J.; Herrera, D.; Chapin, E.A.; Fisher, S.K.; Lewis, G.P.


    To quantify the extent of cellular proliferation and immunohistochemically characterize the proliferating cell types in epiretinal membranes (ERMS) from four different conditions: proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, post-retinal detachment, and idiopathic ERM.

  7. Human immunodeficiency virus type 1 infection of human uterine epithelial cells: viral shedding and cell contact-mediated infectivity. (United States)

    Asin, Susana N; Wildt-Perinic, Dunja; Mason, Sarah I; Howell, Alexandra L; Wira, Charles R; Fanger, Michael W


    We examined the mechanism of human immunodeficiency virus (HIV) type 1 infection of human uterine epithelial cells to gain a clearer understanding of the events by which HIV-1 infects cells within the female reproductive tract. We demonstrated that these cells can be productively infected by HIV-1 and that infection is associated with viral RNA reverse transcription, DNA transcription, and secretion of infectious virus. Levels of viral DNA and secreted virus decreased gradually after infection. Moreover, virus released by the uterine epithelial cells shortly after infection was able to infect human T cell lines, but virus released later did not. In contrast, human CD4(+) T cell lines were infected after cocultivation with epithelial cells at both early and late stages of infection. These data demonstrated that HIV-1 infects human epithelial cells of upper reproductive tract origin and that productive viral infection of epithelial cells may be an important mechanism of transmission of HIV-1 infection in women.

  8. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types (United States)

    Wu, Honglu; Lu, Tao; Yeshitla, Samrawit; Zhang, Ye; Kadhim, Munira


    An early stage of cancer development is believed to be genomic instability (GI) which accelerates the mutation rate in the descendants of the cells surviving radiation exposure. To investigate GI induced by charged particles, we exposed human lymphocytes, human fibroblast cells, and human mammary epithelial cells to high energy protons and Fe ions. In addition, we also investigated GI in bone marrow cells isolated from CBA/CaH (CBA) and C57BL/6 (C57) mice, by analyzing cell survival and chromosome aberrations in the cells after multiple cell divisions. Results analyzed so far from the experiments indicated different sensitivities to charged particles between CBA/CaH (CBA) and C57BL/6 (C57) mouse strains, suggesting that there are two main types of response to irradiation: 1) responses associated with survival of damaged cells and 2) responses associated with the induction of non-clonal chromosomal instability in the surviving progeny of stem cells. Previously, we reported that the RBE for initial chromosome damages was high in human lymphocytes exposed to Fe ions. Our results with different cell types demonstrated different RBE values between different cell types and between early and late chromosomal damages. This study also attempts to offer an explanation for the varying RBE values for different cancer types.

  9. cMyc Regulates the Size of the Premigratory Neural Crest Stem Cell Pool. (United States)

    Kerosuo, Laura; Bronner, Marianne E


    The neural crest is a transient embryonic population that originates within the central nervous system (CNS) and then migrates into the periphery and differentiates into multiple cell types. The mechanisms that govern neural crest stem-like characteristics and self-renewal ability are poorly understood. Here, we show that the proto-oncogene cMyc is a critical factor in the chick dorsal neural tube, where it regulates the size of the premigratory neural crest stem cell pool. Loss of cMyc dramatically decreases the number of emigrating neural crest cells due to reduced self-renewal capacity, increased cell death, and shorter duration of the emigration process. Interestingly, rather than via E-Box binding, cMyc acts in the dorsal neural tube by interacting with another transcription factor, Miz1, to promote self-renewal. The finding that cMyc operates in a non-canonical manner in the premigratory neural crest highlights the importance of examining its role at specific time points and in an in vivo context.

  10. Principles of connectivity among morphologically defined cell types in adult neocortex. (United States)

    Jiang, Xiaolong; Shen, Shan; Cadwell, Cathryn R; Berens, Philipp; Sinz, Fabian; Ecker, Alexander S; Patel, Saumil; Tolias, Andreas S


    Since the work of Ramón y Cajal in the late 19th and early 20th centuries, neuroscientists have speculated that a complete understanding of neuronal cell types and their connections is key to explaining complex brain functions. However, a complete census of the constituent cell types and their wiring diagram in mature neocortex remains elusive. By combining octuple whole-cell recordings with an optimized avidin-biotin-peroxidase staining technique, we carried out a morphological and electrophysiological census of neuronal types in layers 1, 2/3, and 5 of mature neocortex and mapped the connectivity between more than 11,000 pairs of identified neurons. We categorized 15 types of interneurons, and each exhibited a characteristic pattern of connectivity with other interneuron types and pyramidal cells. The essential connectivity structure of the neocortical microcircuit could be captured by only a few connectivity motifs.

  11. Type 1 CD8+ T Cells are Superior to Type 2 CD8+ T Cells in Tumor Immunotherapy due to Their Efficient Cytotoxicity, Prolonged Survival and Type 1 Immune Modulation

    Institute of Scientific and Technical Information of China (English)

    Zhenmin Ye; Chaoke Tang; Shulin Xu; Bei Zhang; Xueshu Zhang; Terence Moyana; Jicheng Yang; Jim Xiang


    CD8+ cytotoxic T (Tc) cells play a crucial role in host immune responses to cancer, and in this context, adoptive CD8+ Tc cell therapy has been studied in numerous animal tumor models. Its antitumor efficacy is, to a large extent,determined by the ability of Tc cells to survive and infiltrate tumors. In clinical trials, such in vitro-activated T cells often die within hours to days, and this greatly limits their therapeutic efficacy. CD8+ Tc cells fall into two subpopulations based upon their differential cytokine secretion. In this study, we in vitro generated that ovalbumin(OVA)-pulsed dendritic cell (DCOVA)-activated CD8+ type 1 Tc (Tc1) cells secreting IFN-γ, and CD8+ type 2 Tc (Tc2)cells secreting IL-4, IL-5 and IL-10, which were derived from OVA-specific T cell receptor (TCR) transgenic OT I mice. We then systemically investigated the in vitro and in vivo effector function and survival of Tc1 and Tc2 cells,and then assessed their survival kinetics after adoptively transferred into C57BL/6 mice, respectively. We demonstrated that, when compared to CD8+ Tc2, Tc1 cells were significantly more effective in perforin-mediated cytotoxicity to tumor cells, had a significantly higher capacity for in vivo survival after the adoptive T cell transfer,and had a significantly stronger therapeutic effect on eradication of well-established tumors expressing OVA in animal models. In addition, CD8+Tc1 and Tc2 cells skewed the phenotype of CD4+ T cells toward Th1 and Th2 type, respectively. Therefore, the information regarding the differential effector function, survival and immune modulation of CD8+ Tc1 and Tc2 cells may provide useful information when preparing in vitro DC-activated CD8+ T cells for adoptive T cell therapy of cancer.

  12. Wide bandgap n-type and p-type semiconductor porous junction devices as photovoltaic cells

    Energy Technology Data Exchange (ETDEWEB)

    Lin, Yuan-Pai; Horng, Sheng-Fu [Institute of Electronics Engineering, National Tsing Hua University, Hsinchu 300, Taiwan (China); Chao, Yu-Chiang; Meng, Hsin-Fei [Institute of Physics, National Chiao Tung University, Hsinchu 300, Taiwan (China); Zan, Hsiao-Wen, E-mail:, E-mail: [Department of Photonics and Institute of Electro-Optical Engineering, National Chiao Tung University, Hsinchu 300, Taiwan (China)


    In junction absorber photovoltaics doped wide bandgap n-type and p-type semiconductors form a porous interpenetrating junction structure with a layer of low bandgap absorber at the interface. The doping concentration is high enough such that the junction depletion width is smaller than the pore size. The highly conductive neutral region then has a dentrite shape with fingers reaching the absorber to effectively collect the photo-carriers swept out by the junction electric field. With doping of 10{sup 19} cm{sup -3} corresponding to a depletion width of 25 nm, pore size of 32 nm, absorber thickness close to exciton diffusion length of 17 nm, absorber bandgap of 1.4 eV and carrier mobility over 10{sup -5} cm{sup 2} V{sup -1} s{sup -1}, numerical calculation shows the power conversion efficiency is as high as 19.4%. It rises to 23% for a triplet exciton absorber.

  13. Type I and Type II Interferon Coordinately Regulate Suppressive Dendritic Cell Fate and Function during Viral Persistence.

    Directory of Open Access Journals (Sweden)

    Cameron R Cunningham


    Full Text Available Persistent viral infections are simultaneously associated with chronic inflammation and highly potent immunosuppressive programs mediated by IL-10 and PDL1 that attenuate antiviral T cell responses. Inhibiting these suppressive signals enhances T cell function to control persistent infection; yet, the underlying signals and mechanisms that program immunosuppressive cell fates and functions are not well understood. Herein, we use lymphocytic choriomeningitis virus infection (LCMV to demonstrate that the induction and functional programming of immunosuppressive dendritic cells (DCs during viral persistence are separable mechanisms programmed by factors primarily considered pro-inflammatory. IFNγ first induces the de novo development of naive monocytes into DCs with immunosuppressive potential. Type I interferon (IFN-I then directly targets these newly generated DCs to program their potent T cell immunosuppressive functions while simultaneously inhibiting conventional DCs with T cell stimulating capacity. These mechanisms of monocyte conversion are constant throughout persistent infection, establishing a system to continuously interpret and shape the immunologic environment. MyD88 signaling was required for the differentiation of suppressive DCs, whereas inhibition of stimulatory DCs was dependent on MAVS signaling, demonstrating a bifurcation in the pathogen recognition pathways that promote distinct elements of IFN-I mediated immunosuppression. Further, a similar suppressive DC origin and differentiation was also observed in Mycobacterium tuberculosis infection, HIV infection and cancer. Ultimately, targeting the underlying mechanisms that induce immunosuppression could simultaneously prevent multiple suppressive signals to further restore T cell function and control persistent infections.

  14. Impact of common metallurgical impurities on ms-Si solar cell efficiency. P-type versus n-type doped ingots

    Energy Technology Data Exchange (ETDEWEB)

    Geerligs, L.J.; Manshanden, P. [ECN Solar Energy, Petten (Netherlands); Solheim, I.; Ovrelid, E.J.; Waernes, A.N. [Sintef materials technology, Trondheim (Norway)


    Silicon solar cells based on n-type silicon wafers are less sensitive to carrier lifetime degradation due to several common metal impurities than p-base cells. The theoretical and experimental indications for this have recently received considerable attention. This paper compares p-type and n-type cells purposely contaminated with relatively high levels of impurities, processed by industrial techniques. The impurities considered are Al, Ti, and Fe, which are the dominant impurities in metallurgical silicon and natural quartz. The work also preliminary addresses the question whether the optimal wafer resistivity is the same for n-type as for p-type base mc-Si cells.

  15. T-type calcium channel expression in cultured human neuroblastoma cells

    Institute of Scientific and Technical Information of China (English)

    Xianjie Wen; Shiyuan Xu; Lingling Wang; Hua Liang; Chengxiang Yang; Hanbing Wang; Hongzhen Liu


    Human neuroblastoma cells (SH-SY5Y) have similar structures and functions as neural cells and have been frequently used for cell culture studies of neural cell functions. Previous studies have revealed Land N-type calcium channels in SH-SY5Y cells. However, the distribution of the low -voltage activated calcium channel (namely called T-type calcium channel, including Cav3.1, Cav3.2, and Cav3.3) in SH-SY5Y cells remains poorly understood. The present study detected mRNA and protein expression of the T-type calcium channel (Cav3.1, Cav3.2, and Cav3.3) in cultured SH-SY5Y cells using real-time polymerase chain reaction (PCR) and western blot analysis. Results revealed mRNA and protein expression from all three T-type calcium channel subtypes in SH-SY5Y cells. Moreover,Cav3.1 was the predominant T-type calcium channel subtype in SH-SY5Y cells.

  16. Type I hair cell degeneration in the utricular macula of the waltzing guinea pig

    DEFF Research Database (Denmark)

    Severinsen, Stig A; Raarup, Merete Krog; Ulfendahl, Mats


    Waltzing guinea pigs are an inbred guinea pig strain with a congenital and progressive balance and hearing disorder. A unique rod-shaped structure is found in the type I vestibular hair cells, that traverses the cell in an axial direction, extending towards the basement membrane. The present study...... estimates the total number of utricular hair cells and supporting cells in waltzing guinea pigs and age-matched control animals using the optical fractionator method. Animals were divided into four age groups (1, 7, 49 and 343 day-old). The number of type I hair cells decreased by 20% in the 343 day......-old waltzing guinea pigs compared to age-matched controls and younger animals. Two-photon confocal laser scanning microscopy using antibodies against fimbrin and betaIII-tubulin showed that the rods were exclusive to type I hair cells. There was no significant change in the length of the filament rods with age...

  17. Importance of Beta Cell Function for the Treatment of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Yoshifumi Saisho


    Full Text Available Type 2 diabetes (T2DM is characterized by insulin resistance and beta cell dysfunction. Recent evidence has emerged that beta cell dysfunction is a common pathogenetic feature of both type 1 and type 2 diabetes, and T2DM never develops without beta cell dysfunction. Therefore, treatment of T2DM should aim to restore beta cell function. Although the treatment of T2DM has greatly improved over the past few decades, remaining issues in the current treatment of T2DM include (1 hypoglycemia; (2 body weight gain; (3 peripheral hyperinsulinemia and (4 postprandial hyperglycemia, which are all associated with inappropriate insulin supplementation, again underpinning the important role of endogenous and physiological insulin secretion in the management of T2DM. This review summarizes the current knowledge on beta cell function in T2DM and discusses the treatment strategy for T2DM in relation to beta cell dysfunction.

  18. Type 1 collagen as a potential niche component for CD133-positive glioblastoma cells. (United States)

    Motegi, Hiroaki; Kamoshima, Yuuta; Terasaka, Shunsuke; Kobayashi, Hiroyuki; Houkin, Kiyohiro


    Cancer stem cells are thought to be closely related to tumor progression and recurrence, making them attractive therapeutic targets. Stem cells of various tissues exist within niches maintaining their stemness. Glioblastoma stem cells (GSCs) are located at tumor capillaries and the perivascular niche, which are considered to have an important role in maintaining GSCs. There were some extracellular matrices (ECM) on the perivascular connective tissue, including type 1 collagen. We here evaluated whether type 1 collagen has a potential niche for GSCs. Imunohistochemical staining of type 1 collagen and CD133, one of the GSCs markers, on glioblastoma (GBM) tissues showed CD133-positive cells were located in immediate proximity to type 1 collagen around tumor vessels. We cultured human GBM cell lines, U87MG and GBM cells obtained from fresh surgical tissues, T472 and T555, with serum-containing medium (SCM) or serum-free medium with some growth factors (SFM) and in non-coated (Non-coat) or type 1 collagen-coated plates (Col). The RNA expression levels of CD133 and Nestin as stem cell markers in each condition were examined. The Col condition not only with SFM but SCM made GBM cells more enhanced in RNA expression of CD133, compared to Non-coat/SCM. Semi-quantitative measurement of CD133-positive cells by immunocytochemistry showed a statistically significant increase of CD133-positive cells in Col/SFM. In addition, T472 cell line cultured in the Col/SFM had capabilities of sphere formation and tumorigenesis. Type 1 collagen was found in the perivascular area and showed a possibility to maintain GSCs. These findings suggest that type 1 collagen could be one important niche component for CD133-positive GSCs and maintain GSCs in adherent culture.

  19. Relationship between Various Chinese Medicine Types and T-cell Subsets in Patients with Ulcerative Colitis

    Institute of Scientific and Technical Information of China (English)

    常廷民; 李秀敏; 赵习德


    Objective:To investigate the relationship between various Chinese medicine(CM) types and T-cell subsets(CD4~+ and CD8~+) in the colonic mucous membranes of patients with ulcerative colitis(UC).Methods: Fifty UC patients were enrolled,after differentiation into four types by CM syndromes,i.e.,the internal heat-damp accumulation type(IHDA),the qi-stagnancy with blood stasis type(QSBS),the Pi(脾)-Shen(肾) yang-deficiency type(PSYD) and the yin-blood deficiency type(YBD).From every patient,3-5 pieces of intest...

  20. Towards identifying host cell-type specific response patterns to bacterial endosymbiosis

    DEFF Research Database (Denmark)

    Gavrilovic, Srdjan

    of view, available techniques have relied heavily on whole organ analyses that disregard specificities of individual cell types. To address this issue we aimed to develop a technology for comparative global analysis of mature mRNA and small RNA populations at the cell type specific level in the model...... plant Lotus japonicus. A powerful approach referred to here as Defined Expression and RNA Affinity co-Purification (DERAP) was developed to study gene expression and small RNA populations in the host roots during early phases of signal exchange at the cell-type level. As a basis for DERAP analysis...

  1. A Novel Cell Type Enables B. subtilis To Escape From Unsuccessful Sporulation In Minimal Medium

    Directory of Open Access Journals (Sweden)

    Herve Joel Defeu Soufo


    Full Text Available Sporulation is the most enduring survival strategy developed by several bacterial species. However, spore development of the model organism Bacillus subtilis has mainly been studied by means of media or conditions optimized for the induction of sporogenesis. Here, I show that during prolonged growth during stationary phase in minimal medium, B. subtilis undergoes an asymmetric cell division that produces small and round-shaped, DNA containing cells. In contrast to wild-type cells, mutants harboring spo0A or spoIIIE/sftA double mutations neither sporulate nor produce this special cell type, providing evidence that the small round cells emerge from the abortion of endospore formation. In most cases observed, the small round cells arise in the presence of sigma H but absence of sigma F activity, different from cases of abortive sporulation described for rich media. These data suggest that in minimal media, many cells are able to initiate but fail to complete spore development, and therefore return to normal growth as rods. This work reveals that the continuation of asymmetric cell division, which results in the formation of the small round cells, is a way for cells to delay or escape from - unsuccessful - sporulation. Based on these findings, I suggest to name the here described cell type as dwarf cells to distinguish them from the well-known minicells observed in mutants defective in septum placement or proper chromosome partitioning.

  2. 柏林中国移民调查与研究%A Survey and Study of Chinese Emigrants to Berlin

    Institute of Scientific and Technical Information of China (English)



    以柏林中国移民为对象,深入研究其生存状态、组织状况、移民目的及意愿,展现中国移民在柏林的历史与现状。结合对德国移民政策与管理的分析,发现政策的严格与管理的不合理使中国人很难将德国视为理想的移民目标国。在丰富欧洲与德国华人移民研究的同时,指出还应当突破传统欧洲华侨华人的研究范畴。此外,认为中国应在移民研究的基础上制定合理的移民政策,促进移民与移民国的共同发展。%Focusing on the living status,composition,and emigration purposes of the Chinese emigrants to Berlin,this paper illustrates the history and present situation of these emigrants.Through the analysis of the German policies and immigration management,the study finds that the strict policies and unreasonable management make it hard for the Chinese to take Germany as an ideal immigration destination.This study not only adds to the previous studies on Chinese emigrants in Europe but also goes beyond the traditional research scope.In addition,it is proposed that China should stipulate rational emigration policies on the basis of academic studies so as to promote the common development of our emigrants and the recipient countries.

  3. CD4+ type II NKT cells mediate ICOS and programmed death-1-dependent regulation of type 1 diabetes

    DEFF Research Database (Denmark)

    Kadri, Nadir; Korpos, Eva; Gupta, Shashank


    Type 1 diabetes (T1D) is a chronic autoimmune disease that results from T cell-mediated destruction of pancreatic ß cells. CD1d-restricted NKT lymphocytes have the ability to regulate immunity, including autoimmunity. We previously demonstrated that CD1d-restricted type II NKT cells, which carry ...

  4. β-cell dysfunction: Its critical role in prevention andmanagement of type 2 diabetes

    Institute of Scientific and Technical Information of China (English)

    Yoshifumi Saisho


    Type 2 diabetes (T2DM) is characterized by insulinresistance and β-cell dysfunction. Although, in contrastto type 1 diabetes, insulin resistance is assumed to bea major pathophysiological feature of T2DM, T2DMnever develops unless β-cells fail to compensate insulinresistance. Recent studies have revealed that a deficitof β-cell functional mass is an essential componentof the pathophysiology of T2DM, implying that β-celldeficit is a common feature of both type 1 and type 2diabetes. β-cell dysfunction is present at the diagnosisof T2DM and progressively worsens with diseaseduration. β-cell dysfunction is associated with worseningof glycemic control and treatment failure; thus, it isimportant to preserve or recover β-cell functional massin the management of T2DM. Since β-cell regenerativecapacity appears somewhat limited in humans, reducingβ-cell workload appears to be the most effective way topreserve β-cell functional mass to date, underpinningthe importance of lifestyle modification and weight lossfor the treatment and prevention of T2DM. This reviewsummarizes the current knowledge on β-cell functionalmass in T2DM and discusses the treatment strategy forT2DM.

  5. Distinct cell clusters touching islet cells induce islet cell replication in association with over-expression of Regenerating Gene (REG protein in fulminant type 1 diabetes.

    Directory of Open Access Journals (Sweden)

    Kaoru Aida

    Full Text Available BACKGROUND: Pancreatic islet endocrine cell-supporting architectures, including islet encapsulating basement membranes (BMs, extracellular matrix (ECM, and possible cell clusters, are unclear. PROCEDURES: The architectures around islet cell clusters, including BMs, ECM, and pancreatic acinar-like cell clusters, were studied in the non-diabetic state and in the inflamed milieu of fulminant type 1 diabetes in humans. RESULT: Immunohistochemical and electron microscopy analyses demonstrated that human islet cell clusters and acinar-like cell clusters adhere directly to each other with desmosomal structures and coated-pit-like structures between the two cell clusters. The two cell-clusters are encapsulated by a continuous capsule composed of common BMs/ECM. The acinar-like cell clusters have vesicles containing regenerating (REG Iα protein. The vesicles containing REG Iα protein are directly secreted to islet cells. In the inflamed milieu of fulminant type 1 diabetes, the acinar-like cell clusters over-expressed REG Iα protein. Islet endocrine cells, including beta-cells and non-beta cells, which were packed with the acinar-like cell clusters, show self-replication with a markedly increased number of Ki67-positive cells. CONCLUSION: The acinar-like cell clusters touching islet endocrine cells are distinct, because the cell clusters are packed with pancreatic islet clusters and surrounded by common BMs/ECM. Furthermore, the acinar-like cell clusters express REG Iα protein and secrete directly to neighboring islet endocrine cells in the non-diabetic state, and the cell clusters over-express REG Iα in the inflamed milieu of fulminant type 1 diabetes with marked self-replication of islet cells.

  6. Hypercalcemic type of small cell carcinoma of the ovary

    Directory of Open Access Journals (Sweden)

    Ilić Milena B.


    Full Text Available Introduction. Extrapulmonary small cell carcinoma is a rare, prognostically bad tumor category. Primary, it can be localized in every organ, even in the ovary, where, due to its clinical specificities, it represents a challenge in diagnosis, as well as in therapy. Small cell ovarian carcinoma (SCOC is biologically very aggressive malignant tumor of unknown histogenesis. We presented a rare case of SCOC with hypercalcemia of aggressive course and fatal outcome in a postmenopausal woman at International Federation of Gynecology and Obstetrics (FIGO Ia stage. Case report. A 60-year-old woman, Caucasian, came to the doctor because of discomfort in the lower abdomen and pain of greater intensity in last few days. Ultrasound examination and CT scan of the abdomen confirmed the presence of large adnexal masses of cystic-solid appearance with the largest diameter of 13 cm, regular structure of the other gynecological organs, without verifying the existence of metastatic deposits. All the results of laboratory analysis gave normal values, except for calcium, which was elevated. Explorative laparotomy with complete hysterectomy, bilateral salpingo-oophorectomy, dissection of lymph nodes and omentectomy were conducted. Based on pathohistological analysis of the operative material, SCOC at FIGO Ia stage was diagnosed. No complications were observed in a postsurgery period and after 10 days the patient was discharged in a good condition and with normal calcemia. The treatment was continued with concurrent radiotherapy and chemotherapy. However, in spite of overall treatment, the disease progressed, and the patient died of disseminated metastatic disease, 26 months after the diagnosis. Conclusion. Small cell carcinoma localized in the ovary is generally a tumor category with bad prognosis depending on the stage of the disease.

  7. 新移民与美国华文教育%New Chinese Emigrants and the Education of Chinese in the United States

    Institute of Scientific and Technical Information of China (English)

    周聿峨; 张树利


    Since the reform and opening, the new Chinese emigrants from Chinese mainland have increased quickly in the United States. Because of the strong sensibility of their ancestral nation, they attach importance to their children' s Chinese education. But in USA, the texts of all the Chinese language schools are printed with Big 5 (the complicated Chinese characters) and Zhuyin symbols (spelling letters), so, another kind of schools aeccommodated to their children' learning habit has been established. The development of these schools associate with the feature of new Chinese emigration, and they influence each other.

  8. Cells that emerge from embryonic explants produce fibers of type IV collagen. (United States)

    Chen, J M; Little, C D


    Double immunofluorescence staining experiments designed to examine the synthesis and deposition of collagen types I and IV in cultured explants of embryonic mouse lung revealed the presence of connective tissue-like fibers that were immunoreactive with anti-type IV collagen antibodies. This observation is contrary to the widely accepted belief that type IV collagen is found only in sheet-like arrangements beneath epithelia or as a sheath-like layer enveloping bundles of nerve or muscle cells. The extracellular matrix produced by cells that migrate from embryonic mouse lung rudiments in vitro was examined by double indirect immunofluorescence microscopy. Affinity-purified monospecific polyclonal antibodies were used to examine cells after growth on glass or native collagen substrata. The data show that embryonic mesenchymal cells can produce organized fibers of type IV collagen that are not contained within a basement membrane, and that embryonic epithelial cells deposit fibers and strands of type IV collagen beneath their basal surface when grown on glass; however, when grown on a rat tail collagen substratum the epithelial cells produce a fine meshwork. To our knowledge this work represents the first report that type IV collagen can be organized by cells into a fibrous extracellular matrix that is not a basement membrane.

  9. Cell type- and isotype-specific expression and regulation of β-tubulins in primary olfactory ensheathing cells and Schwann cells in vitro. (United States)

    Omar, Mohamed; Hansmann, Florian; Kreutzer, Robert; Kreutzer, Mihaela; Brandes, Gudrun; Wewetzer, Konstantin


    Olfactory ensheathing cells (OECs) and Schwann cells (SCs) are closely-related cell types with regeneration-promoting properties. Comparative gene expression analysis is particularly relevant since it may explain cell type-specific effects and guide the use of each cell type into special clinical applications. In the present study, we focused on β-tubulin isotype expression in primary adult canine glia as a translational large animal model. β-tubulins so far have been studied mainly in non-neuronal tumors and implied in tumorigenic growth. We show here that primary OECs and SCs expressed βII-V isotype mRNA. Interestingly, βIII-tubulin mRNA and protein expression was high in OECs and low in SCs, while fibroblast growth factor-2 (FGF-2) induced its down-regulation in both cell types to the same extent. This was in contrast to βV-tubulin mRNA which was similarly expressed in both cell types and unaltered by FGF-2. Immunocytochemical analysis revealed that OEC cultures contained a higher percentage of βIII-tubulin-positive cells compared to SC cultures. Addition of FGF-2 reduced the number of βIII-tubulin-positive cells in both cultures and significantly increased the percentage of cells with a multipolar morphology. Taken together, we demonstrate cell type-specific expression (βIII) and isotype-specific regulation (βIII, βV) of β-tubulin isotypes in OECs and SCs. While differential expression of βIII-tubulin in primary glial cell types with identical proliferative behaviour argues for novel functions unrelated to tumorigenic growth, strong βIII-tubulin expression in OECs may help to explain the specific properties of this glial cell type.

  10. Advances in plant cell type-specific genome-wide studies of gene expression

    Institute of Scientific and Technical Information of China (English)

    Ying WANG; Yuling JIAO


    Cell is the functional unit of life.To study the complex interactions of systems of biological molecules,it is crucial to dissect these molecules at the cell level.In recent years,major progresses have been made by plant biologists to profile gene expression in specific cell types at the genome-wide level.Approaches based on the isolation of cells,polysomes or nuclei have been developed and successfully used for studying the cell types from distinct organs of several plant species.These cell-level data sets revealed previously unrecognized cellular properties,such as cell-specific gene expression modules and hormone response centers,and should serve as essential resources for functional genomic analyses.Newly developed technologies are more affordable to many laboratories and should help to provide new insights at the cellular resolution in the near future.

  11. Parallel differentiation of embryonic stem cells into different cell types by a single gene-based differentiation system. (United States)

    Thoma, Eva C; Maurus, Katja; Wagner, Toni U; Schartl, Manfred


    The generation of defined somatic cell types from pluripotent stem cells represents a promising system for many applications for regenerative therapy or developmental studies. Certain key developmental genes have been shown to be able to influence the fate determination of differentiating stem cells suggesting an alternative differentiation strategy to conventional medium-based methods. Here, we present a system allowing controlled, directed differentiation of embryonic stem cells (ESCs) solely by ectopic expression of single genes. We demonstrate that the myogenic master regulator myoD1 is sufficient to induce formation of skeletal muscle. In contrast to previous studies, our data suggest that myoD1-induced differentiation is independent of additional differentiation-inducing or lineage-promoting signals and occurs even under pluripotency-promoting conditions. Moreover, we demonstrate that single gene-induced differentiation enables the controlled formation of two distinct cell types in parallel. By mixing ES cell lines expressing myoD1 or the neural transcription factor ngn2, respectively, we generated a mixed culture of myocytes and neurons. Our findings provide new insights in the role of key developmental genes during cell fate decisions. Furthermore, this study represents an interesting strategy to obtain mixed cultures of different cells from stem cells, suggesting a valuable tool for cellular development and cell-cell interaction studies.

  12. Modulation of MAA-induced apoptosis in male germ cells: role of Sertoli cell P/Q-type calcium channels

    Directory of Open Access Journals (Sweden)

    Aguanno Salvatore


    Full Text Available Abstract Spontaneous germ cell death by apoptosis occurs during normal spermatogenesis in mammals and is thought to play a role in the physiological mechanism limiting the clonal expansion of such cell population in the male gonad. In the prepubertal rat testis, the most conspicuous dying cells are pachytene spermatocytes, which are also the primary target of the apoptosis experimentally induced by the methoxyacetic acid (MAA. Since we have recently reported that Sertoli cells, the somatic component of the seminiferous epithelium, regulate not only germ cell viability and differentiation but also their death, we have further investigated the mechanism involved in such a control. In this paper we have used the protein clusterin, produced by Sertoli cells and associated with tissue damage or injury, as indicator of germ cell apoptosis in rat seminiferous tubules treated with MAA in the presence or in the absence of omega-agatoxin, a specific inhibitor of P/Q type voltage-operated calcium channels (VOCC's. We performed both a qualitative analysis of clusterin content and germ cell apoptosis by immunofluorescence experiments and a quantitative analysis by in situ end labelling of apoptotic germ cells followed by flow cytometry. The results obtained demonstrate that Sertoli cells modulate germ cell apoptosis induced by methoxyacetic acid also throughout the P/Q-type VOCC's.

  13. Invasiveness of Hepatocellular Carcinoma Cell Lines: Contribution of Membrane-Type 1 Matrix Metalloproteinase

    Directory of Open Access Journals (Sweden)

    Koji Murakami


    Full Text Available Intrahepatic metastasis is one of the malignant features of hepatocellular carcinoma (HCC. Matrix metalloproteoinases (MMPs and urokinase-type plasminogen activator (u-PA/plasmin, are known to be associated with the invasive properties of various types of tumor cells. In this study, we examined which proteinases play a role in the metastatic invasion of human HCC cell lines. JHH-5 and JHH-6 cells constitutively expressed mRNAs for both membrane-type 1 matrix metalloproteinase (MT1-MMP and u-PA and invaded through reconstituted MATRIGEL in vitro, whereas JHH-7 cells expressed u-PA mRNA but not MT1-MMP and did not invade. However, hepatocyte growth factor (HGF induced MT1-MMP expression on the surface of JHH-7 cells and markedly increased invasiveness of JHH-7 in a concentration-dependent manner. Moreover, cleavage activity for pro-MMP-2 was induced in HGF-treated JHH7 cells. MMP inhibitor, rather than serine proteinase inhibitor, potently inhibited HCC cell invasion. Intrahepatic injection of HCC cell lines into athymic nude mice caused visible intrahepatic metastases in vivo. Moreover, JHH-7 tumors showed expression of MT1-MMP mRNA, while in vitro cultured JHH-7 cells did not. These findings suggest that MTi-MMP plays an important role in the invasive properties of HCC cells, and that HGF modifies the invasive properties of noninvasive HCC cells.

  14. C-type lectins do not act as functional receptors for filovirus entry into cells

    Energy Technology Data Exchange (ETDEWEB)

    Matsuno, Keita; Nakayama, Eri; Noyori, Osamu [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo (Japan); Marzi, Andrea; Ebihara, Hideki [Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT (United States); Irimura, Tatsuro [Graduate School of Pharmaceutical Science, University of Tokyo, Tokyo (Japan); Feldmann, Heinz [Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT (United States); Takada, Ayato, E-mail: [Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo (Japan)


    Research highlights: {yields} Filovirus glycoprotein (GP) having a deficient receptor binding region were generated. {yields} Mutant GPs mediated virus entry less efficiently than wild-type GP. {yields} Mutant GPs bound to C-type lectins but not mediated entire steps of cellular entry. {yields} C-type lectins do not independently mediate filovirus entry into cells. {yields} Other molecule(s) are required for C-type lectin-mediated entry of filoviruses. -- Abstract: Cellular C-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (GP). However, it is not clearly known whether interaction between C-type lectins and GP mediates all the steps of virus entry (i.e., attachment, internalization, and membrane fusion). In this study, we generated vesicular stomatitis viruses pseudotyped with mutant GPs that have impaired structures of the putative receptor binding regions and thus reduced ability to infect the monkey kidney cells that are routinely used for virus propagation. We found that infectivities of viruses with the mutant GPs dropped in C-type lectin-expressing cells, parallel with those in the monkey kidney cells, whereas binding activities of these GPs to the C-type lectins were not correlated with the reduced infectivities. These results suggest that C-type lectin-mediated entry of filoviruses requires other cellular molecule(s) that may be involved in virion internalization or membrane fusion.

  15. Adjusting for Cell Type Composition in DNA Methylation Data Using a Regression-Based Approach. (United States)

    Jones, Meaghan J; Islam, Sumaiya A; Edgar, Rachel D; Kobor, Michael S


    Analysis of DNA methylation in a population context has the potential to uncover novel gene and environment interactions as well as markers of health and disease. In order to find such associations it is important to control for factors which may mask or alter DNA methylation signatures. Since tissue of origin and coinciding cell type composition are major contributors to DNA methylation patterns, and can easily confound important findings, it is vital to adjust DNA methylation data for such differences across individuals. Here we describe the use of a regression method to adjust for cell type composition in DNA methylation data. We specifically discuss what information is required to adjust for cell type composition and then provide detailed instructions on how to perform cell type adjustment on high dimensional DNA methylation data. This method has been applied mainly to Illumina 450K data, but can also be adapted to pyrosequencing or genome-wide bisulfite sequencing data.

  16. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology. (United States)

    Xu, Tao; Zhao, Weixin; Zhu, Jian-Ming; Albanna, Mohammad Z; Yoo, James J; Atala, Anthony


    This study was designed to develop a versatile method for fabricating complex and heterogeneous three-dimensional (3D) tissue constructs using simultaneous ink-jetting of multiple cell types. Human amniotic fluid-derived stem cells (hAFSCs), canine smooth muscle cells (dSMCs), and bovine aortic endothelial cells (bECs), were separately mixed with ionic cross-linker calcium chloride (CaCl(2)), loaded into separate ink cartridges and printed using a modified thermal inkjet printer. The three cell types were delivered layer-by-layer to pre-determined locations in a sodium alginate-collagen composite located in a chamber under the printer. The reaction between CaCl(2) and sodium alginate resulted in a rapid formation of a solid composite gel and the printed cells were anchored in designated areas within the gel. The printing process was repeated for several cycles leading to a complex 3D multi-cell hybrid construct. The biological functions of the 3D printed constructs were evaluated in vitro and in vivo. Each of the printed cell types maintained their viability and normal proliferation rates, phenotypic expression, and physiological functions within the heterogeneous constructs. The bioprinted constructs were able to survive and mature into functional tissues with adequate vascularization in vivo. These findings demonstrate the feasibility of fabricating complex heterogeneous tissue constructs containing multiple cell types using inkjet printing technology.

  17. Cell-type-specific enrichment of risk-associated regulatory elements at ovarian cancer susceptibility loci. (United States)

    Coetzee, Simon G; Shen, Howard C; Hazelett, Dennis J; Lawrenson, Kate; Kuchenbaecker, Karoline; Tyrer, Jonathan; Rhie, Suhn K; Levanon, Keren; Karst, Alison; Drapkin, Ronny; Ramus, Susan J; Couch, Fergus J; Offit, Kenneth; Chenevix-Trench, Georgia; Monteiro, Alvaro N A; Antoniou, Antonis; Freedman, Matthew; Coetzee, Gerhard A; Pharoah, Paul D P; Noushmehr, Houtan; Gayther, Simon A


    Understanding the regulatory landscape of the human genome is a central question in complex trait genetics. Most single-nucleotide polymorphisms (SNPs) associated with cancer risk lie in non-protein-coding regions, implicating regulatory DNA elements as functional targets of susceptibility variants. Here, we describe genome-wide annotation of regions of open chromatin and histone modification in fallopian tube and ovarian surface epithelial cells (FTSECs, OSECs), the debated cellular origins of high-grade serous ovarian cancers (HGSOCs) and in endometriosis epithelial cells (EECs), the likely precursor of clear cell ovarian carcinomas (CCOCs). The regulatory architecture of these cell types was compared with normal human mammary epithelial cells and LNCaP prostate cancer cells. We observed similar positional patterns of global enhancer signatures across the three different ovarian cancer precursor cell types, and evidence of tissue-specific regulatory signatures compared to non-gynecological cell types. We found significant enrichment for risk-associated SNPs intersecting regulatory biofeatures at 17 known HGSOC susceptibility loci in FTSECs (P = 3.8 × 10(-30)), OSECs (P = 2.4 × 10(-23)) and HMECs (P = 6.7 × 10(-15)) but not for EECs (P = 0.45) or LNCaP cells (P = 0.88). Hierarchical clustering of risk SNPs conditioned on the six different cell types indicates FTSECs and OSECs are highly related (96% of samples using multi-scale bootstrapping) suggesting both cell types may be precursors of HGSOC. These data represent the first description of regulatory catalogues of normal precursor cells for different ovarian cancer subtypes, and provide unique insights into the tissue specific regulatory variation with respect to the likely functional targets of germline genetic susceptibility variants for ovarian cancer.

  18. Congenic Mesenchymal Stem Cell Therapy Reverses Hyperglycemia in Experimental Type 1 Diabetes



    OBJECTIVE A number of clinical trials are underway to test whether mesenchymal stem cells (MSCs) are effective in treating various diseases, including type 1 diabetes. Although this cell therapy holds great promise, the optimal source of MSCs has yet to be determined with respect to major histocompatibility complex matching. Here, we examine this question by testing the ability of congenic MSCs, obtained from the NOR mouse strain, to reverse recent-onset type 1 diabetes in NOD mice, as well a...

  19. Rotavirus NSP4: Cell type-dependent transport kinetics to the exofacial plasma membrane and release from intact infected cells

    Directory of Open Access Journals (Sweden)

    Parr Rebecca D


    Full Text Available Abstract Background Rotavirus NSP4 localizes to multiple intracellular sites and is multifunctional, contributing to RV morphogenesis, replication and pathogenesis. One function of NSP4 is the induction of early secretory diarrhea by binding surface receptors to initiate signaling events. The aims of this study were to determine the transport kinetics of NSP4 to the exofacial plasma membrane (PM, the subsequent release from intact infected cells, and rebinding to naïve and/or neighboring cells in two cell types. Methods Transport kinetics was evaluated using surface-specific biotinylation/streptavidin pull-downs and exofacial exposure of NSP4 was confirmed by antibody binding to intact cells, and fluorescent resonant energy transfer. Transfected cells similarly were monitored to discern NSP4 movement in the absence of infection or other viral proteins. Endoglycosidase H digestions, preparation of CY3- or CY5- labeled F(ab2 fragments, confocal imaging, and determination of preferential polarized transport employed standard laboratory techniques. Mock-infected, mock-biotinylated and non-specific antibodies served as controls. Results Only full-length (FL, endoglycosidase-sensitive NSP4 was detected on the exofacial surface of two cell types, whereas the corresponding cell lysates showed multiple glycosylated forms. The C-terminus of FL NSP4 was detected on exofacial-membrane surfaces at different times in different cell types prior to its release into culture media. Transport to the PM was rapid and distinct yet FL NSP4 was secreted from both cell types at a time similar to the release of virus. NSP4-containing, clarified media from both cells bound surface molecules of naïve cells, and imaging showed secreted NSP4 from one or more infected cells bound neighboring cell membranes in culture. Preferential sorting to apical or basolateral membranes also was distinct in different polarized cells. Conclusions The intracellular transport of NSP4 to

  20. Hypoxia-induced modulation of apoptosis and BCL-2 family proteins in different cancer cell types.

    Directory of Open Access Journals (Sweden)

    Audrey Sermeus

    Full Text Available Hypoxia plays an important role in the resistance of tumour cells to chemotherapy. However, the exact mechanisms underlying this process are not well understood. Moreover, according to the cell lines, hypoxia differently influences cell death. The study of the effects of hypoxia on the apoptosis induced by 5 chemotherapeutic drugs in 7 cancer cell types showed that hypoxia generally inhibited the drug-induced apoptosis. In most cases, the effect of hypoxia was the same for all the drugs in one cell type. The expression profile of 93 genes involved in apoptosis as well as the protein level of BCL-2 family proteins were then investigated. In HepG2 cells that are strongly protected against cell death by hypoxia, hypoxia decreased the abundance of nearly all the pro-apoptotic BCL-2 family proteins while none of them are decreased in A549 cells that are not protected against cell death by hypoxia. In HepG2 cells, hypoxia decreased NOXA and BAD abundance and modified the electrophoretic mobility of BIM(EL. BIM and NOXA are important mediators of etoposide-induced cell death in HepG2 cells and the hypoxia-induced modification of these proteins abundance or post-translational modifications partly account for chemoresistance. Finally, the modulation of the abundance and/or of the post-translational modifications of most proteins of the BCL-2 family by hypoxia involves p53-dependent and -independent pathways and is cell type-dependent. A better understanding of these cell-to-cell variations is crucial in order to overcome hypoxia-induced resistance and to ameliorate cancer therapy.

  1. Molecular beacon-enabled purification of living cells by targeting cell type-specific mRNAs. (United States)

    Wile, Brian M; Ban, Kiwon; Yoon, Young-Sup; Bao, Gang


    Molecular beacons (MBs) are dual-labeled oligonucleotides that fluoresce only in the presence of complementary mRNA. The use of MBs to target specific mRNAs allows sorting of specific cells from a mixed cell population. In contrast to existing approaches that are limited by available surface markers or selectable metabolic characteristics, the MB-based method enables the isolation of a wide variety of cells. For example, the ability to purify specific cell types derived from pluripotent stem cells (PSCs) is important for basic research and therapeutics. In addition to providing a general protocol for MB design, validation and nucleofection into cells, we describe how to isolate a specific cell population from differentiating PSCs. By using this protocol, we have successfully isolated cardiomyocytes differentiated from mouse or human PSCs (hPSCs) with ∼ 97% purity, as confirmed by electrophysiology and immunocytochemistry. After designing MBs, their ordering and validation requires 2 weeks, and the isolation process requires 3 h.

  2. Gene expression profiles of hepatic cell-type specific marker genes in progression of liver fibrosis

    Institute of Scientific and Technical Information of China (English)

    Yoshiyuki Takahara; Mitsuo Takahashi; Hiroki Wagatsuma; Fumihiko Yokoya; Qing-Wei Zhang; Mutsuyo Yamaguchi; Hiroyuki Aburatani; Norifumi Kawada


    AIM: To determine the gene expression profile data for the whole liver during development of dimethylnitrosamine (DMN)-induced hepatic fibrosis.METHODS: Marker genes were identified for different types of hepatic cells, including hepatic stellate cells (HSCs), Kupffer cells (including other inflammatory cells),and hepatocytes, using independent temporal DNA microarray data obtained from isolated hepatic cells.RESULTS: The cell-type analysis of gene expression gave several key results and led to formation of three hypotheses: (1) changes in the expression of HSCspecific marker genes during fibrosis were similar to gene expression data in in vitro cultured HSCs, suggesting a major role of the self-activating characteristics of HSCs in formation of fibrosis; (2) expression of mast cell-specific marker genes reached a peak during liver fibrosis,suggesting a possible role of mast cells in formation of fibrosis; and (3) abnormal expression of hepatocytespecific marker genes was found across several metabolic pathways during fibrosis, including sulfur-containing amino acid metabolism, fatty acid metabolism, and drug metabolism, suggesting a mechanistic relationship between these abnormalities and symptoms of liver fibrosis.CONCLUSION: Analysis of marker genes for specific hepatic cell types can identify the key aspects of fibrogenesis. Sequential activation of inflammatory cells and the self-supporting properties of HSCs play an important role in development of fibrosis.

  3. Discovering cell types in flow cytometry data with random matrix theory (United States)

    Shen, Yang; Nussenblatt, Robert; Losert, Wolfgang

    Flow cytometry is a widely used experimental technique in immunology research. During the experiments, peripheral blood mononuclear cells (PBMC) from a single patient, labeled with multiple fluorescent stains that bind to different proteins, are illuminated by a laser. The intensity of each stain on a single cell is recorded and reflects the amount of protein expressed by that cell. The data analysis focuses on identifying specific cell types related to a disease. Different cell types can be identified by the type and amount of protein they express. To date, this has most often been done manually by labelling a protein as expressed or not while ignoring the amount of expression. Using a cross correlation matrix of stain intensities, which contains both information on the proteins expressed and their amount, has been largely ignored by researchers as it suffers from measurement noise. Here we present an algorithm to identify cell types in flow cytometry data which uses random matrix theory (RMT) to reduce noise in a cross correlation matrix. We demonstrate our method using a published flow cytometry data set. Compared with previous analysis techniques, we were able to rediscover relevant cell types in an automatic way. Department of Physics, University of Maryland, College Park, MD 20742.

  4. Expression of two types of acetylcholinesterase gene from the silkworm, Bombyx mori, in insect cells

    Institute of Scientific and Technical Information of China (English)



    Complementary DNAs encoding two types of acetylcholinesterase(AChE)were isolated from the silkworm, Bombyx mori. The type 1 (Bmace1) and type 2 (Bmace2) ORFs are 2052 and 1917 bp in length, respectively. Both the complete ORFs of the Bmaces and Cterminal truncated forms were recombined into the Bacmid baculovirus vector under the control of the polyhedrin promoter and expressed in Trichoplusia ni (Tn-5B 1-4) cells. The resulting products exhibited AChE activity and glycosylation of the expressed proteins. An inhibition assay indicated that the ace2-type enzyme was more sensitive than the acel-type enzyme to inhibition by eserine and paraoxon.

  5. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells. (United States)

    Wakao, Shohei; Kuroda, Yasumasa; Ogura, Fumitaka; Shigemoto, Taeko; Dezawa, Mari


    Mesenchymal stem cells (MSCs) are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse) cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  6. Regenerative Effects of Mesenchymal Stem Cells: Contribution of Muse Cells, a Novel Pluripotent Stem Cell Type that Resides in Mesenchymal Cells

    Directory of Open Access Journals (Sweden)

    Mari Dezawa


    Full Text Available Mesenchymal stem cells (MSCs are easily accessible and safe for regenerative medicine. MSCs exert trophic, immunomodulatory, anti-apoptotic, and tissue regeneration effects in a variety of tissues and organs, but their entity remains an enigma. Because MSCs are generally harvested from mesenchymal tissues, such as bone marrow, adipose tissue, or umbilical cord as adherent cells, MSCs comprise crude cell populations and are heterogeneous. The specific cells responsible for each effect have not been clarified. The most interesting property of MSCs is that, despite being adult stem cells that belong to the mesenchymal tissue lineage, they are able to differentiate into a broad spectrum of cells beyond the boundary of mesodermal lineage cells into ectodermal or endodermal lineages, and repair tissues. The broad spectrum of differentiation ability and tissue-repairing effects of MSCs might be mediated in part by the presence of a novel pluripotent stem cell type recently found in adult human mesenchymal tissues, termed multilineage-differentiating stress enduring (Muse cells. Here we review recently updated studies of the regenerative effects of MSCs and discuss their potential in regenerative medicine.

  7. Human oocytes reprogram adult somatic nuclei of a type 1 diabetic to diploid pluripotent stem cells. (United States)

    Yamada, Mitsutoshi; Johannesson, Bjarki; Sagi, Ido; Burnett, Lisa Cole; Kort, Daniel H; Prosser, Robert W; Paull, Daniel; Nestor, Michael W; Freeby, Matthew; Greenberg, Ellen; Goland, Robin S; Leibel, Rudolph L; Solomon, Susan L; Benvenisty, Nissim; Sauer, Mark V; Egli, Dieter


    The transfer of somatic cell nuclei into oocytes can give rise to pluripotent stem cells that are consistently equivalent to embryonic stem cells, holding promise for autologous cell replacement therapy. Although methods to induce pluripotent stem cells from somatic cells by transcription factors are widely used in basic research, numerous differences between induced pluripotent stem cells and embryonic stem cells have been reported, potentially affecting their clinical use. Because of the therapeutic potential of diploid embryonic stem-cell lines derived from adult cells of diseased human subjects, we have systematically investigated the parameters affecting efficiency of blastocyst development and stem-cell derivation. Here we show that improvements to the oocyte activation protocol, including the use of both kinase and translation inhibitors, and cell culture in the presence of histone deacetylase inhibitors, promote development to the blastocyst stage. Developmental efficiency varied between oocyte donors, and was inversely related to the number of days of hormonal stimulation required for oocyte maturation, whereas the daily dose of gonadotropin or the total number of metaphase II oocytes retrieved did not affect developmental outcome. Because the use of concentrated Sendai virus for cell fusion induced an increase in intracellular calcium concentration, causing premature oocyte activation, we used diluted Sendai virus in calcium-free medium. Using this modified nuclear transfer protocol, we derived diploid pluripotent stem-cell lines from somatic cells of a newborn and, for the first time, an adult, a female with type 1 diabetes.

  8. Multifactorial treatment increases endothelial progenitor cells in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Reinhard, H; Jacobsen, P Karl; Lajer, Marianne


    Endothelial progenitor cells (EPC) augment vascular repair and neovascularisation. Patients with type 2 diabetes have reduced EPC and increased risk of cardiovascular disease (CVD), which is reduced by multifactorial intervention. Our aim, therefore, was to evaluate in type 2 diabetic patients...

  9. Characteristics of dysfunction of islet β-cell in newly diagnosed type 2 diabetic patients

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the characteristics of the dysfunction of isletβ-cell in newly diagnosed type 2 diabetic patients. Methods Intravenous glucose tolerance test (IVGTT) was carried out on 352 newly diagnosed type 2 diabetic patients and 48 subjects with normal glucose tolerance (NGT) and then blood samples were collected 1, 2, 4, 6, and 10 minutes later to measure the

  10. Evaluation of prenatal RHD typing strategies on cell-free fetal DNA from maternal plasma

    NARCIS (Netherlands)

    M.G.H.M. Grootkerk-Tax; A.A. Soussan; M. de Haas; P.A. Maaskant-van Wijk; C.E. van der Schoot


    BACKGROUND: The discovery of cell-free fetal DNA in maternal plasma led to the development of assays to predict the fetal D status with RHD-specific sequences. Few assays are designed in such a way that the fetus can be typed in RHD psi mothers and that RHD psi fetuses are correctly typed. Owing to

  11. A probabilistic approach for the interpretation of RNA profiles as cell type evidence

    NARCIS (Netherlands)

    de Zoete, J.; Curran, J.; Sjerps, M.


    DNA profiles can be used as evidence to distinguish between possible donors of a crime stain. In some cases, both the prosecution and the defence claim that the cell material was left by the suspect but they dispute which cell type was left behind. For example, in sexual offense cases the prosecutio

  12. Induction of type XVI collagen expression facilitates proliferation of oral cancer cells. (United States)

    Ratzinger, Sabine; Grässel, Susanne; Dowejko, Albert; Reichert, Torsten E; Bauer, Richard J


    Type XVI collagen belongs to the family of fibril-associated collagens with interrupted triple helices (FACIT). Recently, high affinity to integrin alpha1beta1 has been shown allowing cells expressing those integrins to attach and spread on recombinant type XVI collagen. Here, we show that type XVI collagen is overexpressed in dysplastic areas of mucosal epithelium from oral squamous cell carcinoma (OSCC) patients. Induction of its expression in OSCC cell lines (COLXVI cells) leads to an increased expression of Kindlin-1. Moreover, we demonstrate a significantly increased Kindlin-1/beta1-integrin interaction. Additionally, we detected a higher number of activated beta1-integrins in COLXVI cells and found a neo-expression of alpha1 integrin subunit on these cells. FACS analysis revealed a significantly higher amount of COLXVI cells in S-phase and G2/M-phase 6h after synchronisation leading to a markedly higher proliferation activity. Blocking beta1-integrins with a specific antibody resulted in reduced proliferation of COLXVI cells. In summary, we demonstrate that overexpression of type XVI collagen in aberrant oral keratinocytes leads to Kindlin-1 induction, increased Kindlin-1/beta1-integrin interaction, integrin activation and subsequently to a proliferative cellular phenotype.

  13. Development of Type 1 Diabetes: Monocytes and dendritic cells in the pancreas

    NARCIS (Netherlands)

    J.M.C. Welzen-Coppens (Jojanneke)


    textabstractThis thesis focuses on the presence of precursors for dendritic cells and the characterization of dendritic cell subsets in the normal pancreas in mice and humans as well as in the pancreas of the NOD mouse, a type 1 diabetes mouse model. Therefore, we give a short introduction to dendri

  14. A predictive computational framework for direct reprogramming between human cell types. (United States)

    Rackham, Owen J L; Firas, Jaber; Fang, Hai; Oates, Matt E; Holmes, Melissa L; Knaupp, Anja S; Suzuki, Harukazu; Nefzger, Christian M; Daub, Carsten O; Shin, Jay W; Petretto, Enrico; Forrest, Alistair R R; Hayashizaki, Yoshihide; Polo, Jose M; Gough, Julian


    Transdifferentiation, the process of converting from one cell type to another without going through a pluripotent state, has great promise for regenerative medicine. The identification of key transcription factors for reprogramming is currently limited by the cost of exhaustive experimental testing of plausible sets of factors, an approach that is inefficient and unscalable. Here we present a predictive system (Mogrify) that combines gene expression data with regulatory network information to predict the reprogramming factors necessary to induce cell conversion. We have applied Mogrify to 173 human cell types and 134 tissues, defining an atlas of cellular reprogramming. Mogrify correctly predicts the transcription factors used in known transdifferentiations. Furthermore, we validated two new transdifferentiations predicted by Mogrify. We provide a practical and efficient mechanism for systematically implementing novel cell conversions, facilitating the generalization of reprogramming of human cells. Predictions are made available to help rapidly further the field of cell conversion.

  15. Th17 Cells in Type 1 Diabetes: Role in the Pathogenesis and Regulation by Gut Microbiome

    Directory of Open Access Journals (Sweden)

    Yangyang Li


    Full Text Available Type 1 diabetes (T1D is an autoimmune disease which is characterized by progressive destruction of insulin producing pancreatic islet β cells. The risk of developing T1D is determined by both genetic and environmental factors. A growing body of evidence supports an important role of T helper type 17 (Th17 cells along with impaired T regulatory (Treg cells in the development of T1D in animal models and humans. Alteration of gut microbiota has been implicated to be responsible for the imbalance between Th17 and Treg cells. However, there is controversy concerning a pathogenic versus protective role of Th17 cells in murine models of diabetes in the context of influence of gut microbiota. In this review we will summarize current knowledge about Th17 cells and gut microbiota involved in T1D and propose Th17 targeted therapy in children with islet autoimmunity to prevent progression to overt diabetes.

  16. Inorganic p-Type Semiconductors: Their Applications and Progress in Dye-Sensitized Solar Cells and Perovskite Solar Cells

    Directory of Open Access Journals (Sweden)

    Ming-Hsien Li


    Full Text Available Considering the increasing global demand for energy and the harmful ecological impact of conventional energy sources, it is obvious that development of clean and renewable energy is a necessity. Since the Sun is our only external energy source, harnessing its energy, which is clean, non-hazardous and infinite, satisfies the main objectives of all alternative energy strategies. With attractive features, i.e., good performance, low-cost potential, simple processibility, a wide range of applications from portable power generation to power-windows, photoelectrochemical solar cells like dye-sensitized solar cells (DSCs represent one of the promising methods for future large-scale power production directly from sunlight. While the sensitization of n-type semiconductors (n-SC has been intensively studied, the use of p-type semiconductor (p-SC, e.g., the sensitization of wide bandgap p-SC and hole transport materials with p-SC have also been attracting great attention. Recently, it has been proved that the p-type inorganic semiconductor as a charge selective material or a charge transport material in organometallic lead halide perovskite solar cells (PSCs shows a significant impact on solar cell performance. Therefore the study of p-type semiconductors is important to rationally design efficient DSCs and PSCs. In this review, recent published works on p-type DSCs and PSCs incorporated with an inorganic p-type semiconductor and our perspectives on this topic are discussed.

  17. Behind the lines–actions of bacterial type III effector proteins in plant cells


    Büttner, Daniela


    Pathogenicity of most Gram-negative plant-pathogenic bacteria depends on the type III secretion (T3S) system, which translocates bacterial effector proteins into plant cells. Type III effectors modulate plant cellular pathways to the benefit of the pathogen and promote bacterial multiplication. One major virulence function of type III effectors is the suppression of plant innate immunity, which is triggered upon recognition of pathogen-derived molecular patterns by plant receptor proteins. Ty...

  18. Induction of type I IFN is required for overcoming tumor-specific T-cell tolerance after stem cell transplantation. (United States)

    Horkheimer, Ian; Quigley, Michael; Zhu, Jiangao; Huang, Xiaopei; Chao, Nelson J; Yang, Yiping


    Tumor-specific T-cell tolerance represents one major mechanism of tumor-induced immune evasion. Myeloablative chemotherapy with stem cell transplantation may offer the best chance of achieving a state of minimal residual disease and, thus, minimize tumor-induced immune evasion. However, studies have shown that tumor-specific T-cell tolerance persists after transplantation. Here, we showed that CD4(+)CD25(+) regulatory T (T(Reg)) cells play a critical role in tumor-specific CD8(+) T-cell tolerance after transplantation. Removal of T(Reg) cells from the donor lymphocyte graft did not overcome this tolerance because of rapid conversion of donor CD4(+)CD25(-) T cells into CD4(+)CD25(+)Foxp3(+) T(Reg) cells in recipients after transplantation, and depletion of T(Reg) cells in recipients was necessary for the reversal of tumor-specific tolerance. These results suggest that strategies capable of overcoming T-cell tolerance in recipients are required to promote antitumor immunity after transplantation. Toward this goal, we showed that dendritic cell (DC) vaccines coadministered with the TLR9 ligand, CpG could effectively overcome tumor-specific tolerance, leading to significant prolongation of tumor-free survival after transplantation. We further showed that CpG-induced type I interferon was critical for the reversal of tumor-specific tolerance in vivo. Collectively, these results may suggest effective immunotherapeutic strategies for treating cancer after stem cell transplantation.

  19. Identification of XMRV infection-associated microRNAs in four cell types in culture.

    Directory of Open Access Journals (Sweden)

    Ketha V K Mohan

    Full Text Available INTRODUCTION: XMRV is a gammaretrovirus that was thought to be associated with prostate cancer (PC and chronic fatigue syndrome (CFS in humans until recently. The virus is culturable in various cells of human origin like the lymphocytes, NK cells, neuronal cells, and prostate cell lines. MicroRNAs (miRNA, which regulate gene expression, were so far not identified in cells infected with XMRV in culture. METHODS: Two prostate cell lines (LNCaP and DU145 and two primary cells, Peripheral Blood Lymphocytes [PBL] and Monocyte-derived Macrophages [MDM] were infected with XMRV. Total mRNA was extracted from mock- and virus-infected cells at 6, 24 and 48 hours post infection and evaluated for microRNA profile in a microarray. RESULTS: MicroRNA expression profiles of XMRV-infected continuous prostate cancer cell lines differ from that of virus-infected primary cells (PBL and MDMs. miR-193a-3p and miRPlus-E1245 observed to be specific to XMRV infection in all 4 cell types. While miR-193a-3p levels were down regulated miRPlus-E1245 on the other hand exhibited varied expression profile between the 4 cell types. DISCUSSION: The present study clearly demonstrates that cellular microRNAs are expressed during XMRV infection of human cells and this is the first report demonstrating the regulation of miR193a-3p and miRPlus-E1245 during XMRV infection in four different human cell types.

  20. New World hantaviruses activate IFNlambda production in type I IFN-deficient vero E6 cells.

    Directory of Open Access Journals (Sweden)

    Joseph Prescott

    Full Text Available Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS. These viruses induce a strong interferon-stimulated gene (ISG response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN, rendering them unable to mount an efficient innate immune response to virus infection. Interferon lambda, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner.We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNlambda. Three New World hantaviruses were similarly able to induce IFNlambda expression in this cell line. The IFNlambda contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7 without inducing ISGs.Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNlambda. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNlambda production in these cells might increase their utility

  1. Anaesthetics may change the shape of isolated type I hair cells. (United States)

    Scarfone, E; Ulfendahl, M; Figueroa, L; Flock, A


    Type I hair cells isolated from animals anaesthetised with barbiturates or ether were found to be shorter and to lack a prominent 'neck' region when compared to cells isolated from non-anaesthetised animals. Ketamine did not have this effect. The changes observed could have important implications for the physiology of inner ear receptors. These findings infer that care should be taken in the choice of anaesthetics used in studies on cells from the inner ear.

  2. Efficiency Improvement of HIT Solar Cells on p-Type Si Wafers


    Chun-You Wei; Chu-Hsuan Lin; Hao-Tse Hsiao; Po-Chuan Yang; Chih-Ming Wang; Yen-Chih Pan


    Single crystal silicon solar cells are still predominant in the market due to the abundance of silicon on earth and their acceptable efficiency. Different solar-cell structures of single crystalline Si have been investigated to boost efficiency; the heterojunction with intrinsic thin layer (HIT) structure is currently the leading technology. The record efficiency values of state-of-the art HIT solar cells have always been based on n-type single-crystalline Si wafers. Improving the efficiency ...

  3. Ultrastructural characteristics of type A epithelioid cells during BCG-granulomatosis and treatment with lysosomotropic isoniazid. (United States)

    Shkurupii, V A; Kozyaev, M A; Nadeev, A P


    We studied BCG-granulomas, their cellular composition, and ultrastructure of type A epithelioid cells in the liver of male BALB/c mice with spontaneous granulomatous inflammation. The animals received free isoniazid or isoniazid conjugated with lysosomotropic intracellularly prolonged matrix (dialdehyde dextran, molecular weight 65-75 kDa). Lysosomotropic isoniazid was accumulated in the vacuolar apparatus of epithelioid cells and produced a stimulatory effect on plastic processes in these cells.

  4. Causes of upregulation of glycolysis in lymphocytes upon stimulation. A comparison with other cell types. (United States)

    Stark, Heiko; Fichtner, Maximilian; König, Rainer; Lorkowski, Stefan; Schuster, Stefan


    In this review, we revisit the metabolic shift from respiration to glycolysis in lymphocytes upon activation, which is known as the Warburg effect in tumour cells. We compare the situation in lymphocytes with those in several other cell types, such as muscle cells, Kupffer cells, microglia cells, astrocytes, stem cells, tumour cells and various unicellular organisms (e.g. yeasts). We critically discuss and compare several explanations put forward in the literature for the observation that proliferating cells adopt this apparently less efficient pathway: hypoxia, poisoning of competitors by end products, higher ATP production rate, higher precursor supply, regulatory effects, and avoiding harmful effects (e.g. by reactive oxygen species). We conclude that in the case of lymphocytes, increased ATP production rate and precursor supply are the main advantages of upregulating glycolysis.

  5. The vicious cycle of apoptotic beta-cell death in type 1 diabetes. (United States)

    Kaminitz, Ayelet; Stein, Jerry; Yaniv, Isaac; Askenasy, Nadir


    Autoimmune insulitis, the cause of type 1 diabetes, evolves through several discrete stages that culminate in beta-cell death. In the first stage, antigenic epitopes of B-cell-specific peptides are processed by antigen presenting cells in local lymph nodes, and auto-reactive lymphocyte clones are propagated. Subsequently, cell-mediated and direct cytokine-mediated reactions are generated against the beta-cells, and the beta-cells are sensitized to apoptosis. Ironically, the beta-cells themselves contribute some of the cytokines and chemokines that provoke the immune reaction within the islets. Once this vicious cycle of autoimmunity is fully developed, the fate of the beta-cells in the islets is sealed, and clinical diabetes inevitably ensues. Differences in various aspects of these concurrent events appear to underlie the significant discrepancies in experimental data observed in experimental models that simulate autoimmune insulitis.

  6. B-type suppression: a role played by "regulatory B cells" or "regulatory plasma cells"? (United States)

    Ries, Stefanie; Hilgenberg, Ellen; Lampropoulou, Vicky; Shen, Ping; Dang, Van Duc; Wilantri, Siska; Sakwa, Imme; Fillatreau, Simon


    B-cell depletion can improve disease in some patients with rheumatoid arthritis or multiple sclerosis, indicating the pathogenic contribution of B cells to autoimmunity. However, studies in mice have demonstrated that B cells have immunosuppressive functions as well, with IL-10 being a critical mediator of B-cell-mediated suppression. IL-10-secreting B cells have been shown to promote disease remission in some mouse models of autoimmune disorders. Human B cells also produce IL-10, and evidence is accumulating that human IL-10-producing B cells might inhibit immunity. There is considerable interest in identifying the phenotype of B cells providing IL-10 in a suppressive manner, which would facilitate the analysis of the molecular mechanisms controlling this B-cell property. Here, we review current knowledge on the B-cell subpopulations found to provide suppressive functions in mice, considering both the pathological context in which they were identified and the signals that control their induction. We discuss the phenotype of B cells that have IL-10-dependent regulatory activities in mice, which leads us to propose that antibody-secreting cells are, in some cases at least, the major source of B-cell-derived regulatory IL-10 in vivo. Anti-inflammatory cytokine production by antibody-secreting cells offers a novel mechanism for the coordination of innate and humoral immune responses.

  7. Mesenchymal Stem Cells Sense Three Dimensional Type I Collagen through Discoidin Domain Receptor 1. (United States)

    Lund, A W; Stegemann, J P; Plopper, G E


    The extracellular matrix provides structural and organizational cues for tissue development and defines and maintains cellular phenotype during cell fate determination. Multipotent mesenchymal stem cells use this matrix to tightly regulate the balance between their differentiation potential and self-renewal in the native niche. When understood, the mechanisms that govern cell-matrix crosstalk during differentiation will allow for efficient engineering of natural and synthetic matrices to specifically direct and maintain stem cell phenotype. This work identifies the discoidin domain receptor 1 (DDR1), a collagen activated receptor tyrosine kinase, as a potential link through which stem cells sense and respond to the 3D organization of their extracellular matrix microenvironment. DDR1 is dependent upon both the structure and proteolytic state of its collagen ligand and is specifically expressed and localized in three dimensional type I collagen culture. Inhibition of DDR1 expression results in decreased osteogenic potential, increased cell spreading, stress fiber formation and ERK1/2 phosphorylation. Additionally, loss of DDR1 activity alters the cell-mediated organization of the naïve type I collagen matrix. Taken together, these results demonstrate a role for DDR1 in the stem cell response to and interaction with three dimensional type I collagen. Dynamic changes in cell shape in 3D culture and the tuning of the local ECM microstructure, directs crosstalk between DDR1 and two dimensional mechanisms of osteogenesis that can alter their traditional roles.

  8. Cell-type-specific neuroanatomy of cliques of autism-related genes in the mouse brain

    Directory of Open Access Journals (Sweden)

    Pascal eGrange


    Full Text Available Two cliques of genes identified computationally for their high co-expression in the mouse brain according to the Allen Brain Atlas, and for their enrichment in genes related to autism spectrum disorder, have recently been shown to be highly co-expressed in the cerebellar cortex, compared to what could be expected by chance. Moreover, the expression of these cliques of genes is not homogeneous across the cerebellar cortex, and it has been noted that their expression pattern seems to highlight the granular layer. However, this observation was only made by eye, and recent advances in computational neuroanatomy allow to rank cell types in the mouse brain (characterized by their transcriptome profiles according to the similarity between their spatial density profiles and the expression profiles of the cliques. We establish by Monte Carlo simulation that with probability at least 99%, the expression profiles of the two cliques are more similar to the density profile of granule cells than 99% of the expression of cliques containing the same number of genes (Purkinje cells also score above 99% in one of the cliques. Thresholding the expression profiles shows that the signal is more intense in the granular layer. Finally, we work out pairs of cell types whose combined expression profiles are more similar to the expression profiles of the cliquesthan any single cell type. These pairs predominantly consist of one cortical pyramidal cell and one cerebellar cell (whichcan be either a granule cell or a Purkinje cell.

  9. Burkholderia type VI secretion systems have distinct roles in eukaryotic and bacterial cell interactions

    DEFF Research Database (Denmark)

    Schwarz, Sandra; West, T Eoin; Boyer, Frédéric


    . From a group of 31 diverse bacteria, we identified several organisms that competed less effectively against wild-type B. thai than a strain lacking T6SS-1 function. Inactivation of T6SS-1 renders B. thai greatly more susceptible to cell contact-induced stasis by Pseudomonas putida, Pseudomonas...... fluorescens and Serratia proteamaculans-leaving it 100- to 1000-fold less fit than the wild-type in competition experiments with these organisms. Flow cell biofilm assays showed that T6S-dependent interbacterial interactions are likely relevant in the environment. B. thai cells lacking T6SS-1 were rapidly...

  10. Engineering of red cells of Arabidopsis thaliana and comparative genome-wide gene expression analysis of red cells versus wild-type cells. (United States)

    Shi, Ming-Zhu; Xie, De-Yu


    We report metabolic engineering of Arabidopsis red cells and genome-wide gene expression analysis associated with anthocyanin biosynthesis and other metabolic pathways between red cells and wild-type (WT) cells. Red cells of A. thaliana were engineered for the first time from the leaves of production of anthocyanin pigment 1-Dominant (pap1-D). These red cells produced seven anthocyanin molecules including a new one that was characterized by LC-MS analysis. Wild-type cells established as a control did not produce anthocyanins. A genome-wide microarray analysis revealed that nearly 66 and 65% of genes in the genome were expressed in the red cells and wild-type cells, respectively. In comparison with the WT cells, 3.2% of expressed genes in the red cells were differentially expressed. The expression levels of 14 genes involved in the biosynthetic pathway of anthocyanin were significantly higher in the red cells than in the WT cells. Microarray and RT-PCR analyses demonstrated that the TTG1-GL3/TT8-PAP1 complex regulated the biosynthesis of anthocyanins. Furthermore, most of the genes with significant differential expression levels in the red cells versus the WT cells were characterized with diverse biochemical functions, many of which were mapped to different metabolic pathways (e.g., ribosomal protein biosynthesis, photosynthesis, glycolysis, glyoxylate metabolism, and plant secondary metabolisms) or organelles (e.g., chloroplast). We suggest that the difference in gene expression profiles between the two cell lines likely results from cell types, the overexpression of PAP1, and the high metabolic flux toward anthocyanins.

  11. Collagen Type II Enhances Chondrogenesis in Adipose Tissue-Derived Stem Cells by Affecting Cell Shape

    NARCIS (Netherlands)

    Lu, ZuFu; Doulabi, Behrouz Zandieh; Huang, ChunLing; Bank, Ruud A.; Helder, Marco N.


    Ideally, biomaterials have inductive properties, favoring specific lineage differentiation. For chondrogenic induction, these properties have been attributed to collagen type II. However, the underlying mechanisms are largely unknown. This study aimed to investigate whether collagen type II favors c

  12. Collagen type II enhances chondrogenesis in adipose tissue-derived stem cells by affecting cell shape

    NARCIS (Netherlands)

    Lu, Z.; Doulabi, B.Z.; Huang, C.; Bank, R.A.; Helder, M.N.


    Ideally, biomaterials have inductive properties, favoring specific lineage differentiation. For chondrogenic induction, these properties have been attributed to collagen type II. However, the underlying mechanisms are largely unknown. This study aimed to investigate whether collagen type II favors c

  13. Pestalozzi in Dewey's Realm? Bauhaus Master Josef Albers among the German-Speaking Emigres' Colony at Black Mountain College (1933-1949) (United States)

    Fussl, Karl Heinz


    This article deals with German academic emigres who fled Hitler after 1933 and established their refuge at the American-based Black Mountain College in North Carolina, founded as an alternative to traditional institutions of higher education in that very year. Of particular consideration are the contributions of noted Bauhaus master Josef Albers…

  14. Cutting edge: pulmonary Legionella pneumophila is controlled by plasmacytoid dendritic cells but not type I IFN. (United States)

    Ang, Desmond K Y; Oates, Clare V L; Schuelein, Ralf; Kelly, Michelle; Sansom, Fiona M; Bourges, Dorothée; Boon, Louis; Hertzog, Paul J; Hartland, Elizabeth L; van Driel, Ian R


    Plasmacytoid dendritic cells (pDCs) are well known as the major cell type that secretes type I IFN in response to viral infections. Their role in combating other classes of infectious organisms, including bacteria, and their mechanisms of action are poorly understood. We have found that pDCs play a significant role in the acute response to the intracellular bacterial pathogen Legionella pneumophila. pDCs were rapidly recruited to the lungs of L. pneumophila-infected mice, and depletion of pDCs resulted in increased bacterial load. The ability of pDCs to combat infection did not require type I IFN. This study points to an unappreciated role for pDCs in combating bacterial infections and indicates a novel mechanism of action for this cell type.

  15. Low-cost zinc-plated photoanode for fabric-type dye-sensitized solar cells (United States)

    Kong, Lingfeng; Bao, Yunna; Guo, Wanwan; Cheng, Li; Du, Jun; Liu, Renlong; Wang, Yundong; Fan, Xing; Tao, Changyuan


    Fabric-type flexible solar cells have been recently proposed as a very promising power source for wearable electronics. To increase the photocurrent of fabric-type flexible solar cells, low-cost zinc-plated wire and mesh photoanodes are assembled for the first time through a mild wet process. Given the protection of the compact protection layer, the DSSC device could benefit from the low work function of Zn and self-repairing behavior on the Zn/ZnO interface. An evident current increase by ∼6 mA/cm2 could be observed after coating a layer of metal Zn on various metal substrates, such as traditional stainless steel wire. Given the self-repairing behavior on Zn/ZnO interface, the Zn layer can help to improve the interfacial carrier transfer, leading to better photovoltaic performance, for both liquid-type and solid-type cells.

  16. An atlas of active enhancers across human cell types and tissues

    DEFF Research Database (Denmark)

    Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene


    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples......, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which...... is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility...

  17. Ontogenetic profile and thyroid hormone regulation of type-1 and type-8 glucose transporters in rat Sertoli cells. (United States)

    Carosa, Eleonora; Radico, Carla; Giansante, Nadia; Rossi, Simona; D'Adamo, Fabio; Di Stasi, Savino M; Lenzi, Andrea; Jannini, Emmanuele A


    The glucose transporters (GLUTs) gene encode glycoproteins responsible for facilitating transfer of glucose across plasma membrane. In testis, different members of this family are present. In particular the main GLUT mRNA expression within the adult testis is the type 8, while type 1 is more expressed in prepubertal testis. Thyroid hormone, which receptors and function have been characterized in the testis, plays a crucial role in the cellular energetic metabolism. In fact, in the immature Sertoli cells, GLUT1 is up regulated by l-triiodothyronine (T(3)). The aim of this paper is to investigate the expression profile of GLUT1 and GLUT8 in the testis during development and in adulthood and analyse the role of T(3) on their expression. To analyse the expression of GLUT8 and GLUT1 we performed Northern blot and RT-PCR experiments in the whole testis and in Sertoli cells from rats of different ages. Treatments in vivo and in vitro with T(3) were used to study the effect of thyroid hormones on GLUT1 and GLUT8 expression. The activity of the rat GLUT1 promoter and its regulation by T(3) was studied with transient transfections in gonadal and non-gonadal cell lines and in primary Sertoli cell cultures. GLUT8 is expressed at a low level in the prepubertal testis and Sertoli cells and does not appear to be under T(3) control. GLUT1 is the predominant form in immature Sertoli cells. The effect of T(3) on its mRNA accumulation was quantified and confirmed by RT-PCR (control: 0.65 +/- 0.17; T(3): 1.23 +/- 0.04, arbitrary units, p regulate GLUT1 promoter in any cell line tested. This is confirmed by the evidence that, upon extensive analysis, the rat GLUT1 promoter and the first intron sequence do not shows any thyroid responsive elements. Our data demonstrate that GLUT1 and GLUT8 are both expressed in prepubertal testis, but only GLUT1 is regulated by T(3). In addition, we found that the effect of T(3) cannot be attributed to its action on GLUT1 promoter.

  18. Protective effect of catechin in type I Gaucher disease cells by reducing endoplasmic reticulum stress

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yea-Jin [Department of Biotechnology, Hoseo University, Baebang, Asan, Chungnam, 336-795 (Korea, Republic of); Kim, Sung-Jo, E-mail: [Department of Biotechnology, Hoseo University, Baebang, Asan, Chungnam, 336-795 (Korea, Republic of); Heo, Tae-Hwe, E-mail: [College of Pharmacy, The Catholic University of Korea, Bucheon 420-743 (Korea, Republic of)


    Highlights: {yields} Catechin reduces the expression level of ER stress marker protein in type I Gaucher disease cells. {yields} Catechin induces the proliferation rate of GD cells similar levels to normal cells. {yields} Catechin improves wound healing activity. {yields} Catechin-mediated reductions in ER stress may be associated with enhanced cell survival. {yields} We identified catechin as a protective agent against ER stress in GD cells. -- Abstract: Gaucher disease (GD) is the most common lysosomal storage disorder (LSD) and is divided into three phenotypes, I, II, and III. Type I is the most prevalent form and has its onset in adulthood. The degree of endoplasmic reticulum (ER) stress is one of the factors that determine GD severity. It has recently been reported that antioxidants reduce ER stress and apoptosis by scavenging the oxidants that cause oxidative stress. For this report, we investigated the possibility that catechin can act on type I GD patient cells to alleviate the pathogenic conditions of GD. We treated GD cells with catechin and examined the expression level of GRP78/BiP (an ER stress marker) by western blots and fluorescence microscopy, the proliferation rate of GD cells, and scratch-induced wound healing activity. Our results show that catechin reduces the expression level of GRP78/BiP, leads to cell proliferation rates of GD cells similar levels to normal cells, and improves wound healing activity. We conclude that catechin protects against ER stress in GD cells and catechin-mediated reductions in ER stress may be associated with enhanced cell survival.

  19. Type 3 innate lymphoid cells maintain intestinal epithelial stem cells after tissue damage

    NARCIS (Netherlands)

    P. Aparicio-Domingo (Patricia); M. Romera-Hernandez (Monica); J.J. Karrich (Julien J.); F.H.J. Cornelissen (Ferry); N. Papazian (Natalie); D.J. Lindenbergh-Kortleve (Dicky); J.A. Butler (James A.); L. Boon (Louis); M. Coles (Mark); J.N. Samsom (Janneke); T. Cupedo (Tom)


    textabstractDisruption of the intestinal epithelial barrier allows bacterial translocation and predisposes to destructive inflammation. To ensure proper barrier composition, crypt-residing stem cells continuously proliferate and replenish all intestinal epithelial cells within days. As a consequence

  20. Gene expression profiles and neural activities of Kenyon cell subtypes in the honeybee brain: identification of novel 'middle-type' Kenyon cells. (United States)

    Kaneko, Kumi; Suenami, Shota; Kubo, Takeo


    In the honeybee (Apis mellifera L.), it has long been thought that the mushroom bodies, a higher-order center in the insect brain, comprise three distinct subtypes of intrinsic neurons called Kenyon cells. In class-I large-type Kenyon cells and class-I small-type Kenyon cells, the somata are localized at the edges and in the inner core of the mushroom body calyces, respectively. In class-II Kenyon cells, the somata are localized at the outer surface of the mushroom body calyces. The gene expression profiles of the large- and small-type Kenyon cells are distinct, suggesting that each exhibits distinct cellular characteristics. We recently identified a novel gene, mKast (middle-type Kenyon cell-preferential arrestin-related gene-1), which has a distinctive expression pattern in the Kenyon cells. Detailed expression analyses of mKast led to the discovery of novel 'middle-type' Kenyon cells characterized by their preferential mKast-expression in the mushroom bodies. The somata of the middle-type Kenyon cells are localized between the large- and small-type Kenyon cells, and the size of the middle-type Kenyon cell somata is intermediate between that of large- and small-type Kenyon cells. Middle-type Kenyon cells appear to differentiate from the large- and/or small-type Kenyon cell lineage(s). Neural activity mapping using an immediate early gene, kakusei, suggests that the small-type and some middle-type Kenyon cells are prominently active in the forager brain, suggesting a potential role in processing information during foraging flight. Our findings indicate that honeybee mushroom bodies in fact comprise four types of Kenyon cells with different molecular and cellular characteristics: the previously known class-I large- and small-type Kenyon cells, class-II Kenyon cells, and the newly identified middle-type Kenyon cells described in this review. As the cellular characteristics of the middle-type Kenyon cells are distinct from those of the large- and small-type Kenyon

  1. Cell type mediated resistance of vesicular stomatitis virus and Sendai virus to ribavirin. (United States)

    Shah, Nirav R; Sunderland, Amanda; Grdzelishvili, Valery Z


    Ribavirin (RBV) is a synthetic nucleoside analog with broad spectrum antiviral activity. Although RBV is approved for the treatment of hepatitis C virus, respiratory syncytial virus, and Lassa fever virus infections, its mechanism of action and therapeutic efficacy remains highly controversial. Recent reports show that the development of cell-based resistance after continuous RBV treatment via decreased RBV uptake can greatly limit its efficacy. Here, we examined whether certain cell types are naturally resistant to RBV even without prior drug exposure. Seven different cell lines from various host species were compared for RBV antiviral activity against two nonsegmented negative-strand RNA viruses, vesicular stomatitis virus (VSV, a rhabdovirus) and Sendai virus (SeV, a paramyxovirus). Our results show striking differences between cell types in their response to RBV, ranging from virtually no antiviral effect to very effective inhibition of viral replication. Despite differences in viral replication kinetics for VSV and SeV in the seven cell lines, the observed pattern of RBV resistance was very similar for both viruses, suggesting that cellular rather than viral determinants play a major role in this resistance. While none of the tested cell lines was defective in RBV uptake, dramatic variations were observed in the long-term accumulation of RBV in different cell types, and it correlated with the antiviral efficacy of RBV. While addition of guanosine neutralized RBV only in cells already highly resistant to RBV, actinomycin D almost completely reversed the RBV effect (but not uptake) in all cell lines. Together, our data suggest that RBV may inhibit the same virus via different mechanisms in different cell types depending on the intracellular RBV metabolism. Our results strongly point out the importance of using multiple cell lines of different origin when antiviral efficacy and potency are examined for new as well as established drugs in vitro.

  2. Cell type mediated resistance of vesicular stomatitis virus and Sendai virus to ribavirin.

    Directory of Open Access Journals (Sweden)

    Nirav R Shah

    Full Text Available Ribavirin (RBV is a synthetic nucleoside analog with broad spectrum antiviral activity. Although RBV is approved for the treatment of hepatitis C virus, respiratory syncytial virus, and Lassa fever virus infections, its mechanism of action and therapeutic efficacy remains highly controversial. Recent reports show that the development of cell-based resistance after continuous RBV treatment via decreased RBV uptake can greatly limit its efficacy. Here, we examined whether certain cell types are naturally resistant to RBV even without prior drug exposure. Seven different cell lines from various host species were compared for RBV antiviral activity against two nonsegmented negative-strand RNA viruses, vesicular stomatitis virus (VSV, a rhabdovirus and Sendai virus (SeV, a paramyxovirus. Our results show striking differences between cell types in their response to RBV, ranging from virtually no antiviral effect to very effective inhibition of viral replication. Despite differences in viral replication kinetics for VSV and SeV in the seven cell lines, the observed pattern of RBV resistance was very similar for both viruses, suggesting that cellular rather than viral determinants play a major role in this resistance. While none of the tested cell lines was defective in RBV uptake, dramatic variations were observed in the long-term accumulation of RBV in different cell types, and it correlated with the antiviral efficacy of RBV. While addition of guanosine neutralized RBV only in cells already highly resistant to RBV, actinomycin D almost completely reversed the RBV effect (but not uptake in all cell lines. Together, our data suggest that RBV may inhibit the same virus via different mechanisms in different cell types depending on the intracellular RBV metabolism. Our results strongly point out the importance of using multiple cell lines of different origin when antiviral efficacy and potency are examined for new as well as established drugs in vitro.

  3. Insulitis and β-Cell Mass in the Natural History of Type 1 Diabetes. (United States)

    Campbell-Thompson, Martha; Fu, Ann; Kaddis, John S; Wasserfall, Clive; Schatz, Desmond A; Pugliese, Alberto; Atkinson, Mark A


    Descriptions of insulitis in human islets throughout the natural history of type 1 diabetes are limited. We determined insulitis frequency (the percent of islets displaying insulitis to total islets), infiltrating leukocyte subtypes, and β-cell and α-cell mass in pancreata recovered from organ donors with type 1 diabetes (n = 80), as well as from donors without diabetes, both with islet autoantibodies (AAb(+), n = 18) and without islet autoantibodies (AAb(-), n = 61). Insulitis was observed in four of four donors (100%) with type 1 diabetes duration of ≤1 year and two AAb(+) donors (2 of 18 donors, 11%). Insulitis frequency showed a significant but limited inverse correlation with diabetes duration (r = -0.58, P = 0.01) but not with age at disease onset. Residual β-cells were observed in all type 1 diabetes donors with insulitis, while β-cell area and mass were significantly higher in type 1 diabetes donors with insulitis compared with those without insulitis. Insulitis affected 33% of insulin(+) islets compared with 2% of insulin(-) islets in donors with type 1 diabetes. A significant correlation was observed between insulitis frequency and CD45(+), CD3(+), CD4(+), CD8(+), and CD20(+) cell numbers within the insulitis (r = 0.53-0.73, P = 0.004-0.04), but not CD68(+) or CD11c(+) cells. The presence of β-cells as well as insulitis several years after diagnosis in children and young adults suggests that the chronicity of islet autoimmunity extends well into the postdiagnosis period. This information should aid considerations of therapeutic strategies seeking type 1 diabetes prevention and reversal.

  4. Stem cell factor-mediated wild-type KIT receptor activation is critical for gastrointestinal stromal tumor cell growth

    Institute of Scientific and Technical Information of China (English)

    Chen-Guang Bai; Xiao-Wei Hou; Feng Wang; Cen Qiu; Yan Zhu; Ling Huang; Jing Zhao


    AIM:To clarify the biological role of stem cell factor (SCF)-mediated wild-type KIT receptor activation in gastrointestinal stromal tumor (GIST) growth.METHODS:The co-expression of wild-type KIT receptor and SCF was evaluated in 51 GIST samples using mutation analysis and immunohistochemistry,and the results were correlated with clinicopathological parameters,including the mitotic count,proliferative index (Ki-67 immunohistochemical staining),mitotic index (phospho-histone H3 immunohistochemical staining)and apoptotic index (terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling).Using primary cultured GIST cells,the effect of SCF-mediated wild-type KIT receptor activation was determined by western blotting,methyl thiazolyl tetrazolium (MTT),and apoptosis assays.RESULTS:We found that wild-type KIT receptor and SCF protein were expressed in 100% and 76.5% of the 51 GIST samples,respectively,and the co-expression of wild-type KIT receptor and SCF was associated with known indicators of poor prognosis,including larger tumor size (P =0.0118),higher mitotic count (P =0.0058),higher proliferative index (P =0.0012),higher mitotic index (P =0.0282),lower apoptosis index (P =0.0484),and increased National Institutes of Health risk level (P =0.0012).We also found that the introduction of exogenous SCF potently increased KIT kinase activity,stimulated cell proliferation (P < 0.01) and inhibited apoptosis (P < 0.01) induced by serum starvation,while a KIT immunoblocking antibody suppressed proliferation (P =0.01) and promoted apoptosis (P < 0.01)in cultured GIST cells.CONCLUSION:SCF-mediated wild-type KIT receptor activation plays an important role in GIST cell growth.The inhibition of SCF-mediated wild-type KIT receptor activation may prove to be particularly important for GIST therapy.

  5. Receptive Field Vectors of Genetically-Identified Retinal Ganglion Cells Reveal Cell-Type-Dependent Visual Functions.

    Directory of Open Access Journals (Sweden)

    Matthew L Katz

    Full Text Available Sensory stimuli are encoded by diverse kinds of neurons but the identities of the recorded neurons that are studied are often unknown. We explored in detail the firing patterns of eight previously defined genetically-identified retinal ganglion cell (RGC types from a single transgenic mouse line. We first introduce a new technique of deriving receptive field vectors (RFVs which utilises a modified form of mutual information ("Quadratic Mutual Information". We analysed the firing patterns of RGCs during presentation of short duration (~10 second complex visual scenes (natural movies. We probed the high dimensional space formed by the visual input for a much smaller dimensional subspace of RFVs that give the most information about the response of each cell. The new technique is very efficient and fast and the derivation of novel types of RFVs formed by the natural scene visual input was possible even with limited numbers of spikes per cell. This approach enabled us to estimate the 'visual memory' of each cell type and the corresponding receptive field area by calculating Mutual Information as a function of the number of frames and radius. Finally, we made predictions of biologically relevant functions based on the RFVs of each cell type. RGC class analysis was complemented with results for the cells' response to simple visual input in the form of black and white spot stimulation, and their classification on several key physiological metrics. Thus RFVs lead to predictions of biological roles based on limited data and facilitate analysis of sensory-evoked spiking data from defined cell types.

  6. Cardiorenal Syndrome Type 5 in Sepsis: Role of Endotoxin in Cell Death Pathways and Inflammation

    Directory of Open Access Journals (Sweden)

    Grazia Maria Virzì


    Full Text Available Background/Aims: Cardiorenal Syndrome Type 5 (CRS Type 5 is characterized by concomitant cardiac and renal dysfunction in the setting of different systemic disorders, such as sepsis. In this study, we investigated the possible relationship between endotoxin levels, renal cell death and inflammation in septic patients with CRS Type 5. Methods: We enrolled 11 patients with CRS Type 5. CRS Type 5 was defined according to the current classification system. AKI was defined by Acute Kidney Injury Network (AKIN criteria. Acute cardiac dysfunction was documented by echocardiography as acute left and/or right ventricular dysfunction leading to decreased ejection fraction. Endotoxin activity was measured by the Endotoxin Activity Assay (EAA. Plasma from CRS Type 5 patients was incubated with renal tubular cells (RTCs and cell death levels were evaluated. Plasma cytokines levels were measured as well. Results: Accordingly to EAA levels, patients were divided into two groups: 45.4% of patients had low endotoxin activity level (negative EAA, while 54.5% of patients showed high endotoxin activity (positive EAA. RTCs incubated with plasma from EAA positive patients showed significantly higher apoptosis levels and higher caspase-3 activation compared to cells incubated with plasma from EAA negative patients, and a significant positive correlation was observed between EAA levels and RTC apoptosis levels. Furthermore, IL-6 and IFN-γ levels were significantly higher in CRS Type 5 patients with positive EAA. Conclusion: Our data suggest a possible relationship between endotoxin levels and renal cell death in septic patients with CRS Type 5. Furthermore, this study highlights the presence of renal apoptosis, the immune deregulation and the strong inflammation in CRS Type 5 patients, especially in those with high endotoxin activity.

  7. Novel middle-type Kenyon cells in the honeybee brain revealed by area-preferential gene expression analysis. (United States)

    Kaneko, Kumi; Ikeda, Tsubomi; Nagai, Mirai; Hori, Sayaka; Umatani, Chie; Tadano, Hiroto; Ugajin, Atsushi; Nakaoka, Takayoshi; Paul, Rajib Kumar; Fujiyuki, Tomoko; Shirai, Kenichi; Kunieda, Takekazu; Takeuchi, Hideaki; Kubo, Takeo


    The mushroom bodies (a higher center) of the honeybee (Apis mellifera L) brain were considered to comprise three types of intrinsic neurons, including large- and small-type Kenyon cells that have distinct gene expression profiles. Although previous neural activity mapping using the immediate early gene kakusei suggested that small-type Kenyon cells are mainly active in forager brains, the precise Kenyon cell types that are active in the forager brain remain to be elucidated. We searched for novel gene(s) that are expressed in an area-preferential manner in the honeybee brain. By identifying and analyzing expression of a gene that we termed mKast (middle-type Kenyon cell-preferential arrestin-related protein), we discovered novel 'middle-type Kenyon cells' that are sandwiched between large- and small-type Kenyon cells and have a gene expression profile almost complementary to those of large- and small-type Kenyon cells. Expression analysis of kakusei revealed that both small-type Kenyon cells and some middle-type Kenyon cells are active in the forager brains, suggesting their possible involvement in information processing during the foraging flight. mKast expression began after the differentiation of small- and large-type Kenyon cells during metamorphosis, suggesting that middle-type Kenyon cells differentiate by modifying some characteristics of large- and/or small-type Kenyon cells. Interestingly, CaMKII and mKast, marker genes for large- and middle-type Kenyon cells, respectively, were preferentially expressed in a distinct set of optic lobe (a visual center) neurons. Our findings suggested that it is not simply the Kenyon cell-preferential gene expression profiles, rather, a 'clustering' of neurons with similar gene expression profiles as particular Kenyon cell types that characterize the honeybee mushroom body structure.

  8. Jamming dynamics of stretch-induced surfactant release by alveolar type II cells. (United States)

    Majumdar, Arnab; Arold, Stephen P; Bartolák-Suki, Erzsébet; Parameswaran, Harikrishnan; Suki, Béla


    Secretion of pulmonary surfactant by alveolar epithelial type II cells is vital for the reduction of interfacial surface tension, thus preventing lung collapse. To study secretion dynamics, rat alveolar epithelial type II cells were cultured on elastic membranes and cyclically stretched. The amounts of phosphatidylcholine, the primary lipid component of surfactant, inside and outside the cells, were measured using radiolabeled choline. During and immediately after stretch, cells secreted less surfactant than unstretched cells; however, stretched cells secreted significantly more surfactant than unstretched cells after an extended lag period. We developed a model based on the hypothesis that stretching leads to jamming of surfactant traffic escaping the cell, similar to vehicular traffic jams. In the model, stretch increases surfactant transport from the interior to the exterior of the cell. This transport is mediated by a surface layer with a finite capacity due to the limited number of fusion pores through which secretion occurs. When the amount of surfactant in the surface layer approaches this capacity, interference among lamellar bodies carrying surfactant reduces the rate of secretion, effectively creating a jam. When the stretch stops, the jam takes an extended time to clear, and subsequently the amount of secreted surfactant increases. We solved the model analytically and show that its dynamics are consistent with experimental observations, implying that surfactant secretion is a fundamentally nonlinear process with memory representing collective behavior at the level of single cells. Our results thus highlight the importance of a jamming dynamics in stretch-induced cellular secretory processes.

  9. Therapeutic potential of umbilical cord blood cells for type 1 diabetes mellitus. (United States)

    He, Binbin; Li, Xia; Yu, Haibo; Zhou, Zhiguang


    Type 1 diabetes mellitus (T1DM) is a chronic disorder that results from autoimmune-mediated destruction of pancreatic islet β-cells. However, to date, no conventional intervention has successfully treated the disease. The optimal therapeutic method for T1DM should effectively control the autoimmunity, restore immune homeostasis, preserve residual β-cells, reverse β-cell destruction, and protect the regenerated insulin-producing cells against re-attack. Umbilical cord blood is rich in regulatory T (T(reg)) cells and multiple types of stem cells that exhibit immunomodulating potential and hold promise in their ability to restore peripheral tolerance towards pancreatic islet β-cells through remodeling of immune responses and suppression of autoreactive T cells. Recently, reinfusion of autologous umbilical cord blood or immune cells from cord blood has been proposed as a novel therapy for T1DM, with the advantages of no risk to the donors, minimal ethical concerns, a low incidence of graft-versus-host disease and easy accessibility. In this review, we revisit the role of autologous umbilical cord blood or immune cells from cord blood-based applications for the treatment of T1DM.

  10. In vitro permissivity of bovine cells for wild-type and vaccinal myxoma virus strains. (United States)

    Pignolet, Béatrice; Duteyrat, Jean-Luc; Allemandou, Aude; Gelfi, Jacqueline; Foucras, Gilles; Bertagnoli, Stéphane


    Myxoma virus (MYXV), a leporide-specific poxvirus, represents an attractive candidate for the generation of safe, non-replicative vaccine vector for non-host species. However, there is very little information concerning infection of non-laboratory animals species cells with MYXV. In this study, we investigated interactions between bovine cells and respectively a wild type strain (T1) and a vaccinal strain (SG33) of MYXV. We showed that bovine KOP-R, BT and MDBK cell lines do not support MYXV production. Electron microscopy observations of BT-infected cells revealed the low efficiency of viral entry and the production of defective virions. In addition, infection of bovine peripheral blood mononuclear cells (PBMC) occurred at a very low level, even following non-specific activation, and was always abortive. We did not observe significant differences between the wild type strain and the vaccinal strain of MYXV, indicating that SG33 could be used for new bovine vaccination strategies.

  11. The importance of detailed epigenomic profiling of different cell types within organs. (United States)

    Stueve, Theresa Ryan; Marconett, Crystal N; Zhou, Beiyun; Borok, Zea; Laird-Offringa, Ite A


    The human body consists of hundreds of kinds of cells specified from a single genome overlaid with cell type-specific epigenetic information. Comprehensively profiling the body's distinct epigenetic landscapes will allow researchers to verify cell types used in regenerative medicine and to determine the epigenetic effects of disease, environmental exposures and genetic variation. Key marks/factors that should be investigated include regions of nucleosome-free DNA accessible to regulatory factors, histone marks defining active enhancers and promoters, DNA methylation levels, regulatory RNAs, and factors controlling the three-dimensional conformation of the genome. Here we use the lung to illustrate the importance of investigating an organ's purified cell epigenomes, and outline the challenges and promise of realizing a comprehensive catalog of primary cell epigenomes.

  12. Dependence of Early and Late Chromosomal Aberrations on Radiation Quality and Cell Types (United States)

    Lu, Tao; Zhang, Ye; Krieger, Stephanie; Yeshitla, Samrawit; Goss, Rosalin; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Rohde, Larry; Wu, Honglu


    Exposure to radiation induces different types of DNA damage, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo. The susceptibility of cells to radiation depends on genetic background and growth condition of cells, as well as types of radiation. Mammalian cells of different tissue types and with different genetic background are known to have different survival rate and different mutation rate after cytogenetic insults. Genomic instability, induced by various genetic, metabolic, and environmental factors including radiation, is the driving force of tumorigenesis. Accurate measurements of the relative biological effectiveness (RBE) is important for estimating radiation-related risks. To further understand genomic instability induced by charged particles and their RBE, we exposed human lymphocytes ex vivo, human fibroblast AG1522, human mammary epithelial cells (CH184B5F5/M10), and bone marrow cells isolated from CBA/CaH(CBA) and C57BL/6 (C57) mice to high energy protons and Fe ions. Normal human fibroblasts AG1522 have apparently normal DNA damage response and repair mechanisms, while mammary epithelial cells (M10) are deficient in the repair of DNA DSBs. Mouse strain CBA is radio-sensitive while C57 is radio-resistant. Metaphase chromosomes at different cell divisions after radiation exposure were collected and chromosome aberrations were analyzed as RBE for different cell lines exposed to different radiations at various time points up to one month post irradiation.

  13. The adaptor protein SAP regulates type II NKT-cell development, cytokine production, and cytotoxicity against lymphoma. (United States)

    Weng, Xiufang; Liao, Chia-Min; Bagchi, Sreya; Cardell, Susanna L; Stein, Paul L; Wang, Chyung-Ru


    CD1d-restricted NKT cells represent a unique lineage of immunoregulatory T cells that are divided into two groups, type I and type II, based on their TCR usage. Because there are no specific tools to identify type II NKT cells, little is known about their developmental requirements and functional regulation. In our previous study, we showed that signaling lymphocytic activation molecule associated protein (SAP) is essential for the development of type II NKT cells. Here, using a type II NKT-cell TCR transgenic mouse model, we demonstrated that CD1d-expressing hematopoietic cells, but not thymic epithelial cells, meditate efficient selection of type II NKT cells. Furthermore, we showed that SAP regulates type II NKT-cell development by controlling early growth response 2 protein and promyelocytic leukemia zinc finger expression. SAP-deficient 24αβ transgenic T cells (24αβ T cells) exhibited an immature phenotype with reduced Th2 cytokine-producing capacity and diminished cytotoxicity to CD1d-expressing lymphoma cells. The impaired IL-4 production by SAP-deficient 24αβ T cells was associated with reduced IFN regulatory factor 4 and GATA-3 induction following TCR stimulation. Collectively, these data suggest that SAP is critical for regulating type II NKT cell responses. Aberrant responses of these T cells may contribute to the immune dysregulation observed in X-linked lymphoproliferative disease caused by mutations in SAP.

  14. The Impact of Neural Stem Cell Biology on CNS Carcinogenesis and Tumor Types

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    K. M. Kurian


    Full Text Available The incidence of gliomas is on the increase, according to epidemiological data. This increase is a conundrum because the brain is in a privileged protected site behind the blood-brain barrier, and therefore partially buffered from environmental factors. In addition the brain also has a very low proliferative potential compared with other parts of the body. Recent advances in neural stem cell biology have impacted on our understanding of CNS carcinogenesis and tumor types. This article considers the cancer stem cell theory with regard to CNS cancers, whether CNS tumors arise from human neural stem cells and whether glioma stem cells can be reprogrammed.

  15. Immunotherapy against Metastatic Melanoma with Human iPS Cell-Derived Myeloid Cell Lines Producing Type I Interferons. (United States)

    Miyashita, Azusa; Fukushima, Satoshi; Nakahara, Satoshi; Kubo, Yosuke; Tokuzumi, Aki; Yamashita, Junji; Aoi, Jun; Haruta, Miwa; Senju, Satoru; Nishimura, Yasuharu; Jinnin, Masatoshi; Ihn, Hironobu


    In recent years, immunotherapy for advanced melanoma has been gaining increased attention. The efficacy of anti-cytotoxic T-lymphocyte antigen 4 antibodies, anti-programmed cell death 1 antibodies, and the BRAF(V600E) kinase inhibitor has been proven in metastatic melanoma. At the same time, adoptive cell transfer has significant effects against metastatic melanoma; however, it is difficult to apply on a broad scale because of the problems related to cell preparation. To overcome these problems, we developed immune cell therapy using induced pluripotent stem (iPS) cells. The benefit of our method is that a large number of cells can be readily obtained. We focused on macrophages for immune cell therapy because macrophage infiltration is frequently observed in solid cancers. In this study, the efficacy of human iPS cell-derived myeloid cell lines (iPS-ML) genetically modified to express type I IFNs against human melanoma cells was examined. The morphology, phagocytic ability, and surface markers of iPS-ML were similar to those of macrophages. The iPS-ML that express type I IFNs (iPS-ML-IFN) showed significant effects in inhibiting the growth of disseminated human melanoma cells in SCID mice. The infiltration of iPS-ML into the tumor nests was confirmed immunohistologically. The iPS-ML-IFNs increased the expression of CD169, a marker of M1 macrophages that can activate antitumor immunity. The iPS-ML-IFNs could infiltrate into tumor tissue and exert anticancer effects in the local tumor tissue. In conclusion, this method will provide a new therapeutic modality for metastatic melanoma.

  16. The role of mast cells and fibre type in ischaemia reperfusion injury of murine skeletal muscles

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    Bortolotto Susan K


    Full Text Available Abstract Background Ischaemia reperfusion (IR injury of skeletal muscle, is a significant cause of morbidity following trauma and surgical procedures, in which muscle fibre types exhibit different susceptibilities. The relative degree of mast cell mediated injury, within different muscle types, is not known. Methods In this study we compared susceptibility of the fast-twitch, extensor digitorum longus (EDL, mixed fast/slow-twitch gastrocnemius and the predominately slow-twitch soleus, muscles to ischemia reperfusion (IR injury in four groups of mice that harbour different mast cell densities; C57/DBA mast cell depleted (Wf/Wf, their heterozygous (Wf/+ and normal littermates (+/+ and control C57BL/6 mice. We determined whether susceptibility to IR injury is associated with mast cell content and/or fibre type and/or mouse strain. In experimental groups, the hind limbs of mice were subjected to 70 minutes warm tourniquet ischemia, followed by 24 h reperfusion, and the muscle viability was assessed on fresh whole-mount slices by the nitroblue tetrazolium (NBT histochemical assay. Results Viability was remarkably higher in the Wf/Wf strain irrespective of muscle type. With respect to muscle type, the predominately slow-twitch soleus muscle was significantly more resistant to IR injury than gastrocnemius and the EDL muscles in all groups. Mast cell density was inversely correlated to muscle viability in all types of muscle. Conclusion These results show that in skeletal muscle, IR injury is dependent upon both the presence of mast cells and on fibre type and suggest that a combination of preventative therapies may need to be implemented to optimally protect muscles from IR injury.

  17. Cell-type specific DNA methylation patterns define human breast cellular identity.

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    Petr Novak

    Full Text Available DNA methylation plays a role in a variety of biological processes including embryonic development, imprinting, X-chromosome inactivation, and stem cell differentiation. Tissue specific differential methylation has also been well characterized. We sought to extend these studies to create a map of differential DNA methylation between different cell types derived from a single tissue. Using three pairs of isogenic human mammary epithelial and fibroblast cells, promoter region DNA methylation was characterized using MeDIP coupled to microarray analysis. Comparison of DNA methylation between these cell types revealed nearly three thousand cell-type specific differentially methylated regions (ctDMRs. MassARRAY was performed upon 87 ctDMRs to confirm and quantify differential DNA methylation. Each of the examined regions exhibited statistically significant differences ranging from 10-70%. Gene ontology analysis revealed the overrepresentation of many transcription factors involved in developmental processes. Additionally, we have shown that ctDMRs are associated with histone related epigenetic marks and are often aberrantly methylated in breast cancer. Overall, our data suggest that there are thousands of ctDMRs which consistently exhibit differential DNA methylation and may underlie cell type specificity in human breast tissue. In addition, we describe the pathways affected by these differences and provide insight into the molecular mechanisms and physiological overlap between normal cellular differentiation and breast carcinogenesis.

  18. Arachidonate metabolism increases as rat alveolar type II cells differentiate in vitro

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    Lipchik, R.J.; Chauncey, J.B.; Paine, R.; Simon, R.H.; Peters-Golden, M. (Univ. of Michigan, Ann Arbor (USA))


    Rat type II alveolar epithelial cells are known to undergo morphological and functional changes when maintained in culture for several days. Having previously demonstrated that these cells can deacylate free arachidonic acid (AA) and metabolize it to products of the cyclooxygenase pathway, the present study was undertaken to determine whether in vitro differentiation was accompanied by alterations in the availability and metabolism of AA. We assessed the constitutive and ionophore A23187-induced deacylation and metabolism of endogenous AA, as well as the metabolism of exogenously supplied AA, in primary cultures of rat type II cells at days 2, 4, and 7 after isolation. Levels of free endogenous AA were increased at day 4, whereas eicosanoid synthesis, predominantly prostaglandin E2 and prostacyclin, increased markedly only at day 7. A similar time course of augmentation of prostanoid release was seen in response to exogenous AA. Type II cells cultured on fibronectin, intended to hasten cell flattening and spreading, demonstrated accelerated increases in available free AA in response to A23187; cells cultured on basement membrane derived from Engelbreth-Holm-Swarm mouse sarcoma, known to maintain the type II phenotype, exhibited diminished levels of available free AA. From these findings, we conclude that alterations in arachidonate metabolism are linked to alterations in cellular phenotype. The potentiation of eicosanoid synthesis accompanying in vitro differentiation suggests a possible role for the alveolar epithelium in the modulation of inflammation and fibrosis in the distal lung.

  19. Establishment and culture optimization of a new type of pituitary immortalized cell line

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    Kokubu, Yuko [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Asashima, Makoto [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Life Science Center of TARA, The University of Tsukuba, Ibaraki-ken 305-8577 (Japan); Kurisaki, Akira, E-mail: [Graduate School of Life and Environmental Sciences, The University of Tsukuba, Tsukuba, Ibaraki 305-8562 (Japan); Biotechnology Research Institute for Drug Discovery, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8562 (Japan)


    The pituitary gland is a center of the endocrine system that controls homeostasis in an organism by secreting various hormones. The glandular anterior pituitary consists of five different cell types, each expressing specific hormones. However, their regulation and the appropriate conditions for their in vitro culture are not well defined. Here, we report the immortalization of mouse pituitary cells by introducing TERT, E6, and E7 transgenes. The immortalized cell lines mainly expressed a thyrotroph-specific thyroid stimulating hormone beta (Tshb). After optimization of the culture conditions, these immortalized cells proliferated and maintained morphological characteristics similar to those of primary pituitary cells under sphere culture conditions in DMEM/F12 medium supplemented with N2, B27, basic FGF, and EGF. These cell lines responded to PKA or PKC pathway activators and induced the expression of Tshb mRNA. Moreover, transplantation of the immortalized cell line into subcutaneous regions and kidney capsules of mice further increased Tshb expression. These results suggest that immortalization of pituitary cells with TERT, E6, and E7 transgenes is a useful method for generating proliferating cells for the in vitro analysis of pituitary regulatory mechanisms. - Highlights: • Mouse pituitary cell lines were immortalized by introducing TERT, E6, and E7. • The immortalized cell lines mainly expressed thyroid stimulating hormone beta. • The cell lines responded to PKA or PKC pathway activators, and induced Tshb.

  20. The MicroRNA 29 Family Promotes Type II Cell Differentiation in Developing Lung. (United States)

    Guo, Wei; Benlhabib, Houda; Mendelson, Carole R


    Lung alveolar type II cells uniquely synthesize surfactant, a developmentally regulated lipoprotein that is essential for breathing. Expression of the gene (SFTPA) encoding the major surfactant protein, SP-A, in midgestation human fetal lung (HFL) is dramatically induced by cyclic AMP (cAMP). cAMP induction of SP-A expression is repressed by transforming growth factor β (TGF-β) and by hypoxia. In this study, we found that expression of the microRNA 29 (miR-29) family was significantly upregulated in epithelial cells isolated from mouse fetal lung during late gestation and in epithelial cells isolated from HFL explants during type II cell differentiation in culture. miR-29 expression in cultured HFL epithelial cells was increased by cAMP and inhibited by hypoxia, whereas the miR-29 target, TGF-β2, was coordinately decreased. Knockdown of the miR-29 family in cultured HFL type II cells blocked cAMP-induced SP-A expression and accumulation of surfactant-containing lamellar bodies, suggesting their physiological relevance. This occurred through derepression of TGF-β signaling. Notably, cAMP increased binding of endogenous thyroid transcription factor 1 (TTF-1/Nkx2.1) to the miR-29ab1 promoter in HFL type II cells, and TTF-1 increased miR-29ab1 promoter-driven luciferase activity in cotransfection assays. Together, these findings identify miR-29 family members as TTF-1-driven mediators of SP-A expression and type II cell differentiation through repression of TGF-β signaling.

  1. Can CD44 Be a Mediator of Cell Destruction? The Challenge of Type 1 Diabetes.

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    Nathalie Assayag-Asherie

    Full Text Available CD44 is a multi-functional receptor with multiple of isoforms engaged in modulation of cell trafficking and transmission of apoptotic signals. We have previously shown that injection of anti-CD44 antibody into NOD mice induced resistance to type 1 diabetes (T1D. In this communication we describe our efforts to understand the mechanism underlying this effect. We found that CD44-deficient NOD mice develop stronger resistance to T1D than wild-type littermates. This effect is not explained by the involvement of CD44 in cell migration, because CD44-deficient inflammatory cells surprisingly had greater invasive potential than the corresponding wild type cells, probably owing to molecular redundancy. We have previously reported and we show here again that CD44 expression and hyaluronic acid (HA, the principal ligand for CD44 accumulation are detected in pancreatic islets of diabetic NOD mice, but not of non-diabetic DBA/1 mice. Expression of CD44 on insulin-secreting β cells renders them susceptible to the autoimmune attack, and is associated with a diminution in β-cells function (e.g., less insulin production and/or insulin secretion and possibly also with an enhanced apoptosis rate. The diabetes-supportive effect of CD44 expression on β cells was assessed by the TUNEL assay and further strengthened by functional assays exhibiting increased nitric oxide release, reduced insulin secretion after glucose stimulation and decreased insulin content in β cells. All these parameters could not be detected in CD44-deficient islets. We further suggest that HA-binding to CD44-expressing β cells is implicated in β-cell demise. Altogether, these data agree with the concept that CD44 is a receptor capable of modulating cell fate. This finding is important for other pathologies (e.g., cancer, neurodegenerative diseases in which CD44 and HA appear to be implicated.

  2. Effect of epithelial cell type on in vitro invasion of non-typeable Haemophilus influenzae. (United States)

    Singh, Neeraj Kumar; Kunde, Dale A; Tristram, Stephen G


    Non-typeable Haemophilus influenzae (NTHi) have been shown to have variable ability for in vitro invasion with a range of epithelial cells, and increased invasion of BEAS-2B cells has been associated with altered penicillin binding protein3 (PBP3), which is concerning as these strains are increasing worldwide. The aim of the study was to investigate the effect of respiratory cell type and the presence of altered PBP3 on the in vitro invasion of NTHi. A collection of 16 clinical NTHi isolates was established, 7 had normal PBP3, and 9 had altered PBP3 as defined by an N526K substitution. The isolates were tested for invasion of BEAS-2B, NHBE, A549 and NCI-H292 respiratory epithelial cells in vitro using a gentamicin survival assay, with invasion measured as the percentage of intracellular organisms relative to the initial inoculum. The overall median invasion for the 16 NTHi isolates for cell types BEAS-2B, NHBE, A549 and NCI-H292 cells were 3.17, 2.31, 0.11 and 1.52 respectively. The differences were statistically significant for BEAS-2B compared to A549 (P=0.015) and A549 compared to NCI-H292 (P=0.015), and there were also very marked differences in invasion for some individual isolates depending on the cell type used. There was a consistent bias for invasion of isolates with normal versus abnormal PBP3: and this was statistically significant for BEAS-2B (0.07 to 9.90, P=0.031) and A549 cells (0.02 to 1.68, P=0.037). These results show that NTHi invasion of respiratory epithelial cells in vitro is both strain dependant and influenced significantly by the cell line used, and that the association between altered PBP3 and increased invasion is conserved across multiple cell lines.

  3. Role of Interleukin-33 in Innate-Type Immune Cells in Allergy

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    Susumu Nakae


    Full Text Available Interleukin-33 (IL-33, a member of the IL-1 cytokine family, is preferentially and constitutively expressed in epithelial cells, and it is especially localized in the cells' nucleus. The nuclear IL-33 is released by necrotic cells after tissue injury and/or trauma, and subsequently provokes local inflammation as an alarmin, like high-mobility group box protein-1 (HMGB-1 and IL-1α. IL-33 mainly activates Th2 cells and such innate-type immune cells as mast cells, basophils, eosinophils and natural helper cells that express IL-33R (a heterodimer of IL-1 receptor-like 1 [IL-1RL1; also called ST2, T1, Der4, fit-1] and IL-1 receptor accessory protein [IL-1RAcP]. That activation causes the cells to produce Th2 cytokines, which contribute to host defense against nematodes. On the other hand, excessive and/or inappropriate production of IL-33 is also considered to be involved in the development of such disorders as allergy. In this review, we summarize current knowledge regarding the pathogenic roles of IL-33 in the development of allergic inflammation by focusing on its effects on innate-type immune cells.


    Khilazheva, E D; Boytsova, E B; Pozhilenkova, E A; Solonchuk, Yu R; Salmina, A B


    There are many ways to model blood brain barrier and neurovascular unit in vitro. All existing models have their disadvantages, advantages and some peculiarities of preparation and usage. We obtained the three-cells neurovascular unit model in vitro using progenitor cells isolated from the rat embryos brain (Wistar, 14-16 d). After withdrawal of the progenitor cells the neurospheres were cultured with subsequent differentiation into astrocytes and neurons. Endothelial cells were isolated from embryonic brain too. During the differentiation of progenitor cells the astrocytes monolayer formation occurs after 7-9 d, neurons monolayer--after 10-14 d, endothelial cells monolayer--after 7 d. Our protocol for simultaneous isolation and cultivation of neurons, astrocytes and endothelial cells reduces the time needed to obtain neurovascular unit model in vitro, consisting of three cells types and reduce the number of animals used. It is also important to note the cerebral origin of all cell types, which is also an advantage of our model in vitro.

  5. 900 MHz radiation does not induce micronucleus formation in different cell types. (United States)

    Hintzsche, Henning; Jastrow, Christian; Kleine-Ostmann, Thomas; Schrader, Thorsten; Stopper, Helga


    The exposure of the population to non-ionising electromagnetic radiation is still increasing, mainly due to mobile communication. Whether low-intensity electromagnetic fields can cause other effects apart from heating has been a subject of debate. One of the effects, which were proposed to be caused by mobile phone radiation, is the occurrence of mitotic disturbances. The aim of this study was to investigate possible consequences of these mitotic disturbances as manifest genomic damage, i.e. micronucleus induction. Cells were irradiated at a frequency of 900 MHz, which is located in one of the main frequency bands applied for mobile communication. Two cell types were used, HaCaT cells as human cells and A(L) cells (human-hamster hybrid cells), in which mitotic disturbances had been reported to occur. After different post-exposure incubation periods, cells were fixed and micronucleus frequencies were evaluated. Both cell types did not show any genomic damage after exposure. To adapt the protocol for the micronucleus test into the direction of the protocol for mitotic disturbances, the post-exposure incubation period was reduced and exposure time was extended to one cell cycle length. This did not result in any increase of the genomic damage. In conclusion, micronucleus induction was not observed as a consequence of exposure to non-ionising radiation, even though this agent was reported to cause mitotic disturbances under similar experimental conditions.

  6. Interleukin-1 exerts distinct actions on different cell types of the brain in vitro

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    Ying An


    Full Text Available Ying An, Qun Chen, Ning QuanDepartment of Oral Biology, Ohio State University, Columbus, OH, USAAbstract: Interleukin-1 (IL-1 is a critical neuroinflammatory mediator in the central nervous system (CNS. In this study, we investigated the effect of IL-1 on inducing inflammation-related gene expression in three astrocyte, two microglial, and one brain endothelial cell line. Interleukin-1 beta (IL-1β is found to be produced by the two microglial cell lines constitutively, but these cells do not respond to IL-1β stimulation. The three astrocyte cell lines responded to IL-1ß stimulation by expressing MCP-1, CXCL-1, and VCAM-1, but different subtypes of astrocytes exhibited different expression profiles after IL-1β stimulation. The brain endothelial cells showed strongest response to IL-1β by producing MCP-1, CXCL-1, VCAM-1, ICAM-1, IL-6, and COX-2 mRNA. The induction of endothelial COX-2 mRNA is shown to be mediated by p38 MAPK pathway, whereas the induction of other genes is mediated by the NF-κB pathway. These results demonstrate that IL-1 exerts distinct cell type-specific action in CNS cells and suggest that IL-1-mediated neuroinflammation is the result of the summation of multiple responses from different cell types in the CNS to IL-1.Keywords: astrocyte, microglia, endothelial cells, signal transduction pathways, gene expression 

  7. Establishment and evaluation of a stable cattle type II alveolar epithelial cell line.

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    Feng Su

    Full Text Available Macrophages and dendritic cells are recognized as key players in the defense against mycobacterial infection. Recent research has confirmed that alveolar epithelial cells (AECs also play important roles against mycobacterium infections. Thus, establishing a stable cattle AEC line for future endogenous immune research on bacterial invasion is necessary. In the present study, we first purified and immortalized type II AECs (AEC II cells by transfecting them with a plasmid containing the human telomerase reverse trancriptase gene. We then tested whether or not the immortalized cells retained the basic physiological properties of primary AECs by reverse-transcription polymerase chain reaction and Western blot. Finally, we tested the secretion capacity of immortalized AEC II cells upon stimulation by bacterial invasion. The cattle type II alveolar epithelial cell line (HTERT-AEC II that we established retained lung epithelial cell characteristics: the cells were positive for surfactants A and B, and they secreted tumor necrosis factor-α and interleukin-6 in response to bacterial invasion. Thus, the cell line we established is a potential tool for research on the relationship between AECs and Mycobacterium tuberculosis.

  8. Comparing n- and p-type polycrystalline silicon absorbers in thin-film solar cells

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    Deckers, J. [imec, Kapeldreef 75, B-3001 Heverlee, Leuven (Belgium); ESAT, KU Leuven, Kardinaal Mercierlaan 94, B-3001 Heverlee, Leuven (Belgium); Bourgeois, E. [Institute for Materials Research (IMO), Hasselt University, Wetenschapspark 1, B-3590 Diepenbeek (Belgium); IMOMEC, IMEC vzw, Wetenschapspark 1, B-3590 Diepenbeek (Belgium); Jivanescu, M. [Department of Physics and Astronomy, University of Leuven, Celestijnenlaan 200D, B-3001 Heverlee, Leuven (Belgium); Abass, A. [Photonics Research Group (INTEC), Ghent University-imec, Sint-Pietersnieuwstraat 41, B-9000 Ghent (Belgium); Van Gestel, D.; Van Nieuwenhuysen, K.; Douhard, B. [imec, Kapeldreef 75, B-3001 Heverlee, Leuven (Belgium); D' Haen, J.; Nesladek, M.; Manca, J. [Institute for Materials Research (IMO), Hasselt University, Wetenschapspark 1, B-3590 Diepenbeek (Belgium); IMOMEC, IMEC vzw, Wetenschapspark 1, B-3590 Diepenbeek (Belgium); Gordon, I.; Bender, H. [imec, Kapeldreef 75, B-3001 Heverlee, Leuven (Belgium); Stesmans, A. [Department of Physics and Astronomy, University of Leuven, Celestijnenlaan 200D, B-3001 Heverlee, Leuven (Belgium); Mertens, R.; Poortmans, J. [imec, Kapeldreef 75, B-3001 Heverlee, Leuven (Belgium); ESAT, KU Leuven, Kardinaal Mercierlaan 94, B-3001 Heverlee, Leuven (Belgium)


    We have investigated fine grained polycrystalline silicon thin films grown by direct chemical vapor deposition on oxidized silicon substrates. More specifically, we analyze the influence of the doping type on the properties of this model polycrystalline silicon material. This includes an investigation of defect passivation and benchmarking of minority carrier properties. In our investigation, we use a variety of characterization techniques to probe the properties of the investigated polycrystalline silicon thin films, including Fourier Transform Photoelectron Spectroscopy, Electron Spin Resonance, Conductivity Activation, and Suns-Voc measurements. Amphoteric silicon dangling bond defects are identified as the most prominent defect type present in these layers. They are the primary recombination center in the relatively lowly doped polysilicon thin films at the heart of the current investigation. In contrast with the case of solar cells based on Czochralski silicon or multicrystalline silicon wafers, we conclude that no benefit is found to be associated with the use of n-type dopants over p-type dopants in the active absorber of the investigated polycrystalline silicon thin-film solar cells. - Highlights: • Comparison of n- and p-type absorbers for thin-film poly-Si solar cells • Extensive characterization of the investigated layers' characteristics • Literature review pertaining the use of n-type and p-type dopants in silicon.

  9. Cell type complexity in the basal metazoan Hydra is maintained by both stem cell based mechanisms and transdifferentiation. (United States)

    Siebert, Stefan; Anton-Erxleben, Friederike; Bosch, Thomas C G


    Understanding the mechanisms controlling the stability of the differentiated cell state is a fundamental problem in biology. To characterize the critical regulatory events that control stem cell behavior and cell plasticity in vivo in an organism at the base of animal evolution, we have generated transgenic Hydra lines [Wittlieb, J., Khalturin, K., Lohmann, J., Anton-Erxleben, F., Bosch, T.C.G., 2006. Transgenic Hydra allow in vivo tracking of individual stem cells during morphogenesis. Proc. Natl. Acad. Sci. U. S. A. 103, 6208-6211] which express eGFP in one of the differentiated cell types. Here we present a novel line which expresses eGFP specifically in zymogen gland cells. These cells are derivatives of the interstitial stem cell lineage and have previously been found to express two Dickkopf related genes [Augustin, R., Franke, A., Khalturin, K., Kiko, R., Siebert, S. Hemmrich, G., Bosch, T.C.G., 2006. Dickkopf related genes are components of the positional value gradient in Hydra. Dev. Biol. 296 (1), 62-70]. In the present study we have generated transgenic Hydra in which eGFP expression is under control of the promoter of one of them, HyDkk1/2/4 C. Transgenic Hydra recapitulate faithfully the previously described graded activation of HyDkk1/2/4 C expression along the body column, indicating that the promoter contains all elements essential for spatial and temporal control mechanisms. By in vivo monitoring of eGFP+ gland cells, we provide direct evidence for continuous transdifferentiation of zymogen cells into granular mucous cells in the head region. We also show that in this tissue a subpopulation of mucous gland cells directly derives from interstitial stem cells. These findings indicate that both stem cell-based mechanisms and transdifferentiation are involved in normal development and maintenance of cell type complexity in Hydra. The results demonstrate a remarkable plasticity in the differentiation capacity of cells in an organism which diverged before

  10. Regulatory Domain Selectivity in the Cell-Type Specific PKN-Dependence of Cell Migration


    Sylvie Lachmann; Amy Jevons; Manu De Rycker; Adele Casamassima; Simone Radtke; Alejandra Collazos; Peter J Parker


    The mammalian protein kinase N (PKN) family of Serine/Threonine kinases comprises three isoforms, which are targets for Rho family GTPases. Small GTPases are major regulators of the cellular cytoskeleton, generating interest in the role(s) of specific PKN isoforms in processes such as cell migration and invasion. It has been reported that PKN3 is required for prostate tumour cell invasion but not PKN1 or 2. Here we employ a cell model, the 5637 bladder tumour cell line where PKN2 is relativel...

  11. Global impact of Salmonella type III secretion effector SteA on host cells

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    Cardenal-Muñoz, Elena, E-mail:; Gutiérrez, Gabriel, E-mail:; Ramos-Morales, Francisco, E-mail:


    Highlights: • We analyzed HeLa cells transcriptome in response to Salmonella SteA. • Significant differential expression was detected for 58 human genes. • They are involved in ECM organization and regulation of some signaling pathways. • Cell death, cell adhesion and cell migration were decreased in SteA-expressing cells. • These results contribute to understand the role of SteA during infections. - Abstract: Salmonella enterica is a Gram-negative bacterium that causes gastroenteritis, bacteremia and typhoid fever in several animal species including humans. Its virulence is greatly dependent on two type III secretion systems, encoded in pathogenicity islands 1 and 2. These systems translocate proteins called effectors into eukaryotic host cell. Effectors interfere with host signal transduction pathways to allow the internalization of pathogens and their survival and proliferation inside vacuoles. SteA is one of the few Salmonella effectors that are substrates of both type III secretion systems. Here, we used gene arrays and bioinformatics analysis to study the genetic response of human epithelial cells to SteA. We found that constitutive synthesis of SteA in HeLa cells leads to induction of genes related to extracellular matrix organization and regulation of cell proliferation and serine/threonine kinase signaling pathways. SteA also causes repression of genes related to immune processes and regulation of purine nucleotide synthesis and pathway-restricted SMAD protein phosphorylation. In addition, a cell biology approach revealed that epithelial cells expressing steA show altered cell morphology, and decreased cytotoxicity, cell–cell adhesion and migration.

  12. Cell-type independent MYC target genes reveal a primordial signature involved in biomass accumulation.

    Directory of Open Access Journals (Sweden)

    Hongkai Ji

    Full Text Available The functions of key oncogenic transcription factors independent of context have not been fully delineated despite our richer understanding of the genetic alterations in human cancers. The MYC oncogene, which produces the Myc transcription factor, is frequently altered in human cancer and is a major regulatory hub for many cancers. In this regard, we sought to unravel the primordial signature of Myc function by using high-throughput genomic approaches to identify the cell-type independent core Myc target gene signature. Using a model of human B lymphoma cells bearing inducible MYC, we identified a stringent set of direct Myc target genes via chromatin immunoprecipitation (ChIP, global nuclear run-on assay, and changes in mRNA levels. We also identified direct Myc targets in human embryonic stem cells (ESCs. We further document that a Myc core signature (MCS set of target genes is shared in mouse and human ESCs as well as in four other human cancer cell types. Remarkably, the expression of the MCS correlates with MYC expression in a cell-type independent manner across 8,129 microarray samples, which include 312 cell and tissue types. Furthermore, the expression of the MCS is elevated in vivo in Eμ-Myc transgenic murine lymphoma cells as compared with premalignant or normal B lymphocytes. Expression of the MCS in human B cell lymphomas, acute leukemia, lung cancers or Ewing sarcomas has the highest correlation with MYC expression. Annotation of this gene signature reveals Myc's primordial function in RNA processing, ribosome biogenesis and biomass accumulation as its key roles in cancer and stem cells.

  13. Patterning of cell assemblies regulated by adhesion receptors of the cadherin superfamily. (United States)

    Takeichi, M; Nakagawa, S; Aono, S; Usui, T; Uemura, T


    During morphogenesis, cell-cell association patterns are dynamically altered. We are interested in how cell adhesion molecules can regulate the patterning of cellular assemblies. Cadherins, a group of cell-cell adhesion receptors, are crucial for the organized assembly of many cell types, but they also regulate dynamic aspects of cell association. For example, during neural crest emigration from the neural tube, the cadherin subtypes expressed by crest cells are switched from one subtype to another. Artificial perturbation of this switch results in blocking of their escape from the neural tube. Intracellular modulations of cadherin activity also seem to play a role in regulation of cell adhesion. We identified p120ctn as a regulator of cadherin function in carcinoma cells. With such regulators, cells may make a choice as to whether they should maintain stable cell contacts or disrupt their association. Finally, we found another type of cadherin-mediated cell patterning: Flamingo, a seven-pass transmembrane cadherin, regulates planar cell polarity in Drosophila imaginal discs. Thus, the cadherin superfamily receptors control the patterning of cell assemblies through a variety of mechanisms.

  14. 2,3-Dihydroxybenzoic acid attenuates kanamycin-induced volume reduction in mouse utricular type I hair cells

    DEFF Research Database (Denmark)

    Severinsen, Stig Åvall; Kirkegaard, Mette; Nyengaard, Jens Randel


    injection. Total volume of the utricle, as well as total number of hair and supporting cells, were estimated on light microscopic sections. Total volume and mean volume of hair cell types I and II and supporting cells were estimated on digital transmission electron micrographs. Total volume of the utricular...... macula, hair cell type I and supporting cells decreased significantly in animals injected with kanamycin but not in animals co-treated with DHB. Hair and supporting cell numbers remained unchanged in all three groups. In conclusion, the kanamycin-induced volume reduction of type I hair cells...

  15. Cell proliferation in human epiretinal membranes: characterization of cell types and correlation with disease condition and duration


    Lesnik Oberstein, S.Y.; Byun, J; Herrera, D; Chapin, E.A.; Fisher, S K; Lewis, G.P.


    Purpose To quantify the extent of cellular proliferation and immunohistochemically characterize the proliferating cell types in epiretinal membranes (ERMs) from four different conditions: proliferative vitreoretinopathy (PVR), proliferative diabetic retinopathy, post–retinal detachment, and idiopathic ERM. Methods Forty-six ERMs were removed from patients undergoing vitrectomy and immediately fixed in paraformaldehyde. The membranes were processed whole and immunolabeled with either anti-MIB-...

  16. Restricted TET2 Expression in Germinal Center Type B Cells Promotes Stringent Epstein-Barr Virus Latency. (United States)

    Wille, Coral K; Li, Yangguang; Rui, Lixin; Johannsen, Eric C; Kenney, Shannon C


    Epstein-Barr virus (EBV) latently infects normal B cells and contributes to the development of certain human lymphomas. Newly infected B cells support a highly transforming form (type III) of viral latency; however, long-term EBV infection in immunocompetent hosts is limited to B cells with a more restricted form of latency (type I) in which most viral gene expression is silenced by promoter DNA methylation. How EBV converts latency type is unclear, although it is known that type I latency is associated with a germinal center (GC) B cell phenotype, and type III latency with an activated B cell (ABC) phenotype. In this study, we have examined whether expression of TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates EBV latency type in B cells. We found that TET2 expression is inhibited in normal GC cells and GC type lymphomas. In contrast, TET2 is expressed in normal naive B cells and ABC type lymphomas. We also demonstrate that GC type cell lines have increased 5mC levels and reduced 5hmC levels in comparison to those of ABC type lines. Finally, we show that TET2 promotes the ability of the EBV transcription factor EBNA2 to convert EBV-infected cells from type I to type III latency. These findings demonstrate that TET2 expression is repressed in GC cells independent of EBV infection and suggest that TET2 promotes type III EBV latency in B cells with an ABC or naive phenotype by enhancing EBNA2 activation of methylated EBV promoters.IMPORTANCE EBV establishes several different types of viral latency in B cells. However, cellular factors that determine whether EBV enters the highly transforming type III latency, versus the more restricted type I latency, have not been well characterized. Here we show that TET2, a cellular enzyme that initiates DNA demethylation by converting 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC), regulates EBV latency type in B cells by

  17. A new type quasi-solid state electrolyte for dye-sensitized solar cells

    Institute of Scientific and Technical Information of China (English)

    WANG Miao; YANG Lei; ZHOU Xiaowen; LIN Yuan; LI Xueping; FENG Shujing; XIAO Xurui


    A new type quasi-solid state electrolyte was prepared by solidifying liquid electrolytes containing organic solvents (such as mixture of ethylene carbonate (EC) and propylene carbonate (PC), 3-methoxypropinitrile (NMP) and N-methyl-oxazolidinone (NMO)) with comb-like molten salt type polymer,and was for the first time employed in dyesensitized solar cells (DSSCs). The optimal electrolyte composition was obtained by regulating the polymer content in the electrolytes and optimizing performance data of the electrolytes and assembled cells, yielding a maximum conversion efficiency of 6.58% (AM 1.5,100 Furthermore, the existence of this new type polymer in the electrolyte suppresses the evaporation of organic solvent and improves the stability of the cells.

  18. Rules of tissue packing involving different cell types: human muscle organization. (United States)

    Sánchez-Gutiérrez, Daniel; Sáez, Aurora; Gómez-Gálvez, Pedro; Paradas, Carmen; Escudero, Luis M


    Natural packed tissues are assembled as tessellations of polygonal cells. These include skeletal muscles and epithelial sheets. Skeletal muscles appear as a mosaic composed of two different types of cells: the "slow" and "fast" fibres. Their relative distribution is important for the muscle function but little is known about how the fibre arrangement is established and maintained. In this work we capture the organizational pattern in two different healthy muscles: biceps brachii and quadriceps. Here we show that the biceps brachii muscle presents a particular arrangement, based on the different sizes of slow and fast fibres. By contrast, in the quadriceps muscle an unbiased distribution exists. Our results indicate that the relative size of each cellular type imposes an intrinsic organization into natural tessellations. These findings establish a new framework for the analysis of any packed tissue where two or more cell types exist.

  19. Chloroquine Inhibits Dengue Virus Type 2 Replication in Vero Cells but Not in C6/36 Cells

    Directory of Open Access Journals (Sweden)

    Kleber Juvenal Silva Farias


    Full Text Available Dengue viruses are the most important arthropod-borne viruses in terms of morbidity and mortality in the world. Since there is no dengue vaccine available for human use, we have set out to investigate the use of chloroquine as an antiviral drug against dengue. Chloroquine, an amine acidotropic drug known to affect intracellular exocytic pathways by increasing endosomal pH, was used in the in vitro treatment of Vero and C6/36 cells infected with dengue virus type 2 (DENV-2. Real-time RT-PCR and plaque assays were used to quantify the DENV-2 load in infected Vero and C6/36 cells after chloroquine treatment. Our results showed that a dose of 50 μg/ml of chloroquine was not toxic to the cells and induced a statistically significant inhibition of virus production in infected Vero cells when compared to untreated cells. In C6/36 cells, chloroquine does not induce a statistically significant difference in viral replication when compared to untreated cells, showing that this virus uses an unlikely pathway of penetration in these cells, and results were also confirmed by the plaque assay (PFU. These data suggest that the inhibition of virus infection induced by chloroquine is due to interference with acidic vesicles in mammalian cells.

  20. Comparative Study on Cancer Cell Apoptosis between Gastric and Intestinal-type Human Gastric Carcinoma

    Institute of Scientific and Technical Information of China (English)


    Apoptosis of cancer cells between the gastric and intestinal-type human gastric carcinoma were compared in terms of the expression of oncogene MDM2 and CD68, the histological types, the infiltration depth, and lymph node metastasis. Terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) assay was employed to stain apoptotic cells.Histochemical method(AB-PAS) was applied to stain mucus that is neutral or acidic in nature. Immunohistochemical method (SABC) was used to detect expression of MDM2 and CD6. The results showed that the mean apoptosis index (AI) of total 48 cases was 8.60±2.60. AI in the 30 intestinal type cases was significantly higher than that in the 18 gastric type cases (t=4.67, P<0.01). In the 30intestinal type cases, the spontaneous apoptosis index of MDM2 negative cases was significantly higher than that of the positive cases (t=7.16, P<0.01). And in the 18 gastric type cases, the same result was found. (t=11.39, P<0.01). The MDM2 positive ratio in gastric type cases was higher than that in intestinal type cases (x2=4.68, P<0.05). There is no significant difference in AI between cases of lymph node metastasis and non-metastasis cases in intestinal type cases (t=0.26, P>0.05). But in the gastric type cases, a significant difference existed (t=5.87, P<0.01). A significant difference in lymph node metastasis ratio was found between the two gastric carcinoma types (x2=4.48, P<0.05).The CD68 expression ratio in the 30 intestinal type cases was much lower than that in the 18 gastric type cases (t=4.29, P<0.01). AI of 25 MDM2-positive cases was much lower than that of the 23MDM2-negative cases (t=7.80, P<0.01). CD68 positive ratio in the 25 MDM2-negative cases was much lower than that in the 23 negative cases. The difference was statistically significant (t=10.90,P<0.01). Except for few cells scattering within the cancer nest, most CD68 positive cells infiltrated in the interstitium around the cancer

  1. The regulated secretory pathway in CD4(+ T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse.

    Directory of Open Access Journals (Sweden)

    Clare Jolly


    Full Text Available Direct cell-cell spread of Human Immunodeficiency Virus type-1 (HIV-1 at the virological synapse (VS is an efficient mode of dissemination between CD4(+ T cells but the mechanisms by which HIV-1 proteins are directed towards intercellular contacts is unclear. We have used confocal microscopy and electron tomography coupled with functional virology and cell biology of primary CD4(+ T cells from normal individuals and patients with Chediak-Higashi Syndrome and report that the HIV-1 VS displays a regulated secretion phenotype that shares features with polarized secretion at the T cell immunological synapse (IS. Cell-cell contact at the VS re-orientates the microtubule organizing center (MTOC and organelles within the HIV-1-infected T cell towards the engaged target T cell, concomitant with polarization of viral proteins. Directed secretion of proteins at the T cell IS requires specialized organelles termed secretory lysosomes (SL and we show that the HIV-1 envelope glycoprotein (Env localizes with CTLA-4 and FasL in SL-related compartments and at the VS. Finally, CD4(+ T cells that are disabled for regulated secretion are less able to support productive cell-to-cell HIV-1 spread. We propose that HIV-1 hijacks the regulated secretory pathway of CD4(+ T cells to enhance its dissemination.

  2. Epithelial cells derived from human embryonic stem cells display p16INK4A senescence, hypermotility, and differentiation properties shared by many P63+ somatic cell types

    DEFF Research Database (Denmark)

    Dabelsteen, Sally; Hercule, Paula; Barron, Patricia


    Human embryonic stem (hES) cells can generate cells expressing p63, K14, and involucrin, which have been proposed to be keratinocytes. Although these hES-derived, keratinocyte-like (hESderK) cells form epithelioid colonies when cultured in a fibroblast feeder system optimal for normal tissue......(+)/K14(+) urothelial and tracheobronchial epithelial cells. Primary and immortalized lines of these cell types had growth requirements and hypermotility responses similar to keratinocytes and bmi1 expression facilitated their immortalization by engineering to express the catalytic subunit of telomerase...

  3. Detection of cell type and marker specificity of nuclear binding sites for anionic carbohydrate ligands. (United States)

    Chovanec, M; Smetana, K; Purkrábková, T; Holíková, Z; Dvoránková, B; André, S; Pytlík, R; Hozák, P; Plzák, J; Sedo, A; Vacík, J; Gabius, H


    The emerging functionality of glycosaminoglycan chains engenders interest in localizing specific binding sites using cytochemical tools. We investigated nuclear binding of labeled heparin, heparan sulfate, a sulfated fucan, chondroitin sulfate, and hyaluronic acid in epidermal keratinocytes, bone marrow stromal cells, 3T3 fibroblasts and glioma cells using chemically prepared biotinylated probes. Binding of the markers was cell-type specific and influenced by extraction of histones, but was not markedly affected by degree of proliferation, differentiation or malignancy. Cell uptake of labeled heparin and other selected probes and their transport into the nucleus also was monitored. Differences between keratinocytes and bone marrow stromal cells were found. Preincubation of permeabilized bone marrow stromal cells with label-free heparin reduced the binding of carrier-immobilized hydrocortisone to its nuclear receptors. Thus, these tools enabled binding sites for glycosaminoglycans to be monitored in routine assays.

  4. Single-cell forensic short tandem repeat typing within microfluidic droplets. (United States)

    Geng, Tao; Novak, Richard; Mathies, Richard A


    A short tandem repeat (STR) typing method is developed for forensic identification of individual cells. In our strategy, monodisperse 1.5 nL agarose-in-oil droplets are produced with a high frequency using a microfluidic droplet generator. Statistically dilute single cells, along with primer-functionalized microbeads, are randomly compartmentalized in the droplets. Massively parallel single-cell droplet polymerase chain reaction (PCR) is performed to transfer replicas of desired STR targets from the single-cell genomic DNA onto the coencapsulated microbeads. These DNA-conjugated beads are subsequently harvested and reamplified under statistically dilute conditions for conventional capillary electrophoresis (CE) STR fragment size analysis. The 9-plex STR profiles of single cells from both pure and mixed populations of GM09947 and GM09948 human lymphoid cells show that all alleles are correctly called and allelic drop-in/drop-out is not observed. The cell mixture study exhibits a good linear relationship between the observed and input cell ratios in the range of 1:1 to 10:1. Additionally, the STR profile of GM09947 cells could be deduced even in the presence of a high concentration of cell-free contaminating 9948 genomic DNA. Our method will be valuable for the STR analysis of samples containing mixtures of cells/DNA from multiple contributors and for low-concentration samples.

  5. Type 1 Innate Lymphoid Cell Biology: Lessons Learnt from Natural Killer Cells. (United States)

    Jiao, Yuhao; Huntington, Nicholas D; Belz, Gabrielle T; Seillet, Cyril


    Group 1 innate lymphoid cells (ILCs) comprise the natural killer (NK) cells and ILC1s that reside within peripheral tissues. Several different ILC1 subsets have recently been characterized; however, no unique markers have been identified that uniquely define these subsets. Whether ILC1s and NK cells are in fact distinct lineages, or alternately exhibit transitional molecular programs that allow them to adapt to different tissue niches remains an open question. NK cells are the prototypic member of the Group 1 ILCs and have been historically assigned the functions of what now appears to be a multi-subset family that are distributed throughout the body. This raises the question of whether each of these populations mediate distinct functions during infection and tumor immunosurveillance. Here, we review the diversity of the Group 1 ILC subsets in their transcriptional regulation, localization, mobility, and receptor expression, and highlight the challenges in unraveling the individual functions of these different populations of cells.

  6. Construction of cell type-specific logic models of signaling networks using CellNOpt. (United States)

    Morris, Melody K; Melas, Ioannis; Saez-Rodriguez, Julio


    Mathematical models are useful tools for understanding protein signaling networks because they provide an integrated view of pharmacological and toxicological processes at the molecular level. Here we describe an approach previously introduced based on logic modeling to generate cell-specific, mechanistic and predictive models of signal transduction. Models are derived from a network encoding prior knowledge that is trained to signaling data, and can be either binary (based on Boolean logic) or quantitative (using a recently developed formalism, constrained fuzzy logic). The approach is implemented in the freely available tool CellNetOptimizer (CellNOpt). We explain the process CellNOpt uses to train a prior knowledge network to data and illustrate its application with a toy example as well as a realistic case describing signaling networks in the HepG2 liver cancer cell line.

  7. Renal type a intercalated cells contain albumin in organelles with aldosterone-regulated abundance.

    Directory of Open Access Journals (Sweden)

    Thomas Buus Jensen

    Full Text Available Albumin has been identified in preparations of renal distal tubules and collecting ducts by mass spectrometry. This study aimed to establish whether albumin was a contaminant in those studies or actually present in the tubular cells, and if so, identify the albumin containing cells and commence exploration of the origin of the intracellular albumin. In addition to the expected proximal tubular albumin immunoreactivity, albumin was localized to mouse renal type-A intercalated cells and cells in the interstitium by three anti-albumin antibodies. Albumin did not colocalize with markers for early endosomes (EEA1, late endosomes/lysosomes (cathepsin D or recycling endosomes (Rab11. Immuno-gold electron microscopy confirmed the presence of albumin-containing large spherical membrane associated bodies in the basal parts of intercalated cells. Message for albumin was detected in mouse renal cortex as well as in a wide variety of other tissues by RT-PCR, but was absent from isolated connecting tubules and cortical collecting ducts. Wild type I MDCK cells showed robust uptake of fluorescein-albumin from the basolateral side but not from the apical side when grown on permeable support. Only a subset of cells with low peanut agglutinin binding took up albumin. Albumin-aldosterone conjugates were also internalized from the basolateral side by MDCK cells. Aldosterone administration for 24 and 48 hours decreased albumin abundance in connecting tubules and cortical collecting ducts from mouse kidneys. We suggest that albumin is produced within the renal interstitium and taken up from the basolateral side by type-A intercalated cells by clathrin and dynamin independent pathways and speculate that the protein might act as a carrier of less water-soluble substances across the renal interstitium from the capillaries to the tubular cells.

  8. Mouse B-Type Lamins Are Required for Proper Organogenesis But Not by Embryonic Stem Cells (United States)

    Kim, Youngjo; Sharov, Alexei A.; McDole, Katie; Cheng, Melody; Hao, Haiping; Fan, Chen-Ming; Gaiano, Nicholas; Ko, Minoru S. H.; Zheng, Yixian


    B-type lamins, the major components of the nuclear lamina, are believed to be essential for cell proliferation and survival. We found that mouse embryonic stem cells (ESCs) do not need any lamins for self-renewal and pluripotency. Although genome-wide lamin-B binding profiles correlate with reduced gene expression, such binding is not directly required for gene silencing in ESCs or trophectoderm cells. However, B-type lamins are required for proper organogenesis. Defects in spindle orientation in neural progenitor cells and migration of neurons probably cause brain disorganizations found in lamin-B null mice. Thus, our studies not only disprove several prevailing views of lamin-Bs but also establish a foundation for redefining the function of the nuclear lamina in the context of tissue building and homeostasis. PMID:22116031

  9. Proton and Fe Ion-Induced Early and Late Chromosome Aberrations in Different Cell Types (United States)

    Lu, Tao; Zhang, Ye; Yeshitla, Samrawit; Bowler, Deborah; Kadhim, Munira; Wilson, Bobby; Wu, Honglu


    Genomic instability, induced by various metabolic, genetic, and environmental factors, is the driving force of tumorigenesis. Radiation exposure from different types of radiation sources induces different types of DNA damages, increases mutation and chromosome aberration rates, and increases cellular transformation in vitro and in vivo experiments. The cell survival rates and frequency of chromosome aberrations depend on the genetic background and radiation sources. To further understand genomic instability induced by charged particles, we exposed human lymphocytes ex vivo, human fibroblast cells, human mammary epithelial cells, and bone marrow cells isolated from CBA/CaH and C57BL/6 mice to high energy protons and Fe ions, and collected chromosomes at different generations after exposure. Chromosome aberrations were analyzed with fluorescent in situ hybridization with whole chromosome specific probes.

  10. Chemotransduction in the Carotid Body: K+ Current Modulated by Po2 in Type I Chemoreceptor Cells (United States)

    Lopez-Barneo, Jose; Lopez-Lopez, Jose R.; Urena, Juan; Gonzalez, Constancio


    The ionic currents of carotid body type I cells and their possible involvement in the detection of oxygen tension (Po2) in arterial blood are unknown. The electrical properties of these cells were studied with the whole-cell patch clamp technique, and the hypothesis that ionic conductances can be altered by changes in Po2 was tested. The results show that type I cells have voltage-dependent sodium, calcium, and potassium channels. Sodium and calcium currents were unaffected by a decrease in Po2 from 150 to 10 millimeters of mercury, whereas, with the same experimental protocol, potassium currents were reversibly reduced by 25 to 50 percent. The effect of hypoxia was independent of internal adenosine triphosphate and calcium. Thus, ionic conductances, and particularly the O2-sensitive potassium current, play a key role in the transduction mechanism of arterial chemoreceptors.

  11. Cancer-associated fibroblasts as another polarized cell type of the tumor microenvironment

    Directory of Open Access Journals (Sweden)

    Martin eAugsten


    Full Text Available Tumor- or cancer-associated fibroblasts (CAFs are one of the most abundant stromal cell types in different carcinomas and comprise a heterogeneous cell population. Classically, CAFs are assigned with pro-tumorigenic effects stimulating tumor growth and progression. More recent studies demonstrated also tumor-inhibitory effects of CAFs suggesting that tumor-residing fibroblasts exhibit a similar degree of plasticity as other stromal cell types. Reciprocal interactions with the tumor milieu and different sources of origin are emerging as two important factors underlying CAF heterogeneity. This review highlights recent advances in our understanding of CAF biology and proposes to expand the term of cellular ´polarization´, previously introduced to describe different activation states of various immune cells, onto CAFs to reflect their phenotypic diversity.

  12. Endoplasmic Reticulum Stress in the β-Cell Pathogenesis of Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Sung Hoon Back


    Full Text Available Type 2 diabetes is a complex metabolic disorder characterized by high blood glucose in the context of insulin resistance and relative insulin deficiency by β-cell failure. Even if the mechanisms underlying the pathogenesis of β-cell failure are still under investigation, recent increasing genetic, experimental, and clinical evidence indicate that hyperactivation of the unfolded protein response (UPR to counteract metabolic stresses is closely related to β-cell dysfunction and apoptosis. Signaling pathways of the UPR are “a double-edged sword” that can promote adaptation or apoptosis depending on the nature of the ER stress condition. In this paper, we summarized our current understanding of the mechanisms and components related to ER stress in the β-cell pathogenesis of type 2 diabetes.

  13. Activation of Sonic Hedgehog Signaling Pathway in S-type Neuroblastoma Cell Lines

    Institute of Scientific and Technical Information of China (English)

    周昱男; 戴若连; 毛玲; 夏远鹏; 姚玉芳; 杨雪; 胡波


    The effects of Sonic hedgehog(Shh) signaling pathway activation on S-type neuroblastoma(NB) cell lines and its role in NB tumorigenesis were investigated.Immunohistochemistry was used to detect the expression of Shh pathway components- Patched1(PTCH1) and Gli1 in 40 human primary NB samples.Western blotting and RT-PCR were used to examine the protein expression and mRNA levels of PTCH1 and Gli1 in three kinds of S-type NB cell lines(SK-N-AS,SK-N-SH and SHEP1),respectively.Exogenous Shh was administrated to ...

  14. Transition to chaos in random networks with cell-type-specific connectivity (United States)

    Aljadeff, Johnatan; Stern, Merav; Sharpee, Tatyana


    In neural circuits, statistical connectivity rules strongly depend on cell-type identity. We study dynamics of neural networks with cell-type specific connectivity by extending the dynamic mean field method, and find that these networks exhibit a phase transition between silent and chaotic activity. By analyzing the locus of this transition, we derive a new result in random matrix theory: the spectral radius of a random connectivity matrix with block-structured variances. We apply our results to show how a small group of hyper-excitable neurons within the network can significantly increase the network’s computational capacity by bringing it into the chaotic regime. PMID:25768781

  15. Angiogenesis and collagen type IV expression in different endothelial cell culture systems. (United States)

    Bahramsoltani, M; Slosarek, I; De Spiegelaere, W; Plendl, J


    In vitro angiogenesis assays constitute an important tool for studying the mechanisms of angiogenesis and for identification of pro- and anti-angiogenic substances. Therefore, endothelial cell and media systems used for in vitro angiogenesis assays are required to mimic the angiogenic process in vivo including endothelial capability to express collagen type IV as a component of the basement membrane. In this study, the expression of collagen type IV and its α chains (α1-6) was investigated in different endothelial cell culture systems in vitro qualitatively and quantitatively. These systems included four different batches of microvascular endothelial cells derived from the human skin, heart and lung, from which only two batches were found to be angiogenic and two batches were classified as non-angiogenic. Distribution of the transcripts of the α chains of collagen type IV was similar in all cell and media systems investigated. However, secretion and deposition of a stable extracellular network of collagen type IV could only be observed in the angiogenic cultures. In conclusion, the consecutive steps of the angiogenic cascade in vivo as well as in vitro depend on an increasing secretion and subsequent extracellular deposition of collagen type IV.

  16. Type I Interferons as Regulators of Human Antigen Presenting Cell Functions

    Directory of Open Access Journals (Sweden)

    Sandra Gessani


    Full Text Available Type I interferons (IFNs are pleiotropic cytokines, initially described for their antiviral activity. These cytokines exhibit a long record of clinical use in patients with some types of cancer, viral infections and chronic inflammatory diseases. It is now well established that IFN action mostly relies on their ability to modulate host innate and adaptive immune responses. Work in recent years has begun to elucidate the mechanisms by which type I IFNs modify the immune response, and this is now recognized to be due to effects on multiple cell types, including monocytes, dendritic cells (DCs, NK cells, T and B lymphocytes. An ensemble of results from both animal models and in vitro studies emphasized the key role of type I IFNs in the development and function of DCs, suggesting the existence of a natural alliance between these cytokines and DCs in linking innate to adaptive immunity. The identification of IFN signatures in DCs and their dysregulation under pathological conditions will therefore be pivotal to decipher the complexity of this DC-IFN interaction and to better exploit the therapeutic potential of these cells.

  17. Chitin recognition via chitotriosidase promotes pathologic type-2 helper T cell responses to cryptococcal infection.

    Directory of Open Access Journals (Sweden)

    Darin L Wiesner


    Full Text Available Pulmonary mycoses are often associated with type-2 helper T (Th2 cell responses. However, mechanisms of Th2 cell accumulation are multifactorial and incompletely known. To investigate Th2 cell responses to pulmonary fungal infection, we developed a peptide-MHCII tetramer to track antigen-specific CD4+ T cells produced in response to infection with the fungal pathogen Cryptococcus neoformans. We noted massive accruement of pathologic cryptococcal antigen-specific Th2 cells in the lungs following infection that was coordinated by lung-resident CD11b+ IRF4-dependent conventional dendritic cells. Other researchers have demonstrated that this dendritic cell subset is also capable of priming protective Th17 cell responses to another pulmonary fungal infection, Aspergillus fumigatus. Thus, higher order detection of specific features of fungal infection by these dendritic cells must direct Th2 cell lineage commitment. Since chitin-containing parasites commonly elicit Th2 responses, we hypothesized that recognition of fungal chitin is an important determinant of Th2 cell-mediated mycosis. Using C. neoformans mutants or purified chitin, we found that chitin abundance impacted Th2 cell accumulation and disease. Importantly, we determined Th2 cell induction depended on cleavage of chitin via the mammalian chitinase, chitotriosidase, an enzyme that was also prevalent in humans experiencing overt cryptococcosis. The data presented herein offers a new perspective on fungal disease susceptibility, whereby chitin recognition via chitotriosidase leads to the initiation of harmful Th2 cell differentiation by CD11b+ conventional dendritic cells in response to pulmonary fungal infection.

  18. Cellular behavior in micropatterned hydrogels by bioprinting system depended on the cell types and cellular interaction. (United States)

    Hong, Soyoung; Song, Seung-Joon; Lee, Jae Yeon; Jang, Hwanseok; Choi, Jaesoon; Sun, Kyung; Park, Yongdoo


    The fabrication of patterned microstructures within three-dimensional (3D) matrices is a challenging subject in tissue engineering and regenerative medicine. A 3D, free-moving bioprinting system was developed and hydrogels were patterned by varying the process parameters of z-axis moving velocity and ejection velocity. The patterning of hydrogel based microfibers in a 3D matrigel was achieved with dimensions of 4.5 mm length and widths from 79 to 200 μm. Hyaluronan-based hydrogels mixed with fibroblasts (L929), mouse endothelial cells (MS1), or human mesenchymal stem cells (hMSCs) were patterned using a 3D moving axis bioprinter and cell behavior was monitored in culture for up to 16 days. L929 and MS1 cells and hMSCs in patterned hydrogel revealed cell-cell interactions and a morphological dependency on cell types. HMSCs formed spheres through cell aggregation, while L929 cells increased in cellular mass without cell aggregation and MS1 dispersed into the matrix instead of aggregating. The aggregation of hMSCs was attenuated by treatment with Rho kinase (ROCK) inhibitor and cadherin antibody. This reflected the close relationship between cell aggregation and migration with RhoA and cell-cell adhesion molecules. Angiogenic-specific gene expression profiles showed that expression of CD105 decreased to 22% in the ROCK inhibitor group compared to control group. These results showed that cell-based patterns in a 3D matrix are highly dependent on both cell aggregation and migration over time.

  19. Protein conservation and variation suggest mechanisms of cell type-specific modulation of signaling pathways.

    Directory of Open Access Journals (Sweden)

    Martin H Schaefer


    Full Text Available Many proteins and signaling pathways are present in most cell types and tissues and yet perform specialized functions. To elucidate mechanisms by which these ubiquitous pathways are modulated, we overlaid information about cross-cell line protein abundance and variability, and evolutionary conservation onto functional pathway components and topological layers in the pathway hierarchy. We found that the input (receptors and the output (transcription factors layers evolve more rapidly than proteins in the intermediary transmission layer. In contrast, protein expression variability decreases from the input to the output layer. We observed that the differences in protein variability between the input and transmission layer can be attributed to both the network position and the tendency of variable proteins to physically interact with constitutively expressed proteins. Differences in protein expression variability and conservation are also accompanied by the tendency of conserved and constitutively expressed proteins to acquire somatic mutations, while germline mutations tend to occur in cell type-specific proteins. Thus, conserved core proteins in the transmission layer could perform a fundamental role in most cell types and are therefore less tolerant to germline mutations. In summary, we propose that the core signal transmission machinery is largely modulated by a variable input layer through physical protein interactions. We hypothesize that the bow-tie organization of cellular signaling on the level of protein abundance variability contributes to the specificity of the signal response in different cell types.

  20. An atlas of active enhancers across human cell types and tissues (United States)

    Andersson, Robin; Gebhard, Claudia; Miguel-Escalada, Irene; Hoof, Ilka; Bornholdt, Jette; Boyd, Mette; Chen, Yun; Zhao, Xiaobei; Schmidl, Christian; Suzuki, Takahiro; Ntini, Evgenia; Arner, Erik; Valen, Eivind; Li, Kang; Schwarzfischer, Lucia; Glatz, Dagmar; Raithel, Johanna; Lilje, Berit; Rapin, Nicolas; Bagger, Frederik Otzen; Jørgensen, Mette; Andersen, Peter Refsing; Bertin, Nicolas; Rackham, Owen; Burroughs, A. Maxwell; Baillie, J. Kenneth; Ishizu, Yuri; Shimizu, Yuri; Furuhata, Erina; Maeda, Shiori; Negishi, Yutaka; Mungall, Christopher J.; Meehan, Terrence F.; Lassmann, Timo; Itoh, Masayoshi; Kawaji, Hideya; Kondo, Naoto; Kawai, Jun; Lennartsson, Andreas; Daub, Carsten O.; Heutink, Peter; Hume, David A.; Jensen, Torben Heick; Suzuki, Harukazu; Hayashizaki, Yoshihide; Müller, Ferenc; Consortium, The Fantom; Forrest, Alistair R. R.; Carninci, Piero; Rehli, Michael; Sandelin, Albin


    Enhancers control the correct temporal and cell-type-specific activation of gene expression in multicellular eukaryotes. Knowing their properties, regulatory activity and targets is crucial to understand the regulation of differentiation and homeostasis. Here we use the FANTOM5 panel of samples, covering the majority of human tissues and cell types, to produce an atlas of active, in vivo-transcribed enhancers. We show that enhancers share properties with CpG-poor messenger RNA promoters but produce bidirectional, exosome-sensitive, relatively short unspliced RNAs, the generation of which is strongly related to enhancer activity. The atlas is used to compare regulatory programs between different cells at unprecedented depth, to identify disease-associated regulatory single nucleotide polymorphisms, and to classify cell-type-specific and ubiquitous enhancers. We further explore the utility of enhancer redundancy, which explains gene expression strength rather than expression patterns. The online FANTOM5 enhancer atlas represents a unique resource for studies on cell-type-specific enhancers and gene regulation.

  1. Myositis in Griscelli syndrome type 2 treated with hematopoietic cell transplantation

    DEFF Research Database (Denmark)

    Born, Alfred Peter; Müller, Klaus; Marquart, Hanne Vibeke;


    Griscelli syndrome is an autosomal recessive disorder characterized by pigmentary dilution and is occasionally associated with a hemophagocytic syndrome (type 2). We present a 13-year-old girl with Griscelli syndrome type 2, who developed a hemophagocytic syndrome along with marked muscle weakness...... and elevated plasma creatine kinase. Muscle biopsy showed massive inflammatory changes in some fascicles, while other fascicles were relatively spared. Clinical symptoms and biopsy changes resolved after immunosuppression and allogeneic hematopoietic cell transplantation. Our results suggest that muscle...

  2. Suggestions for Ecological Environment Improvement of Emigration Vil ages--with Ecological Emigration Vil ages of Xiji County in Ningxia as Examples%对移民搬迁出村庄生态环境治理的意见和建议--以宁夏西吉县生态移民迁出村为例

    Institute of Scientific and Technical Information of China (English)



    With the ecological emigration villages of Xiji County in Ningxia as the examples, the existing problems in the e-cological environment improvement of the emigration villages are analyzed and some suggestions for the ecological environ-ment improvement are put forward aiming at the problems.%以宁夏西吉县生态移民迁出村为例,分析了移民搬迁出村庄生态环境治理上存在的问题,并针对问题提出了生态环境治理建议。

  3. Cell type-specific translational repression of Cyclin B during meiosis in males. (United States)

    Baker, Catherine Craig; Gim, Byung Soo; Fuller, Margaret T


    The unique cell cycle dynamics of meiosis are controlled by layers of regulation imposed on core mitotic cell cycle machinery components by the program of germ cell development. Although the mechanisms that regulate Cdk1/Cyclin B activity in meiosis in oocytes have been well studied, little is known about the trans-acting factors responsible for developmental control of these factors in male gametogenesis. During meiotic prophase in Drosophila males, transcript for the core cell cycle protein Cyclin B1 (CycB) is expressed in spermatocytes, but the protein does not accumulate in spermatocytes until just before the meiotic divisions. Here, we show that two interacting proteins, Rbp4 and Fest, expressed at the onset of spermatocyte differentiation under control of the developmental program of male gametogenesis, function to direct cell type- and stage-specific repression of translation of the core G2/M cell cycle component cycB during the specialized cell cycle of male meiosis. Binding of Fest to Rbp4 requires a 31-amino acid region within Rbp4. Rbp4 and Fest are required for translational repression of cycB in immature spermatocytes, with Rbp4 binding sequences in a cell type-specific shortened form of the cycB 3' UTR. Finally, we show that Fest is required for proper execution of meiosis I.

  4. Mesenchymal Stem Cells: Rising Concerns over Their Application in Treatment of Type One Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Seyed Jafar Hashemian


    Full Text Available Type 1 diabetes mellitus (T1DM is an autoimmune disorder that leads to beta cell destruction and lowered insulin production. In recent years, stem cell therapies have opened up new horizons to treatment of diabetes mellitus. Among all kinds of stem cells, mesenchymal stem cells (MSCs have been shown to be an interesting therapeutic option based on their immunomodulatory properties and differentiation potentials confirmed in various experimental and clinical trial studies. In this review, we discuss MSCs differential potentials in differentiation into insulin-producing cells (IPCs from various sources and also have an overview on currently understood mechanisms through which MSCs exhibit their immunomodulatory effects. Other important issues that are provided in this review, due to their importance in the field of cell therapy, are genetic manipulations (as a new biotechnological method, routes of transplantation, combination of MSCs with other cell types, frequency of transplantation, and special considerations regarding diabetic patients’ autologous MSCs transplantation. At the end, utilization of biomaterials either as encapsulation tools or as scaffolds to prevent immune rejection, preparation of tridimensional vascularized microenvironment, and completed or ongoing clinical trials using MSCs are discussed. Despite all unresolved concerns about clinical applications of MSCs, this group of stem cells still remains a promising therapeutic modality for treatment of diabetes.

  5. Immunoenhancing activity of protopanaxatriol-type ginsenoside-F3 in murine spleen cells

    Institute of Scientific and Technical Information of China (English)

    Jun-li YU; De-qiang DOU; Xiao-hong CHEN; Hong-zhen YANG; Na GUO; Gui-fang CHENG


    AIM: To investigate the immunoenhancing activity of ginsenoside-F3 in murine spleen cells and explore its mechanism.METHODS: The enhancing effect of ginsenoside-F3 on murine spleen cell proliferation was studied using [3H]thymidine incorporation assay. Effects of ginsenoside-F3 on the production of type 1 cytokines IL-2, IFN-γ, and type 2 cytokines IL-4 and IL-10 from murine spleen cells were detected by ELISA method. Effects of ginsenosideF3 on mRNA level of cytokines IL-4, IFN-γ, and transcription factors T-bet and GATA-3 were evaluated by RTPCR analysis. Effect of ginsenoside-F3 on NF-κB DNA binding activity in murine spleen cells was investigated by electrophoretic mobility shift assays (EMSA). RESULTS: Ginsenoside-F3 at 0.1-100μmol/L not only promoted the murine spleen cell proliferation, but also increased the production of IL-2 and IFN-γ, while decreased the production of IL-4 and IL-10 from murine spleen cells with the maximal effect at 10μmol/L. RT-PCR analysis displayed that ginsenoside-F3 enhanced the IFN-γ and T-bet gene expression and decreased IL-4 and GATA-3 gene expression. EMSA experiment showed that ginsenoside-F3 10μmol/L enhanced the NF-κB DNA binding activity induced by ConA in murine spleen cells. CONCLUSION: Ginsenoside-F3 has immunoenhancing activity by regulating production and gene expression of type 1 cytokines and type 2 cytokines in murine spleen cells.

  6. High power n-type metal-wrap-through cells and modules using industrial processes

    Energy Technology Data Exchange (ETDEWEB)

    Guillevin, N.; Heurtault, B.J.B.; Geerligs, L.J.; Van Aken, B.B.; Bennett, I.J.; Jansen, M.J.; Weeber, A.W.; Bultman, J.H. [ECN Solar Energy, P.O. Box 1, NL-1755 ZG Petten (Netherlands); Jianming, Wang; Ziqian, Wang; Jinye, Zhai; Zhiliang, Wan; Shuquan, Tian; Wenchao, Zhao; Zhiyan, Hu; Gaofei, Li; Bo, Yu; Jingfeng, Xiong [Yingli Green Energy Holding Co.,Ltd. 3399 North Chaoyang Avenue, Baoding (China)


    This paper reviews our recent progress in the development of metal wrap through (MWT) cells and modules, produced from n-type Czochralski silicon wafers. The use of n-type silicon as base material allows for high efficiencies: for front emitter-contacted industrial cells, efficiencies above 20% have been reported. N-type MWT (nMWT) cells produced by industrial process technologies allow even higher efficiency due to reduced front metal coverage. Based on the same industrial technology, the efficiency of the bifacial n-MWT cells exceeds the efficiency of the n-type front-and-rear contact and bifacial 'Pasha' technology (n-Pasha) by 0.1-0.2% absolute, with a maximum nMWT efficiency of 20.1% so far. Additionally, full back-contacting of the MWT cells in a module results in reduced cell to module (CTM) fill factor losses. In a direct 60-cell module performance comparison, the n-MWT module, based on integrated backfoil, produced 3% higher power output than the comparable tabbed front emitter-contacted n-Pasha module. Thanks to reduced resistive losses in copper circuitry on the backfoil compared to traditional tabs, the CTM FF loss of the MWT module was reduced by about 2.2%abs. compared to the tabbed front emitter contact module. A full-size module made using MWT cells of 19.6% average efficiency resulted in a power output close to 280W. Latest results of the development of the n-MWT technology at cell and module level are discussed in this paper, including a recent direct comparison run between n-MWT and n-Pasha cells and results of n-MWT cells from 140{mu}m thin mono-crystalline wafers, with only very slight loss (1% of Isc) for the thin cells. Also reverse characteristics and effects of reverse bias for extended time at cell and module level are reported, where we find a higher tolerance of MWT modules than tabbed front contact modules for hotspots.

  7. Identification of Type VI Collagen Synthesizing Cells in Human Diabetic Glomerulosclerosis Using Renal Biopsy Sections

    Directory of Open Access Journals (Sweden)

    Mohammed Shawkat Razzaque


    Full Text Available Although the role of extracellular matrices in the development of glomerulosclerosis has been discussed widely, the cellular origin of type VI collagen in diabetic nephropathy (DN has remained relatively unexplored. This study reports the distribution and cellular origin of type VI collagen in DN. Type VI collagen‐specific oligonucleotide probes and monoclonal antibody were used to assess the relative expression of mRNA for \\alpha1 (VI chain and its translated protein in paraffin‐embedded renal biopsy sections of DN. By immunohistochemistry, compared to the control, increased deposition of type VI collagen was noted in the diffuse and nodular lesions of diabetic glomeruli. For cellular localization of type VI collagen mRNA, paraffin‐embedded renal sections of the control and DN were hybridized in situ with digoxigenin (Dig‐labeled antisense oligo‐DNA probe complementary to a part of \\alpha1 (VI mRNA. In comparison to the control kidney sections, increased numbers of intraglomerular cells (both mesangial and epithelial cells were positive for α1 (VI mRNA in renal biopsy sections of DN. From the results, we conclude that overexpression of type VI collagen by intraglomerular cells with its increased deposition might significantly contribute to the glomerulosclerosis found in DN.

  8. Stem cell therapy for type 1 diabetes mellitus: a review of recent clinical trials

    Directory of Open Access Journals (Sweden)

    Couri Carlos


    Full Text Available Abstract Stem cell therapy is one of the most promising treatments for the near future. It is expected that this kind of therapy can ameliorate or even reverse some diseases. With regard to type 1 diabetes, studies analyzing the therapeutic effects of stem cells in humans began in 2003 in the Hospital das Clínicas of the Faculty of Medicine of Ribeirão Preto - SP USP, Brazil, and since then other centers in different countries started to randomize patients in their clinical trials. Herein we summarize recent data about beta cell regeneration, different ways of immune intervention and what is being employed in type 1 diabetic patients with regard to stem cell repertoire to promote regeneration and/or preservation of beta cell mass. The Diabetes Control and Complications Trial (DCCT was a 7-year longitudinal study that demonstrated the importance of the intensive insulin therapy when compared to conventional treatment in the development of chronic complications in patients with type 1 diabetes mellitus (T1DM. This study also demonstrated another important issue: there is a reverse relationship between C-peptide levels (endogenous indicator of insulin secretion chronic complications - that is, the higher the C-peptide levels, the lower the incidence of nephropathy, retinopathy and hypoglycemia. From such data, beta cell preservation has become an additional target in the management of T1DM 1.

  9. Regenerative Therapy of Type 1 Diabetes Mellitus: From Pancreatic Islet Transplantation to Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Nadine E. Rekittke


    Full Text Available Type 1 diabetes is an autoimmune disease resulting in the permanent destruction of pancreatic islets. Islet transplantation to portal vein provides an approach to compensate for loss of insulin producing cells. Clinical trials demonstrated that even partial islet graft function reduces severe hypoglycemic events in patients. However, therapeutic impact is restrained due to shortage of pancreas organ donors and instant inflammation occurring in the hepatic environment of the graft. We summarize on what is known about regenerative therapy in type 1 diabetes focusing on pancreatic islet transplantation and new avenues of cell substitution. Metabolic pathways and energy production of transplanted cells are required to be balanced and protection from inflammation in their intravascular bed is desired. Mesenchymal stem cells (MSCs have anti-inflammatory features, and so they are interesting as a therapy for type 1 diabetes. Recently, they were reported to reduce hyperglycemia in diabetic rodents, and they were even discussed as being turned into endodermal or pancreatic progenitor cells. MSCs are recognized to meet the demand of an individual therapy not raising the concerns of embryonic or induced pluripotent stem cells for therapy.

  10. Characterization and development of an inner ear type I fibrocyte cell culture. (United States)

    Gratton, M A; Schulte, B A; Hazen-Martin, D J


    A method has been developed that allows successful maintenance of secondary cell cultures derived from explants of the cochlear lateral wall of young adult gerbils. The secondary cultures were characterized morphologically with light and transmission electron microscopy and immunocytochemically with protein markers specific to various lateral wall cell types. Structural studies revealed fusiform-shaped cells with a paucity of cytoplasm surrounding the nucleus and slender processes. The cells showed little evidence of intercellular contact even when confluent. The cultures were immunopositive for vimentin, carbonic anhydrase isozyme II, creatine kinase isozyme BB and smooth endoplasmic reticulum Ca-ATPase, but lacked reactivity for cytokeratins and Na,K-ATPase. The results indicate that the cultures are comprised of type I fibrocytes from the spiral ligament. These findings are the first to demonstrate that inner ear spiral ligament cells can be isolated and maintained in secondary culture while retaining many of their in vivo characteristics. Based upon their location and content of ion transport enzymes, type I fibrocytes are thought to be involved in the recycling of potassium from perilymph into the stria vascularis. The establishment of this cell line provides a means to analyze the role of spiral ligament fibrocytes in maintenance of inner ear homeostasis.

  11. Nanoparticle (NP) uptake by type I alveolar epithelial cells and their oxidant stress response (United States)

    VanWinkle, Beth A.; de Mesy Bentley, Karen L.; Malecki, Jonathan M.; Gunter, Karlene K.; Evans, Irene M.; Elder, Alison; Finkelstein, Jacob N.; Oberdörster, Günter; Gunter, Thomas E.


    Mammalian cells take up nanoparticles (NPs) and some NPs increase ROS. We use imaging and measure ROS in parallel to evaluate NP-cell interactions with type I-like alveolar epithelial cells exposed to NPs at 1.2 µg/cm2 . Titanium dioxide (Ti02), gold (Au), silver (Ag), and manganese (Mn) were internalized by R3-1 cells; copper (Cu) NPs were observed at the cell surface only. TiO2 and Au did not increase cell death but Mn and Cu did, with surviving cells recovering after initial Cu exposure. Ag NPs caused 80% of R3-1 cells to lift off the slides within one hour. Amplex Red was used to report H2O2 production after exposure to 0.4 µg/cm2 TiO2, Au, Cu, Mn and Ag. TiO2, Au, and Ag caused no significant increase in H2O2 while Cu and Mn increased H2O2. NPs that give up electrons, increase ROS production and cause cell death in R3-1 cells. PMID:20563262

  12. A feedback mechanism controlling SCRAMBLED receptor accumulation and cell-type pattern in Arabidopsis. (United States)

    Kwak, Su-Hwan; Schiefelbein, John


    Cellular pattern formation in the root epidermis of Arabidopsis occurs in a position-dependent manner, generating root-hair (H) cells contacting two underlying cortical cells and nonhair (N) cells contacting one cortical cell. SCRAMBLED (SCM), a leucine-rich repeat receptor-like kinase (LRR-RLK), mediates this process through its effect on a downstream transcription factor regulatory network. After perception of a positional cue, the SCM signaling pathway is proposed to preferentially repress WEREWOLF (WER) transcription factor expression in H cells and thereby bias the outcome of mutual lateral inhibition acting between H and N cells. However, the molecular mechanism responsible for this preferential SCM signaling is unknown. Here, we analyze the distribution of the SCM receptor and the biological effect of altering its accumulation pattern. We find that SCM expression and accumulation in the epidermal cell layer is necessary and sufficient to direct the cell-type pattern. Further, SCM preferentially accumulates in H cells, and this accumulation pattern is dependent on the downstream transcription factors. Thus, SCM participates in an autoregulatory feedback loop, enabling cells engaged in SCM signaling to maintain high levels of SCM receptor, which provides a simple mechanism for reinforcing a bias in receptor-mediated signaling to ensure robust pattern formation.

  13. Sox2-positive dermal papilla cells specify hair follicle type in mammalian epidermis. (United States)

    Driskell, Ryan R; Giangreco, Adam; Jensen, Kim B; Mulder, Klaas W; Watt, Fiona M


    The dermal papilla comprises the specialised mesenchymal cells at the base of the hair follicle. Communication between dermal papilla cells and the overlying epithelium is essential for differentiation of the hair follicle lineages. We report that Sox2 is expressed in all dermal papillae at E16.5, but from E18.5 onwards expression is confined to a subset of dermal papillae. In postnatal skin, Sox2 is only expressed in the dermal papillae of guard/awl/auchene follicles, whereas CD133 is expressed both in guard/awl/auchene and in zigzag dermal papillae. Using transgenic mice that express GFP under the control of the Sox2 promoter, we isolated Sox2(+) (GFP(+)) CD133(+) cells and compared them with Sox2(-) (GFP(-)) CD133(+) dermal papilla cells. In addition to the 'core' dermal papilla gene signature, each subpopulation expressed distinct sets of genes. GFP(+) CD133(+) cells had upregulated Wnt, FGF and BMP pathways and expressed neural crest markers. In GFP(-) CD133(+) cells, the hedgehog, IGF, Notch and integrin pathways were prominent. In skin reconstitution assays, hair follicles failed to form when dermis was depleted of both GFP(+) CD133(+) and GFP(-) CD133(+) cells. In the absence of GFP(+) CD133(+) cells, awl/auchene hairs failed to form and only zigzag hairs were found. We have thus demonstrated a previously unrecognised heterogeneity in dermal papilla cells and shown that Sox2-positive cells specify particular hair follicle types.

  14. Preliminary study on Herpes simplex virus type 1 infection of human oral epithelial cell in vitro

    Institute of Scientific and Technical Information of China (English)

    Jie Zhao; Weibin Sun; Juan Wang


    Objective: To explore the functions and mechanisms of herpes simplex virus type 1(HSV-1) while infecting human oral epithelial cells in vitro(being similar to the infection in vivo). Methods:An abundance of HSV-1 strains amplified in Vero cells were used to infect human oral epithelial cells. The culture supernatant was collected to infect Veto cells again. Morphology of HSV-1 was identified by inverted microscope and transmission electron microscope. Nucleic acid of the virus was detected by PCR. Results:The infected human oral epithelial cells didn't display an obvious cytopathic effect(CPE) under inverted microscope(while Veto cells which were infected by the culture supematant showed typical(CPE). The virus particles were not observed in the cytoplasm nor in nucleus of human oral epithelial cells, however under transmission electron microscope in the cytoplasm of Vero cells, the nucleic acid of HSV-1 could be detected in infected human oral epithelial cells, by PCR. Conclusion:HSV-1 can successfully infect human oral epithelial cells. This model may provide a useful approach for studying the pathogenesis of herpes virus-associated periodontal disease.

  15. Potential contribution of Type I lung epithelial cells to chronic neonatal lung disease

    Directory of Open Access Journals (Sweden)

    Henry J. Rozycki


    Full Text Available The alveolar surface is covered by large flat Type I cells (alveolar epithelial cells 1, AEC1. The normal physiological function of AEC1s involves gas exchange, based on their location in approximation to the capillary endothelium and their thinness, and in ion and water flux, as shown by the presence of solute active transport proteins, water channels, and impermeable tight junctions between cells. With the recent ability to produce relatively pure cultures of AEC1 cells, new functions have been described. These may be relevant to lung injury, repair and the abnormal development that characterizes bronchopulmonary dysplasia. To hypothesize a potential role for AEC1 in the development of lung injury and abnormal repair/development in premature lungs, evidence is presented for their presence in the developing lung, how their source may not be the Type II cell (AEC2 as has been assumed for forty years, and how the cell can be damaged by same type of stressors as those which lead to bronchopulmonary dysplasia (BPD. Recent work shows that the cells are part of the innate immune response, capable of producing pro-inflammatory mediators, which could contribute to the increase in inflammation seen in early bronchopulmonary dysplasia. One of the receptors found exclusively on AEC1 cells in the lung, called RAGE, may also have a role in increased inflammation, and to alveolar simplification. While the current evidence for AEC1 involvement in BPD is circumstantial and limited at present, the accumulating data supports several hypotheses and questions regarding potential differences in the behavior of AEC1 cells from newborn and premature lung compared with the adult lung.

  16. Epigenetic regulation of normal human mammary cell type-specific miRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Vrba, Lukas [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Inst. of Plant Molecular Biology, Ceske Budejovice (Czech Republic). Biology Centre ASCR; Garbe, James C. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Stampfer, Martha R. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Center; Futscher, Bernard W. [Univ. of Arizona, Tucson, AZ (United States). Arizona Cancer Center and Dept. of Pharmacology & Toxicology


    Epigenetic mechanisms are important regulators of cell type–specific genes, including miRNAs. In order to identify cell type-specific miRNAs regulated by epigenetic mechanisms, we undertook a global analysis of miRNA expression and epigenetic states in three isogenic pairs of human mammary epithelial cells (HMEC) and human mammary fibroblasts (HMF), which represent two differentiated cell types typically present within a given organ, each with a distinct phenotype and a distinct epigenotype. While miRNA expression and epigenetic states showed strong interindividual concordance within a given cell type, almost 10% of the expressed miRNA showed a cell type–specific pattern of expression that was linked to the epigenetic state of their promoter. The tissue-specific miRNA genes were epigenetically repressed in nonexpressing cells by DNA methylation (38%) and H3K27me3 (58%), with only a small set of miRNAs (21%) showing a dual epigenetic repression where both DNA methylation and H3K27me3 were present at their promoters, such as MIR10A and MIR10B. Individual miRNA clusters of closely related miRNA gene families can each display cell type–specific repression by the same or complementary epigenetic mechanisms, such as the MIR200 family, and MIR205, where fibroblasts repress MIR200C/141 by DNA methylation, MIR200A/200B/429 by H3K27me3, and MIR205 by both DNA methylation and H3K27me3. Since deregulation of many of the epigenetically regulated miRNAs that we identified have been linked to disease processes such as cancer, it is predicted that compromise of the epigenetic control mechanisms is important for this process. Overall, these results highlight the importance of epigenetic regulation in the control of normal cell type–specific miRNA expression.

  17. HCMV Displays a Unique Transcriptome of Immunomodulatory Genes in Primary Monocyte-Derived Cell Types (United States)

    Van Damme, Ellen; Thys, Kim; Tuefferd, Marianne; Van Hove, Carl; Aerssens, Jeroen; Van Loock, Marnix


    Human cytomegalovirus (HCMV) is a betaherpesvirus which rarely presents problems in healthy individuals, yet may result in severe morbidity in immunocompromised patients and in immune-naïve neonates. HCMV has a large 235 kb genome with a coding capacity of at least 165 open reading frames (ORFs). This large genome allows complex gene regulation resulting in different sets of transcripts during lytic and latent infection. While latent virus mainly resides within monocytes and CD34+ progenitor cells, reactivation to lytic infection is driven by differentiation towards terminally differentiated myeloid dendritic cells and macrophages. Consequently, it has been suggested that macrophages and dendritic cells contribute to viral spread in vivo. Thus far only limited knowledge is available on the expression of HCMV genes in terminally differentiated myeloid primary cells and whether or not the virus exhibits a different set of lytic genes in primary cells compared with lytic infection in NHDF fibroblasts. To address these questions, we used Illumina next generation sequencing to determine the HCMV transcriptome in macrophages and dendritic cells during lytic infection and compared it to the transcriptome in NHDF fibroblasts. Here, we demonstrate unique expression profiles in macrophages and dendritic cells which significantly differ from the transcriptome in fibroblasts mainly by modulating the expression of viral transcripts involved in immune modulation, cell tropism and viral spread. In a head to head comparison between macrophages and dendritic cells, we observed that factors involved in viral spread and virion composition are differentially regulated suggesting that the plasticity of the virion facilitates the infection of surrounding cells. Taken together, this study provides the full transcript expression analysis of lytic HCMV genes in monocyte-derived type 1 and type 2 macrophages as well as in monocyte-derived dendritic cells. Thereby underlining the potential

  18. Comparison of Different Adult Stem Cell Types for Treatment of Myocardial Ischemia (United States)

    van der Bogt, Koen E.A.; Sheikh, Ahmad Y.; Schrepfer, Sonja; Hoyt, Grant; Cao, Feng; Ransohoff, Katie; Swijnenburg, Rutger-Jan; Pearl, Jeremy; Fischbein, Michael; Contag, Christopher H.; Robbins, Robert C.; Wu, Joseph C.


    Introduction A comparative analysis of the efficacy of different cell candidates for the treatment of heart disease remains to be described. This study is designed to evaluate the therapeutic efficacy of 4 cell types in a murine model of myocardial infarction. Methods Bone marrow mononuclear cells (MN), mesenchymal stem cells (MSC), skeletal myoblasts (SkMb) and fibroblasts (Fibro) were isolated from male L2G transgenic mice (FVB background) that constitutively express firefly luciferase (Fluc) and green fluorescence protein (GFP). Cells were characterized by flow cytometry, bioluminescence imaging (BLI), and luminometry. Female FVB mice (n=60) underwent LAD ligation and were randomized into 5 groups to intramyocardially receive one cell type (5 × 105) or PBS as control. Cell survival was measured in vivo by BLI and ex vivo by TaqMan PCR at week 6. Cardiac function was assessed by echocardiography and invasive hemodynamic measurements were made at week 6. Results Fluc expression correlated with the cell number in all groups (r2 >0.93). In vivo BLI revealed acute donor cell death of MSC, SkMb, and Fibro within 3 weeks after transplantation. By contrast, cardiac signals were still present after 6 weeks in the MN group, as confirmed by TaqMan PCR (P<0.01). Echocardiography showed significant preservation of fractional shortening in the MN group compared to controls (P<0.05). Measurements of left ventricular end-systolic/diastolic volumes revealed that the least amount of ventricular dilatation occurred in the MN group (P<0.05). Histology confirmed the presence of MN, although there was no evidence of transdifferentiation by donor MN into cardiomyocytes. Conclusion This is the first study to directly compare a variety of cell candidates for myocardial therapy. Compared to MSC, SkMB, and Fibro, our results suggest that MN cells exhibit a more favorable survival pattern, which translates into a more robust preservation of cardiac function. PMID:18824743

  19. Influence of type-I Interferon receptor expression level on the response to type-I Interferons in human pancreatic cancer cells. (United States)

    Booy, Stephanie; van Eijck, Casper H J; Dogan, Fadime; van Koetsveld, Peter M; Hofland, Leo J


    Pancreatic cancer is a highly aggressive malignancy with limited treatment options. Type-I interferons (e.g. IFN-α/-β) have several anti-tumour activities. Over the past few years, clinical studies evaluating the effect of adjuvant IFN-α therapy in pancreatic cancer yielded equivocal results. Although IFN-α and -β act via the type-I IFN receptor, the role of the number of receptors present on tumour cells is still unknown. Therefore, this study associated, for the first time, in a large panel of pancreatic cancer cell lines the effects of IFN-α/-β with the expression of type-I IFN receptors. The anti-tumour effects of IFN-α or IFN-β on cell proliferation and apoptosis were evaluated in 11 human pancreatic cell lines. Type-I IFN receptor expression was determined on both the mRNA and protein level. After 7 days of incubation, IFN-α significantly reduced cell growth in eight cell lines by 5-67%. IFN-β inhibited cell growth statistically significant in all cell lines by 43-100%. After 3 days of treatment, IFN-β induced significantly more apoptosis than IFN-α. The cell lines variably expressed the type-I IFN receptor. The maximal inhibitory effect of IFN-α was positively correlated with the IFNAR-1 mRNA (P interferon receptor expression and seems, therefore, more promising than IFN-α.

  20. Cdk4 functions in multiple cell types to control Drosophila intestinal stem cell proliferation and differentiation

    Directory of Open Access Journals (Sweden)

    Mojca Adlesic


    Full Text Available The proliferation of intestinal stem cells (ISCs and differentiation of enteroblasts to form mature enteroendocrine cells and enterocytes in the Drosophila intestinal epithelium must be tightly regulated to maintain homeostasis. We show that genetic modulation of CyclinD/Cdk4 activity or mTOR-dependent signalling cell-autonomously regulates enterocyte growth, which influences ISC proliferation and enteroblast differentiation. Increased enterocyte growth results in higher numbers of ISCs and defective enterocyte growth reduces ISC abundance and proliferation in the midgut. Adult midguts deficient for Cdk4 show severe disruption of intestinal homeostasis characterised by decreased ISC self-renewal, enteroblast differentiation defects and low enteroendocrine cell and enterocyte numbers. The ISC/enteroblast phenotypes result from a combination of cell autonomous and non-autonomous requirements for Cdk4 function. One non-autonomous consequence of Cdk4-dependent deficient enterocyte growth is high expression of Delta in ISCs and Delta retention in enteroblasts. We postulate that aberrant activation of the Delta–Notch pathway is a possible partial cause of lost ISC stemness. These results support the idea that enterocytes contribute to a putative stem cell niche that maintains intestinal homeostasis in the Drosophila anterior midgut.

  1. A new type counter electrode for dye-sensitized solar cells

    Institute of Scientific and Technical Information of China (English)

    JI WeiWei; CAI Ning; ZHAO Ying; ZHANG XiaoDan; SUN Jian; WEI ChangChun; YUAN CunDa; LI Yuan; SU Yan; XIONG ShaoZhen


    A new type counter electrode for dye-sensitized solar cells (DSCs) was proposed which consists of aubstrate, aluminum film and platinum film. The new type counter electrode can obviously improve the photoelectric conversion efficiency of DSCs from 3.46% to 7.07% under the standard AM1.5 irradiation condition. Advantages and shortcomings of this new type counter electrode in terms of electrical properties, optical properties and anti-corrosive properties were analyzed. As a result, some improvements were proposed.

  2. Extranodal Natural Killer/T-Cell Lymphoma of the Nasal Type with Skin Metastases

    Directory of Open Access Journals (Sweden)

    Fadi Al Akhrass


    Full Text Available Extranodal natural killer/T-cell lymphoma (ENKL of the nasal type is a rare, clinically aggressive disease. ENKL of the nasal type is often localized in the upper aerodigestive tract, including the nasal cavity, nasopharynx, paranasal sinuses, tonsils, hypopharynx and larynx, and usually presents as stage I/II. Extranasal involvement can occur, and a common site of extranasal involvement or metastatic disease includes the skin. Identifying skin metastases is important for the appropriate staging and treatment. We report a case of ENKL of the nasal type that presented with localized disease and subsequent skin lesions that were consistent with skin metastases.

  3. The Event of Forcefully Emigrating Cherkesses and Contemporary Echo%强迁切尔克斯人事件与当代回声

    Institute of Scientific and Technical Information of China (English)



      19世纪50年代到70年代初,大批高加索山民迁到土耳其。此中有三种情形:一是俄军强制迁徙,二是俄政府征得山民同意后有组织的迁徙,三是山民自发迁徙。但后两种情形也是在受到俄军和政府高压之下的无奈之举。俄土两国因此受益,高加索山民则遭受了巨大的苦难。迁徙高加索民族甚至为苏联解决国内问题积累了经验,成为其政治文化的一部分。目前,高加索民族迁徙的话题已被高度政治化,各方都在利用该话题达到自己的目的。%From the 50s to the 70s of the 19th century, a lot of Caucasian mountaineers moved to Turkey. There are three kinds of circumstances among it:first, the Russian army forced them to emigrate;second, the Russian government organized them to emigrate after asking for their agreement; third, the mountaineers emigrated spontaneously, but the last two circumstances are also what they had to do under the high-handed policy of the Russian army and government. Russia and Turkey gained benefits from their emigration, but the mountaineers suffered a lot. Emigrating Caucasian tribes accumulated some experience for the Soviet Union to resolve domestic problems and became a part of its political culture. At present, the topic of Caucasian emigration has been highly politicized. Each uses this topic to attain his own goal.

  4. Cell-type specificity of ChIP-predicted transcription factor binding sites

    Directory of Open Access Journals (Sweden)

    Håndstad Tony


    Full Text Available Abstract Background Context-dependent transcription factor (TF binding is one reason for differences in gene expression patterns between different cellular states. Chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq identifies genome-wide TF binding sites for one particular context—the cells used in the experiment. But can such ChIP-seq data predict TF binding in other cellular contexts and is it possible to distinguish context-dependent from ubiquitous TF binding? Results We compared ChIP-seq data on TF binding for multiple TFs in two different cell types and found that on average only a third of ChIP-seq peak regions are common to both cell types. Expectedly, common peaks occur more frequently in certain genomic contexts, such as CpG-rich promoters, whereas chromatin differences characterize cell-type specific TF binding. We also find, however, that genotype differences between the cell types can explain differences in binding. Moreover, ChIP-seq signal intensity and peak clustering are the strongest predictors of common peaks. Compared with strong peaks located in regions containing peaks for multiple transcription factors, weak and isolated peaks are less common between the cell types and are less associated with data that indicate regulatory activity. Conclusions Together, the results suggest that experimental noise is prevalent among weak peaks, whereas strong and clustered peaks represent high-confidence binding events that often occur in other cellular contexts. Nevertheless, 30-40% of the strongest and most clustered peaks show context-dependent regulation. We show that by combining signal intensity with additional data—ranging from context independent information such as binding site conservation and position weight matrix scores to context dependent chromatin structure—we can predict whether a ChIP-seq peak is likely to be present in other cellular contexts.

  5. The Vibrio parahaemolyticus Type III Secretion Systems manipulate host cell MAPK for critical steps in pathogenesis.

    LENUS (Irish Health Repository)

    Matlawska-Wasowska, Ksenia


    Vibrio parahaemolyticus is a food-borne pathogen causing inflammation of the gastrointestinal epithelium. Pathogenic strains of this bacterium possess two Type III Secretion Systems (TTSS) that deliver effector proteins into host cells. In order to better understand human host cell responses to V. parahaemolyticus, the modulation of Mitogen Activated Protein Kinase (MAPK) activation in epithelial cells by an O3:K6 clinical isolate, RIMD2210633, was investigated. The importance of MAPK activation for the ability of the bacterium to be cytotoxic and to induce secretion of Interleukin-8 (IL-8) was determined.

  6. Transient expression of P-type ATPases in tobacco epidermal cells

    DEFF Research Database (Denmark)

    Poulsen, Lisbeth Rosager; Palmgren, Michael Broberg; Lopez Marques, Rosa Laura


    Transient expression in tobacco cells is a convenient method for several purposes such as analysis of protein-protein interactions and the subcellular localization of plant proteins. A suspension of Agrobacterium tumefaciens cells carrying the plasmid of interest is injected into the intracellular...... for example protein-protein interaction studies. In this chapter, we describe the procedure to transiently express P-type ATPases in tobacco epidermal cells, with focus on subcellular localization of the protein complexes formed by P4-ATPases and their β-subunits....

  7. Differences in indicators of malignancy between luminal epithelial cell type and myoepithelial cell type of simple solid carcinoma in the canine mammary gland. (United States)

    Yoshimura, H; Nakahira, R; Kishimoto, T E; Michishita, M; Ohkusu-Tsukada, K; Takahashi, K


    Routinely diagnosed simple solid carcinoma (SSC) of the canine mammary gland comprises a heterogeneous group of tumors. Seventy-two cases that had been diagnosed as SSC based on hematoxylin and eosin-stained tissue sections were reclassified immunohistochemically on the basis of myoepithelial markers p63 and α-smooth muscle actin, as well as a luminal epithelial marker cytokeratin 8. Only 23 cases (32%) were true SSC, composed only of luminal epithelial cells, whereas 11 cases (15%) were malignant myoepithelioma (MM), composed predominantly of myoepithelial cells, and 38 cases (53%) were biphasic carcinoma (BC), characterized by biphasic proliferation of luminal epithelial and basal/myoepithelial components. As the pathological parameters were compared between the reclassified tumor types, infiltrative potential, vascular/lymphatic invasion, lymph node metastasis, and Ki-67 labeling index were higher in true SSC compared with MM and BC, suggesting that the former may exhibit a poorer prognosis compared with the latter two.

  8. Frequency of islet cell autoantibodies (IA-2 and GAD in young Brazilian type 1 diabetes patients

    Directory of Open Access Journals (Sweden)

    V.C. Pardini


    Full Text Available Type 1 diabetes, as an autoimmune disease, presents several islet cell-specific autoantibodies such as islet cell antibody (ICA, anti-insulin, anti-glutamic acid decarboxylase (GAD and the antibody (Ab against tyrosine phosphatase (PTP-like protein known as ICA-512 (IA-2. In order to determine the frequency of the anti-GAD and anti-IA-2 autoantibodies in Brazilian type 1 diabetes patients we studied 35 diabetes mellitus (DM type 1 patients with recent-onset disease (£12 months and 37 type 1 diabetes patients with long-duration diabetes (>12 months who were compared to 12 children with normal fasting glucose. Anti-GAD65 and anti-IA-2 autoantibodies were detected with commercial immunoprecipitation assays. The frequency of positive results in recent-onset DM type 1 patients was 80.0% for GADAb, 62.9% for IA-2Ab and 82.9% for GADAb and/or IA-2Ab. The long-duration type 1 diabetes subjects presented frequencies of 54.1% for GADAb and IA-2Ab, and 67.5% for GAD and/or IA-2 antibodies. The control group showed no positive cases. Anti-GAD and IA-2 assays showed a high frequency of positivity in these Brazilian type 1 diabetes patients, who presented the same prevalence as a Caucasian population.

  9. Fluorescence in situ hybridization-flow cytometry-cell sorting-based method for separation and enrichment of type I and type II methanotroph populations. (United States)

    Kalyuzhnaya, Marina G; Zabinsky, Rebecca; Bowerman, Sarah; Baker, David R; Lidstrom, Mary E; Chistoserdova, Ludmila


    A fluorescence in situ hybridization-flow cytometry (FISH/FC)-based method was optimized using artificial mixtures of pure cultures of methanotrophic bacteria. Traditional oligonucleotide probes targeting 16S rRNAs of type I (MG84/705 probe) and type II (MA450 probe) methanotrophs were labeled with fluorescein or Alexa fluor and used for FISH, followed by fluorescence-activated FC analysis and cell sorting (FACS). The method resulted in efficient separation of target cells (type I or type II methanotrophs) from the artificial mixtures. The method was then applied for detection and enrichment of type I and type II methanotroph populations from a natural sample, Lake Washington sediment. Cells were extracted from the sediment, fixed, and subjected to FISH/FC/FACS. The resulting subpopulations were analyzed by reverse transcriptase PCR surveys of 16S rRNA, pmoA (encoding a subunit of particulate methane monooxygenase), and fae (encoding formaldehyde-activating enzyme) genes. The functional gene analysis indicated specific separation of the type I and type II methanotroph populations. 16S rRNA gene analysis revealed that type I methanotrophs comprised 59% of the subpopulation separated using the type I-specific probe and that type II methanotrophs comprised 47.5% of the subpopulation separated using the type II-specific probe. Our data indicate that the FISH/FC/FACS protocol described can provide significant enrichment of microbial populations of interest from complex natural communities and that these can be used for genetic tests. We further tested the possibility of direct whole-genome amplification (WGA) from limited numbers of sorted cells, using artificial mixtures of microbes whose genome sequences are known. We demonstrated that efficient WGA can be achieved using 10(4) or more cells separated by 16S rRNA-specific FISH/FC/FACS, while fewer cells resulted in less specific WGA.

  10. Optimizing Staining Protocols for Laser Microdissection of Specific Cell Types from the Testis Including Carcinoma In Situ

    DEFF Research Database (Denmark)

    Sonne, Si Brask; Dalgaard, Marlene D; Nielsen, John Erik


    Microarray and RT-PCR based methods are important tools for analysis of gene expression; however, in tissues containing many different cells types, such as the testis, characterization of gene expression in specific cell types can be severely hampered by noise from other cells. The laser...... microdissection technology allows for enrichment of specific cell types. However, when the cells are not morphologically distinguishable, it is necessary to use a specific staining method for the target cells. In this study we have tested different fixatives, storage conditions for frozen sections and staining...

  11. Behind the lines–actions of bacterial type III effector proteins in plant cells (United States)

    Büttner, Daniela


    Pathogenicity of most Gram-negative plant-pathogenic bacteria depends on the type III secretion (T3S) system, which translocates bacterial effector proteins into plant cells. Type III effectors modulate plant cellular pathways to the benefit of the pathogen and promote bacterial multiplication. One major virulence function of type III effectors is the suppression of plant innate immunity, which is triggered upon recognition of pathogen-derived molecular patterns by plant receptor proteins. Type III effectors also interfere with additional plant cellular processes including proteasome-dependent protein degradation, phytohormone signaling, the formation of the cytoskeleton, vesicle transport and gene expression. This review summarizes our current knowledge on the molecular functions of type III effector proteins with known plant target molecules. Furthermore, plant defense strategies for the detection of effector protein activities or effector-triggered alterations in plant targets are discussed. PMID:27526699

  12. A survey of physical and psychological health status of senior emigrants and non-emigrants in Three Gorges Reservoir area%三峡库区移民与非移民老年人身心健康状况的调查

    Institute of Scientific and Technical Information of China (English)

    汪波; 杨辉; 宁洁; 范征莉; 刘智; 邱建国; 周建初


    Objective To study the physical and psychological health status of senior emigrants and non emigrants in Three Got ges Reservoir area. Methods Multistage stratified random sampling method was employed to choose senior people over 60 years old in Three Gorges Reservoir area,and divided them into emigrant group(n= 376) and control group(n= 228) according to whether they were emigrants. Self-made questionaire of senior people situation,Cornell medical index(CMI) and social support rating scale (SSRS) were adopted to analyze their general situation, physical and psychological health status and social support rating. Results Comparison with general situation of emigrant group and control group,there was no statistically difference(P>0.05). Total score of CMI in emigrant group was (30.03±11.68) points,which was higher than that in control group[(27.73±13.32)points] (P<0.05). Comparison with emigrant group and control group, no statistically difference was showed in positve detectable rates of somatopyschic disturbance(P>0.05). The first major factor of psychiatric symptom of emigrant group and control group were both depression, with the contribution rates were 39. 248 % and 41.958 %, respectively(P>0.05). Subjective social support rate of emigrant group was lower,compared to that in control group(P<0.01). Conclusion The overall level of physical and psychological health of senior emigrants is lower than that of senior non-emigrants in Three Gorges Reservoir area, but no significant difference observed in somatopyschic disturbance between them.%目的 研究三峡库区老年移民群体身心健康状况.方法 采用多级分层随机抽样法选择三峡库区年龄在60岁及以上的老年人进行调查,按是否移民,将其分为移民组(n=376)与对照组(n=228),应用自编老年人状况调查表、康奈尔医学指数(CMI)及社会支持评定量表(SSRS)对其一般情况、身心健康状况及社会支持度进行研究.结果 移民组

  13. Ammonium accumulation and cell death in a rat 3D brain cell model of glutaric aciduria type I.

    Directory of Open Access Journals (Sweden)

    Paris Jafari

    Full Text Available Glutaric aciduria type I (glutaryl-CoA dehydrogenase deficiency is an inborn error of metabolism that usually manifests in infancy by an acute encephalopathic crisis and often results in permanent motor handicap. Biochemical hallmarks of this disease are elevated levels of glutarate and 3-hydroxyglutarate in blood and urine. The neuropathology of this disease is still poorly understood, as low lysine diet and carnitine supplementation do not always prevent brain damage, even in early-treated patients. We used a 3D in vitro model of rat organotypic brain cell cultures in aggregates to mimic glutaric aciduria type I by repeated administration of 1 mM glutarate or 3-hydroxyglutarate at two time points representing different developmental stages. Both metabolites were deleterious for the developing brain cells, with 3-hydroxyglutarate being the most toxic metabolite in our model. Astrocytes were the cells most strongly affected by metabolite exposure. In culture medium, we observed an up to 11-fold increase of ammonium in the culture medium with a concomitant decrease of glutamine. We further observed an increase in lactate and a concomitant decrease in glucose. Exposure to 3-hydroxyglutarate led to a significantly increased cell death rate. Thus, we propose a three step model for brain damage in glutaric aciduria type I: (i 3-OHGA causes the death of astrocytes, (ii deficiency of the astrocytic enzyme glutamine synthetase leads to intracerebral ammonium accumulation, and (iii high ammonium triggers secondary death of other brain cells. These unexpected findings need to be further investigated and verified in vivo. They suggest that intracerebral ammonium accumulation might be an important target for the development of more effective treatment strategies to prevent brain damage in patients with glutaric aciduria type I.

  14. Primary Culture of Alveolar Epithelial TypeCells and Its Bionomic Study

    Institute of Scientific and Technical Information of China (English)

    SHI Xuemei; NI Wang; ZHANG Huilan; XIONG Shengdao; ZHEN Guohua; XIONG Weining; ZHANG Zhenxiang; XU Yongjian; HU Qiongjie; ZHAO Jianping


    To establish a better method of primary culture for alveolar epithelial typecells (AEC Ⅱ) and to study its bionomics, alveolar epithelial typecells were isolated by digestion with tryp- sin and collagenase, which were then purified by plated into culture flask coated with rat immu- noglobulin G. The purified AEC Ⅱ were identified by alkaline phosphatase staining, electron mi-croscopy, immunocytochemical staining of pulmonary surfactant protein A (SPA). The SPA expres-sion and transfection characteristics were compared with those of A549 cell line. The results showed that AEC Ⅱ could be isolated by digestion with trysin and collagenase and purified by adhesive pu- rification by using IgG, with a yield of about 2-3×107, and a purity of about 75%-84 %. Cells could be quickly identified with AKP staining. AEC Ⅱ were different from A549 cell line in terms of SPA expression and transfection characteristics. It is concluded that adhesive purification with IgG can improve the purity of AEC Ⅱ, and AKP staining is simple in cell identification. AEC Ⅱ can not be completely replaced by A549 cells in some studies because the differences between them, such as SPA expression.

  15. Cell-type-specific, Aptamer-functionalized Agents for Targeted Disease Therapy. (United States)

    Zhou, Jiehua; Rossi, John J


    One hundred years ago, Dr. Paul Ehrlich popularized the "magic bullet" concept for cancer therapy in which an ideal therapeutic agent would only kill the specific tumor cells it targeted. Since then, "targeted therapy" that specifically targets the molecular defects responsible for a patient's condition has become a long-standing goal for treating human disease. However, safe and efficient drug delivery during the treatment of cancer and infectious disease remains a major challenge for clinical translation and the development of new therapies. The advent of SELEX technology has inspired many groundbreaking studies that successfully adapted cell-specific aptamers for targeted delivery of active drug substances in both in vitro and in vivo models. By covalently linking or physically functionalizing the cell-specific aptamers with therapeutic agents, such as siRNA, microRNA, chemotherapeutics or toxins, or delivery vehicles, such as organic or inorganic nanocarriers, the targeted cells and tissues can be specifically recognized and the therapeutic compounds internalized, thereby improving the local concentration of the drug and its therapeutic efficacy. Currently, many cell-type-specific aptamers have been developed that can target distinct diseases or tissues in a cell-type-specific manner. In this review, we discuss recent advances in the use of cell-specific aptamers for targeted disease therapy, as well as conjugation strategies and challenges.

  16. The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Samuel S. Duffy


    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system characterised by widespread areas of focal demyelination. Its aetiology and pathogenesis remain unclear despite substantial insights gained through studies of animal models, most notably experimental autoimmune encephalomyelitis (EAE. MS is widely believed to be immune-mediated and pathologically attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS research has expanded beyond its focus on CD4+ T cells to recognise the contributions of multiple immune and glial cell types to the development, progression, and amelioration of the disease. This review summarises evidence of T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and oligodendroglial involvement in both EAE and MS and the intercommunication and influence of each cell subset in the inflammatory process. Despite important advances in the understanding of the involvement of these cell types in MS, many questions still remain regarding the various subsets within each cell population and their exact contribution to different stages of the disease.

  17. Type I collagen aging impairs discoidin domain receptor 2-mediated tumor cell growth suppression. (United States)

    Saby, Charles; Buache, Emilie; Brassart-Pasco, Sylvie; El Btaouri, Hassan; Courageot, Marie-Pierre; Van Gulick, Laurence; Garnotel, Roselyne; Jeannesson, Pierre; Morjani, Hamid


    Tumor cells are confronted to a type I collagen rich environment which regulates cell proliferation and invasion. Biological aging has been associated with structural changes of type I collagen. Here, we address the effect of collagen aging on cell proliferation in a three-dimensional context (3D).We provide evidence for an inhibitory effect of adult collagen, but not of the old one, on proliferation of human fibrosarcoma HT-1080 cells. This effect involves both the activation of the tyrosine kinase Discoidin Domain Receptor 2 (DDR2) and the tyrosine phosphatase SHP-2. DDR2 and SHP-2 were less activated in old collagen. DDR2 inhibition decreased SHP-2 phosphorylation in adult collagen and increased cell proliferation to a level similar to that observed in old collagen.In the presence of old collagen, a high level of JAK2 and ERK1/2 phosphorylation was observed while expression of the cell cycle negative regulator p21CIP1 was decreased. Inhibition of DDR2 kinase function also led to an increase in ERK1/2 phosphorylation and a decrease in p21CIP1 expression. Similar signaling profile was observed when DDR2 was inhibited in adult collagen. Altogether, these data suggest that biological collagen aging could increase tumor cell proliferation by reducingthe activation of the key matrix sensor DDR2.

  18. Variability in contrast agent uptake by different but similar stem cell types

    Directory of Open Access Journals (Sweden)

    Ketkar-Atre A


    Full Text Available Ashwini Ketkar-Atre,1 Tom Struys,1,2 Stefaan J Soenen,3 Ivo Lambrichts,2 Catherine M Verfaillie,4 Marcel De Cuyper,5 Uwe Himmelreich1 1Biomedical MRI/MoSAIC, Department of Imaging and Pathology, Biomedical Sciences Group, Katholieke Universiteit Leuven, Leuven, Belgium; 2Lab of Histology, Biomedical Research Institute, Hasselt University, Campus Diepenbeek, Agoralaan, Diepenbeek, Belgium; 3Lab for General Biochemistry and Physical Pharmacy, Faculty of Pharmacy, Ghent University, Ghent, Belgium; 4Interdepartmental Stem Cell Institute, O&N IV, Katholieke Universiteit Leuven, Leuven, Belgium; 5Laboratory of BioNanoColloids, Interdisciplinary Research Centre, Katholieke Universiteit Leuven, Kortrijk, Belgium Abstract: The need to track and evaluate the fate of transplanted cells is an important issue in regenerative medicine. In order to accomplish this, pre-labelling cells with magnetic resonance imaging (MRI contrast agents is a well-established method. Uptake of MRI contrast agents by non-phagocytic stem cells, and factors such as cell homeostasis or the adverse effects of contrast agents on cell biology have been extensively studied, but in the context of nanoparticle (NP-specific parameters. Here, we have studied three different types of NPs (Endorem®, magnetoliposomes [MLs], and citrate coated C-200 to label relatively larger, mesenchymal stem cells (MSCs and, much smaller yet faster proliferating, multipotent adult progenitor cells (MAPCs. Both cell types are similar, as they are isolated from bone marrow and have substantial regenerative potential, which make them interesting candidates for comparative experiments. Using NPs with different surface coatings and sizes, we found that differences in the proliferative and morphological characteristics of the cells used in the study are mainly responsible for the fate of endocytosed iron, intracellular iron concentration, and cytotoxic responses. The quantitative analysis, using high

  19. In Vitro Efficient Expansion of Tumor Cells Deriving from Different Types of Human Tumor Samples

    Directory of Open Access Journals (Sweden)

    Ilaria Turin


    Full Text Available Obtaining human tumor cell lines from fresh tumors is essential to advance our understanding of antitumor immune surveillance mechanisms and to develop new ex vivo strategies to generate an efficient anti-tumor response. The present study delineates a simple and rapid method for efficiently establishing primary cultures starting from tumor samples of different types, while maintaining the immuno-histochemical characteristics of the original tumor. We compared two different strategies to disaggregate tumor specimens. After short or long term in vitro expansion, cells analyzed for the presence of malignant cells demonstrated their neoplastic origin. Considering that tumor cells may be isolated in a closed system with high efficiency, we propose this methodology for the ex vivo expansion of tumor cells to be used to evaluate suitable new drugs or to generate tumor-specific cytotoxic T lymphocytes or vaccines.

  20. Genetic Variability Overrides the Impact of Parental Cell Type and Determines iPSC Differentiation Potential

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    Aija Kyttälä


    Full Text Available Reports on the retention of somatic cell memory in induced pluripotent stem cells (iPSCs have complicated the selection of the optimal cell type for the generation of iPSC biobanks. To address this issue we compared transcriptomic, epigenetic