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  1. SENP3 grants tight junction integrity and cytoskeleton architecture in mouse Sertoli cells.

    Science.gov (United States)

    Wu, Di; Huang, Chun-Jie; Khan, Faheem Ahmed; Jiao, Xiao-Fei; Liu, Xiao-Ming; Pandupuspitasari, Nuruliarizki Shinta; Brohi, Rahim Dad; Huo, Li-Jun

    2017-08-29

    Germ cells develop in a sophisticated immune privileged microenvironment provided by specialized junctions contiguous the basement membrane of the adjacent Sertoli cells that constituted the blood-testis barrier (BTB) in seminiferous epithelium of testis in mammals. Deciphering the molecular regulatory machinery of BTB activity is central to improve male fertility and the role of post-translational modification including SUMOylation pathway is one of the key factors. Herein, we unveiled the mystery of the SUMO-2/3 specific protease SENP3 (Sentrin-specific protease 3) in BTB dynamics regulation. SENP3 is predominantly expressed in the nucleus of Sertoli and spermatocyte cells in adult mouse testis, and knockdown of SENP3 compromises tight junction in Sertoli cells by destructing the permeability function with a concomitant decline in trans-epithelial electrical resistance in primary Sertoli cells, which could attribute to the conspicuous dysfunction of tight junction (TJ) proteins (e.g., ZO-1, occludin) at the cell-cell interface due to the inactivation of STAT3. Moreover, SENP3 knockdown disrupts F-actin architecture in Sertoli cells through intervening Rac1/CDC42-N-WASP-Arp2/3 signaling pathway and Profilin-1 abundance. Our study pinpoints SENP3 might be a novel determinant of multiple pathways governing BTB dynamics in testis to support germ cells development in mammals.

  2. Claudin-11 and occludin are major contributors to Sertoli cell tight junction function, in vitro

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    Mark J McCabe

    2016-01-01

    Full Text Available The Sertoli cell tight junction (TJ is the key component of the blood-testis barrier, where it sequesters developing germ cells undergoing spermatogenesis within the seminiferous tubules. Hormonally regulated claudin-11 is a critical transmembrane protein involved in barrier function and its murine knockout results in infertility. We aimed to assess quantitatively the significance of the contribution of claudin-11 to TJ function, in vitro, using siRNA-mediated gene silencing. We also conducted an analysis of the contribution of occludin, another intrinsic transmembrane protein of the TJ. Silencing of claudin-11 and/or occludin was conducted using siRNA in an immature rat Sertoli cell culture model. Transepithelial electrical resistance was used to assess quantitatively TJ function throughout the culture. Two days after siRNA treatment, cells were fixed for immunocytochemical localization of junction proteins or lyzed for RT-PCR assessment of mRNA expression. Silencing of claudin-11, occludin, or both resulted in significant decreases in TJ function of 55% (P < 0.01, 51% (P < 0.01, and 62% (P < 0.01, respectively. Data were concomitant with significant decreases in mRNA expression and marked reductions in the localization of targeted proteins to the Sertoli cell TJ. We provide quantitative evidence that claudin-11 contributes significantly (P < 0.01 to Sertoli cell TJ function in vitro. Interestingly, occludin, which is hormonally regulated but not implicated in infertility until late adulthood, is also a significant (P < 0.01 contributor to barrier function. Our data are consistent with in vivo studies that clearly demonstrate a role for these proteins in maintaining normal TJ barrier structure and function.

  3. Gonadotropin suppression in men leads to a reduction in claudin-11 at the Sertoli cell tight junction.

    Science.gov (United States)

    McCabe, M J; Tarulli, G A; Laven-Law, G; Matthiesson, K L; Meachem, S J; McLachlan, R I; Dinger, M E; Stanton, P G

    2016-04-01

    Are Sertoli cell tight junctions (TJs) disrupted in men undergoing hormonal contraception? Localization of the key Sertoli cell TJ protein, claudin-11, was markedly disrupted by 8 weeks of gonadotropin suppression, the degree of which was related to the extent of adluminal germ cell suppression. Sertoli cell TJs are vital components of the blood-testis barrier (BTB) that sequester developing adluminal meiotic germ cells and spermatids from the vascular compartment. Claudin-11 knockout mice are infertile; additionally claudin-11 is spatially disrupted in chronically gonadotropin-suppressed rats coincident with a loss of BTB function, and claudin-11 is disorganized in various human testicular disorders. These data support the Sertoli cell TJ as a potential site of hormonal contraceptive action. BTB proteins were assessed by immunohistochemistry (n = 16 samples) and mRNA (n = 18 samples) expression levels in available archived testis tissue from a previous study of 22 men who had undergone 8 weeks of gonadotropin suppression and for whom meiotic and post-meiotic germ cell numbers were available. The gonadotropin suppression regimens were (i) testosterone enanthate (TE) plus the GnRH antagonist, acyline (A); (ii) TE + the progestin, levonorgestrel, (LNG); (iii) TE + LNG + A or (iv) TE + LNG + the 5α-reductase inhibitor, dutasteride (D). A control group consisted of seven additional men, with three archived samples available for this study. Immunohistochemical localization of claudin-11 (TJ) and other junctional type markers [ZO-1 (cytoplasmic plaque), β-catenin (adherens junction), connexin-43 (gap junction), vinculin (ectoplasmic specialization) and β-actin (cytoskeleton)] and quantitative PCR was conducted using matched frozen testis tissue. Claudin-11 formed a continuous staining pattern at the BTB in control men. Regardless of gonadotropin suppression treatment, claudin-11 localization was markedly disrupted and was broadly associated with the extent of meiotic

  4. Cardiotonic steroid ouabain stimulates expression of blood-testis barrier proteins claudin-1 and -11 and formation of tight junctions in Sertoli cells.

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    Dietze, Raimund; Shihan, Mazen; Stammler, Angelika; Konrad, Lutz; Scheiner-Bobis, Georgios

    2015-04-15

    The interaction of ouabain with the sodium pump induces signalling cascades resembling those triggered by hormone/receptor interactions. In the rat Sertoli cell line 93RS2, ouabain at low concentrations stimulates the c-Src/c-Raf/Erk1/2 signalling cascade via its interaction with the α4 isoform of the sodium pump expressed in these cells, leading to the activation of the transcription factor CREB. As a result of this signalling sequence, ouabain stimulates expression of claudin-1 and claudin-11, which are also controlled by a CRE promoter. Both of these proteins are known to be essential constituents of tight junctions (TJ) between Sertoli cells, and as a result of the ouabain-induced signalling TJ formation between neighbouring Sertoli cells is significantly enhanced by the steroid. Thus, ouabain-treated cell monolayers display higher transepithelial resistance and reduced free diffusion of FITC-coupled dextran in tracer diffusion assays. Taking into consideration that the formation of TJ is indispensable for the maintenance of the blood-testis barrier (BTB) and therefore for male fertility, the actions of ouabain described here and the fact that this and other related cardiotonic steroids (CTS) are produced endogenously suggest a direct influence of ouabain/sodium pump interactions on the maintenance of the BTB and thereby an effect on male fertility. Since claudin-1 and claudin-11 are also present in other blood-tissue barriers, one can speculate that ouabain and perhaps other CTS influence the dynamics of these barriers as well. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Sertoli-Leydig cell tumor

    Science.gov (United States)

    Sertoli-Leydig cell tumor (SLCT) is a rare cancer of the ovaries. The cancer cells produce and release a male sex hormone ... lead to cancer. SLCT starts in the female ovaries. The cancer cells release a male sex hormone. As a ...

  6. Endocytic activity of Sertoli cells grown in bicameral culture chambers

    International Nuclear Information System (INIS)

    Dai, R.X.; Djakiew, D.; Dym, M.

    1987-01-01

    Immature rat Sertoli cells were cultured for 7 to 14 days on Millipore filters impregnated with a reconstituted basement membrane extract in dual-environment (bicameral) culture chambers. Electron microscopy of the cultured cells revealed the presence of rod-shaped mitochondria, Golgi apparatus, rough endoplasmic reticulum, and Sertoli-Sertoli tight junctions, typical of these cells in vivo. The endocytic activity of both the apical and basal surfaces of the Sertoli cells was examined by either adding alpha 2-macroglobulin (alpha 2-M) conjugated to 20 nm gold particles to the apical chamber or by adding 125 I labeled alpha 2-M to the basal chamber. During endocytosis from the apical surface of Sertoli cells, the alpha 2-M-gold particles were bound initially to coated pits and then internalized into coated vesicles within 5 minutes. After 10 minutes, the alpha 2-M-gold was found in multi-vesicular bodies (MVBs) and by 30 minutes it was present in the lysosomes. The proportion of alpha 2-M-gold found within endocytic cell organelles after 1 hour of uptake was used to estimate the approximate time that this ligand spent in each type of organelle. The alpha 2-M-gold was present in coated pits, coated vesicles, multivesicular bodies, and lysosomes for approximately 3, 11, 22, and 24 minutes, respectively. This indicates that the initial stages of endocytosis are rapid, whereas MVBs and lysosomes are relatively long-lived

  7. Cortactin and phagocytosis in isolated Sertoli cells

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    Wolski Katja M

    2005-12-01

    Full Text Available Abstract Background Cortactin, an actin binding protein, has been associated with Sertoli cell ectoplasmic specializations in vivo, based on its immunolocalization around the heads of elongated spermatids, but not previously identified in isolated Sertoli cells. In an in vitro model of Sertoli cell-spermatid binding, cortactin was identified around debris and dead germ cells. Based on this observation, we hypothesized that this actin binding protein may be associated with a non-junction-related physiological function, such as phagocytosis. The purpose of this study was to identify the presence and distribution of cortactin in isolated rat Sertoli cells active in phagocytic activity following the addition of 0.8 μm latex beads. Results Sertoli cell monocultures were incubated with or without follicle stimulating hormone (FSH; 0.1 μg/ml in the presence or absence of cytochalasin D (2 μM, as an actin disrupter. Cortactin was identified by standard immunostaining with anti-cortactin, clone 4F11 (Upstate after incubation times of 15 min, 2 hr, and 24 hr with or without beads. Cells exposed to no hormone and no beads appeared to have a ubiquitous distribution of cortactin throughout the cytoplasm. In the presence of cytochalasin D, cortactin immunostaining was punctate and distributed in a pattern similar to that reported for actin in cells exposed to cytochalasin D. Sertoli cells not exposed to FSH, but activated with beads, did not show cortactin immunostaining around the phagocytized beads at any of the time periods. FSH exposure did not alter the distribution of cortactin within Sertoli cells, even when phagocytic activity was upregulated by the presence of beads. Conclusion Results of this study suggest cortactin is not associated with peripheralized actin at junctional or phagocytic sites. Further studies are necessary to clarify the role of cortactin in Sertoli cells.

  8. A survey of Sertoli cell differentiation in men after gonadotropin suppression and in testicular cancer

    DEFF Research Database (Denmark)

    Tarulli, Gerard A; Stanton, Peter G; Loveland, Kate L

    2013-01-01

    It is widely held that the somatic cell population that is responsible for sperm development and output (Sertoli cells) is terminally differentiated and unmodifiable in adults. It is postulated, with little evidence, that Sertoli cells are not terminally differentiated in some phenotypes of infer...... tubules with CIS and the emergence of strong JAM-A reactivity in seminoma. These findings indicate that adult human Sertoli cells exhibit characteristics of an undifferentiated state in oligospermic men and patients with CIS and seminoma in the presence of germ cell neoplasia....... of infertility and testicular cancer. This study sought to compare markers of Sertoli cell differentiation in normospermic men, oligospermic men (undergoing gonadotropin suppression) and testicular carcinoma in situ (CIS) and seminoma samples. Confocal microscopy was used to assess the expression of markers...... of proliferation (PCNA and Ki67) and functional differentiation (androgen receptor). As additional markers of differentiation, the organization of Sertoli cell tight junction and associated proteins were assessed in specimens with carcinoma in situ. In normal men, Sertoli cells exhibited a differentiated phenotype...

  9. Garlic (Allium sativum) feeding impairs Sertoli cell junctional proteins in male Wistar rat testis: microscopy study.

    Science.gov (United States)

    Hammami, I; Nahdi, A; Atig, F; El May, A; El May, M V

    2016-12-01

    Sertoli cell junctions, such as adhesion junction (AJ), gap junction (GJ) and tight junction (TJ), are important for maintaining spermatogenesis. In previous studies, we showed the inhibitory effect of crude garlic (Allium sativum, As) on spermatogenesis and steroidogenesis. The aim of this work was to complete our investigation on the impact of this plant, especially on Sertoli cell junctional proteins (SCJPs). During 1 month, 24 male rats were divided into groups: group control (0% of As) and treated groups fed 5%, 10% and 15% of As. Light and electron microscopy observations were performed to localise junctional proteins: connexin-43, Zona Occluding-1 and N-cadherin (immunohistochemistry) and to describe junctions. We showed that the specific cells involved in the localisation of the SCJP were similar in both control and treated groups, but with different immunoreactivity intensity between them. The electron microscopy observation focused on TJs between Sertoli cells, constituting the blood-testis barrier, showed ultrastructural changes such as fragmentation of TJs between adjacent Sertoli cell membranes and dilatation of rough endoplasmic reticulum saccules giving an aspect of scale to these junctions. We concluded that crude garlic consumption during 1 month induces perturbations on Sertoli cell junctions. These alterations can explain apoptosis in testicular germ cells previously showed. © 2016 Blackwell Verlag GmbH.

  10. A Rare Cause of Prepubertal Gynecomastia: Sertoli Cell Tumor

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    Fatma Dursun

    2015-01-01

    Full Text Available Prepubertal gynecomastia due to testis tumors is a very rare condition. Nearly 5% of the patients with testicular mass present with gynecomastia. Sertoli cell tumors are sporadic in 60% of the reported cases, while the remaining is a component of multiple neoplasia syndromes such as Peutz-Jeghers syndrome and Carney complex. We present a 4-year-old boy with gynecomastia due to Sertoli cell tumor with no evidence of Peutz-Jeghers syndrome or Carney complex.

  11. Characteristics of retinol accumulation from serum retinol-binding protein by cultured sertoli cells

    International Nuclear Information System (INIS)

    Shingleton, J.L.; Skinner, M.K.; Ong, D.E.

    1989-01-01

    The uptake of retinol was examined in cultured Sertoli cells when retinol was provided as a complex with the transport protein retinol-binding protein (RBP). Sertoil cells accumulated [ 3 H]retinol in a time- and temperature-dependent manner. The change in rate of retinol accumulation occurred when the cells had accumulated approximately 0.53 pmol of retinol/μg of cellular DNA. Extraction and HPLC analysis of the cell-associated radioactivity yielded retinol and retinyl esters, indicating that a significant proportion of the accumulated retinol was esterified. Excess unlabeled retinol-RBP competed with [ 3 H]retinol-RBP for [ 3 H]retinol delivery to the cells, indicating that RBP delivery of retinol was a saturable and competable process. However, free [ 3 H]retinol associated with Sertoli cells in a noncompetable manner. The transport constant for specific retinol accumulation from RBP was 3.0 μM. Neither iodinated nor reductively methylated RBP was accumulated by or tightly bound to Sertoli cells. Competition studies indicated, however, that protein recognition is important in the retinol uptake process. RBP, CRBP, and CRBP(II) competed with [ 3 H]retinol-RBP for [ 3 H]retinol accumulation, but free retinol, retinol-bovine serum albumin, and retinol-β-lactoglobulin did not. These studies indicated that Sertoli cell uptake of retinol involved recognition of the retinol-RBP complex at the cell surface with subsequent internalization of retinol, but not RBP

  12. Assessment of estradiol-induced gene regulation and proliferation in an immortalized mouse immature Sertoli cell line.

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    Kumar, Narender; Srivastava, Swati; Burek, Malgorzata; Förster, Carola Y; Roy, Partha

    2016-03-01

    The number of Sertoli cells during proliferative phase determines the fate of the germ cells in male reproductive system. A well-characterized cell line may help in better understanding of Sertoli cell biology. Hence, the present study assessed estradiol signaling in a mouse immature Sertoli cell line (MSC-1) as an alternative model in place of primary culture of Sertoli cells. In this study, we used MSC-1 cell line, derived from 10-day old mice. The cell cycle parameters were assessed, and the expression and regulation of Sertoli cell-specific secretory genes (ABP; androgen-binding protein) and tight junction genes (claudin-5, occludin, and vimentin) in response to estradiol was studied. The results obtained suggested the presence of both estrogen receptors (ERα and ERβ) in MSC-1 cells. In vitro scratch assay and cell-cycle analysis suggested the proliferative effects of estradiol in both time- and dose-dependent manner. The gene expression profiles of ABP, claudin-5, and occludin showed biphasic regulation at low and high doses of estradiol. Analysis of signaling pathways suggested the activation of extracellular signal-regulated kinase (ERK) pathway with significantly increased pERK/ERK ratio (p<0.05). The results also suggested down regulation in the expression of mir-17 family members (mir-17, mir-20b, and mir-106a) (p<0.05). Considering the limited number of Sertoli cell lines and long-term survival inability of primary culture of Sertoli cells, MSC-1 cells could be a potential cell line for understanding the mechanisms of various cellular events in Sertoli cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Retinol uptake and esterification in the rate sertoli cell

    International Nuclear Information System (INIS)

    Shingleton, J.L.

    1989-01-01

    The mechanism by which Sertoli cells accumulate retinol from retinol-binding protein (RBP) and the cellular metabolism of the accumulated retinol were investigated here using primary cultures of Sertoli cells isolated from 20 day-old rats. Cells incubated with [ 3 H]retinol-RBP accumulated [ 3 H]retinol in a time- and temperature dependent manner. The rate of [ 3 H] retinol accumulation declined when cellular [ 3 H] retinol concentrations reached approximately 0.53 pmol of retinol per μg of cellular DNA, equivalent to the cellular content of cellular retinol-binding protein (CRBP). Excess unlabeled retinol-RBP competed with [ 3 H] retinol-RBP for [ 3 H] retinol delivery to the cells but free retinol did not. Furthermore, free [ 3 H] retinol associated with Sertoli cells in a non-saturable manner. The transport constant for specific retinol accumulation from RBP was 1.9 μM, suggesting that any change in the normal circulating retinol-RBP level would directly affect the rate of retinol accumulation. Competition studies and studies using labeled RBP, cellular energy inhibitors, and lysosomal poisons indicated that the specific retinol accumulation by Sertoli cells occurs by interaction with a cell-surface receptor that internalizes retinol without concomitant internalization of RBP. Extraction and HPLC analysis of the radioactivity associated with Sertoli cells after incubation with [ 3 H] retinol-RBP yielded retinol and retinyl esters

  14. Glycogen Synthase in Sertoli Cells: More Than Glycogenesis?

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    Maldonado, Rodrigo; Mancilla, Héctor; Villarroel-Espíndola, Franz; Slebe, Felipe; Slebe, Juan Carlos; Méndez, Raúl; Guinovart, Joan J; Concha, Ilona I

    2016-11-01

    Sertoli cell metabolism actively maintains the nutritional needs of germ cells. It has been described that after glucose incorporation in Sertoli cells, less than 1% is converted to glycogen suggesting low levels of glycogen synthase activity. Phosphorylation of muscle glycogen synthase (MGS) at serine 640 (pS640MGS) decreases its activity, and this form of the enzyme was discovered as a non-ribosomal protein that modulates the translation of a subset of transcripts in HeLa cells. The aim of our study was to functionally characterize MGS in cultured Sertoli cells, as well as to explore this new feature related to RNA molecules. We detected MGS in the cytoplasm of Sertoli cells as well as in the nuclei. The activity rates of the enzyme were extremely low indicating that MGS is expressed but almost inactive. Protein targeting to glycogen (PTG) overexpression was performed to activate MGS by dephosphorylation. PTG induced glycogen synthesis massively, confirming that this enzyme is present but inactive. This finding correlates with high levels of pS640MGS, which were assayed by phosphatase treatment. To explore a putative new function for MGS in Sertoli cells, we performed RNA immunoprecipitation coupled to microarray studies. The results revealed that MGS co-immunoprecipitated with the several mRNAs and also rRNAs. These findings indicate that MGS is expressed Sertoli cells but in an inactive form, and also support a possibly novel feature of this metabolic enzyme associated with RNA-related molecules. J. Cell. Biochem. 117: 2597-2607, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  15. Rescue of perfluorooctanesulfonate (PFOS)-mediated Sertoli cell injury by overexpression of gap junction protein connexin 43

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    Li, Nan; Mruk, Dolores D.; Chen, Haiqi; Wong, Chris K. C.; Lee, Will M.; Cheng, C. Yan

    2016-07-01

    Perfluorooctanesulfonate (PFOS) is an environmental toxicant used in developing countries, including China, as a stain repellent for clothing, carpets and draperies, but it has been banned in the U.S. and Canada since the late 2000s. PFOS perturbed the Sertoli cell tight junction (TJ)-permeability barrier, causing disruption of actin microfilaments in cell cytosol, perturbing the localization of cell junction proteins (e.g., occluden-ZO-1, N-cadherin-ß-catenin). These changes destabilized Sertoli cell blood-testis barrier (BTB) integrity. These findings suggest that human exposure to PFOS might induce BTB dysfunction and infertility. Interestingly, PFOS-induced Sertoli cell injury associated with a down-regulation of the gap junction (GJ) protein connexin43 (Cx43). We next investigated if overexpression of Cx43 in Sertoli cells could rescue the PFOS-induced cell injury. Indeed, overexpression of Cx43 in Sertoli cells with an established TJ-barrier blocked the disruption in PFOS-induced GJ-intercellular communication, resulting in the re-organization of actin microfilaments, which rendered them similar to those in control cells. Furthermore, cell adhesion proteins that utilized F-actin for attachment became properly distributed at the cell-cell interface, resealing the disrupted TJ-barrier. In summary, Cx43 is a good target that might be used to manage PFOS-induced reproductive dysfunction.

  16. Sertoli cells maintain Leydig cell number and peritubular myoid cell activity in the adult mouse testis.

    Directory of Open Access Journals (Sweden)

    Diane Rebourcet

    Full Text Available The Sertoli cells are critical regulators of testis differentiation and development. In the adult, however, their known function is restricted largely to maintenance of spermatogenesis. To determine whether the Sertoli cells regulate other aspects of adult testis biology we have used a novel transgenic mouse model in which Amh-Cre induces expression of the receptor for Diphtheria toxin (iDTR specifically within Sertoli cells. This causes controlled, cell-specific and acute ablation of the Sertoli cell population in the adult animal following Diphtheria toxin injection. Results show that Sertoli cell ablation leads to rapid loss of all germ cell populations. In addition, adult Leydig cell numbers decline by 75% with the remaining cells concentrated around the rete and in the sub-capsular region. In the absence of Sertoli cells, peritubular myoid cell activity is reduced but the cells retain an ability to exclude immune cells from the seminiferous tubules. These data demonstrate that, in addition to support of spermatogenesis, Sertoli cells are required in the adult testis both for retention of the normal adult Leydig cell population and for support of normal peritubular myoid cell function. This has implications for our understanding of male reproductive disorders and wider androgen-related conditions affecting male health.

  17. Prostatic Adenocarcinoma with Concurrent Sertoli Cell Tumor in a Dog

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    Gill, C. W.

    1981-01-01

    A case of metastatic prostatic adenocarcinoma with concurrent Sertoli cell tumor is presented in an old, miniature Schnauzer dog. The prostatic neoplasm was highly anaplastic and had metastasized widely. Clinical signs were compatible with increased estrogen production. It is interesting to note that the prostatic carcinoma, usually considered to be androgen dependent, developed and metastasized, despite the presence of apparently increased estrogen levels. ImagesFigure 1.Figure 2.Figure 3.Figure 4.Figure 5.Figure 6. PMID:7340923

  18. Sertoli cell origin of testicular androgen-binding protein (ABP)

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    Hagenaes, L [Pediatric Endocrinology Unit, Stockholm; Ritzen, E M; Ploeen, L; Hansson, V; French, F S; Nayfeh, S N

    1975-05-01

    In this report it is suggested that the specific androgen-binding protein (ABP), previously shown to originate in the testes of rat and other species, is produced by the Sertoli cells. This suggestion is based upon the following experimental findings: (1) ABP was found in high concentrations in testicular efferent duct fluid but only in trace amounts in inter-tubular lymph. (2) ABP could be recovered from crude preparations of testes tubules, but not from Leydig cells from the same testes. (3) Testes whose germinal epithelium had been severely damaged by gamma irradiation showed no decrease in ABP content. The transport of ABP to epididymis was also preserved as judged from the levels of ABP in caput epididymis. (4) Testes that were completely devoid of germ cells following prenatal gamma irradiation showed high levels of ABP. These high levels approached zero following hypophysectomy, but could be restored by FSH administration to the hypophysectomized animals. ABP has been well characterized and now provides a valuable experimental tool as an indicator of Sertoli cell function.

  19. Testicular Sertoli cells influence the proliferation and immunogenicity of co-cultured endothelial cells

    International Nuclear Information System (INIS)

    Fan, Ping; He, Lan; Pu, Dan; Lv, Xiaohong; Zhou, Wenxu; Sun, Yining; Hu, Nan

    2011-01-01

    Research highlights: → The proliferation of dramatic increased by co-cultured with Sertoli cells. → VEGF receptor-2 expression of ECs was up-regulated by co-cultured with Sertoli cells. → The MHC expression of ECs induced by INF-γ and IL-6, IL-8 and sICAM induced by TNF-α decreased respectively after co-cultured with Sertoli cells. → ECs co-cultured with Sertoli cells also didn't increase the stimulation index of spleen lymphocytes. -- Abstract: The major problem of the application of endothelial cells (ECs) in transplantation is the lack of proliferation and their immunogenicity. In this study, we co-cultured ECs with Sertoli cells to monitor whether Sertoli cells can influence the proliferation and immunogenicity of co-cultured ECs. Sertoli cells were isolated from adult testicular tissue. ECs were divided into the control group and the experimental group, which included three sub-groups co-cultured with 1 x 10 3 , 1 x 10 4 or 1 x 10 5 cell/ml of Sertoli cells. The growth and proliferation of ECs were observed microscopically, and the expression of vascular endothelial growth factor (VEGF) receptor-2 (KDR) was examined by Western blotting. In another experiment, ECs were divided into the control group, the single culture group and the co-culture group with the optimal concentration of Sertoli cells. After INF-γ and TNF-α were added to the culture medium, MHC II antigen expression was detected by immunofluorescence staining and western blotting; interleukin (IL)-6, IL-8 and soluble intercellular adhesion molecule (sICAM) were measured in the culture medium by ELISA. We demonstrated that 1 x 10 4 cell/ml Sertoli cells promoted the proliferation of co-cultured ECs more dramatically than that in other groups (P 4 cell/ml of the Sertoli cells was most effective in the up-regulation of KDR expression in the co-cultured ECs (P < 0.05). Sertoli cells can effectively suppress INF-γ-induced MHC II antigen expression in co-cultured ECs compared with single

  20. Co-culture with Sertoli cells promotes proliferation and migration of umbilical cord mesenchymal stem cells

    International Nuclear Information System (INIS)

    Zhang, Fenxi; Hong, Yan; Liang, Wenmei; Ren, Tongming; Jing, Suhua; Lin, Juntang

    2012-01-01

    Highlights: ► Co-culture of Sertoli cells (SCs) with human umbilical cord mesenchymal stem cells (UCMSCs). ► Presence of SCs dramatically increased proliferation and migration of UCMSCs. ► Presence of SCs stimulated expression of Mdm2, Akt, CDC2, Cyclin D, CXCR4, MAPKs. -- Abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in transplant therapy. The proliferation and migration of MSCs are the determinants of the efficiency of MSC transplant therapy. Sertoli cells are a kind of “nurse” cells that support the development of sperm cells. Recent studies show that Sertoli cells promote proliferation of endothelial cells and neural stem cells in co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also promote proliferation and migration of UCMSCs. To examine this hypothesis, we isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co-cultured them using a Transwell system. We found that UCMSCs exhibited strong proliferation ability and potential to differentiate to other cell lineages such as osteocytes and adipocytes. The presence of Sertoli cells in co-culture significantly enhanced the proliferation and migration potential of UCMSCs (P < 0.01). Moreover, these phenotypic changes were accompanied with upregulation of multiple genes involved in cell proliferation and migration including phospho-Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC proliferation and migration potential.

  1. Co-culture with Sertoli cells promotes proliferation and migration of umbilical cord mesenchymal stem cells

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    Zhang, Fenxi, E-mail: fxzhang0824@gmail.com [Department of Anatomy, Sanquan College, Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Hong, Yan; Liang, Wenmei [Department of Histology and Embryology, Guiyang Medical University, Guizhou 550004, People' s Republic of China (China); Ren, Tongming [Department of Anatomy, Sanquan College, Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Jing, Suhua [ICU Center, The Third Hospital of Xinxiang Medical University, Henan 453003, People' s Republic of China (China); Lin, Juntang [Stem Cell Center, Xinxiang Medical University, Henan 453003, People' s Republic of China (China)

    2012-10-12

    Highlights: Black-Right-Pointing-Pointer Co-culture of Sertoli cells (SCs) with human umbilical cord mesenchymal stem cells (UCMSCs). Black-Right-Pointing-Pointer Presence of SCs dramatically increased proliferation and migration of UCMSCs. Black-Right-Pointing-Pointer Presence of SCs stimulated expression of Mdm2, Akt, CDC2, Cyclin D, CXCR4, MAPKs. -- Abstract: Human umbilical cord mesenchymal stem cells (hUCMSCs) have been recently used in transplant therapy. The proliferation and migration of MSCs are the determinants of the efficiency of MSC transplant therapy. Sertoli cells are a kind of 'nurse' cells that support the development of sperm cells. Recent studies show that Sertoli cells promote proliferation of endothelial cells and neural stem cells in co-culture. We hypothesized that co-culture of UCMSCs with Sertoli cells may also promote proliferation and migration of UCMSCs. To examine this hypothesis, we isolated UCMSCs from human cords and Sertoli cells from mouse testes, and co-cultured them using a Transwell system. We found that UCMSCs exhibited strong proliferation ability and potential to differentiate to other cell lineages such as osteocytes and adipocytes. The presence of Sertoli cells in co-culture significantly enhanced the proliferation and migration potential of UCMSCs (P < 0.01). Moreover, these phenotypic changes were accompanied with upregulation of multiple genes involved in cell proliferation and migration including phospho-Akt, Mdm2, phospho-CDC2, Cyclin D1, Cyclin D3 as well as CXCR4, phospho-p44 MAPK and phospho-p38 MAPK. These findings indicate that Sertoli cells boost UCMSC proliferation and migration potential.

  2. Roles of miRNAs in microcystin-LR-induced Sertoli cell toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Yuan [Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); Wang, Hui [The Centre for Individualized Medication, Linköping University Hospital, Linköping University, Linköping SE-58185 (Sweden); Wang, Cong [Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); Qiu, Xuefeng [Department of Urology, Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008 (China); Benson, Mikael [The Centre for Individualized Medication, Linköping University Hospital, Linköping University, Linköping SE-58185 (Sweden); Yin, Xiaoqin [Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); Xiang, Zou [Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, University of Gothenburg, Gothenburg (Sweden); Li, Dongmei, E-mail: lidm@nju.edu.cn [Immunology and Reproduction Biology Laboratory & State Key Laboratory of Analytical Chemistry for Life Science, Medical School, Nanjing University, Nanjing, Jiangsu 210093 (China); Jiangsu Key Laboratory of Molecular Medicine, Nanjing University, Nanjing, Jiangsu 210093 (China); and others

    2015-08-15

    Microcystin (MC)-LR, a cyclic heptapeptide, is a potent reproductive system toxin. To understand the molecular mechanisms of MC-induced reproductive system cytotoxicity, we evaluated global changes of miRNA and mRNA expression in mouse Sertoli cells following MC-LR treatment. Our results revealed that the exposure to MC-LR resulted in an altered miRNA expression profile that might be responsible for the modulation of mRNA expression. Bio-functional analysis indicated that the altered genes were involved in specific cellular processes, including cell death and proliferation. Target gene analysis suggested that junction injury in Sertoli cells exposed to MC-LR might be mediated by miRNAs through the regulation of the Sertoli cell-Sertoli cell pathway. Collectively, these findings may enhance our understanding on the modes of action of MC-LR on mouse Sertoli cells as well as the molecular mechanisms underlying the toxicity of MC-LR on the male reproductive system. - Highlights: • miRNAs were altered in Sertoli cells exposed to MC-LR. • Alerted genes were involved in different cell functions including the cell morphology. • MC-LR adversely affected Sertoli cell junction formation through the regulating miRNAs.

  3. Proliferation of Sertoli cells during development of the human testis assessed by stereological methods

    DEFF Research Database (Denmark)

    Cortes, D; Müller, J; Skakkebaek, N E

    1987-01-01

    Sertoli cells were studied using stereological methods in testes obtained from five children who were stillborn, and 31 individuals between 3 months and 40 years of age, who had suffered from sudden, unexpected death. The mean nuclear volume of the Sertoli cells, the numerical density of Sertoli...... cells, and the total number of Sertoli cells per individual were determined by point- and profile-counting of 0.5 micron sections. The nuclear volume of Sertoli cells increased from a median of 120 microns3 (range 53-130) during the period of 3 months to 10 years to 210 microns3 (170-260) in adults...... (greater than 25 years). The numerical density of Sertoli cells decreased from a median of 1200 X 10(6)/cm3 (870-1400) during childhood (3 months to 10 years) to 140 X 10(6)/cm3 (110-260) in adults (greater than 25 years). The total number of Sertoli cells per individual increased significantly from...

  4. Structural characterization of proteoglycans produced by testicular peritubular cells and Sertoli cells

    International Nuclear Information System (INIS)

    Skinner, M.K.; Fritz, I.B.

    1985-01-01

    The structural characteristics of proteoglycans produced by seminiferous peritubular cells and by Sertoli cells are defined. Peritubular cells secrete two proteoglycans designated PC I and PC II. PC I is a high molecular mass protein containing chondroitin glycosaminoglycan (GAG) chains (maximum 70 kDa). PC II has a protein core of 45 kDa and also contains chondroitin GAG chains (maximum 70 kDa). Preliminary results imply that PC II may be a degraded or processed form of PC I. Sertoli cells secrete two different proteoglycans, designated SC I and SC II. SC I is a large protein containing both chondroitin (maximum 62 kDa) and heparin (maximum 15 kDa) GAG chains. Results obtained suggest that this novel proteoglycan contains both chondroitin and heparin GAG chains bound to the same core protein. SC II has a 50-kDa protein core and contains chondroitin (maximum 25 kDa) GAG chains. A proteoglycan obtained from extracts of Sertoli cells is described which contains heparin (maximum 48 kDa) GAG chains. In addition, Sertoli cells secrete a sulfoprotein, SC III, which is not a proteoglycan. The stimulation by follicle-stimulating hormone of the incorporation of [ 35 S]SO 2 ) -4 ) into moieties secreted by Sertoli cells is shown to represent an increased production or sulfation of SC III, and not an increased production or sulfation of proteoglycans. Results are discussed in relation to the possible functions of proteoglycans in the seminiferous tubule

  5. Transplantation of co-aggregates of Sertoli cells and islet cells into liver without immunosuppression.

    Science.gov (United States)

    Takemoto, Naohiro; Liu, Xibao; Takii, Kento; Teramura, Yuji; Iwata, Hiroo

    2014-02-15

    Transplantation of islets of Langerhans (islets) was used to treat insulin-dependent diabetes mellitus. However, islet grafts must be maintained by administration of immunosuppressive drugs, which can lead to complications in the long term. An approach that avoids immunosuppressive drug use is desirable. Co-aggregates of Sertoli cells and islet cells from BALB/c mice that were prepared by the hanging drop method were transplanted into C57BL/6 mouse liver through the portal vein as in human clinical islet transplantation. The core part of the aggregates contained mainly Sertoli cells, and these cells were surrounded by islet cells. The co-aggregates retained the functions of both Sertoli and islet cells. When 800 co-aggregates were transplanted into seven C57BL/6 mice via the portal vein, six of seven recipient mice demonstrated quasi-normoglycemia for more than 100 days. The hanging drop method is suitable for preparing aggregates of Sertoli and islet cells for transplantation. Notably, transplantation of these allogeneic co-aggregates into mice with chemically induced diabetes via the portal vein resulted in long-term graft survival without systemic immunosuppression.

  6. Efficient transfection of DNA into primarily cultured rat sertoli cells by electroporation.

    Science.gov (United States)

    Li, Fuping; Yamaguchi, Kohei; Okada, Keisuke; Matsushita, Kei; Enatsu, Noritoshi; Chiba, Koji; Yue, Huanxun; Fujisawa, Masato

    2013-03-01

    The expression of exogenous DNA in Sertoli cells is essential for studying its functional genomics, pathway analysis, and medical applications. Electroporation is a valuable tool for nucleic acid delivery, even in primarily cultured cells, which are considered difficult to transfect. In this study, we developed an optimized protocol for electroporation-based transfection of Sertoli cells and compared its efficiency with conventional lipofection. Sertoli cells were transfected with pCMV-GFP plasmid by square-wave electroporation under different conditions. After transfection of plasmid into Sertoli cells, enhanced green fluorescent protein (EGFP) expression could be easily detected by fluorescent microscopy, and cell survival was evaluated by dye exclusion assay using Trypan blue. In terms of both cell survival and the percentage expressing EGFP, 250 V was determined to produce the greatest number of transiently transfected cells. Keeping the voltage constant (250 V), relatively high cell survival (76.5% ± 3.4%) and transfection efficiency (30.6% ± 5.6%) were observed with a pulse length of 20 μm. The number of pulses significantly affected cell survival and EGFP expression (P transfection methods, the transfection efficiency of electroporation (21.5% ± 5.7%) was significantly higher than those of Lipofectamine 2000 (2.9% ± 1.0%) and Effectene (1.9% ± 0.8%) in this experiment (P transfection of Sertoli cells.

  7. Sertoli cell-specific ablation of miR-17-92 cluster significantly alters whole testis transcriptome without apparent phenotypic effects.

    Science.gov (United States)

    Hurtado, Alicia; Real, Francisca M; Palomino, Rogelio; Carmona, Francisco David; Burgos, Miguel; Jiménez, Rafael; Barrionuevo, Francisco J

    2018-01-01

    MicroRNAs are frequently organized into polycistronic clusters whose transcription is controlled by a single promoter. The miR-17-92 cluster is expressed in most embryonic and postnatal organs. It is a potent oncogene associated to several types of cancer and it is involved in several important developmental processes. In the testis, expression of the miR-17-92 cluster in the germ cells is necessary to maintain normal spermatogenesis. This cluster is also expressed in Sertoli cells (the somatic cells of the seminiferous tubules), which require miRNAs for correct cell development and survival. To study the possible role of miR-17-92 in Sertoli cell development and function and, in order to overcome the postnatal lethality of miR-17-92-/ mice, we conditionally deleted it in embryonic Sertoli cells shortly after the sex determination stage using an Amh-Cre allele. Mutant mice developed apparently normal testes and were fertile, but their testis transcriptomes contained hundreds of moderately deregulated genes, indicating that testis homeostasis is tightly controlled in mammals and that miR-17-92 expression in Sertoli cells contribute to maintain normal gene expression levels, but is unnecessary for testis development and function. Our results show that significant deregulation of hundreds of genes might have no functional consequences.

  8. The interaction between Sertoli cells and luekemia inhibitory factor on the propagation and differentiation of spermatogonial stem cells in vitro.

    Science.gov (United States)

    Rastegar, Tayebeh; Habibi Roudkenar, Mehryar; Parvari, Soraya; Baazm, Maryam

    2015-11-01

    Sertoli cells play a pivotal role in creating microenvironments essential for spermatogonial stem cells (SSCs) self-renewal and commitment to differentiation. Maintenance of SSCs and or induction of in vitro spermiogenesis may provide a therapeutic strategy to treat male infertility. This study investigated the role of luekemia inhibitory factor (LIF) on the propagation of SSCs and both functions of Sertoli cells on the proliferation and differentiation of these cells. SSCs were sorted from the testes of adult male mice by magnetic activated cell sorting and thymus cell antigen 1 antibody. On the other hand, isolated Sertoli cells were enriched using lectin coated plates. SSCs were cultured on Sertoli cells for 7 days in the absence or presence of LIF. The effects of these conditions were evaluated by microscopy and expression of meiotic and post meiotic transcripts by reverse transcriptase polymerase chain reaction. Our data showed that SSCs co-cultured with Sertoli cells in the presence of LIF formed colonies on top of the Sertoli cells. These colonies had alkaline phosphatesase activity and expressed SSCs specific genes. SSCs were enjoyed limited development after the mere removal of LIF, and exhibiting expression of meiotic and postmeiotic transcript and loss of SSCs specific gene expression (p< 0.05). Our findings represent co-culture of SSCs with Sertoli cells provides conditions that may allow efficient proliferation and differentiation of SSCs for male infertility treatment.

  9. The interaction between Sertoli cells and luekemia inhibitory factor on the propagation and differentiation of spermatogonial stem cells in vitro

    Directory of Open Access Journals (Sweden)

    Tayebeh Rastegar

    2015-11-01

    Full Text Available Background: Sertoli cells play a pivotal role in creating microenvironments essential for spermatogonial stem cells (SSCs self-renewal and commitment to differentiation. Maintenance of SSCs and or induction of in vitro spermiogenesis may provide a therapeutic strategy to treat male infertility. Objective: This study investigated the role of luekemia inhibitory factor (LIF on the propagation of SSCs and both functions of Sertoli cells on the proliferation and differentiation of these cells. Materials and Methods: SSCs were sorted from the testes of adult male mice by magnetic activated cell sorting and thymus cell antigen 1 antibody. On the other hand, isolated Sertoli cells were enriched using lectin coated plates. SSCs were cultured on Sertoli cells for 7 days in the absence or presence of LIF. The effects of these conditions were evaluated by microscopy and expression of meiotic and post meiotic transcripts by reverse transcriptase polymerase chain reaction. Results: Our data showed that SSCs co-cultured with Sertoli cells in the presence of LIF formed colonies on top of the Sertoli cells. These colonies had alkaline phosphatesase activity and expressed SSCs specific genes. SSCs were enjoyed limited development after the mere removal of LIF, and exhibiting expression of meiotic and postmeiotic transcript and loss of SSCs specific gene expression (p< 0.05. Conclusion: Our findings represent co-culture of SSCs with Sertoli cells provides conditions that may allow efficient proliferation and differentiation of SSCs for male infertility treatment.

  10. Altered lipid homeostasis in Sertoli cells stressed by mild hyperthermia.

    Directory of Open Access Journals (Sweden)

    Ana S Vallés

    Full Text Available Spermatogenesis is known to be vulnerable to temperature. Exposures of rat testis to moderate hyperthermia result in loss of germ cells with survival of Sertoli cells (SC. Because SC provide structural and metabolic support to germ cells, our aim was to test the hypothesis that these exposures affect SC functions, thus contributing to germ cell damage. In vivo, regularly repeated exposures (one of 15 min per day, once a day during 5 days of rat testes to 43 °C led to accumulation of neutral lipids. This SC-specific lipid function took 1-2 weeks after the last of these exposures to be maximal. In cultured SC, similar daily exposures for 15 min to 43 °C resulted in significant increase in triacylglycerol levels and accumulation of lipid droplets. After incubations with [3H]arachidonate, the labeling of cardiolipin decreased more than that of other lipid classes. Another specifically mitochondrial lipid metabolic function, fatty acid oxidation, also declined. These lipid changes suggested that temperature affects SC mitochondrial physiology, which was confirmed by significantly increased degrees of membrane depolarization and ROS production. This concurred with reduced expression of two SC-specific proteins, transferrin, and Wilms' Tumor 1 protein, markers of SC secretion and differentiation functions, respectively, and with an intense SC cytoskeletal perturbation, evident by loss of microtubule network (α-tubulin and microfilament (f-actin organization. Albeit temporary and potentially reversible, hyperthermia-induced SC structural and metabolic alterations may be long-lasting and/or extensive enough to respond for the decreased survival of the germ cells they normally foster.

  11. In vitro production of haploid cells after coculture of CD49f+ with Sertoli cells from testicular sperm extraction in nonobstructive azoospermic patients.

    Science.gov (United States)

    Riboldi, Marcia; Rubio, Carmen; Pellicer, Antonio; Gil-Salom, Manuel; Simón, Carlos

    2012-09-01

    To isolate CD49f+ cells from testicular sperm extraction (TESE) samples of azoospermic patients and induce meiosis by coculturing these cells with Sertoli cells. Prospective analysis. Research center. Obstructive azoospermic (OA) and nonobstructive azoospermic (NOA) patients. TESE, with enzymatic dissociation of samples to obtain a cell suspension, which was cultured for 4 days with 4 ng/mL GDNF. The CD49f+ cells were sorted using fluorescence-activated cell sorting (FACS) as a marker to identify spermatogonial stem cells (SSCs), which were cocultured with Sertoli cells expressing red fluorescent protein (RFP) in knockout serum replacement (KSR) media with addition of 1,000 IU/mL of follicle-stimulating hormone (FSH), 1 μM testosterone, 40 ng/mL of GDNF, and 2 μM retinoic acid (RA) for 15 days in culture at 37°C and 5% CO(2) to induce meiotic progression. Cells were collected and analyzed by immunofluorescence for meiosis progression with specific markers SCP3 and CREST, and they were confirmed by fluorescence in situ hybridization (FISH). Isolation of CD49f+ cells and coculture with Sertoli cells, meiosis progression in vitro, assessment of SSCs and meiotic markers real-time polymerase chain reaction (RT-PCR), immunohistochemical analysis, and FISH. The CD49f+ isolated from the of total cell count in the TESE samples of azoospermic patients varied from 5.45% in OA to 2.36% in NOA. Sertoli cells were obtained from the same TESE samples, and established protocols were used to characterize them as positive for SCF, rGDNF, WT1, GATA-4, and vimentin, with the presence of tight junctions and lipid droplets shown by oil red staining. After isolation, the CD49f+ cells were cocultured with RFP Sertoli cells in a 15-day time-course experiment. Positive immunostaining for meiosis markers SCP3 and CREST on days 3 to 5 was noted in the samples obtained from one NOA patient. A FISH analysis for chromosomes 13, 18, 21, X, and Y confirmed the presence of haploid cells on day

  12. Experimental induction of ovarian Sertoli cell tumors in rats by N-nitrosoureas.

    Science.gov (United States)

    Maekawa, A; Onodera, H; Tanigawa, H; Furuta, K; Kanno, J; Ogiu, T; Hayashi, Y

    1987-01-01

    Spontaneous ovarian tumors are very rare in ACI, Wistar, F344 and Donryu rats; the few neoplasms found are of the granulosa/theca cell type. Ovarian tumors were also rare in these strains of rats when given high doses of N-alkyl-N-nitrosoureas continuously in the drinking water for their life-span; however, relatively high incidences of Sertoli cell tumors or Sertoli cell tumors mixed with granulosa cell tumors were induced in Donryu rats after administration of either a 400 ppm N-ethyl-N-nitrosourea solution in the drinking water for 4 weeks or as a single dose of 200 mg N-propyl-N-nitrosourea per kg body weight by stomach tube. Typical Sertoli cell tumors consisted of solid areas showing tubular formation. The tubules were lined by tall, columnar cells, with abundant, faintly eosinophilic, often vacuolated cytoplasm, and basally oriented, round nuclei, resembling seminiferous tubules in the testes. In some cases, Sertoli cell tumor elements were found mixed with areas of granulosa cells. The induction of ovarian Sertoli cell tumors in Donryu rats by low doses of nitrosoureas may provide a useful model for these tumors in man. Images PLATE 1. PLATE 2. PLATE 3. PLATE 4. PLATE 5. PLATE 6. PLATE 7. PLATE 8. PLATE 9. PLATE 10. PLATE 11. PLATE 12. PLATE 13. PLATE 14. PLATE 15. PLATE 16. PMID:3665856

  13. Identification of Proliferative and Apoptotic Sertoli Cells Using Fluorescence and Confocal Microscopy.

    Science.gov (United States)

    Martínez-Hernández, Jesús; Seco-Rovira, Vicente; Beltrán-Frutos, Ester; Quesada-Cubo, Victor; Ferrer, Concepción; Pastor, Luis Miguel

    2018-01-01

    Sertoli cells, the testicular somatic cells of the seminiferous epithelium, are vital for the survival of the epithelium. They undergo proliferation and apoptosis during fetal, neonatal, and prepubertal development. Apoptosis is increased in certain situations such as exposure to many substances, for example, toxics, or short photoperiod in the non-breeding season of some mammals. Therefore, it has always been considered that Sertoli cells that reach adulthood are quiescent cells, that is to say, nonproliferative, do not die, are terminally differentiated, and whose numbers remain constant. Recently, a degree of both proliferation and apoptosis has been observed in normal adult conditions, suggesting that consideration of this cell as quiescent may be subject to change. All this make it necessary to use histochemical techniques to demonstrate whether Sertoli cells are undergoing proliferation or apoptosis in histological sections and to allow the qualitative and quantitative study of these. In this chapter, we present two double-staining techniques that can be used for identifying Sertoli cells in proliferation or apoptosis by fluorescence microscopy. In both, the Sertoli cells are identified by an immunohistochemistry for vimentin followed by an immunohistochemistry for PCNA or a TUNEL histochemistry.

  14. Selective ablation of the androgen receptor in mouse sertoli cells affects sertoli cell maturation, barrier formation and cytoskeletal development.

    Directory of Open Access Journals (Sweden)

    Ariane Willems

    2010-11-01

    Full Text Available The observation that mice with a selective ablation of the androgen receptor (AR in Sertoli cells (SC (SCARKO mice display a complete block in meiosis supports the contention that SC play a pivotal role in the control of germ cell development by androgens. To delineate the physiological and molecular mechanism responsible for this control, we compared tubular development in pubertal SCARKO mice and littermate controls. Particular attention was paid to differences in SC maturation, SC barrier formation and cytoskeletal organization and to the molecular mediators potentially involved. Functional analysis of SC barrier development by hypertonic perfusion and lanthanum permeation techniques and immunohistochemical analysis of junction formation showed that SCARKO mice still attempt to produce a barrier separating basal and adluminal compartment but that barrier formation is delayed and defective. Defective barrier formation was accompanied by disturbances in SC nuclear maturation (immature shape, absence of prominent, tripartite nucleoli and SC polarization (aberrant positioning of SC nuclei and cytoskeletal elements such as vimentin. Quantitative RT-PCR was used to study the transcript levels of genes potentially related to the described phenomena between day 8 and 35. Differences in the expression of SC genes known to play a role in junction formation could be shown from day 8 for Cldn11, from day 15 for Cldn3 and Espn, from day 20 for Cdh2 and Jam3 and from day 35 for ZO-1. Marked differences were also noted in the transcript levels of several genes that are also related to cell adhesion and cytoskeletal dynamics but that have not yet been studied in SC (Actn3, Ank3, Anxa9, Scin, Emb, Mpzl2. It is concluded that absence of a functional AR in SC impedes the remodeling of testicular tubules expected at the onset of spermatogenesis and interferes with the creation of the specific environment needed for germ cell development.

  15. STEREOLOGICAL QUANTITATION OF LEYDIG AND SERTOLI CELLS IN THE TESTIS FROM YOUNG AND OLD MEN

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    Peter M Petersen

    2011-05-01

    Full Text Available One of the newer stereological methods, the optical fractionator, was applied to the study of the effects of ageing on the human testis. The estimated total number of Sertoli and Leydig cells per testis in men younger than 30 years were 430×106 (CV = SD/mean = 0.35 and 117×106 (CV = 0.53, respectively, while in men older than 50 years the estimated total Sertoli cell number was 266×106 (CV = 0.46 and the mean Leydig cell number 83×106 (CV = 0.53. The difference between the number of Sertoli cells in men younger than 30 years compared with men older than 50 years was close to statistical significance (p = 0.052 while no differences was found in total Leydig cell number (p = 0.22.

  16. The roles of Sertoli cells in fate determinations of spermatogonial stem cells

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    Maryam Khanehzad

    2016-03-01

    Full Text Available Background: Spermatogenesis is a complex and highly organized process of proliferation and differentiation of spermatogonial stem cells. Spermatogonial stem cells (SSCs as a unique stem cell have the potential to self-renewal, differentiation and transmit genetic information to the next generation and play a vital role in maintaining fertility. Sertoli cells as the only somatic cells within the seminiferous epithelium play central roles in the formation of niche and balance between self-renewal and differentiation by secrete many growth factors. Given the importance and widespread use of SSCs, particularly in the treatment of infertility, the aim of this study was to create an optimal environment for the proliferation of SSCs. So we decided to study of undifferentiated (ID4 and differentiated (c-Kit gene expression in SSCs followed by co-culture with Sertoli cells for a one-month. Methods: This experimental study was conducted from November 2013 to December 2014 in Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, on immature NMRI mouse (6-3 days old. Initially, Sertoli cells and SSCs were isolated from neonates mouse testes during the two-step enzymatic digestion characteristics Sertoli cells with vimentin marker and SSCs with promyelocytic leukemia zinc-finger (PLZF marker were confirmed. Then SSCs were cultured in two groups: co-culture with Sertoli and without co-culture (control. Undifferentiated (ID4 and differentiation (c-Kit gene expression were evaluated by Real-time PCR technique. Results: Spermatogonial stem cells purity was obtained 66.91% by flow cytometry. The relative expression levels of gene ID4 in co-culture group at the end of each week, compared to the control group showed a significant increase (P<0.05. While the expression of this gene significantly decreased in each group over time (P<0.05. The results of the comparison of the relative expression of c-Kit gene in co-culture group are

  17. Testosterone regulates the autophagic clearance of androgen binding protein in rat Sertoli cells

    Science.gov (United States)

    Ma, Yi; Yang, Hao-Zheng; Xu, Long-Mei; Huang, Yi-Ran; Dai, Hui-Li; Kang, Xiao-Nan

    2015-01-01

    Dysregulation of androgen-binding protein (ABP) is associated with a number of endocrine and andrology diseases. However, the ABP metabolism in Sertoli cells is largely unknown. We report that autophagy degrades ABP in rat Sertoli cells, and the autophagic clearance of ABP is regulated by testosterone, which prolongs the ABP biological half-life by inhibiting autophagy. Further studies identified that the autophagic clearance of ABP might be selectively regulated by testosterone, independent of stress (hypoxia)-induced autophagic degradation. These data demonstrate that testosterone up-regulates ABP expression at least partially by suppressing the autophagic degradation. We report a novel finding with respect to the mechanisms by which ABP is cleared, and by which the process is regulated in Sertoli cells. PMID:25745956

  18. Lipopolysaccharide inhibits the self-renewal of spermatogonial stem cells in vitro via downregulation of GDNF expression in Sertoli cells.

    Science.gov (United States)

    Zhang, Xiaoli; Shi, Kun; Li, Yi; Zhang, Haiyu; Hao, Jing

    2014-06-01

    Lipopolysaccharide (LPS) can reduce sperm count and sperm quality. The molecular mechanisms underlying this process are not fully understood. In this report, we investigated the effects of LPS-treated Sertoli cells on self-renewal and differentiation of spermatogoinial stem cells (SSCs). Sertoli cell cultures were established and incubated with LPS (10μg/ml) for 1, 2 or 3 days, respectively. The culture media were collected and used as conditioned media (CM) to culture SSCs. The expression of glial cell-derived neurotrophic factor (GDNF), stem cell factor (SCF) and bone morphogenetic protein 4 (BMP4) in Sertoli cells treated with LPS was analyzed by RT-PCR and Western blotting. The results showed that the expression of SSC differentiation markers, c-kit and Sohlh2, was increased, while the expression of SSC self-renewal markers, plzf, oct4, and PCNA, was repressed when cultured in CM from LPS-treated Sertoli cells. GDNF levels in Sertoli cells and CM reduced dramatically after LPS treatments, while SCF and BMP4 levels did not show any significant changes. Moreover, correlated with the GDNF levels in CM, GDNF target genes, Bcl6b and Etv5, were reduced markedly in SSCs. Our results suggest that LPS inhibits the expression of GDNF in Sertoli cells, and might prevent the SSC self-renewal via down-regulation of GDNF target genes. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Bilateral sertoli-leydig cell tumor of the ovary: A rare case report

    OpenAIRE

    Alam Kiran; Maheshwari Veena; Rashid Seema; Bhargava Shruti

    2009-01-01

    Sertoli leydig cell tumors also known as arrhenoblastoma, are a rare member of the sex cord-stromal tumor group of ovarian and testicular cancers, comprising less than 1% of all ovarian tumors, which occur in young adults and are almost always unilateral. We hereby report a case of a 17-year-old female presenting with a short history of irregular menses and an abdominal lump, which was histologically proven to be a bilateral sertoli leydig cell tumor of the ovary, an exceptionally rare...

  20. Bilateral sertoli-leydig cell tumor of the ovary: A rare case report

    Directory of Open Access Journals (Sweden)

    Alam Kiran

    2009-01-01

    Full Text Available Sertoli leydig cell tumors also known as arrhenoblastoma, are a rare member of the sex cord-stromal tumor group of ovarian and testicular cancers, comprising less than 1% of all ovarian tumors, which occur in young adults and are almost always unilateral. We hereby report a case of a 17-year-old female presenting with a short history of irregular menses and an abdominal lump, which was histologically proven to be a bilateral sertoli leydig cell tumor of the ovary, an exceptionally rare entity in itself.

  1. Intrauterine bisphenol A exposure leads to stimulatory effects on Sertoli cell number in rats

    International Nuclear Information System (INIS)

    Wistuba, Joachim; Brinkworth, Martin H.; Schlatt, Stefan; Chahoud Ibrahim; Nieschlag, Eberhard

    2003-01-01

    Using the optical disector for quantifying cell numbers, we investigated whether oral treatment of rats on days 6-21 of gestation with the weakly estrogenic bisphenol A (BPA, 0.1 or 50 mg/kg) or the highly estrogenic ethinyl estradiol (EE, 0.02 mg/kg) alters testicular histology, in those offspring 9-12 month of age. Since production of male germ cells depends on Sertoli cell number, possible changes in that parameter were investigated using unbiased stereology. Spermatogenesis was qualitatively normal in all groups. BPA increases Sertoli cell number per organ but not when expressed as per gram testis. EE did not affect cell number per organ but did affect numbers on a per gram testis basis due to a lowered testis weight. I contrast to the lowering of Sertoli cell numbers that might have been expected according to the estrogen hypothesis, intrauterine administration of these xenoestrogens in fact resulted in minor increases in Sertoli cell numbers and had no qualitative effect on spermatogenesis

  2. Protein secretory patterns of rat Sertoli and peritubular cells are influenced by culture conditions

    International Nuclear Information System (INIS)

    Kierszenbaum, A.L.; Crowell, J.A.; Shabanowitz, R.B.; DePhilip, R.M.; Tres, L.L.

    1986-01-01

    An approach combining two-dimensional gel electrophoresis and autoradiography was used to correlate patterns of secretory proteins in cultures of Sertoli and peritubular cells with those observed in the incubation medium from segments of seminiferous tubules. Sertoli cells in culture and in seminiferous tubules secreted three proteins designated S70 (Mr 72,000-70,000), S45 (Mr 45,000), and S35 (Mr 35,000). Cultured Sertoli and peritubular cells and incubated seminiferous tubules secreted two proteins designated SP1 (Mr 42,000) and SP2 (Mr 50,000). SP1 and S45 have similar Mr but differ from each other in isoelectric point (pI). Cultured peritubular cells secreted a protein designated P40 (Mr 40,000) that was also seen in intact seminiferous tubules but not in seminiferous tubules lacking the peritubular cell wall. However, a large number of high-Mr proteins were observed only in the medium of cultured peritubular cells but not in the incubation medium of intact seminiferous tubules. Culture conditions influence the morphology and patterns of protein secretion of cultured peritubular cells. Peritubular cells that display a flat-stellate shape transition when placed in culture medium free of serum (with or without hormones and growth factors), accumulate various proteins in the medium that are less apparent when these cells are maintained in medium supplemented with serum. Two secretory proteins stimulated by follicle-stimulating hormone (FSH) (designated SCm1 and SCm2) previously found in the medium of cultured Sertoli cells, were also observed in the incubation medium of seminiferous tubular segments stimulated by FSH. Results of this study show that, although cultured Sertoli and peritubular cells synthesize and secrete proteins also observed in segments of incubated seminiferous tubules anther group of proteins lacks seminiferous tubular correlates

  3. Exploration of intrinsic and extrinsic apoptotic pathways in zearalenone-treated rat sertoli cells.

    Science.gov (United States)

    Xu, Ming-Long; Hu, Jin; Guo, Bao-Ping; Niu, Ya-Ru; Xiao, Cheng; Xu, Yin-Xue

    2016-12-01

    Zearalenone (ZEA) is a nonsteroidal estrogenic mycotoxin produced mainly by Fusarium. ZEA causes reproductive disorders and is both cytotoxic and genotoxic in animals; however, little is known regarding the molecular mechanism(s) leading to ZEA toxicity. Sertoli cells are somatic cells that support the development of spermatogenic cells. The objective of this study was to explore the effects of ZEA on the proliferation, apoptosis, and necrosis of rat Sertoli cells to uncover signaling pathways underlying ZEA cytotoxicity. ZEA reduced the proliferation of rat Sertoli cells in a dose-dependent manner, as indicated by a CCK8 assay, while flow cytometry revealed that ZEA caused both apoptosis and necrosis. Immunoblotting revealed that ZEA treatment increased the ratio of Bax/Bcl-2, as well as the expression of FasL and caspases-3, -8, and -9, in a dose-dependent manner. Collectively, these data suggest that ZEA induced apoptosis and necrosis in rat Sertoli cells via extrinsic and intrinsic apoptotic pathways. This study provides new insights into the molecular mechanisms by which ZEA exhibits cytotoxicity. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1731-1739, 2016. © 2015 Wiley Periodicals, Inc.

  4. CTNNB1 signaling in sertoli cells downregulates spermatogonial stem cell activity via WNT4.

    Directory of Open Access Journals (Sweden)

    Alexandre Boyer

    Full Text Available Constitutive activation of the WNT signaling effector CTNNB1 (β-catenin in the Sertoli cells of the Ctnnb1(tm1Mmt/+;Amhr2(tm3(creBhr/+ mouse model results in progressive germ cell loss and sterility. In this study, we sought to determine if this phenotype could be due to a loss of spermatogonial stem cell (SSC activity. Reciprocal SSC transplants between Ctnnb1(tm1Mmt/+;Amhr2(tm3(creBhr/+ and wild-type mice showed that SSC activity is lost in Ctnnb1(tm1Mmt/+;Amhr2(tm3(creBhr/+ testes over time, whereas the mutant testes could not support colonization by wild-type SSCs. Microarray analyses performed on cultured Sertoli cells showed that CTNNB1 induces the expression of genes associated with the female sex determination pathway, which was also found to occur in Ctnnb1(tm1Mmt/+;Amhr2(tm3(creBhr/+ testes. One CTNNB1 target gene encoded the secreted signaling molecule WNT4. We therefore tested the effects of WNT4 on SSC-enriched germ cell cultures, and found that WNT4 induced cell death and reduced SSC activity without affecting cell cycle. Conversely, conditional inactivation of Wnt4 in the Ctnnb1(tm1Mmt/+;Amhr2(tm3(creBhr/+ model rescued spermatogenesis and male fertility, indicating that WNT4 is the major effector downstream of CTNNB1 responsible for germ cell loss. Furthermore, WNT4 was found to signal via the CTNNB1 pathway in Sertoli cells, suggesting a self-reinforcing positive feedback loop. Collectively, these data indicate for the first time that ectopic activation of a signaling cascade in the stem cell niche depletes SSC activity through a paracrine factor. These findings may provide insight into the pathogenesis of male infertility, as well as embryonic gonadal development.

  5. The effects of the obesogen tributyltin on the metabolism of Sertoli cells cultured ex vivo.

    Science.gov (United States)

    Cardoso, Ana M; Alves, Marco G; Sousa, Ana C; Jarak, Ivana; Carvalho, Rui A; Oliveira, Pedro F; Cavaco, José E; Rato, Luís

    2018-02-01

    Human exposure to environmental contaminants is widespread. Some of these contaminants have the ability to interfere with adipogenesis, being thus considered as obesogens. Recently, obesogens have been singled out as a cause of male infertility. Sertoli cells (SCs) are essential for male fertility and their metabolic performance, especially glucose metabolism, is under a tight endocrine control, being essential for the success of spermatogenesis. Herein, we studied the impact of the model obesogen tributyltin in the metabolic profile of SCs. For that, ex vivo-cultured rat SCs were exposed to increasing doses of tributyltin. SCs proliferation was evaluated by the sulforhodamine B assay and the maturation state of the cells was assessed by the expression of specific markers (inhibin B and the androgen receptor) by quantitative polymerase chain reaction. The metabolic profile of SCs was established by studying metabolites consumption/production by nuclear magnetic resonance spectroscopy and by analyzing the expression of key transporters and enzymes involved in glycolysis by Western blot. The proliferation of SCs was only affected in the cells exposed to the highest dose (1000 nM) of tributyltin. Notably, SCs exposed to 10 nM tributyltin decreased the consumption of glucose and pyruvate, as well as the production of lactate. The decreased lactate production hampers the development of germ cells. Intriguingly, the lowest levels of tributyltin were more prone to modulate the expression of key players of the glycolytic pathway. This is the first study showing that tributyltin reprograms glucose metabolism of SCs under ex vivo conditions, suggesting new targets and mechanisms through which obesogens modulate the metabolism of SCs and thus male (in)fertility.

  6. miR-26a suppresses autophagy in swine Sertoli cells by targeting ULK2.

    Science.gov (United States)

    Ran, M; Li, Z; Cao, R; Weng, B; Peng, F; He, C; Chen, B

    2018-05-14

    A large number of microRNAs (miRNAs) have been detected from porcine testicular tissues thanks to the development of high-throughput sequencing technology. However, the regulatory roles of most identified miRNAs in swine testicular development or spermatogenesis are poorly understood. In our previous study, ULK2 (uncoordinated-51-like kinase 2) was predicted as a target gene of miR-26a. In this study, we aimed to investigate the role of miR-26a in swine Sertoli cell autophagy. The relative expression of miR-26a and ULK2 levels has a significant negative correlation (R 2  = .5964, p ≤ .01) in nine developmental stages of swine testicular tissue. Dual-luciferase reporter assay results show that miR-26a directly targets the 3'UTR of the ULK2 gene (position 618-624). In addition, both the mRNA and protein expression of ULK2 were downregulated by miR-26a in swine Sertoli cells. These results indicate that miR-26a targets the ULK2 gene and downregulates its expression in swine Sertoli cells. Based on the expression of marker genes (LC3, p62 and Beclin-1), overexpression of miR-26a or knock-down of ULK2 inhibits swine Sertoli cell autophagy. Taken together, these findings demonstrate that miR-26a suppresses autophagy in swine Sertoli cells by targeting ULK2. © 2018 Blackwell Verlag GmbH.

  7. Different roles of prepubertal and postpubertal germ cells and Sertoli cells in the regulation of serum inhibin B levels

    DEFF Research Database (Denmark)

    Andersson, A M; Müller, J; Skakkebaek, N E

    1998-01-01

    testis, intense immunostaining for the betaB-subunit was evident in germ cells from the pachytene spermatocyte to early spermatid stages and to a lesser degree in Leydig cells, but not in Sertoli cells or other stages of germ cells. Thus, surprisingly, in adult men the two subunits constituting inhibin B......-subunit. The correlation in adult men between serum inhibin B levels and spermatogenesis may be due to the fact that inhibin B in adult men is possibly a joint product of Sertoli cells and germ cells, including the stages from pachytene spermatocytes to early spermatids....

  8. Metabolic modulation induced by oestradiol and DHT in immature rat Sertoli cells cultured in vitro.

    Science.gov (United States)

    Rato, Luís; Alves, Marco G; Socorro, Sílvia; Carvalho, Rui A; Cavaco, José E; Oliveira, Pedro F

    2012-02-01

    Sertoli cells actively metabolize glucose that is converted into lactate, which is used by developing germ cells for their energy metabolism. Androgens and oestrogens have general metabolic roles that reach far beyond reproductive processes. Hence, the main purpose of this study was to examine the effect of sex hormones on metabolite secretion/consumption in primary cultures of rat Sertoli cells. Sertoli cell-enriched cultures were maintained in a defined medium for 50 h. Glucose and pyruvate consumption, and lactate and alanine secretion were determined, by 1H-NMR (proton NMR) spectra analysis, in the presence or absence of 100 nM E2 (17β-oestradiol) or 100 nM 5α-DHT (dihydrotestosterone). Cells cultured in the absence (control) or presence of E2 consumed the same amount of glucose (29±2 pmol/cell) at similar rates during the 50 h. After 25 h of treatment with DHT, glucose consumption and glucose consumption rate significantly increased. Control and E2-treated cells secreted similar amounts of lactate during the 50 h, while the amount of lactate secreted by DHT-treated cells was significantly lower. Such a decrease was concomitant with a significant decrease in LDH A [LDH (lactate dehydrogenase) chain A] and MCT4 [MCT (monocarboxylate transporter) isoform 4] mRNA levels after 50 h treatment in hormonally treated groups, being more pronounced in DHT-treated groups. Finally, alanine production was significantly increased in E2-treated cells after 25 h treatment, which indicated a lower redox/higher oxidative state for the cells in those conditions. Together, these results support the existence of a relation between sex hormones action and energy metabolism, providing an important assessment of androgens and oestrogens as metabolic modulators in rat Sertoli cells.

  9. Environmentally induced epigenetic transgenerational inheritance of altered Sertoli cell transcriptome and epigenome: molecular etiology of male infertility.

    Directory of Open Access Journals (Sweden)

    Carlos Guerrero-Bosagna

    Full Text Available Environmental toxicants have been shown to induce the epigenetic transgenerational inheritance of adult onset disease, including testis disease and male infertility. The current study was designed to determine the impact of an altered sperm epigenome on the subsequent development of an adult somatic cell (Sertoli cell that influences the onset of a specific disease (male infertility. A gestating female rat (F0 generation was exposed to the agriculture fungicide vinclozolin during gonadal sex determination and then the subsequent F3 generation progeny used for the isolation of Sertoli cells and assessment of testis disease. As previously observed, enhanced spermatogenic cell apoptosis was observed. The Sertoli cells provide the physical and nutritional support for the spermatogenic cells. Over 400 genes were differentially expressed in the F3 generation control versus vinclozolin lineage Sertoli cells. A number of specific cellular pathways were identified to be transgenerationally altered. One of the key metabolic processes affected was pyruvate/lactate production that is directly linked to spermatogenic cell viability. The Sertoli cell epigenome was also altered with over 100 promoter differential DNA methylation regions (DMR modified. The genomic features and overlap with the sperm DMR were investigated. Observations demonstrate that the transgenerational sperm epigenetic alterations subsequently alters the development of a specific somatic cell (Sertoli cell epigenome and transcriptome that correlates with adult onset disease (male infertility. The environmentally induced epigenetic transgenerational inheritance of testis disease appears to be a component of the molecular etiology of male infertility.

  10. Sertoli cell death by apoptosis in the immature rat testis following x-irradiation

    International Nuclear Information System (INIS)

    Allan, D.J.; Gobe, G.C.; Harmon, B.V.

    1988-01-01

    The importance of the morphological study of cell death has recently been emphasized by the recognition that the ultrastructural features of dying cells allow categorization of the death as either apoptosis or necrosis. This classification enables inferences to be drawn about the mechanism and biological significance of the death occurring in a particular set of circumstances. In this study, Sertoli cell death induced in the immature testis of three and four day old rats by 5 Gy (500 rads) x-irradiation was described by light and transmission electron microscopy with the objective of categorizing the death as apoptosis or necrosis. The testes were examined 1, 2, 3, 4, 8, and 24 h after irradiation. Following irradiation, there was a wave of apoptosis of the Sertoli cells starting in three to four hours and reaching a peak between four and eight hours. At 24 hours, only 61% of the expected number of Sertoli cells remained. These findings are in accord with recent ultrastructural reports that ionizing radiation induces cell death by apoptosis in rapidly proliferating cell populations. New insights into the pathogenesis of radiation-induced cell death might thus be expected to stem from future elucidation of the general molecular events involved in triggering apoptosis

  11. Hemicastration causes and testosterone prevents enhanced uptake of [3H]thymidine by Sertoli cells in testes of immature rats

    International Nuclear Information System (INIS)

    Orth, J.M.; Higginbotham, C.A.; Salisbury, R.L.

    1984-01-01

    Rat pups were hemicastrated and uptake of [ 3 H]thymidine by Sertoli cells in the remaining testis was compared to that in testes of sham-operated pups at intervals of from 8 h to 21 days after surgery. Labeled thymidine was administered subcutaneously 2 h before sacrifice. Testes were processed for light microscope autoradiography and the percent of Sertoli cell nuclei that had incorporated [ 3 H]thymidine was determined by scoring nuclei in tissue sections as labeled or unlabeled. The percentage of cells labeled was increased in hemicastrates over intact controls by 8 h after surgery and testicular hypertrophy became apparent in hemicastrates by the following day. Labeling of Sertoli cells in hemicastrates remained elevated for 4 days and then returned to normal. When plasma levels of gonadotropins were measured in both groups 4 days after surgery, follicle-stimulating hormone (FSH) was found to be more than twice normal in hemicastrates while luteinizing hormone (LH) was unchanged. The effect of testosterone on the response of Sertoli cells to hemicastration was also examined. In hemicastrates, 2 days of androgen therapy depressed, and an additional 2 days abolished, the proliferative response of the Sertoli cells. Our findings suggest that increased proliferation of Sertoli cells within the remaining testis is involved in the enlargement of the testis that follows hemicastration. They also imply that prevention of compensatory hypertrophy by testosterone involves interference with this response of Sertoli cells in some way. Finally, our data implicate FSH in control of Sertoli cell proliferation in vivo in immature rats

  12. Intratubular large cell hyalinizing Sertoli cell tumor of the testis presenting with prepubertal gynecomastia: a case report.

    Science.gov (United States)

    Tuhan, Hale; Abaci, Ayhan; Sarsık, Banu; Öztürk, Tülay; Olguner, Mustafa; Catli, Gonul; Anik, Ahmet; Olgun, Nur; Bober, Ece

    2017-08-01

    Intratubular large cell hyalinizing Sertoli cell neoplasia (ITLCHSCN) resulting from Sertoli cells of the testis are mainly reported in young adults and these are rarely seen in childhood. The most common presenting symptoms of the patients diagnosed with ITLCHSCN are gynecomastia, enlargement in the testicles, increase in growth velocity, and advanced bone age. Symptoms are basically resulting from increased aromatase enzyme activity in Sertoli cells. In this case report, an eight-and-a-half-year-old case presenting with complaint of bilateral gynecomastia since two years, showing no endocrine abnormality in laboratory during two years of follow-up, determined to have progression in bilateral gynecomastia, increase in testicular volumes, advanced bone age, increase in growth velocity in the clinical follow-up, and diagnosed with ITLCHSCN after testis biopsy was presented.

  13. Effect of continuous low-dose γ-irradiation on rat Sertoli cell function

    International Nuclear Information System (INIS)

    Kamtchouing, P.; Papadopoulos, V.; Drosdowsky, M.A.; Carreau, S.; Pinon-Lataillade, G.; Maas, J.; Guillaumin, J.M.; Bardos, P.; Perreau, C.; Hochereau de Reviers, M.T.

    1988-01-01

    Continuous low-dose γ-irradiation of mature rats induced a progressive degeneration of the germ cells. Blood FSH increased by 127, 176 and 214%, respectively, after 55, 70 and 85 days of treatment when compared to FSH levels in control rats (8.50 ± 0.60 ng/ml); conversely, serum LH and testosterone levels were unchanged. The Sertoli cell function was affected by the treatment from 70 days on, as attested by androgen binding protein (ABP) and transferrin secretions which diminished 35-40%. Serum ABP levels were not altered, whatever the duration of irradiation, even though epididymal ABP contents (as well as concentrations) diminished 34-60% when compared to those of the controls. Moreover, in purified Leydig cells, LH-stimulated intracellular cAMP levels, which were decreased by seminiferous tubule medium (STM) from control rats, were enhanced in presence of STM from treated animals. Testosterone output was stimulated 9-fold in presence of oLH and further increased (46-76%) from stages XIV-V by STM prepared from control and irradiated rats, respectively. After 85 days the STM effects on both cAMP and testosterone syntheses were zero. These results demonstrate a probable alteration of Sertoli cell function after irradiation, but also a role of the germ cells in the regulation of the synthesis of ABP, transferrin and Sertoli cell paracrine factors

  14. Sertoli cell index and spermatic reserves in adult captive African lions (Panthera leo, Linnaeus, 1758).

    Science.gov (United States)

    de Barros, João Bosco Gonçalves; de Paula, Tarcízio Antônio Rego; da Matta, Sérgio Luis Pinto; Fonseca, Cláudio César; Leite, Flaviana Lima Guião; Rossi, João Luiz; de Oliveira, Priscila Carvalho; da Costa, Eduardo Paulino

    2007-12-01

    The intrinsic yield of spermatogenesis and the supporting indexes of the Sertoli cells are the best indicators for the spermatic production capacity in a species. The aim of the present study was to quantify the intrinsic yield of the spermatogenetic process, as well as the Sertoli cell index and spermatic reserves. Testicular fragments of five adult African lions was fixed in 4% glutaric aldehyde, dehydrated at increasing alcohol concentrations, included into hydroxyethyl methacrylate, and were cut into 4 microm thickness. In the seminiferous epithelium of the African lions, 10.3 primary spermatocytes at pre-leptotene phase are produced by the type-A spermatogonia. During meiotic divisions, only 2.7 spermatids were produced from the primary spermatocytes. The general spermatogenesis production in the African lions was approximately 22.1 cells, and each Sertoli cell was able to sustain and maintain approximately 14.9 cells of the germinative line, from which 7.9 are round spermatids. A total of 103x10(6) spermatozoa are produced by each testis gram at each cycle of the seminiferous epithelium. The spermatic reserve of lion is below the amplitude observed in mammals.

  15. Disruption of gap junctional intercellular communication by antibiotic gentamicin is associated with aberrant localization of occludin, N-cadherin, connexin 43, and vimentin in SerW3 Sertoli cells in vitro.

    Science.gov (United States)

    Bekheet, Souad H M; Stahlmann, Ralf

    2009-09-01

    Spermatogenesis is a very complex process by which male germ cells differentiate into mature spermatozoa. The sophisticated communication network that controls spermatogenesis can be derailed so that dysfunction of one cell type propagates to all types as a cascade. This accounts for the particular vulnerability of the testis to environmental factors such as drugs and xenobiotics. Sertoli cells play an important role in protecting developing germ cells by forming a physiological barrier, limiting exposure to potentially toxic substrates, or conversely, facilitating uptake of xenobiotics within the testis. In this study, cells from the rat Sertoli line (SerW3) were incubated for 3, 6 and 9 subsequent days in serum free DMEM (SFDM) composed of DMEM supplemented with three different concentrations of antibiotic gentamicin (10, 30, and 100 μg). The effect of the three different concentrations of this antibiotic was determined on Sertoli cell-cell interaction through impaired expression of their constitutive tight junction proteins as early targets for different toxicants in vitro by immunochemistry analysis. The Sertoli SerW3 cell line illustrated the cytotoxicity of GS, as the intercellular junction proteins such as occludin, N-cadherin, connexin 43, and vimentin were delocalized from the membrane to the cytoplasmic compartment during exposure to the antibiotic. This study underlines the potential deleterious effects of the routine use of antibiotics during continuous cell culture.

  16. Low maternal nutrition during pregnancy reduces the number of Sertoli cells in the newborn lamb.

    Science.gov (United States)

    Alejandro, Bielli; Pérez, Raquel; Pedrana, Graciela; Milton, John T B; Lopez, Alvaro; Blackberry, Margaret A; Duncombe, Gregory; Rodriguez-Martinez, Heriberto; Martin, Graeme B

    2002-01-01

    The nutritional status of females during pregnancy can play a critical role in the postnatal growth and development of the offspring, often leading to permanent changes ('fetal programming'). The Sertoli cells are a strong candidate for fetal programming of future performance because the number of Sertoli cells is highly correlated with adult testicular size and the maximum rate of sperm production. For Merino ewes, we imposed different levels of metabolizable energy (ME) intake (LowME: 70% of requirements for maintenance of ewe body mass and normal growth of conceptus (n = 13); HighME: 110% of those requirements (n = 12)) from Week 10 of pregnancy until parturition and then tested for effects on testicular histology in newborn males. Pregnant ewes were weighed weekly and lambs were weighed at birth and 2 days later. Blood was sampled at the same times. LowME ewes did not gain weight, whereas HighME ewes gained 17% over their pretreatment weight. Birthweights were higher in HighME lambs than in LowME lambs. Paired testes tended to be heavier in the HighME group than in the LowME group (P=0.08). The diameter of the testicular cords did not differ. The absolute volume of testicular cords (0.36 +/- 0.02 v. 0.30 +/- 0.02 mL for HighME v. LowME, respectively; P=0.03) and the number of Sertoli cells (43.0 +/- 2.5 v. 34.5 +/- 2.0 x 10(8) for HighME v. LowME, respectively; P=0.018) per testis were both greater in the HighME than in the LowME group. Plasma follicle-stimulating hormone concentrations were not significantly affected at birth or 2 days later. We conclude that undernutrition during pregnancy can reduce testicular development in the newborn. Depending on the ability of the Sertoli cell population to recover between birth and puberty, this may limit the ultimate number of Sertoli cells and, hence, the future capacity for sperm production and fertility.

  17. Zika Virus Infects Human Sertoli Cells and Modulates the Integrity of the In Vitro Blood-Testis Barrier Model.

    Science.gov (United States)

    Siemann, David N; Strange, Daniel P; Maharaj, Payal N; Shi, Pei-Yong; Verma, Saguna

    2017-11-15

    Confirmed reports of Zika virus (ZIKV) in human seminal fluid for months after the clearance of viremia suggest the ability of ZIKV to establish persistent infection in the seminiferous tubules, an immune-privileged site in the testis protected by the blood-testis barrier, also called the Sertoli cell (SC) barrier (SCB). However, cellular targets of ZIKV in human testis and mechanisms by which the virus enters seminiferous tubules remain unclear. We demonstrate that primary human SCs were highly susceptible to ZIKV compared to the closely related dengue virus and induced the expression of alpha interferon (IFN-α), key cytokines, and cell adhesion molecules (vascular cell adhesion molecule 1 [VCAM-1] and intracellular adhesion molecule 1 [ICAM-1]). Furthermore, using an in vitro SCB model, we show that ZIKV was released on the adluminal side of the SCB model with a higher efficiency than in the blood-brain barrier model. ZIKV-infected SCs exhibited enhanced adhesion of leukocytes that correlated with decreases in SCB integrity. ZIKV infection did not affect the expression of tight and adherens junction proteins such as ZO-1, claudin, and JAM-A; however, exposure of SCs to inflammatory mediators derived from ZIKV-infected macrophages led to the degradation of the ZO-1 protein, which correlated with increased SCB permeability. Taken together, our data suggest that infection of SCs may be one of the crucial steps by which ZIKV gains access to the site of spermatozoon development and identify SCs as a therapeutic target to clear testicular infections. The SCB model opens up opportunities to assess interactions of SCs with other testicular cells and to test the ability of anti-ZIKV drugs to cross the barrier. IMPORTANCE Recent outbreaks of ZIKV, a neglected mosquito-borne flavivirus, have identified sexual transmission as a new route of disease spread, which has not been reported for other flaviviruses. To be able to sexually transmit for months after the clearance of

  18. Serum androgen binding protein and follicle stimulating hormone as indices of Sertoli cell function in the irradiated testis

    International Nuclear Information System (INIS)

    Delic, J.I.; Hendry, J.H.; Shalet, S.M.; Morris, I.D.

    1986-01-01

    The present study presents evidence of radiation-induced Sertoli cell damage in both the pubertal and adult rat. The indirect measurement of Sertoli cell function, serum follicle stimulating hormone (FSH), in general mirrored the changes seen in androgen binding protein (ABP), again indicating Sertoli cell dysfunction. Although FSH remained elevated in adult rats after 5 Gy and above and in pubertal rats after 10 and 20 Gy, the elevation was not as great as that observed in castrates. This suggests that FSH secretion was still inhibited by some factor. As ABP was reduced to near 'background' (castrate) levels after these high doses, suggesting Sertoli cell dysfunction, this may indicate that serum ABP levels may not adequately reflect all Sertoli cell functions. Alternatively FSH may have been inhibited by by Leydig cell androgens, which have been demonstrated to modulate, in part, FSH secretion. Although the Leydig cells were damaged, androgen secretion was not entirely reduced during the study. In general, FSH was elevated when severe damage to spermatogenesis was noted. Whether the changes were related to the absence of a specific spermatogenic cell type could not be determined. (UK)

  19. Cancer of rat ovaries: Sertoli cell or granulosa-theca cell tumours

    International Nuclear Information System (INIS)

    Knowles, J.F.

    1983-01-01

    The effects of X-radiation (0-1.25 Gy) given 24 hours after neonatal injections of the carcinogen ethyl nitrosourea (ENU) (0-10 mg/kg) in female rats were studied. Twelve out of 118 rats bore single ovarian tumours. A substantial excess of ovarian tumours occurred in the rats given 4 mg/kg ENU and 1.25 GY X-rays but not in others given ENU alone, radiation alone or 10 mg/kg ENU and 1.25 Gy. The tumours were all found in old rats (657-1085 days). In all of the tumours the presence of tubular formations suggested a diagnosis of ovarian Sertoli cell tumour. In two tumours, only a few tubular structures were seen and fibrous stromal tissue predominated, suggesting a diagnosis of granulosa-theca cell tumour. All other tumours were a mixture of both elements. (U.K.)

  20. The total number of Leydig and Sertoli cells in the testes of men across various age groups - a stereological study

    DEFF Research Database (Denmark)

    Petersen, Peter M; Seierøe, Karina; Pakkenberg, Bente

    2015-01-01

    is particularly sensitive to methodological problems. Therefore, using the optical fractionator technique and a sampling design specifically optimized for human testes, we estimated the total number of Sertoli and Leydig cells in the testes from 26 post mortem male subjects ranging in age from 16 to 80 years...... of Sertoli cells with age; no such decline was found for Leydig cells. Quantitative stereological analysis of post mortem tissue may help understand the influence of age or disease on the number of human testicular cells....

  1. SERTOLI-LEYDIG CELL TUMOR; A RARE CASE IN A POSTMENOPAUSAL PATIENT – CASE REPORT

    Directory of Open Access Journals (Sweden)

    Petra Krajnc

    2018-02-01

    Full Text Available Background. Sertoli-Leydig cell tumors belong to the group of sex cord stromal tumors of the ovary. They account for less than 0.5 % of all ovarian tumors and occur primarily in young women between 20 and 30 years of age. This type of tumors can secrete androgens, causing virilisation, and are extremely rarely presented in postmenopausis. Methods. A 73-year old multiparous woman was presented to our institution with complaints of abdominal distention and abdominal pain in her lower abdomen. On physical examination, she had a large, fixed palpable abdominal mass, approximately 20 cm in diameter, arising from the pelvis. The laboratoric tests revealed an elevated level of CA125 of 221.3 U/ml of serum. The ultrasound showed a complex cystic and solid pelvic tumor. There was no sign of ascites. Her hormonal status was within normal range and she also showed no signs of virilisation. On laparotomy a complex left ovarian mass, measuring 30 × 27 × 15 cm was found and sent to frozen section. The result of frozen section was a malignant tumor of unknown origin, therefore a radical surgical procedure was performed. The histopathological examination established the diagnosis of a malignant Sertoli-Leydig cell tumor of the left ovary, of intermediate differentiation. Other removed tissue was free of malignant cells. The early postoperative course was uneventful and the patient was released from hospital 10 days after surgery. However, she returned to our institution 16 days after surgery due to a proximal thrombosis of v. saphena magna. The patient was treated with low-molecularweight heparin and later warfarin for 6 weeks post operation. 16 months after the operation she was symptomatically treated for severe microcytic anemia. She showed no signs of a relapse. 27 months after primary surgery she was operated for the second time due to acute bowel obstruction. She had large masses of necrotic tumor removed from abdomen and transversostomia was performed

  2. Recurrent ovarian Sertoli?Leydig cell tumor in a child with Peutz?Jeghers syndrome

    OpenAIRE

    Bellfield, Edward J.; Alemzadeh, Ramin

    2016-01-01

    We present a female child with Peutz?Jeghers syndrome (PJS) with a recurrent ovarian Sertoli?Leydig cell tumor (SLCT). SLCTs are relatively rare sex cord neoplasms that can occur in PJS. The patient was an African-American female who first presented at the age of 3 years with precocious puberty, and then at the age of 17 years with abdominal pain and irregular menses. In each case, she had resection of the mass, which included oophorectomy. To our knowledge, this is the first reported case in...

  3. Effect of Rosmarinic acid on sertoli cells apoptosis and serum ...

    African Journals Online (AJOL)

    inflammatory and antimicrobial activities and help to prevent cell damage caused by free radicals. The objective was to study the effect of Rosmarinic acid on sertolli cells apoptosis and serum antioxidant levels in rats after they were exposed to ...

  4. Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiang; Zhao, Fang [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Lv, Zhong-ming; Shi, Wei-qin [Jiangsu Provincial Center for Disease Control and Prevention, Nanjing (China); Zhang, Lu-yong, E-mail: lyzhang@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China); Key Laboratory of Drug Quality Control and Pharmacovigilance, China Pharmaceutical University, Nanjing (China); State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009 (China); Yan, Ming, E-mail: brookming@cpu.edu.cn [Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009 (China)

    2016-11-01

    Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

  5. Triptolide disrupts the actin-based Sertoli-germ cells adherens junctions by inhibiting Rho GTPases expression

    International Nuclear Information System (INIS)

    Wang, Xiang; Zhao, Fang; Lv, Zhong-ming; Shi, Wei-qin; Zhang, Lu-yong; Yan, Ming

    2016-01-01

    Triptolide (TP), derived from the medicinal plant Triterygium wilfordii Hook. f. (TWHF), is a diterpene triepoxide with variety biological and pharmacological activities. However, TP has been restricted in clinical application due to its narrow therapeutic window especially in reproductive system. During spermatogenesis, Sertoli cell cytoskeleton plays an essential role in facilitating germ cell movement and cell-cell actin-based adherens junctions (AJ). At Sertoli cell-spermatid interface, the anchoring device is a kind of AJ, known as ectoplasmic specializations (ES). In this study, we demonstrate that β-actin, an important component of cytoskeleton, has been significantly down-regulated after TP treatment. TP can inhibit the expression of Rho GTPase such as, RhoA, RhoB, Cdc42 and Rac1. Downstream of Rho GTPase, Rho-associated protein kinase (ROCKs) gene expressions were also suppressed by TP. F-actin immunofluorescence proved that TP disrupts Sertoli cells cytoskeleton network. As a result of β-actin down-regulation, TP treatment increased expression of testin, which indicating ES has been disassembled. In summary, this report illustrates that TP induces cytoskeleton dysfunction and disrupts cell-cell adherens junctions via inhibition of Rho GTPases. - Highlights: • Triptolide induced the disruption of Sertoli-germ cell adherens junction. • Rho GTPases expression and actin dynamics have been suppressed by triptolide. • Actin-based adherens junction is a potential antifertility target of triptolide. • Rho-Rock is involved in the regulation of actin dynamics.

  6. Metformin and male reproduction: effects on Sertoli cell metabolism

    Directory of Open Access Journals (Sweden)

    2014-08-01

    Full Text Available Metformin, widely used for the treatment of type 2 diabetes, is increasingly becoming the subject of research in other areas of medicine. Apart form antihyperglycemic effect of metformin has an inhibitory effect on the proliferation of various tumor cells both in vivo and in vitro. Metformin is well established in the treatment of anovulatory infertility in polycystic ovary syndrome, while its influence male reproductive function are poorly understood.

  7. In-vitro secretion of inhibin-like activity by Sertoli cells from normal and prenatally irradiated immature rats

    International Nuclear Information System (INIS)

    Ultee-van Gessel, A.M.; Leemborg, F.G.; Jong, F.H. de; Molen, H.J. van der

    1986-01-01

    The influence of in-vitro conditions on the production of inhibin by Sertoli cells from 21-day-old normal and prenatally irradiated rat testes was studied by measuring inhibin activity in culture media, using the suppression of the release of FSH from cultured rat pituitary cells. Sertoli cells secreted inhibin-like activity during at least 21 days of culture, and cells cultured at 37 0 C produced significantly more inhibin than those cultured at 32 0 C. The presence of fetal calf serum had no significant effect on inhibin production at 32 0 C, while at 37 0 C the production was decreased. The presence of ovine FSH stimulated inhibin secretion, while inhibin concentrations in Sertoli cell culture media were decreased after the addition of testosterone. Testosterone, added together with ovine FSH, suppressed inhibin secretion when compared with the levels found in the presence of FSH alone. The presence of spermatogenic cells decreased the release of inhibin. From these results it was concluded that both Sertoli cells isolated from normal immature rat testes and those from testes without spermatogenic cells can secrete inhibin-like activity in culture. A number of discrepancies with in-vivo observations was observed. (author)

  8. A PLK4 mutation causing azoospermia in a man with Sertoli cell-only syndrome.

    Science.gov (United States)

    Miyamoto, T; Bando, Y; Koh, E; Tsujimura, A; Miyagawa, Y; Iijima, M; Namiki, M; Shiina, M; Ogata, K; Matsumoto, N; Sengoku, K

    2016-01-01

    About 15% of couples wishing to have children are infertile; approximately half these cases involve a male factor. Polo-like kinase 4 (PLK-4) is a member of the polo protein family and a key regulator of centriole duplication. Male mice with a point mutation in the Plk4 gene show azoospermia associated with germ cell loss. Mutational analysis of 81 patients with azoospermia and Sertoli cell-only syndrome (SCOS) identified one man with a heterozygous 13-bp deletion in the Ser/Thr kinase domain of PLK4. Division of centrioles occurred in wild-type PLK4-transfected cells, but was hampered in PLK-4-mutant transfectants, which also showed abnormal nuclei. Thus, this PLK4 mutation might be a cause of human SCOS and nonobstructive azoospermia. © 2015 American Society of Andrology and European Academy of Andrology.

  9. Reversal of experimental Laron Syndrome by xenotransplantation of microencapsulated porcine Sertoli cells.

    Science.gov (United States)

    Luca, Giovanni; Calvitti, Mario; Mancuso, Francesca; Falabella, Giulia; Arato, Iva; Bellucci, Catia; List, Edward O; Bellezza, Enrico; Angeli, Giovanni; Lilli, Cinzia; Bodo, Maria; Becchetti, Ennio; Kopchick, John J; Cameron, Don F; Baroni, Tiziano; Calafiore, Riccardo

    2013-01-10

    Recombinant human IGF-1 currently represents the only available treatment option for the Laron Syndrome, a rare human disorder caused by defects in the gene encoding growth hormone receptor, resulting in irreversibly retarded growth. Unfortunately, this treatment therapy, poorly impacts longitudinal growth (13% in females and 19% in males), while burdening the patients with severe side effects, including hypoglycemia, in association with the unfair chore of taking multiple daily injections that cause local intense pain. In this study, we have demonstrated that a single intraperitoneal graft of microencapsulated pig Sertoli cells, producing pig insulin-like growth factor-1, successfully promoted significant proportional growth in the Laron mouse, a unique animal model of the human Laron Syndrome. These findings indicate a novel, simply, safe and successful method for the cell therapy-based cure of the Laron Syndrome, potentially applicable to humans. Copyright © 2012 Elsevier B.V. All rights reserved.

  10. Sertoli cell tumor arising in a cryptorchid testis presenting as a content of inguinal hernial sac

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    Kusuma Venkatesh

    2016-01-01

    Full Text Available Sertoli cell tumors (SCTs are rare tumors accounting for <1% of all testicular tumors. Here, we report a rare case of SCT in a 60-year-old man presenting as a painless swelling in the right groin since childhood. Clinically, he presented with right-sided inguinal hernia with absence of the right testis. He had normal left testis and had no gynecomastia or infertility. The specimen of hernial sac showed testis with a 1.6 cm × 1.5 cm nodular mass having gray tan-cut surface. Histopathologically, the testis showed atrophy and the nodular portion showed tumor cells arranged in tubular and microcystic pattern, with no solid pattern or necrosis. The diagnosis of SCT was confirmed with immunohistochemical staining for inhibin which showed fine granular cytoplasmic positivity. Cryptorchid testis having SCT and presenting as a content of inguinal hernia is a rare occurrence.

  11. Retiform Sertoli-Leydig Cell Tumor in a 38-Year-Old Woman: A Case Report, Retrospective Review, and Review of Current Literature

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    Laura C. Nwogu

    2017-01-01

    Full Text Available Ovarian sex cord-stromal tumors arise from the stromal cells that surround and support the oocytes. Sertoli-Leydig cell tumors belong to this category of ovarian neoplasms. We present the case of a 38-year-old woman who was found to have a right ovarian mass. The mass was resected and diagnosed as Stage I Sertoli-Leydig cell tumor, retiform variant, following histopathologic and immunohistochemical examination. This case is unusual given the rarity of the retiform variant of Sertoli-Leydig cell tumor and the atypically older age of 38 years at presentation.

  12. KATNAL1 regulation of sertoli cell microtubule dynamics is essential for spermiogenesis and male fertility.

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    Lee B Smith

    Full Text Available Spermatogenesis is a complex process reliant upon interactions between germ cells (GC and supporting somatic cells. Testicular Sertoli cells (SC support GCs during maturation through physical attachment, the provision of nutrients, and protection from immunological attack. This role is facilitated by an active cytoskeleton of parallel microtubule arrays that permit transport of nutrients to GCs, as well as translocation of spermatids through the seminiferous epithelium during maturation. It is well established that chemical perturbation of SC microtubule remodelling leads to premature GC exfoliation demonstrating that microtubule remodelling is an essential component of male fertility, yet the genes responsible for this process remain unknown. Using a random ENU mutagenesis approach, we have identified a novel mouse line displaying male-specific infertility, due to a point mutation in the highly conserved ATPase domain of the novel KATANIN p60-related microtubule severing protein Katanin p60 subunit A-like1 (KATNAL1. We demonstrate that Katnal1 is expressed in testicular Sertoli cells (SC from 15.5 days post-coitum (dpc and that, consistent with chemical disruption models, loss of function of KATNAL1 leads to male-specific infertility through disruption of SC microtubule dynamics and premature exfoliation of spermatids from the seminiferous epithelium. The identification of KATNAL1 as an essential regulator of male fertility provides a significant novel entry point into advancing our understanding of how SC microtubule dynamics promotes male fertility. Such information will have resonance both for future treatment of male fertility and the development of non-hormonal male contraceptives.

  13. Profiling spermatogenic failure in adult testes bearing Sox9-deficient Sertoli cells identifies genes involved in feminization, inflammation and stress

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    Barrionuevo Francisco

    2010-12-01

    Full Text Available Abstract Background Sox9 (Sry box containing gene 9 is a DNA-binding transcription factor involved in chondrocyte development and sex determination. The protein's absence in testicular Sertoli nurse cells has been shown to disrupt testicular function in adults but little is known at the genome-wide level about molecular events concomitant with testicular break-down. Methods To determine the genome-wide effect on mRNA concentrations triggered by the absence of Sox9 in Sertoli cells we analysed adult testicular tissue from wild-type versus mutant mice with high-density oligonucleotide microarrays and integrated the output of this experiment with regulatory motif predictions and protein-protein network data. Results We report the genome-wide mRNA signature of adult testes lacking Sox9 in Sertoli cells before and after the onset of late spermatogenic failure as compared to fertile controls. The GeneChip data integrated with evolutionarily conserved Sox9 DNA binding motifs and regulatory network data identified genes involved in feminization, stress response and inflammation. Conclusions Our results extend previous observations that genes required for female gonadogenesis are up-regulated in the absence of Sox9 in fetal Sertoli cells to the adult stage. Importantly, we identify gene networks involved in immunological processes and stress response which is reminiscent of a phenomenon occurring in a sub-group of infertile men. This suggests mice lacking Sox9 in their Sertoli cells to be a potentially useful model for adult human testicular failure.

  14. Long-Term Survival of Neonatal Porcine Islets Without Sertoli Cells in Rabbits

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    Rafael Vald and eacute;s-Gonz and aacute;lez

    2013-04-01

    Full Text Available Cell-based therapy is a promising treatment for metabolic disorders such as type-1 diabetes. Transplantation protocols have investigated several anatomical sites for cell implantation; however, some of these procedures, such as intraportal infusion, can cause organ failure or thrombosis secondarily. Bio-artificial organs could be the choice, although concerns still remain. Using a subcutaneous device, we are able to preserve neonatal porcine islets without sertoli cells in healthy New Zealand rabbits. Devices were implanted in the back of the animals underneath the skin, and after 3 months the islets were transplanted. Histology showed the presence of inflammatory cells, predominantly eosinophils; however, insulin- and glucagon-positive cell clusters were identified inside the device at different time points for at least 90 days, and porcine C-peptide was also detected during the follow-up, indicating graft functionality. We have found that our device induces the deposition of a fibrous matrix enriched in blood vessels, which forms a good place for cell grafting, and this model is probably able to induce an immunoprivileged site. Under these conditions, transplanted porcine islet cells have the capability of producing insulin and glucagon for at least three months. [Arch Clin Exp Surg 2013; 2(2.000: 101-108

  15. Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results in Impaired Male Fertility in Mice.

    Science.gov (United States)

    Welborn, Joshua P; Davis, Matthew G; Ebers, Steven D; Stodden, Genna R; Hayashi, Kanako; Cheatwood, Joseph L; Rao, Manjeet K; MacLean, James A

    2015-07-01

    The reproductive homeobox X-linked, Rhox, genes encode transcription factors that are selectively expressed in reproductive tissues. While there are 33 Rhox genes in mice, only Rhox and Rhox8 are expressed in Sertoli cells, suggesting that they may regulate the expression of somatic-cell gene products crucial for germ cell development. We previously characterized Rhox5-null mice, which are subfertile, exhibiting excessive germ cell apoptosis and compromised sperm motility. To assess the role of Rhox8 in Sertoli cells, we used a tissue-specific RNAi approach to knockdown RHOX8 in vivo, in which the Rhox5 promoter was used to drive Rhox8-siRNA transgene expression in the postnatal Sertoli cells. Western and immunohistochemical analysis confirmed Sertoli-specific knockdown of RHOX8. However, other Sertoli markers, Gata1 and Rhox5, maintained normal expression patterns, suggesting that the knockdown was specific. Interestingly, male RHOX8-knockdown animals showed significantly reduced spermatogenic output, increased germ cell apoptosis, and compromised sperm motility, leading to impaired fertility. Importantly, our results revealed that while some RHOX5-dependent factors were also misregulated in Sertoli cells of RHOX8-knockdown animals, the majority were not, and novel putative RHOX8-regulated genes were identified. This suggests that while reduction in levels of RHOX5 and RHOX8 in Sertoli cells elicits similar phenotypes, these genes are not entirely redundant. Taken together, our study underscores the importance of Rhox genes in male fertility and suggests that Sertoli cell-specific expression of Rhox5 and Rhox8 is critical for complete male fertility. © 2015 by the Society for the Study of Reproduction, Inc.

  16. Rhox8 Ablation in the Sertoli Cells Using a Tissue-Specific RNAi Approach Results in Impaired Male Fertility in Mice1

    Science.gov (United States)

    Welborn, Joshua P.; Davis, Matthew G.; Ebers, Steven D.; Stodden, Genna R.; Hayashi, Kanako; Cheatwood, Joseph L.; Rao, Manjeet K.; MacLean, James A.

    2015-01-01

    The reproductive homeobox X-linked, Rhox, genes encode transcription factors that are selectively expressed in reproductive tissues. While there are 33 Rhox genes in mice, only Rhox and Rhox8 are expressed in Sertoli cells, suggesting that they may regulate the expression of somatic-cell gene products crucial for germ cell development. We previously characterized Rhox5-null mice, which are subfertile, exhibiting excessive germ cell apoptosis and compromised sperm motility. To assess the role of Rhox8 in Sertoli cells, we used a tissue-specific RNAi approach to knockdown RHOX8 in vivo, in which the Rhox5 promoter was used to drive Rhox8-siRNA transgene expression in the postnatal Sertoli cells. Western and immunohistochemical analysis confirmed Sertoli-specific knockdown of RHOX8. However, other Sertoli markers, Gata1 and Rhox5, maintained normal expression patterns, suggesting that the knockdown was specific. Interestingly, male RHOX8-knockdown animals showed significantly reduced spermatogenic output, increased germ cell apoptosis, and compromised sperm motility, leading to impaired fertility. Importantly, our results revealed that while some RHOX5-dependent factors were also misregulated in Sertoli cells of RHOX8-knockdown animals, the majority were not, and novel putative RHOX8-regulated genes were identified. This suggests that while reduction in levels of RHOX5 and RHOX8 in Sertoli cells elicits similar phenotypes, these genes are not entirely redundant. Taken together, our study underscores the importance of Rhox genes in male fertility and suggests that Sertoli cell-specific expression of Rhox5 and Rhox8 is critical for complete male fertility. PMID:25972016

  17. Cyclical and patch-like GDNF distribution along the basal surface of Sertoli cells in mouse and hamster testes.

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    Takeshi Sato

    Full Text Available BACKGROUND AND AIMS: In mammalian spermatogenesis, glial cell line-derived neurotrophic factor (GDNF is one of the major Sertoli cell-derived factors which regulates the maintenance of undifferentiated spermatogonia including spermatogonial stem cells (SSCs through GDNF family receptor α1 (GFRα1. It remains unclear as to when, where and how GDNF molecules are produced and exposed to the GFRα1-positive spermatogonia in vivo. METHODOLOGY AND PRINCIPAL FINDINGS: Here we show the cyclical and patch-like distribution of immunoreactive GDNF-positive signals and their close co-localization with a subpopulation of GFRα1-positive spermatogonia along the basal surface of Sertoli cells in mice and hamsters. Anti-GDNF section immunostaining revealed that GDNF-positive signals are mainly cytoplasmic and observed specifically in the Sertoli cells in a species-specific as well as a seminiferous cycle- and spermatogenic activity-dependent manner. In contrast to the ubiquitous GDNF signals in mouse testes, high levels of its signals were cyclically observed in hamster testes prior to spermiation. Whole-mount anti-GDNF staining of the seminiferous tubules successfully visualized the cyclical and patch-like extracellular distribution of GDNF-positive granular deposits along the basal surface of Sertoli cells in both species. Double-staining of GDNF and GFRα1 demonstrated the close co-localization of GDNF deposits and a subpopulation of GFRα1-positive spermatogonia. In both species, GFRα1-positive cells showed a slender bipolar shape as well as a tendency for increased cell numbers in the GDNF-enriched area, as compared with those in the GDNF-low/negative area of the seminiferous tubules. CONCLUSION/SIGNIFICANCE: Our data provide direct evidence of regionally defined patch-like GDNF-positive signal site in which GFRα1-positive spermatogonia possibly interact with GDNF in the basal compartment of the seminiferous tubules.

  18. A Hard Ball for a Tennis Player: A Rare Case of Large Calcifying Sertoli Cell Testicular Tumor

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    Simone Albisinni

    2017-07-01

    Full Text Available A 46 year old tennis player was addressed to our clinic after incidental finding of right testicular calcification on plain x-ray of the spine. Urologic consultation revealed a hard non-tender testicular mass which required inguinal orchiectomy. Final histology revealed large cell calcifying Sertoli cell tumor: we herein present the case and review current physiopathology of such rare testicular disease.

  19. Ultrastructural analysis of early toxic effects produced by bee venom phospholipase A2 and melittin in Sertoli cells in rats.

    Science.gov (United States)

    Tilinca, Mariana; Florea, Adrian

    2018-01-01

    In this study, we aimed to investigate the testicular toxicity of two molecules derived from bee venom (BV): phospholipase A2 (PlA2) and melittin (Mlt). Ultrastructural effects of purified BV PlA2 and Mlt were assessed consecutive to repeated dose (30 days) and acute toxicity studies. For the subchronic treatment, PlA2 and Mlt were injected in daily doses equivalent to those released by a bee sting (105 μg PlA2/kg/day and 350 μg Mlt/kg/day), while in the acute treatment their doses corresponded to those released by 100 bee stings (9.3 mg PlA2/kg and 31 mg Mlt/kg). Both PlA2 and Mlt affected the Leydig cells and the cells in seminiferous tubules, the Sertoli cells first of all. PlA2 injection resulted in detachment of the Sertoli cells from the surrounding cells, and extracellular vacuolations, cytoplasmic vacuolations in their basal region and in branches as well, detachment of spermatids, residual bodies and sometimes even spermatocytes into the lumen, changes that had a higher magnitude after the acute treatment. Mlt injection induced similar ultrastructural alterations, but more severe, including degeneration of cellular organelles and cellular necrosis, resulting into rarefaction of the seminiferous epithelium; the ultrastructural changes had a higher magnitude after the 30 repeated dose treatment. We concluded that either of the two molecules tested here, PlA2 and Mlt, were Sertoli cells toxicants at the used doses, and they participated both in the BV testicular toxicity. We consider the observed changes as part of a preceding mechanism of the more severe alterations produced by the BV. It also remains possible that these early unspecific changes reported here could represent the response of the SCs not only to the components of bee venom, but to molecules of other venoms as well. The Sertoli cells were the primary target of PlA2 and Mlt in the spermatogenic epithelium, and their alteration led to further degenerative changes of the germ cells. Since

  20. Sox9-dependent expression of Gstm6 in Sertoli cells during testis development in mice.

    Science.gov (United States)

    Beverdam, Annemiek; Svingen, Terje; Bagheri-Fam, Stefan; Bernard, Pascal; McClive, Peter; Robson, Mathew; Khojasteh, Mahdi Banan; Salehi, Mahboubeh; Sinclair, Andrew H; Harley, Vincent R; Koopman, Peter

    2009-03-01

    Glutathione S-transferases (GSTs) are an important family of multifunctional enzymes that play a role in the protection of tissues by the detoxification of hazardous and carcinogenic compounds. We found previously that Gstm6 is upregulated in the somatic cells of male mouse fetal gonads relative to female gonads. In this study, we describe the spatial and temporal expression pattern of Gstm6 during mouse development. We show that Gstm6 is predominantly expressed in the reproductive system, at significantly higher levels in XY gonads compared with XX gonads from 11.5 dpc onwards, and remains expressed in the testes in adult mice. Its expression is associated with the Sertoli cell lineage, and is dependent on the expression of the male sex-determining gene Sox9. Our data suggest that Gstm6 plays a male-specific role in gonad development or function, possibly by modulating the exposure of somatic tissue and/or germ cells to endogenous or exogenous toxicants.

  1. Androgen Receptor Localizes to Plasma Membrane by Binding to Caveolin-1 in Mouse Sertoli Cells

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    Qiong Deng

    2017-01-01

    Full Text Available The nonclassical androgen signaling pathway translates signals into alterations in cellular function within minutes, and this action is proposed to be mediated by an androgen receptor (AR localized to the plasma membrane. This study was designed to determine the mechanism underlying the membrane association of androgen receptor in TM4 cells, a mouse Sertoli cell line. Western blot analysis indicated testosterone-induced AR translocation to the cell membrane. Data from coimmunoprecipitation indicated that AR is associated with caveolin-1, and testosterone enhanced this association. Knockdown of caveolin-1 by shRNA decreased the amount of AR localized to membrane fraction and prevented AR membrane trafficking after being exposed to testosterone at physiological concentration. The palmitoylation inhibitor 2-bromopalmitate decreased AR membrane localization in basal condition and completely blocked testosterone-induced AR translocation to membrane fraction. These data suggested that AR localized to membrane fraction by binding with caveolin-1 through palmitoylation of the cysteine residue. This study provided a new evidence for AR membrane localization and its application for clarifying the nonclassical signaling pathway of androgens.

  2. Combined strategy of endothelial cells coating, Sertoli cells coculture and infusion improves vascularization and rejection protection of islet graft.

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    Yang Li

    Full Text Available Improving islet graft revascularization and inhibiting rejection become crucial tasks for prolonging islet graft survival. Endothelial cells (ECs are the basis of islet vascularization and Sertoli cells (SCs have the talent to provide nutritional support and exert immunosuppressive effects. We construct a combined strategy of ECs coating in the presence of nutritious and immune factors supplied by SCs in a co-culture system to investigate the effect of vascularization and rejection inhibition for islet graft. In vivo, the combined strategy improved the survival and vascularization as well as inhibited lymphocytes and inflammatory cytokines. In vitro, we found the combinatorial strategy improved the function of islets and the effect of ECs-coating on islets. Combined strategy treated islets revealed higher levels of anti-apoptotic signal molecules (Bcl-2 and HSP-32, survival and function related molecules (PDX-1, Ki-67, ERK1/2 and Akt and demonstrated increased vascular endothelial growth factor receptor 2 (KDR and angiogenesis signal molecules (FAk and PLC-γ. SCs effectively inhibited the activation of lymphocyte stimulated by islets and ECs. Predominantly immunosuppressive cytokines could be detected in culture supernatants of the SCs coculture group. These results suggest that ECs-coating and Sertoli cells co-culture or infusion synergistically enhance islet survival and function after transplantation.

  3. Differential proliferation and metabolic activity of Sertoli cells in the testes of broiler and layer breeder chickens.

    Science.gov (United States)

    Faure, Mélanie; Guibert, Edith; Crochet, Sabine; Chartrin, Pascal; Brillard, Jean-Pierre; Collin, Anne; Froment, Pascal

    2017-07-01

    Decades of genetic selection have generated 2 different, highly specialized types of chickens in which 1 type, known as the layer-type chicken, expresses high laying performance while the other type, known as the broiler-type chicken, is dedicated to the production of fast-growing birds. Selected lines for the latter type often express disorders in their reproductive performance including early sexual maturation and accelerated, non-reversible seasonal decline of their semen production and mating behavior. The aim of the present study was to characterize some metabolic markers of the Sertoli cell populations. Sertoli cells are somatic cells known to support, coordinate, nourish, and protect the germ cell populations from onset to the end of their meiotic process. Comparisons of gonadal development between males of the 2 genetic types taken at their pre-pubertal period indicated that the testes of layer-type chickens are significantly less developed than in broiler-type males taken at the same age. In addition, cultures of purified Sertoli cells from the 2 types revealed in vitro a higher proliferative capacity when issued from layer compared to broiler-type chickens. This was associated with a higher expression of the genes involved in the beta-oxidation of fatty acids (CPT1; PPARβ) as well as a 4-fold increase in the Lactate Dehydrogenase-A expression and activity. In contrast, Sertoli cells from broiler-type chickens presented an elevated activity of citrate synthase and mitochondria, suggesting a better efficacy of aerobic metabolism in Sertoli cells from broiler compared to layer-type chickens. Moreover, the testis from broiler-type chickens seems to be more sensitive to oxidative stress due to the lower global antioxidant capacity compared to layer-type chickens.In conclusion, these results suggest that the metabolic activity of testicular tissues is different in the layer and broiler breeder chickens. The aerobic metabolism more prevalent in broiler

  4. An in vitro prototype of a porcine biomimetic testis-like cell culture system: a novel tool for the study of reassembled Sertoli and Leydig cells

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    Iva Arato

    2018-01-01

    Full Text Available At present, there is no reliable in vitro assembled prepubertal testis-like biomimetic organ culture system designed to assess the functional effects of human gonadotropins on Sertoli and Leydig cells. Spermatogenesis is regulated by endocrine, paracrine, and juxtacrine factors (testicular cross-talk, mainly orchestrated by gonadotropins such as luteinizing hormone (LH and follicle-stimulating hormone (FSH that play a pivotal role by stimulating Leydig and Sertoli cells, respectively. The aim of our study was to set up an in vitro prepubertal porcine bioengineered construct as a new model for experimental studies on reassembled Sertoli and Leydig cells. We have evaluated Sertoli and Leydig cells obtained from 15- to 20-day-old neonatal pig testes in terms of purity and function. Subsequently, purified Sertoli and enriched Leydig cells were subjected to coincubation to obtain an in vitro prepubertal porcine testis-like culture system. We performed enzyme-linked immunosorbent assay (ELISA for anti-Müllerian hormone (AMH, inhibin B, and testosterone secretion in the medium, and Real-Time PCR analysis of AMH, inhibin B, FSH-r, aromatase, LHr, and 3β-HSD mRNA expression levels. This in vitro testis-like system was highly responsive to the effects of human gonadotropins and testosterone. AMH mRNA expression and secretion declined, and inhibin-B increased, while FSH-receptor expression was downregulated upon FSH/LH exposure/treatment. Finally, the production of testosterone was increased selectively upon LH treatment. In summary, our proposed model could help to better determine the action of human gonadotropins on Sertoli and Leydig cells. The potential usefulness of the system for shedding light into male infertility-related issues is evident.

  5. Effect of an acute exposure of rat testes to gamma rays on germ cells and on Sertoli and Leydig cell functions

    International Nuclear Information System (INIS)

    Pinon-Lataillade, G.; Maas, J.; Viguier-Martinez, M.C.; Touzalin, A.M.; Jegou, B.

    1991-01-01

    Germ cells and Sertoli and Leydig cell functions were studied from 7 to 180 days after an acute exposure of 2-month-old rat testes to 9 Gy of γ rays. Body weight, testis and epididymal weights were recorded. Sertoli cell parameters (androgen-binding protein, ABP, in caput epididymis and plasma follicle stimulating hormone, FSH) and Leydig cell parameters (plasma luteinizing hormone, LH, testosterone and prostate and seminal vesicle weights) were determined together with the number of germ cells and Sertoli cells. Irradiation did not affect body weight but significantly reduced testicular and epididymal weights from day 7 and day 15 post-irradiation respectively. The cells killed by irradiation were mainly spermatogonia and preleptotene spermatocytes engaged in replicating their DNA at the time of exposure, but all spermatocytes seemed damaged as they gave abnormal descendent cells. By day 34, only elongated spermatids remained in a few tubules and thereafter very little regeneration of the seminiferous epithelium occurred, except for one rat which showed a better regeneration. Levels of ABP decreased by day 15 when the germ cell depletion had reached the pachytene spermatocytes, whereas FSH and LH levels rose when the number of elongated spermatids decreased. Levels of testosterone and the weight of the seminal vesicles did not change; occasionally, the prostate weight was slightly reduced. These results support our hypothesis that pachytene spermatocytes and elongated spermatids are involved in influencing some aspects of Sertoli cell function in the adult rat

  6. Ovarian Sertoli-Leydig cell tumor with heterologous elements of gastrointestinal type associated with elevated serum alpha-fetoprotein level: an unusual case and literature review.

    Science.gov (United States)

    Horta, Mariana; Cunha, Teresa Margarida; Marques, Rita Canas; Félix, Ana

    2014-11-01

    Here we describe the case of a 19-year-old woman with a poorly differentiated ovarian Sertoli-Leydig cell tumor and an elevated serum alpha-fetoprotein level. The patient presented with diffuse abdominal pain and bloating. Physical examination, ultrasound, and magnetic resonance imaging revealed a right ovarian tumor that was histopathologically diagnosed as a poorly differentiated Sertoli-Leydig cell tumor with heterologous elements. Her alpha-fetoprotein serum level was undetectable after tumor resection. Sertoli-Leydig cell tumors are rare sex cord-stromal tumors that account for 0.5% of all ovarian neoplasms. Sertoli-Leydig cell tumors tend to be unilateral and occur in women under 30 years of age. Although they are the most common virilizing tumor of the ovary, about 60% are endocrine-inactive tumors. Elevated serum levels of alpha-fetoprotein are rarely associated with Sertoli-Leydig cell tumors, with only approximately 30 such cases previously reported in the literature. The differential diagnosis should include common alpha-fetoprotein-producing ovarian entities such as germ cell tumors, as well as other non-germ cell tumors that have been rarely reported to produce this tumor marker.

  7. The role of PGC-1α and MRP1 in lead-induced mitochondrial toxicity in testicular Sertoli cells

    International Nuclear Information System (INIS)

    Li, Zhen; Liu, Xi; Wang, Lu; Wang, Yan; Du, Chuang; Xu, Siyuan; Zhang, Yucheng; Wang, Chunhong; Yang, Chengfeng

    2016-01-01

    The lead-induced toxic effect on mitochondria in Sertoli cells is not well studied and the underlying mechanism is poorly understood. Here we reported the potential role of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and multidrug resistance protein 1 (MRP1) in lead acetate-induced mitochondrial toxicity in mouse testicular Sertoli cells TM4 line. We found that lead acetate treatment significantly reduced the expression level of PGC-1α, but increased the level of MRP1 in mitochondria of TM4 cells. To determine the role of PGC-1α and MRP1 in lead acetate-induced mitochondrial toxicity, we then generated PGC-1α stable overexpression and MRP1 stable knockdown TM4 cells, respectively. The lead acetate treatment caused TM4 cell mitochondrial ultrastructure damages, a decrease in ATP synthesis, an increase in ROS levels, and apoptotic cell death. In contrast, stably overexpressing PGC-1α significantly ameliorated the lead acetate treatment-caused mitochondrial toxicity and apoptosis. Moreover, it was also found that stably knocking down the level of MRP1 increased the TM4 cell mitochondrial lead-accumulation by 4–6 folds. Together, the findings from this study suggest that PGC-1α and MRP1 plays important roles in protecting TM4 cells against lead-induced mitochondrial toxicity, providing a better understanding of lead-induced mitochondrial toxicity.

  8. Cardiotonic steroids trigger non-classical testosterone signaling in Sertoli cells via the α4 isoform of the sodium pump.

    Science.gov (United States)

    Konrad, Lutz; Dietze, Raimund; Kirch, Ulrike; Kirch, Herbert; Eva, Alexander; Scheiner-Bobis, Georgios

    2011-12-01

    The α4 isoform of the Na(+),K(+)-ATPase (sodium pump) is known to be expressed in spermatozoa and to be critical for their motility. In the investigation presented here, we find that the rat-derived Sertoli cell line 93RS2 also expresses considerable amounts of the α4 isoform in addition to the α1 isoform. Since Sertoli cells are not motile, one can assume that the function of the α4 isoform in these cells must differ from that in spermatozoa. Thus, we assessed a potential involvement of this isoform in signaling pathways that are activated by the cardiotonic steroid (CTS) ouabain, a highly specific sodium pump ligand. Treatment of 93RS2 cells with ouabain leads to activation of the c-Src/c-Raf/Erk1/2 signaling cascade. Furthermore, we show for the first time that the activation of this cascade by ouabain results in phosphorylation and activation of the transcription factor CREB. This signaling cascade is induced at low nanomolar concentrations of ouabain, consistent with the involvement of the α4 isoform. This is further supported by experiments involving siRNA: silencing of α4 expression entirely blocks ouabain-induced activation of Erk1/2 whereas silencing of α1 has no effect. The findings of this study unveil new aspects in CTS/sodium pump interactions by demonstrating for the first time ouabain-induced signaling through the α4 isoform. The c-Src/c-Raf/Erk1/2/CREB cascade activated by ouabain is identical to the so-called non-classical signaling cascade that is normally triggered in Sertoli cells by testosterone. Taking into consideration that CTS are produced endogenously, our results may help to gain new insights into the physiological mechanisms associated with male fertility and reproduction. Copyright © 2011 Elsevier B.V. All rights reserved.

  9. Full field optical coherence tomography can identify spermatogenesis in a rodent sertoli-cell only model.

    Science.gov (United States)

    Ramasamy, Ranjith; Sterling, Joshua; Manzoor, Maryem; Salamoon, Bekheit; Jain, Manu; Fisher, Erik; Li, Phillip S; Schlegel, Peter N; Mukherjee, Sushmita

    2012-01-01

    Microdissection testicular sperm extraction (micro-TESE) has replaced conventional testis biopsies as a method of choice for obtaining sperm for in vitro fertilization for men with nonobstructive azoospermia. A technical challenge of micro-TESE is that the low magnification inspection of the tubules with a surgical microscope is insufficient to definitively identify sperm-containing tubules, necessitating tissue removal and cytologic assessment. Full field optical coherence tomography (FFOCT) uses white light interference microscopy to generate quick high-resolution tomographic images of fresh (unprocessed and unstained) tissue. Furthermore, by using a nonlaser safe light source (150 W halogen lamp) for tissue illumination, it ensures that the sperm extracted for in vitro fertilization are not photo-damaged or mutagenized. A focal Sertoli-cell only rodent model was created with busulfan injection in adult rats. Ex vivo testicular tissues from both normal and busulfan-treated rats were imaged with a commercial modified FFOCT system, Light-CT™, and the images were correlated with gold standard hematoxylin and eosin staining. Light-CT™ identified spermatogenesis within the seminiferous tubules in freshly excised testicular tissue, without the use of exogenous contrast or fixation. Normal adult rats exhibited tubules with uniform size and shape (diameter 328 ±11 μm). The busulfan-treated animals showed marked heterogeneity in tubular size and shape (diameter 178 ± 35 μm) and only 10% contained sperm within the lumen. FFOCT has the potential to facilitate real-time visualization of spermatogenesis in humans, and aid in micro-TESE for men with infertility.

  10. Regulation of the phosphoinositide pathway in cultured Sertoli cells from immature rats: effects of follicle-stimulating hormone and fluoride

    International Nuclear Information System (INIS)

    Quirk, S.M.; Reichert, L.E. Jr.

    1988-01-01

    Many hormones elicit effects on target cells by stimulating the enzyme phospholipase-C, which catalyzes the hydrolysis of phosphoinositides to the intracellular second messengers diacylglycerol and inositol phosphates. The present study examined the roles of FSH and guanine nucleotide-binding proteins (G-proteins) in regulating the hydrolysis of phosphoinositides in Sertoli cells. Sertoli cell cultures prepared from 16- to 18-day-old rats were incubated for 24 h with myo-[2-3H] inositol to label endogenous phospholipids. Treatment of cells from 0.5-20 min with preparations of ovine FSH ranging in potency from 1-60 times that of NIH FSH S1 did not affect accumulation of inositol phosphates. Levels of total [3H]inositol phosphates [[3H]inositol mono-, di-, and triphosphates (IP, IP2, and IP3)] in FSH-treated cultures was 75-120% the levels in control cultures over the various time intervals studied. Addition of testosterone and the combination of testosterone plus retinoic acid, agents that have been shown to potentiate effects of FSH in other systems, did not affect accumulation of inositol phosphates in response to FSH. In contrast to the lack of effect on accumulation of inositol phosphates, FSH stimulated 4- to 11-fold increases in estradiol secretion over 24 h of culture, indicating that Sertoli cells were viable and responsive to FSH. AIF4- has been shown to activate G-proteins involved in regulation of adenylate cyclase activity. In the present study, AIF4- induced 4- to 5-fold increases in IP, IP2, and IP3 in experiments wherein FSH had no effect. Pretreatment of Sertoli cells with pertussis toxin (100 and 1000 ng/ml) for 24 h inhibited fluoride-induced generation of IP, IP2, and IP3 by 24-51%. Similar treatment with cholera toxin had no effect on basal or fluoride-induced generation of IP2 or IP3, but increased fluoride-induced generation of IP by 20-34%

  11. Immunofluorescence Analysis of Testicular Biopsies With Germ Cell and Sertoli Cell Markers Shows Significant MVH Negative Germ Cell Depletion With Older Age of Orchidopexy

    DEFF Research Database (Denmark)

    Li, Ruili; Thorup, Jørgen Mogens; Sun, Cong

    2014-01-01

    Undescended testis is the most common defect in newborn boys. It is associated with increased risks of infertility and testicular malignancy due to abnormal germ cell development in these testes. Early surgery may limit such risks. The aim of our study was to analyse germ cell development verses ...... age of orchidopexy using a germ cell marker and a Sertoli cell marker on testicular biopsies.......Undescended testis is the most common defect in newborn boys. It is associated with increased risks of infertility and testicular malignancy due to abnormal germ cell development in these testes. Early surgery may limit such risks. The aim of our study was to analyse germ cell development verses...

  12. p,p′-DDE Induces Apoptosis of Rat Sertoli Cells via a FasL-Dependent Pathway

    Directory of Open Access Journals (Sweden)

    Yuqin Shi

    2009-01-01

    Full Text Available One,1-dichloro-2,2 bis(p-chlorophenyl ethylene (p,p′-DDE, the major metabolite of 2,2-bis(4-Chlorophenyl-1,1,1-trichloroethane (DDT, is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p′-DDE exposure causes male reproductive toxicity remains unknown. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in p,p′-DDE-induced toxicity in male reproductive system. The results indicated that p,p′-DDE exposure at over 30 μM showed the induction of apoptotic cell death. p,p′-DDE could induce increases in FasL mRNA and protein, which could be blocked by an antioxidant agent, N-acetyl-l-cysteine (NAC. In addition, caspase-3 and -8 were activated by p,p′-DDE treatment in these cells. The activation of NF-κB was enhanced with the increase of p,p′-DDE dose. Taken together, these results suggested that exposure to p,p′-DDE might induce apoptosis of rat Sertoli cells through a FasL-dependent pathway.

  13. Formulants of glyphosate-based herbicides have more deleterious impact than glyphosate on TM4 Sertoli cells.

    Science.gov (United States)

    Vanlaeys, Alison; Dubuisson, Florine; Seralini, Gilles-Eric; Travert, Carine

    2018-05-15

    Roundup and Glyphogan are glyphosate-based herbicides containing the same concentration of glyphosate and confidential formulants. Formulants are declared as inert diluents but some are more toxic than glyphosate, such as the family of polyethoxylated alkylamines (POEA). We tested glyphosate alone, glyphosate-based herbicide formulations and POEA on the immature mouse Sertoli cell line (TM4), at concentrations ranging from environmental to agricultural-use levels. Our results show that formulations of glyphosate-based herbicides induce TM4 mitochondrial dysfunction (like glyphosate, but to a lesser extent), disruption of cell detoxification systems, lipid droplet accumulation and mortality at sub-agricultural doses. Formulants, especially those present in Glyphogan, are more deleterious than glyphosate and thus should be considered as active principles of these pesticides. Lipid droplet accumulation after acute exposure to POEA suggests the rapid penetration and accumulation of formulants, leading to mortality after 24 h. As Sertoli cells are essential for testicular development and normal onset of spermatogenesis, disturbance of their function by glyphosate-based herbicides could contribute to disruption of reproductive function demonstrated in mammals exposed to these pesticides at a prepubertal stage of development. Copyright © 2017. Published by Elsevier Ltd.

  14. The Oncogenic Roles of DICER1 RNase IIIb Domain Mutations in Ovarian Sertoli-Leydig Cell Tumors

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    Yemin Wang

    2015-08-01

    Full Text Available DICER1, an endoribonuclease required for microRNA (miRNA biogenesis, is essential for embryogenesis and the development of many organs including ovaries. We have recently identified somatic hotspot mutations in RNase IIIb domain of DICER1 in half of ovarian Sertoli-Leydig cell tumors, a rare class of sex-cord stromal cell tumors in young women. These hotspot mutations lost IIIb cleavage activity of DICER1 in vitro and failed to produce 5p-derived miRNAs in mouse Dicer1-null ES cells. However, the oncogenic potential of these hotspot DICER1 mutations has not been studied. Here, we further revealed that the global expression of 5p-derived miRNAs was dramatically reduced in ovarian Sertoli-Leydig cell tumors carrying DICER1 hotspot mutations compared with those without DICER1 hotspot mutation. The miRNA production defect was associated with the deregulation of genes controlling cell proliferation and the cell fate. Using an immortalized human granulosa cell line, SVOG3e, we determined that the D1709N-DICER1 hotspot mutation failed to produce 5p-derived miRNAs, deregulated the expression of several genes that control gonadal differentiation and cell proliferation, and promoted cell growth. Re-expression of let-7 significantly inhibited the growth of D1709N-DICER1 SVOG3e cells, accompanied by the suppression of key regulators of cell cycle control and ovarian gonad differentiation. Taken together, our data revealed that DICER1 hotspot mutations cause systemic loss of 5p-miRNAs that can both drive pseudodifferentiation of testicular elements and cause oncogenic transformation in the ovary.

  15. The Sertoli Cell Only Syndrome and Glaucoma in a Sex - Determining Region Y (SRY) Positive XX Infertile Male.

    Science.gov (United States)

    Jain, Manish; V, Veeramohan; Chaudhary, Isha; Halder, Ashutosh

    2013-07-01

    The XX male syndrome is a rare genetic disorder. The phenotype is variable; it ranges from a severe impairment of the external genitalia to a normal male phenotype with infertility. It generally results from an unequal crossing over between the short arms of the sex chromosomes (X and Y). We are reporting a case of a 38-year-old man who presented with infertility and the features of hypogonadism and glaucoma. The examinations revealed normal external male genitalia, soft small testes, gynaecomastia and glaucoma. The semen analysis showed azoospermia. The serum gonadotropins were high, with low Anti Mullerian Hormone (AMH) and Inhibin B levels. The chromosomal analysis demonstrated a 46, XX karyotype. Fluorescent In-Situ Hybridization (FISH) and Polymerase Chain Reaction (PCR) revealed the presence of a Sex-determining Region Y (SRY). Testicular Fine Needle Aspiration Cytology (FNAC) revealed the Sertoli Cell Only Syndrome (SCOS). The presence of only Sertoli Cells in the testes, with glaucoma in the XX male syndrome, to our knowledge, has not been reported in the literature.

  16. Gonadotrophins, testosterone and spermatogenesis in neonatally irradiated male rates: evidence for a role of the Sertoli cell in follicle-stimulating hormone feedback

    International Nuclear Information System (INIS)

    De Jong, F.H.; Sharpe, R.M.

    1977-01-01

    Peripheral concentrations of FSH in the male rat seem to be regulated in parts by a protein hormone, inhibin, which originates from the testes. In an attempt to ascertain which type of testicular cell secretes inhibin, groups of male rats were irradiated prenatally or on days 4, 6 or 8 of postnatal life, and killed at 21, 51 or 81 days of age together with castrated and intact controls. The concentrations of FSH and LH in the pituitary gland, and FSH, LH and testosterone in the plasma were estimated for each animal, and the numbers of each class of intratubular cell in the testes were calculated. Rats irradiated neonatally had fewer Sertoli cells than controls at all ages studied, while the numbers of Sertoli cells in rats irradiated prenatally were higher than those in controls on day 21. The number of spermatogenic cells was usually decreased in rats irradiated postnatally. In the rats irradiated prenatally normal numbers of spermatogenic cells were found at day 51. Numbers of spermatogenic cells were significantly correlated with the number of Sertoli cells at the ages of 51 and 81 days. The concentration of FSH in the plasma usually increased in the postnatally irradiated animals on days 21 and 51, but not on day 81; prenatal irradiation did not result in altered levels of FSH at any age. Peripheral levels of LH and testosterone were not affected by irradiation. The concentration of FSH in the plasma was negatively correlated with the number of Sertoli cells in all age groups, whereas significant correlations between the levels of FSH and the number of spermatogenic cells were only found at days 51 and 81. It is concluded from these data that the Sertoli cell is the most likely source of inhibin. (author)

  17. Sertoli cells in culture secrete paracrine factor(s) that inhibit peritubular myoid cell proliferation: identification of heparinoids as likely candidates

    International Nuclear Information System (INIS)

    Tung, P.S.; Fritz, I.B.

    1991-01-01

    Conditioned medium from Sertoli cells, prepared from testes of 20-day-old rats, contains component(s) that inhibit the incorporation of [3H]-thymidine into DNA of peritubular myoid cells (PMC) and inhibit the proliferation of PMC. These components are trypsin-resistant, heat-stable compounds having a molecular weight less than 30,000. The active inhibitory components in Sertoli cell conditioned medium are inactivated by treatment with heparinase, but not by treatment with hyaluronidase or chondroitin sulfate lyases. Addition of heparin or heparan sulfate results in inhibition of DNA synthesis by PMC in a dose-dependent manner, whereas other glycosaminoglycans (GAGs) examined (hyaluronic acid, keratan sulfate, and chondroitin sulfate) have no detectable effects. Heparin and heparan sulfate are unique among GAGs tested in inhibiting the characteristic multilayer growth pattern of PMC following the attainment of confluence in serum-rich medium. On the basis of these and other data presented, it is concluded that heparin and other heparin-like GAGs synthesized by Sertoli cells are implicated in the modulation of growth of PMC in vitro during co-culture. It is postulated that heparin may play a similar role in maintaining the quiescent peritubular myoid cell phenotype in vivo

  18. Opioid system manipulation during testicular development: results on sperm production and sertoli cells population - doi: 10.4025/actascibiolsci.v33i2.5940 Opioid system manipulation during testicular development: results on sperm production and sertoli cells population - doi: 10.4025/actascibiolsci.v33i2.5940

    Directory of Open Access Journals (Sweden)

    Valdemiro Amaro Silva Júnior

    2011-05-01

    Full Text Available The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through β-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1 during fetal and neonatal period in Wistar rats. According to the results, the manipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.The Sertoli cell has fundamental importance to the development and maintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal period through β-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine and reproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1 during fetal and neonatal period in Wistar rats. According to the results

  19. Persistent Mullerian duct syndrome in a Miniature Schnauzer dog with signs of feminization and a Sertoli cell tumour.

    Science.gov (United States)

    Vegter, A R; Kooistra, H S; van Sluijs, F J; van Bruggen, L W L; Ijzer, J; Zijlstra, C; Okkens, A C

    2010-06-01

    A 5-year-old male Miniature Schnauzer was presented with unilateral cryptorchidism and signs of feminization. Abdominal ultrasonography revealed an enlarged right testis and a large, fluid-filled cavity that appeared to arise from the prostate. Computed tomography revealed the cavity to be consistent with an enlarged uterine body, arising from the prostate, and showed two structures resembling uterine horns that terminated close to the adjacent testes. The dog had a normal male karyotype, 78 XY. Gonadohysterectomy was performed and both the surgical and the histological findings confirmed the presence of a uterus in this male animal, resulting in a diagnosis of persistent Mullerian duct syndrome (PMDS). The enlarged intra-abdominal testis contained a Sertoli cell tumour. Computed tomography proved to be an excellent diagnostic tool for PMDS.

  20. A case of persistent Müllerian duct syndrome with sertoli cell tumor and hydrometra in a dog.

    Science.gov (United States)

    Matsuu, Aya; Hashizume, Takuya; Kanda, Teppei; Nagano, Masashi; Sugiyama, Akihiko; Okamoto, Yoshiharu; Hikasa, Yoshiaki

    2009-03-01

    A 10-year-old Miniature Schnauzer with bilateral cryptorchidism and male external genitalia was referred with a history of abdominal enlargement. Upon exploratory laparotomy, two tumors and a connecting structure similar to fluid-filled uterus were recognized. After cytological and bacterial examinations of the fluid and histological examination, this dog was diagnosed with bilateral Sertoli cell tumor with hydrometra. The karyotype of this dog was 78, XY and the sry gene was detected positive by PCR. We diagnosed this dog as a case of persistent Müllerian duct syndrome (PMDS), which is male pseudohermaphroditism. This is the first report regarding the incidence of PMDS in Miniature Schnauzers in Japan, and it suggests the involvement of a gene carrier.

  1. Use of Aromatase Inhibitors in Large Cell Calcifying Sertoli Cell Tumors: Effects on Gynecomastia, Growth Velocity, and Bone Age

    Science.gov (United States)

    Crocker, Melissa K.; Gourgari, Evgenia; Stratakis, Constantine A.

    2014-01-01

    Context: Large cell calcifying Sertoli cell tumors (LCCSCT) present in isolation or, especially in children, in association with Carney Complex (CNC) or Peutz-Jeghers Syndrome (PJS). These tumors overexpress aromatase (CYP19A1), which leads to increased conversion of delta-4-androstenedione to estrone and testosterone to estradiol. Prepubertal boys may present with growth acceleration, advanced bone age, and gynecomastia. Objective: To investigate the outcomes of aromatase inhibitor therapy (AIT) in prepubertal boys with LCCSCTs. Design: Case series of a very rare tumor and chart review of cases treated at other institutions. Setting: Tertiary care and referral center. Patients: Six boys, five with PJS and one with CNC, were referred to the National Institutes of Health for treatment of LCCSCT. All patients had gynecomastia, testicular enlargement, and advanced bone ages, and were being treated by their referring physicians with AIT. Interventions: Patients were treated for a total of 6–60 months on AIT. Main Outcome Measures: Height, breast tissue mass, and testicular size were all followed; physical examination, scrotal ultrasounds, and bone ages were obtained, and hormonal concentrations and tumor markers were measured. Results: Tumor markers were negative. All patients had decreases in breast tissue while on therapy. Height percentiles declined, and predicted adult height moved closer to midparental height as bone age advancement slowed. Testicular enlargement stabilized until entry into central puberty. Only one patient required unilateral orchiectomy. Conclusions: Patients with LCCSCT benefit from AIT with reduction and/or elimination of gynecomastia and slowing of linear growth and bone age advancement. Further study of long-term outcomes and safety monitoring are needed but these preliminary data suggest that mammoplasty and/or orchiectomy may be foregone in light of the availability of medical therapy. PMID:25226294

  2. Opioid system manipulation during testicular development: results on sperm production and sertoli cells population = Manipulação do sistema opioidérgico durante o desenvolvimento testicular: consequência sobre a produção espermática e a população de células de sertoli

    Directory of Open Access Journals (Sweden)

    Fernanda Mafra Cajú

    2011-04-01

    Full Text Available The Sertoli cell has fundamental importance to the development andmaintenance of spermatogenesis, as well as it has a directly proportional numerical relationship to sperm production. The proliferative period of this cell in rats occurs between 13 days pre-natal and 21 days pos-natal, when is established the final population in adult animals. The Leydig cell can modulate the Sertoli cell proliferation during fetal and neonatal periodƒn throughƒnƒnƒÒ-endorphin. The manipulation of opioidergic system can promote changes in parameters related to development of nervous, endocrine andreproductive systems. By the way, the main purpose of this present work was to compare the effects of the blockade of opioid receptor blocking in Sertoli cells using naltrexone (50 mg kg-1 during fetal and neonatal period in Wistar rats. According to the results, themanipulation of opioidergic system during pre-natal period reduced the total length of seminiferous tubule and Sertoli cell population in adult rats, but sperm production was normal because this cell has had a compensatory response for spermatozoids support capacity.As celulas de Sertoli tem fundamental importancia para o desenvolvimento e manutencao da espermatogenese, bem como possuem uma relacao numerica diretamente proporcional com a producao espermatica. O periodo proliferativo destas celulas em ratos ocorre entre 13 dias pre-natal e 21 dias pos-natal, resultando na definicao da populacao decelulas de Sertoli nos animais adultos. As celulas de Leydig podem modular a proliferacao das celulas de Sertoli durante o periodo fetal e neonatal por meio da ƒÒ-endorfina. A manipulacao do sistema opioidergico durante esta fase pode promover alteracoes em parametros relacionados com o desenvolvimento dos sistemas nervoso, endocrino ereprodutivo. Em virtude disto, o objetivo do presente trabalho foi comparar os efeitos do bloqueio de receptores opioides nas celulas de Sertoli, utilizando o naltrexone (50 mg kg

  3. Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 5: intercellular junctions and contacts between germs cells and Sertoli cells and their regulatory interactions, testicular cholesterol, and genes/proteins associated with more than one germ cell generation.

    Science.gov (United States)

    Hermo, Louis; Pelletier, R-Marc; Cyr, Daniel G; Smith, Charles E

    2010-04-01

    In the testis, cell adhesion and junctional molecules permit specific interactions and intracellular communication between germ and Sertoli cells and apposed Sertoli cells. Among the many adhesion family of proteins, NCAM, nectin and nectin-like, catenins, and cadherens will be discussed, along with gap junctions between germ and Sertoli cells and the many members of the connexin family. The blood-testis barrier separates the haploid spermatids from blood borne elements. In the barrier, the intercellular junctions consist of many proteins such as occludin, tricellulin, and claudins. Changes in the expression of cell adhesion molecules are also an essential part of the mechanism that allows germ cells to move from the basal compartment of the seminiferous tubule to the adluminal compartment thus crossing the blood-testis barrier and well-defined proteins have been shown to assist in this process. Several structural components show interactions between germ cells to Sertoli cells such as the ectoplasmic specialization which are more closely related to Sertoli cells and tubulobulbar complexes that are processes of elongating spermatids embedded into Sertoli cells. Germ cells also modify several Sertoli functions and this also appears to be the case for residual bodies. Cholesterol plays a significant role during spermatogenesis and is essential for germ cell development. Lastly, we list genes/proteins that are expressed not only in any one specific generation of germ cells but across more than one generation. Copyright 2009 Wiley-Liss, Inc.

  4. The Effects of Sertoli Cells Condition Medium and Retinoic Acid on the Number of Colonies of Bone Marrow Mesenchymal Stem Cells

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    Maryam Salem

    2017-04-01

    Full Text Available Background & objectives: According to importance of bone marrow mesenchymal stem cells in production of different cell lines, transplantation of these cells are used for treatment of many different diseases during cell therapy. Viability and proliferation of these cells after transplantation are very important. Since infertility is as public health problem in men and women, the scientists attempt to produce germ cells from differentiation of stem cells. It is supposed to use these cells for treatment of different illnesses especially for men with lack of germ cells in testes in future. However, in using stem cells for cell therapy the culture medium should be designed to increase the number of cells and efficiency of transplantation and to guarantee the health of the cells in terms of DNA damage. This study designed a suitable culture medium in order to increase the number of colonies and decrease the cell injuries. Methods: In this study mesenchymal stem cells isolated from bone marrow of mice and exposed to retinoic acid (RA with concentration of 10-6 M and Sertoli cells condition medium. Since mesenchymal stem cells (MSCs produce fibroblastic colonies so the number of colonies was counted every 3 days after culture (days of 2, 5, 8, 11, and 15 under inverted microscope. The staining of ethidium bromide-acridine orange was also done for determination of apoptotic nucleus in days of 10 and 15 after culture. Results: The results showed that the effects of retinoic acid on grow and viability of MSCs is related to the time. It seems that RA increased the proliferation of the cells and the number of colonies increased in low time but the apoptotic cells elevated with increasing the time of culture. Condition medium of Sertoli cells also increased the proliferation of bone marrow stem cells. Conclusion: According to proliferative properties of condition medium, it seems that using condition medium together with RA is better than RA alone for

  5. Development of a Cytocompatible Scaffold from Pig Immature Testicular Tissue Allowing Human Sertoli Cell Attachment, Proliferation and Functionality

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    Maxime Vermeulen

    2018-01-01

    Full Text Available Cryopreservation of immature testicular tissue before chemo/radiotherapy is the only option to preserve fertility of cancer-affected prepubertal boys. To avoid reintroduction of malignant cells, development of a transplantable scaffold by decellularization of pig immature testicular tissue (ITT able to support decontaminated testicular cells could be an option for fertility restoration in these patients. We, therefore, compared decellularization protocols to produce a cytocompatible scaffold. Fragments of ITT from 15 piglets were decellularized using three protocols: sodium dodecyl sulfate (SDS-Triton (ST, Triton-SDS-Triton (TST and trypsin 0.05%/ethylenediaminetetraacetic acid (EDTA 0.02%-Triton (TET with varying detergent concentrations. All protocols were able to lower DNA levels. Collagen retention was demonstrated in all groups except ST 1%, and a significant decrease in glycosaminoglycans was observed in the TST 1% and TET 1% groups. When Sertoli cells (SCs were cultured with decellularized tissue, no signs of cytotoxicity were detected. A higher SC proliferation rate and greater stem cell factor secretion were observed than with SCs cultured without scaffold. ST 0.01% and TET 3% conditions offered the best compromise in terms of DNA elimination and extracellular matrix (ECM preservation, while ensuring good attachment, proliferation and functionality of human SCs. This study demonstrates the potential of using decellularized pig ITT for human testicular tissue engineering purposes.

  6. Zearalenone altered the cytoskeletal structure via ER stress- autophagy- oxidative stress pathway in mouse TM4 Sertoli cells.

    Science.gov (United States)

    Zheng, Wanglong; Wang, Bingjie; Si, Mengxue; Zou, Hui; Song, Ruilong; Gu, Jianhong; Yuan, Yan; Liu, Xuezhong; Zhu, Guoqiang; Bai, Jianfa; Bian, Jianchun; Liu, ZongPing

    2018-02-20

    The aim of this study was to investigate the molecular mechanisms of the destruction of cytoskeletal structure by Zearalenone (ZEA) in mouse-derived TM4 cells. In order to investigate the role of autophagy, oxidative stress and endoplasmic reticulum(ER) stress in the process of destruction of cytoskeletal structure, the effects of ZEA on the cell viability, cytoskeletal structure, autophagy, oxidative stress, ER stress, MAPK and PI3K- AKT- mTOR signaling pathways were studied. The data demonstrated that ZEA damaged the cytoskeletal structure through the induction of autophagy that leads to the alteration of cytoskeletal structure via elevated oxidative stress. Our results further showed that the autophagy was stimulated by ZEA through PI3K-AKT-mTOR and MAPK signaling pathways in TM4 cells. In addition, ZEA also induced the ER stress which was involved in the induction of the autophagy through inhibiting the ERK signal pathway to suppress the phosphorylation of mTOR. ER stress was involved in the damage of cytoskeletal structure through induction of autophagy by producing ROS. Taken together, this study revealed that ZEA altered the cytoskeletal structure via oxidative stress - autophagy- ER stress pathway in mouse TM4 Sertoli cells.

  7. Tributyltin chloride induced testicular toxicity by JNK and p38 activation, redox imbalance and cell death in sertoli-germ cell co-culture.

    Science.gov (United States)

    Mitra, Sumonto; Srivastava, Ankit; Khandelwal, Shashi

    2013-12-06

    The widespread use of tributyltin (TBT) as biocides in antifouling paints and agricultural chemicals has led to environmental and marine pollution. Human exposure occurs mainly through TBT contaminated seafood and drinking water. It is a well known endocrine disruptor in mammals, but its molecular mechanism in testicular damage is largely unexplored. This study was therefore, designed to ascertain effects of tributyltin chloride (TBTC) on sertoli-germ cell co-culture in ex-vivo and in the testicular tissue in-vivo conditions. An initial Ca(2+) rise followed by ROS generation and glutathione depletion resulted in oxidative damage and cell death. We observed p38 and JNK phosphorylation, stress proteins (Nrf2, MT and GST) induction and mitochondrial depolarization leading to caspase-3 activation. Prevention of TBTC reduced cell survival and cell death by Ca(2+) inhibitors and free radical scavengers specify definitive role of Ca(2+) and ROS. Sertoli cells were found to be more severely affected which in turn can hamper germ cells functionality. TBTC exposure in-vivo resulted in increased tin content in the testis with enhanced Evans blue leakage into the testicular tissue indicating blood-testis barrier disruption. Tesmin levels were significantly diminished and histopathological studies revealed marked tissue damage. Our data collectively indicates the toxic manifestations of TBTC on the male reproductive system and the mechanisms involved. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  8. Kinetic study of internalization and degradation of 131I-labeled follicle-stimulating hormone in mouse Sertoli cells and its relevance to other systems

    International Nuclear Information System (INIS)

    Shimizu, A.; Kawashima, S.

    1989-01-01

    The behavior of 131I-labeled follicle-stimulating hormone (FSH) after binding to cell-surface receptors in cultured Sertoli cells of C57BL/6NCrj mice was investigated. Sertoli cells cultured in F12/DME were pulse-labeled with 131I-FSH for 10 min at 4 degrees C, followed by cold chase for various periods of time. After the cold chase Sertoli cells were treated with 0.2 M acetate (pH 2.5) to dissociate membrane-bound 131I-FSH (surface radioactivity). The medium containing radioactivity after cold chase was mixed with 20% trichloroacetic acid, centrifuged, and the radioactivity of the supernatant was measured (degraded hormone). The radiolabeled materials associated with each process (surface binding, internalization, and degradation) were concentrated with ultrafiltration and characterized with gel filtration and/or thin layer chromatography. The effects of lysosomotropic agents, NH4Cl and chloroquine, were studied. The cold chase study at 32 degrees C showed that the surface radioactivity was the largest among the three kinds of radioactivities associated with each process immediately after pulse labeling, but the surface radioactivity rapidly decreased, while the internalized radioactivity increased. The cold chase study at 4 degrees C did not show such time-related changes in radioactivities, and a high level of surface radioactivity constantly persisted. The surface and internalized radioactivities were due to 131I-FSH, and the degraded radioactivity was mainly due to [131I]monoiodotyrosine. When Sertoli cells were cultured with lysosomotropic agents, the internalized radioactivity increased, while the degraded radioactivity decreased. Based on these observations, a kinetic model was proposed and the relationships among the surface, internalized, and degraded radioactivities and cold chase time were calculated algebraically

  9. Stage and season effects on cell cycle and apoptotic activities of germ cells and Sertoli cells during spermatogenesis in the spiny dogfish (Squalus acanthias).

    Science.gov (United States)

    McClusky, L M

    2005-01-01

    To understand the processes involved in the spatial and temporal maturation of testicular cells in Squalus acanthias, we used standard morphometry, proliferating-cell nuclear antigen (PCNA) and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) immunohistochemistry. Except for immature spermatocysts (germinal zone, GZ; early-stage pre-meiotic, E-PrM), the number of cysts in all subsequent stages and the total number of cysts in the spermatogenic progression varied seasonally. The spermatogenic cycle spans about 2 years and is interrupted by germcell clone deletion via apoptosis at the mitosis-meiosis transition in April/May, manifesting as a zone of degeneration (ZD). Rate of displacement of the ZD across the testis diameter indicates that late-stage premeiotic (L-PrM) generations 12-13 require 9-10 months to reach the mature-spermatid stage. Also, the number of cysts completing spermatogenesis is approximately 4-5-fold less than the number that entered spermatogenesis proper 2 years earlier. Pronounced gonocytogenesis in the germinal ridge was coincident with ZD formation in April/May, but it was absent in the fall when mature spermatogonial and meiotic activities had resumed. Whereas strong Sertoli cell PCNA immunoreactivity dominated the GZ cyst cell-cycle activities throughout the year, except during the spring/summer months, the spermatogonial- and Sertoli-cell PCNA indices in E-PrM cysts were inversely related. PCNA immunoreactivity in spermatocytes was seasonal and dependent on the stage of meiosis. TUNEL labelling was limited to spermatogonia and increased stage-dependently in the PrM region (L-PrM = mid-stage PrM >E-PrM >GZ), correlating with ZD formation, in a season-dependent manner. Results imply that effects of normal regulatory factors in Squalus are stage- and process-specific.

  10. Retiform Sertoli-Leydig cell tumor of ovary in a 9-year-old girl: case report and review of the literature.

    Science.gov (United States)

    Lou, Weizhen; Cao, Dongyan; Yang, Jiaxin; Guo, Lina; Shen, Keng

    2011-12-01

    The management of the retiform variant of Sertoli-Leydig cell tumor remains a challenge for the gynecologist. Surgery is the preferred treatment, but it is still inconclusive whether complete staging or postoperative adjuvant therapy is necessary. A 9-year-old girl was admitted with a well-circumscribed, solid cystic mass in the lower abdomen, of size corresponding to a 20-week gravid uterus, without any androgenic manifestations. Per-operatively, the mass arose from left ovary, which had a smooth outer surface with intact capsule. A cut section was almost multiloculated with cysts ranging from 0.5 to 2.5 cm in diameter and filled with thin yellow or brown serous fluid. Left salpingo-oophorectomy, bilateral lymph node dissection, infracolic omentectomy and appendectomy were performed. The pathological diagnosis was retiform pattern of intermediate to poorly differentiated Sertoli-Leydig cell tumor. The clinical stage was IA. The patient was followed up 3-monthly, and was disease-free at 18-month follow-up after the initial treatment. After review of the literature, we conclude that the retiform variant is a special subtype of Sertoli-Leydig cell tumors. Because of their young age, the uncertain malignant potential and rare bilaterality, patients should be treated conservatively whenever possible. There is at present no good evidence that postoperative adjuvant therapy is effective in preventing recurrence.

  11. Tight multilattices calculated by extended-cell cylindrization

    Energy Technology Data Exchange (ETDEWEB)

    Segev, M; Carmona, S

    1983-01-01

    Among the common features of advanced LWR concepts are the tightness of lattices and the symbiotic setting of different fuels. Such symbioses often come in the form of multilattices, whose numerically-repeated unit is a configuration of several pins, typically with one pin type at the center and pins of a second type surrounding the center pin. If this extended-cell (EC) unit is cylindricized, then a simple transport calculation of the unit will be possible. If the lattice of such units is tight, there is further an a priori reason to expect the cylindrization to introduce only a small distortion of the true neutron fluxes in the lattice. A strict numerical validation of the EC cylindrization approximation is impractical, but similar validations can be carried out for regular lattices, viewed as being made up of multicell units whose centers are moderators and whose peripheries are fuel pins. In these comparisons the EC cylindrization approximation gives good results.

  12. Smad2/3 Upregulates the Expression of Vimentin and Affects Its Distribution in DBP-Exposed Sertoli Cells

    Directory of Open Access Journals (Sweden)

    Xi Zhang

    2015-01-01

    Full Text Available Sertoli cells (SCs in the testes provide physical and nutritional support to germ cells. The vimentin cytoskeleton in SCs is disrupted by dibutyl phthalate (DBP, which leads to SCs dysfunction. In a previous study, we found that peroxisome proliferator-activated receptor alpha (PPARα influenced the distribution of vimentin by affecting its phosphorylation in DBP-exposed SCs. In the present study, we investigated the role of Smad2/3 in regulating the expression of vimentin in DBP-exposed SCs. We hypothesized that Smad2/3 affects the distribution of vimentin by regulating its expression and that there is cross talk between Smad2/3 and PPARα. The real-time PCR and ChIP-qPCR results showed that SB431542 (an inhibitor of Smad2/3 could significantly attenuate the expression of vimentin induced by DBP in SCs. Phosphorylated and soluble vimentin were both downregulated by SB431542 pretreatment. WY14643 (an agonist of PPARα pretreatment stimulated, while GW6471 (an antagonist of PPARα inhibited, the activity of Smad2/3; SB431542 pretreatment also inhibited the activity of PPARα, but it did not rescue the DBP-induced collapse in vimentin. Our results suggest that, in addition to promoting the phosphorylation of vimentin, DBP also stimulates the expression of vimentin by activating Smad2/3 in SCs and thereby induces irregular vimentin distribution.

  13. Action mechanism of inhibin α-subunit on the development of Sertoli cells and first wave of spermatogenesis in mice.

    Directory of Open Access Journals (Sweden)

    Kailai Cai

    Full Text Available Inhibin is an important marker of Sertoli cell (SC activity in animals with impaired spermatogenesis. However, the precise relationship between inhibin and SC activity is unknown. To investigate this relationship, we partially silenced both the transcription and translation of the gene for the α-subunit of inhibin, Inha, using recombinant pshRNA vectors developed with RNAi-Ready pSIREN-RetroQ-ZsGreen Vector (Clontech Laboratories, Mountain View, Calif. We found that Inha silencing suppresses the cell-cycle regulators Cyclin D1 and Cyclin E and up-regulates the cell-cycle inhibitor P21 (as detected by Western blot analysis, thereby increasing the number of SCs in the G1 phase of the cell cycle and decreasing the amount in the S-phase of the cell cycle (as detected by flow cytometry. Inha silencing also suppressed Pdgfa, Igf1, and Kitl mRNA levels and up-regulated Tgfbrs, Inhba, Inhbb, Cyp11a1, Dhh, and Tjp1 mRNA levels (as indicated by real-time polymerase chain reaction [PCR] analysis. These findings indicate that Inha has the potential to influence the availability of the ligand inhibin and its antagonist activin in the SC in an autocrine manner and inhibit the progression of SC from G1 to S. It may also participate in the development of the blood-testis barrier, Leydig cells, and spermatogenesis through its effect on Dhh, Tjp1, Kitl, and Pdgfa. Real-time PCR and Western blot analyses of Inha, Inhba, and Inhbb mRNA and Inha levels over time show that Inha plays an important role in the formation of round spermatid during the first wave of spermatogenesis in mice.

  14. Histopathological and ultrastructural changes experimentally induced by bee venom in seminiferous epithelium via structural-functional alteration of Sertoli cells.

    Science.gov (United States)

    Florea, Adrian; Puică, Constantin; Hamed, Sami; Tilinca, Mariana; Matei, Horea

    2017-11-01

    We tested here the ability of bee venom (BV) to interfere with spermatogenesis in rats in two experimental conditions. The histopathological changes were assessed with brightfield microscopy using a novel staining technique, based on methylene blue, orange G and ponceau xylidine. Transmission electron microscopy was also used to identify fine subcellular changes. BV injection for 30days in daily doses of 700μg BV/kg resulted in reducing testicular weight, along with significant larger diameters of seminiferous tubules and reduced number of Sertoli cells (SCs). SCs were vacuolated, detached from the basement membrane, many necrosed, leading to the basement membrane denudation. Germ cells layers were separated by empty spaces conferring a rarefied aspect to the tissue, and spermatids were detached into lumen. Thus, the seminiferous epithelium was significantly thinned. Many Leydig cells (LCs) were in a necrotic state, with disrupted plasma membrane and without smooth endoplasmic reticulum. The acute treatment with a single LD50 of 62mgBV/kg, was followed by focal disruptions of the basement membrane and localized areas of necrosis, mainly affecting the SCs. Most of the observed SCs as well as some spermatogonia were highly vacuoled, empty spaces being observed within the epithelium. The SCs count was significantly decreased. Spermatids had also the tendency of separation from the SCs, and the significant larger diameter of the tubules found was associated with a thicker epithelium. Many LCs were necrosed, with disrupted plasma membrane, swollen mitochondria, no endoplasmic reticulum and implicitly showing rarefied cytoplasm. We concluded that BV was a testicular toxicant affecting both the LCs and the seminiferous tubules. The SCs cells represented the primary target site of BV whose effects were next extended upon the germ cells. In all cells, BV triggered unspecific degenerative changes that could impaire spermatogenesis. The present study also proposes an

  15. Retinol-induced changes in the phosphorylation levels of histones and high mobility group proteins from Sertoli cells

    Directory of Open Access Journals (Sweden)

    Moreira J.C.F.

    2000-01-01

    Full Text Available Chromatin proteins play a role in the organization and functions of DNA. Covalent modifications of nuclear proteins modulate their interactions with DNA sequences and are probably one of the multiple factors involved in the process of switch on/off transcriptionally active regions of DNA. Histones and high mobility group proteins (HMG are subject to many covalent modifications that may modulate their capacity to bind to DNA. We investigated the changes induced in the phosphorylation pattern of cultured Wistar rat Sertoli cell histones and high mobility group protein subfamilies exposed to 7 µM retinol for up to 48 h. In each experiment, 6 h before the end of the retinol treatment each culture flask received 370 KBq/ml [32P]-phosphate. The histone and HMGs were isolated as previously described [Moreira et al. Medical Science Research (1994 22: 783-784]. The total protein obtained by either method was quantified and electrophoresed as described by Spiker [Analytical Biochemistry (1980 108: 263-265]. The gels were stained with Coomassie brilliant blue R-250 and the stained bands were cut and dissolved in 0.5 ml 30% H2O2 at 60oC for 12 h. The vials were chilled and 5.0 ml scintillation liquid was added. The radioactivity in each vial was determined with a liquid scintillation counter. Retinol treatment significantly changed the pattern of each subfamily of histone and high mobility group proteins.

  16. Sertoli cell specific knockdown of RAR-related orphan receptor (ROR) alpha at puberty reduces sperm count in rats.

    Science.gov (United States)

    Mandal, Kamal; Sarkar, Rajesh K; Sen Sharma, Souvik; Jain, Ayushi; Majumdar, Subeer S

    2018-01-30

    Globally, there is an alarming decline in sperm count. Very often hormonal supplementation fails to restore normal sperm count. Sertoli cells (Sc) present within seminiferous tubules provide appropriate niche and factors required for the differentiation of germ cells (Gc) into mature sperm (spermatogenesis). Functionally compromised Sc may be one of the reasons for failure of hormones to facilitate normal spermatogenesis. Although role of secretory proteins and signaling molecules of Sc has been studied well, role of transcription factors regulating sperm count has not been addressed appropriately. Retinoic acid receptor-related orphan receptor (ROR)-alpha is one of such transcription factors reported in testis but its role in testicular function is not yet known. In a separate study, we found abundant ROR-alpha binding sites on promoter regions of several genes upregulated in pubertal rat Sc as compared to infant Sc. Immunostaining studies also revealed presence of ROR alpha in nucleus of pubertal Sc. We generated a transgenic knockdown rat model expressing shRNA targeted to ROR-alpha under Sc specific promoter, which is transcriptionally active only at and after puberty. ROR-alpha knockdown animals were found to have abnormal association of Sc and Gc, including Gc sloughing and restricted release of sperm. The knockdown animals displayed compromised spermatogenesis leading to significant reduction in sperm count. This is the first report describing the Sc specific role of ROR-alpha in maintaining quantitatively normal sperm output. Identification of various such molecules can generate avenues to limit or reverse an alarmingly declining sperm count witnessed globally in men. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility?

    Science.gov (United States)

    Martins, Ana D; Moreira, Ana C; Sá, Rosália; Monteiro, Mariana P; Sousa, Mário; Carvalho, Rui A; Silva, Branca M; Oliveira, Pedro F; Alves, Marco G

    2015-09-01

    Human feeding behavior and lifestyle are gradually being altered, favoring the development of metabolic diseases, particularly type 2 diabetes and obesity. Leptin is produced by the adipose tissue acting as a satiety signal. Its levels have been positively correlated with fat mass and hyperleptinemia has been proposed to negatively affect male reproductive function. Nevertheless, the molecular mechanisms by which this hormone affects male fertility remain unknown. Herein, we hypothesize that leptin acts on human Sertoli cells (hSCs), the "nurse cells" of spermatogenesis, altering their metabolism. To test our hypothesis, hSCs were cultured without or with leptin (5, 25 and 50ng/mL). Leptin receptor was identified by qPCR and Western blot. Protein levels of glucose transporters (GLUT1, GLUT2 and GLUT3), phosphofructokinase, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 (MCT4) were determined by Western Blot. LDH activity was assessed and metabolite production/consumption determined by proton nuclear magnetic resonance. Oxidative damage was evaluated by assessing lipid peroxidation, protein carbonilation and nitration. Our data shows that leptin receptor is expressed in hSCs. The concentration of leptin found in lean, healthy patients, upregulated GLUT2 protein levels and concentrations of leptin found in lean and obese patients increased LDH activity. Of note, all leptin concentrations decreased hSCs acetate production illustrating a novel mechanism for this hormone action. Moreover, our data shows that leptin does not induce or protect hSCs from oxidative damage. We report that this hormone modulates the nutritional support of spermatogenesis, illustrating a novel mechanism that may be linked to obesity-induced male infertility. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Yes-associated protein and WW-containing transcription regulator 1 regulate the expression of sex-determining genes in Sertoli cells, but their inactivation does not cause sex reversal.

    Science.gov (United States)

    Levasseur, Adrien; Paquet, Marilène; Boerboom, Derek; Boyer, Alexandre

    2017-07-01

    Yes-associated protein (YAP) and WW-containing transcription regulator 1 (WWTR1) are two functionally redundant transcriptional regulators that are downstream effectors of the Hippo signaling pathway, and that act as major regulators of cell growth and differentiation. To elucidate their role in Sertoli cells, primary Sertoli cell culture from Yapflox/flox; Wwtr1flox/flox animals were infected with a Cre recombinase-expressing adenovirus. Concomitant inactivation of Yap and Wwtr1 resulted in a decrease in the mRNA levels of the male sex differentiation genes Dhh, Dmrt1, Sox9, and Wt1, whereas those of genes involved in female differentiation (Wnt4, Rspo1, and Foxl2) were induced. SOX9, FOXL2, and WNT4 proteins were regulated in the same manner as their mRNAs in response to loss of YAP and WWTR1. To further characterize the role of YAP and WWTR1 in Sertoli cells, we generated a mouse model (Yapflox/flox; Wwtr1flox/flox; Amhcre/+) in which Yap and Wwtr1 were conditionally deleted in Sertoli cells. An increase in the number of apoptotic cells was observed in the seminiferous tubules of 4 dpp mutant mice, leading to a reduction in testis weights and a decrease in the number of Sertoli cells in adult animals. Gene expression analyses of testes from 4 dpp Yapflox/flox; Wwtr1flox/flox; Amhcre/+ mice showed that Sertoli cell differentiation is initially altered, as Dhh, Dmrt1, and Sox9 mRNA levels were downregulated, whereas Wnt4 mRNA levels were increased. However, expression of these genes was not changed in older animals. Together, these results suggest a novel role of the Hippo signaling pathway in the mechanisms of sex differentiation. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  19. Endocrine and paracrine regulation of zebrafish spermatogenesis : The Sertoli cell perspective

    NARCIS (Netherlands)

    Schulz, R. W.; Nóbrega, R. H.; Vidal de Souza Morais, Roberto Daltro; De Waal, P. P.; França, L. R.; Bogerd, J.

    2015-01-01

    Spermatogonial stem cells (SSCs) either self-renew or differentiate into spermatogonia that further develop into spermatozoa. Self-renewal occurs when residing in a specific micro-environment (niche) while displacement from the niche would tip the signalling balance towards differentiation.

  20. Identification and characterization of Xenopus tropicalis common progenitors of Sertoli and peritubular myoid cell lineages

    Czech Academy of Sciences Publication Activity Database

    Tlapáková, T.; Nguyen, T.M.X.; Vegrichtova, M.; Šídová, Monika; Strnadova, K.; Bláhová, M.; Krylov, V.

    2016-01-01

    Roč. 5, č. 9 (2016), s. 1275-1282 ISSN 2046-6390 R&D Projects: GA AV ČR LK21305; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:86652036 Keywords : Testicular somatic cells * Xenopus tropicalis * Migration potential Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.095, year: 2016

  1. A Rare Case of Intra-Endometrial Leiomyoma of Uterus Simulating Degenerated Submucosal Leiomyoma Accompanied by a Large Sertoli-Leydig Cell Tumor.

    Science.gov (United States)

    Jeong, Kyungah; Lee, Sa Ra; Park, Sanghui

    2016-03-01

    A 50-year-old peri-menopausal woman presented with hard palpable mass on her lower abdomen and anemia from heavy menstrual bleeding. Ultrasonography showed a 13×12 cm sized hypoechoic solid mass in pelvis and a 2.5×2 cm hypoechoic cystic mass in uterine endometrium. Abdomino-pelvic computed tomography revealed a hypodense pelvic mass without enhancement, suggesting a leiomyoma of intraligamentary type or sex cord tumor of right ovary with submucosal myoma of uterus. Laparoscopy revealed a large Sertoli-Leydig cell tumor of right ovary with a very rare entity of intra-endometrial uterine leiomyoma accompanied by adenomyosis. The final diagnosis of ovarian sex-cord tumor (Sertoli-Leydig cell), stage Ia with intra-endometrial leiomyoma with adenomyosis, was made. Considering the large size of the tumor and poorly differentiated nature, 6 cycles of chemotherapy with Taxol and Carboplatin regimen were administered. There is neither evidence of major complications nor recurrence during 20 months' follow-up.

  2. Assessment of testicular function after acute and chronic irradiation: Further evidence for an influence of late spermatids on Sertoli cell function in the adult rat

    International Nuclear Information System (INIS)

    Pineau, C.; Velez de la Calle, J.F.; Pinon-Lataillade, G.; Jegou, B.

    1989-01-01

    To study cell to cell communications within the testis of adult Sprague-Dawley rats, we used acute whole body neutron plus gamma-irradiation over 7-121 days postirradiation and chronic whole body gamma-irradiation over 14-84 days of irradiation and 7-86 days postirradiation. Neither irradiation protocol had an effect on the body weight of the animals. Neutron plus gamma-rays induced dramatic damages to spermatogonia, preleptotene spermatocytes, spermatozoa, and, to a lesser extent, pachytene spermatocytes. In contrast, gamma-rays induced a selective destruction of spermatogonia. Subsequently, in both experiments a maturation-depletion process led to a marked decrease in all germ cell types. A complete or near complete recovery of the different germ cell types and spermatozoa took place during the two postirradiation periods. Under both irradiation protocols Sertoli cells number was unchanged. Androgen-binding protein and FSH levels were normal in spite of the disappearance of most germ cells from spermatogonia to early spermatids. However, the decline of androgen-binding protein as well as the rise of FSH and their subsequent recovery were highly correlated to the number of late spermatids and spermatozoa. Moreover, it appeared that spermatocytes may also interfere with the production of inhibin (Exp B). With neither irradiation was Leydig cell function altered, except in Exp B in which elevated LH levels were temporarily observed. Correlation analysis suggested a relationship between preleptotene spermatocytes and Leydig cell function. In conclusion, this study establishes that chronic gamma-irradiation is particularly useful in the study of intratesticular paracrine regulation in vivo and provides further support to the concept that late spermatids play a major role in controlling some aspects of Sertoli cell function in the adult rat

  3. [The ultrastructure of Sertoli cells and spermatogonia in the rats exposed to radiation under conditions of therapeutic and prophylactic application of low-intensity electromagnetic emission].

    Science.gov (United States)

    Korolev, Y N; Bobrovnitskii, I P; Geniatulina, M S; Nikulina, L A; Mikhailik, L V

    2018-04-09

    it has been demonstrated in various experimental studies that radiation exposure produces a negative impact on the processes of spermatogenesis associated with the disturbances of the microcirculation processes in the testes and the development of cellular and intracellular disintegration expressed as destructive changes in the cells leading to their death. The objective of the present study was to detect the ultrastructural abnormalities in the cells of Sertoli and spermatogonia under conditions of their exposure to radiation and to identify the peculiarities of their regeneration under the influence of the therapeutic and prophylactic application of low-intensity ultra-high frequency (UHF) electromagnetic radiation (EMR) and low-intensity low-frequency magnetic field (MF). The experiments were carried out on 28 non-pedigree mature male rats with the body weight 180-220 g that were divided into four groups. The first study group was comprised of the animals exposed to radiation followed by the application of low-intensity ultra-high frequency UHF electromagnetic radiation EMR. The rats in the second study group experienced effects of radiation and low-intensity low-frequency MF. The animals of the third (control) group were exposed to radiation alone, and those comprising the fourth group 1 (only radiation exposure) were considered to be intact. The studies with the use of electron microscopy showed that the therapeutic and prophylactic application of low-intensity ultra-high frequency (UHF) electromagnetic radiation and low-intensity low-frequency magnetic field caused the decrease in the number and the severity of post-radiation defects in the treated cells together with the increase of the number and size of mitochondria as well as hyperplasia of ribosomes; moreover, it promoted cellular and intracellular regeneration. UHF electromagnetic radiation had a more pronounced stimulating effect on the regeneration processes as compared with low-frequency MF

  4. Pregnancy and live birth after follicle-stimulating hormone treatment for an infertile couple including a male affected by Sertoli cell-only syndrome

    Directory of Open Access Journals (Sweden)

    Paulis G

    2017-10-01

    Full Text Available Gianni Paulis,1,2 Luca Paulis,3 Gennaro Romano,4 Carmen Concas,5 Marika Di Sarno,5 Renata Pagano,5 Antonio Di Filippo,5 Maria Luisa Di Petrillo5 1Andrology Center, Regina Apostolorum Hospital, Rome, Italy; 2Department of Uro-Andrology, Castelfidardo Medical Team, Peyronie’s Disease Care Center, Rome, Italy; 3Section of Pharmacology and Research, Department of Uro-Andrology, Castelfidardo Medical Team, Peyronie’s Disease Care Center, Rome, Italy; 4Department of Urologic Oncology, Italian League Against Cancer, Avellino, Italy; 5Department of Reproductive Medicine and Biology, Caran Center, Caserta, Italy Abstract: In males with nonobstructive azoospermia, one of the main histopathologic patterns of the testis is Sertoli cell-only syndrome (SCOS, in which no germ cells are present and only Sertoli cells are contained in the seminiferous tubules. There is not any formal treatment for this pathological condition. However, several studies reported the possibility to perform testicular sperm extraction in patients with SCOS, although, according to some authors, sperm retrieval is possible only in the presence of focal spermatogenesis. We report the case of an infertile couple in whom the 30-year-old male was azoospermic. After the diagnosis, the patient underwent multiple bilateral testicular biopsies, which showed a histological pattern corresponding to SCOS. We administered a cycle of hormone stimulation followed by medically assisted procreation procedures to the male patient. Therefore, the male patient was treated with follicle-stimulating hormone gonadotropin for a total of 7 months (150 IU recombinant human follicle stimulating hormone three times per week. After carrying out a new multiple testicular sperm extraction, several spermatozoa were microscopically observed, and it was then possible to perform an intracytoplasmic sperm injection with subsequent embryo transfer of the blastocyst into the wife’s uterus, and so pregnancy was

  5. Maternal undernutrition does not alter Sertoli cell numbers or the expression of key developmental markers in the mid-gestation ovine fetal testis

    Directory of Open Access Journals (Sweden)

    Andrade Luis P

    2013-01-01

    Full Text Available Abstract Background The aim of this study was to determine the effects of maternal undernutrition on ovine fetal testis morphology and expression of relevant histological indicators. Maternal undernutrition, in sheep, has been reported, previously, to alter fetal ovary development, as indicated by delayed folliculogenesis and the altered expression of ovarian apoptosis-regulating gene products, at day 110 of gestation. It is not known whether or not maternal undernutrition alters the same gene products in the day 110 fetal testis. Design and methods Mature Scottish Blackface ewes were fed either 100% (Control; C or 50% (low; L of estimated metabolisable energy requirements of a pregnant ewe, from mating to day 110 of gestation. All pregnant ewes were euthanized at day 110 and a sub-set of male fetuses was randomly selected (6 C and 9 L for histology studies designed to address the effect of nutritional state on several indices of testis development. Sertoli cell numbers were measured using a stereological method and Ki67 (cell proliferation index, Bax (pro-apoptosis, Mcl-1 (anti-apoptosis, SCF and c-kit ligand (development and apoptosis gene expression was measured in Bouins-fixed fetal testis using immunohistochemistry. Results No significant differences were observed in numbers of Sertoli cells or testicular Ki67 positive cells. The latter were localised to the testicular cords and interstitium. Bax and Mcl-1 were localised specifically to the germ cells whereas c-kit was localised to both the cords and interstitium. SCF staining was very sparse. No treatment effects were observed for any of the markers examined. Conclusions These data suggest that, unlike in the fetal ovary, maternal undernutrition for the first 110 days of gestation affects neither the morphology of the fetal testis nor the expression of gene products which regulate apoptosis. It is postulated that the effects of fetal undernutrition on testis function may be expressed

  6. Cardiac glycoside ouabain induces activation of ATF-1 and StAR expression by interacting with the α4 isoform of the sodium pump in Sertoli cells.

    Science.gov (United States)

    Dietze, Raimund; Konrad, Lutz; Shihan, Mazen; Kirch, Ulrike; Scheiner-Bobis, Georgios

    2013-03-01

    Sertoli cells express α1 and α4 isoforms of the catalytic subunit of Na(+),K(+)-ATPase (sodium pump). Our recent findings demonstrated that interactions of the α4 isoform with cardiotonic steroids (CTS) like ouabain induce signaling cascades that resemble the so-called non-classical testosterone pathway characterized by activation of the c-Src/c-Raf/Erk1/2/CREB signaling cascade. Here we investigate a possible physiological significance of the activated cascade. The results obtained in the current investigation show that the ouabain-induced signaling cascade also leads to the activation of the CREB-related activating transcription factor 1 (ATF-1) in the Sertoli cell line 93RS2 in a concentration- and time-dependent manner, as demonstrated by detection of ATF-1 phosphorylated on Ser63 in western blots. The ouabain-activated ATF-1 protein was found to localize to the cell nuclei. The sodium pump α4 isoform mediates this activation, as it is ablated when cells are incubated with siRNA to the α4 isoform. Ouabain also leads to increased expression of steroidogenic acute regulator (StAR) protein, which has been shown to be a downstream consequence of CREB/ATF-1 activation. Taking into consideration that CTS are most likely produced endogenously, the demonstrated induction of StAR expression by ouabain establishes a link between CTS, the α4 isoform of the sodium pump, and steroidogenesis crucial for male fertility and reproduction. Copyright © 2012 Elsevier B.V. All rights reserved.

  7. Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B as a Cause of Secondary Amenorrhea in an Adolescent with Germ Line DICER1 Mutation.

    Science.gov (United States)

    Luke, Amy M; Moroney, John W; Snitchler, Andrea; Whiteway, Susan L

    2017-10-01

    Ovarian tumors, although uncommon in children, can retain endocrine function that disrupts normal feedback mechanisms leading to amenorrhea. Inheritance of germline DICER1 mutations can lead to increased risk for development of ovarian Sertoli-Leydig cell tumors (SLCTs). We report, to our knowledge, the first case of secondary amenorrhea due to elevated inhibin B levels in a female adolescent with an ovarian SLCT. Ovarian tumors should be included in the differential diagnosis for pediatric patients who present with menstrual irregularities. Early evaluation of the hypothalamic-pituitary-ovarian axis and inhibin levels is appropriate. Our case also emphasizes the need for testing for DICER1 mutations in pediatric patients with ovarian SLCTs. Published by Elsevier Inc.

  8. Defining suitable reference genes for RT-qPCR analysis on human sertoli cells after 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure.

    Science.gov (United States)

    Ribeiro, Mariana Antunes; dos Reis, Mariana Bisarro; de Moraes, Leonardo Nazário; Briton-Jones, Christine; Rainho, Cláudia Aparecida; Scarano, Wellerson Rodrigo

    2014-11-01

    Quantitative real-time RT-PCR (qPCR) has proven to be a valuable molecular technique to quantify gene expression. There are few studies in the literature that describe suitable reference genes to normalize gene expression data. Studies of transcriptionally disruptive toxins, like tetrachlorodibenzo-p-dioxin (TCDD), require careful consideration of reference genes. The present study was designed to validate potential reference genes in human Sertoli cells after exposure to TCDD. 32 candidate reference genes were analyzed to determine their applicability. geNorm and NormFinder softwares were used to obtain an estimation of the expression stability of the 32 genes and to identify the most suitable genes for qPCR data normalization.

  9. Regulation of follitropin-sensitive adenylate cyclase by stimulatory and inhibitory forms of the guanine nucleotide regulatory protein in immature rat Sertoli cells

    International Nuclear Information System (INIS)

    Johnson, G.P.

    1987-01-01

    Studies have been designed to examine the role of guanine nucleotides in mediating FSH-sensitive adenylate cyclase activity in Sertoli cell plasma membranes. Analysis of [ 3 H]GDP binding to plasma membranes suggested a single high affinity site with a K d = 0.24 uM. Competition studies indicated that GTP γ S was 7-fold more potent than GDP β S. Bound GDP could be released by FSH in the presence of GTP γ S, but not by FSH alone. Adenylate cyclase activity was enhanced 5-fold by FSH in the presence of GTP. Addition of GDP β S to the activated enzyme (FSH plus GTP) resulted in a time-dependent decay to basal activity within 20 sec. GDP β S competitively inhibited GTP γ S-stimulated adenylate cyclase activity with a K i = 0.18 uM. Adenylate cyclase activity was also demonstrated to be sensitive to the nucleotide bound state. In the presence of FSH, only the GTP γ S-bound form persisted even if GDP β S previously occupied all available binding sites. Two membrane proteins, M r = 43,000 and 48,000, were ADP·ribosylated using cholera toxin and labeling was enhanced 2 to 4-fold by GTP γ S but not by GDP β S. The M r = 43,000 and 48,000 proteins represented variant forms of G S . A single protein of M r = 40,000 (G i ) was ADP-ribosylated by pertussis toxin in vitro. GTP inhibited forskolin-stimulated adenylate cyclase activity with an IC 50 = 0.1 uM. The adenosine analog, N 6 ·phenylisopropyl adenosine enhanced GTP inhibition of forskolin-stimulated adenylate cyclase activity by an additional 15%. GTP-dependent inhibition of forskolin-sensitive adenylate cyclase activity was abolished in membranes prepared from Sertoli cells treated in culture with pertussis toxin

  10. mTOR is involved in 17β-estradiol-induced, cultured immature boar Sertoli cell proliferation via regulating the expression of SKP2, CCND1, and CCNE1.

    Science.gov (United States)

    Yang, Wei-Rong; Wang, Yong; Wang, Yi; Zhang, Jiao-Jiao; Zhang, Jia-Hua; Lu, Cheng; Wang, Xian-Zhong

    2015-04-01

    Mammalian target of rapamycin (mTOR) is known to be involved in mammalian cell proliferation, while S-phase kinase-associated protein 2 (SKP2) plays a vital role in the cell cycle. Within the testis, estrogen also plays an important role in Sertoli cell proliferation, although it is not clear how. The present study asked if mTOR is involved in 17β-estradiol-dependent Sertoli cell proliferation. We specifically assessed if extracellular signal-regulated kinase 1/2 (ERK1/2) and/or phosphoinositide 3-kinase/protein kinase B (PI3K/AKT) exert convergent effects toward the activation of mTOR signaling, and if this signaling regulates the expression of SKP2 through retinoblastoma (RB) and early mitotic inhibitor 1 (EMI1) protein and on CCNE1 and CCND1 mRNA levels. Treatment with 17β-estradiol for 15-90 min activated mTOR, with mTOR phosphorylation peaking after 30 min. U0126 (5 μM), a specific inhibitor of (MEK1/2), and 10-DEBC (2 μM), a selective inhibitor of AKT, both significantly reduced 17β-estradiol-induced phosphorylation of mTOR. Rapamycin suppressed 17β-estradiol-induced Sertoli cell proliferation, appearing to act by reducing the abundance of SKP2, CCND1, and CCNE1 mRNA as well as RB and EMI1 protein. These data indicated that 17β-estradiol enhances Sertoli cell proliferation via mTOR activation, which involves both ERK1/2 and PI3K/AKT signaling. Activated mTOR subsequently increases SKP2 mRNA and protein expression by enhancing the expression of CCND1 and CCNE1, and inhibits SKP2 protein degradation by increasing EMI1 abundance. © 2015 Wiley Periodicals, Inc.

  11. Hexavalent chromium at low concentration alters Sertoli cell barrier and connexin 43 gap junction but not claudin-11 and N-cadherin in the rat seminiferous tubule culture model

    Energy Technology Data Exchange (ETDEWEB)

    Carette, Diane [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Perrard, Marie-Hélène, E-mail: marie-helene.durand@ens-lyon.fr [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Prisant, Nadia [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Gilleron, Jérome; Pointis, Georges [INSERM U 1065, Team 5 “Physiopathology of Germ Cell Control: Genomic and Non Genomic Mechanisms” C3M, University of Nice Sophia Antipolis, Nice (France); Segretain, Dominique [University of Versailles/St Quentin-en-Yvelines (France); UMR S775, University Paris Descartes, 45 rue des Saints Pères, 75006, Paris (France); Durand, Philippe [Institut de Génomique Fonctionnelle de Lyon, Université de Lyon, Université Lyon I, CNRS, INRA, Ecole Normale Supérieure de Lyon, Lyon (France); Kallistem SAS Ecole Normale Supérieure de Lyon, Lyon (France)

    2013-04-01

    Exposure to toxic metals, specifically those belonging to the nonessential group leads to human health defects and among them reprotoxic effects. The mechanisms by which these metals produce their negative effects on spermatogenesis have not been fully elucidated. By using the Durand's validated seminiferous tubule culture model, which mimics the in vivo situation, we recently reported that concentrations of hexavalent chromium, reported in the literature to be closed to that found in the blood circulation of men, increase the number of germ cell cytogenetic abnormalities. Since this metal is also known to affect cellular junctions, we investigated, in the present study, its potential influence on the Sertoli cell barrier and on junctional proteins present at this level such as connexin 43, claudin-11 and N-cadherin. Cultured seminiferous tubules in bicameral chambers expressed the three junctional proteins and ZO-1 for at least 12 days. Exposure to low concentrations of chromium (10 μg/l) increased the trans-epithelial resistance without major changes of claudin-11 and N-cadherin expressions but strongly delocalized the gap junction protein connexin 43 from the membrane to the cytoplasm of Sertoli cells. The possibility that the hexavalent chromium-induced alteration of connexin 43 indirectly mediates the effect of the toxic metal on the blood–testis barrier dynamic is postulated. - Highlights: ► Influence of Cr(VI) on the Sertoli cell barrier and on junctional proteins ► Use of cultured seminiferous tubules in bicameral chambers ► Low concentrations of Cr(VI) (10 μg/l) altered the trans-epithelial resistance. ► Cr(VI) did not alter claudin-11 and N-cadherin. ► Cr(VI) delocalized connexin 43 from the membrane to the cytoplasm of Sertoli cells.

  12. Elderly Men Have Low Levels of Anti-Müllerian Hormone and Inhibin B, but with High Interpersonal Variation: A Cross-Sectional Study of the Sertoli Cell Hormones in 615 Community-Dwelling Men

    Science.gov (United States)

    Chong, Yih Harng; Dennis, Nicola A.; Connolly, Martin J.; Teh, Ruth; Jones, Gregory T.; van Rij, Andre M.; Farrand, Stephanie; Campbell, A. John; MLennan, Ian S.

    2013-01-01

    The Sertoli cells of the testes secrete anti-Müllerian hormone (Müllerian inhibiting Substance, AMH) and inhibin B (InhB). AMH triggers the degeneration of the uterine precursor in male embryos, whereas InhB is part of the gonadal-pituitary axis for the regulation of sperm production in adults. However, both hormones are also putative regulators of homeostasis, and age-related changes in these hormones may therefore be important to the health status of elderly men. The levels of AMH in elderly men are unknown, with limited information being available about age-related changes in InhB. We have therefore used ELISAs to measure Sertoli cell hormone levels in 3 cohorts of community-dwelling men in New Zealand. In total, 615 men were examined, 493 of which were aged 65 or older. Serum AMH and InhB levels inversely correlated with age in men older than 50 years (p<0.001) but not in the younger men. A minority of elderly men had undetectable levels of AMH and InhB. The variation in hormone levels between similarly aged men increased with the age of men. AMH and InhB partially correlated with each other as expected (r = 0.48, p<0.001). However, the ratio of the two Sertoli hormones varied significantly between men, with this variation increasing with age. Elderly men selected for the absence of cardiovascular disease had AMH levels similar to those of young men whereas their InhB levels did not differ from aged-matched controls. These data suggests that Sertoli cell number and function changes with age, but with the extent and nature of the changes varying between men. PMID:23940675

  13. Single-nucleotide polymorphisms in the SEPTIN12 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.

    Science.gov (United States)

    Miyakawa, Hiroe; Miyamoto, Toshinobu; Koh, Eitetsu; Tsujimura, Akira; Miyagawa, Yasushi; Saijo, Yasuaki; Namiki, Mikio; Sengoku, Kazuo

    2012-01-01

    Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, 10 novel genes involved in human spermatogenesis, including human SEPTIN12, were identified by expression microarray analysis of human testicular tissue. Septin12 is a member of the septin family of conserved cytoskeletal GTPases that form heteropolymeric filamentous structures in interphase cells. It is expressed specifically in the testis. Therefore, we hypothesized that mutation or polymorphisms of SEPTIN12 participate in male infertility, especially Sertoli cell-only syndrome (SCOS). To investigate whether SEPTIN12 gene defects are associated with azoospermia caused by SCOS, mutational analysis was performed in 100 Japanese patients by direct sequencing of coding regions. Statistical analysis was performed in patients with SCOS and in 140 healthy control men. No mutations were found in SEPTIN12 ; however, 8 coding single-nucleotide polymorphisms (SNP1-SNP8) could be detected in the patients with SCOS. The genotype and allele frequencies in SNP3, SNP4, and SNP6 were notably higher in the SCOS group than in the control group (P < .001). These results suggest that SEPTIN12 might play a critical role in human spermatogenesis.

  14. Proteomic Analysis to Identify Tightly-Bound Cell Wall Protein in Rice Calli

    OpenAIRE

    Cho, Won Kyong; Hyun, Tae Kyung; Kumar, Dhinesh; Rim, Yeonggil; Chen, Xiong Yan; Jo, Yeonhwa; Kim, Suwha; Lee, Keun Woo; Park, Zee-Yong; Lucas, William J.; Kim, Jae-Yean

    2015-01-01

    Rice is a model plant widely used for basic and applied research programs. Plant cell wall proteins play key roles in a broad range of biological processes. However, presently, knowledge on the rice cell wall proteome is rudimentary in nature. In the present study, the tightly-bound cell wall proteome of rice callus cultured cells using sequential extraction protocols was developed using mass spectrometry and bioinformatics methods, leading to the identification of 1568 candidate proteins. Ba...

  15. PI3K/Akt Activated by GPR30 and Src Regulates 17β-Estradiol-Induced Cultured Immature Boar Sertoli Cells Proliferation.

    Science.gov (United States)

    Yang, Wei-Rong; Zhu, Feng-Wei; Zhang, Jiao-Jiao; Wang, Yi; Zhang, Jia-Hua; Lu, Cheng; Wang, Xian-Zhong

    2016-05-24

    Sertoli cell (SC) is a key element in the process of spermatogenesis. Accumulating research show that estrogen plays an important role in regulating boar SC proliferation. However, it is unclear whether phosphatidylinositol-4,5-bisphosphate 3-kinase/protein kinase B (PI3K/Akt) is involved in this process. In the present study, the role of PI3K/Akt on the 17β-estradiol-induced piglet SC proliferation was explored. In addition, we also explained the roles of G-protein-coupled estrogen receptor (GPR30) and Sarcoma protein (Src) in this process. Our study demonstrated that, 17β-estradiol induced activation of PI3K in a time-dependent manner. Both G-15 (an antagonist of GPR30, 0.1 μmol/L) and PP2 (an inhibitor of Src, 2.0 μmol/L) inhibited 17β-estradiol-induced activation of PI3K, reduced SC proliferation, and decreased messenger RNA (mRNA) and protein expression of S-phase kinase-associated protein 2 (Skp2). We also found that 17β-estradiol induced activation of Akt in a time-dependent manner. Both LY294002 (an inhibitor of PI3K) and 10-DEBC (an inhibitor of Akt) significantly reduced 17β-estradiol-induced SC proliferation and reduced mRNA and protein expression of Skp2. In addition, LY294002 inhibited 17β-estradiol-induced activation of Akt. The results indicated that 17β-estradiol regulates SC proliferation by activating PI3K/Akt. Both GPR30 and Src are involved in 17β-estradiol-induced phosphorylation of PI3K/Akt. Activation of PI3K/Akt enhances the expression of Skp2, which promotes SC proliferation. © The Author(s) 2016.

  16. Conditioned medium from LS 174T goblet cells treated with oxyresveratrol strengthens tight junctions in Caco-2 cells.

    Science.gov (United States)

    Hwang, Dahyun; Jo, HyunA; Hwang, Seonwook; Kim, Jeong-Keun; Kim, In-Ho; Lim, Young-Hee

    2017-01-01

    Strengthening of intestinal tight junctions provides an effective barrier from the external environment. Goblet cell-derived trefoil factor 3 (TFF3) increases transepithelial resistance by upregulating the expression of tight junction proteins. Oxyresveratrol (OXY) is a hydroxyl-substituted stilbene found in the roots, leaves, stems, and fruit of many plants and known to have various biological activities. In this study, we investigated the strengthening effect of OXY on intestinal tight junctions through stimulation of TFF production in goblet cells. We prepared conditioned medium from LS 174T goblet cells treated with OXY (GCO-CM) and investigated the effect of GCO-CM on strengthening tight junctions of Caco-2 cells. The mRNA and protein expression levels of major tight junction components (claudin-1, occludin, and ZO-1) were measured by quantitative real-time PCR and western blotting, respectively. Transepithelial electric resistance (TEER) was measured using an ohm/V meter. Monolayer permeability was evaluated by paracellular transport of fluorescein isothiocyanate-dextran. OXY showed a strong antioxidant activity. It significantly increased the expression level of TFF3 in LS 174T goblet cells. GCO-CM prepared by treatment with 2.5, 5, and 10μg/ml OXY did not show cytotoxicity in Caco-2 cells. GCO-CM increased the mRNA and protein expression levels of claudin-1, occludin, and ZO-1. It also significantly increased tight junction integrity and reduced permeability in a dose-dependent manner. OXY stimulates the expression of TFF3 in goblet cells, which might increase the integrity of the intestinal tight junction barrier. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  17. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1990-01-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel

  18. Follicle-stimulating hormone receptor-mediated uptake of sup 45 Ca sup 2+ by cultured rat Sertoli cells does not require activation of cholera toxin- or pertussis toxin-sensitive guanine nucleotide binding proteins or adenylate cyclase

    Energy Technology Data Exchange (ETDEWEB)

    Grasso, P.; Reichert, L.E. Jr. (Albany Medical College, NY (USA))

    1990-08-01

    We have previously reported that FSH stimulates flux of 45Ca2+ into cultured Sertoli cells from immature rats via voltage-sensitive and voltage-independent calcium channels. In the present study, we show that this effect of FSH does not require cholera toxin (CT)- or pertussis toxin (PT)-sensitive guanine nucleotide binding (G) protein or activation of adenylate cyclase (AC). Significant stimulation of 45Ca2+ influx was observed within 1 min, and maximal response (3.2-fold over basal levels) was achieved within 2 min after exposure to FSH. FSH-stimulated elevations in cellular cAMP paralleled increases in 45Ca2+ uptake, suggesting a possible coupling of AC activation to 45Ca2+ influx. (Bu)2cAMP, however, was not able to enhance 45Ca2+ uptake over basal levels at a final concentration of 1000 microM, although a concentration-related increase in androstenedione conversion to estradiol was evident. Exposure of Sertoli cells to CT (10 ng/ml) consistently stimulated basal levels of androstenedione conversion to estradiol but had no effect on basal levels of 45Ca2+ uptake. Similarly, CT had no effect on FSH-induced 45Ca2+ uptake, but potentiated FSH-stimulated estradiol synthesis. PT (10 ng/ml) augmented basal and FSH-stimulated estradiol secretion without affecting 45Ca2+ influx. The adenosine analog N6-phenylisopropyladenosine, which binds to Gi-coupled adenosine receptors on Sertoli cells, inhibited FSH-stimulated androgen conversion to estradiol in a dose-related (1-1000 nM) manner, but FSH-stimulated 45Ca2+ influx remained unchanged. Our results show that in contrast to FSH-stimulated estradiol synthesis, the flux of 45Ca2+ into Sertoli cells in response to FSH is not mediated either directly or indirectly by CT- or PT-sensitive G protein, nor does it require activation of AC. Our data further suggest that the FSH receptor itself may function as a calcium channel.

  19. Sodium caprate transiently opens claudin-5-containing barriers at tight junctions of epithelial and endothelial cells

    DEFF Research Database (Denmark)

    Del Vecchio, Giovanna; Tscheik, Christian; Tenz, Kareen

    2012-01-01

    Claudin-5 is a tight junction (TJ) protein which limits the diffusion of small hydrophilic molecules. Thus, it represents a potential pharmacological target to improve drug delivery to the tissues protected by claudin-5-dependent barriers. Sodium caprate is known as an absorption enhancer which...... opens the paracellular space acting on TJ proteins and actin cytoskeleton. Its action on claudin-5 is not understood so far. Epithelial and endothelial systems were used to evaluate the effect of caprate on claudin-5 in TJ-free cells and on claudin-5 fully integrated in TJ. To this aim, confocal...... of endothelial and epithelial cells. In conclusion, the study further elucidates the cellular effects of caprate at the tight junctions....

  20. Effects of adenine nucleotide and sterol depletion on tight junction structure and function in MDCK cells

    International Nuclear Information System (INIS)

    Ladino, C.A.

    1988-01-01

    The antitumor agent Hadacidin (H), N-formyl-hydroxyamino-acetic acid, reversibly inhibited the multiplication of clone 4 Madin-Darby canine kidney (MDCK) cells at a 4 mM concentration within 24-48 hours. Treated cells were arrested in the S phase of the cell cycle. Accompanying this action was a 16-fold increase in the area occupied b the cells and a refractoriness to trypsin treatment. To test whether this effect was due to an increase in tight junction integrity, electrical resistance (TER) was measured across H-treated monolayers. Addition of H at the onset of junction formation reversibly prevented the development of TER. ATP and cAMP levels were decreased by H, as well as the rate of [ 3 H]-leucine incorporation into protein. When 1 mM dibutyryl-cAMP (d.cAMP) and theophylline were added, H had no effect on cell division or protein synthesis, and TER was partially restored. The addition of 1 mM d.cAMP and 1 mM theophylline to control cultures decreased TER, indicating a biphasic effect on TER development/maintenance. In a separate study, the effect of sterol depletion on tight junctions formation/maintenance in wild-type MDCK cells was investigated

  1. Tumor necrosis factor alpha increases epithelial barrier permeability by disrupting tight junctions in Caco-2 cells

    Directory of Open Access Journals (Sweden)

    W. Cui

    2010-04-01

    Full Text Available The objectives of this study were to determine the effect of tumor necrosis factor alpha (TNF-α on intestinal epithelial cell permeability and the expression of tight junction proteins. Caco-2 cells were plated onto Transwell® microporous filters and treated with TNF-α (10 or 100 ng/mL for 0, 4, 8, 16, or 24 h. The transepithelial electrical resistance and the mucosal-to-serosal flux rates of the established paracellular marker Lucifer yellow were measured in filter-grown monolayers of Caco-2 intestinal cells. The localization and expression of the tight junction protein occludin were detected by immunofluorescence and Western blot analysis, respectively. SYBR-Green-based real-time PCR was used to measure the expression of occludin mRNA. TNF-α treatment produced concentration- and time-dependent decreases in Caco-2 transepithelial resistance and increases in transepithelial permeability to the paracellular marker Lucifer yellow. Western blot results indicated that TNF-α decreased the expression of phosphorylated occludin in detergent-insoluble fractions but did not affect the expression of non-phosphorylated occludin protein. Real-time RT-PCR data showed that TNF-α did not affect the expression of occludin mRNA. Taken together, our data demonstrate that TNF-α increases Caco-2 monolayer permeability, decreases occludin protein expression and disturbs intercellular junctions.

  2. Behavior of tight-junction, adherens-junction and cell polarity proteins during HNF-4α-induced epithelial polarization

    International Nuclear Information System (INIS)

    Satohisa, Seiro; Chiba, Hideki; Osanai, Makoto; Ohno, Shigeo; Kojima, Takashi; Saito, Tsuyoshi; Sawada, Norimasa

    2005-01-01

    We previously reported that expression of tight-junction molecules occludin, claudin-6 and claudin-7, as well as establishment of epithelial polarity, was triggered in mouse F9 cells expressing hepatocyte nuclear factor (HNF)-4α [H. Chiba, T. Gotoh, T. Kojima, S. Satohisa, K. Kikuchi, M. Osanai, N. Sawada. Hepatocyte nuclear factor (HNF)-4α triggers formation of functional tight junctions and establishment of polarized epithelial morphology in F9 embryonal carcinoma cells, Exp. Cell Res. 286 (2003) 288-297]. Using these cells, we examined in the present study behavior of tight-junction, adherens-junction and cell polarity proteins and elucidated the molecular mechanism behind HNF-4α-initiated junction formation and epithelial polarization. We herein show that not only ZO-1 and ZO-2, but also ZO-3, junctional adhesion molecule (JAM)-B, JAM-C and cell polarity proteins PAR-3, PAR-6 and atypical protein kinase C (aPKC) accumulate at primordial adherens junctions in undifferentiated F9 cells. In contrast, CRB3, Pals1 and PATJ appeared to exhibit distinct subcellular localization in immature cells. Induced expression of HNF-4α led to translocation of these tight-junction and cell polarity proteins to beltlike tight junctions, where occludin, claudin-6 and claudin-7 were assembled, in differentiated cells. Interestingly, PAR-6, aPKC, CRB3 and Pals1, but not PAR-3 or PATJ, were also concentrated on the apical membranes in differentiated cells. These findings indicate that HNF-4α provokes not only expression of tight-junction adhesion molecules, but also modulation of subcellular distribution of junction and cell polarity proteins, resulting in junction formation and epithelial polarization

  3. Effect of cAMP derivates on assembly and maintenance of tight junctions in human umbilical vein endothelial cells

    Directory of Open Access Journals (Sweden)

    Beese Michaela

    2010-09-01

    Full Text Available Abstract Background Endothelial tight and adherens junctions control a variety of physiological processes like adhesion, paracellular transport of solutes or trafficking of activated leukocytes. Formation and maintenance of endothelial junctions largely depend on the microenvironment of the specific vascular bed and on interactions of the endothelium with adjacent cell types. Consequently, primary cultures of endothelial cells often lose their specific junctional pattern and fail to establish tight monolayer in vitro. This is also true for endothelial cells isolated from the vein of human umbilical cords (HUVEC which are widely used as model for endothelial cell-related studies. Results We here compared the effect of cyclic 3'-5'-adenosine monophosphate (cAMP and its derivates on formation and stabilization of tight junctions and on alterations in paracellular permeability in HUVEC. We demonstrated by light and confocal laser microscopy that for shorter time periods the sodium salt of 8-bromoadenosine-cAMP (8-Br-cAMP/Na and for longer incubation periods 8-(4-chlorophenylthio-cAMP (pCPT-cAMP exerted the greatest effects of all compounds tested here on formation of continuous tight junction strands in HUVEC. We further demonstrated that although all compounds induced protein kinase A-dependent expression of the tight junction proteins claudin-5 and occludin only pCPT-cAMP slightly enhanced paracellular barrier functions. Moreover, we showed that pCPT-cAMP and 8-Br-cAMP/Na induced expression and membrane translocation of tricellulin. Conclusions pCPT-cAMP and, to a lesser extend, 8-Br-cAMP/Na improved formation of continuous tight junction strands and decreased paracellular permeability in primary HUVEC. We concluded that under these conditions HUVEC represent a feasible in vitro model to study formation and disassembly of endothelial tight junctions and to characterize tight junction-associated proteins

  4. Follicle-stimulating hormone receptor-mediated uptake of 45Ca2+ by proteoliposomes and cultured rat sertoli cells: Evidence for involvement of voltage-activated and voltage-independent calcium channels

    International Nuclear Information System (INIS)

    Grasso, P.; Reichert, L.E. Jr.

    1989-01-01

    We have previously reported incorporation into liposomes of Triton X-100-solubilized FSH receptor-G-protein complexes derived from purified bovine calf testis membranes. In the present study we have used this model system to show that FSH induces flux of 45Ca2+ into such proteoliposomes in a hormone-specific concentration-dependent manner. FSH, inactivated by boiling, had no stimulatory effect on 45Ca2+ flux, nor did isolated alpha- or beta-subunits of FSH. Addition of GTP (or its analogs 5'-guanylylimidodiphosphate and guanosine-5'-O-[3-thiotriphosphate]) or sodium fluoride (in the presence or absence of GTP or its analogs) failed to induce 45Ca2+ flux into proteoliposomes, suggesting that the uptake of 45Ca2+ was receptor, and not G-protein, related. Voltage-independent (ruthenium red and gadolinium chloride) and voltage-activated (methyoxyverapamil and nifedipine) calcium channel-blocking agents reduced FSH-stimulated 45Ca2+ flux into proteoliposomes to control levels. FSH also induced uptake of 45Ca2+ by cultured rat Sertoli cells. Ruthenium red and gadolinium chloride had no effect on basal levels of 45Ca2+ uptake or estradiol secretion by cultured rat Sertoli cells, nor did methoxyverapamil or nifedipine. All four calcium channel blockers, however, were able to reduce FSH-induced 45Ca2+ uptake to basal levels and FSH-stimulated conversion of androstenedione to estradiol by up to 50%, indicating an involvement of Ca2+ in FSH-stimulated steroidogenesis. Our results suggest that the well documented changes in intracellular calcium levels consequent to FSH binding may be due, at least in part, to an influx of calcium through FSH receptor-regulated calcium channels

  5. Double strand break repair: two mechanisms in competition but tightly linked to cell cycle

    International Nuclear Information System (INIS)

    Delacote, F.

    2002-11-01

    DNA double strand breaks (DSB) are highly toxic damage although they can be induced to create genetic diversity. Two distinct pathways can repair DSB: Homologous Recombination (HR) and Non Homologous End Joining (NHEJ). If un- or mis-repaired, this damage can lead to cancer. Thus, it is essential to investigate how these two pathways are regulated for DSB repair. NHEJ inhibition leads to HR DSB repair stimulation. However, this channeling to HR is tightly linked to cell cycle since NHEJ and HR are active in G1/early S and late S/G2, respectively. Our results suggest that G1-unrepaired DSB go through S phase to be repaired by HR in G2. Those results allow a better understanding of DSB repair mechanisms regulation. (author)

  6. Particulate matter air pollution disrupts endothelial cell barrier via calpain-mediated tight junction protein degradation

    Directory of Open Access Journals (Sweden)

    Wang Ting

    2012-08-01

    Full Text Available Abstract Background Exposure to particulate matter (PM is a significant risk factor for increased cardiopulmonary morbidity and mortality. The mechanism of PM-mediated pathophysiology remains unknown. However, PM is proinflammatory to the endothelium and increases vascular permeability in vitro and in vivo via ROS generation. Objectives We explored the role of tight junction proteins as targets for PM-induced loss of lung endothelial cell (EC barrier integrity and enhanced cardiopulmonary dysfunction. Methods Changes in human lung EC monolayer permeability were assessed by Transendothelial Electrical Resistance (TER in response to PM challenge (collected from Ft. McHenry Tunnel, Baltimore, MD, particle size >0.1 μm. Biochemical assessment of ROS generation and Ca2+ mobilization were also measured. Results PM exposure induced tight junction protein Zona occludens-1 (ZO-1 relocation from the cell periphery, which was accompanied by significant reductions in ZO-1 protein levels but not in adherens junction proteins (VE-cadherin and β-catenin. N-acetyl-cysteine (NAC, 5 mM reduced PM-induced ROS generation in ECs, which further prevented TER decreases and atteneuated ZO-1 degradation. PM also mediated intracellular calcium mobilization via the transient receptor potential cation channel M2 (TRPM2, in a ROS-dependent manner with subsequent activation of the Ca2+-dependent protease calpain. PM-activated calpain is responsible for ZO-1 degradation and EC barrier disruption. Overexpression of ZO-1 attenuated PM-induced endothelial barrier disruption and vascular hyperpermeability in vivo and in vitro. Conclusions These results demonstrate that PM induces marked increases in vascular permeability via ROS-mediated calcium leakage via activated TRPM2, and via ZO-1 degradation by activated calpain. These findings support a novel mechanism for PM-induced lung damage and adverse cardiovascular outcomes.

  7. Effect of Chum Salmon Egg Lectin on Tight Junctions in Caco-2 Cell Monolayers

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    Ryo Nemoto

    2015-05-01

    Full Text Available The effect of a chum salmon egg lectin (CSL3 on tight junction (TJ of Caco-2 cell monolayers was investigated. The lectin opened TJ as indicated by the decrease of the transepithelial electrical resistance (TER value and the increase of the permeation of lucifer yellow, which is transported via the TJ-mediated paracellular pathway. The effects of CSL3 were inhibited by the addition of 10 mM L-rhamnose or D-galactose which were specific sugars for CSL3. The lectin increased the intracellular Ca2+ of Caco-2 cell monolayers, that could be inhibited by the addition of L-rhamnose. The fluorescence immunostaining of β-actin in Caco-2 cell monolayers revealed that the cytoskeleton was changed by the CSL3 treatment, suggesting that CSL3 depolymerized β-actin to cause reversible TJ structural and functional disruption. Although Japanese jack bean lectin and wheat germ lectin showed similar effects in the decrease of the TER values and the increase of the intracellular Ca2+, they could not be inhibited by the same concentrations of simple sugars, such as D-glucose and N-acetyl-D-glucosamine.

  8. Dioscorin protects tight junction protein expression in A549 human airway epithelium cells from dust mite damage.

    Science.gov (United States)

    Fu, Lin Shien; Ko, Ying Hsien; Lin, Kuo Wei; Hsu, Jeng Yuan; Chu, Jao Jia; Chi, Chin Shiang

    2009-12-01

    In addition to being an allergen, the trypsin activity of dust mite extract also destroys the tight junctions of bronchial epithelium. Such damage can lead to airway leakage, which increases airway exposure to allergens, irritants, and other pathogens. Dioscorin, the storage protein of yam, demonstrates anti-trypsin activity, as well as other potential anti-inflammatory effects. This study investigated the protective role of dioscorin for tight junctions. The immunofluorescence stains of zonula occludens (ZO-1), E-cadherin (EC) and desmoplakin (DP) proteins were compared. A cultured A549 cell line was used as a control and A549 cells were incubated with mite extract 100 mg/mL for 16 h, with or without dioscorin 100 mg/mL pretreatment for 8 h and with dioscorin 100 mg/mL alone for 16 h. Western blot was performed to detect changes in ZO-1, EC, and DP in the treated A549 cell lines. Loss of tight junction protein expression (ZO-1, EC, DP) was demonstrated after 16-h mite extract incubation. The defect could be restored if cells were pretreated with dioscorin for 8 h. In addition, dioscorin did not cause damage to the A549 cell lines in terms of cell survival or morphology. Western blot showed no change in the amount of tight junction protein under various conditions. Dioscorin is a potential protector of airway damage caused by mite extract.

  9. Cdt1 revisited: complex and tight regulation during the cell cycle and consequences of deregulation in mammalian cells

    Directory of Open Access Journals (Sweden)

    Fujita Masatoshi

    2006-10-01

    Full Text Available Abstract In eukaryotic cells, replication of genomic DNA initiates from multiple replication origins distributed on multiple chromosomes. To ensure that each origin is activated precisely only once during each S phase, a system has evolved which features periodic assembly and disassembly of essential pre-replication complexes (pre-RCs at replication origins. The pre-RC assembly reaction involves the loading of a presumptive replicative helicase, the MCM2-7 complexes, onto chromatin by the origin recognition complex (ORC and two essential factors, CDC6 and Cdt1. The eukaryotic cell cycle is driven by the periodic activation and inactivation of cyclin-dependent kinases (Cdks and assembly of pre-RCs can only occur during the low Cdk activity period from late mitosis through G1 phase, with inappropriate re-assembly suppressed during S, G2, and M phases. It was originally suggested that inhibition of Cdt1 function after S phase in vertebrate cells is due to geminin binding and that Cdt1 hyperfunction resulting from Cdt1-geminin imbalance induces re-replication. However, recent progress has revealed that Cdt1 activity is more strictly regulated by two other mechanisms in addition to geminin: (1 functional and SCFSkp2-mediated proteolytic regulation through phosphorylation by Cdks; and (2 replication-coupled proteolysis mediated by the Cullin4-DDB1Cdt2 ubiquitin ligase and PCNA, an eukaryotic sliding clamp stimulating replicative DNA polymerases. The tight regulation implies that Cdt1 control is especially critical for the regulation of DNA replication in mammalian cells. Indeed, Cdt1 overexpression evokes chromosomal damage even without re-replication. Furthermore, deregulated Cdt1 induces chromosomal instability in normal human cells. Since Cdt1 is overexpressed in cancer cells, this could be a new molecular mechanism leading to carcinogenesis. In this review, recent insights into Cdt1 function and regulation in mammalian cells are discussed.

  10. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Shiwei [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Dong, Yushu [Department of Neurosurgery, 463rd Hospital of PLA, Shenyang 110042 (China); Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng [Department of Urology, 174th Hospital of PLA, Fujian 361001 (China); Hou, Wugang, E-mail: gangwuhou@163.com [Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032 (China); Li, Wei, E-mail: liweipepeyato@163.com [Department of Human Anatomy, Histology and Embryology, Fourth Military Medical University, Xi’an 710032 (China)

    2013-11-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury.

  11. Involvement of a chromatin modifier in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell injury: Probably an indirect action via the regulation of NFκB/FasL circuitry

    International Nuclear Information System (INIS)

    Chen, Shiwei; Dong, Yushu; Xu, Chun; Jiang, Liming; Chen, Yongjie; Jiang, Cheng; Hou, Wugang; Li, Wei

    2013-01-01

    Highlights: •MTA1 expression is upregulated in SCs upon MEHP treatment. •Knockdown of MTA1 in SCs impairs the MEHP-induced NFκB signaling activation. •Knockdown of MTA1 inhibits recruitment of NFκB onto FasL promoter in MEHP-treated SCs. -- Abstract: The Fas/FasL signaling pathway, controlled by nuclear factor-κB (NFκB) at the transcriptional level, is critical for triggering germ cell apoptosis in response to mono-(2-ethylhexyl) phthalate (MEHP)-induced Sertoli cell (SC) injury, but the exact regulation mechanism remain unknown. Here, we discovered that expression level of Metastasis associated protein 1 (MTA1), a component of the Mi-2/nucleosome remodeling and deacetylase complex, was upregulated in SCs during the early recovery after MEHP exposure. This expression change was in line with the dynamic changes in germ cell apoptosis in response to MEHP treatment. Furthermore, a knockdown of MTA1 by RNAi in SCs was found to impair the MEHP-induced early activation of NFκB pathway and abolish the recruitment of NFκB onto FasL promoter, which consequently diminished the MEHP-triggered FasL induction. Considering that Fas/FasL is a well characterized apoptosis initiating signaling during SCs injury, our results point to a potential “switch on” effect of MTA1, which may govern the activation of NFκB/FasL cascade in MEHP-insulted SCs. Overall, the MTA1/NFκB/FasL circuit may serve as an important defensive/repairing mechanism to help to control the germ cell quality after SCs injury

  12. Tight junction between endothelial cells: the interaction between nanoparticles and blood vessels

    Directory of Open Access Journals (Sweden)

    Yue Zhang

    2016-05-01

    Full Text Available Since nanoparticles are now widely applied as food additives, in cosmetics and other industries, especially in medical therapy and diagnosis, we ask here whether nanoparticles can cause several adverse effects to human health. In this review, based on research on nanotoxicity, we mainly discuss the negative influence of nanoparticles on blood vessels in several aspects and the potential mechanism for nanoparticles to penetrate endothelial layers of blood vessels, which are the sites of phosphorylation of tight junction proteins (claudins, occludins, and ZO (Zonula occludens proteins, oxidative stress and shear stress. We propose a connection between the presence of nanoparticles and the regulation of the tight junction, which might be the key approach for nanoparticles to penetrate endothelial layers and then have an impact on other tissues and organs.

  13. 3D-fibroblast tissues constructed by a cell-coat technology enhance tight-junction formation of human colon epithelial cells.

    Science.gov (United States)

    Matsusaki, Michiya; Hikimoto, Daichi; Nishiguchi, Akihiro; Kadowaki, Koji; Ohura, Kayoko; Imai, Teruko; Akashi, Mitsuru

    2015-02-13

    Caco-2, human colon carcinoma cell line, has been widely used as a model system for intestinal epithelial permeability because Caco-2 cells express tight-junctions, microvilli, and a number of enzymes and transporters characteristic of enterocytes. However, the functional differentiation and polarization of Caco-2 cells to express sufficient tight-junctions (a barrier) usually takes over 21 days in culture. This may be due to the cell culture environment, for example inflammation induced by plastic petri dishes. Three-dimensional (3D) sufficient cell microenvironments similar to in vivo natural conditions (proteins and cells), will promote rapid differentiation and higher functional expression of tight junctions. Herein we report for the first time an enhancement in tight-junction formation by 3D-cultures of Caco-2 cells on monolayered (1L) and eight layered (8L) normal human dermal fibroblasts (NHDF). Trans epithelial electric resistance (TEER) of Caco-2 cells was enhanced in the 3D-cultures, especially 8L-NHDF tissues, depending on culture times and only 10 days was enough to reach the same TEER value of Caco-2 monolayers after a 21 day incubation. Relative mRNA expression of tight-junction proteins of Caco-2 cells on 3D-cultures showed higher values than those in monolayer structures. Transporter gene expression patterns of Caco-2 cells on 3D-constructs were almost the same as those of Caco-2 monolayers, suggesting that there was no effect of 3D-cultures on transporter protein expression. The expression correlation between carboxylesterase 1 and 2 in 3D-cultures represented similar trends with human small intestines. The results of this study clearly represent a valuable application of 3D-Caco-2 tissues for pharmaceutical applications. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. miR-Let7A Controls the Cell Death and Tight Junction Density of Brain Endothelial Cells under High Glucose Condition.

    Science.gov (United States)

    Song, Juhyun; Yoon, So Ra; Kim, Oh Yoen

    2017-01-01

    Hyperglycemia-induced stress in the brain of patients with diabetes triggers the disruption of blood-brain barrier (BBB), leading to diverse neurological diseases including stroke and dementia. Recently, the role of microRNA becomes an interest in the research for deciphering the mechanism of brain endothelial cell damage under hyperglycemia. Therefore, we investigated whether mircoRNA Let7A (miR-Let7A) controls the damage of brain endothelial (bEnd.3) cells against high glucose condition. Cell viability, cell death marker expressions (p-53, Bax, and cleaved poly ADP-ribose polymerase), the loss of tight junction proteins (ZO-1 and claudin-5), proinflammatory response (interleukin-6, tumor necrosis factor- α ), inducible nitric oxide synthase, and nitrite production were confirmed using MTT, reverse transcription-PCR, quantitative-PCR, Western blotting, immunofluorescence, and Griess reagent assay. miR-Let7A overexpression significantly prevented cell death and loss of tight junction proteins and attenuated proinflammatory response and nitrite production in the bEnd.3 cells under high glucose condition. Taken together, we suggest that miR-Let7A may attenuate brain endothelial cell damage by controlling cell death signaling, loss of tight junction proteins, and proinflammatory response against high glucose stress. In the future, the manipulation of miR-Let7A may be a novel solution in controlling BBB disruption which leads to the central nervous system diseases.

  15. Expression patterns of tight junction components induced by CD24 in an oral epithelial cell-culture model correlated to affected periodontal tissues.

    Science.gov (United States)

    Ye, P; Yu, H; Simonian, M; Hunter, N

    2014-04-01

    Previously we demonstrated uniformly strong expression of CD24 in the epithelial attachment to the tooth and in the migrating epithelium of the periodontitis lesion. Titers of serum antibodies autoreactive with CD24 peptide correlated with reduced severity of periodontal disease. Ligation of CD24 expressed by oral epithelial cells induced formation of tight junctions that limited paracellular diffusion. In this study, we aimed to reveal that the lack of uniform expression of tight junction components in the pocket epithelium of periodontitis lesions is likely to contribute to increased paracellular permeability to bacterial products. This is proposed as a potential driver of the immunopathology of periodontitis. An epithelial culture model with close correspondence for expression patterns for tight junction components in periodontal epithelia was used. Immunohistochemical staining and confocal laser scanning microscopy were used to analyse patterns of expression of gingival epithelial tight junction components. The minimally inflamed gingival attachment was characterized by uniformly strong staining at cell contacts for the tight junction components zona occludens-1, zona occludens-2, occludin, junction adhesion molecule-A, claudin-4 and claudin-15. In contrast, the pocket epithelium of the periodontal lesion showed scattered, uneven staining for these components. This pattern correlated closely with that of unstimulated oral epithelial cells in culture. Following ligation of CD24 expressed by these cells, the pattern of tight junction component expression of the minimally inflamed gingival attachment developed rapidly. There was evidence for non-uniform and focal expression only of tight junction components in the pocket epithelium. In the cell-culture model, ligation of CD24 induced a tight junction expression profile equivalent to that observed for the minimally inflamed gingival attachment. Ligation of CD24 expressed by gingival epithelial cells by lectin

  16. Possible role of HIWI2 in modulating tight junction proteins in retinal pigment epithelial cells through Akt signaling pathway.

    Science.gov (United States)

    Sivagurunathan, Suganya; Palanisamy, Karthikka; Arunachalam, Jayamuruga Pandian; Chidambaram, Subbulakshmi

    2017-03-01

    PIWI subfamily of proteins is shown to be primarily expressed in germline cells. They maintain the genomic integrity by silencing the transposable elements. Although the role of PIWI proteins in germ cells has been documented, their presence and function in somatic cells remains unclear. Intriguingly, we detected all four members of PIWI-like proteins in human ocular tissues and somatic cell lines. When HIWI2 was knocked down in retinal pigment epithelial cells, the typical honeycomb morphology was affected. Further analysis showed that the expression of tight junction (TJ) proteins, CLDN1, and TJP1 were altered in HIWI2 knockdown. Moreover, confocal imaging revealed disrupted TJP1 assembly at the TJ. Previous studies report the role of GSK3β in regulating TJ proteins. Accordingly, phospho-kinase proteome profiler array indicated increased phosphorylation of Akt and GSK3α/β in HIWI2 knockdown, suggesting that HIWI2 might affect TJ proteins through Akt-GSK3α/β signaling axis. Moreover, treating the HIWI2 knockdown cells with wortmannin increased the levels of TJP1 and CLDN1. Taken together, our study demonstrates the presence of PIWI-like proteins in somatic cells and the possible role of HIWI2 in preserving the functional integrity of epithelial cells probably by modulating the phosphorylation status of Akt.

  17. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    Directory of Open Access Journals (Sweden)

    Irna Sufiawati

    Full Text Available Herpes simplex virus (HSV types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD. Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals.

  18. Tight turns

    CERN Multimedia

    Anaïs Schaeffer

    2012-01-01

    The Italian National Institute for Nuclear Physics (INFN) has successfully tested the first model of a new fast-ramping curved dipole magnet. This is great news for CERN, which sees the advance as holding potential for the future of the SPS.   The first model of a new fast-ramping curved dipole magnet being prepared for cryogenic testing at the LASA laboratory (INFN Milano, Italy). On 16 July INFN introduced an innovative dipole magnet. With a length of some 4 metres, it can produce a 4.5 Tesla magnetic field and achieve a tighter bend than ever before (the bending radius has been squeezed to a remarkable 66.7 metres). This new magnet was designed in the first instance for GSI’s SIS300 synchrotron (in Germany), which will require 60 dipoles of this type. "Achieving such a tight bend demanded a major R&D effort," stressed Pasquale Fabbricatore, the spokesman of the INFN collaboration responsible for the magnet’s development. "We had to not o...

  19. Large-scale calculations of solid oxide fuel cell cermet anode by tight-binding quantum chemistry method

    International Nuclear Information System (INIS)

    Koyama, Michihisa; Kubo, Momoji; Miyamoto, Akira

    2005-01-01

    Improvement of anode characteristics of solid oxide fuel cells is important for the better cell performance and especially the direct use of hydrocarbons. A mixture of ceramics and metal is generally used as anode, and different combinations of ceramics and metals lead to different electrode characteristics. We performed large-scale calculations to investigate the characteristics of Ni/CeO 2 and Cu/CeO 2 anodes at the electronic level using our tight-binding quantum chemical molecular dynamics program. Charge distribution analysis clarified the electron transfer from metal to oxide in both anodes. The calculations of density of states clarified different contributions of Ni and Cu orbitals to the energy levels at around Fermi level in each cermet. Based on the obtained results, we made considerations to explain different characteristics of both cermet anodes. The effectiveness of our approach for the investigation of complex cermet system was proved

  20. Lecithin-Bound Iodine Prevents Disruption of Tight Junctions of Retinal Pigment Epithelial Cells under Hypoxic Stress

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    Masahiko Sugimoto

    2016-01-01

    Full Text Available Aim. We investigated whether lecithin-bound iodine (LBI can protect the integrity of tight junctions of retinal pigment epithelial cells from hypoxia. Method. Cultured human retinal pigment epithelial (ARPE-19 cells were pretreated with LBI. To mimic hypoxic conditions, cells were incubated with CoCl2. We compared the integrity of the tight junctions (TJs of control to cells with either LBI alone, CoCl2 alone, or LBI + CoCl2. The levels of cytokines in the conditioned media were also determined. Results. Significant decrease in the zonula occludens-1 (ZO-1 intensity in the CoCl2 group compared to the control (5787.7 ± 4126.4 in CoCl2 group versus 29244.6 ± 2981.2 in control; average ± standard deviation. But the decrease was not significant in the LBI + CoCl2 (27189.0 ± 11231.1. The levels of monocyte chemoattractant protein-1 (MCP-1 and Chemokine (C-C Motif Ligand 11 (CCL-11 were significantly higher in the CoCl2 than in the control (340.8 ± 43.3 versus 279.7 ± 68.3 pg/mL for MCP-1, and 15.2 ± 12.9 versus 12.5 ± 6.1 pg/mL for CCL-11. With LBI pretreatment, the levels of both cytokines were decreased to 182.6 ± 23.8 (MCP-1 and 5.46 ± 1.9 pg/mL for CCL-11. Blockade of MCP-1 or CCL-11 also shows similar result representing TJ protection from hypoxic stress. Conclusions. LBI results in a protective action from hypoxia.

  1. Calcium oxalate crystals induces tight junction disruption in distal renal tubular epithelial cells by activating ROS/Akt/p38 MAPK signaling pathway.

    Science.gov (United States)

    Yu, Lei; Gan, Xiuguo; Liu, Xukun; An, Ruihua

    2017-11-01

    Tight junction plays important roles in regulating paracellular transports and maintaining cell polarity. Calcium oxalate monohydrate (COM) crystals, the major crystalline composition of kidney stones, have been demonstrated to be able to cause tight junction disruption to accelerate renal cell injury. However, the cellular signaling involved in COM crystal-induced tight junction disruption remains largely to be investigated. In the present study, we proved that COM crystals induced tight junction disruption by activating ROS/Akt/p38 MAPK pathway. Treating Madin-Darby canine kidney (MDCK) cells with COM crystals induced a substantial increasing of ROS generation and activation of Akt that triggered subsequential activation of ASK1 and p38 mitogen-activated protein kinase (MAPK). Western blot revealed a significantly decreased expression of ZO-1 and occludin, two important structural proteins of tight junction. Besides, redistribution and dissociation of ZO-1 were observed by COM crystals treatment. Inhibition of ROS by N-acetyl-l-cysteine (NAC) attenuated the activation of Akt, ASK1, p38 MAPK, and down-regulation of ZO-1 and occludin. The redistribution and dissociation of ZO-1 were also alleviated by NAC treatment. These results indicated that ROS were involved in the regulation of tight junction disruption induced by COM crystals. In addition, the down-regulation of ZO-1 and occludin, the phosphorylation of ASK1 and p38 MAPK were also attenuated by MK-2206, an inhibitor of Akt kinase, implying Akt was involved in the disruption of tight junction upstream of p38 MAPK. Thus, these results suggested that ROS-Akt-p38 MAPK signaling pathway was activated in COM crystal-induced disruption of tight junction in MDCK cells.

  2. Analysis of Differences in Void Coefficient Predictions for Mixed-Oxide-Fueled Tight-Pitch Light Water Reactor Cells

    International Nuclear Information System (INIS)

    Unesaki, Hironobu; Shiroya, Seiji; Kanda, Keiji; Cathalau, Stephane; Carre, Franck-Olivier; Aizawa, Otohiko; Takeda, Toshikazu

    2000-01-01

    Analysis of the benchmark problems on the void coefficient of mixed-oxide (MOX)-fueled tight-pitch cells has been performed using the Japanese SRAC code system with the JENDL-3.2 library and the French APOLLO-2 code with the CEA93 library based on JEF-2.2. The benchmark problems have been specified to investigate the physical phenomena occurring during the progressive voidage of MOX-fueled tight-pitch lattices, such as high conversion light water reactor lattices, and to evaluate the impact of nuclear data and calculational methods. Despite the most recently compiled nuclear data libraries and the sophisticated calculation schemes employed in both code systems, the k ∞ and void reactivity values obtained by the two code systems show considerable discrepancy especially in the highly voided state. The discrepancy of k ∞ values shows an obvious dependence on void fraction and also has been shown to be sensitive to the isotopic composition of plutonium. The observed discrepancies are analyzed by being decomposed into contributing isotopes and reactions and have been shown to be caused by a complicated balance of both negative and positive components, which are mainly attributable to differences in a limited number of isotopes including 239 Pu, 241 Pu, 16 O, and stainless steel

  3. Modified expression of cytoplasmic isocitrate dehydrogenase electrophoretic isoforms in seminal plasma of men with sertoli-cell-only syndrome and seminoma.

    Science.gov (United States)

    Starita-Geribaldi, Mireille; Samson, Michel; Guigonis, Jean-Marie; Pointis, Georges; Fenichel, Patrick

    2008-06-01

    Two isoforms of human cytoplasmic isocitrate dehydrogenase (IDPc) of close molecular weights and different isoelectric points were identified in human seminal plasma (SP) by two-dimensional gel electrophoresis (2-DE) followed by mass spectrometry (MS). These two isoforms were detected in the normospermic men SP and their expressions were markedly altered in patients with testicular seminoma, the most frequent testicular germ cell cancer (TGCC): increase of the more acidic spot and decrease of the more basic one. Since oligospermia has been considered as a high risk pathological condition for developing a testicular cancer, the two IDPc isoforms were analyzed in SP of a group of secretory azoospermic patients. In this group the two spots displayed similar variations of expression to those observed in testicular seminoma. These results propose IDPc as a promising SP biomarker of testicular seminoma. Whether IDPc alteration in secretory azoospermia is predictive of testicular seminoma remains to be elucidated. (c) 2007 Wiley-Liss, Inc.

  4. Tight coupling between nucleus and cell migration through the perinuclear actin cap

    Science.gov (United States)

    Kim, Dong-Hwee; Cho, Sangkyun; Wirtz, Denis

    2014-01-01

    ABSTRACT Although eukaryotic cells are known to alternate between ‘advancing’ episodes of fast and persistent movement and ‘hesitation’ episodes of low speed and low persistence, the molecular mechanism that controls the dynamic changes in morphology, speed and persistence of eukaryotic migratory cells remains unclear. Here, we show that the movement of the interphase nucleus during random cell migration switches intermittently between two distinct modes – rotation and translocation – that follow with high fidelity the sequential rounded and elongated morphologies of the nucleus and cell body, respectively. Nuclear rotation and translocation mediate the stop-and-go motion of the cell through the dynamic formation and dissolution, respectively, of the contractile perinuclear actin cap, which is dynamically coupled to the nuclear lamina and the nuclear envelope through LINC complexes. A persistent cell movement and nuclear translocation driven by the actin cap are halted following the disruption of the actin cap, which in turn allows the cell to repolarize for its next persistent move owing to nuclear rotation mediated by cytoplasmic dynein light intermediate chain 2. PMID:24639463

  5. Tight junctions and human diseases.

    Science.gov (United States)

    Sawada, Norimasa; Murata, Masaki; Kikuchi, Keisuke; Osanai, Makoto; Tobioka, Hirotoshi; Kojima, Takashi; Chiba, Hideki

    2003-09-01

    Tight junctions are intercellular junctions adjacent to the apical end of the lateral membrane surface. They have two functions, the barrier (or gate) function and the fence function. The barrier function of tight junctions regulates the passage of ions, water, and various macromolecules, even of cancer cells, through paracellular spaces. The barrier function is thus relevant to edema, jaundice, diarrhea, and blood-borne metastasis. On the other hand, the fence function maintains cell polarity. In other words, tight junctions work as a fence to prevent intermixing of molecules in the apical membrane with those in the lateral membrane. This function is deeply involved in cancer cell biology, in terms of loss of cell polarity. Of the proteins comprising tight junctions, integral membrane proteins occludin, claudins, and JAMs have been recently discovered. Of these molecules, claudins are exclusively responsible for the formation of tight-junction strands and are connected with the actin cytoskeleton mediated by ZO-1. Thus, both functions of tight junctions are dependent on the integrity of the actin cytoskeleton as well as ATP. Mutations in the claudin14 and the claudin16 genes result in hereditary deafness and hereditary hypomagnesemia, respectively. Some pathogenic bacteria and viruses target and affect the tight-junction function, leading to diseases. In this review, the relationship between tight junctions and human diseases is summarized.

  6. Single-nucleotide polymorphisms in the LRWD1 gene may be a genetic risk factor for Japanese patients with Sertoli cell-only syndrome.

    Science.gov (United States)

    Miyamoto, T; Koh, E; Tsujimura, A; Miyagawa, Y; Saijo, Y; Namiki, M; Sengoku, K

    2014-04-01

    Genetic mechanisms have been implicated as a cause of some cases of male infertility. Recently, ten novel genes involved in human spermatogenesis, including human LRWD1, have been identified by expression microarray analysis of human testictissue. The human LRWD1 protein mediates the origin recognition complex in chromatin, which is critical for the initiation of pre-replication complex assembly in G1 and chromatin organization in post-G1 cells. The Lrwd1 gene expression is specific to the testis in mice. Therefore, we hypothesized that mutation or polymorphisms of LRWD1 participate in male infertility, especially azoospermia. To investigate whether LRWD1 gene defects are associated with azoospermia caused by SCOS and meiotic arrest (MA), mutational analysis was performed in 100 and 30 Japanese patients by direct sequencing of the coding regions, respectively. Statistical analysis was performed for patients with SCOS and MA and in 100 healthy control men. No mutations were found in LRWD1; however, three coding single-nucleotide polymorphisms (SNP1-SNP3) could be detected in the patients. The genotype and allele frequencies in SNP1 and SNP2 were notably higher in the SCOS group than in the control group (P < 0.05). These results suggest the critical role of LRWD1 in human spermatogenesis. © 2013 Blackwell Verlag GmbH.

  7. Inhibiting Invasion into Human Bladder Carcinoma 5637 Cells with Diallyl Trisulfide by Inhibiting Matrix Metalloproteinase Activities and Tightening Tight Junctions

    Directory of Open Access Journals (Sweden)

    Yung Hyun Choi

    2013-10-01

    Full Text Available Diallyl trisulfide (DATS, an organosulfur compound in garlic, possesses pronounced anti-cancer potential. However, the anti-invasive mechanism of this compound in human bladder carcinoma is not fully understood. In this study, we evaluated the anti-invasive effects of DATS on a human bladder carcinoma (5637 cell line and investigated the underlying mechanism. The results indicated that DATS suppressed migration and invasion of 5637 cells by reducing the activities and expression of matrix metalloproteinase (MMP-2 and MMP-9 at both the protein and mRNA levels. DATS treatment up-regulated expression of tissue inhibitor of metalloproteinase (TIMP-1 and TIMP-2 in 5637 cells. The inhibitory effects of DATS on invasiveness were associated with an increase in transepithelial electrical resistance and repression of the levels of claudin family members. Although further studies are needed, our data demonstrate that DATS exhibits anti-invasive effects in 5637 cells by down-regulating the activity of tight junctions and MMPs. DATS may have future utility in clinical applications for treating bladder cancer.

  8. TRPV4 Regulates Tight Junctions and Affects Differentiation in a Cell Culture Model of the Corneal Epithelium.

    Science.gov (United States)

    Martínez-Rendón, Jacqueline; Sánchez-Guzmán, Erika; Rueda, Angélica; González, James; Gulias-Cañizo, Rosario; Aquino-Jarquín, Guillermo; Castro-Muñozledo, Federico; García-Villegas, Refugio

    2017-07-01

    TRPV4 (transient receptor potential vanilloid 4) is a cation channel activated by hypotonicity, moderate heat, or shear stress. We describe the expression of TRPV4 during the differentiation of a corneal epithelial cell model, RCE1(5T5) cells. TRPV4 is a late differentiation feature that is concentrated in the apical membrane of the outmost cell layer of the stratified epithelia. Ca 2+ imaging experiments showed that TRPV4 activation with GSK1016790A produced an influx of calcium that was blunted by the specific TRPV4 blocker RN-1734. We analyzed the involvement of TRPV4 in RCE1(5T5) epithelial differentiation by measuring the development of transepithelial electrical resistance (TER) as an indicator of the tight junction (TJ) assembly. We showed that TRPV4 activity was necessary to establish the TJ. In differentiated epithelia, activation of TRPV4 increases the TER and the accumulation of claudin-4 in cell-cell contacts. Epidermal Growth Factor (EGF) up-regulates the TER of corneal epithelial cultures, and we show here that TRPV4 activation mimicked this EGF effect. Conversely, TRPV4 inhibition or knock down by specific shRNA prevented the increase in TER. Moreover, TRPP2, an EGF-activated channel that forms heteromeric complexes with TRPV4, is also concentrated in the outmost cell layer of differentiated RCE1(5T5) sheets. This suggests that the EGF regulation of the TJ may involve a heterotetrameric TRPV4-TRPP2 channel. These results demonstrated TRPV4 activity was necessary for the correct establishment of TJ in corneal epithelia and as well as the regulation of both the barrier function of TJ and its ability to respond to EGF. J. Cell. Physiol. 232: 1794-1807, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. Malignant tumour stroma gonads Sertoli-Leydig:a communication clinic case and bibliographic review

    International Nuclear Information System (INIS)

    Krygier Waltier, G.; Rodriguez Lemes, R.; Carlevaro Elizondo, T.

    1995-01-01

    The malignant tumors of the stroma gonads represent 0.2% of all the tumors of the testicle, and they are almost exclusive of the relatively refractory to the radiotherapy and the chemotherapy, and the medium survive of the illness is of two years. it presents a clinical case of tumour to cells of Sertoli-Leydig in a 45 year-old man that heI consulted for sterility . A review of the literature it is made for finish [es

  10. Design considerations for teleoperation systems operating in gas-tight argon cells

    Directory of Open Access Journals (Sweden)

    Seungnam Yu

    2017-12-01

    Full Text Available In the nuclear industry, mechanical engineers spend a significant portion of their time designing equipment such as manipulators, bogies, mechanical grippers, and so on. Some customized designs can be considered as standard mechanical equipment in this area, although it is not unusual to find that an existing design cannot simply be copied from one project to another. Varied performance requirements can dictate that redesign, often quite extensive redesign, is required. However, if something similar has been done before, engineers could use that as a starting point for the new project. In this regard, this study presents several guidelines inspired by previous design knowledge for similar development cases. Moreover, this study presents more detailed suggestions such as design guidelines for an argon-based hot cell atmosphere and design experience for a large-scale practical hot cell facility. Design considerations and case studies dealt with in this study are dedicated to teleoperation manipulators that are used at a large-scale argon cell facility for pyroprocess integrated inactive demonstration (PRIDE, at the Korea Atomic Energy Research Institute. In particular, for case studies to support the suggested recommendations, a fabricated telemanipulator system for PRIDE is introduced, and several kinds of experimental results associated with it are presented.

  11. Caveolin1 Is Required for Th1 Cell Infiltration, but Not Tight Junction Remodeling, at the Blood-Brain Barrier in Autoimmune Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Sarah E. Lutz

    2017-11-01

    Full Text Available Lymphocytes cross vascular boundaries via either disrupted tight junctions (TJs or caveolae to induce tissue inflammation. In the CNS, Th17 lymphocytes cross the blood-brain barrier (BBB before Th1 cells; yet this differential crossing is poorly understood. We have used intravital two-photon imaging of the spinal cord in wild-type and caveolae-deficient mice with fluorescently labeled endothelial tight junctions to determine how tight junction remodeling and caveolae regulate CNS entry of lymphocytes during the experimental autoimmune encephalomyelitis (EAE model for multiple sclerosis. We find that dynamic tight junction remodeling occurs early in EAE but does not depend upon caveolar transport. Moreover, Th1, but not Th17, lymphocytes are significantly reduced in the inflamed CNS of mice lacking caveolae. Therefore, tight junction remodeling facilitates Th17 migration across the BBB, whereas caveolae promote Th1 entry into the CNS. Moreover, therapies that target both tight junction degradation and caveolar transcytosis may limit lymphocyte infiltration during inflammation.

  12. Aberrant expression of the tight junction molecules claudin-1 and zonula occludens-1 mediates cell growth and invasion in oral squamous cell carcinoma.

    Science.gov (United States)

    Babkair, Hamzah; Yamazaki, Manabu; Uddin, Md Shihab; Maruyama, Satoshi; Abé, Tatsuya; Essa, Ahmed; Sumita, Yoshimasa; Ahsan, Md Shahidul; Swelam, Wael; Cheng, Jun; Saku, Takashi

    2016-11-01

    We reported that altered cell contact mediated by E-cadherin is an initial event in the pathogenesis of oral epithelial malignancies. To assess other effects of cell adhesion, we examined the expression levels of tight junction (TJ) molecules in oral carcinoma in situ (CIS) and squamous cell carcinoma (SCC). To identify changes in the expression of TJ molecules, we conducted an analysis of the immunohistochemical profiles of claudin-1 (CLDN-1) and zonula occludens-1 (ZO-1) in surgical specimens acquired from patients with oral SCC containing foci of epithelial dysplasia or from patients with CIS. We used immunofluorescence, Western blotting, reverse-transcription polymerase chain reaction, and RNA interference to evaluate the functions of CLDN-1 and ZO-1 in cultured oral SCC cells. TJ molecules were not detected in normal oral epithelial tissues but were expressed in SCC/CIS cells. ZO-1 was localized within the nucleus of proliferating cells. When CLDN-1 expression was inhibited by transfecting cells with specific small interference RNAs, SCC cells dissociated, and their ability to proliferate and invade Matrigel was inhibited. In contrast, although RNA interference-mediated inhibition of ZO-1 expression did not affect cell morphology, it inhibited cell proliferation and invasiveness. Our findings indicated that the detection of TJ molecules in the oral epithelia may serve as a marker for the malignant phenotype of cells in which CLDN-1 regulates proliferation and invasion. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. c-Yes regulates cell adhesion at the apical ectoplasmic specialization-blood-testis barrier axis via its effects on protein recruitment and distribution

    Science.gov (United States)

    Xiao, Xiang; Mruk, Dolores D.

    2013-01-01

    During spermatogenesis, extensive restructuring takes place at the cell-cell interface since developing germ cells migrate progressively from the basal to the adluminal compartment of the seminiferous epithelium. Since germ cells per se are not motile cells, their movement relies almost exclusively on the Sertoli cell. Nonetheless, extensive exchanges in signaling take place between these cells in the seminiferous epithelium. c-Yes, a nonreceptor protein tyrosine kinase belonging to the Src family kinases (SFKs) and a crucial signaling protein, was recently shown to be upregulated at the Sertoli cell-cell interface at the blood-testis barrier (BTB) at stages VIII–IX of the seminiferous epithelial cycle of spermatogenesis. It was also highly expressed at the Sertoli cell-spermatid interface known as apical ectoplasmic specialization (apical ES) at stage V to early stage VIII of the epithelial cycle during spermiogenesis. Herein, it was shown that the knockdown of c-Yes by RNAi in vitro and in vivo affected both Sertoli cell adhesion at the BTB and spermatid adhesion at the apical ES, causing a disruption of the Sertoli cell tight junction-permeability barrier function, germ cell loss from the seminiferous epithelium, and also a loss of spermatid polarity. These effects were shown to be mediated by changes in distribution and/or localization of adhesion proteins at the BTB (e.g., occludin, N-cadherin) and at the apical ES (e.g., nectin-3) and possibly the result of changes in the underlying actin filaments at the BTB and the apical ES. These findings implicate that c-Yes is a likely target of male contraceptive research. PMID:23169788

  14. Type 2 innate lymphoid cells disrupt bronchial epithelial barrier integrity by targeting tight junctions through IL-13 in asthmatic patients.

    Science.gov (United States)

    Sugita, Kazunari; Steer, Catherine A; Martinez-Gonzalez, Itziar; Altunbulakli, Can; Morita, Hideaki; Castro-Giner, Francesc; Kubo, Terufumi; Wawrzyniak, Paulina; Rückert, Beate; Sudo, Katsuko; Nakae, Susumu; Matsumoto, Kenji; O'Mahony, Liam; Akdis, Mübeccel; Takei, Fumio; Akdis, Cezmi A

    2018-01-01

    Bronchial epithelial barrier leakiness and type 2 innate lymphoid cells (ILC2s) have been separately linked to asthma pathogenesis; however, the influence of ILC2s on the bronchial epithelial barrier has not been investigated previously. We investigated the role of ILC2s in the regulation of bronchial epithelial tight junctions (TJs) and barrier function both in bronchial epithelial cells of asthmatic patients and healthy subjects and general innate lymphoid cell- and ILC2-deficient mice. Cocultures of human ILC2s and bronchial epithelial cells were used to determine transepithelial electrical resistance, paracellular flux, and TJ mRNA and protein expressions. The effect of ILC2s on TJs was examined by using a murine model of IL-33-induced airway inflammation in wild-type, recombination-activating gene 2 (Rag2) -/- , Rag2 -/- Il2rg -/- , and Rora sg/sg mice undergoing bone marrow transplantation to analyze the in vivo relevance of barrier disruption by ILC2s. ILC2s significantly impaired the epithelial barrier, as demonstrated by reduced transepithelial electrical resistance and increased fluorescein isothiocyanate-dextran permeability in air-liquid interface cultures of human bronchial epithelial cells. This was in parallel to decreased mRNAs and disrupted protein expression of TJ proteins and was restored by neutralization of IL-13. Intranasal administration of recombinant IL-33 to wild-type and Rag2 -/- mice lacking T and B cells triggered TJ disruption, whereas Rag2 -/- Il2rg -/- and Rora sg/sg mice undergoing bone marrow transplantation that lack ILC2s did not show any barrier leakiness. Direct nasal administration of IL-13 was sufficient to induce deficiency in the TJ barrier in the bronchial epithelium of mice in vivo. These data highlight an essential mechanism in asthma pathogenesis by demonstrating that ILC2s are responsible for bronchial epithelial TJ barrier leakiness through IL-13. Copyright © 2017 American Academy of Allergy, Asthma & Immunology

  15. Ketamine alleviates bradykinin-induced disruption of the mouse cerebrovascular endothelial cell-constructed tight junction barrier via a calcium-mediated redistribution of occludin polymerization

    International Nuclear Information System (INIS)

    Chen, Jui-Tai; Lin, Yi-Ling; Chen, Ta-Liang; Tai, Yu-Ting; Chen, Cheng-Yu; Chen, Ruei-Ming

    2016-01-01

    Highlights: • Ketamine could suppress bradykinin-induced intracellular calcium mobilization. • Ketamine induced B1R protein and mRNA expressions but did not change B2R protein levels. • Ketamine attenuated bradykinin-induced redistribution of occludin tight junctions. • Ketamine prevented bradykinin-induced breakage of the MCEC-constructed tight junction barrier. - Abstract: Following brain injury, a sequence of mechanisms leads to disruption of the blood-brain barrier (BBB) and subsequent cerebral edema, which is thought to begin with activation of bradykinin. Our previous studies showed that ketamine, a widely used intravenous anesthetic agent, can suppress bradykinin-induced cell dysfunction. This study further aimed to evaluate the protective effects of ketamine against bradykinin-induced disruption of the mouse cerebrovascular endothelial cell (MCEC)-constructed tight junction barrier and the possible mechanisms. Exposure of MCECs to bradykinin increased intracellular calcium (Ca 2+ ) concentrations in a time-dependent manner. However, pretreatment of MCECs with ketamine time- and concentration-dependently lowered the bradykinin-induced calcium influx. As to the mechanisms, although exposure of MCECs to ketamine induced bradykinin R1 receptor protein and mRNA expression, this anesthetic did not change levels of the bradykinin R2 receptor, a major receptor that responds to bradykinin stimulation. Bradykinin increased amounts of soluble occludin in MCECs, but pretreatment with ketamine alleviated this disturbance in occludin polymerization. Consequently, exposure to bradykinin decreased the transendothelial electronic resistance in the MCEC-constructed tight junction barrier. However, pretreatment with ketamine attenuated the bradykinin-induced disruption of the tight junction barrier. Taken together, this study shows that ketamine at a therapeutic concentration can protect against bradykinin-induced breakage of the BBB via suppressing calcium

  16. Claudin-2 knockout by TALEN-mediated gene targeting in MDCK cells: claudin-2 independently determines the leaky property of tight junctions in MDCK cells.

    Directory of Open Access Journals (Sweden)

    Shinsaku Tokuda

    Full Text Available Tight junctions (TJs regulate the movements of substances through the paracellular pathway, and claudins are major determinants of TJ permeability. Claudin-2 forms high conductive cation pores in TJs. The suppression of claudin-2 expression by RNA interference in Madin-Darby canine kidney (MDCK II cells (a low-resistance strain of MDCK cells was shown to induce a three-fold increase in transepithelial electrical resistance (TER, which, however, was still lower than in high-resistance strains of MDCK cells. Because RNA interference-mediated knockdown is not complete and only reduces gene function, we considered the possibility that the remaining claudin-2 expression in the knockdown study caused the lower TER in claudin-2 knockdown cells. Therefore, we investigated the effects of claudin-2 knockout in MDCK II cells by establishing claudin-2 knockout clones using transcription activator-like effector nucleases (TALENs, a recently developed genome editing method for gene knockout. Surprisingly, claudin-2 knockout increased TER by more than 50-fold in MDCK II cells, and TER values in these cells (3000-4000 Ω·cm2 were comparable to those in the high-resistance strains of MDCK cells. Claudin-2 re-expression restored the TER of claudin-2 knockout cells dependent upon claudin-2 protein levels. In addition, we investigated the localization of claudin-1, -2, -3, -4, and -7 at TJs between control MDCK cells and their respective knockout cells using their TALENs. Claudin-2 and -7 were less efficiently localized at TJs between control and their knockout cells. Our results indicate that claudin-2 independently determines the 'leaky' property of TJs in MDCK II cells and suggest the importance of knockout analysis in cultured cells.

  17. Time-dependent effects of low-temperature atmospheric-pressure argon plasma on epithelial cell attachment, viability and tight junction formation in vitro

    International Nuclear Information System (INIS)

    Hoentsch, Maxi; Barbara Nebe, J; Von Woedtke, Thomas; Weltmann, Klaus-Dieter

    2012-01-01

    The application of physical plasma to living tissues is expected to promote wound healing by plasma disinfection and stimulation of tissue regeneration. However, the effects of plasma on healthy cells must be studied and understood. In our experiments we used an argon plasma jet (kINPen®09) to gain insights into time-dependent plasma effects on cell attachment, viability and tight junction formation in vitro. Murine epithelial cells mHepR1 were suspended in complete cell culture medium and were irradiated with argon plasma (direct approach) for 30, 60 and 120 s. Suspecting that physical plasma may exert its effect via the medium, cell culture medium alone was first treated with argon plasma (indirect approach) and immediately afterwards, cells were added and also cultured for 24 h. Cell morphology and vitality were verified using light microscopy and an enzyme-linked immunosorbent assay. Already after 30 s of treatment the mHepR1 cells lost their capability to adhere and the cell vitality decreased with increasing treatment time. Interestingly, the same inhibitory effect was observed in the indirect approach. Furthermore, the argon plasma-treated culture medium-induced large openings of the cell's tight junctions, were verified by the zonula occludens protein ZO-1, which we observed for the first time in confluently grown epithelial cells. (paper)

  18. Transformation of a beta gamma hot-cell under air in a tight hot-cell under inert gas

    International Nuclear Information System (INIS)

    Lambert, G.

    1981-05-01

    For several years now, fuel elements from graphite gas reactors have been stored in pools at the Cadarache Center after having been subjected (in general) to laboratory examinations. The CEA has adopted the following re-transfer procedure for these fuel elements while awaiting reprocessing: the fuel elements are extracted from their existing cartridges and transferred into new welded stainless steel containers capable of assuring long term storage. The storage, however, envisaged is temporary and is realized in the Pegase pool, specially adapted for this purpose. This re-transfer operation is envisaged for some 2.300 containers. All the appropriate safety measures will be taken. The various different fuel materials handled are often highly irradiated. The presence of water in certain containers due to loss of leaktightness has led to a series of chemical reactions (corrosion of uranium by water, reactions with magnesium, formation of hydrides). As a result, existing envelopes can contain UO 2 , UH 3 and hydrogen; operations must therefore being carried out in an inert atmosphere (preferably argon). The re-transfer process can not therefore be carried out in a conventional cell. It is therefore envisaged to carry out this work in a leaktight cell in an inert atmosphere. A laboratory cell could be modified to perform these functions. This cell would be reconverted to its original state when operations terminate (in about 3 years time) [fr

  19. Prime tight frames

    DEFF Research Database (Denmark)

    Lemvig, Jakob; Miller, Christopher; Okoudjou, Kasso A.

    2014-01-01

    to suggest effective analysis and synthesis computation strategies for such frames. Finally, we describe all prime frames constructed from the spectral tetris method, and, as a byproduct, we obtain a characterization of when the spectral tetris construction works for redundancies below two.......We introduce a class of finite tight frames called prime tight frames and prove some of their elementary properties. In particular, we show that any finite tight frame can be written as a union of prime tight frames. We then characterize all prime harmonic tight frames and use thischaracterization...

  20. Staying Tight: Plasmodesmal Membrane Contact Sites and the Control of Cell-to-Cell Connectivity in Plants.

    Science.gov (United States)

    Tilsner, Jens; Nicolas, William; Rosado, Abel; Bayer, Emmanuelle M

    2016-04-29

    Multicellularity differs in plants and animals in that the cytoplasm, plasma membrane, and endomembrane of plants are connected between cells through plasmodesmal pores. Plasmodesmata (PDs) are essential for plant life and serve as conduits for the transport of proteins, small RNAs, hormones, and metabolites during developmental and defense signaling. They are also the only pathways available for viruses to spread within plant hosts. The membrane organization of PDs is unique, characterized by the close apposition of the endoplasmic reticulum and the plasma membrane and spoke-like filamentous structures linking the two membranes, which define PDs as membrane contact sites (MCSs). This specialized membrane arrangement is likely critical for PD function. Here, we review how PDs govern developmental and defensive signaling in plants, compare them with other types of MCSs, and discuss in detail the potential functional significance of the MCS nature of PDs.

  1. Fibroblast growth factor receptor 2 regulates proliferation and Sertoli differentiation during male sex determination

    Science.gov (United States)

    Kim, Yuna; Bingham, Nathan; Sekido, Ryohei; Parker, Keith L.; Lovell-Badge, Robin; Capel, Blanche

    2007-01-01

    Targeted mutagenesis of Fgf9 in mice causes male-to-female sex reversal. Among the four FGF receptors, FGFR2 showed two highly specific patterns based on antibody staining, suggesting that it might be the receptor-mediating FGF9 signaling in the gonad. FGFR2 was detected at the plasma membrane in proliferating coelomic epithelial cells and in the nucleus in Sertoli progenitor cells. This expression pattern suggested that Fgfr2 might play more than one role in testis development. To test the hypothesis that Fgfr2 is required for male sex determination, we crossed mice carrying a floxed allele of Fgfr2 with two different Cre lines to induce a temporal or cell-specific deletion of this receptor. Results show that deletion of Fgfr2 in embryonic gonads phenocopies deletion of Fgf9 and leads to male-to-female sex reversal. Using these two Cre lines, we provide the first genetic evidence that Fgfr2 plays distinct roles in proliferation and Sertoli cell differentiation during testis development. PMID:17940049

  2. Effects of ethanol and acetaldehyde on tight junction integrity: in vitro study in a three dimensional intestinal epithelial cell culture model.

    Directory of Open Access Journals (Sweden)

    Elhaseen Elamin

    Full Text Available BACKGROUND: Intestinal barrier dysfunction and translocation of endotoxins are involved in the pathogenesis of alcoholic liver disease. Exposure to ethanol and its metabolite, acetaldehyde at relatively high concentrations have been shown to disrupt intestinal epithelial tight junctions in the conventional two dimensional cell culture models. The present study investigated quantitatively and qualitatively the effects of ethanol at concentrations detected in the blood after moderate ethanol consumption, of its metabolite acetaldehyde and of the combination of both compounds on intestinal barrier function in a three-dimensional cell culture model. METHODS AND FINDINGS: Caco-2 cells were grown in a basement membrane matrix (Matrigel™ to induce spheroid formation and were then exposed to the compounds at the basolateral side. Morphological differentiation of the spheroids was assessed by immunocytochemistry and transmission electron microscopy. The barrier function was assessed by the flux of FITC-labeled dextran from the basal side into the spheroids' luminal compartment using confocal microscopy. Caco-2 cells grown on Matrigel assembled into fully differentiated and polarized spheroids with a central lumen, closely resembling enterocytes in vivo and provide an excellent model to study epithelial barrier functionality. Exposure to ethanol (10-40 mM or acetaldehyde (25-200 µM for 3 h, dose-dependently and additively increased the paracellular permeability and induced redistribution of ZO-1 and occludin without affecting cell viability or tight junction-encoding gene expression. Furthermore, ethanol and acetaldehyde induced lysine residue and microtubules hyperacetylation. CONCLUSIONS: These results indicate that ethanol at concentrations found in the blood after moderate drinking and acetaldehyde, alone and in combination, can increase the intestinal epithelial permeability. The data also point to the involvement of protein hyperacetylation in

  3. Downregulation of tight junction-associated MARVEL protein marvelD3 during epithelial-mesenchymal transition in human pancreatic cancer cells.

    Science.gov (United States)

    Kojima, Takashi; Takasawa, Akira; Kyuno, Daisuke; Ito, Tatsuya; Yamaguchi, Hiroshi; Hirata, Koichi; Tsujiwaki, Mitsuhiro; Murata, Masaki; Tanaka, Satoshi; Sawada, Norimasa

    2011-10-01

    The novel tight junction protein marvelD3 contains a conserved MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain like occludin and tricellulin. However, little is yet known about the detailed role and regulation of marvelD3 in normal epithelial cells and cancer cells, including pancreatic cancer. In the present study, we investigated marvelD3 expression in well and poorly differentiated human pancreatic cancer cell lines and normal pancreatic duct epithelial cells in which the hTERT gene was introduced into human pancreatic duct epithelial cells in primary culture, and the changes of marvelD3 during Snail-induced epithelial-mesenchymal transition (EMT) under hypoxia, TGF-β treatment and knockdown of FOXA2 in well differentiated pancreatic cancer HPAC cells. MarvelD3 was transcriptionally downregulated in poorly differentiated pancreatic cancer cells and during Snail-induced EMT of pancreatic cancer cells in which Snail was highly expressed and the fence function downregulated, whereas it was maintained in well differentiated human pancreatic cancer cells and normal pancreatic duct epithelial cells. Depletion of marvelD3 by siRNAs in HPAC cells resulted in downregulation of barrier functions indicated as a decrease in transepithelial electric resistance and an increase of permeability to fluorescent dextran tracers, whereas it did not affect fence function of tight junctions. In conclusion, marvelD3 is transcriptionally downregulated in Snail-induced EMT during the progression for the pancreatic cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  4. Effects of Human Parvovirus B19 and Bocavirus VP1 Unique Region on Tight Junction of Human Airway Epithelial A549 Cells

    Science.gov (United States)

    Chiu, Chun-Ching; Shi, Ya-Fang; Yang, Jiann-Jou; Hsiao, Yuan-Chao; Tzang, Bor-Show; Hsu, Tsai-Ching

    2014-01-01

    As is widely recognized, human parvovirus B19 (B19) and human bocavirus (HBoV) are important human pathogens. Obviously, both VP1 unique region (VP1u) of B19 and HBoV exhibit the secreted phospholipase A2 (sPLA2)-like enzymatic activity and are recognized to participate in the pathogenesis of lower respiratory tract illnesses. However, exactly how, both VP1u from B19 and HBoV affect tight junction has seldom been addressed. Therefore, this study investigates how B19-VP1u and HBoV-VP1u may affect the tight junction of the airway epithelial A549 cells by examining phospholipase A2 activity and transepithelial electrical resistance (TEER) as well as performing immunoblotting analyses. Experimental results indicate that TEER is more significantly decreased in A549 cells by treatment with TNF-α (10 ng), two dosages of B19-VP1u and BoV-VP1u (400 ng and 4000 ng) or bee venom PLA2 (10 ng) than that of the control. Accordingly, more significantly increased claudin-1 and decreased occludin are detected in A549 cells by treatment with TNF-α or both dosages of HBoV-VP1u than that of the control. Additionally, more significantly decreased Na+/K+ ATPase is observed in A549 cells by treatment with TNF-α, high dosage of B19-VP1u or both dosages of BoV-VP1u than that of the control. Above findings suggest that HBoV-VP1u rather than B19 VP1u likely plays more important roles in the disruption of tight junction in the airway tract. Meanwhile, this discrepancy appears not to be associated with the secreted phospholipase A2 (sPLA2)-like enzymatic activity. PMID:25268969

  5. Ablation of CD11c(hi) dendritic cells exacerbates Japanese encephalitis by regulating blood-brain barrier permeability and altering tight junction/adhesion molecules.

    Science.gov (United States)

    Kim, Jin Hyoung; Hossain, Ferdaus Mohd Altaf; Patil, Ajit Mahadev; Choi, Jin Young; Kim, Seong Bum; Uyangaa, Erdenebelig; Park, Sang-Youel; Lee, John-Hwa; Kim, Bumseok; Kim, Koanhoi; Eo, Seong Kug

    2016-10-01

    Japanese encephalitis (JE), characterized by extensive neuroinflammation following infection with neurotropic JE virus (JEV), is becoming a leading cause of viral encephalitis due to rapid changes in climate and demography. The blood-brain barrier (BBB) plays an important role in restricting neuroinvasion of peripheral leukocytes and virus, thereby regulating the progression of viral encephalitis. In this study, we explored the role of CD11c(hi) dendritic cells (DCs) in regulating BBB integrity and JE progression using a conditional depletion model of CD11c(hi) DCs. Transient ablation of CD11c(hi) DCs resulted in markedly increased susceptibility to JE progression along with highly increased neuro-invasion of JEV. In addition, exacerbated JE progression in CD11c(hi) DC-ablated hosts was closely associated with increased expression of proinflammatory cytokines (IFN-β, IL-6, and TNF-α) and CC chemokines (CCL2, CCL3, CXCL2) in the brain. Moreover, our results revealed that the exacerbation of JE progression in CD11c(hi) DC-ablated hosts was correlated with enhanced BBB permeability and reduced expression of tight junction and adhesion molecules (claudin-5, ZO-1, occluding, JAMs). Ultimately, our data conclude that the ablation of CD11c(hi) DCs provided a subsidiary impact on BBB integrity and the expression of tight junction/adhesion molecules, thereby leading to exacerbated JE progression. These findings provide insight into the secondary role of CD11c(hi) DCs in JE progression through regulation of BBB integrity and the expression of tight junction/adhesion molecules. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Acrolein Disrupts Tight Junction Proteins and Causes Endoplasmic Reticulum Stress-Mediated Epithelial Cell Death Leading to Intestinal Barrier Dysfunction and Permeability.

    Science.gov (United States)

    Chen, Wei-Yang; Wang, Min; Zhang, Jingwen; Barve, Shirish S; McClain, Craig J; Joshi-Barve, Swati

    2017-12-01

    Increasing evidence suggests that environmental and dietary factors can affect intestinal epithelial integrity leading to gut permeability and bacterial translocation. Intestinal barrier dysfunction is a pathogenic process associated with many chronic disorders. Acrolein is an environmental and dietary pollutant and a lipid-derived endogenous metabolite. The impact of acrolein on the intestine has not been investigated before and is evaluated in this study, both in vitro and in vivo. Our data demonstrate that oral acrolein exposure in mice caused damage to the intestinal epithelial barrier, resulting in increased permeability and subsequently translocation of bacterial endotoxin-lipopolysaccharide into the blood. Similar results were seen in vitro using established Caco-2 cell monolayers wherein acrolein decreased barrier function and increased permeability. Acrolein also caused the down-regulation and/or redistribution of three representative tight junction proteins (ie, zonula occludens-1, Occludin, Claudin-1) that critically regulate epithelial paracellular permeability. In addition, acrolein induced endoplasmic reticulum stress-mediated death of epithelial cells, which is an important mechanism contributing to intestinal barrier damage/dysfunction, and gut permeability. Overall, we demonstrate that exposure to acrolein affects the intestinal epithelium by decrease/redistribution of tight junction proteins and endoplasmic reticulum stress-mediated epithelial cell death, thereby resulting in loss of barrier integrity and function. Our findings highlight the adverse consequences of environmental and dietary pollutants on intestinal barrier integrity/function with relevance to gut permeability and the development of disease. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  7. 21-Benzylidene Digoxin: A Proapoptotic Cardenolide of Cancer Cells That Up-Regulates Na,K-ATPase and Epithelial Tight Junctions

    Science.gov (United States)

    Rocha, Sayonarah C.; Pessoa, Marco T. C.; Neves, Luiza D. R.; Alves, Silmara L. G.; Silva, Luciana M.; Santos, Herica L.; Oliveira, Soraya M. F.; Taranto, Alex G.; Comar, Moacyr; Gomes, Isabella V.; Santos, Fabio V.; Paixão, Natasha; Quintas, Luis E. M.; Noël, François; Pereira, Antonio F.; Tessis, Ana C. S. C.; Gomes, Natalia L. S.; Moreira, Otacilio C.; Rincon-Heredia, Ruth; Varotti, Fernando P.; Blanco, Gustavo; Villar, Jose A. F. P.; Contreras, Rubén G.; Barbosa, Leandro A.

    2014-01-01

    Cardiotonic steroids are used to treat heart failure and arrhythmia and have promising anticancer effects. The prototypic cardiotonic steroid ouabain may also be a hormone that modulates epithelial cell adhesion. Cardiotonic steroids consist of a steroid nucleus and a lactone ring, and their biological effects depend on the binding to their receptor, Na,K-ATPase, through which, they inhibit Na+ and K+ ion transport and activate of several intracellular signaling pathways. In this study, we added a styrene group to the lactone ring of the cardiotonic steroid digoxin, to obtain 21-benzylidene digoxin (21-BD), and investigated the effects of this synthetic cardiotonic steroid in different cell models. Molecular modeling indicates that 21-BD binds to its target Na,K-ATPase with low affinity, adopting a different pharmacophoric conformation when bound to its receptor than digoxin. Accordingly, 21-DB, at relatively high µM amounts inhibits the activity of Na,K-ATPase α1, but not α2 and α3 isoforms. In addition, 21-BD targets other proteins outside the Na,K-ATPase, inhibiting the multidrug exporter Pdr5p. When used on whole cells at low µM concentrations, 21-BD produces several effects, including: 1) up-regulation of Na,K-ATPase expression and activity in HeLa and RKO cancer cells, which is not found for digoxin, 2) cell specific changes in cell viability, reducing it in HeLa and RKO cancer cells, but increasing it in normal epithelial MDCK cells, which is different from the response to digoxin, and 3) changes in cell-cell interaction, altering the molecular composition of tight junctions and elevating transepithelial electrical resistance of MDCK monolayers, an effect previously found for ouabain. These results indicate that modification of the lactone ring of digoxin provides new properties to the compound, and shows that the structural change introduced could be used for the design of cardiotonic steroid with novel functions. PMID:25290152

  8. [Effect of eicosapentaenoic acid on mRNA expression of tight junction protein ZO-1 in intestinal epithelial cells after Escherichia coli LF82 infection].

    Science.gov (United States)

    Hao, Li-Jun; Lin, Yan; Zhang, Wei; Tian, Jiao; Wang, Ya; Chen, Peng-De; Hu, Chong-Kang; Zeng, Ling-Chao; Yang, Jie; Wang, Bao-Xi; Jiang, Xun

    2017-06-01

    To investigate the change in the expression of tight junction protein ZO-1 in intestinal epithelial cells (Caco-2 cells) and the protective effect of eicosapentaenoic acid (EPA) after adherent-invasive Escherichia coli (E.coli) LF82 infection. The Caco-2 cell line was used to establish an in vitro model of tight junction of intestinal epithelial cells. Caco-2 cells were divided into EPA treatment groups (0, 25, 50, 100, and 200 μmol/L EPA) and EPA (0, 25, 50, 100, and 200 μmol/L EPA)+E.coli LF82 treatment (0, 6, and 12 hours) groups. A microscope was used to observe the morphological characteristics of the cells. MTT assay was used to determine the cell growth curve. The activity of alkaline phosphatase (ALP) at both sides of the cell membrane was compared to evaluate the Caco-2 cell model. MTT assay and flow cytometry were used to investigate the effects of different concentrations of EPA on the survival rate and apoptosis rate of Caco-2 cells. RT-qPCR was used to measure the mRNA expression of ZO-1 in Caco-2 cells after EPA and/or E.coli LF82 treatment. ELISA was used to measure the change in the level of tumor necrosis factor-α (TNF-α) in culture supernatant. After EPA treatment (25 and 50 μmol/L), the proliferation of Caco-2 cells was induced in a dose-dependent manner. The survival rates of the cells were significantly higher than those in the control group (PE.coli LF82 treatment groups had decreasing mRNA expression of ZO-1 in Caco-2 cells over the time of treatment and had significantly lower mRNA expression of ZO-1 than the untreated group (PE.coli LF82 and 25 or 50 μmol/L EPA for 6 or 12 hours showed an increase in the mRNA expression of ZO-1 with the increasing concentration of EPA, as well as significantly higher mRNA expression of ZO-1 than the Caco-2 cells treated with E.coli LF82 alone (PE.coli LF82 alone for 6 or 12 hours had increasing secretion of TNF-α over the time of treatment and had significantly higher secretion than the untreated

  9. Proinflammatory cytokines tumor necrosis factor-alpha and interferon-gamma alter tight junction structure and function in the rat parotid gland Par-C10 cell line.

    Science.gov (United States)

    Baker, Olga J; Camden, Jean M; Redman, Robert S; Jones, Jonathan E; Seye, Cheikh I; Erb, Laurie; Weisman, Gary A

    2008-11-01

    Sjögren's syndrome (SS) is an autoimmune disorder characterized by inflammation and dysfunction of salivary glands, resulting in impaired secretory function. The production of the proinflammatory cytokines tumor necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) is elevated in exocrine glands of patients with SS, although little is known about the effects of these cytokines on salivary epithelial cell functions necessary for saliva secretion, including tight junction (TJ) integrity and the establishment of transepithelial ion gradients. The present study demonstrates that chronic exposure of polarized rat parotid gland (Par-C10) epithelial cell monolayers to TNF-alpha and IFN-gamma decreases transepithelial resistance (TER) and anion secretion, as measured by changes in short-circuit current (I(sc)) induced by carbachol, a muscarinic cholinergic receptor agonist, or UTP, a P2Y(2) nucleotide receptor agonist. In contrast, TNF-alpha and IFN-gamma had no effect on agonist-induced increases in the intracellular calcium concentration [Ca(2+)](i) in Par-C10 cells. Furthermore, treatment of Par-C10 cell monolayers with TNF-alpha and IFN-gamma increased paracellular permeability to normally impermeant proteins, altered cell and TJ morphology, and downregulated the expression of the TJ protein, claudin-1, but not other TJ proteins expressed in Par-C10 cells. The decreases in TER, agonist-induced transepithelial anion secretion, and claudin-1 expression caused by TNF-alpha, but not IFN-gamma, were reversible by incubation of Par-C10 cell monolayers with cytokine-free medium for 24 h, indicating that IFN-gamma causes irreversible inhibition of cellular activities associated with fluid secretion in salivary glands. Our results suggest that cytokine production is an important contributor to secretory dysfunction in SS by disrupting TJ integrity of salivary epithelium.

  10. Time-dependent retinal ganglion cell loss, microglial activation and blood-retina-barrier tightness in an acute model of ocular hypertension.

    Science.gov (United States)

    Trost, A; Motloch, K; Bruckner, D; Schroedl, F; Bogner, B; Kaser-Eichberger, A; Runge, C; Strohmaier, C; Klein, B; Aigner, L; Reitsamer, H A

    2015-07-01

    Glaucoma is a group of neurodegenerative diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons, and is the second leading cause of blindness worldwide. Elevated intraocular pressure is a well known risk factor for the development of glaucomatous optic neuropathy and pharmacological or surgical lowering of intraocular pressure represents a standard procedure in glaucoma treatment. However, the treatment options are limited and although lowering of intraocular pressure impedes disease progression, glaucoma cannot be cured by the currently available therapy concepts. In an acute short-term ocular hypertension model in rat, we characterize RGC loss, but also microglial cell activation and vascular alterations of the retina at certain time points. The combination of these three parameters might facilitate a better evaluation of the disease progression, and could further serve as a new model to test novel treatment strategies at certain time points. Acute ocular hypertension (OHT) was induced by the injection of magnetic microbeads into the rat anterior chamber angle (n = 22) with magnetic position control, leading to constant elevation of IOP. At certain time points post injection (4d, 7d, 10d, 14d and 21d), RGC loss, microglial activation, and microvascular pericyte (PC) coverage was analyzed using immunohistochemistry with corresponding specific markers (Brn3a, Iba1, NG2). Additionally, the tightness of the retinal vasculature was determined via injections of Texas Red labeled dextran (10 kDa) and subsequently analyzed for vascular leakage. For documentation, confocal laser-scanning microscopy was used, followed by cell counts, capillary length measurements and morphological and statistical analysis. The injection of magnetic microbeads led to a progressive loss of RGCs at the five time points investigated (20.07%, 29.52%, 41.80%, 61.40% and 76.57%). Microglial cells increased in number and displayed an activated morphology

  11. Arsenic downregulates tight junction claudin proteins through p38 and NF-κB in intestinal epithelial cell line, HT-29

    International Nuclear Information System (INIS)

    Jeong, Chang Hee; Seok, Jin Sil; Petriello, Michael C.; Han, Sung Gu

    2017-01-01

    Arsenic is a naturally occurring metalloid that often is found in foods and drinking water. Human exposure to arsenic is associated with the development of gastrointestinal problems such as fluid loss, diarrhea and gastritis. Arsenic is also known to induce toxic responses including oxidative stress in cells of the gastrointestinal track. Tight junctions (TJs) regulate paracellular permeability and play a barrier role by inhibiting the movement of water, solutes and microorganisms in the paracellular space. Since oxidative stress and TJ damage are known to be associated, we examined whether arsenic produces TJ damage such as downregulation of claudins in the human colorectal cell line, HT-29. To confirm the importance of oxidative stress in arsenic-induced TJ damage, effects of the antioxidant compound (e.g., N-acetylcysteine (NAC)) were also determined in cells. HT-29 cells were treated with arsenic trioxide (40 μM, 12 h) to observe the modified expression of TJ proteins. Arsenic decreased expression of TJ proteins (i.e., claudin-1 and claudin-5) and transepithelial electrical resistance (TEER) whereas pretreatment of NAC (5–10 mM, 1 h) attenuated the observed claudins downregulation and TEER. Arsenic treatment produced cellular oxidative stress via superoxide generation and lowering glutathione (GSH) levels, while NAC restored cellular GSH levels and decreased oxidative stress. Arsenic increased phosphorylation of p38 and nuclear translocation of nuclear factor-kappa B (NF-κB) p65, while NAC attenuated these intracellular events. Results demonstrated that arsenic can damage intestinal epithelial cells by proinflammatory process (oxidative stress, p38 and NF-κB) which resulted in the downregulation of claudins and NAC can protect intestinal TJs from arsenic toxicity.

  12. Cell polarity, cell adhesion, and spermatogenesis: role of cytoskeletons [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Linxi Li

    2017-08-01

    Full Text Available In the rat testis, studies have shown that cell polarity, in particular spermatid polarity, to support spermatogenesis is conferred by the coordinated efforts of the Par-, Crumbs-, and Scribble-based polarity complexes in the seminiferous epithelium. Furthermore, planar cell polarity (PCP is conferred by PCP proteins such as Van Gogh-like 2 (Vangl2 in the testis. On the other hand, cell junctions at the Sertoli cell–spermatid (steps 8–19 interface are exclusively supported by adhesion protein complexes (for example, α6β1-integrin-laminin-α3,β3,γ3 and nectin-3-afadin at the actin-rich apical ectoplasmic specialization (ES since the apical ES is the only anchoring device in step 8–19 spermatids. For cell junctions at the Sertoli cell–cell interface, they are supported by adhesion complexes at the actin-based basal ES (for example, N-cadherin-β-catenin and nectin-2-afadin, tight junction (occludin-ZO-1 and claudin 11-ZO-1, and gap junction (connexin 43-plakophilin-2 and also intermediate filament-based desmosome (for example, desmoglein-2-desmocollin-2. In short, the testis-specific actin-rich anchoring device known as ES is crucial to support spermatid and Sertoli cell adhesion. Accumulating evidence has shown that the Par-, Crumbs-, and Scribble-based polarity complexes and the PCP Vangl2 are working in concert with actin- or microtubule-based cytoskeletons (or both and these polarity (or PCP protein complexes exert their effects through changes in the organization of the cytoskeletal elements across the seminiferous epithelium of adult rat testes. As such, there is an intimate relationship between cell polarity, cell adhesion, and cytoskeletal function in the testis. Herein, we critically evaluate these recent findings based on studies on different animal models. We also suggest some crucial future studies to be performed.

  13. Tight regulation between cell survival and programmed cell death in GBM stem-like cells by EGFR/GSK3b/PP2A signaling.

    Science.gov (United States)

    Gürsel, Demirkan B; Banu, Matei A; Berry, Nicholas; Marongiu, Roberta; Burkhardt, Jan-Karl; Kobylarz, Keith; Kaplitt, Michael G; Rafii, Shahin; Boockvar, John A

    2015-01-01

    Malignant gliomas represent one of the most aggressive forms of cancer, displaying high mortality rates and limited treatment options. Specific subpopulations of cells residing in the tumor niche with stem-like characteristics have been postulated to initiate and maintain neoplasticity while resisting conventional therapies. The study presented here aims to define the role of glycogen synthase kinase 3 beta (GSK3b) in patient-derived glioblastoma (GBM) stem-like cell (GSC) proliferation, apoptosis and invasion. To evaluate the potential role of GSK3b in GBM, protein profiles from 68 GBM patients and 20 normal brain samples were analyzed for EGFR-mediated PI3kinase/Akt and GSK3b signaling molecules including protein phosphatase 2A (PP2A). To better understand the function of GSK3b in GBM, GSCs were isolated from GBM patient samples. Blocking GSK3b phosphorylation at Serine 9 attenuated cell proliferation while concomitantly stimulating apoptosis through activation of Caspase-3 in patient-derived GSCs. Increasing GSK3b protein content resulted in the inhibition of cell proliferation, colony formation and stimulated programmed cell death. Depleting GSK3b in GSCs down regulated PP2A. Furthermore, knocking down PP2A or blocking its activity by okadaic acid inactivated GSK3b by increasing GSK3b phosphorylation at Serine 9. Our data suggests that GSK3b may function as a regulator of apoptosis and tumorigenesis in GSCs. Therapeutic approaches targeting GSK3b in glioblastoma stem-like cells may be a useful addition to our current therapeutic armamentarium.

  14. Simulation of thermal stresses in anode-supported solid oxide fuel cell stacks. Part II: Loss of gas-tightness, electrical contact and thermal buckling

    Science.gov (United States)

    Nakajo, Arata; Wuillemin, Zacharie; Van herle, Jan; Favrat, Daniel

    Structural stability issues in planar solid oxide fuel cells arise from the mismatch between the coefficients of thermal expansion of the components. The stress state at operating temperature is the superposition of several contributions, which differ depending on the component. First, the cells accumulate residual stresses due to the sintering phase during the manufacturing process. Further, the load applied during assembly of the stack to ensure electric contact and flatten the cells prevents a completely stress-free expansion of each component during the heat-up. Finally, thermal gradients cause additional stresses in operation. The temperature profile generated by a thermo-electrochemical model implemented in an equation-oriented process modelling tool (gPROMS) was imported into finite-element software (ABAQUS) to calculate the distribution of stress and contact pressure on all components of a standard solid oxide fuel cell repeat unit. The different layers of the cell in exception of the cathode, i.e. anode, electrolyte and compensating layer were considered in the analysis to account for the cell curvature. Both steady-state and dynamic simulations were performed, with an emphasis on the cycling of the electrical load. The study includes two different types of cell, operation under both thermal partial oxidation and internal steam-methane reforming and two different initial thicknesses of the air and fuel compressive sealing gaskets. The results generated by the models are presented in two papers: Part I focuses on cell cracking. In the present paper, Part II, the occurrences of loss of gas-tightness in the compressive gaskets and/or electrical contact in the gas diffusion layer were identified. In addition, the dependence on temperature of both coefficients of thermal expansion and Young's modulus of the metallic interconnect (MIC) were implemented in the finite-element model to compute the plastic deformation, while the possibilities of thermal buckling

  15. Continuous Shearlet Tight Frames

    KAUST Repository

    Grohs, Philipp

    2010-10-22

    Based on the shearlet transform we present a general construction of continuous tight frames for L2(ℝ2) from any sufficiently smooth function with anisotropic moments. This includes for example compactly supported systems, piecewise polynomial systems, or both. From our earlier results in Grohs (Technical report, KAUST, 2009) it follows that these systems enjoy the same desirable approximation properties for directional data as the previous bandlimited and very specific constructions due to Kutyniok and Labate (Trans. Am. Math. Soc. 361:2719-2754, 2009). We also show that the representation formulas we derive are in a sense optimal for the shearlet transform. © 2010 Springer Science+Business Media, LLC.

  16. Stereological Quantification of Leydig and Sertoli Cells: Technique ...

    African Journals Online (AJOL)

    A total of 105 adult male and 50 female wistar rats weighing 170±10g (70-90 day old) were used for the experiment. The rats were randomly divided into a control and experimental groups. There were four major groups with 5 subgroups consisting of 5 rats each. Varying doses of metronidazole were used depending on the ...

  17. Less-Tight versus Tight Control of Hypertension in Pregnancy

    NARCIS (Netherlands)

    Magee, Laura A.; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E.; Menzies, Jennifer; Sanchez, Johanna; Singer, Joel; Gafni, Amiram; Gruslin, Andrée; Helewa, Michael; Hutton, Eileen; Lee, Shoo K.; Lee, Terry; Logan, Alexander G.; Ganzevoort, Wessel; Welch, Ross; Thornton, Jim G.; Moutquin, Jean-Marie

    2015-01-01

    BACKGROUND The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear. METHODS We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational

  18. Assessment of Density-Functional Tight-Binding Ionization Potentials and Electron Affinities of Molecules of Interest for Organic Solar Cells Against First-Principles GW Calculations

    Directory of Open Access Journals (Sweden)

    Ala Aldin M. H. M. Darghouth

    2015-12-01

    Full Text Available Ionization potentials (IPs and electron affinities (EAs are important quantities input into most models for calculating the open-circuit voltage (Voc of organic solar cells. We assess the semi-empirical density-functional tight-binding (DFTB method with the third-order self-consistent charge (SCC correction and the 3ob parameter set (the third-order DFTB (DFTB3 organic and biochemistry parameter set against experiments (for smaller molecules and against first-principles GW (Green’s function, G, times the screened potential, W calculations (for larger molecules of interest in organic electronics for the calculation of IPs and EAs. Since GW calculations are relatively new for molecules of this size, we have also taken care to validate these calculations against experiments. As expected, DFTB is found to behave very much like density-functional theory (DFT, but with some loss of accuracy in predicting IPs and EAs. For small molecules, the best results were found with ΔSCF (Δ self-consistent field SCC-DFTB calculations for first IPs (good to ± 0.649 eV. When considering several IPs of the same molecule, it is convenient to use the negative of the orbital energies (which we refer to as Koopmans’ theorem (KT IPs as an indication of trends. Linear regression analysis shows that KT SCC-DFTB IPs are nearly as accurate as ΔSCF SCC-DFTB eigenvalues (± 0.852 eV for first IPs, but ± 0.706 eV for all of the IPs considered here for small molecules. For larger molecules, SCC-DFTB was also the ideal choice with IP/EA errors of ± 0.489/0.740 eV from ΔSCF calculations and of ± 0.326/0.458 eV from (KT orbital energies. Interestingly, the linear least squares fit for the KT IPs of the larger molecules also proves to have good predictive value for the lower energy KT IPs of smaller molecules, with significant deviations appearing only for IPs of 15–20 eV or larger. We believe that this quantitative analysis of errors in SCC-DFTB IPs and EAs may be of

  19. Tight closure and vanishing theorems

    International Nuclear Information System (INIS)

    Smith, K.E.

    2001-01-01

    Tight closure has become a thriving branch of commutative algebra since it was first introduced by Mel Hochster and Craig Huneke in 1986. Over the past few years, it has become increasingly clear that tight closure has deep connections with complex algebraic geometry as well, especially with those areas of algebraic geometry where vanishing theorems play a starring role. The purpose of these lectures is to introduce tight closure and to explain some of these connections with algebraic geometry. Tight closure is basically a technique for harnessing the power of the Frobenius map. The use of the Frobenius map to prove theorems about complex algebraic varieties is a familiar technique in algebraic geometry, so it should perhaps come as no surprise that tight closure is applicable to algebraic geometry. On the other hand, it seems that so far we are only seeing the tip of a large and very beautiful iceberg in terms of tight closure's interpretation and applications to algebraic geometry. Interestingly, although tight closure is a 'characteristic p' tool, many of the problems where tight closure has proved useful have also yielded to analytic (L2) techniques. Despite some striking parallels, there had been no specific result directly linking tight closure and L∼ techniques. Recently, however, the equivalence of an ideal central to the theory of tight closure was shown to be equivalent to a certain 'multiplier ideal' first defined using L2 methods. Presumably, deeper connections will continue to emerge. There are two main types of problems for which tight closure has been helpful: in identifying nice structure and in establishing uniform behavior. The original algebraic applications of tight closure include, for example, a quick proof of the Hochster-Roberts theorem on the Cohen-Macaulayness of rings of invariants, and also a refined version of the Brianqon-Skoda theorem on the uniform behaviour of integral closures of powers of ideals. More recent, geometric

  20. Less-tight versus tight control of hypertension in pregnancy.

    Science.gov (United States)

    Magee, Laura A; von Dadelszen, Peter; Rey, Evelyne; Ross, Susan; Asztalos, Elizabeth; Murphy, Kellie E; Menzies, Jennifer; Sanchez, Johanna; Singer, Joel; Gafni, Amiram; Gruslin, Andrée; Helewa, Michael; Hutton, Eileen; Lee, Shoo K; Lee, Terry; Logan, Alexander G; Ganzevoort, Wessel; Welch, Ross; Thornton, Jim G; Moutquin, Jean-Marie

    2015-01-29

    The effects of less-tight versus tight control of hypertension on pregnancy complications are unclear. We performed an open, international, multicenter trial involving women at 14 weeks 0 days to 33 weeks 6 days of gestation who had nonproteinuric preexisting or gestational hypertension, office diastolic blood pressure of 90 to 105 mm Hg (or 85 to 105 mm Hg if the woman was taking antihypertensive medications), and a live fetus. Women were randomly assigned to less-tight control (target diastolic blood pressure, 100 mm Hg) or tight control (target diastolic blood pressure, 85 mm Hg). The composite primary outcome was pregnancy loss or high-level neonatal care for more than 48 hours during the first 28 postnatal days. The secondary outcome was serious maternal complications occurring up to 6 weeks post partum or until hospital discharge, whichever was later. Included in the analysis were 987 women; 74.6% had preexisting hypertension. The primary-outcome rates were similar among 493 women assigned to less-tight control and 488 women assigned to tight control (31.4% and 30.7%, respectively; adjusted odds ratio, 1.02; 95% confidence interval [CI], 0.77 to 1.35), as were the rates of serious maternal complications (3.7% and 2.0%, respectively; adjusted odds ratio, 1.74; 95% CI, 0.79 to 3.84), despite a mean diastolic blood pressure that was higher in the less-tight-control group by 4.6 mm Hg (95% CI, 3.7 to 5.4). Severe hypertension (≥160/110 mm Hg) developed in 40.6% of the women in the less-tight-control group and 27.5% of the women in the tight-control group (Phypertension. (Funded by the Canadian Institutes of Health Research; CHIPS Current Controlled Trials number, ISRCTN71416914; ClinicalTrials.gov number, NCT01192412.).

  1. Regulation of Tight Junctions in Upper Airway Epithelium

    Directory of Open Access Journals (Sweden)

    Takashi Kojima

    2013-01-01

    Full Text Available The mucosal barrier of the upper respiratory tract including the nasal cavity, which is the first site of exposure to inhaled antigens, plays an important role in host defense in terms of innate immunity and is regulated in large part by tight junctions of epithelial cells. Tight junction molecules are expressed in both M cells and dendritic cells as well as epithelial cells of upper airway. Various antigens are sampled, transported, and released to lymphocytes through the cells in nasal mucosa while they maintain the integrity of the barrier. Expression of tight junction molecules and the barrier function in normal human nasal epithelial cells (HNECs are affected by various stimuli including growth factor, TLR ligand, and cytokine. In addition, epithelial-derived thymic stromal lymphopoietin (TSLP, which is a master switch for allergic inflammatory diseases including allergic rhinitis, enhances the barrier function together with an increase of tight junction molecules in HNECs. Furthermore, respiratory syncytial virus infection in HNECs in vitro induces expression of tight junction molecules and the barrier function together with proinflammatory cytokine release. This paper summarizes the recent progress in our understanding of the regulation of tight junctions in the upper airway epithelium under normal, allergic, and RSV-infected conditions.

  2. Are tight gas resources overstated?

    Energy Technology Data Exchange (ETDEWEB)

    Roche, P.

    2004-11-01

    According to conventional wisdom, North America's tight gas resources are continuous, regional accumulations of water-free methane, trapped in low-permeability rock, and involving very little exploration risk. Backing up conventional wisdom, EnCana Corporation is investing heavily in technology-intensive and capital-intensive tight gas plays in Western Canada and the Rocky Mountain regions of the United States. On the other hand, a recent study in the Greater Green River Basin of southwestern Wyoming says that tight gas resources have been significantly overestimated, by as much as three to five times too high, and the risks of exploration are every bit as high as those for conventional exploration. This study essentially dismisses the whole idea of tight gas, or basin-centred gas as a myth, the authors being firmly convinced that tight gas formations should be viewed as conventional hydrocarbon systems, with the usual risks of exploration. This paper discusses the controversy created by this recent study and the implications for natural gas reserves on a basin and individual company level, and the risks associated with exploration. The views of EnCana Corporation, being the company most heavily involved in tight gas and coalbed methane, and those of John Masters, co-founder of Canadian Hunter Exploration Ltd., and discoverer of the blockbuster Elsmworth tight gas deposit in northeastern Alberta in the mid-1970s, are explained in considerable detail, in an effort to dismiss the doubters. EnCana officials and Masters argue that the points raised by the authors of the Greater Green River study do not hold water: Tight gas or basin gas is a distinct hydrocarbon formation, characterized by low permeability, therefore it is to be expected that the gas will take longer to come out of the ground. Neither is the role of water in basin-centred gas systems the major problem as claimed by the doubters. They also characterize it as imprudent to claim to know what the

  3. Baicalin Protects against TNF-α-Induced Injury by Down-Regulating miR-191a That Targets the Tight Junction Protein ZO-1 in IEC-6 Cells.

    Science.gov (United States)

    Wang, Li; Zhang, Ren; Chen, Jian; Wu, Qihui; Kuang, Zaoyuan

    2017-04-01

    Tumor necrosis factor-alpha (TNF-α) plays an important role in the developing process of inflammatory bowel disease. Tight junction protein zonula occludens-1 (ZO-1), one of epithelial junctional proteins, maintains the permeability of intestinal barrier. The objective of this study was to investigate the mechanism of the protective effect of baicalin on TNF-α-induced injury and ZO-1 expression in intestinal epithelial cells (IECs). We found that baicalin pretreatment significantly improved cell viability and cell migration following TNF-α stimulation. miR-191a inhibitor increased the protective effect of baicalin on cell motility injured by TNF-α. In addition, miR-191a down-regulated the mRNA and protein level of its target gene ZO-1. TNF-α stimulation increased miR-191a expression, leading to the decline of ZO-1 mRNA and protein. Moreover, pretreatment with baicalin reversed TNF-α induced decrease of ZO-1 and increase of miR-191a, miR-191a inhibitor significantly enhanced ZO-1 protein expression restored by baicalin. These results indicate that baicalin exerts a protective effect on IEC-6 (rat small intestinal epithelial cells) cells against TNF-α-induced injury, which is at least partly via inhibiting the expression of miR-191a, thus increasing ZO-1 mRNA and protein levels.

  4. Tightness of voter model interfaces

    Czech Academy of Sciences Publication Activity Database

    Sturm, A.; Swart, Jan M.

    2008-01-01

    Roč. 13, - (2008), s. 165-174 ISSN 1083-589X R&D Projects: GA ČR GA201/06/1323; GA ČR GA201/07/0237 Institutional research plan: CEZ:AV0Z10750506 Keywords : long range voter model * swapping voter model * interface tightness * exclusion process Subject RIV: BD - Theory of Information Impact factor: 0.392, year: 2008 http://www.emis.de/journals/EJP-ECP/_ejpecp/index.html

  5. Tight or sick building syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Thirumalaikolundusubramanian, P; Shanmuganadan, S [Madurai Kamaraj Univ. (India). Dept. of Geography; Uma, A [Madurai Medical Coll. (India). Dept. of Medicine and Microbiology

    1991-01-01

    Modern buildings are designed with the usual heating, air-conditioning and ventilation equipment. In most of these buildings, air is continuously recirculated and, as a result, workers suffer from tight or sick building syndrome. This syndrome is discussed with reference to symptoms of air contamination, ventilation system standards and research needs. The most common symptoms of tight building syndrome are eye, nose and throat irritation, headache, fatigue, sneezing, difficulty in wearing contact lenses, chest tightness, nausea, dizziness and dermatitis. Symptoms experienced by 50 doctors and 50 paramedical personnel working in an air-conditioned intensive care unit and operating theatres of the Government Rajaji Hospital, Madurai in India were studied by means of a questionnaire survey. In the present study, respiratory and ocular symptoms were observed more in those working in operating theatres and were believed to be due to excessive use of formaldehyde used for sterilization. Various suggestions were made to prevent sick building syndrome. Moreover, the physicians treating sick individuals should be aware of the symptoms caused by indoor air pollutants as sufferers invariably require a change of environment rather than drugs. (orig.).

  6. Cross-talk between miR-471-5p and autophagy component proteins regulates LC3-associated phagocytosis (LAP) of apoptotic germ cells.

    Science.gov (United States)

    Panneerdoss, Subbarayalu; Viswanadhapalli, Suryavathi; Abdelfattah, Nourhan; Onyeagucha, Benjamin C; Timilsina, Santosh; Mohammad, Tabrez A; Chen, Yidong; Drake, Michael; Vuori, Kristiina; Kumar, T Rajendra; Rao, Manjeet K

    2017-09-19

    Phagocytic clearance of apoptotic germ cells by Sertoli cells is vital for germ cell development and differentiation. Here, using a tissue-specific miRNA transgenic mouse model, we show that interaction between miR-471-5p and autophagy member proteins regulates clearance of apoptotic germ cells via LC3-associated phagocytosis (LAP). Transgenic mice expressing miR-471-5p in Sertoli cells show increased germ cell apoptosis and compromised male fertility. Those effects are due to defective engulfment and impaired LAP-mediated clearance of apoptotic germ cells as miR-471-5p transgenic mice show lower levels of Dock180, LC3, Atg12, Becn1, Rab5 and Rubicon in Sertoli cells. Our results reveal that Dock180 interacts with autophagy member proteins to constitute a functional LC3-dependent phagocytic complex. We find that androgen regulates Sertoli cell phagocytosis by controlling expression of miR-471-5p and its target proteins. These findings suggest that recruitment of autophagy machinery is essential for efficient clearance of apoptotic germ cells by Sertoli cells using LAP.Although phagocytic clearance of apoptotic germ cells by Sertoli cells is essential for spermatogenesis, little of the mechanism is known. Here the authors show that Sertoli cells employ LC3-associated phagocytosis (LAP) by recruiting autophagy member proteins to clear apoptotic germ cells.

  7. iP-gp , a novel cell line with tight barrier function and expression of human P-glycoprotein (ABCB1) for drug screening

    DEFF Research Database (Denmark)

    Brodin, Birger; Ozgür, Burak; Saaby, Lasse

    that new API's are evaluated with respect to P-gp interactions.  Aim : The aim of the present work was to validate the suitability of the newly developed iP-gp cell line for investigating P-gp interactions with human P-gp. Methods: IPEC-J2 MDR1 (iP-gp) cells were cultured on permeable supports for 17......Background : The efflux transporter P-glycoprotein (P-gp, product of the MDR1/ABCB1 gene) hinders uptake of drug compounds to the brain, limits intestinal uptake, is a cause of resistance to chemoterapeutics and a potential "site" for drug-drug interaction. Regulatory agencies therefore recommend.......04 +/- 0.01 µM in transport experiments including digoxin and rhodamine 123, respectively. Summary/Conclusion : The iP-gp cell line may become a useful screening tool for interactions between drug compounds and human P-gp....

  8. Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp.

    Science.gov (United States)

    Gao, Shiqiang; Nagpal, Jatin; Schneider, Martin W; Kozjak-Pavlovic, Vera; Nagel, Georg; Gottschalk, Alexander

    2015-09-08

    Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. In sensory neurons, cGMP permits signal modulation, amplification and encoding, before depolarization. Here we implement a guanylyl cyclase rhodopsin from Blastocladiella emersonii as a new optogenetic tool (BeCyclOp), enabling rapid light-triggered cGMP increase in heterologous cells (Xenopus oocytes, HEK293T cells) and in Caenorhabditis elegans. Among five different fungal CyclOps, exhibiting unusual eight transmembrane topologies and cytosolic N-termini, BeCyclOp is the superior optogenetic tool (light/dark activity ratio: 5,000; no cAMP production; turnover (20 °C) ∼17 cGMP s(-1)). Via co-expressed CNG channels (OLF in oocytes, TAX-2/4 in C. elegans muscle), BeCyclOp photoactivation induces a rapid conductance increase and depolarization at very low light intensities. In O2/CO2 sensory neurons of C. elegans, BeCyclOp activation evokes behavioural responses consistent with their normal sensory function. BeCyclOp therefore enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals.

  9. The Effects of Glucagon-like Peptide-2 on the Tight Junction and Barrier Function in IPEC-J2 Cells through Phosphatidylinositol 3-kinase–Protein Kinase B–Mammalian Target of Rapamycin Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Changsong Yu

    2016-05-01

    Full Text Available Glucagon-like peptide-2 (GLP-2 is important for intestinal barrier function and regulation of tight junction (TJ proteins, but the intracellular mechanisms of action remain undefined. The purpose of this research was to determine the protective effect of GLP-2 mediated TJ and transepithelial electrical resistance (TER in lipopolysaccharide (LPS stressed IPEC-J2 cells and to test the hypothesis that GLP-2 regulate TJ and TER through the phosphatidylinositol 3-kinase (PI3K-protein kinase B (Akt-mammalian target of rapamycin (mTOR signaling pathway in IPEC-J2 cells. Wortmannin and LY294002 are specific inhibitors of PI3K. The results showed that 100 μg/mL LPS stress decreased TER and TJ proteins occludin, claudin-1 and zonula occludens protein 1 (ZO-1 mRNA, proteins expressions (p<0.01 respectively. GLP-2 (100 nmol/L promote TER and TJ proteins occludin, claudin-1, and zo-1 mRNA, proteins expressions in LPS stressed and normal IPEC-J2 cells (p<0.01 respectively. In normal cells, both wortmannin and LY294002, PI3K inhibitors, prevented the mRNA and protein expressions of Akt and mTOR increase induced by GLP-2 (p<0.01 following with the significant decreasing of occludin, claudin-1, ZO-1 mRNA and proteins expressions and TER (p<0.01. In conclusion, these results indicated that GLP-2 can promote TJ’s expression and TER in LPS stressed and normal IPEC-J2 cells and GLP-2 could regulate TJ and TER through the PI3K/Akt/mTOR pathway.

  10. Tightly Controlled Expression of bHLH142 Is Essential for Timely Tapetal Programmed Cell Death and Pollen Development in Rice

    Directory of Open Access Journals (Sweden)

    Swee-Suak Ko

    2017-07-01

    Full Text Available Male sterility is important for hybrid seed production. Pollen development is regulated by a complex network. We previously showed that knockout of bHLH142 in rice (Oryza sativa causes pollen sterility by interrupting tapetal programmed cell death (PCD and bHLH142 coordinates with TDR to modulate the expression of EAT1. In this study, we demonstrated that overexpression of bHLH142 (OE142 under the control of the ubiquitin promoter also leads to male sterility in rice by triggering the premature onset of PCD. Protein of bHLH142 was found to accumulate specifically in the OE142 anthers. Overexpression of bHLH142 induced early expression of several key regulatory transcription factors in pollen development. In particular, the upregulation of EAT1 at the early stage of pollen development promoted premature PCD in the OE142 anthers, while its downregulation at the late stage impaired pollen development by suppressing genes involved in pollen wall biosynthesis, ROS scavenging and PCD. Collectively, these events led to male sterility in OE142. Analyses of related mutants further revealed the hierarchy of the pollen development regulatory gene network. Thus, the findings of this study advance our understanding of the central role played by bHLH142 in the regulatory network leading to pollen development in rice and how overexpression of its expression affects pollen development. Exploitation of this novel functionality of bHLH142 may confer a big advantage to hybrid seed production.

  11. Diagnosing the tight building syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, S.A.

    1987-12-01

    Formaldehyde is but one of many chemicals capable of causing the tight building syndrome or environmentally induced illness (EI). The spectrum of symptoms it may induce includes attacks of headache, flushing, laryngitis, dizziness, nausea, extreme weakness, arthralgia, unwarranted depression, dysphonia, exhaustion, inability to think clearly, arrhythmia or muscle spasms. The nonspecificity of such symptoms can baffle physicians from many specialties. Presented herein is a simple office method for demonstrating that formaldehyde is among the etiologic agents triggering these symptoms. The very symptoms that patients complain of can be provoked within minutes, and subsequently abolished, with an intradermal injection of the appropriate strength of formaldehyde. This injection aids in convincing the patient of the cause of the symptoms so he can initiate measure to bring his disease under control.

  12. Invasive tightly coupled processor arrays

    CERN Document Server

    LARI, VAHID

    2016-01-01

    This book introduces new massively parallel computer (MPSoC) architectures called invasive tightly coupled processor arrays. It proposes strategies, architecture designs, and programming interfaces for invasive TCPAs that allow invading and subsequently executing loop programs with strict requirements or guarantees of non-functional execution qualities such as performance, power consumption, and reliability. For the first time, such a configurable processor array architecture consisting of locally interconnected VLIW processing elements can be claimed by programs, either in full or in part, using the principle of invasive computing. Invasive TCPAs provide unprecedented energy efficiency for the parallel execution of nested loop programs by avoiding any global memory access such as GPUs and may even support loops with complex dependencies such as loop-carried dependencies that are not amenable to parallel execution on GPUs. For this purpose, the book proposes different invasion strategies for claiming a desire...

  13. Tightly Secure Signatures From Lossy Identification Schemes

    OpenAIRE

    Abdalla , Michel; Fouque , Pierre-Alain; Lyubashevsky , Vadim; Tibouchi , Mehdi

    2015-01-01

    International audience; In this paper, we present three digital signature schemes with tight security reductions in the random oracle model. Our first signature scheme is a particularly efficient version of the short exponent discrete log-based scheme of Girault et al. (J Cryptol 19(4):463–487, 2006). Our scheme has a tight reduction to the decisional short discrete logarithm problem, while still maintaining the non-tight reduction to the computational version of the problem upon which the or...

  14. Indigenous lactobacilli strains of food and human sources reverse enteropathogenic E. coli O26:H11-induced damage in intestinal epithelial cell lines: effect on redistribution of tight junction proteins.

    Science.gov (United States)

    Jariwala, Ruchi; Mandal, Hemanti; Bagchi, Tamishraha

    2017-09-01

    The aim of the study was to investigate the neutralizing effect of lactobacilli isolated from indigenous food and human sources on enteropathogenic Escherichia coli (EPEC) O26 : H11-induced epithelial barrier dysfunction in vitro. This was assessed by transepithelial electrical resistance (TEER) and permeability assays using intestinal cell lines, HT-29 and Caco-2. Furthermore, the expression and distribution of tight junction (TJ) proteins were analysed by qRT-PCR and immunofluorescence assay, respectively. The nine strains used in the study were from different species viz. Lactobacillus fermentum, Lactobacillushelveticus, Lactobacillus salivarius and Lactobacillus plantarum. All strains were able to reverse the decrease in TEER and corresponding increase in permeability across E. coli-infected monolayers. Maximum reversal was observed after 18 h [up to 93.8±2.0 % by L. rhamnosus GG followed by L. fermentum IIs11.2 (92.6±2.2 %) and L. plantarum GRI-2 (91.9±0.9 %)] of lactobacilli exposure following EPEC O26 : H11 infection. All strains were able to redistribute the TJ proteins to the cell periphery either partially or completely. Moreover, L. helveticus FA-7 was also able to significantly increase the mRNA expression of ZO-1 and claudin-1 (2.5-fold and 3.0-fold, respectively; PGRI-2 were good in all the aspects studied, and the other strains were good in some aspects. L. helveticus FA-7, L. fermentum FA-1 and L. plantarum GRI-2 can therefore be used for potential therapeutic purpose against intestinal epithelial dysfunction.

  15. Steam and electroheating remediation of tight soils

    Energy Technology Data Exchange (ETDEWEB)

    Balshaw-Biddle, K.; Oubre, C.L.; Ward, C.H. [eds.; Dablow, J.F. III; Pearce, J.A.; Johnson, P.C.

    2000-07-01

    In the past few decades the need for soil remediation has become urgent, even more necessary--innovative, cost effective methods. Steam and Electroheating Remediation of Tight Soils presents the results of a field study testing the cleanup of semi-volatile fuels from tight soils using combination of hydraulic fracturing and soil heating technologies.

  16. Tight connection between fission gas discharge channels

    International Nuclear Information System (INIS)

    Jung, W.; Peehs, M.; Rau, P.; Krug, W.; Stechemesser, H.

    1978-01-01

    The invention is concerned with the tight connection between the fission gas discharge channel, leading away from the support plate of a gas-cooled reactor, and the top of the fuel element suspended from this support plate. The closure is designed to be gas-tight for the suspended as well as for the released fuel element. The tight connection has got an annular body resting on the core support plate in the mouth region of the fission gas discharge channel. This body is connected with the fission gas discharge channel in the fuel element top fitting via a gas-tight part and supported by a compression spring. Care is taken for sealing if the fuel element is removal. (RW) [de

  17. An introduction to finite tight frames

    CERN Document Server

    Waldron, Shayne F D

    2018-01-01

    This textbook is an introduction to the theory and applications of finite tight frames, an area that has developed rapidly in the last decade. Stimulating much of this growth are the applications of finite frames to diverse fields such as signal processing, quantum information theory, multivariate orthogonal polynomials, and remote sensing. Key features and topics: * First book entirely devoted to finite frames * Extensive exercises and MATLAB examples for classroom use * Important examples, such as harmonic and Heisenberg frames, are presented in preliminary chapters, encouraging readers to explore and develop an intuitive feeling for tight frames * Later chapters delve into general theory details and recent research results * Many illustrations showing the special aspects of the geometry of finite frames * Provides an overview of the field of finite tight frames * Discusses future research directions in the field Featuring exercises and MATLAB examples in each chapter, the book is well suited as a textbook ...

  18. Hermetic compartments leak-tightness enhancement

    International Nuclear Information System (INIS)

    Murani, J.

    2000-01-01

    In connection with the enhancement of the nuclear safety of the Jaslovske Bohunice V-1 NPP actions for the increase of the leak tightness are performed. The reconstruction has been done in the following directions: hermetic compartments leak tightness enhancement; air lock installation; installation of air lock in SP 4 vent system; integrated leakage rate test to hermetic compartments with leak detection. After 'major' leaks on the hermetic boundary components had been eliminated, since 1994 works on a higher qualitative level began. The essence of the works consists in the detection and identification of leaks in the structural component of the hermetic boundary during the planned refueling outages. The results of the Small Reconstruction and gradual enhancement of leak tightness are presented

  19. Advanced Hydraulic Fracturing Technology for Unconventional Tight Gas Reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Stephen Holditch; A. Daniel Hill; D. Zhu

    2007-06-19

    The objectives of this project are to develop and test new techniques for creating extensive, conductive hydraulic fractures in unconventional tight gas reservoirs by statistically assessing the productivity achieved in hundreds of field treatments with a variety of current fracturing practices ranging from 'water fracs' to conventional gel fracture treatments; by laboratory measurements of the conductivity created with high rate proppant fracturing using an entirely new conductivity test - the 'dynamic fracture conductivity test'; and by developing design models to implement the optimal fracture treatments determined from the field assessment and the laboratory measurements. One of the tasks of this project is to create an 'advisor' or expert system for completion, production and stimulation of tight gas reservoirs. A central part of this study is an extensive survey of the productivity of hundreds of tight gas wells that have been hydraulically fractured. We have been doing an extensive literature search of the SPE eLibrary, DOE, Gas Technology Institute (GTI), Bureau of Economic Geology and IHS Energy, for publicly available technical reports about procedures of drilling, completion and production of the tight gas wells. We have downloaded numerous papers and read and summarized the information to build a database that will contain field treatment data, organized by geographic location, and hydraulic fracture treatment design data, organized by the treatment type. We have conducted experimental study on 'dynamic fracture conductivity' created when proppant slurries are pumped into hydraulic fractures in tight gas sands. Unlike conventional fracture conductivity tests in which proppant is loaded into the fracture artificially; we pump proppant/frac fluid slurries into a fracture cell, dynamically placing the proppant just as it occurs in the field. From such tests, we expect to gain new insights into some of the critical

  20. Absolute tightness: the chemists hesitate to invest

    International Nuclear Information System (INIS)

    Anon.

    1996-01-01

    The safety requirements of industries as nuclear plants and the strengthening of regulations in the field of environment (more particularly those related to volatile organic compounds) have lead the manufacturers to build absolute tightness pumps. But these equipments do not answer all the problems and represent a high investment cost. In consequence, the chemists hesitate to invest. (O.L.)

  1. Role of the Adherens Junction Protein Fascin in the Regulation of Tight Junction Permeability in the Mouse Mammary Gland

    National Research Council Canada - National Science Library

    Beeman, Neal

    2001-01-01

    .... Transduced cells are morphologically normal and produce milk. This gene delivery system was used to express an N-terminally truncated mutant of the tight junction protein occluding in the mammary gland and in cultured cells...

  2. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    International Nuclear Information System (INIS)

    Li, Zhao; Jin, Zhu-Qiu

    2012-01-01

    Highlights: ► Cardiac tight junctions are present between coronary endothelial cells. ► Ischemic preconditioning preserves the structural and functional integrity of tight junctions. ► Myocardial edema is prevented in hearts subjected to ischemic preconditioning. ► Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood–heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs–Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC enhanced the translocation of ZO-2 from cytosol to cytoskeleton. In conclusion, TJs occur in

  3. Improving horizontal completions on heterogeneous tight shales

    Energy Technology Data Exchange (ETDEWEB)

    Suarez-Rivera, Roberto; Deenadayalu, Chaitanya; Chertov, Maxim; Novalo Hartanto, Ricardo; Gathogo, Patrick [Schlumberger (United States); Kunjir, Rahul [University of Utah (United States)

    2011-07-01

    Evaluation of the two formation characteristics conducive to economic well production is important when tight shale formation characterization and completion design are being considered. This paper presents the basic understanding required to improve the efficiency of horizontal completions in oil and gas producing shales. Guidelines are defined for effective perforation and fracturing to improve the efficiency and sustainability of horizontal completions using extensive laboratory characterization of mechanical properties on core, core/log integration and continuous mapping of these properties by logging-while-drilling (LWD) methods. The objective is to improve completion design efficiency. This is accomplished by suitable selection of perforation intervals based on an understanding of the relevant physical processes and rock characterization. Conditions at two reservoir regions, the near-wellbore and the far-wellbore, are outlined and are essential to completion design. From the study, it can be concluded that tight shales are strongly anisotropic and cannot be approximated using isotropic models.

  4. Tight fitting garter springs-MODAR

    Energy Technology Data Exchange (ETDEWEB)

    Kazimer, D. [Bruce Power, Tiverton, Ontario (Canada)

    2011-07-01

    Annulus spacers are used in CANDU reactors to maintain the annular gap between two tubes - an inner pressure tube (PT) and the outer calandria tube (CT). Typically four annulus spacers are used in one fuel channel assembly, each at a specified axial position. Bruce Unit 8 and many other CANDU units were constructed with tight-fitting garter springs (TFGS). The TFGS were not designed to be detected or relocated by the conventional tool, Spacer Location And Repositioning (SLAR) processes. Due to non-optimal 'As Left' construction locations for the Bruce Unit 8 TFGS, PT/CT contact has been predicted to occur well prior to its End of Life (EOL). Bruce Power entered a Project with AECL-CRL to design, manufacture and test and implement a new tooling system that would detect and reposition tight fitting annulus spacers. (author)

  5. Expression of Tight Junction Protein Claudin-1 in Human Crescentic Glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Ryo Koda

    2014-01-01

    Full Text Available The origin of crescent forming cells in human glomerulonephritis (GN remains unknown. Some animal studies demonstrated that parietal epithelial cells of Bowman’s capsule (PECs were the main component of proliferating cells and PEC-specific tight junction protein claudin-1 was expressed in crescentic lesions. We investigated the expression of claudin-1 in human GN. Immunohistochemistry for claudin-1 was performed on 17 kidney biopsy samples with crescent formation. Colocalization of claudin-1 with intracellular tight junction protein ZO-1 was also evaluated by immunofluorescence double staining. Claudin-1 is expressed mainly at the cell to cell contact site of proliferating cells in cellular crescentic lesions in patients with these forms of human GN. Small numbers of crescent forming cells showed extrajunctional localization of claudin-1. Colocalization of claudin-1 with ZO-1 was found at cell to cell contact sites of adjacent proliferating cells. In control samples, staining of claudin-1 was positive in PECs, but not in podocytes. Our findings suggest that claudin-1 contributes to crescent formation as a component of the tight junction protein complex that includes ZO-1. Co-localization of claudin-1 with ZO-1 implies the formation of functional tight junction complexes in crescentic lesions to prevent the interstitial damage caused by penetration of filtered molecules from Bowman’s space.

  6. Surface Passivation in Empirical Tight Binding

    OpenAIRE

    He, Yu; Tan, Yaohua; Jiang, Zhengping; Povolotskyi, Michael; Klimeck, Gerhard; Kubis, Tillmann

    2015-01-01

    Empirical Tight Binding (TB) methods are widely used in atomistic device simulations. Existing TB methods to passivate dangling bonds fall into two categories: 1) Method that explicitly includes passivation atoms is limited to passivation with atoms and small molecules only. 2) Method that implicitly incorporates passivation does not distinguish passivation atom types. This work introduces an implicit passivation method that is applicable to any passivation scenario with appropriate parameter...

  7. Equiangular tight frames and unistochastic matrices

    Czech Academy of Sciences Publication Activity Database

    Goyeneche, D.; Turek, Ondřej

    2017-01-01

    Roč. 50, č. 24 (2017), č. článku 245304. ISSN 1751-8113 R&D Projects: GA ČR GA17-01706S Institutional support: RVO:61389005 Keywords : equiangular tight frames * unistochastic matrices * SIC POVM Subject RIV: BE - Theoretical Physics OBOR OECD: Atomic, molecular and chemical physics (physics of atoms and molecules including collision, interaction with radiation, magnetic resonances, Mössbauer effect) Impact factor: 1.857, year: 2016

  8. Electron microscopic observation of 137Cs-irradiated rat testis. Production of basal laminae for germ cells, despite their absence

    International Nuclear Information System (INIS)

    Sawada, Hajime; Esaki, Michiyo

    2003-01-01

    Whole body γ-ray irradiation of rats with caesium-137 ( 137 Cs) at embryonic day 20 induced marked reduction of the weight of the testis. Body weight and other tissues, however, seemed to remain normal. By light microscopy, complete loss of germ cells was observed in the testis. Other components, such as Sertoli cells and interstitial cells, seemed to be normal. The testes from day 8 postpartum rats contained very few spermatogonia compared with newborn rats, indicating loss of germ cells between days 0 and 8. In the adult, 137 Cs-irradiated testes showed two conspicuous features other than the loss of germ cells: empty vacuolar spaces between Sertoli cells and multilayered seminiferous tubule basal laminae (lamina densa). The junctional structures (ectoplasmic specializations) between Sertoli cells, however, seemed normal. The thickness of each layer of multilayered basal laminae was the same as that of normal rats and electron-lucent layers similar to lamina lucida were interposed between them. Of the empty vacuolar spaces between Sertoli cells, basal laminae bridge the gap. The basal laminae contained laminin, type IV collagen and heparan sulphate proteoglycan evenly distributed among layers, suggesting a normal composition. Rough estimation of the amount of basal laminae deposited in 137 Cs-irradiated rats indicates that it is within a range similar to that in normal testis. These features imply that Sertoli cells are, in part, determined perinatally to produce basal laminae for germ-line cells. (author)

  9. Macroorchidism in FMR1 knockout mice is caused by increased Sertoli cell proliferation during testicular development

    NARCIS (Netherlands)

    K.E. Slegtenhorst-Eegdeman; D.G. de Rooij; M. Verhoef-Post (Miriam); H.J.G. van de Kant (Henk); C.E. Bakker (Cathy); B.A. Oostra (Ben); J.A. Grootegoed (Anton); A.P.N. Themmen (Axel)

    1998-01-01

    textabstractThe fragile X syndrome is the most frequent hereditary form of mental retardation. This X-linked disorder is, in most cases, caused by an unstable and expanding trinucleotide CGG repeat located in the 5'-untranslated region of the gene involved, the fragile

  10. Tight Reference Frame–Independent Quantum Teleportation

    Directory of Open Access Journals (Sweden)

    Dominic Verdon

    2017-01-01

    Full Text Available We give a tight scheme for teleporting a quantum state between two parties whose reference frames are misaligned by an action of a finite symmetry group. Unlike previously proposed schemes, ours requires no additional tokens or data to be passed between the participants; the same amount of classical information is transferred as for ordinary quantum teleportation, and the Hilbert space of the entangled resource is of the same size. In the terminology of Peres and Scudo, our protocol relies on classical communication of unspeakable information.

  11. Tightly sealed facility of excellent in durability

    International Nuclear Information System (INIS)

    Shirano, Kenji; Chatani, Michio; Ebe, Shinji; Shimizu, Masatoshi; Seguchi, Tadao; Fukushima, Susumu; Hirata, Masaru; Shiosawa, Ken-ichi.

    1992-01-01

    It is found that a cross linked methacryl resin using an appropriate amount of a cross linking monomer also has a useful characteristic of an excellent chemical resistance and excellent γ-ray resistance. Then in the present invention, a cross linked methacryl resin molding product comprising 60 to 98 % by weight of methyl methacrylate units and 2 to 40 % by weight of cross linking monomer units is used as a material for transparent partition walls. A tightly sealed facility having the transparent partition wall materials of excellent radiation resistance in addition to acid resistance can be attained. (T.M.)

  12. Germ cells are not required to establish the female pathway in mouse fetal gonads.

    Directory of Open Access Journals (Sweden)

    Danielle M Maatouk

    Full Text Available The fetal gonad is composed of a mixture of somatic cell lineages and germ cells. The fate of the gonad, male or female, is determined by a population of somatic cells that differentiate into Sertoli or granulosa cells and direct testis or ovary development. It is well established that germ cells are not required for the establishment or maintenance of Sertoli cells or testis cords in the male gonad. However, in the agametic ovary, follicles do not form suggesting that germ cells may influence granulosa cell development. Prior investigations of ovaries in which pre-meiotic germ cells were ablated during fetal life reported no histological changes during stages prior to birth. However, whether granulosa cells underwent normal molecular differentiation was not investigated. In cases where germ cell loss occurred secondary to other mutations, transdifferentiation of granulosa cells towards a Sertoli cell fate was observed, raising questions about whether germ cells play an active role in establishing or maintaining the fate of granulosa cells. We developed a group of molecular markers associated with ovarian development, and show here that the loss of pre-meiotic germ cells does not disrupt the somatic ovarian differentiation program during fetal life, or cause transdifferentiation as defined by expression of Sertoli markers. Since we do not find defects in the ovarian somatic program, the subsequent failure to form follicles at perinatal stages is likely attributable to the absence of germ cells rather than to defects in the somatic cells.

  13. Germ Cells Are Not Required to Establish the Female Pathway in Mouse Fetal Gonads

    Science.gov (United States)

    Maatouk, Danielle M.; Mork, Lindsey; Hinson, Ashley; Kobayashi, Akio; McMahon, Andrew P.; Capel, Blanche

    2012-01-01

    The fetal gonad is composed of a mixture of somatic cell lineages and germ cells. The fate of the gonad, male or female, is determined by a population of somatic cells that differentiate into Sertoli or granulosa cells and direct testis or ovary development. It is well established that germ cells are not required for the establishment or maintenance of Sertoli cells or testis cords in the male gonad. However, in the agametic ovary, follicles do not form suggesting that germ cells may influence granulosa cell development. Prior investigations of ovaries in which pre-meiotic germ cells were ablated during fetal life reported no histological changes during stages prior to birth. However, whether granulosa cells underwent normal molecular differentiation was not investigated. In cases where germ cell loss occurred secondary to other mutations, transdifferentiation of granulosa cells towards a Sertoli cell fate was observed, raising questions about whether germ cells play an active role in establishing or maintaining the fate of granulosa cells. We developed a group of molecular markers associated with ovarian development, and show here that the loss of pre-meiotic germ cells does not disrupt the somatic ovarian differentiation program during fetal life, or cause transdifferentiation as defined by expression of Sertoli markers. Since we do not find defects in the ovarian somatic program, the subsequent failure to form follicles at perinatal stages is likely attributable to the absence of germ cells rather than to defects in the somatic cells. PMID:23091613

  14. Exploiting the Gastric Epithelial Barrier: Helicobacter pylori's Attack on Tight and Adherens Junctions.

    Science.gov (United States)

    Backert, Steffen; Schmidt, Thomas P; Harrer, Aileen; Wessler, Silja

    2017-01-01

    Highly organized intercellular tight and adherens junctions are crucial structural components for establishing and maintenance of epithelial barrier functions, which control the microbiota and protect against intruding pathogens in humans. Alterations in these complexes represent key events in the development and progression of multiple infectious diseases as well as various cancers. The gastric pathogen Helicobacter pylori exerts an amazing set of strategies to manipulate these epithelial cell-to-cell junctions, which are implicated in changing cell polarity, migration and invasive growth as well as pro-inflammatory and proliferative responses. This chapter focuses on the H. pylori pathogenicity factors VacA, CagA, HtrA and urease, and how they can induce host cell signaling involved in altering cell-to-cell permeability. We propose a stepwise model for how H. pylori targets components of tight and adherens junctions in order to disrupt the gastric epithelial cell layer, giving fresh insights into the pathogenesis of this important bacterium.

  15. Ischemic preconditioning enhances integrity of coronary endothelial tight junctions

    Energy Technology Data Exchange (ETDEWEB)

    Li, Zhao [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States); Jin, Zhu-Qiu, E-mail: zhu-qiu.jin@sdstate.edu [Department of Pharmaceutical Sciences, College of Pharmacy, South Dakota State University, Brookings, SD 57007 (United States)

    2012-08-31

    Highlights: Black-Right-Pointing-Pointer Cardiac tight junctions are present between coronary endothelial cells. Black-Right-Pointing-Pointer Ischemic preconditioning preserves the structural and functional integrity of tight junctions. Black-Right-Pointing-Pointer Myocardial edema is prevented in hearts subjected to ischemic preconditioning. Black-Right-Pointing-Pointer Ischemic preconditioning enhances translocation of ZO-2 from cytosol to cytoskeleton. -- Abstract: Ischemic preconditioning (IPC) is one of the most effective procedures known to protect hearts against ischemia/reperfusion (IR) injury. Tight junction (TJ) barriers occur between coronary endothelial cells. TJs provide barrier function to maintain the homeostasis of the inner environment of tissues. However, the effect of IPC on the structure and function of cardiac TJs remains unknown. We tested the hypothesis that myocardial IR injury ruptures the structure of TJs and impairs endothelial permeability whereas IPC preserves the structural and functional integrity of TJs in the blood-heart barrier. Langendorff hearts from C57BL/6J mice were prepared and perfused with Krebs-Henseleit buffer. Cardiac function, creatine kinase release, and myocardial edema were measured. Cardiac TJ function was evaluated by measuring Evans blue-conjugated albumin (EBA) content in the extravascular compartment of hearts. Expression and translocation of zonula occludens (ZO)-2 in IR and IPC hearts were detected with Western blot. A subset of hearts was processed for the observation of ultra-structure of cardiac TJs with transmission electron microscopy. There were clear TJs between coronary endothelial cells of mouse hearts. IR caused the collapse of TJs whereas IPC sustained the structure of TJs. IR increased extravascular EBA content in the heart and myocardial edema but decreased the expression of ZO-2 in the cytoskeleton. IPC maintained the structure of TJs. Cardiac EBA content and edema were reduced in IPC hearts. IPC

  16. Modulation of Tight Junction Structure and Function by Kinases and Phosphatases Targeting Occludin

    Directory of Open Access Journals (Sweden)

    Max Johannes Dörfel

    2012-01-01

    Full Text Available Tight junctions (TJs typically represent the most apical contacts in epithelial and endothelial cell layers where they play an essential role in the separation of extracellular or luminal spaces from underlying tissues in the body. Depending on the protein composition, TJs define the barrier characteristics and in addition maintain cell polarity. Two major families of integral membrane proteins form the typical TJ strand network, the tight junction-associated MARVEL protein (TAMP family members occludin, tricellulin, and MarvelD3 as well as a specific set of claudins. Occludin was the first identified member of these tetraspanins and is now widely accepted as a regulator of TJ assembly and function. Therefore, occludin itself has to be tightly regulated. Phosphorylation of occludin appears to be of central importance in this context. Here we want to summarize current knowledge on the kinases and phosphatases directly modifying occludin, and their role in the regulation of TJ structure, function, and dynamics.

  17. Equiangular tight frames and unistochastic matrices

    International Nuclear Information System (INIS)

    Goyeneche, Dardo; Turek, Ondřej

    2017-01-01

    We demonstrate that a complex equiangular tight frame composed of N vectors in dimension d , denoted ETF ( d , N ), exists if and only if a certain bistochastic matrix, univocally determined by N and d , belongs to a special class of unistochastic matrices. This connection allows us to find new complex ETFs in infinitely many dimensions and to derive a method to introduce non-trivial free parameters in ETFs. We present an explicit six-parametric family of complex ETF(6,16), which defines a family of symmetric POVMs. Minimal and maximal possible average entanglement of the vectors within this qubit–qutrit family are described. Furthermore, we propose an efficient numerical procedure to compute the unitary matrix underlying a unistochastic matrix, which we apply to find all existing classes of complex ETFs containing up to 20 vectors. (paper)

  18. Evaluation of tight-pitch PWR cores

    International Nuclear Information System (INIS)

    Correa, F.; Driscoll, M.J.; Lanning, D.D.

    1979-08-01

    The impact of tight pinch cores on the consumption of natural uranium ore has been evaluated for two systems of coupled PWR's namely one particular type of thorium system - 235 U/UO 2 : Pu/ThO 2 : 233 U/ThO 2 - and the conventional recycle-mode uranium system - 235 U/UO 2 : Pu/UO 2 . The basic parameter varied was the fuel-to-moderator volume ratio (F/M) of the (uniform) lattice for the last core in each sequence. Although methods and data verification in the range of present interest, 0.5 (current lattices) 1.0, the EPRI-LEOPARD and LASER programs used for the thorium and uranium calculations, respectively, were successfully benchmarked against several of the more pertinent experiments

  19. Surface Passivation in Empirical Tight Binding

    Science.gov (United States)

    He, Yu; Tan, Yaohua; Jiang, Zhengping; Povolotskyi, Michael; Klimeck, Gerhard; Kubis, Tillmann

    2016-03-01

    Empirical Tight Binding (TB) methods are widely used in atomistic device simulations. Existing TB methods to passivate dangling bonds fall into two categories: 1) Method that explicitly includes passivation atoms is limited to passivation with atoms and small molecules only. 2) Method that implicitly incorporates passivation does not distinguish passivation atom types. This work introduces an implicit passivation method that is applicable to any passivation scenario with appropriate parameters. This method is applied to a Si quantum well and a Si ultra-thin body transistor oxidized with SiO2 in several oxidation configurations. Comparison with ab-initio results and experiments verifies the presented method. Oxidation configurations that severely hamper the transistor performance are identified. It is also shown that the commonly used implicit H atom passivation overestimates the transistor performance.

  20. Naturally fractured tight gas reservoir detection optimization

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-06-01

    Building upon the partitioning of the Greater Green River Basin (GGRB) that was conducted last quarter, the goal of the work this quarter has been to conclude evaluation of the Stratos well and the prototypical Green River Deep partition, and perform the fill resource evaluation of the Upper Cretaceous tight gas play, with the goal of defining target areas of enhanced natural fracturing. The work plan for the quarter of November 1-December 31, 1998 comprised four tasks: (1) Evaluation of the Green River Deep partition and the Stratos well and examination of potential opportunity for expanding the use of E and P technology to low permeability, naturally fractured gas reservoirs, (2) Gas field studies, and (3) Resource analysis of the balance of the partitions.

  1. Random walks and polygons in tight confinement

    International Nuclear Information System (INIS)

    Diao, Y; Ernst, C; Ziegler, U

    2014-01-01

    We discuss the effect of confinement on the topology and geometry of tightly confined random walks and polygons. Here the walks and polygons are confined in a sphere of radius R ≥ 1/2 and the polygons are equilateral with n edges of unit length. We illustrate numerically that for a fixed length of random polygons the knotting probability increases to one as the radius decreases to 1/2. We also demonstrate that for random polygons (walks) the curvature increases to πn (π(n – 1)) as the radius approaches 1/2 and that the torsion decreases to ≈ πn/3 (≈ π(n – 1)/3). In addition we show the effect of length and confinement on the average crossing number of a random polygon

  2. Tight gas sand tax credit yields opportunities

    International Nuclear Information System (INIS)

    Lewis, F.W.; Osburn, A.S.

    1991-01-01

    The U.S. Internal Revenue Service on Apr. 1, 1991, released the inflation adjustments used in the calculations of Non-Conventional Fuel Tax Credits for 1990. The inflation adjustment, 1.6730, when applied to the base price of $3/bbl of oil equivalent, adjusts the tax credit to $5.019/bbl for oil and 86.53 cents/MMBTU for gas. The conversion factor for equivalent fuels is 5.8 MMBTU/bbl. Unfortunately, the tax credit for tight formation gas continues to be unadjusted for inflation and remains 52 cents/MMBTU. As many producers are aware, the Omnibus Budget Reconciliation Act of 1990 expanded the dates of eligibility and the usage for-Non-Conventional Fuel Tax Credits. Among other provisions, eligible wells may be placed in service until Jan. 1, 1992, and once in place may utilize the credit for production through Dec. 31, 2002. Both dates are 2 year extensions from previous regulations

  3. Trends in drug delivery through tissue barriers containing tight junctions.

    Science.gov (United States)

    Tscheik, Christian; Blasig, Ingolf E; Winkler, Lars

    2013-04-01

    A limitation in the uptake of many drugs is the restricted permeation through tissue barriers. There are two general ways to cross barriers formed by cell layers: by transcytosis or by diffusion through the intercellular space. In the latter, tight junctions (TJs) play the decisive role in the regulation of the barrier permeability. Thus, transient modulation of TJs is a potent strategy to improve drug delivery. There have been extensive studies on surfactant-like absorption enhancers. One of the most effective enhancers found is sodium caprate. However, this modulates TJs in an unspecific fashion. A novel approach would be the specific modulation of TJ-associated marvel proteins and claudins, which are the main structural components of the TJs. Recent studies have identified synthetic peptidomimetics and RNA interference techniques to downregulate the expression of targeted TJ proteins. This review summarizes current progress and discusses the impact on TJs' barrier function.

  4. Identification of MarvelD3 as a tight junction-associated transmembrane protein of the occludin family

    Directory of Open Access Journals (Sweden)

    Balda Maria S

    2009-12-01

    Full Text Available Abstract Background Tight junctions are an intercellular adhesion complex of epithelial and endothelial cells, and form a paracellular barrier that restricts the diffusion of solutes on the basis of size and charge. Tight junctions are formed by multiprotein complexes containing cytosolic and transmembrane proteins. How these components work together to form functional tight junctions is still not well understood and will require a complete understanding of the molecular composition of the junction. Results Here we identify a new transmembrane component of tight junctions: MarvelD3, a four-span transmembrane protein. Its predicted transmembrane helices form a Marvel (MAL and related proteins for vesicle traffic and membrane link domain, a structural motif originally discovered in proteins involved in membrane apposition and fusion events, such as the tight junction proteins occludin and tricellulin. In mammals, MarvelD3 is expressed as two alternatively spliced isoforms. Both isoforms exhibit a broad tissue distribution and are expressed by different types of epithelial as well as endothelial cells. MarvelD3 co-localises with occludin at tight junctions in intestinal and corneal epithelial cells. RNA interference experiments in Caco-2 cells indicate that normal MarvelD3 expression is not required for the formation of functional tight junctions but depletion results in monolayers with increased transepithelial electrical resistance. Conclusions Our data indicate that MarvelD3 is a third member of the tight junction-associated occludin family of transmembrane proteins. Similar to occludin, normal expression of MarvelD3 is not essential for the formation of functional tight junctions. However, MarvelD3 functions as a determinant of epithelial paracellular permeability properties.

  5. MANAGING TIGHT BINDING RECEPTORS FOR NEW SPEARATIONS TECHNOLOGIES

    Energy Technology Data Exchange (ETDEWEB)

    DARYLE H BUSCH RICHARD S GIVENS

    2004-12-10

    even more interesting. They convert from rings to structures that wrap around a metal ion to form a cage. These ligands are called cryptands. Switch release is accomplished by photolytic cleavage of a bond to convert a cyclic ligand into a linear ligand or to break similar bonds in a cryptate. Our studies have demonstrated switch binding and switch release with cryptates of calcium. These remarkable cyclic ligands and cage-like ligands are indeed tight-binding and may, in principle, be incorporated in various separations methodologies, including the soil poultice. The soil poultice mimics the way in which microbes secrete extremely powerful ligands into the soil in order to harvest iron. The cellular membrane of the microbe recognizes the iron/ligand complex and admits it into the cell. The soil poultice uses molecularly imprinted polymers (MIPs) to play the role of the cellular membrane. Imprinting involves creation of the polymer in the presence of the metal/ligand complex. In principle, a well design ligand/MIP combination can be highly selective toward almost any targeted metal ion. The principles for that design are the focus of these investigations. An imprinting molecule can interact with the polymer through any, some, or all of the so-called supramolecular modes; e.g., hydrogen bonding, electrostatic charge, minor ligand bonding, Pi-Pi stacking, and hydrophobic and van der Waals interactions. Historically these modes of binding have given MIPs only small re-binding capacities and very limited selectivities. This program has shown that each mode of interaction can be made more powerful than previously suspected and that combinations of different supramolecular interaction modes can produce remarkable synergisms. The results of this systematic study provide a firm foundation for tailoring molecular imprinted polymers for reclamation of specific metal ion, including those important to the DOE EM mission.

  6. Protecting intestinal epithelial integrity by galacto-oligosaccharides: Keeping it tight

    NARCIS (Netherlands)

    Akbari, P.

    2016-01-01

    The intestinal barrier serves as a first line of host defense against potentially harmful stressors from the environment ingested with food, and is primarily formed by epithelial cells connected by tight junctions. Oligosaccharides have been identified as components in milk, particularly in

  7. Intracellular pH is a tightly controlled signal in yeast

    NARCIS (Netherlands)

    Orij, R.; Brul, S.; Smits, G.J.

    2011-01-01

    Background: Nearly all processes in living cells are pH dependent, which is why intracellular pH (pHi) is a tightly regulated physiological parameter in all cellular systems. However, in microbes such as yeast, pHi responds to extracellular conditions such as the availability of nutrients. This

  8. Global Coal Trade. From Tightness to Oversupply

    International Nuclear Information System (INIS)

    Cornot-Gandolphe, Sylvie

    2013-01-01

    Over the past four years, international coal trade has been reshaped by China's surging imports. China, which was still a net exporter in 2008, became the world's first coal importer in 2011, taking over the position that Japan has occupied for three decades. Its imports have continued their rising trend and reached a record level in 2012, despite the country's economic slowdown. China imported 289 million tons of coal in 2012, up 30% over 2011. It now accounts for 23% of global imports. Although China is the world's largest coal producer, several factors have contributed to the sudden rise in its imports, including the higher cost of domestic coal relative to international prices and bottlenecks in transporting domestic coal to south-eastern provinces. More recently, another event shook the international coal business: the United States have been back on the market. The collapse of U.S. gas prices, to $4/million Btu in 2011 and even $2.75/million Btu in 2012, linked with the 'shale gas revolution', has made coal uncompetitive in the electricity sector, its main outlet on the U.S. market. U.S. coal demand dropped 4% in 2011 and 11% in 2012. The reduction in domestic demand has forced U.S. miners to look for overseas outlets. Their exports surged by 31% in 2011 and 16% in 2012. They reached 112 million tons in 2012, more than twice the level of 2009. The United States, which almost disappeared from the international steam coal market in the 2000's, have regained a larger share of the total coal export market, 9% in 2012, against 6% in 2009. These developments, although not directly linked, have a huge impact on the global market and pricing of coal. Chinese imports have helped the market to quickly recover from its low level of 2008-2009. The speed and magnitude of China's coal imports even shifts the market from a sluggish to a tight situation. Prices started to rise after their collapse in the second half of 2008 caused by the economic and financial crisis

  9. Bifurcation and stability of forced convection in tightly coiled ducts: multiplicity

    International Nuclear Information System (INIS)

    Wang Liqiu; Pang, Ophelia; Cheng Lin

    2005-01-01

    A numerical study is made on the fully developed bifurcation structure of the forced convection in tightly coiled ducts of square cross-section. In addition to the examination of structural changes of three known solution branches found in loosely coiled ducts, three new solution branches are found. These new branches are isolated from the three known branches. The flows on these new branches are in a symmetric 4-cell state, a symmetric 8-cell state, an asymmetric 2-cell state, an asymmetric 5-cell state, an asymmetric 7-cell state, or an asymmetric 8-cell structure

  10. Tightness Entropic Uncertainty Relation in Quantum Markovian-Davies Environment

    Science.gov (United States)

    Zhang, Jun; Liu, Liang; Han, Yan

    2018-05-01

    In this paper, we investigate the tightness of entropic uncertainty relation in the absence (presence) of the quantum memory which the memory particle being weakly coupled to a decohering Davies-type Markovian environment. The results show that the tightness of the quantum uncertainty relation can be controlled by the energy relaxation time F, the dephasing time G and the rescaled temperature p, the perfect tightness can be arrived by dephasing and energy relaxation satisfying F = 2G and p = 1/2. In addition, the tightness of the memory-assisted entropic uncertainty relation and the entropic uncertainty relation can be influenced mainly by the purity. While in memory-assisted model, the purity and quantum correlation can also influence the tightness actively while the quantum entanglement can influence the tightness slightly.

  11. Improved Density Functional Tight Binding Potentials for Metalloid Aluminum Clusters

    Science.gov (United States)

    2016-06-01

    unlimited IMPROVED DENSITY-FUNCTIONAL TIGHT BINDING POTENTIALS FOR METALLOID ALUMINUM CLUSTERS by Joon H. Kim June 2016 Thesis Advisor...DATES COVERED Master’s thesis 4. TITLE AND SUBTITLE IMPROVED DENSITY-FUNCTIONAL TIGHT BINDING POTENTIALS FOR METALLOID ALUMINUM CLUSTERS 5. FUNDING...repulsive potentials for use in density-functional tight binding (DFTB) simulations of low-valence aluminum metalloid clusters . These systems are under

  12. Naturally fractured tight gas reservoir detection optimization

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1999-04-30

    In March, work continued on characterizing probabilities for determining natural fracturing associated with the GGRB for the Upper Cretaceous tight gas plays. Structural complexity, based on potential field data and remote sensing data was completed. A resource estimate for the Frontier and Mesa Verde play was also completed. Further, work was also conducted to determine threshold economics for the play based on limited current production in the plays in the Wamsutter Ridge area. These analyses culminated in a presentation at FETC on 24 March 1999 where quantified natural fracture domains, mapped on a partition basis, which establish ''sweet spot'' probability for natural fracturing, were reviewed. That presentation is reproduced here as Appendix 1. The work plan for the quarter of January 1, 1999--March 31, 1999 comprised five tasks: (1) Evaluation of the GGRB partitions for structural complexity that can be associated with natural fractures, (2) Continued resource analysis of the balance of the partitions to determine areas with higher relative gas richness, (3) Gas field studies, (4) Threshold resource economics to determine which partitions would be the most prospective, and (5) Examination of the area around the Table Rock 4H well.

  13. House Dust Mite Der p 1 Effects on Sinonasal Epithelial Tight Junctions

    Science.gov (United States)

    Henriquez, Oswaldo A.; Beste, Kyle Den; Hoddeson, Elizabeth K.; Parkos, Charles A.; Nusrat, Asma; Wise, Sarah K.

    2013-01-01

    Background Epithelial permeability is highly dependent upon the integrity of tight junctions, cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer. Methods Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen versus control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of tight junction proteins was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total. Results Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1 exposed cultured sinonasal cells versus controls. Conclusion Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis. PMID:23592402

  14. Digital Rock Studies of Tight Porous Media

    Energy Technology Data Exchange (ETDEWEB)

    Silin, Dmitriy [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2012-08-07

    This technical report summarizes some recently developed approaches to studies of rock properties at a pore scale. Digital rock approach is complementary to laboratory and field studies. It can be especially helpful in situations where experimental data are uncertain, or are difficult or impossible to obtain. Digitized binary images of the pore geometries of natural rocks obtained by different imaging techniques are the input data. Computer-generated models of natural rocks can be used instead of images in a case where microtomography data are unavailable, or the resolution of the tools is insufficient to adequately characterize the features of interest. Simulations of creeping viscous flow in pores produce estimates of Darcy permeability. Maximal Inscribed Spheres calculations estimate two-phase fluid distribution in capillary equilibrium. A combination of both produce relative permeability curves. Computer-generated rock models were employed to study two-phase properties of fractured rocks, or tight sands with slit-like pores, too narrow to be characterized with micro-tomography. Various scenarios can simulate different fluid displacement mechanisms, from piston-like drainage to liquid dropout at the dew point. A finite differences discretization of Stokes equation is developed to simulate flow in the pore space of natural rocks. The numerical schemes are capable to handle both no-slip and slippage flows. An upscaling procedure estimates the permeability by subsampling a large data set. Capillary equilibrium and capillary pressure curves are efficiently estimated with the method of maximal inscribed spheres both an arbitrary contact angle. The algorithms can handle gigobytes of data on a desktop workstation. Customized QuickHull algorithms model natural rocks. Capillary pressure curves evaluated from computer-generated images mimic those obtained for microtomography data.

  15. US production of natural gas from tight reservoirs

    International Nuclear Information System (INIS)

    1993-01-01

    For the purposes of this report, tight gas reservoirs are defined as those that meet the Federal Energy Regulatory Commission's (FERC) definition of tight. They are generally characterized by an average reservoir rock permeability to gas of 0.1 millidarcy or less and, absent artificial stimulation of production, by production rates that do not exceed 5 barrels of oil per day and certain specified daily volumes of gas which increase with the depth of the reservoir. All of the statistics presented in this report pertain to wells that have been classified, from 1978 through 1991, as tight according to the FERC; i.e., they are ''legally tight'' reservoirs. Additional production from ''geologically tight'' reservoirs that have not been classified tight according to the FERC rules has been excluded. This category includes all producing wells drilled into legally designated tight gas reservoirs prior to 1978 and all producing wells drilled into physically tight gas reservoirs that have not been designated legally tight. Therefore, all gas production referenced herein is eligible for the Section 29 tax credit. Although the qualification period for the credit expired at the end of 1992, wells that were spudded (began to be drilled) between 1978 and May 1988, and from November 5, 1990, through year end 1992, are eligible for the tax credit for a subsequent period of 10 years. This report updates the EIA's tight gas production information through 1991 and considers further the history and effect on tight gas production of the Federal Government's regulatory and tax policy actions. It also provides some high points of the geologic background needed to understand the nature and location of low-permeability reservoirs

  16. Air tightness measurements in older Danish single-family houses

    DEFF Research Database (Denmark)

    Mortensen, Lone Hedegaard; Bergsøe, Niels Christian

    2017-01-01

    of the building envelope of older buildings despite the fact that the air tightness has a major influence on the energy use. In connection with renovation of the Danish building stock, the coming years will see increased focus on the air tightness of the building envelope like in other countries. This paper...

  17. Differences between tight and loose cultures : A 33-nation study

    NARCIS (Netherlands)

    Gelfand, M.J.; Raver, R.L.; Nishii, L.; Leslie, L.M.; Lun, J.; Lim, B.C.; Van de Vliert, E.

    2011-01-01

    With data from 33 nations, we illustrate the differences between cultures that are tight (have many strong norms and a low tolerance of deviant behavior) versus loose (have weak social norms and a high tolerance of deviant behavior). Tightness-looseness is part of a complex, loosely integrated

  18. Dielectric response of molecules in empirical tight-binding theory

    Science.gov (United States)

    Boykin, Timothy B.; Vogl, P.

    2002-01-01

    In this paper we generalize our previous approach to electromagnetic interactions within empirical tight-binding theory to encompass molecular solids and isolated molecules. In order to guarantee physically meaningful results, we rederive the expressions for relevant observables using commutation relations appropriate to the finite tight-binding Hilbert space. In carrying out this generalization, we examine in detail the consequences of various prescriptions for the position and momentum operators in tight binding. We show that attempting to fit parameters of the momentum matrix directly generally results in a momentum operator which is incompatible with the underlying tight-binding model, while adding extra position parameters results in numerous difficulties, including the loss of gauge invariance. We have applied our scheme, which we term the Peierls-coupling tight-binding method, to the optical dielectric function of the molecular solid PPP, showing that this approach successfully predicts its known optical properties even in the limit of isolated molecules.

  19. The proliferative activity of testicular cell types and the effect of postnatal X-irradiation in the developing mouse testis

    International Nuclear Information System (INIS)

    Vergouwen, R.P.F.A.; Huiskamp, R.; Davids, J.A.G.; Rooij, D.G. de

    1991-01-01

    The authors describe the effects of x-irradiation on the developing mouse testis, particularly in relation to A spermatogonia, Sertoli cells, Leydig cells and mesenchymal cells commonly regarded as Leydig precursors. It was concluded that radiosensitivity is highest during the first week after birth and decreases thereafter, with the exception of A spermatogonia which are radiosensitive at all ages. (UK)

  20. Two-Finger Tightness: What Is It? Measuring Torque and Reproducibility in a Simulated Model.

    Science.gov (United States)

    Acker, William B; Tai, Bruce L; Belmont, Barry; Shih, Albert J; Irwin, Todd A; Holmes, James R

    2016-05-01

    Residents in training are often directed to insert screws using "two-finger tightness" to impart adequate torque but minimize the chance of a screw stripping in bone. This study seeks to quantify and describe two-finger tightness and to assess the variability of its application by residents in training. Cortical bone was simulated using a polyurethane foam block (30-pcf density) that was prepared with predrilled holes for tightening 3.5 × 14-mm long cortical screws and mounted to a custom-built apparatus on a load cell to capture torque data. Thirty-three residents in training, ranging from the first through fifth years of residency, along with 8 staff members, were directed to tighten 6 screws to two-finger tightness in the test block, and peak torque values were recorded. The participants were blinded to their torque values. Stripping torque (2.73 ± 0.56 N·m) was determined from 36 trials and served as a threshold for failed screw placement. The average torques varied substantially with regard to absolute torque values, thus poorly defining two-finger tightness. Junior residents less consistently reproduced torque compared with other groups (0.29 and 0.32, respectively). These data quantify absolute values of two-finger tightness but demonstrate considerable variability in absolute torque values, percentage of stripping torque, and ability to consistently reproduce given torque levels. Increased years in training are weakly correlated with reproducibility, but experience does not seem to affect absolute torque levels. These results question the usefulness of two-finger tightness as a teaching tool and highlight the need for improvement in resident motor skill training and development within a teaching curriculum. Torque measuring devices may be a useful simulation tools for this purpose.

  1. Differentiation of Bovine Spermatogonial Stem Cells into Osteoblasts

    OpenAIRE

    Qasemi-Panahi, Babak; Tajik, Parviz; Movahedin, Mansoureh; Moghaddam, Gholamali; Barzgar, Younes; Heidari-Vala, Hamed

    2011-01-01

    Spermatogonial Stem Cell (SSC) technologies provide multiple opportunities for research in the field of biotechnology and regenerative medicine. The therapeutic use of Embryonic Stem Cells (ESCs) is restricted due to severe ethical and immunological concerns. Therefore, we need a new pluripotent cell type. Despite well-known role of germ cells in the gametogenesis, some facts apparently show their multipotentiality. In the present study, bovine SSCs were co-cultured with Sertoli cell for 7 da...

  2. Three-dimensional measurement of a tightly focused laser beam

    Directory of Open Access Journals (Sweden)

    Xiangsheng Xie

    2013-02-01

    Full Text Available The spatial structure of a tightly focused light field is measured with a double knife-edge scanning method. The measurement method is based on the use of a high-quality double knife-edge fabricated from a right-angled silicon fragment mounted on a photodetector. The reconstruction of the three-dimensional structures of tightly focused spots is carried out with both uniform and partially obstructed linearly polarized incident light beams. The optical field distribution is found to deviate substantially from the input beam profile in the tightly focused region, which is in good agreement with the results of numerical simulations.

  3. Claudin-21 Has a Paracellular Channel Role at Tight Junctions

    KAUST Repository

    Tanaka, Hiroo; Yamamoto, Yasuko; Kashihara, Hiroka; Yamazaki, Yuji; Tani, Kazutoshi; Fujiyoshi, Yoshinori; Mineta, Katsuhiko; Takeuchi, Kosei; Tamura, Atsushi; Tsukita, Sachiko

    2016-01-01

    Claudin protein family members, of which there are at least 27 in humans and mice, polymerize to form tight junctions (TJs) between epithelial cells, in a tissue- and developmental stage-specific manner. Claudins have a paracellular barrier function. In addition, certain claudins function as paracellular channels for small ions and/or solutes by forming selective pores at the TJs, although the specific claudins involved and their functional mechanisms are still in question. Here we show for the first time that claudin-21, which is more highly expressed in the embryonic than the postnatal stages, acts as a paracellular channel for small cations, such as Na+, similar to the typical channel-type claudins claudin-2 and -15. Claudin-21 also allows the paracellular passage of larger solutes. Our findings suggest that claudin-21-based TJs allow the passage of small and larger solutes by both paracellular channel-based and some additional mechanisms. © 2016, American Society for Microbiology. All Rights Reserved.

  4. Claudin-21 Has a Paracellular Channel Role at Tight Junctions

    KAUST Repository

    Tanaka, Hiroo

    2016-01-05

    Claudin protein family members, of which there are at least 27 in humans and mice, polymerize to form tight junctions (TJs) between epithelial cells, in a tissue- and developmental stage-specific manner. Claudins have a paracellular barrier function. In addition, certain claudins function as paracellular channels for small ions and/or solutes by forming selective pores at the TJs, although the specific claudins involved and their functional mechanisms are still in question. Here we show for the first time that claudin-21, which is more highly expressed in the embryonic than the postnatal stages, acts as a paracellular channel for small cations, such as Na+, similar to the typical channel-type claudins claudin-2 and -15. Claudin-21 also allows the paracellular passage of larger solutes. Our findings suggest that claudin-21-based TJs allow the passage of small and larger solutes by both paracellular channel-based and some additional mechanisms. © 2016, American Society for Microbiology. All Rights Reserved.

  5. On tight multiparty Bell inequalities for many settings

    OpenAIRE

    Zukowski, Marek

    2006-01-01

    A derivation method is given which leads to a series of tight Bell inequalities for experiments involving N parties, with binary observables, and three possible local settings. The approach can be generalized to more settings. Ramifications are presented.

  6. Protecting intestinal epithelial integrity by galacto-oligosaccharides: Keeping it tight

    OpenAIRE

    Akbari, P.

    2016-01-01

    The intestinal barrier serves as a first line of host defense against potentially harmful stressors from the environment ingested with food, and is primarily formed by epithelial cells connected by tight junctions. Oligosaccharides have been identified as components in milk, particularly in colostrum, that support the development of intestinal microbiota in the early phase of life and contribute to the maturation of the immune system in infants. Currently, galacto-oligosaccharides (GOS) are u...

  7. Elucidating the principles of the molecular organization of heteropolymeric tight junction strands

    OpenAIRE

    Piontek, Jörg; Fritzsche, Susanne; Cording, Jimmi; Richter, Sandra; Hartwig, Jens; Walter, Maria; Yu, Dan; Turner, Jerrold R.; Gehring, Claudia; Rahn, Hans-Peter; Wolburg, Hartwig; Blasig, Ingolf E.

    2011-01-01

    Paracellular barrier properties of tissues are mainly determined by the composition of claudin hetero-polymers. To analyze the molecular organization of tight junctions (TJ), we investigated the ability of claudins (Cld) to form homo- and heteromers. Cld1, -2, -3, -5, and -12 expressed in cerebral barriers were investigated. TJ-strands were reconstituted by claudin-transfection of HEK293-cells. cis-Interactions and/or spatial proximity were analyzed by fluorescence resonance energy transfer i...

  8. Western tight gas sands advanced logging workshop proceedings

    Energy Technology Data Exchange (ETDEWEB)

    Jennings, J B; Carroll, Jr, H B [eds.

    1982-04-01

    An advanced logging research program is one major aspect of the Western Tight Sands Program. Purpose of this workshop is to help BETC define critical logging needs for tight gas sands and to allow free interchange of ideas on all aspects of the current logging research program. Sixteen papers and abstracts are included together with discussions. Separate abstracts have been prepared for the 12 papers. (DLC)

  9. Hamstring tightness and Scheuermann's disease a pilot study.

    Science.gov (United States)

    Fisk, J W; Baigent, M L

    1981-06-01

    The lateral radiographs of the dorsal spines of 20 patients presenting with mainly low back pain are studied. These patients had clinically evident loss of flexion in the low dorsal spine and very tight hamstring muscles. 85% of them showed definite evidence of previous Scheuermann's Disease. The possibility that tight hamstrings may be an important factor in the aetiology of this disease is discussed, and a further large scale study is proposed.

  10. Contraption and Prediction of Exhalation Tight Brownstone in Exhalation Cistern

    OpenAIRE

    XhingZhiwang, -; Xuchao, -

    2012-01-01

    The reservoir connate water saturation is high and gas wells generally produce water which seriously affects the productivity of gas wells in Xujiahe tight sandstone gas reservoirs in Sichuan Basin. Take the sixth formation for example, there are 39 wells producing water unequally in the 42 commissioning wells, and the excessive water production leads to the production of the gas well declining rapidly. Studying of the mechanism of water production in tight sandstone gas reservoirs and predic...

  11. A tightly coupled scheme for neutronics and thermal–hydraulics using open-source software

    International Nuclear Information System (INIS)

    Wu, Hsingtzu; Rizwan-uddin

    2016-01-01

    Highlights: • A novel tight coupling scheme called “the Integrated Tight Coupling (ITC) method” is proposed. • The ITC method is implemented using DRAGON and OpenFOAM. • The ITC method is verified using a 1.5-D example. - Abstract: Coupling neutronic and thermal–hydraulic analyses of a nuclear reactor core is important because it helps identify the most relevant safety issues without conservative assumptions. Currently coupled computations solve the same governing equations using different coupling methods, which can be sorted into two categories: loose coupling and tight coupling. This paper proposes and verifies a third coupling approach called “the Integrated Tight Coupling (ITC) method”. The mathematical equations in the nuclear fuel are rearranged to be integrated via a novel concept of the energy-group function. In addition, the data from the neutron cross section library can be used directly. The ITC method is implemented using two open-source codes: the DRAGON code and OpenFOAM. Additionally, a coupled computation using these two codes is new and has not been done. The ITC method is verified using a 1.5-D (1-D neutronics and 2-D thermal–hydraulics) symmetric unit cell example. The mesh of the tightly integrated computation is 25% coarser than the loosely coupled one. Starting from a similar initial guess, the number of iterations for the ITC method is 24% fewer than that for the loosely coupled computation to reach the same accuracy. In addition, the ITC method is tested with different initial guesses. For all cases tested, the scheme converged to the same solution. With further improvement and additional testing, the ITC method has the potential to be incorporated with other neutronics and thermal–hydraulics codes.

  12. Relaxin affects cell organization and early and late stages of spermatogenesis in a coculture of rat testicular cells.

    Science.gov (United States)

    Pimenta, M T; Francisco, R A R; Silva, R P; Porto, C S; Lazari, M F M

    2015-07-01

    Relaxin and its receptor RXFP1 are co-expressed in Sertoli cells, and relaxin can stimulate proliferation of Sertoli cells. In this study, we investigated a role of relaxin in spermatogenesis, using a short-term culture of testicular cells of the rat that allowed differentiation of spermatogonia to spermatids. Sertoli, germ, and peritubular myoid cells were the predominant cell types in the culture. Sertoli and germ cells expressed RXFP1. Cultures were incubated without (control) or with 0.5% fetal bovine serum (FBS) or 100 ng/mL H2 relaxin (RLN) for 2 days. Cell organization, number, and differentiation were analyzed after 2 (D2), 5 (D5) or 8 (D8) days of culturing. Although the proportion of germ cells decayed from D2 to D5, the relative contribution of HC, 1C, 2C, and 4C germ cell populations remained constant in the control group during the whole culture. RLN did not affect the proportion of germ cell populations compared with control, but increased gene and/or protein expression of the undifferentiated and differentiated spermatogonia markers PLZF and c-KIT, and of the post-meiotic marker Odf2 in D5. RLN favored organization of cells in tubule-like structures, the arrangement of myoid cells around the tubules, arrangement of c-KIT-positive spermatogonia at the basal region of the tubules, and expression of the cell junction protein β-catenin close to the plasma membrane region. Knockdown of relaxin with small interfering RNA (siRNA) reduced expression of β-catenin at the cell junctions, and shifted its expression to the nucleus. We propose that relaxin may affect spermatogenesis by modulating spermatogonial self renewal and favoring cell contact. © 2015 American Society of Andrology and European Academy of Andrology.

  13. House dust mite allergen Der p 1 effects on sinonasal epithelial tight junctions.

    Science.gov (United States)

    Henriquez, Oswaldo A; Den Beste, Kyle; Hoddeson, Elizabeth K; Parkos, Charles A; Nusrat, Asma; Wise, Sarah K

    2013-08-01

    Epithelial permeability is highly dependent upon the integrity of tight junctions, which are cell-cell adhesion complexes located at the apical aspect of the lateral membrane of polarized epithelial cells. We hypothesize that sinonasal epithelial exposure to Der p 1 house dust mite antigen decreases expression of tight junction proteins (TJPs), representing a potential mechanism for increased permeability and presentation of antigens across the sinonasal epithelial layer. Confluent cultured primary human sinonasal epithelial cells were exposed to recombinant Der p 1 antigen vs control, and transepithelial resistance measurements were performed over 24 hours. Antibody staining for a panel of TJPs was examined with immunofluorescence/confocal microscopy and Western blotting. Tissue for these experiments was obtained from 4 patients total. Der p 1 exposed sinonasal cells showed a marked decrease in transepithelial resistance when compared to control cells. In addition, results of Western immunoblot and immunofluorescent labeling demonstrated decreased expression of TJPs claudin-1 and junction adhesion molecule-A (JAM-A) in Der p 1-exposed cultured sinonasal cells vs controls. Der p 1 antigen exposure decreases sinonasal epithelium TJP expression, most notably seen in JAM-A and claudin-1 in these preliminary experiments. This decreased TJP expression likely contributes to increased epithelial permeability and represents a potential mechanism for transepithelial antigen exposure in allergic rhinitis. © 2013 ARS-AAOA, LLC.

  14. Petri Net-Based Model of Helicobacter pylori Mediated Disruption of Tight Junction Proteins in Stomach Lining during Gastric Carcinoma

    Directory of Open Access Journals (Sweden)

    Anam Naz

    2017-09-01

    Full Text Available Tight junctions help prevent the passage of digestive enzymes and microorganisms through the space between adjacent epithelial cells lining. However, Helicobacter pylori encoded virulence factors negatively regulate these tight junctions and contribute to dysfunction of gastric mucosa. Here, we have predicted the regulation of important tight junction proteins, such as Zonula occludens-1, Claudin-2 and Connexin32 in the presence of pathogenic proteins. Molecular events such as post translational modifications and crosstalk between phosphorylation, O-glycosylation, palmitoylation and methylation are explored which may compromise the integrity of these tight junction proteins. Furthermore, the signaling pathways disrupted by dysregulated kinases, proteins and post-translational modifications are reviewed to design an abstracted computational model showing the situation-dependent dynamic behaviors of these biological processes and entities. A qualitative hybrid Petri Net model is therefore constructed showing the altered host pathways in the presence of virulence factor cytotoxin-associated gene A, leading to the disruption of tight junction proteins. The model is qualitative logic-based, which does not depend on any kinetic parameter and quantitative data and depends on knowledge derived from experiments. The designed model provides insights into the tight junction disruption and disease progression. Model is then verified by the available experimental data, nevertheless formal in vitro experimentation is a promising way to ensure its validation. The major findings propose that H. pylori activated kinases are responsible to trigger specific post translational modifications within tight junction proteins, at specific sites. These modifications may favor alterations in gastric barrier and provide a route to bacterial invasion into host cells.

  15. Tightly confined atoms in optical dipole traps

    International Nuclear Information System (INIS)

    Schulz, M.

    2002-12-01

    This thesis reports on the design and setup of a new atom trap apparatus, which is developed to confine few rubidium atoms in ultrahigh vacuum and make them available for controlled manipulations. To maintain low background pressure, atoms of a vapour cell are transferred into a cold atomic beam by laser cooling techniques, and accumulated by a magneto-optic trap (MOT) in a separate part of the vacuum system. The laser cooled atoms are then transferred into dipole traps made of focused far-off-resonant laser fields in single- or crossed-beam geometry, which are superimposed with the center of the MOT. Gaussian as well as hollow Laguerre-Gaussian (LG$ ( 01)$) beam profiles are used with red-detuned or blue-detuned light, respectively. Microfabricated dielectric phase objects allow efficient and robust mode conversion of Gaussian into Laguerre-Gaussian laser beams. Trap geometries can easily be changed due to the highly flexible experimental setup. The dipole trap laser beams are focused to below 10 microns at a power of several hundred milliwatts. Typical trap parameters, at a detuning of several ten nanometers from the atomic resonance, are trag depths of few millikelvin, trap frequencies near 30-kHz, trap light scattering rates of few hundred photons per atom and second, and lifetimes of several seconds. The number of dipole-trapped atoms ranges from more than ten thousand to below ten. The dipole-trapped atoms are detected either by a photon counting system with very efficient straylight discrimination, or by recapture into the MOT, which is imaged onto a sensitive photodiode and a CCD-camera. Due to the strong AC-Stark shift imposed by the high intensity trapping light, energy-selective resonant excitation and detection of the atoms is possible. The measured energy distribution is consistent with a harmonic potential shape and allows the determination of temperatures and heating rates. In first measurements, the thermal energy is found to be about 10 % of the

  16. Differentiation of bovine spermatogonial stem cells into osteoblasts.

    Science.gov (United States)

    Qasemi-Panahi, Babak; Tajik, Parviz; Movahedin, Mansoureh; Moghaddam, Gholamali; Barzgar, Younes; Heidari-Vala, Hamed

    2011-07-01

    Spermatogonial Stem Cell (SSC) technologies provide multiple opportunities for research in the field of biotechnology and regenerative medicine. The therapeutic use of Embryonic Stem Cells (ESCs) is restricted due to severe ethical and immunological concerns. Therefore, we need a new pluripotent cell type. Despite well-known role of germ cells in the gametogenesis, some facts apparently show their multipotentiality. In the present study, bovine SSCs were co-cultured with Sertoli cell for 7 days. Sertoli cells and SSCs were identified by Vimentin and Oct-4 immunocytochemical staining method, respectively. In order to differentiate SSCs into osteoblasts, we used consecutive inducer media without separation of the colonies. We characterized osteoblasts using Alizarin red staining.

  17. Strain-dependent augmentation of tight-junction barrier function in human primary epidermal keratinocytes by Lactobacillus and Bifidobacterium lysates.

    Science.gov (United States)

    Sultana, Reshma; McBain, Andrew J; O'Neill, Catherine A

    2013-08-01

    In this study, we investigated whether probiotic lysates can modify the tight-junction function of human primary keratinocytes. The keratinocytes were grown on cell culture inserts and treated with lysates from Bifidobacterium longum, Lactobacillus plantarum, Lactobacillus reuteri, Lactobacillus fermentum, or Lactobacillus rhamnosus GG. With the exception of L. fermentum (which decreased cell viability), all strains markedly enhanced tight-junction barrier function within 24 h, as assessed by measurements of transepithelial electrical resistance (TEER). However, B. longum and L. rhamnosus GG were the most efficacious, producing dose-dependent increases in resistance that were maintained for 4 days. These increases in TEER correlated with elevated expression of tight-junction protein components. Neutralization of Toll-like receptor 2 abolished both the increase in TEER and expression of tight-junction proteins induced by B. longum, but not L. rhamnosus GG. These data suggest that some bacterial strains increase tight-junction function via modulation of protein components but the different pathways involved may vary depending on the bacterial strain.

  18. Human zonulin, a potential modulator of intestinal tight junctions.

    Science.gov (United States)

    Wang, W; Uzzau, S; Goldblum, S E; Fasano, A

    2000-12-01

    Intercellular tight junctions are dynamic structures involved in vectorial transport of water and electrolytes across the intestinal epithelium. Zonula occludens toxin derived from Vibrio cholerae interacts with a specific intestinal epithelial surface receptor, with subsequent activation of a complex intracellular cascade of events that regulate tight junction permeability. We postulated that this toxin may mimic the effect of a functionally and immunologically related endogenous modulator of intestinal tight junctions. Affinity-purified anti-zonula occludens toxin antibodies and the Ussing chamber assay were used to screen for one or more mammalian zonula occludens toxin analogues in both fetal and adult human intestine. A novel protein, zonulin, was identified that induces tight junction disassembly in non-human primate intestinal epithelia mounted in Ussing chambers. Comparison of amino acids in the active zonula occludens toxin fragment and zonulin permitted the identification of the putative receptor binding domain within the N-terminal region of the two proteins. Zonulin likely plays a pivotal role in tight junction regulation during developmental, physiological, and pathological processes, including tissue morphogenesis, movement of fluid, macromolecules and leukocytes between the intestinal lumen and the interstitium, and inflammatory/autoimmune disorders.

  19. The media of sociology: tight or loose translations?

    Science.gov (United States)

    Guggenheim, Michael

    2015-06-01

    Sociologists have increasingly come to recognize that the discipline has unduly privileged textual representations, but efforts to incorporate visual and other media are still only in their beginning. This paper develops an analysis of the ways objects of knowledge are translated into other media, in order to understand the visual practices of sociology and to point out unused possibilities. I argue that the discourse on visual sociology, by assuming that photographs are less objective than text, is based on an asymmetric media-determinism and on a misleading notion of objectivity. Instead, I suggest to analyse media with the concept of translations. I introduce several kinds of translations, most centrally the distinction between tight and loose ones. I show that many sciences, such as biology, focus on tight translations, using a variety of media and manipulating both research objects and representations. Sociology, in contrast, uses both tight and loose translations, but uses the latter only for texts. For visuals, sociology restricts itself to what I call 'the documentary': focusing on mechanical recording technologies without manipulating either the object of research or the representation. I conclude by discussing three rare examples of what is largely excluded in sociology: visual loose translations, visual tight translations based on non-mechanical recording technologies, and visual tight translations based on mechanical recording technologies that include the manipulation of both object and representation. © London School of Economics and Political Science 2015.

  20. Experimental study on reflooding in advanced tight lattice PWR

    International Nuclear Information System (INIS)

    Hori, K.; Kodama, J.; Teramae, T.

    2000-01-01

    This paper is related to the experimental study on the feasibility of core cooling by re-flooding in a large break loss of coolant accident (LOCA) for the advanced tight lattice pressurized water reactor (PWR). The tight lattice core design should be adopted to improve the conversion ratio. Major one of the key questions of such tight lattice core is the cooling capability under the re-flood condition in a large break LOCA. Forced feed bottom re-flooding experiments have been performed by use of a 4x4 triangular array rod bundle. The rod gap is 0.5 mm, 1.0 mm, or 1.5 mm. The measured peak temperature is below around 1273 K even in case of 1.0/0.5 mm rod gap. And, the evaluation based on the experimental results of rod temperatures and core pressure drop also shows that the core cooling under re-flooding condition is feasible. (author)

  1. Numerical simulation of flow behavior in tight lattice rod bundle

    International Nuclear Information System (INIS)

    Yu Yiqi; Yang Yanhua; Gu Hanyang; Cheng Xu; Song Xiaoming; Wang Xiaojun

    2009-01-01

    The Numerical investigation is performed on the air turbulent flow in triangular rod bundle array. Based on the experimental data, the eddy viscosity turbulent model and the Reynold stress turbulent model are evaluated to simulate the flow behavior in the tight lattice. The results show that SSG Reynolds Stress Model has shown superior predictive performance than other Reynolds-stress models, which indicates that the simulation of the anisotropy of the turbulence is significant in the tight lattice. The result with different Reynolds number and geometry shows that the magnitude of the secondary flow is almost independent of the Reynolds number, but it increases with the decrease of the P/D. (authors)

  2. No Change in Bicarbonate Transport but Tight-Junction Formation Is Delayed by Fluoride in a Novel Ameloblast Model

    Directory of Open Access Journals (Sweden)

    Róbert Rácz

    2017-12-01

    Full Text Available We have recently developed a novel in vitro model using HAT-7 rat ameloblast cells to functionally study epithelial ion transport during amelogenesis. Our present aims were to identify key transporters of bicarbonate in HAT-7 cells and also to examine the effects of fluoride exposure on vectorial bicarbonate transport, cell viability, and the development of transepithelial resistance. To obtain monolayers, the HAT-7 cells were cultured on Transwell permeable filters. We monitored transepithelial resistance (TER as an indicator of tight junction formation and polarization. We evaluated intracellular pH changes by microfluorometry using the fluorescent indicator BCECF. Activities of ion transporters were tested by withdrawal of various ions from the bathing medium, by using transporter specific inhibitors, and by activation of transporters with forskolin and ATP. Cell survival was estimated by alamarBlue assay. Changes in gene expression were monitored by qPCR. We identified the activity of several ion transporters, NBCe1, NHE1, NKCC1, and AE2, which are involved in intracellular pH regulation and vectorial bicarbonate and chloride transport. Bicarbonate secretion by HAT-7 cells was not affected by acute fluoride exposure over a wide range of concentrations. However, tight-junction formation was inhibited by 1 mM fluoride, a concentration which did not substantially reduce cell viability, suggesting an effect of fluoride on paracellular permeability and tight-junction formation. Cell viability was only reduced by prolonged exposure to fluoride concentrations greater than 1 mM. In conclusion, cultured HAT-7 cells are functionally polarized and are able to transport bicarbonate ions from the basolateral to the apical fluid spaces. Exposure to 1 mM fluoride has little effect on bicarbonate secretion or cell viability but delays tight-junction formation, suggesting a novel mechanism that may contribute to dental fluorosis.

  3. Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK.

    Directory of Open Access Journals (Sweden)

    Xiao Xiao Tang

    2010-08-01

    Full Text Available The tight junctions (TJs, characteristically located at the apicolateral borders of adjacent epithelial cells, are required for the proper formation of epithelial cell polarity as well as for sustaining the mucosal barrier to the external environment. The observation that lymphocytes are recruited by epithelial cells to the sites of infection [1] suggests that they may play a role in the modulation of epithelial barrier function and thus contribute to host defense. To test the ability of lymphocytes to modulate tight junction assembly in epithelial cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin-Darby canine kidney (MDCK cells, a well-established model cell line for studying epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an infection state. In a typical calcium switch experiment, the TJ assembly in co-culture was found to be accelerated compared to that in MDCK cells alone. This accelaration was found to be mediated by AMP-activated protein kinase (AMPK. AMPK activation was independent of changes in cellular ATP levels but it was found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated the accelerating effect of lymphocytes on TJ formation. Similar results were also observed in a co-culture with lymphocytes and Calu-3 human airway epithelial cells, suggesting that the activation of AMPK may be a general mechanism underlying lymphocyte-accelerated TJ assembly in different epithelia. These results suggest that signals from lymphocytes, such as cytokines, facilitate TJ assembly in epithelial cells via the activation of AMPK.

  4. Tight Temporal Bounds for Dataflow Applications Mapped onto Shared Resources

    NARCIS (Netherlands)

    Alizadeh Ara, H.; Geilen, M.; Basten, T.; Behrouzian, A.R.B.; Hendriks, M.; Goswami, D.

    2016-01-01

    We present an analysis method that provides tight temporal bounds for applications modeled by Synchronous Dataflow Graphs and mapped to shared resources. We consider the resource sharing effects on the temporal behaviour of the application by embedding worst case resource availability curves in the

  5. Ultra-Tightly Coupled GNSS/INS for small UAVs

    DEFF Research Database (Denmark)

    Olesen, Daniel; Jakobsen, Jakob; Knudsen, Per

    2017-01-01

    This paper describes an ultra-tight integration of a Global Navigation Satellite System ( GNSS) receiver and an Inertial Navigation System ( INS) for small Unmanned Aerial Vehicles ( UAVs). The system is based on a low-cost and low-weight GNSS Intermediate Frequency ( IF) sampler which has been...

  6. Management of Small Urethrocutaneous Fistula by Tight Ligation ...

    African Journals Online (AJOL)

    After identifying the fistulous opening, the fistula tract was circumferentially and meticulously dissected ,then the dissected tract was lifted up and the base was ligated tightly with 5/0 vicryl, the external epithelium of the dissected tract was fulgurated with the diathermy, then a second layer of local soft tissue was secured over ...

  7. A characterization of tight and dual generalized translation invariant frames

    DEFF Research Database (Denmark)

    Jakobsen, Mads Sielemann; Lemvig, Jakob

    2015-01-01

    such systems form tight frames, and when two GTI Bessel systems form dual frames for L2(G). In particular, this offers a unified approach to the theory of discrete and continuous frames and, e.g., yields well known results for discrete and continuous Gabor and wavelet systems....

  8. Envelopes of Sets of Measures, Tightness, and Markov Control Processes

    International Nuclear Information System (INIS)

    Gonzalez-Hernandez, J.; Hernandez-Lerma, O.

    1999-01-01

    We introduce upper and lower envelopes for sets of measures on an arbitrary topological space, which are then used to give a tightness criterion. These concepts are applied to show the existence of optimal policies for a class of Markov control processes

  9. Local thermal-hydraulic behaviour in tight 7-rod bundles

    International Nuclear Information System (INIS)

    Cheng, X.; Yu, Y.Q.

    2009-01-01

    Advanced water-cooled reactor concepts with tight lattices have been proposed worldwide to improve the fuel utilization and the economic competitiveness. In the present work, experimental investigations were performed on thermal-hydraulic behaviour in tight hexagonal 7-rod bundles under both single-phase and two-phase conditions. Freon-12 was used as working fluid due to its convenient operating parameters. Tests were carried out under both single-phase and two-phase flow conditions. Rod surface temperatures are measured at a fixed axial elevation and in various circumferential positions. Test data with different radial power distributions are analyzed. Measured surface temperatures of unheated rods are used for the assessment of and comparison with numerical codes. In addition, numerical simulation using sub-channel analysis code MATRA and the computational fluid dynamics (CFD) code ANSYS-10 is carried out to understand the experimental data and to assess the validity of these codes in the prediction of flow and heat transfer behaviour in tight rod bundle geometries. Numerical results are compared with experimental data. A good agreement between the measured temperatures on the unheated rod surface and the CFD calculation is obtained. Both sub-channel analysis and CFD calculation indicates that the turbulent mixing in the tight rod bundle is significantly stronger than that computed with a well established correlation.

  10. Trapping of Rydberg atoms in tight magnetic microtraps

    NARCIS (Netherlands)

    Boetes, A.Q.G.; Skannrup, R.V.; Naber, J.; Kokkelmans, S.J.J.M.F.; Spreeuw, R.J.C.

    2018-01-01

    We explore the possibility to trap Rydberg atoms in tightly confining magnetic microtraps. The trapping frequencies for Rydberg atoms are expected to be influenced strongly by magnetic-field gradients. We show that there are regimes where Rydberg atoms can be trapped. Moreover, we show that

  11. Dielectric constant of graphene-on-polarized substrate: A tight ...

    Indian Academy of Sciences (India)

    Sivabrata Sahu

    Corresponding author. E-mail: gcr@iopb.res.in. Published online 24 June 2017. Abstract. We report here a microscopic tight-binding theoretical study of the dynamic dielectric response of graphene-on-polarizable substrate with impurity. The Hamiltonian consists of first, second and third nearest- neighbour electron hopping ...

  12. Dielectric constant of graphene-on-polarized substrate: A tight ...

    Indian Academy of Sciences (India)

    2017-06-24

    Jun 24, 2017 ... We report here a microscopic tight-binding theoretical study of the dynamic dielectric response of graphene-on-polarizable substrate with impurity. The Hamiltonian consists of first, second and third nearest neighbour electron hopping interactions besides doping and substrate-induced effects on graphene.

  13. Loosen up? Cultural tightness and national entrepreneurial activity

    NARCIS (Netherlands)

    Harms, Rainer; Groen, Arend J.

    The level of entrepreneurship between countries differs consistently. A source of this variance lies in national culture differences. Recently, the cultural dimension “tightness” has been introduced in the literature. Tightness refers to the degree to which a nation has strong norms and a low

  14. Prediction of Gas Leak Tightness of Superplastically Formed Products

    NARCIS (Netherlands)

    Snippe, Q.H.C.; Meinders, Vincent T.; Barlat, F; Moon, Y.H.; Lee, M.G.

    2010-01-01

    In some applications, in this case an aluminium box in a subatomic particle detector containing highly sensitive detecting devices, it is important that a formed sheet should show no gas leak from one side to the other. In order to prevent a trial-and-error procedure to make this leak tight box, a

  15. Sit-Tight Syndrome and Tenure Elongation in African Politics ...

    African Journals Online (AJOL)

    The post-independence politics of African countries has been dominated by the phenomenon of sit-tight African heads of state and government who had acceeded to office by election or coup d'etat. This paper examines this recurring problem in post-independence African politics by examining its general and specific ...

  16. Initial observations of cell-mediated drug delivery to the deep lung.

    Science.gov (United States)

    Kumar, Arun; Glaum, Mark; El-Badri, Nagwa; Mohapatra, Shyam; Haller, Edward; Park, Seungjoo; Patrick, Leslie; Nattkemper, Leigh; Vo, Dawn; Cameron, Don F

    2011-01-01

    Using current methodologies, drug delivery to small airways, terminal bronchioles, and alveoli (deep lung) is inefficient, especially to the lower lungs. Urgent lung pathologies such as acute respiratory distress syndrome (ARDS) and post-lung transplantation complications are difficult to treat, in part due to the methodological limitations in targeting the deep lung with high efficiency drug distribution to the site of pathology. To overcome drug delivery limitations inhibiting the optimization of deep lung therapy, isolated rat Sertoli cells preloaded with chitosan nanoparticles were use to obtain a high-density distribution and concentration (92%) of the nanoparticles in the lungs of mice by way of the peripheral venous vasculature rather than the more commonly used pulmonary route. Additionally, Sertoli cells were preloaded with chitosan nanoparticles coupled with the anti-inflammatory compound curcumin and then injected intravenously into control or experimental mice with deep lung inflammation. By 24 h postinjection, most of the curcumin load (∼90%) delivered in the injected Sertoli cells was present and distributed throughout the lungs, including the perialveloar sac area in the lower lungs. This was based on the high-density, positive quantification of both nanoparticles and curcumin in the lungs. There was a marked positive therapeutic effect achieved 24 h following curcumin treatment delivered by this Sertoli cell nanoparticle protocol (SNAP). Results identify a novel and efficient protocol for targeted delivery of drugs to the deep lung mediated by extratesticular Sertoli cells. Utilization of SNAP delivery may optimize drug therapy for conditions such as ARDS, status asthmaticus, pulmonary hypertension, lung cancer, and complications following lung transplantation where the use of high concentrations of anti-inflammatory drugs is desirable, but often limited by risks of systemic drug toxicity.

  17. Follicle stimulating hormone increases spermatogonial stem cell colonization during in vitro co-culture.

    Science.gov (United States)

    Narenji Sani, Reza; Tajik, Parviz; Yousefi, Mohammad Hassan; Movahedin, Mansoureh; Qasemi-Panahi, Babak; Shafiei, Shiva; Ahmadi Hamedani, Mahmood

    2013-01-01

    The complex process of spermatogenesis is regulated by various factors. Studies on spermatogonial stem cells (SCCs) have provided very important tool to improve herd genetic and different field. 0.2 to 0.3 percent of total cells of seminiferous tubules is consist of spermatogonial stem cells. To investigate and biomanipulation of these cells, proliferation and viability rate of cells should be increased in vitro, at first. Follicle stimulating hormone (FSH) has been suggested to play a determinant role in the survival of germ cells in addition to increasing spermatogonial proliferation. In this study, the in vitro effects of FSH on spermatogonial cell colony formation were investigated. Sertoli and spermatogonial cells were isolated from 3-5 months old calves. The identity of the Sertoli cells and spermatogonial stem cells were confirmed through immunocytochemistry and colony morphology, respectively. Co-cultured Sertoli and spermatogonial cells were treated with FSH in different dose of 10, 20 and 40 IU mL(-1) FSH, before colony assay. Results indicated that, FSH increased in vitro colonization of spermatogonial cells in comparison with control group. In conclusion, using FSH provided proper bovine spermatogonial stem cell culture medium for in vitro study of these cells.

  18. Unconventional Tight Reservoirs Characterization with Nuclear Magnetic Resonance

    Science.gov (United States)

    Santiago, C. J. S.; Solatpour, R.; Kantzas, A.

    2017-12-01

    The increase in tight reservoir exploitation projects causes producing many papers each year on new, modern, and modified methods and techniques on estimating characteristics of these reservoirs. The most ambiguous of all basic reservoir property estimations deals with permeability. One of the logging methods that is advertised to predict permeability but is always met by skepticism is Nuclear Magnetic Resonance (NMR). The ability of NMR to differentiate between bound and movable fluids and providing porosity increased the capability of NMR as a permeability prediction technique. This leads to a multitude of publications and the motivation of a review paper on this subject by Babadagli et al. (2002). The first part of this presentation is dedicated to an extensive review of the existing correlation models for NMR based estimates of tight reservoir permeability to update this topic. On the second part, the collected literature information is used to analyze new experimental data. The data are collected from tight reservoirs from Canada, the Middle East, and China. A case study is created to apply NMR measurement in the prediction of reservoir characterization parameters such as porosity, permeability, cut-offs, irreducible saturations etc. Moreover, permeability correlations are utilized to predict permeability. NMR experiments were conducted on water saturated cores. NMR T2 relaxation times were measured. NMR porosity, the geometric mean relaxation time (T2gm), Irreducible Bulk Volume (BVI), and Movable Bulk Volume (BVM) were calculated. The correlation coefficients were computed based on multiple regression analysis. Results are cross plots of NMR permeability versus the independently measured Klinkenberg corrected permeability. More complicated equations are discussed. Error analysis of models is presented and compared. This presentation is beneficial in understanding existing tight reservoir permeability models. The results can be used as a guide for choosing

  19. Formation of tight junctions between neighboring podocytes is an early ultrastructural feature in experimental crescentic glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Succar L

    2016-11-01

    Full Text Available Lena Succar,1 Ross A Boadle,2 David C Harris,1,3 Gopala K Rangan1,3 1Centre for Transplant and Renal Research, The Westmead Institute for Medical Research, The University of Sydney, 2Electron Microscopy Laboratory, Institute of Clinical Pathology and Medical Research, Westmead Hospital, 3Department of Renal Medicine, Westmead Hospital, Western Sydney Local Health District, Westmead, Sydney, NSW, Australia Purpose: In crescentic glomerulonephritis (CGN, the development of cellular bridges between podocytes and parietal epithelial cells (PECs triggers glomerular crescent formation. However, the sequential changes in glomerular ultrastructure in CGN are not well defined. This study investigated the time course of glomerular ultrastructure in experimental CGN. Methods: Transmission electron microscopy (TEM was performed using kidney samples from rats with nephrotoxic serum nephritis (NSN from day 1 to day 14. Morphometric analysis was conducted on randomly selected glomeruli captured on TEM digital images. Results: On day 1 of NSN, there was widespread formation of focal contacts between the cell bodies of neighboring podocytes, and tight junctions were evident at the site of cell-to-cell contact. This was confirmed by the increased expression of the tight junction molecule, zonula occludens-1 (ZO-1, which localized to the points of podocyte cell–cell body contact. On day 2, the interpodocyte distance decreased and the glomerular basement membrane thickness increased. Foot process effacement (FPE was segmental on day 3 and diffuse by day 5, accompanied by the formation of podocyte cellular bridges with Bowman’s capsule, as confirmed by a decrease in podocyte-to-PEC distance. Fibrinoid necrosis and cellular crescents were evident in all glomeruli by days 7 and 14. In vitro, the exposure of podocytes to macrophage-conditioned media altered cellular morphology and caused an intracellular redistribution of ZO-1. Conclusion: The formation of tight

  20. Persistent Mullerian duct syndrome in a Miniature Schnauzer dog with signs of feminization and a Sertoli cell tumour

    NARCIS (Netherlands)

    Vegter, A. R.; Kooistra, H. S.; van Sluijs, F. J.; van Bruggen, L. W. L.; Ijzer, J.; Zijlstra, C.; Okkens, A. C.

    2010-01-01

    A 5-year-old male Miniature Schnauzer was presented with unilateral cryptorchidism and signs of feminization. Abdominal ultrasonography revealed an enlarged right testis and a large, fluid-filled cavity that appeared to arise from the prostate. Computed tomography revealed the cavity to be

  1. Postnatal Changes in Testicular Position are Associated with IGF-I and Function of Sertoli and Leydig Cells

    DEFF Research Database (Denmark)

    Koskenniemi, Jaakko J; Virtanen, Helena E; Wohlfahrt-Veje, Christine

    2018-01-01

    position during childhood. Design: Testicular position (the distance from the pubic bone to the upper pole of the testes) at birth, 3 months, 18 months, 36 months, 7 years and reproductive hormones at three months were measured. Setting: Prenatally recruited, prospective longitudinal birth cohort....... Participants: In total 2545 boys were recruited prenatally in a Danish-Finnish birth cohort and had testicular position examination available. A subset of 680 Danish and 362 Finnish boys had serum reproductive hormone concentrations and insulin-like growth factor I (IGF-I) determined at three months. Main...

  2. Sex-reversed somatic cell cloning in the mouse.

    Science.gov (United States)

    Inoue, Kimiko; Ogonuki, Narumi; Mekada, Kazuyuki; Yoshiki, Atsushi; Sado, Takashi; Ogura, Atsuo

    2009-10-01

    Somatic cell nuclear transfer has many potential applications in the fields of basic and applied sciences. However, it has a disadvantage that can never be overcome technically-the inflexibility of the sex of the offspring. Here, we report an accidental birth of a female mouse following nuclear transfer using an immature Sertoli cell. We produced a batch of 27 clones in a nuclear transfer experiment using Sertoli cells collected from neonatal male mice. Among them, one pup was female. This "male-derived female" clone grew into a normal adult and produced offspring by natural mating with a littermate. Chromosomal analysis revealed that the female clone had a 39,X karyotype, indicating that the Y chromosome had been deleted in the donor cell or at some early step during nuclear transfer. This finding suggests the possibility of resuming sexual reproduction after a single male is cloned, which should be especially useful for reviving extinct or endangered species.

  3. Follicle stimulating hormone increases spermatogonial stem cell colonization during in vitro co - culture

    Directory of Open Access Journals (Sweden)

    Reza Narenji Sani

    2013-03-01

    Full Text Available The complex process of spermatogenesis is regulated by various factors. Studies onspermatogonial stem cells(SCCshave provided very important tool to improve herd geneticand different field. 0.2 to 0.3 percent of total cells of seminiferous tubules is consist ofspermatogonial stem cells. To investigate and biomanipulation of these cells, proliferationand viability rate of cells should be increasedin vitro, at first. Follicle stimulating hormone(FSH has been suggested to play a determinant role in the survival of germ cells in additionto increasing spermatogonial proliferation. In this study, thein vitroeffects ofFSHonspermatogonial cell colony formation were investigated. Sertoli and spermatogonial cellswere isolated from 3-5 months old calves. The identity of theSertoli cells and spermatogonialstem cells were confirmed through immunocytochemistry and colony morphology,respectively. Co-cultured Sertoli and spermatogonial cells were treatedwithFSHin differentdose of10, 20 and 40 IU mL-1FSH, before colony assay.Results indicated that,FSHincreasedin vitrocolonization of spermatogonial cells in comparison with control group. In conclusion,usingFSHprovided proper bovine spermatogonial stem cell culture medium forin vitrostudy of these cells.

  4. Design of sealing arrangements for development of leak tight articulated manipulator for waste management and reprocessing plants

    International Nuclear Information System (INIS)

    Patil, Satish B.; Mudaiya, Avinash K.

    2016-01-01

    As a part of development of Remote handling equipment and gadgets, Leak tight Articulated Manipulator (ARTM) has been developed for shielded facilities of Nuclear Recycle Plant. The ARTM is a Master Slave Manipulator having 8 Kg Payload capacity and most suitable for shielded sampling cubicles of Waste Management plants and dilution hot cells of Reprocessing plants. All the motions and forces are transmitted from Master to slave arm through the mechanical linkages, which are housed inside the wall tube. The mechanical linkages and wall tube run across the shielded wall. The applications involving seal tightness of the glove boxes and dilution hot cells intend to use all the accessories including MSMs to be leak tight. During the design of leak tight ARTM, all the potential leak paths through the components of existing ARTM were examined critically and static and dynamic seals were designed based on the geometry and requirement of particular leak path. A leak proof testing set up was fabricated for evaluating the leak rates across the manipulator contemplating the actual operating conditions. The manipulator was subjected to the Friction, Rigidity and Leak tests. The results of the tests are satisfactory and as per the International standards available. The leak rates measured for different manipulators were in the range of 0.05 to 0.1 % of air volume/hr @ 200 mm of water columndifferential negative pressure. (author)

  5. Preconditioning Filter Bank Decomposition Using Structured Normalized Tight Frames

    Directory of Open Access Journals (Sweden)

    Martin Ehler

    2015-01-01

    Full Text Available We turn a given filter bank into a filtering scheme that provides perfect reconstruction, synthesis is the adjoint of the analysis part (so-called unitary filter banks, all filters have equal norm, and the essential features of the original filter bank are preserved. Unitary filter banks providing perfect reconstruction are induced by tight generalized frames, which enable signal decomposition using a set of linear operators. If, in addition, frame elements have equal norm, then the signal energy is spread through the various filter bank channels in some uniform fashion, which is often more suitable for further signal processing. We start with a given generalized frame whose elements allow for fast matrix vector multiplication, as, for instance, convolution operators, and compute a normalized tight frame, for which signal analysis and synthesis still preserve those fast algorithmic schemes.

  6. Empirical tight-binding parameters for solid C60

    International Nuclear Information System (INIS)

    Tit, N.; Kumar, V.

    1993-01-01

    We present a tight-binding model for the electronic structure of C 60 using four (1s and 3p) orbitals per carbon atom. The model has been developed by fitting the tight-binding parameters to the ab-initio pseudopotential calculation of Troullier and Martins (Phys. Rev. B46, 1754 (1992)) in the face-centered cubic (Fm3-bar) phase. Following this, calculations of the energy bands and the density of electronic states have been carried out as a function of the lattice constant. Good agreement has been obtained with the observed lattice-constant dependence of T c using McMillan's formula. Furthermore, calculations of the electronic structure are presented in the simple cubic (Pa3-bar) phase. (author). 43 refs, 3 figs, 1 tab

  7. Critical heat flux experiments in tight lattice core

    Energy Technology Data Exchange (ETDEWEB)

    Kureta, Masatoshi [Japan Atomic Energy Research Inst., Tokai, Ibaraki (Japan). Tokai Research Establishment

    2002-12-01

    Fuel rods of the Reduced-Moderation Water Reactor (RMWR) are so designed to be in tight lattices as to reduce moderation and achieve higher conversion ratio. As for the BWR type reactor coolant flow rate is reduced small compared with the existing BWR, so average void fraction comes to be langer. In order to evaluate thermo hydraulic characteristics of designed cores, critical heat flux experiments in tight lattice core have been conducted using simulated high pressure coolant loops for both the PWR and BWR seven fuel rod bundles. Experimental data on critical heat flux for full bundles have been accumulated and applied to assess the critical power of designed cores using existing codes. Evaluated results are conservative enough to satisfy the limiting condition. Further experiments on axial power distribution effects and 37 fuel rod bundle tests will be performed to validate thermohydraulic characteristics of designed cores. (T. Tanaka)

  8. Critical heat flux experiments in tight lattice core

    International Nuclear Information System (INIS)

    Kureta, Masatoshi

    2002-01-01

    Fuel rods of the Reduced-Moderation Water Reactor (RMWR) are so designed to be in tight lattices as to reduce moderation and achieve higher conversion ratio. As for the BWR type reactor coolant flow rate is reduced small compared with the existing BWR, so average void fraction comes to be langer. In order to evaluate thermo hydraulic characteristics of designed cores, critical heat flux experiments in tight lattice core have been conducted using simulated high pressure coolant loops for both the PWR and BWR seven fuel rod bundles. Experimental data on critical heat flux for full bundles have been accumulated and applied to assess the critical power of designed cores using existing codes. Evaluated results are conservative enough to satisfy the limiting condition. Further experiments on axial power distribution effects and 37 fuel rod bundle tests will be performed to validate thermohydraulic characteristics of designed cores. (T. Tanaka)

  9. Testicular Cell Indices and Peripheral Blood Testosterone Concentrations in Relation to Age and Semen Quality in Crossbred (Holstein Friesian×Tharparkar Bulls

    Directory of Open Access Journals (Sweden)

    S. K. Rajak

    2014-11-01

    Full Text Available Present study analyzed the changes in peripheral blood testosterone concentrations and testicular cytogram in relation to age and semen quality in crossbred males. Three different age groups of crossbred males viz. bull calves (6 months, n = 5, young bulls (15 months, n = 5 and adult bulls (4 to 6 years, n = 8 were utilized for the study. Testicular fine needle aspiration cytology technique was used to quantify testicular cytology and their indices. Peripheral blood testosterone concentrations were measured using enzyme-linked immunosorbent assay method. Semen samples collected from adult bulls were microscopically evaluated for quality parameters. Mean peripheral blood testosterone concentrations in bull calves, young bulls and adult bulls were 2.28±0.09 ng/mL, 1.42±0.22 ng/mL and 5.66±1.08 ng/mL respectively, and that in adult bulls were significantly different (p<0.01 from young bulls and bull calves. There was no significant difference between the proportion of different testicular cells in bull calves and young bulls. Between young and adult bulls, significant differences (p<0.01 were observed in the proportion of spermatocytes, spermatozoa, and sperm: Sertoli cell ratio. The proportions of Sertoli cells showed a significant difference (p<0.01 between the three age groups. The number of primary spermatocytes had a positive correlation with peripheral blood testosterone concentrations in bull calves (r = 0.719, p<0.01. Number of Sertoli cells per 100 germ cells was negatively correlated with blood testosterone concentration in young bulls (r = −0.713, p<0.01. Among different semen parameters in adult bulls, ejaculate volume (r = 0.790, p<0.05 had positive relationship, and sperm motility had significant negative correlation (r = −0.711, p<0.05 with testosterone concentrations. The number of Sertoli cells and Sertoli cell index had a positive correlation with various semen quality parameters (p<0.001. Results of the present study

  10. Tight Network Topology Dependent Bounds on Rounds of Communication

    OpenAIRE

    Chattopadhyay, Arkadev; Langberg, Michael; Li, Shi; Rudra, Atri

    2016-01-01

    We prove tight network topology dependent bounds on the round complexity of computing well studied $k$-party functions such as set disjointness and element distinctness. Unlike the usual case in the CONGEST model in distributed computing, we fix the function and then vary the underlying network topology. This complements the recent such results on total communication that have received some attention. We also present some applications to distributed graph computation problems. Our main contri...

  11. Integral tightness measurements at the Paks-1 nuclear reactor

    Energy Technology Data Exchange (ETDEWEB)

    Taubner, R.; Techy, Z. (Villamosenergiaipari Kutato Intezet, Budapest (Hungary))

    1983-01-01

    The containment system experiments of the Paks-1 nuclear reactor are described. The integrated tightness measurements of the hermetic system were completed in 1982. The principles and methods and the evaluation of the results of the measurements are discussed. Some features of the filtration characteristics are demonstrated using relative values and a method enabling the description of the physical contents of the characteristics by flow technical functions is outlined.

  12. Quantum tight-binding chains with dissipative coupling

    International Nuclear Information System (INIS)

    Mogilevtsev, D; Slepyan, G Ya; Garusov, E; Kilin, S Ya; Korolkova, N

    2015-01-01

    We present a one-dimensional tight-binding chain of two-level systems coupled only through common dissipative Markovian reservoirs. This quantum chain can demonstrate anomalous thermodynamic behavior contradicting Fourier law. Population dynamics of individual systems of the chain is polynomial with the order determined by the initial state of the chain. The chain can simulate classically hard problems, such as multi-dimensional random walks. (paper)

  13. Thermography Control of Heat Insulation and Tightness of Buildings,

    Science.gov (United States)

    1980-11-01

    construction. The method is pedagogical . Results from thermography studies are suitable for use when giving experience feedback. (Excellent complement...visual inspection Instrument Various tools and measures. Principle The construction is opened, and the workmanship of insulation and tight- ness is...most IR cameras. At -196 C (77K) it is sensitive within the wavelength range 0 - 5.6 jam. The lower - 24 - FIGURE 3: Photography with IR camera, AGA

  14. Tightly localized stationary pulses in a multilevel atomic system

    International Nuclear Information System (INIS)

    Liu, Xiong-Jun; Oh, C. H.; Liu, Xin; Liu, Zheng-Xin; Kwek, L. C.

    2007-01-01

    We show that the pulse matching phenomenon can be obtained in the general multilevel system with electromagnetically induced transparency. For this we find a different way to create tightly localized stationary pulses by using counterpropagating pump fields. The present process is a spatial compression of excitation so that it allows us to shape and further intensify the localized stationary pulses, without using standing waves of pump fields or spatially modulated pump fields

  15. Tight junction regulates epidermal calcium ion gradient and differentiation

    International Nuclear Information System (INIS)

    Kurasawa, Masumi; Maeda, Tetsuo; Oba, Ai; Yamamoto, Takuya; Sasaki, Hiroyuki

    2011-01-01

    Research highlights: → We disrupted epidermal tight junction barrier in reconstructed epidermis. → It altered Ca 2+ distribution and consequentially differentiation state as well. → Tight junction should affect epidermal homeostasis by maintaining Ca 2+ gradient. -- Abstract: It is well known that calcium ions (Ca 2+ ) induce keratinocyte differentiation. Ca 2+ distributes to form a vertical gradient that peaks at the stratum granulosum. It is thought that the stratum corneum (SC) forms the Ca 2+ gradient since it is considered the only permeability barrier in the skin. However, the epidermal tight junction (TJ) in the granulosum has recently been suggested to restrict molecular movement to assist the SC as a secondary barrier. The objective of this study was to clarify the contribution of the TJ to Ca 2+ gradient and epidermal differentiation in reconstructed human epidermis. When the epidermal TJ barrier was disrupted by sodium caprate treatment, Ca 2+ flux increased and the gradient changed in ion-capture cytochemistry images. Alterations of ultrastructures and proliferation/differentiation markers revealed that both hyperproliferation and precocious differentiation occurred regionally in the epidermis. These results suggest that the TJ plays a crucial role in maintaining epidermal homeostasis by controlling the Ca 2+ gradient.

  16. DHT deficiency perturbs the integrity of the rat seminiferous epithelium by disrupting tight and adherens junctions.

    Science.gov (United States)

    Kolasa, Agnieszka; Marchlewicz, Mariola; Wenda-Różewicka, Lidia; Wiszniewska, Barbara

    2011-01-01

    In rats with a DHT deficiency induced by finasteride, morphological changes in the seminiferous epithelium were observed. The structural alterations were manifested by the premature germ cells sloughing into the lumen of seminiferous tubules. The etiology of this disorder could be connected with intercellular junctions disintegration. We showed in the immunohistochemical study the changes in expression of some proteins building tight and adherens junctions. The depression of N-cadherin, β-catenin and occludin immunoexpressions could be the reason for the release of immature germ cells from the seminiferous epithelium. However, the observed increase of the immunohistochemical reaction intensity of vinculin, one of the cadherin/catenin complex regulators, could be insufficient to maintain the proper function of adherens junctions. The hormonal imbalance appears to influence the pattern of expression of junctional proteins in the seminiferous epithelium. It could lead to untimely germ cells sloughing, and ultimately could impair fertility.

  17. Tight junctions: a barrier to the initiation and progression of breast cancer?

    LENUS (Irish Health Repository)

    Brennan, Kieran

    2010-01-01

    Breast cancer is a complex and heterogeneous disease that arises from epithelial cells lining the breast ducts and lobules. Correct adhesion between adjacent epithelial cells is important in determining the normal structure and function of epithelial tissues, and there is accumulating evidence that dysregulated cell-cell adhesion is associated with many cancers. This review will focus on one cell-cell adhesion complex, the tight junction (TJ), and summarize recent evidence that TJs may participate in breast cancer development or progression. We will first outline the protein composition of TJs and discuss the functions of the TJ complex. Secondly we will examine how alterations in these functions might facilitate breast cancer initiation or progression; by focussing on the regulatory influence of TJs on cell polarity, cell fate and cell migration. Finally we will outline how pharmacological targeting of TJ proteins may be useful in limiting breast cancer progression. Overall we hope to illustrate that the relationship between TJ alterations and breast cancer is a complex one; but that this area offers promise in uncovering fundamental mechanisms linked to breast cancer progression.

  18. You Shall Not Pass – Tight junctions of the Blood Brain Barrier.

    Directory of Open Access Journals (Sweden)

    Hans-Christian eBauer

    2014-12-01

    Full Text Available Tissue barriers restricting the free diffusion of substances between the central nervous system and the systemic circulation are of great medical interest. Excessive leakage of blood-borne molecules into the parenchyma and the concomitant fluctuations in the microenvironment following a transient breakdown of the blood-brain barrier (BBB during ischemic/hypoxic conditions or due to an autoimmune disease are detrimental to the physiology of nervous tissue.On the other hand, the treatment of neurological disorders is often hampered as only minimal amounts of therapeutic agents are able to penetrate a functional BBB or blood cerebrospinal fluid barrier. At the basis of the BBB are, next to an elaborate transporting machinery, intimate cell-cell contacts (tight junctions creating not only a paracellular diffusion constraint but also enabling the vectorial transport across cell monolayers.More recent findings indicate that functional barriers are already established during development, protecting the fetal brain. As an understanding of the biogenesis of TJs might reveal the underlying mechanisms of barrier formation during ontogenic development numerous in vitro systems have been developed to study the assembly and disassembly of TJs. In addition, monitoring the stage-specific expression of TJ proteins during development has brought much insight into the developmental tightening of tissue barriers. Further, over the last two decades a detailed molecular map of tight junctions has emerged.TJs not only represent a cell-cell adhesion structure, but integrate various signaling pathways, thereby directly or indirectly impacting upon processes such as cell proliferation, cytoskeletal rearrangement, and transcriptional control.This review will provide a brief overview on the establishment of the BBB during embryonic development in mammals and a detailed description of the ultrastructure, biogenesis, and molecular composition of epithelial and endothelial

  19. Autoradiographic studies on the kinetics of fetal supporting cells and wall cells in rats 19 days after conception

    International Nuclear Information System (INIS)

    Lugani-Mehta, S.

    1980-01-01

    The duration of the S-phase of supporting cells and wall cells of rat fetuses aged 19 days was determined by the ''labelled mitosis'' method. The supporting cells are predecessors of the sertoli cells while the wall cells are predecessors of the boundary tissue and, possibly, of part of the peritubular Leydig cell system. The S-phase of the supporting cells was found to last 10.1 h while the S-phase of the wall cells lasted 9.2 h. The data were not in agreement with the data of other authors. (orig./MG) [de

  20. Estrogen decreases tight junction protein ZO-1 expression in human primary gut tissues.

    Science.gov (United States)

    Zhou, Zejun; Zhang, Lumin; Ding, Miao; Luo, Zhenwu; Yuan, Shao; Bansal, Meena B; Gilkeson, Gary; Lang, Ren; Jiang, Wei

    2017-10-01

    Females have a higher prevalence of most autoimmune diseases; however, the mechanism is unknown. In this study, we examined the expression of tight junction protein zonula occludens 1 (ZO-1) and estrogen receptor (ER)-α/β in human primary gut tissues by immunohistochemistry, immunofluorescence and qPCR. The expression of ZO-1 and ER-β but not ER-α was present in both male and female gut tissues. There was no sex difference in ER-β expression, but ZO-1 expression was decreased in females compared to males. In vitro, estrogen treatment decreased ZO-1 mRNA and protein expression, ZO-1 promoter activity, IL-6 production, and NF-κB activation in human primary gut tissues or the Caco-2 cells, but increased the ER-β expression in Caco-2 cells. Consistently, plasma IL-6 levels in females were reduced relative to males in vivo. Our finding indicates that estrogen may play a role in gut tight junction expression and permeability. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Cellular entry of G3.5 poly (amido amine) dendrimers by clathrin- and dynamin-dependent endocytosis promotes tight junctional opening in intestinal epithelia.

    Science.gov (United States)

    Goldberg, Deborah S; Ghandehari, Hamidreza; Swaan, Peter W

    2010-08-01

    This study investigates the mechanisms of G3.5 poly (amido amine) dendrimer cellular uptake, intracellular trafficking, transepithelial transport and tight junction modulation in Caco-2 cells in the context of oral drug delivery. Chemical inhibitors blocking clathrin-, caveolin- and dynamin-dependent endocytosis pathways were used to investigate the mechanisms of dendrimer cellular uptake and transport across Caco-2 cells using flow cytometry and confocal microscopy. Dendrimer cellular uptake was found to be dynamin-dependent and was reduced by both clathrin and caveolin endocytosis inhibitors, while transepithelial transport was only dependent on dynamin- and clathrin-mediated endocytosis. Dendrimers were quickly trafficked to the lysosomes after 15 min of incubation and showed increased endosomal accumulation at later time points, suggesting saturation of this pathway. Dendrimers were unable to open tight junctions in cell monolayers treated with dynasore, a selective inhibitor of dynamin, confirming that dendrimer internalization promotes tight junction modulation. G3.5 PAMAM dendrimers take advantage of several receptor-mediated endocytosis pathways for cellular entry in Caco-2 cells. Dendrimer internalization by dynamin-dependent mechanisms promotes tight junction opening, suggesting that dendrimers act on intracellular cytoskeletal proteins to modulate tight junctions, thus catalyzing their own transport via the paracellular route.

  2. Flow and Transport in Tight and Shale Formations: A Review

    KAUST Repository

    Salama, Amgad

    2017-09-18

    A review on the recent advances of the flow and transport phenomena in tight and shale formations is presented in this work. Exploration of oil and gas in resources that were once considered inaccessible opened the door to highlight interesting phenomena that require attention and understanding. The length scales associated with transport phenomena in tight and shale formations are rich. From nanoscale phenomena to field-scale applications, a unified frame that is able to encounter the varieties of phenomena associated with each scale may not be possible. Each scale has its own tools and limitations that may not, probably, be suitable at other scales. Multiscale algorithms that effectively couple simulations among various scales of porous media are therefore important. In this article, a review of the different length scales and the tools associated with each scale is introduced. Highlights on the different phenomena pertinent to each scale are summarized. Furthermore, the governing equations describing flow and transport phenomena at different scales are investigated. In addition, methods to solve these equations using numerical techniques are introduced. Cross-scale analysis and derivation of linear and nonlinear Darcy\\'s scale laws from pore-scale governing equations are described. Phenomena occurring at molecular scales and their thermodynamics are discussed. Flow slippage at the nanosize pores and its upscaling to Darcy\\'s scale are highlighted. Pore network models are discussed as a viable tool to estimate macroscopic parameters that are otherwise difficult to measure. Then, the environmental aspects associated with the different technologies used in stimulating the gas stored in tight and shale formations are briefly discussed.

  3. Flow and Transport in Tight and Shale Formations: A Review

    KAUST Repository

    Salama, Amgad; El-Amin, Mohamed; Kumar, Kundan; Sun, Shuyu

    2017-01-01

    A review on the recent advances of the flow and transport phenomena in tight and shale formations is presented in this work. Exploration of oil and gas in resources that were once considered inaccessible opened the door to highlight interesting phenomena that require attention and understanding. The length scales associated with transport phenomena in tight and shale formations are rich. From nanoscale phenomena to field-scale applications, a unified frame that is able to encounter the varieties of phenomena associated with each scale may not be possible. Each scale has its own tools and limitations that may not, probably, be suitable at other scales. Multiscale algorithms that effectively couple simulations among various scales of porous media are therefore important. In this article, a review of the different length scales and the tools associated with each scale is introduced. Highlights on the different phenomena pertinent to each scale are summarized. Furthermore, the governing equations describing flow and transport phenomena at different scales are investigated. In addition, methods to solve these equations using numerical techniques are introduced. Cross-scale analysis and derivation of linear and nonlinear Darcy's scale laws from pore-scale governing equations are described. Phenomena occurring at molecular scales and their thermodynamics are discussed. Flow slippage at the nanosize pores and its upscaling to Darcy's scale are highlighted. Pore network models are discussed as a viable tool to estimate macroscopic parameters that are otherwise difficult to measure. Then, the environmental aspects associated with the different technologies used in stimulating the gas stored in tight and shale formations are briefly discussed.

  4. Intestinal epithelial barrier function and tight junction proteins with heat and exercise

    DEFF Research Database (Denmark)

    Dokladny, Karol; Zuhl, Micah N; Moseley, Pope L

    2016-01-01

    A single layer of enterocytes and tight junctions (intercellular multiprotein complexes) form the intestinal epithelial barrier that controls transport of molecules through transcellular and paracellular pathways. A dysfunctional or "leaky" intestinal tight junction barrier allows augmented perme...

  5. Tight focusing of radially polarized circular Airy vortex beams

    Science.gov (United States)

    Chen, Musheng; Huang, Sujuan; Shao, Wei

    2017-11-01

    Tight focusing properties of radially polarized circular Airy vortex beams (CAVB) are studied numerically. The light field expressions for the focused fields are derived based on vectorial Debye theory. We also study the relationship between focal profiles, such as light intensity distribution, radius of focal spot and focal length, and the parameters of CAVB. Numerical results demonstrate that we can generate a radially polarized CAVB with super-long focal length, super-strong longitudinal intensity or subwavelength focused spot at the focal plane by properly choosing the parameters of incident light and high numerical aperture (NA) lens. These results have potential applications for optical trapping, optical storage and particle acceleration.

  6. Tight-Binding Parametrization for Photonic Band Gap Materials

    International Nuclear Information System (INIS)

    Lidorikis, E.; Sigalas, M.M.; Soukoulis, C.M.; Economou, E.N.; Soukoulis, C.M.

    1998-01-01

    The idea of the linear combination of atomic orbitals method, well known from the study of electrons, is extended to the classical wave case. The Mie resonances of the isolated scatterer in the classical wave case are analogous to the atomic orbitals in the electronic case. The matrix elements of the two-dimensional tight-binding (TB) Hamiltonian are obtained by fitting to ab initio results. The transferability of the TB model is tested by reproducing accurately the band structure of different 2D lattices, with and without defects, and at two different dielectric contrasts. copyright 1998 The American Physical Society

  7. Tight Bound on Randomness for Violating the CHSH Inequality

    OpenAIRE

    Teng, Yifeng; Yang, Shenghao; Wang, Siwei; Zhao, Mingfei

    2015-01-01

    Free will (or randomness) has been studied to achieve loophole-free Bell's inequality test and to provide device-independent quantum key distribution security proofs. The required randomness such that a local hidden variable model (LHVM) can violate the Clauser-Horne-Shimony-Holt (CHSH) inequality has been studied, but a tight bound has not been proved for a practical case that i) the device settings of the two parties in the Bell test are independent; and ii) the device settings of each part...

  8. Quantum correlations are tightly bound by the exclusivity principle.

    Science.gov (United States)

    Yan, Bin

    2013-06-28

    It is a fundamental problem in physics of what principle limits the correlations as predicted by our current description of nature, based on quantum mechanics. One possible explanation is the "global exclusivity" principle recently discussed in Phys. Rev. Lett. 110, 060402 (2013). In this work we show that this principle actually has a much stronger restriction on the probability distribution. We provide a tight constraint inequality imposed by this principle and prove that this principle singles out quantum correlations in scenarios represented by any graph. Our result implies that the exclusivity principle might be one of the fundamental principles of nature.

  9. Tight glycemic control in the ICU - is the earth flat?

    Science.gov (United States)

    Steil, Garry M; Agus, Michael S D

    2014-06-27

    Tight glycemic control in the ICU has been shown to reduce mortality in some but not all prospective randomized control trials. Confounding the interpretation of these studies are differences in how the control was achieved and underlying incidence of hypoglycemia, which can be expected to be affected by the introduction of continuous glucose monitoring (CGM). In this issue of Critical Care, a consensus panel provides a list of the research priorities they believe are needed for CGM to become routine practice in the ICU. We reflect on these recommendations and consider the implications for using CGM today.

  10. Containment leak-tightness enhancement at VVER 440 NPPs

    International Nuclear Information System (INIS)

    Prandorfy, M.

    2001-01-01

    The hermetic compartments of VVER 440 NPPs fulfil the function of the containment used at NPPs all over the word. The purpose of the containment is to protect the NPP personal against radioactive impact as well as to prevent radioactive leakage to the environment during a lost of coolant accident. Leak-tightness enhancement in NPPs with VVER 440/213 and VVER 440/230 reactors is an important safety issue. New procedures, measures and methods were adopted at NPPs in Mochovce, J. Bohunice, Dukovany and Paks for leak identification and sealing works performed by VUEZ Levice. (authors)

  11. Tight aspect ratio tokamak power reactor with superconducting TF coils

    International Nuclear Information System (INIS)

    Nishio, S.; Tobita, K.; Konishi, S.; Ando, T.; Hiroki, S.; Kuroda, T.; Yamauchi, M.; Azumi, M.; Nagata, M.

    2003-01-01

    Tight aspect ratio tokamak power reactor with super-conducting toroidal field (TF) coils has been proposed. A center solenoid coil system and an inboard blanket were discarded. The key point was how to find the engineering design solution of the TF coil system with the high field and high current density. The coil system with the center post radius of less than 1 m can generate the maximum field of ∼ 20 T. This coil system causes a compact reactor concept, where the plasma major and minor radii of 3.75 m and 1.9 m, respectively and the fusion power of 1.8 GW. (author)

  12. OLIFE: Tight Binding Code for Transmission Coefficient Calculation

    Science.gov (United States)

    Mijbil, Zainelabideen Yousif

    2018-05-01

    A new and human friendly transport calculation code has been developed. It requires a simple tight binding Hamiltonian as the only input file and uses a convenient graphical user interface to control calculations. The effect of magnetic field on junction has also been included. Furthermore the transmission coefficient can be calculated between any two points on the scatterer which ensures high flexibility to check the system. Therefore Olife can highly be recommended as an essential tool for pretesting studying and teaching electron transport in molecular devices that saves a lot of time and effort.

  13. Containment leak-tightness enhancement at VVER 440 NPPs

    International Nuclear Information System (INIS)

    Prandorfy, M.

    2000-01-01

    The hermetic compartments of WWER 440 NPPs fulfil the function of the containment used at NPPs all over the world. The purpose of the containment is to protect the NPP personnel against radioactive impact as well as to prevent radioactive leakage to the. environ ent during a lost of coolant accident. Leak-tightness enhancement in NPPs with WWER 440/213 and WWER 440/230 reactors is an important safety issue. New procedures, measures and methods were adopted at NPPs in Mochovce, Jaslovske Bohunice, Dukovany and PAKS for leak identification and sealing works performed by VUEZ Levice. (authors)

  14. Comparative testing of women's tights, which are realized in the Ukrainian market

    OpenAIRE

    Мартосенко, Марина Григорьевна; Браилко, Анна Сергеевна

    2015-01-01

    Assortment of women's tights represented on the Ukrainian market is diverse: medical and corrective tights, classic thin and warm, simple and exclusive, ornamental and sports, for pregnant women and moisturizing effect. The size, density, pattern, material composition, visual appearance, matching fashion trends, colors, pricing policy – all these are criteria for the selection of women's tights.With such huge and diverse range of women's tights in the Ukrainian market, the problem of quality ...

  15. Is the FSHR 2039A>G variant associated with susceptibility to testicular germ cell cancer?

    DEFF Research Database (Denmark)

    Bang, A K; Busch, A S; Almstrup, K

    2018-01-01

    Testicular germ cell cancer (TGCC) is derived from germ cell neoplasia in situ (GCNIS), which arises due to niche disturbances affecting the Sertoli cells. It is believed that exogenous endocrine factors have a crucial role in governing neoplastic transformation but on a strong hereditary...... background. Follicle-stimulating hormone (FSH) is the major regulatory hormone of the Sertoli cells. FSH signalling-related single-nucleotide polymorphisms (SNPs) have previously been shown to affect FSH action in men at different levels. We aimed to investigate whether three FSH-related SNPs (FSHR 2039A......>G, FSHR -29G>A and FSHB -211G>T) are associated with development of TGCC. A total of 752 Danish and German patients with TGCC from two tertiary andrological referral centres were included. Three control groups comprising 2020 men from the general population, 679 fertile men and 417 infertile men, were...

  16. Tight-binding tunneling amplitude of an optical lattice

    International Nuclear Information System (INIS)

    Arzamasovs, Maksims; Liu, Bo

    2017-01-01

    The particle in a periodic potential is an important topic in an undergraduate quantum mechanics curriculum and a stepping stone on the way to more advanced topics, such as courses on interacting electrons in crystalline solids, and graduate-level research in solid-state and condensed matter physics. The interacting many-body phenomena are usually described in terms of the second quantized lattice Hamiltonians which treat single-particle physics on the level of tight-binding approximation and add interactions on top of it. The aim of this paper is to show how the tight-binding tunneling amplitude can be related to the strength of the periodic potential for the case of a cosine potential used in the burgeoning field of ultracold atoms. We show how to approach the problem of computing the tunneling amplitude of a deep lattice using the JWKB (Jeffreys–Wentzel–Kramers–Brillouin, also known as semiclassical) approximation. We also point out that care should be taken when applying the method of the linear combination of atomic orbitals (LCAO) in an optical lattice context. A summary of the exact solution in terms of Mathieu functions is also given. (paper)

  17. Tight-binding tunneling amplitude of an optical lattice

    Science.gov (United States)

    Arzamasovs, Maksims; Liu, Bo

    2017-11-01

    The particle in a periodic potential is an important topic in an undergraduate quantum mechanics curriculum and a stepping stone on the way to more advanced topics, such as courses on interacting electrons in crystalline solids, and graduate-level research in solid-state and condensed matter physics. The interacting many-body phenomena are usually described in terms of the second quantized lattice Hamiltonians which treat single-particle physics on the level of tight-binding approximation and add interactions on top of it. The aim of this paper is to show how the tight-binding tunneling amplitude can be related to the strength of the periodic potential for the case of a cosine potential used in the burgeoning field of ultracold atoms. We show how to approach the problem of computing the tunneling amplitude of a deep lattice using the JWKB (Jeffreys-Wentzel-Kramers-Brillouin, also known as semiclassical) approximation. We also point out that care should be taken when applying the method of the linear combination of atomic orbitals (LCAO) in an optical lattice context. A summary of the exact solution in terms of Mathieu functions is also given.

  18. Maintaining leak tightness capability of Caorso BWR containment

    International Nuclear Information System (INIS)

    Barsanti, P.; Di Palo, L.; Grimaldi, G.

    1988-01-01

    In 1987 the local leak rate test (LLRT) results of the primary containment were revised, with the following main goals: to highlight recurring problems, leading to lack of leak tightness of the primary containment; to individuate the pertinent degradation mechanisms; to assess the corrective actions already implemented and to plan further improvements, if necessary; and to optimize the preventive maintenance program on the containment, particularly the inspection frequency. All LLRTs in the past operating period, both before (as found) and after (as left) maintenance were analyzed, in terms of leakage rate and equivalent area of leak, for each penetration. Corrective actions already implemented included replacement of some valves with better quality type one, passivation of the carbon steel pipes and improvement of the pertinent surveillance procedures. Long term corrective actions, now under consideration, will include the following: more extensive passivation of pipes, carrying humid air, so that oxidation could be drastically reduced; better chemistry control in fluid systems; extensive replacement of the butterfly valves presently used; implementation of the LLRT practice, such to quantitatively measure the leakage rate, also in presence of large leak; and reduction of the time interval between periodical tests, on the basis of the results of the previous ones. Following these guidelines, future overall leakage tests would be performed in as found condition, aimed to verify the effectiveness of the entire maintenance and testing program of the primary containment and of its capability to maintain leak tightness during the time between two subsequent tests

  19. Adaptive wavelet tight frame construction for accelerating MRI reconstruction

    Directory of Open Access Journals (Sweden)

    Genjiao Zhou

    2017-09-01

    Full Text Available The sparsity regularization approach, which assumes that the image of interest is likely to have sparse representation in some transform domain, has been an active research area in image processing and medical image reconstruction. Although various sparsifying transforms have been used in medical image reconstruction such as wavelet, contourlet, and total variation (TV etc., the efficiency of these transforms typically rely on the special structure of the underlying image. A better way to address this issue is to develop an overcomplete dictionary from the input data in order to get a better sparsifying transform for the underlying image. However, the general overcomplete dictionaries do not satisfy the so-called perfect reconstruction property which ensures that the given signal can be perfectly represented by its canonical coefficients in a manner similar to orthonormal bases, resulting in time consuming in the iterative image reconstruction. This work is to develop an adaptive wavelet tight frame method for magnetic resonance image reconstruction. The proposed scheme incorporates the adaptive wavelet tight frame approach into the magnetic resonance image reconstruction by solving a l0-regularized minimization problem. Numerical results show that the proposed approach provides significant time savings as compared to the over-complete dictionary based methods with comparable performance in terms of both peak signal-to-noise ratio and subjective visual quality.

  20. Expanding to teleoperation of a tight modular workshop for dismantling radioactive components

    International Nuclear Information System (INIS)

    Gasc, B.

    1990-01-01

    The CEA (French Nuclear Energy Commission) in connection with TECHNICATOME developed a tight modular workshop for the dismantling of AT1 plant facilities in LA HAGUE. This workshop constructed of reusable stainless steel panels assembled by bolting provides a tight and decontaminable working zone compatible with any building configuration. This being the case, the operators bearing ventilated suits may work under the best safety conditions on alpha-contaminated materials. For the purpose of expanding the working capacities of this workshop it was decided to develop special components for teleoperation from the outside as in a conventional cell. To meet this objective which is within the scope of the contract signed with the CEC, the following components were developed and constructed: - manipulator holder panel, - swivelling hatch panel, - wall equipment sealed transfer device and, - modular biological protection. The design, construction and tests of these new components led to their qualification and further incorporation in the list of components of the modular workshop liable to be used for teleoperation procedures

  1. Revenue Risk of U.S. Tight-Oil Firms

    Directory of Open Access Journals (Sweden)

    Luis Mª Abadie

    2016-10-01

    Full Text Available American U.S. crude oil prices have dropped significantly of late down to a low of less than $30 a barrel in early 2016. At the same time price volatility has increased and crude in storage has reached record amounts in the U.S. America. Low oil prices in particular pose quite a challenge for the survival of U.S. America’s tight-oil industry. In this paper we assess the current profitability and future prospects of this industry. The question could be broadly stated as: should producers stop operation immediately or continue in the hope that prices will rise in the medium term? Our assessment is based on a stochastic volatility model with three risk factors, namely the oil spot price, the long-term oil price, and the spot price volatility; we allow for these sources of risk to be correlated and display mean reversion. We then use information from spot and futures West Texas Intermediate (WTI oil prices to estimate this model. Our aim is to show how the development of the oil price in the future may affect the prospective revenues of firms and hence their operation decisions at present. With the numerical estimates of the model’s parameters we can compute the value of an operating tight-oil field over a certain time horizon. Thus, the present value (PV of the prospective revenues up to ten years from now is $37.07/bbl in the base case. Consequently, provided that the cost of producing a barrel of oil is less than $37.07 production from an operating field would make economic sense. Obviously this is just a point estimate. We further perform a Monte Carlo (MC simulation to derive the risk profile of this activity and calculate two standard measures of risk, namely the value at risk (VaR and the expected shortfall (ES (for a given confidence level. In this sense, the PV of the prospective revenues will fall below $22.22/bbl in the worst 5% of the cases; and the average value across these worst scenarios is $19.77/bbl. Last we undertake two

  2. Approximate equiangular tight frames for compressed sensing and CDMA applications

    Science.gov (United States)

    Tsiligianni, Evaggelia; Kondi, Lisimachos P.; Katsaggelos, Aggelos K.

    2017-12-01

    Performance guarantees for recovery algorithms employed in sparse representations, and compressed sensing highlights the importance of incoherence. Optimal bounds of incoherence are attained by equiangular unit norm tight frames (ETFs). Although ETFs are important in many applications, they do not exist for all dimensions, while their construction has been proven extremely difficult. In this paper, we construct frames that are close to ETFs. According to results from frame and graph theory, the existence of an ETF depends on the existence of its signature matrix, that is, a symmetric matrix with certain structure and spectrum consisting of two distinct eigenvalues. We view the construction of a signature matrix as an inverse eigenvalue problem and propose a method that produces frames of any dimensions that are close to ETFs. Due to the achieved equiangularity property, the so obtained frames can be employed as spreading sequences in synchronous code-division multiple access (s-CDMA) systems, besides compressed sensing.

  3. Crude oil prices: Are our oil markets too tight?

    International Nuclear Information System (INIS)

    Simmons, M.R.

    1997-01-01

    The answer to the question posed in the title is that tightness in the market will surely prevail through 1997. And as discussed herein, with worldwide demand expected to continue to grow, there will be a strong call on extra oil supply. Meeting those demands, however, will not be straightforward--as many observers wrongly believe--considering the industry's practice of maintaining crude stocks at ''Just in time'' inventory levels. Further, impact will be felt from the growing rig shortage, particularly for deepwater units, and down-stream capacity limits. While these factors indicate 1997 should be another good year for the service industry, it is difficult to get any kind of consensus view from the oil price market. With most observers' information dominated by the rarely optimistic futures price of crude, as reflected by the NYMEX, the important fact is that oil prices have remained stable for three years and increased steadily through 1996

  4. The tightly bound nuclei in the liquid drop model

    Science.gov (United States)

    Sree Harsha, N. R.

    2018-05-01

    In this paper, we shall maximise the binding energy per nucleon function in the semi-empirical mass formula of the liquid drop model of the atomic nuclei to analytically prove that the mean binding energy per nucleon curve has local extrema at A ≈ 58.6960, Z ≈ 26.3908 and at A ≈ 62.0178, Z ≈ 27.7506. The Lagrange method of multipliers is used to arrive at these results, while we have let the values of A and Z take continuous fractional values. The shell model that shows why 62Ni is the most tightly bound nucleus is outlined. A brief account on stellar nucleosynthesis is presented to show why 56Fe is more abundant than 62Ni and 58Fe. We believe that the analytical proof presented in this paper can be a useful tool to the instructors to introduce the nucleus with the highest mean binding energy per nucleon.

  5. Critical heat flux in tubes and tight hexagonal rod lattices

    International Nuclear Information System (INIS)

    Erbacher, F.J.; Cheng Xu; Zeggel, W.

    1994-01-01

    The critical heat flux (CHF) in small-diameter tubes and in tight hexagonal 7-rod and 37-rod bundles was investigated in the KRISTA test facility, using Freon 12 as the working fluid. The measurements in tubes showed that the influence of the tube diameter on CHF cannot be described as suggested by earlier publications with sufficient accuracy. CHF in bundles is lower than in tubes under comparable conditions. The influence of spacers (grid spacers, wire wraps) on CHF was found to be governed by local steam qualities. A comparison of the test results with some CHF prediction methods showed that the look-up table method reproduces the test results in circular tubes most accurately. Combined with CHF look-up tables, subchannel analysis and Ahmad's fluid-to-fluid scaling law, Freon experiments have proven to be a suitable tool for CHF prediction in water-cooled rod bundles. (orig.) [de

  6. Tight junction proteins contribute to barrier properties in human pleura.

    Science.gov (United States)

    Markov, Alexander G; Voronkova, Maria A; Volgin, George N; Yablonsky, Piotr K; Fromm, Michael; Amasheh, Salah

    2011-03-15

    The permeability of pleural mesothelium helps to control the volume and composition of the liquid lubricating pleural surfaces. Information on pleural barrier function in health and disease, however, is scarce. Tissue specimens of human pleura were mounted in Ussing chambers for measurement of transmesothelial resistance. Expression of tight junction (TJ) proteins was studied by Western blots and immune fluorescence confocal microscopy. Both visceral and parietal pleura showed barrier properties represented by transmesothelial resistance. Occludin, claudin-1, -3, -5, and -7, were detected in visceral pleura. In parietal pleura, the same TJ proteins were detected, except claudin-7. In tissues from patients with pleural inflammation these tightening claudins were decreased and in visceral pleura claudin-2, a paracellular channel former, became apparent. We report that barrier function in human pleura coincides with expression of claudins known to be key determinants of epithelial barrier properties. In inflamed tissue, claudin expression indicates a reduced barrier function. Copyright © 2010 Elsevier B.V. All rights reserved.

  7. Laser material processing with tightly focused cylindrical vector beams

    Energy Technology Data Exchange (ETDEWEB)

    Drevinskas, Rokas, E-mail: rd1c12@soton.ac.uk; Zhang, Jingyu; Beresna, Martynas; Gecevičius, Mindaugas; Kazansky, Peter G. [Optoelectronics Research Centre, University of Southampton, Southampton SO17 1BJ (United Kingdom); Kazanskii, Andrey G. [Physics Department, M.V. Lomonosov Moscow State University, Moscow 119991 (Russian Federation); Svirko, Yuri P. [Physics Department, M.V. Lomonosov Moscow State University, Moscow 119991 (Russian Federation); Institute of Photonics, University of Eastern Finland, P.O.BOX 111, FI-80101 Joensuu (Finland)

    2016-05-30

    We demonstrate a comprehensive modification study of silica glass, crystalline silicon, and amorphous silicon film, irradiated by tightly focused cylindrical vector beams with azimuthal and radial polarizations. The evidence of the longitudinal field associated with radial polarization is revealed by second harmonic generation in z-cut lithium niobate crystal. Despite the lower threshold of ring-shaped modification of silicon materials, the modification in the center of single pulse radially polarized beam is not observed. The phenomenon is interpreted in terms of the enhanced reflection of longitudinal component at the interface with high-index contrast, demonstrating that the longitudinal component is inefficient for the flat surface modification. Enhanced interaction of the longitudinal light field with silicon nanopillar structures produced by the first pulse of double-pulse irradiation is also demonstrated.

  8. Tightly Coupled Multiphysics Algorithm for Pebble Bed Reactors

    International Nuclear Information System (INIS)

    Park, HyeongKae; Knoll, Dana; Gaston, Derek; Martineau, Richard

    2010-01-01

    We have developed a tightly coupled multiphysics simulation tool for the pebble-bed reactor (PBR) concept, a type of Very High-Temperature gas-cooled Reactor (VHTR). The simulation tool, PRONGHORN, takes advantages of the Multiphysics Object-Oriented Simulation Environment library, and is capable of solving multidimensional thermal-fluid and neutronics problems implicitly with a Newton-based approach. Expensive Jacobian matrix formation is alleviated via the Jacobian-free Newton-Krylov method, and physics-based preconditioning is applied to minimize Krylov iterations. Motivation for the work is provided via analysis and numerical experiments on simpler multiphysics reactor models. We then provide detail of the physical models and numerical methods in PRONGHORN. Finally, PRONGHORN's algorithmic capability is demonstrated on a number of PBR test cases.

  9. Tightly coupled transient analysis of EBR-II

    International Nuclear Information System (INIS)

    Makowitz, H.; Lehto, W.K.; Sackett, J.I.

    1988-01-01

    A Tightly Coupled transient analysis system for the Experimental Breeder Reactor-II (EBR-II) is currently being tested. The system consists of a faster than real time high fidelity reactor simulation, advanced graphics displays, expert system coupling, and real time data coupling via the EBR-II data acquisition system to and from the plant and the control system. The base, first generation software has been developed and is presently being tested. Various subsystem couplings and the total system integration are being checked out. This system should enhance the diagnostic and prognostic capability of EBR-II in the near term and provide automatic control during startup and power maneuvering in the future, as well as serve as a testbed for new control system development for advanced reactors

  10. Efficient self-consistency for magnetic tight binding

    Science.gov (United States)

    Soin, Preetma; Horsfield, A. P.; Nguyen-Manh, D.

    2011-06-01

    Tight binding can be extended to magnetic systems by including an exchange interaction on an atomic site that favours net spin polarisation. We have used a published model, extended to include long-ranged Coulomb interactions, to study defects in iron. We have found that achieving self-consistency using conventional techniques was either unstable or very slow. By formulating the problem of achieving charge and spin self-consistency as a search for stationary points of a Harris-Foulkes functional, extended to include spin, we have derived a much more efficient scheme based on a Newton-Raphson procedure. We demonstrate the capabilities of our method by looking at vacancies and self-interstitials in iron. Self-consistency can indeed be achieved in a more efficient and stable manner, but care needs to be taken to manage this. The algorithm is implemented in the code PLATO. Program summaryProgram title:PLATO Catalogue identifier: AEFC_v2_0 Program summary URL:http://cpc.cs.qub.ac.uk/summaries/AEFC_v2_0.html Program obtainable from: CPC Program Library, Queen's University, Belfast, N. Ireland Licensing provisions: Standard CPC licence, http://cpc.cs.qub.ac.uk/licence/licence.html No. of lines in distributed program, including test data, etc.: 228 747 No. of bytes in distributed program, including test data, etc.: 1 880 369 Distribution format: tar.gz Programming language: C and PERL Computer: Apple Macintosh, PC, Unix machines Operating system: Unix, Linux, Mac OS X, Windows XP Has the code been vectorised or parallelised?: Yes. Up to 256 processors tested RAM: Up to 2 Gbytes per processor Classification: 7.3 External routines: LAPACK, BLAS and optionally ScaLAPACK, BLACS, PBLAS, FFTW Catalogue identifier of previous version: AEFC_v1_0 Journal reference of previous version: Comput. Phys. Comm. 180 (2009) 2616 Does the new version supersede the previous version?: Yes Nature of problem: Achieving charge and spin self-consistency in magnetic tight binding can be very

  11. Zonulin, regulation of tight junctions, and autoimmune diseases.

    Science.gov (United States)

    Fasano, Alessio

    2012-07-01

    Recent studies indicate that besides digestion and absorption of nutrients and water and electrolytes homeostasis, another key function of the intestine is to regulate the trafficking of environmental antigens across the host mucosal barrier. Intestinal tight junctions (TJs) create gradients for the optimal absorption and transport of nutrients and control the balance between tolerance and immunity to nonself antigens. To meet diverse physiological challenges, intestinal epithelial TJs must be modified rapidly and in a coordinated fashion by regulatory systems that orchestrate the state of assembly of the TJ multiprotein network. While considerable knowledge exists about TJ ultrastructure, relatively little is known about their physiological and pathophysiological regulation. Our discovery of zonulin, the only known physiologic modulator of intercellular TJs described so far, has increased our understanding of the intricate mechanisms that regulate the intestinal epithelial paracellular pathway and has led us to appreciate that its upregulation in genetically susceptible individuals leads to autoimmune diseases. © 2012 New York Academy of Sciences.

  12. Economic evaluation on tight sandstone gas development projects in China and recommendation on fiscal and taxation support policies

    OpenAIRE

    Zhen Yang; Lingfeng Kong; Min Du; Chenhui Zhao

    2016-01-01

    China is rich in tight sandstone gas resources (“tight gas” for short). For example, the Sulige Gasfield in the Ordos Basin and the Upper Triassic Xujiahe Fm gas reservoir in the Sichuan Basin are typical tight gas reservoirs. In the past decade, tight gas reserve and production both have increased rapidly in China, but tight gas reservoirs are always managed as conventional gas reservoirs without effective fiscal, taxation and policy supports. The potential of sustainable tight gas productio...

  13. Coalbed methane and tight gas no longer unconventional resources

    International Nuclear Information System (INIS)

    Gatens, M.

    2006-01-01

    Unconventional gas refers to natural gas contained in difficult-to-produce formations that require special drilling and completion techniques to achieve commercial production. It includes tight gas, coal seams, organic shales, and gas hydrates. Canada's vast unconventional gas resource is becoming an increasingly important part of the country's gas supply. The emergence of unconventional gas production in Canada over the past several years has made the unconventional increasingly conventional in terms of industry activity. It was suggested that in order to realize the potential for unconventional gas in Canada, all stakeholders should engage to ensure the development is environmentally responsible. Unconventional gas accounts for nearly one third of U.S. gas production. It also accounts for nearly 5 Bcf per day and growing. The impetus to this sudden growth has been the gradual and increasing contribution of tight sands and limes to Canadian production, which accounts for more than 4 Bcf per day. Coalbed methane (CBM) is at 0.5 Bcf per day and growing. In response to expectations that CBM will reach 2 to 3 Bcf per day over the next 2 decades, Canadian producers are placing more emphasis on unconventional resource plays, including organic shales and gas hydrates. As such, significant growth of unconventional gas is anticipated. This growth will be facilitated by the adoption of U.S..-developed technologies and new Canadian technologies. It was suggested that research and development will be key to unlocking the unconventional gas potential. It was also suggested that the already existing, strong regulatory structure should continue in order to accommodate this growth in a sustainable manner. figs

  14. Tight-binding molecular dynamics simulation of charge state effects in semiconductors

    CERN Document Server

    Khakimov, Z M; Sulaymonov, N T; Kiv, A E; Levin, A A

    2002-01-01

    New model of Si-H bond dissociation has been proposed and tested in the cluster Si sub 1 sub 0 H sub 1 sub 6 by the simulation approach that combines classical molecular dynamics method and the self-consistent tight-binding electronic and total energy calculation one. It is shown that the monohydride Si-H bond is unstable with respect to formation of silicon dangling bond and bend bridge Si-H-Si bond when this cluster traps the single positive charge. In this case hydrogen atom migrates rather rotating around Si-Si bond than crossing the center of this bond (the bond-centered position). The model can be useful for understanding hydrogen related phenomena at surfaces, interfaces, internal voids of various hydrogenated silicon systems: electronic devices, silicon solar cells, and nanocrystalline and porous silicon. (author)

  15. Effects of Tight Versus Non Tight Control of Metabolic Acidosis on Early Renal Function After Kidney Transplantation

    Directory of Open Access Journals (Sweden)

    Farhad Etezadi

    2012-09-01

    Full Text Available Background Recently, several studies have been conducted to determine the optimal strategy for intraoperative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods:120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE [less than or equal to] 15 mEq/L or bicarbonate [less than or equal to] 10 mEq/L or PH [less than or equal to] 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results:In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion:Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

  16. Effects of tight versus non tight control of metabolic acidosis on early renal function after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Etezadi Farhad

    2012-09-01

    Full Text Available Abstract Background Recently, several studies have been conducted to determine the optimal strategy for intra-operative fluid replacement therapy in renal transplantation surgery. Since infusion of sodium bicarbonate as a buffer seems to be safer than other buffer compounds (lactate, gluconate, acetatethat indirectly convert into it within the liver, We hypothesized tight control of metabolic acidosis by infusion of sodium bicarbonate may improve early post-operative renal function in renal transplant recipients. Methods 120 patients were randomly divided into two equal groups. In group A, bicarbonate was infused intra-operatively according to Base Excess (BE measurements to achieve the normal values of BE (−5 to +5 mEq/L. In group B, infusion of bicarbonate was allowed only in case of severe metabolic acidosis (BE ≤ −15 mEq/L or bicarbonate ≤ 10 mEq/L or PH ≤ 7.15. Minute ventilation was adjusted to keep PaCO2 within the normal range. Primary end-point was sampling of serum creatinine level in first, second, third and seventh post-operative days for statistical comparison between groups. Secondary objectives were comparison of cumulative urine volumes in the first 24 h of post-operative period and serum BUN levels which were obtained in first, second, third and seventh post-operative days. Results In group A, all of consecutive serum creatinine levels were significantly lower in comparison with group B. With regard to secondary outcomes, no significant difference between groups was observed. Conclusion Intra-operative tight control of metabolic acidosis by infusion of Sodium Bicarbonate in renal transplant recipients may improve early post-operative renal function.

  17. Vector fields in a tight laser focus: comparison of models.

    Science.gov (United States)

    Peatross, Justin; Berrondo, Manuel; Smith, Dallas; Ware, Michael

    2017-06-26

    We assess several widely used vector models of a Gaussian laser beam in the context of more accurate vector diffraction integration. For the analysis, we present a streamlined derivation of the vector fields of a uniformly polarized beam reflected from an ideal parabolic mirror, both inside and outside of the resulting focus. This exact solution to Maxwell's equations, first developed in 1920 by V. S. Ignatovsky, is highly relevant to high-intensity laser experiments since the boundary conditions at a focusing optic dictate the form of the focus in a manner analogous to a physical experiment. In contrast, many models simply assume a field profile near the focus and develop the surrounding vector fields consistent with Maxwell's equations. In comparing the Ignatovsky result with popular closed-form analytic vector models of a Gaussian beam, we find that the relatively simple model developed by Erikson and Singh in 1994 provides good agreement in the paraxial limit. Models involving a Lax expansion introduce a divergences outside of the focus while providing little if any improvement in the focal region. Extremely tight focusing produces a somewhat complicated structure in the focus, and requires the Ignatovsky model for accurate representation.

  18. Fuel assembly leak tightness control on WWER-1000 reactor

    International Nuclear Information System (INIS)

    Ivanova, R.; Gerchev, N.; Mateev, A.

    2001-01-01

    The main index for integrity of the fuel rods cladding is the specific activity value of the primary coolant. This value determines the safe operation of the reactor. The limit for safe operation of WWER-1000 reactor is the value of the total activity of Iodine isotopes in the primary coolant 5.0x10 -3 Ci/l. The paper briefly describes the methodology for performing a fuel tightness test (sipping test) and shows the results from these tests performed during the period 1987 -1999 in units 5 and 6 at the Kozloduy NPP. An additional index related to the safe operation is defined to characterize the fuel cladding integrity Fuel Reliability Index (FRI). The FRI is defined as value of the average activity of 131 I in the primary coolant, corrected with a part of precipitated 235 U migration and fixed to the general permanent purification frequency. Two criteria (quantitative and statistic) are determined to qualify the fuel cladding integrity. The results from sipping tests show good reliability of the fuel irradiated in unit 5 and 6 at the Kozloduy NPP

  19. Air-tight disposing device for solid radioactive waste

    International Nuclear Information System (INIS)

    Aoyama, Saburo.

    1976-01-01

    Object: In a construction for air-tightly connecting radioactive material handling equipment with a radioactive waste container through a vinyl bag, to use a multi-stage expansion tube to introduce the radioactive waste into the waste container in safe and positive manner. Structure: During normal operation in the radioactive material handling equipment, a multi-stage expansion cylinder is extended by operation of a remote shaft to suitably throw the waste in a state with a vinyl bag protected, whereas when the waste is disposed away from the equipment, the multi-stage expansion cylinder is contracted and received into a holder, and the vinyl bag is heated and sealed at a given position and cut, after which a cover of an outer container for disposal is closed and carried out. The vinyl bag remained on the side of the holder after sealed and cut is put into the waste container after a fresh vinyl bag, in which another waste container is received, has been secured to the holder. (Taniai, N.)

  20. Nanoscale capacitance: A quantum tight-binding model

    Science.gov (United States)

    Zhai, Feng; Wu, Jian; Li, Yang; Lu, Jun-Qiang

    2017-01-01

    Landauer-Buttiker formalism with the assumption of semi-infinite electrodes as reservoirs has been the standard approach in modeling steady electron transport through nanoscale devices. However, modeling dynamic electron transport properties, especially nanoscale capacitance, is a challenging problem because of dynamic contributions from electrodes, which is neglectable in modeling macroscopic capacitance and mesoscopic conductance. We implement a self-consistent quantum tight-binding model to calculate capacitance of a nano-gap system consisting of an electrode capacitance C‧ and an effective capacitance Cd of the middle device. From the calculations on a nano-gap made of carbon nanotube with a buckyball therein, we show that when the electrode length increases, the electrode capacitance C‧ moves up while the effective capacitance Cd converges to a value which is much smaller than the electrode capacitance C‧. Our results reveal the importance of electrodes in modeling nanoscale ac circuits, and indicate that the concepts of semi-infinite electrodes and reservoirs well-accepted in the steady electron transport theory may be not applicable in modeling dynamic transport properties.

  1. B-spline tight frame based force matching method

    Science.gov (United States)

    Yang, Jianbin; Zhu, Guanhua; Tong, Dudu; Lu, Lanyuan; Shen, Zuowei

    2018-06-01

    In molecular dynamics simulations, compared with popular all-atom force field approaches, coarse-grained (CG) methods are frequently used for the rapid investigations of long time- and length-scale processes in many important biological and soft matter studies. The typical task in coarse-graining is to derive interaction force functions between different CG site types in terms of their distance, bond angle or dihedral angle. In this paper, an ℓ1-regularized least squares model is applied to form the force functions, which makes additional use of the B-spline wavelet frame transform in order to preserve the important features of force functions. The B-spline tight frames system has a simple explicit expression which is useful for representing our force functions. Moreover, the redundancy of the system offers more resilience to the effects of noise and is useful in the case of lossy data. Numerical results for molecular systems involving pairwise non-bonded, three and four-body bonded interactions are obtained to demonstrate the effectiveness of our approach.

  2. Pre-Darcy flow in tight and shale formations

    Science.gov (United States)

    Dejam, Morteza; Hassanzadeh, Hassan; Chen, Zhangxin

    2017-11-01

    There are evidences that the fluid flow in tight and shale formations does not follow Darcy law, which is identified as pre-Darcy flow. Here, the unsteady linear flow of a slightly compressible fluid under the action of pre-Darcy flow is modeled and a generalized Boltzmann transformation technique is used to solve the corresponding highly nonlinear diffusivity equation analytically. The effect of pre-Darcy flow on the pressure diffusion in a homogenous formation is studied in terms of the nonlinear exponent, m, and the threshold pressure gradient, G1. In addition, the pressure gradient, flux, and cumulative production per unit area for different m and G1 are compared with the classical solution of the diffusivity equation based on Darcy flow. Department of Petroleum Engineering in College of Engineering and Applied Science at University of Wyoming and NSERC/AI-EES(AERI)/Foundation CMG and AITF (iCORE) Chairs in Department of Chemical and Petroleum Engineering at University of Calgary.

  3. Testing underground tanks for leak tightness at LLNL

    International Nuclear Information System (INIS)

    Henry, R.K.; Sites, R.L.; Sledge, M.

    1986-01-01

    Two types of tank systems are present at the Livermore Site: tanks and associated piping for the storage of fuel (forty-three systems), and tanks or sumps and associated piping for the retention of potentially contaminated wastewater (forty systems). The fuel systems were tested using commercially available test methods: Petro-Tite, Hunter Leak Lokator, Ezy-Chek, and Associated Environmental Systems (A.E.S.). In contrast to fuel tank systems, wastewater systems have containers that are predominantly open at the top and not readily testable. Therefore, a project to test and evaluate all available testing methods was initiated and completed. The commercial method Tank Auditor was determined to be appropriate for testing open-top tanks and sumps and this was the method used to test the majority of the open-top containers. Of the 81 tanks tested, 61 were found to be leak tight, 9 were shown to have leaks, and 11 yielded inconclusive results. Two tanks have not yet been tested because of operational constraints; they are sheduled to be tested within the next two months. Schedules are being developed for the retesting of tanks and for remedial actions

  4. Engineering feasibility of tight aspect ratio Tokamak (spherical torus) reactors

    International Nuclear Information System (INIS)

    Peng, Y-K.M.; Hicks, J.B.

    1990-01-01

    Engineering solutions are identified and analyzed for key high-power-density components of tight aspect ratio tokamak reactors (spherical torus reactors). The potentially extreme divertor heat loads can be reduced to about 3 MW/m 2 in expanded divertors using coils inside the demountable toroidal field coils. Given the long and narrow divertor channels, gaseous divertor targets become possible, which eliminate sputtering and increase the divertor life. The unshielded centre conductor post (CCP) of the toroidal field coil can be made of a single dispersion strengthened copper conductor cooled by high-velocity pressurized water to maintain acceptable copper temperature and strength. Damage and activation of the CCP at a neutron fluence of 10 MW-a/m 2 are also tolerable. Annual replacement of the centre post, the divertor assemblies and the blanket can be accomplished with vertical access for all torus components, which are modularized to reduce size and weight. The technical requirements of these solutions are shown to be comparable with, if not less demanding than, those estimated for conventional tokamak reactors. (author)

  5. Stability of spinor Fermi gases in tight waveguides

    International Nuclear Information System (INIS)

    Campo, A. del; Muga, J. G.; Girardeau, M. D.

    2007-01-01

    The two- and three-body correlation functions of the ground state of an optically trapped ultracold spin-(1/2) Fermi gas (SFG) in a tight waveguide [one-dimensional (1D) regime] are calculated in the plane of even- and odd-wave coupling constants, assuming a 1D attractive zero-range odd-wave interaction induced by a 3D p-wave Feshbach resonance, as well as the usual repulsive zero-range even-wave interaction stemming from 3D s-wave scattering. The calculations are based on the exact mapping from the SFG to a 'Lieb-Liniger-Heisenberg' model with delta-function repulsions depending on isotropic Heisenberg spin-spin interactions, and indicate that the SFG should be stable against three-body recombination in a large region of the coupling constant plane encompassing parts of both the ferromagnetic and antiferromagnetic phases. However, the limiting case of the fermionic Tonks-Girardeau gas, a spin-aligned 1D Fermi gas with infinitely attractive p-wave interactions, is unstable in this sense. Effects due to the dipolar interaction and a Zeeman term due to a resonance-generating magnetic field do not lead to shrinkage of the region of stability of the SFG

  6. Phononic crystals of spherical particles: A tight binding approach

    Energy Technology Data Exchange (ETDEWEB)

    Mattarelli, M., E-mail: maurizio.mattarelli@fisica.unipg.it [NiPS Laboratory, Dipartimento di Fisica, Università di Perugia, Via Pascoli, 06100 Perugia (Italy); Secchi, M. [CMM - Fondazione Bruno Kessler, Via Sommarive 18, 38123 Trento (Italy); Dipartimento di Fisica, Università di Trento, Via Sommarive 14, 38123 Trento (Italy); Montagna, M. [Dipartimento di Fisica, Università di Trento, Via Sommarive 14, 38123 Trento (Italy)

    2013-11-07

    The vibrational dynamics of a fcc phononic crystal of spheres is studied and compared with that of a single free sphere, modelled either by a continuous homogeneous medium or by a finite cluster of atoms. For weak interaction among the spheres, the vibrational dynamics of the phononic crystal is described by shallow bands, with low degree of dispersion, corresponding to the acoustic spheroidal and torsional modes of the single sphere. The phonon displacements are therefore related to the vibrations of a sphere, as the electron wave functions in a crystal are related to the atomic wave functions in a tight binding model. Important dispersion is found for the two lowest phonon bands, which correspond to zero frequency free translation and rotation of a free sphere. Brillouin scattering spectra are calculated at some values of the exchanged wavevectors of the light, and compared with those of a single sphere. With weak interaction between particles, given the high acoustic impedance mismatch in dry systems, the density of phonon states consist of sharp bands separated by large gaps, which can be well accounted for by a single particle model. Based on the width of the frequency gaps, tunable with the particle size, and on the small number of dispersive acoustic phonons, such systems may provide excellent materials for application as sound or heat filters.

  7. Pyridoxal 5'-phosphate is a slow tight binding inhibitor of E. coli pyridoxal kinase.

    Directory of Open Access Journals (Sweden)

    Mohini S Ghatge

    Full Text Available Pyridoxal 5'-phosphate (PLP is a cofactor for dozens of B(6 requiring enzymes. PLP reacts with apo-B(6 enzymes by forming an aldimine linkage with the ε-amino group of an active site lysine residue, thus yielding the catalytically active holo-B(6 enzyme. During protein turnover, the PLP is salvaged by first converting it to pyridoxal by a phosphatase and then back to PLP by pyridoxal kinase. Nonetheless, PLP poses a potential toxicity problem for the cell since its reactive 4'-aldehyde moiety forms covalent adducts with other compounds and non-B(6 proteins containing thiol or amino groups. The regulation of PLP homeostasis in the cell is thus an important, yet unresolved issue. In this report, using site-directed mutagenesis, kinetic, spectroscopic and chromatographic studies we show that pyridoxal kinase from E. coli forms a complex with the product PLP to form an inactive enzyme complex. Evidence is presented that, in the inhibited complex, PLP has formed an aldimine bond with an active site lysine residue during catalytic turnover. The rate of dissociation of PLP from the complex is very slow, being only partially released after a 2-hour incubation with PLP phosphatase. Interestingly, the inactive pyridoxal kinase•PLP complex can be partially reactivated by transferring the tightly bound PLP to an apo-B(6 enzyme. These results open new perspectives on the mechanism of regulation and role of pyridoxal kinase in the Escherichia coli cell.

  8. Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation

    Directory of Open Access Journals (Sweden)

    Luissint Anny-Claude

    2012-11-01

    Full Text Available Abstract The Blood–brain barrier (BBB, present at the level of the endothelium of cerebral blood vessels, selectively restricts the blood-to-brain paracellular diffusion of compounds; it is mandatory for cerebral homeostasis and proper neuronal function. The barrier properties of these specialized endothelial cells notably depend on tight junctions (TJs between adjacent cells: TJs are dynamic structures consisting of a number of transmembrane and membrane-associated cytoplasmic proteins, which are assembled in a multimolecular complex and acting as a platform for intracellular signaling. Although the structural composition of these complexes has been well described in the recent years, our knowledge about their functional regulation still remains fragmentary. Importantly, pericytes, embedded in the vascular basement membrane, and perivascular microglial cells, astrocytes and neurons contribute to the regulation of endothelial TJs and BBB function, altogether constituting the so-called neurovascular unit. The present review summarizes our current understanding of the structure and functional regulation of endothelial TJs at the BBB. Accumulating evidence points to a correlation between BBB dysfunction, alteration of TJ complexes and progression of a variety of CNS diseases, such as stroke, multiple sclerosis and brain tumors, as well as neurodegenerative diseases like Parkinson’s and Alzheimer’s diseases. Understanding how TJ integrity is controlled may thus help improve drug delivery across the BBB and the design of therapeutic strategies for neurological disorders.

  9. Molecular and cellular mechanisms of tight junction dysfunction in the irritable bowel syndrome.

    Science.gov (United States)

    Cheng, Peng; Yao, Jianning; Wang, Chunfeng; Zhang, Lianfeng; Kong, Wuming

    2015-09-01

    The pathophysiological mechanisms of the irritable bowel syndrome (IBS), one of the most prevalent gastrointestinal disorders, are complex and have not been fully elucidated. The present study aimed to investigate the molecular and cellular mechanisms of tight junction (TJ) dysfunction in IBS. Intestinal tissues of IBS and non‑IBS patients were examined to observe cellular changes by cell chemical tracer electron microscopy and transmission electron microscopy, and intestinal claudin‑1 protein was detected by immunohistochemistry, western blot analysis and fluorescence quantitative polymerase chain reaction. Compared with the control group, TJ broadening and the tracer extravasation phenomenon were observed in the diarrhea‑predominant IBS group, and a greater number of neuroendocrine cells and mast cells filled with high‑density particles in the endocrine package pulp as well as a certain extent of vacuolization were present. The expression of claudin‑1 in diarrhea‑predominant IBS patients was decreased, while it was increased in constipation‑predominant IBS patients. In conclusion, the results of the present study indicated that changes in cellular structure and claudin‑1 levels were associated with Tjs in IBS.

  10. Matriptase autoactivation is tightly regulated by the cellular chemical environments.

    Directory of Open Access Journals (Sweden)

    Jehng-Kang Wang

    Full Text Available The ability of cells to rapidly detect and react to alterations in their chemical environment, such as pH, ionic strength and redox potential, is essential for cell function and survival. We present here evidence that cells can respond to such environmental alterations by rapid induction of matriptase autoactivation. Specifically, we show that matriptase autoactivation can occur spontaneously at physiological pH, and is significantly enhanced by acidic pH, both in a cell-free system and in living cells. The acid-accelerated autoactivation can be attenuated by chloride, a property that may be part of a safety mechanism to prevent unregulated matriptase autoactivation. Additionally, the thio-redox balance of the environment also modulates matriptase autoactivation. Using the cell-free system, we show that matriptase autoactivation is suppressed by cytosolic reductive factors, with this cytosolic suppression being reverted by the addition of oxidizing agents. In living cells, we observed rapid induction of matriptase autoactivation upon exposure to toxic metal ions known to induce oxidative stress, including CoCl2 and CdCl2. The metal-induced matriptase autoactivation is suppressed by N-acetylcysteine, supporting the putative role of altered cellular redox state in metal induced matriptase autoactivation. Furthermore, matriptase knockdown rendered cells more susceptible to CdCl2-induced cell death compared to control cells. This observation implies that the metal-induced matriptase autoactivation confers cells with the ability to survive exposure to toxic metals and/or oxidative stress. Our results suggest that matriptase can act as a cellular sensor of the chemical environment of the cell that allows the cell to respond to and protect itself from changes in the chemical milieu.

  11. Surface passivation for tight-binding calculations of covalent solids

    International Nuclear Information System (INIS)

    Bernstein, N

    2007-01-01

    Simulation of a cluster representing a finite portion of a larger covalently bonded system requires the passivation of the cluster surface. We compute the effects of an explicit hybrid orbital passivation (EHOP) on the atomic structure in a model bulk, three-dimensional, narrow gap semiconductor, which is very different from the wide gap, quasi-one-dimensional organic molecules where most passivation schemes have been studied in detail. The EHOP approach is directly applicable to minimal atomic orbital basis methods such as tight-binding. Each broken bond is passivated by a hybrid created from an explicitly expressed linear combination of basis orbitals, chosen to represent the contribution of the missing neighbour, e.g. a sp 3 hybrid for a single bond. The method is tested by computing the forces on atoms near a point defect as a function of cluster geometry. We show that, compared to alternatives such as pseudo-hydrogen passivation, the force on an atom converges to the correct bulk limit more quickly as a function of cluster radius, and that the force is more stable with respect to perturbations in the position of the cluster centre. The EHOP method also obviates the need for parameterizing the interactions between the system atoms and the passivating atoms. The method is useful for cluster calculations of non-periodic defects in large systems and for hybrid schemes that simulate large systems by treating finite regions with a quantum-mechanical model, coupled to an interatomic potential description of the rest of the system

  12. Tightness of the thermal envelope of office and educational buildings; Klimaskaermens taethed i kontor- og undervisningsbygninger

    Energy Technology Data Exchange (ETDEWEB)

    Bergsoee, N.C. (SBi, Aalborg (Denmark)); Radisch, N.H.; Nickel, J.; Treldal, J. (Ramboell Danmark A/S, Koebenhavn (Denmark)); Bundesen, E.W.; Nielsen, Carsten (DanEjendomme, Hellerup (Denmark))

    2011-07-01

    In 2006 tightening of the energy regulations in the Danish Building Regulations were introduced including requirements regarding the tightness of the building envelope. The requirements are, with minor changes, continued in the current Building Regulations, BR10. During the past few years experience has been gained regarding both the actual execution of air tightness measurements and solutions that will lead to more air tight building envelopes. Experiences, however, are primarily related to single family houses. The report presents results of measurements in large buildings and discusses reasons for lack of knowledge and experience on the tightness of the building envelope in large buildings. Apparently, there is a need for dissemination of knowledge on the importance of a tight building envelope both in terms of energy consumption and indoor climate and in terms of the difficulties and costs associated with repairing leaks in a completed envelope. Air tightness must be brought into focus at an early stage in the planning process, and during the construction phase air tightness measurements should be performed, e.g. on facade sections or in parts of the building. The project team has attended a number of measurements in large buildings and further gained access to results of a large number of measurements. In summary, the results show that it is possible to achieve the required tightness, and in most buildings the results are better than the requirement of a maximum of 1.5 l/s per m{sub 2}. (Author)

  13. Tightness of M-estimators for multiple linear regression in time series

    DEFF Research Database (Denmark)

    Johansen, Søren; Nielsen, Bent

    We show tightness of a general M-estimator for multiple linear regression in time series. The positive criterion function for the M-estimator is assumed lower semi-continuous and sufficiently large for large argument: Particular cases are the Huber-skip and quantile regression. Tightness requires...

  14. The tight junction protein Z O-2 has several functional nuclear export signals

    International Nuclear Information System (INIS)

    Gonzalez-Mariscal, Lorenza; Ponce, Arturo; Alarcon, Lourdes; Jaramillo, Blanca Estela

    2006-01-01

    The tight junction (TJ) protein ZO-2 changes its subcellular distribution according to the state of confluency of the culture. Thus in confluent monolayers, it localizes at the TJ region whereas in sparse cultures it concentrates at the nucleus. The canine sequence of ZO-2 displays four putative nuclear export signals (NES), two at the second PDZ domain (NES-0 and NES-1) and the rest at the GK region (NES-2 and NES-3). The functionality of NES-0 and NES-3 was unknown, hence here we have explored it with a nuclear export assay, injecting into the nucleus of MDCK cells peptides corresponding to the ZO-2 NES sequences chemically coupled to ovalbumin. We show that both NES-0 and NES-3 are functional and sensitive to leptomycin B. We also demonstrate that NES-1, previously characterized as a non functional NES, is rendered capable of nuclear export upon the acquisition of a negative charge at its Ser369 residue. Experiments performed injecting at the nucleus WT and mutated ZO-2-GST fusion proteins revealed the need of both NES-0 and NES-1, and NES-2 and NES-3 for attaining an efficient nuclear exit of the respective amino and middle segments of ZO-2. Moreover, the transfection of MDCK cells with full-length ZO-2 revealed that the mutation of any of the NES present in the molecule was sufficient to induce nuclear accumulation of the protein

  15. Transferable tight-binding model for strained group IV and III-V materials and heterostructures

    Science.gov (United States)

    Tan, Yaohua; Povolotskyi, Michael; Kubis, Tillmann; Boykin, Timothy B.; Klimeck, Gerhard

    2016-07-01

    It is critical to capture the effect due to strain and material interface for device level transistor modeling. We introduce a transferable s p3d5s* tight-binding model with nearest-neighbor interactions for arbitrarily strained group IV and III-V materials. The tight-binding model is parametrized with respect to hybrid functional (HSE06) calculations for varieties of strained systems. The tight-binding calculations of ultrasmall superlattices formed by group IV and group III-V materials show good agreement with the corresponding HSE06 calculations. The application of the tight-binding model to superlattices demonstrates that the transferable tight-binding model with nearest-neighbor interactions can be obtained for group IV and III-V materials.

  16. A casein-kinase-2-related protein kinase is tightly associated with the large T antigen of simian virus 40

    DEFF Research Database (Denmark)

    Götz, C; Koenig, M G; Issinger, O G

    1995-01-01

    by the addition of protein kinase CK2 suggest that at least one of the T-antigen-associated protein kinases is CK2 or a protein-kinase-CK2-related enzyme. The association of recombinant CK2 with T antigen was strongly confirmed by in vitro binding studies. Experiments with temperature-sensitive SV40-transformed......The simian virus 40 (SV40) large T antigen is a multifunctional protein involved in SV40 cell transformation and lytic virus infection. Some of its activities are regulated by interaction with cellular proteins and/or by phosphorylation of T antigen by various protein kinases. In this study, we...... show that immuno-purified T antigen from SV40-transformed cells and from baculovirus-infected insect cells is tightly associated with a protein kinase that phosphorylates T antigen in vitro. In the presence of heparin or a peptide resembling a protein kinase CK2 recognition site, the phosphorylation...

  17. Autophagy and tight junction proteins in the intestine and intestinal diseases

    Directory of Open Access Journals (Sweden)

    Chien-An A. Hu

    2015-09-01

    Full Text Available The intestinal epithelium (IE forms an indispensible barrier and interface between the intestinal interstitium and the luminal environment. The IE regulates water, ion and nutrient transport while providing a barrier against toxins, pathogens (bacteria, fungi and virus and antigens. The apical intercellular tight junctions (TJ are responsible for the paracellular barrier function and regulate trans-epithelial flux of ions and solutes between adjacent cells. Increased intestinal permeability caused by defects in the IE TJ barrier is considered an important pathogenic factor for the development of intestinal inflammation, diarrhea and malnutrition in humans and animals. In fact, defects in the IE TJ barrier allow increased antigenic penetration, resulting in an amplified inflammatory response in inflammatory bowel disease (IBD, necrotizing enterocolitis and ischemia-reperfusion injury. Conversely, the beneficial enhancement of the intestinal TJ barrier has been shown to resolve intestinal inflammation and apoptosis in both animal models of IBD and human IBD. Autophagy (self-eating mechanism is an intracellular lysosome-dependent degradation and recycling pathway essential for cell survival and homeostasis. Dysregulated autophagy has been shown to be directly associated with many pathological processes, including IBD. Importantly, the crosstalk between IE TJ and autophagy has been revealed recently. We showed that autophagy enhanced IE TJ barrier function by increasing transepithelial resistance and reducing the paracellular permeability of small solutes and ions, which is, in part, by targeting claudin-2, a cation-selective, pore-forming, transmembrane TJ protein, for lysosome (autophagy-mediated degradation. Interestingly, previous studies have shown that the inflamed intestinal mucosa in patients with active IBD has increased claudin-2 expression. In addition, inflammatory cytokines (for example, tumor necrosis factor-α, interleukin-6

  18. Study on water leak-tightness of small leaks on a 1 inch cylinder valve

    International Nuclear Information System (INIS)

    Miyazawa, T.; Kasai, Y.; Inabe, N.; Aritomi, M.

    2002-01-01

    Practical thresholds for water leak-tightness of small leaks were determined by experimentation. Measurements for small leak samples were taken of air leakage rates and water leakage rates for identical leak samples in order to identify parameters that influence water leak-tightness threshold. Four types of leaks were evaluated: a fine wire inserted in an O-ring seal, a glass capillary tube, a stainless steel orifice, and a scratched valve stem on a 1 inch UF 6 cylinder valve. Experimental results demonstrated that the key parameter for water leak-tightness is the opening size of the leak hole. The maximum allowable hole size to achieve water leak-tightness ranged from 10 to 20 μm in diameter in this study. Experimental results with 1 inch UF 6 cylinder valve samples demonstrated that the acceptance criteria for preshipment leakage test, 1x10 -3 ref-cm 3 .s -1 , as prescribed in ANSI N14.5 is an appropriate value from the point of view of water leak-tightness for enriched UF 6 packages. The mechanism of water leak-tightness is plugging by tiny particles existing in water. The water used in experiments in this study contained far fewer particles than in water assumed to be encountered under accident conditions of transport. Therefore, the water leak-tightness threshold determined in this study is a conservative value in a practical evaluation. (author)

  19. Impact of Air Tightness on the Evaluation of Building Energy Performance in Lithuania

    Directory of Open Access Journals (Sweden)

    Jolanta Šadauskienė

    2014-08-01

    Full Text Available In order to fulfil the European Energy Performance of Buildings Directive (EPBD requirements for the reduction of energy consumption, European national requirements have been created for building envelope thermal properties and calculation methodology to determine if building energy efficiency is created. This is however not true in all methodologies. The necessity of building air tightness appears only for new A class buildings, and there are no requirements for air tightness for other building classes. Therefore, the aim of this work is to improve the methodology for the calculation of energy efficiency of buildings, while taking into account the air tightness of the buildings. In order to achieve this aim, the sum energy consumption of investigated buildings was calculated, energy efficiency classes were determined, air tightness of the buildings was measured, and reasons for insufficient air tightness were analyzed. Investigation results show that the average value of air tightness of A energy efficiency class buildings is 0.6 h−1. The results of other investigated buildings, corresponding to B and C energy efficiency classes, show insufficient air tightness (the average n50 value is 6 h−1; herewith, energy consumption for heating is higher than calculated, according to the energy efficiency methodology. This paper provides an energy performance evaluation scheme, under which performed evaluation of energy performance of buildings ensures high quality construction work, building durability, and the reliability of heat-loss calculations.

  20. Cell context-specific expression of primary cilia in the human testis and ciliary coordination of Hedgehog signalling in mouse Leydig cells

    DEFF Research Database (Denmark)

    Berg Nygaard, Marie; Almstrup, Kristian; Lindbæk, Louise

    2015-01-01

    Primary cilia are sensory organelles that coordinate numerous cellular signalling pathways during development and adulthood. Defects in ciliary assembly or function lead to a series of developmental disorders and diseases commonly referred to as ciliopathies. Still, little is known about...... cells of mature seminiferous epithelium, but present in Sertoli cell-only tubules in Klinefelter syndrome testis. Peritubular cells in atrophic testis produce overly long cilia. Furthermore cultures of growth-arrested immature mouse Leydig cells express primary cilia that are enriched in components...

  1. Visualization and quantitative analysis of reconstituted tight junctions using localization microscopy.

    Directory of Open Access Journals (Sweden)

    Rainer Kaufmann

    Full Text Available Tight Junctions (TJ regulate paracellular permeability of tissue barriers. Claudins (Cld form the backbone of TJ-strands. Pore-forming claudins determine the permeability for ions, whereas that for solutes and macromolecules is assumed to be crucially restricted by the strand morphology (i.e., density, branching and continuity. To investigate determinants of the morphology of TJ-strands we established a novel approach using localization microscopy.TJ-strands were reconstituted by stable transfection of HEK293 cells with the barrier-forming Cld3 or Cld5. Strands were investigated at cell-cell contacts by Spectral Position Determination Microscopy (SPDM, a method of localization microscopy using standard fluorophores. Extended TJ-networks of Cld3-YFP and Cld5-YFP were observed. For each network, 200,000 to 1,100,000 individual molecules were detected with a mean localization accuracy of ∼20 nm, yielding a mean structural resolution of ∼50 nm. Compared to conventional fluorescence microscopy, this strongly improved the visualization of strand networks and enabled quantitative morphometric analysis. Two populations of elliptic meshes (mean diameter <100 nm and 300-600 nm, respectively were revealed. For Cld5 the two populations were more separated than for Cld3. Discrimination of non-polymeric molecules and molecules within polymeric strands was achieved. For both subtypes of claudins the mean density of detected molecules was similar and estimated to be ∼24 times higher within the strands than outside the strands.The morphometry and single molecule information provided advances the mechanistic analysis of paracellular barriers. Applying this novel method to different TJ-proteins is expected to significantly improve the understanding of TJ on the molecular level.

  2. Application of radiotracer method for tightness control and leakage localization in industrial objects

    International Nuclear Information System (INIS)

    Kras, J; Walis, L.; Myczkowski, S.

    2001-01-01

    Application of 82 Br in the form of gaseous CH 3 Br for tightness control and leakage localization in large industrial apparatus as chemical reactors, columns, vessels, pipelines etc. has been presented. The tracer has been prepared at the place of measurements in a specially designed mobile chemical reactor. The paper presents different variants of the method convenient for: tightness control of underground pipelines, leakage control of technological objects working in chemical and petrochemical industry, tightness control of large metal vessels localized underground and on surface. The radiometric devices used in mentioned variants have ben performed as well

  3. Tight Money, Real Interest Rates, and Inflation in Sub-Saharan Africa

    OpenAIRE

    Edward F. Buffie

    2003-01-01

    The consequences of tight monetary policy are analyzed in an optimizing currency-substitution model of a small, open economy that operates under an open capital account and a flexible exchange rate. There is a reasonably good fit between the dynamics generated by the model and the stylized facts in the tight-money episodes that occurred in Kenya in 1993 and Nigeria in 1989-91. The study's results shed light on two issues: why tight money has provoked stupendous increases in inflation and the ...

  4. Installation of the light tight cover for the SSD modules (the modules are behind the aluminium plate). The silicon sensors are sensitive to light tight, so ambient light will increase the noise and may even damage them.

    CERN Multimedia

    Nooren, G.

    2004-01-01

    Installation of the light tight cover for the SSD modules (the modules are behind the aluminium plate). The silicon sensors are sensitive to light tight , so ambient light will increase the noise and may even damage them.

  5. Aberrant methylation of GCNT2 is tightly related to lymph node metastasis of primary CRC.

    Science.gov (United States)

    Nakamura, Kazunori; Yamashita, Keishi; Sawaki, Hiromichi; Waraya, Mina; Katoh, Hiroshi; Nakayama, Nobukazu; Kawamata, Hiroshi; Nishimiya, Hiroshi; Ema, Akira; Narimatsu, Hisashi; Watanabe, Masahiko

    2015-03-01

    Glycoprotein expression profile is dramatically altered in human cancers; however, specific glycogenes have not been fully identified. A comprehensive real-time polymerase chain reaction (PCR) system for glycogenes (CRPS-G) identified several outstanding glycogenes. GCNT2 was of particular interest after GCNT2 expression and epigenetics were rigorously investigated in primary colorectal cancer (CRC). The highlights of this work can be summarized as follows: (i) Expression of GCNT2 was remarkably suppressed. (ii) Silenced expression of GCNT2 was reactivated by combined demethylating agents. (iii) Promoter DNA methylation of GCNT2 was silenced in CRC cell lines and tissues. Hypomethylation of GCNT2 variant 2 is tightly associated with lymph node metastasis in primary CRC. (iv) GCNT2 methylation level in the normal tissues also showed a close association with that in the tumor tissues and reflected lymph node metastasis. We identified aberrant expression of GCNT2, which can be explained by promoter DNA hypermethylation. Hypomethylation of the GCNT2 variant 2 reflected lymph node metastasis of CRC in the tumor and normal tissues. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  6. Empirical tight-binding modeling of ordered and disordered semiconductor structures; Empirische Tight-Binding-Modellierung geordneter und ungeordneter Halbleiterstrukturen

    Energy Technology Data Exchange (ETDEWEB)

    Mourad, Daniel

    2010-11-30

    In this thesis, we investigate the electronic and optical properties of pure as well as of substitutionally alloyed II-VI and III-V bulk semiconductors and corresponding semiconductor quantum dots by means of an empirical tight-binding (TB) model. In the case of the alloyed systems of the type A{sub x}B{sub 1-x}, where A and B are the pure compound semiconductor materials, we study the influence of the disorder by means of several extensions of the TB model with different levels of sophistication. Our methods range from rather simple mean-field approaches (virtual crystal approximation, VCA) over a dynamical mean-field approach (coherent potential approximation, CPA) up to calculations where substitutional disorder is incorporated on a finite ensemble of microscopically distinct configurations. In the first part of this thesis, we cover the necessary fundamentals in order to properly introduce the TB model of our choice, the effective bond-orbital model (EBOM). In this model, one s- and three p-orbitals per spin direction are localized on the sites of the underlying Bravais lattice. The matrix elements between these orbitals are treated as free parameters in order to reproduce the properties of one conduction and three valence bands per spin direction and can then be used in supercell calculations in order to model mixed bulk materials or pure as well as mixed quantum dots. Part II of this thesis deals with unalloyed systems. Here, we use the EBOM in combination with configuration interaction calculations for the investigation of the electronic and optical properties of truncated pyramidal GaN quantum dots embedded in AlN with an underlying zincblende structure. Furthermore, we develop a parametrization of the EBOM for materials with a wurtzite structure, which allows for a fit of one conduction and three valence bands per spin direction throughout the whole Brillouin zone of the hexagonal system. In Part III, we focus on the influence of alloying on the electronic

  7. Changes of Tight Junction Protein Claudins in Small Intestine and Kidney Tissues of Mice Fed a DDC Diet.

    Science.gov (United States)

    Abiko, Yukie; Kojima, Takashi; Murata, Masaki; Tsujiwaki, Mitsuhiro; Takeuchi, Masaya; Sawada, Norimasa; Mori, Michio

    2013-12-01

    DDC (3,5-diethoxycarbonyl-1,4-dihydrocollidine)-fed mice are widely used as a model for cholestatic liver disease. We examined the expression of tight junction protein claudin subspecies by immunofluorescent histochemistry in small intestine and kidney tissues of mice fed a DDC diet for 12 weeks. In the small intestine, decreases in claudin-3, claudin-7 and claudin-15 were observed in villous epithelial cells corresponding to the severity of histological changes while leaving the abundance of these claudin subspecies unchanged in crypt cells. Nevertheless, the proliferative activity of intestinal crypt cells measured by immunohistochemistry for Ki-67 decreased in the mice fed the DDC diet compared with that of control mice. These results suggest the possibility that DDC feeding affects the barrier function of villous epithelial cells and thus inhibits the proliferative activity of crypt epithelial cells. On the other hand, in the kidney, remarkable changes were found in the subcellular localization of claudin subspecies in a segment-specific manner, although histological changes of renal epithelial cells were quite minimal. These results indicate that immunohistochemistry for claudin subspecies can serve as a useful tool for detecting minute functional alterations of intestinal and renal epithelial cells.

  8. A surgical technique for lengthening tight hamstring muscles in patients with low back pain.

    Science.gov (United States)

    Anglès, F G; Manubens, X B; Anglès, F C

    1997-01-01

    An original technique for lengthening primary tight semitendinosus and semimembranosus muscles in their proximal portion is presented. The authors consider that primary shortening of these muscles rebounds on hip biomechanics and on the spine kinematics chain.

  9. Wounds caused by tight contact with the barrel-cylinder gap of revolvers.

    Science.gov (United States)

    Rogers, D R

    1984-06-01

    A case is presented in which the recognition of a tight cylinder gap contact wound was crucial. Experiments were carried out to reproduce the wound which was noted on the hand of a robbery suspect. Tight contact with the cylinder gap of a revolver produces a characteristic, readily recognizable wound. It is characterized by an L-shaped pattern of powder residue. Along one axis a searing burn may occur which may be deep and which may lead to significant tissue destruction.

  10. Adaptive tight frame based medical image reconstruction: a proof-of-concept study for computed tomography

    International Nuclear Information System (INIS)

    Zhou, Weifeng; Cai, Jian-Feng; Gao, Hao

    2013-01-01

    A popular approach for medical image reconstruction has been through the sparsity regularization, assuming the targeted image can be well approximated by sparse coefficients under some properly designed system. The wavelet tight frame is such a widely used system due to its capability for sparsely approximating piecewise-smooth functions, such as medical images. However, using a fixed system may not always be optimal for reconstructing a variety of diversified images. Recently, the method based on the adaptive over-complete dictionary that is specific to structures of the targeted images has demonstrated its superiority for image processing. This work is to develop the adaptive wavelet tight frame method image reconstruction. The proposed scheme first constructs the adaptive wavelet tight frame that is task specific, and then reconstructs the image of interest by solving an l 1 -regularized minimization problem using the constructed adaptive tight frame system. The proof-of-concept study is performed for computed tomography (CT), and the simulation results suggest that the adaptive tight frame method improves the reconstructed CT image quality from the traditional tight frame method. (paper)

  11. Active stretching for lower extremity muscle tightness in pediatric patients with lumbar spondylolysis.

    Science.gov (United States)

    Sato, Masahiro; Mase, Yasuyoshi; Sairyo, Koichi

    2017-01-01

    It was reported that hamstring muscle tightness may increase mechanical loading on the lumbar spine. Therefore, we attempt to decrease tightness in the leg muscles in pediatric patients. Forty-six pediatric patients with spondylolysis underwent rehabilitation. We applied active stretching to the hamstrings, quadriceps, and triceps surae. Tightness in each muscle was graded as good, fair, or poor. We educated each patient on how to perform active stretching at home. They were re-evaluated for muscle tightness 2 months later. Tightness at baseline and after 2 months was as follows: for the hamstrings, good in 3 patients, fair in 9, and poor in 34 and significant improved after 2 months (p<0.05), with improvement by least 1 grade seen in 86% of patients with fair or poor at baseline; for the quadriceps, 7, 3, and 30 patients had good, fair and poor, with significant improvements in 72% (p<0.05). For the triceps surae, 6, 3 and 10 patients had good, fair and poor, which improved significantly (p<0.05). Home-based active stretching was effective for relieving muscle tightness in the leg in a pediatric population. Adolescent athletes should perform such exercise to maintain flexibility and prevent lumbar disorders. J. Med. Invest. 64: 136-139, February, 2017.

  12. Injuries and disorders among young ice skaters: relationship with generalized joint laxity and tightness

    Directory of Open Access Journals (Sweden)

    Okamura S

    2014-08-01

    Full Text Available Shinobu Okamura,1 Naoki Wada,1 Masayuki Tazawa,1 Makoto Sohmiya,1 Yoko Ibe,1 Toru Shimizu,1 Shigeru Usuda,2 Kenji Shirakura1 1Department of Rehabilitation Medicine, Gunma University Graduate School of Medicine, Maebashi, Gunma, Japan; 2Department of Physical Therapy, Gunma University School of Health Science, Maebashi, Gunma, Japan Abstract: This study retrospectively investigated 192 teenage speed and figure skaters with prior injuries documented by an athletes’ questionnaire, who underwent a physical examination to assess their muscle tightness and generalized joint laxity. In all athletes, the degree of muscle tightness and joint laxity were measured by a standardized physical examination. A descriptive report of the types of injuries showed a predominance of fractures, ligament injuries, enthesitis, and lower back pain. Approximately 5% of all skaters tested positive for tightness, while 25.8% of figure skaters and 15.2% of speed skaters had generalized ligamentous laxity. Statistical testing showed an association between ankle sprains and muscle tightness, and an association between knee enthesitis and muscle tightness in skating athletes. There was also an association between lower back pain and generalized joint laxity, which held true only for the male skaters. Keywords: sports injury, skating, junior athlete, tightness, joint laxity, medical checkup

  13. Performance Improvement of Receivers Based on Ultra-Tight Integration in GNSS-Challenged Environments

    Directory of Open Access Journals (Sweden)

    Feng Qin

    2013-12-01

    Full Text Available Ultra-tight integration was first proposed by Abbott in 2003 with the purpose of integrating a global navigation satellite system (GNSS and an inertial navigation system (INS. This technology can improve the tracking performances of a receiver by reconfiguring the tracking loops in GNSS-challenged environments. In this paper, the models of all error sources known to date in the phase lock loops (PLLs of a standard receiver and an ultra-tightly integrated GNSS/INS receiver are built, respectively. Based on these models, the tracking performances of the two receivers are compared to verify the improvement due to the ultra-tight integration. Meanwhile, the PLL error distributions of the two receivers are also depicted to analyze the error changes of the tracking loops. These results show that the tracking error is significantly reduced in the ultra-tightly integrated GNSS/INS receiver since the receiver’s dynamics are estimated and compensated by an INS. Moreover, the mathematical relationship between the tracking performances of the ultra-tightly integrated GNSS/INS receiver and the quality of the selected inertial measurement unit (IMU is derived from the error models and proved by the error comparisons of four ultra-tightly integrated GNSS/INS receivers aided by different grade IMUs.

  14. Leakage detecting method and device for water tight vessel of wet-type container apparatus

    International Nuclear Information System (INIS)

    Tanaka, Yoshimi.

    1995-01-01

    The present invention provides a method of and a device for detecting leakage of a water tight vessel of a wet-type container apparatus for containing a reactor pressure vessel while immersing it water in a reactor container. Namely, in the wet-type container apparatus, the periphery of the pressure vessel is coated with a heat insulation material and the periphery of the heat insulation material is coated with a water tight vessel. The water tight vessel is immersed under water in the reactor container. As a method of detecting leakage of the wet-type container apparatus, gases mixed with helium are supplied into the water tight vessel at a pressure higher than the inner pressure of the reactor container at a lowest position of the reactor pressure vessel. A water level in the reactor container is determined so as to form a space at the top portion of the inside of the reactor container. The helium at the top portion is detected to monitor the leakage of the water tight vessel. With such procedures, even if the water tight vessel is ruptured at any position, helium mixed to the gases is released to water in the reactor container and rise up to the top space and detected by a helium leakage detection device. (I.S.)

  15. Tight junction protein ZO-2 expression and relative function of ZO-1 and ZO-2 during mouse blastocyst formation

    International Nuclear Information System (INIS)

    Sheth, Bhavwanti; Nowak, Rachael L.; Anderson, Rebecca; Kwong, Wing Yee; Papenbrock, Thomas; Fleming, Tom P.

    2008-01-01

    Apicolateral tight junctions (TJs) between epithelial cells are multiprotein complexes regulating membrane polarity and paracellular transport and also contribute to signalling pathways affecting cell proliferation and gene expression. ZO-2 and other ZO family members form a sub-membranous scaffold for binding TJ constituents. We investigated ZO-2 contribution to TJ biogenesis and function during trophectoderm epithelium differentiation in mouse preimplantation embryos. Our data indicate that ZO-2 is expressed from maternal and embryonic genomes with maternal ZO-2 protein associated with nuclei in zygotes and particularly early cleavage stages. Embryonic ZO-2 assembled at outer blastomere apicolateral junctional sites from the late 16-cell stage. Junctional ZO-2 first co-localised with E-cadherin in a transient complex comprising adherens junction and TJ constituents before segregating to TJs after their separation from the blastocyst stage (32-cell onwards). ZO-2 siRNA microinjection into zygotes or 2-cell embryos resulted in specific knockdown of ZO-2 mRNA and protein within blastocysts. Embryos lacking ZO-2 protein at trophectoderm TJs exhibited delayed blastocoel cavity formation but underwent normal cell proliferation and outgrowth morphogenesis. Quantitative analysis of trophectoderm TJs in ZO-2-deficient embryos revealed increased assembly of ZO-1 but not occludin, indicating ZO protein redundancy as a compensatory mechanism contributing to the mild phenotype observed. In contrast, ZO-1 knockdown, or combined ZO-1 and ZO-2 knockdown, generated a more severe inhibition of blastocoel formation indicating distinct roles for ZO proteins in blastocyst morphogenesis

  16. Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions

    International Nuclear Information System (INIS)

    Imamura, Masafumi; Kojima, Takashi; Lan, Mengdong; Son, Seiichi; Murata, Masaki; Osanai, Makoto; Chiba, Hideki; Hirata, Koichi; Sawada, Norimasa

    2007-01-01

    In rodent livers, integral tight junction (TJ) proteins claudin-1, -2, -3, -5 and -14 are detected and play crucial roles in the barrier to keep bile in bile canaculi away from the blood circulation. Claudin-2 shows a lobular gradient increasing from periportal to pericentral hepatocytes, whereas claudin-1 and -3 are expressed in the whole liver lobule. Although claudin-2 expression induces cation-selective channels in tight junctions of epithelial cells, the physiological functions and regulation of claudin-2 in hepatocytes remain unclear. Oncostatin M (OSM) is a multifunctional cytokine implicated in the differentiation of hepatocytes that induces formation of E-cadherin-based adherens junctions in fetal hepatocytes. In this study, we examined whether OSM could induce expression and function of claudin-2 in rodent hepatocytes, immortalized mouse and primary cultured proliferative rat hepatocytes. In the immortalized mouse and primary cultured proliferative rat hepatocytes, treatment with OSM markedly increased mRNA and protein of claudin-2 together with formation of developed networks of TJ strands. The increase of claudin-2 enhanced the paracellular barrier function which depended on molecular size. The increase of claudin-2 expression induced by OSM in rodent hepatocytes was regulated through distinct signaling pathways including PKC. These results suggest that expression of claudin-2 in rodent hepatocytes may play a specific role as controlling the size of paracellular permeability in the barrier to keep bile in bile canaculi

  17. Thermophysical instruments for non-destructive examination of tightness and internal gas pressure or irradiated power reactor fuel rods

    International Nuclear Information System (INIS)

    Pastoushin, V.V.; Novikov, A.Yu.; Bibilashvili, Yu.K.

    1998-01-01

    The developed thermophysical method and technical instruments for non-destructive leak-tightness and gas pressure inspection inside irradiated power reactor fuel rods and FAs under poolside and hot cell conditions are described. The method of gas pressure measuring based on the examination of parameters of thermal convection that aroused in gas volume of rod plenum by special technical instruments. The developed method and technique allows accurate value determination of not only one of the main critical rod parameters, namely total internal gas pressure, that forms rod mean life in the reactor core, but also the partial pressure of every main constituent of gaseous mixture inside irradiated fuel rod, that provides the feasibility of authentic and reliable leak-tightness detection. The described techniques were experimentally checked during the examination of all types power reactor fuel rods existing in Russia (WWER, BN, RBMK) and could form the basis for new technique development for non-destructive examination of PWR (and other) type rods and FAs having gas plenum filled with spring or another elements of design. (author)

  18. IP3 Receptor-Dependent Cytoplasmic Ca2+ Signals Are Tightly Controlled by Cavβ3

    Directory of Open Access Journals (Sweden)

    Anouar Belkacemi

    2018-01-01

    Full Text Available Voltage-gated calcium channels (Cavs are major Ca2+ entry pathways in excitable cells. Their β subunits facilitate membrane trafficking of the channel’s ion-conducting α1 pore and modulate its gating properties. We report that one β subunit, β3, reduces Ca2+ release following stimulation of phospholipase C-coupled receptors and inositol 1,4,5-trisphosphate (IP3 formation. This effect requires the SH3-HOOK domain of Cavβ3, includes physical β3/IP3 receptor interaction, and prevails when agonist-induced IP3 formation is bypassed by photolysis of caged IP3. In agreement with β3 acting as a brake on Ca2+ release, fibroblast migration is enhanced in vitro, and in vivo, closure of skin wounds is accelerated in the absence of β3. To mediate specific physiological responses and to prevent Ca2+ toxicity, cytoplasmic Ca2+ signals must be tightly controlled. The described function of β3, unrelated to its function as a Cav subunit, adds to this tight control.

  19. Gas leak tightness of SiC/SiC composites at elevated temperature

    Energy Technology Data Exchange (ETDEWEB)

    Hayasaka, Daisuke, E-mail: hayasaka@oasis.muroran-it.ac.jp [OASIS, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Graduate School of Engineering, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Park, Joon-Soo. [OASIS, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Kishimoto, Hirotatsu [OASIS, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Graduate School of Engineering, Muroran Institute of Technology, Muroran, Hokkaido (Japan); Kohyama, Akira [OASIS, Muroran Institute of Technology, Muroran, Hokkaido (Japan)

    2016-11-01

    Highlights: • NITE-SiC/SiC has extremely densified microstructure compared with other SiC/SiC composite like CVI. • Excellent helium and hydrogen gas-leak tightness of SiC/SiC composites by DEMO-NITE method from prototype industrialization production line was presented. • The excellence against stainless steel and Zircaloy at elevated temperature, together with generic excellent properties of SiC will be inevitable for innovative blanket and divertors for DEMO- and power- fusion reactors. - Abstract: SiC/SiC composite materials are attractive candidates for high heat flux components and blanket of fusion reactor, mainly due to their high temperature properties, radiation damage tolerance and low induced radioactivity. One of the challenges for SiC/SiC application in fusion reactors is to satisfy sufficient gas leak tightness of hydrogen and helium isotopes. Although many efforts have been carried-out, SiC/SiC composites by conventional processes have not been successful to satisfy the requirements, except SiC/SiC composites by NITE-methods. Toward the early realization of SiC/SiC components into fusion reactor systems process development of NITE-process has been continued. Followed to the brief introduction of recently developed DEMO-NITE process, baseline properties and hydrogen and helium gas leak tightness is presented. SiC/SiC claddings with 10 mm in diameter and 1 mm in wall thickness are tested by gas leak tightness system developed. The leak tightness measurements are done room temperature to 400 °C. Excellent gas leak tightness equivalent or superior to Zircaloy claddings for light water fission reactors is confirmed. The excellent gas leak tightness suggests nearly perfect suppression of large gas leak path in DEMO-NITE SiC/SiC.

  20. Feasibility study on application of volume acid fracturing technology to tight gas carbonate reservoir development

    Directory of Open Access Journals (Sweden)

    Nianyin Li

    2015-09-01

    Full Text Available How to effectively develop tight-gas carbonate reservoir and achieve high recovery is always a problem for the oil and gas industry. To solve this problem, domestic petroleum engineers use the combination of the successful experiences of North American shale gas pools development by stimulated reservoir volume (SRV fracturing with the research achievements of Chinese tight gas development by acid fracturing to propose volume acid fracturing technology for fractured tight-gas carbonate reservoir, which has achieved a good stimulation effect in the pilot tests. To determine what reservoir conditions are suitable to carry out volume acid fracturing, this paper firstly introduces volume acid fracturing technology by giving the stimulation mechanism and technical ideas, and initially analyzes the feasibility by the comparison of reservoir characteristics of shale gas with tight-gas carbonate. Then, this paper analyzes the validity and limitation of the volume acid fracturing technology via the analyses of control conditions for volume acid fracturing in reservoir fracturing performance, natural fracture, horizontal principal stress difference, orientation of in-situ stress and natural fracture, and gives the solution for the limitation. The study results show that the volume acid fracturing process can be used to greatly improve the flow environment of tight-gas carbonate reservoir and increase production; the incremental or stimulation response is closely related with reservoir fracturing performance, the degree of development of natural fracture, the small intersection angle between hydraulic fracture and natural fracture, the large horizontal principal stress difference is easy to form a narrow fracture zone, and it is disadvantageous to create fracture network, but the degradable fiber diversion technology may largely weaken the disadvantage. The practices indicate that the application of volume acid fracturing process to the tight-gas carbonate

  1. Process of tight junction recovery in the injured vocal fold epithelium: Morphological and paracellular permeability analysis.

    Science.gov (United States)

    Suzuki, Ryo; Katsuno, Tatsuya; Kishimoto, Yo; Nakamura, Ryosuke; Mizuta, Masanobu; Suehiro, Atsushi; Yamashita, Masaru; Nakamura, Tatsuo; Tateya, Ichiro; Omori, Koichi

    2018-04-01

    The vocal fold epithelium that includes tight junction (TJ)-based barrier function protects underlying connective tissues from external insults. TJs play an important role to control paracellular permeability of not only solutes but also ions, and preserve the vocal fold homeostasis. However, the distribution of TJs and paracellular diffusion barrier across the entire vocal fold epithelium are still unknown. The aim of this study was to identify the distribution of TJs in the vocal fold epithelium and to characterize the recovery process of TJ-based paracellular diffusion barrier in a rat model of vocal fold injury. Animal experiments with controls. Normal and vocal fold-injured rats were used. Larynges were harvested for immunohistochemical examination of TJ proteins. For functional analysis, a tracer permeability assay was performed using EZ-Link Sulfo-NHS-LC-Biotin. TJ proteins occludin and zonula occludens 1 signals were localized to the junctional regions of the most luminal cell layers of the vocal fold epithelium. The injured region had been recovered with epithelium at 5 days postinjury, but the paracellular diffusion barrier assays revealed that biotinylation reagents diffused into the lamina propria at 5 days postinjury, and were blocked at the epithelium at 14 and 28 days postinjury. It was strongly suggested that TJs in the vocal fold epithelium exist at the junctional regions of the first layer of stratified squamous epithelium. TJ-based paracellular diffusion barrier following vocal fold injury is recovered by 14 days postinjury, and this period corresponds with the time course of structural changes in the regenerating epithelium layer. NA. Laryngoscope, 128:E150-E156, 2018. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

  2. A role for tight junction-associated MARVEL proteins in larval sea lamprey (Petromyzon marinus) osmoregulation.

    Science.gov (United States)

    Kolosov, Dennis; Bui, Phuong; Donini, Andrew; Wilkie, Mike P; Kelly, Scott P

    2017-10-15

    This study reports on tight junction-associated MARVEL proteins of larval sea lamprey ( Petromyzon marinus ) and their potential role in ammocoete osmoregulation. Two occludin isoforms (designated Ocln and Ocln-a) and a tricellulin (Tric) were identified. Transcripts encoding ocln , ocln-a and tric were broadly expressed in larval lamprey, with the greatest abundance of ocln in the gut, liver and kidney, ocln-a in the gill and skin, and tric in the kidney. Ocln and Ocln-a resolved as ∼63 kDa and ∼35 kDa MW proteins, respectively, while Tric resolved as a ∼50 kDa protein. Ocln immunolocalized to the gill vasculature and in gill mucous cells while Ocln-a localized to the gill pouch and gill epithelium. Both Ocln and Ocln-a localized in the nephron, the epidermis and the luminal side of the gut. In branchial tissue, Tric exhibited punctate localization, consistent with its presence at regions of tricellular contact. Following ion-poor water (IPW) acclimation of ammocoetes, serum [Na + ] and [Cl - ] decreased, but not [Ca 2+ ], and carcass moisture content increased. In association, Ocln abundance increased in the skin and kidney, but reduced in the gill of IPW-acclimated ammocoetes while Ocln-a abundance reduced in the kidney only. Tric abundance increased in the gill. Region-specific alterations in ocln , ocln-a and tric mRNA abundance were also observed in the gut. Data support a role for Ocln, Ocln-a and Tric in the osmoregulatory strategies of a basal vertebrate. © 2017. Published by The Company of Biologists Ltd.

  3. Toward Reanalysis of the Tight-Pitch HCLWR-PROTEUS Phase II Experiments

    Science.gov (United States)

    Perret, Grégory; Vlassopoulos, Efstathios; Hursin, Mathieu; Pautz, Andreas

    2016-03-01

    The HCLWR-Proteus Phase II experiments were conducted from 1985 to 1990 in the zero-power reactor Proteus at PSI in Switzerland. The experimental program was dedicated to the physics of high conversion light water reactors and in particular to the measurement of reactor parameters such as reaction rate traverses, spectral indices, absorber reactivity worths and void coefficients. The HCLWR experiments are especially interesting because they generated knowledge in the epithermal range of the neutron flux spectrum, for which little integral experimental data is available. In an effort to assess the interest of this experimental data to validate modern nuclear data and improve their uncertainties, a preliminary re-analysis of selected configurations was conducted with Monte-Carlo codes (MCNP6/SERPENT2) and modern nuclear data libraries (ENDF/B-VII.0, JEFF-3.1.1 and JENDL-4.0). The spectral ndices, flux spectra and sensitivity coefficients on k∞ were calculated using cell models representative of the tight-pitch measurement configurations containing 11% PuO2-UO2 fuel rods in different moderation conditions (air, water and dowtherm). Spectral index predictions using the three nuclear data libraries agreed within two standard deviations with the measured values. The only exception is the Pu-242-capture-to-Pu-239-fission ratio, which was overestimated with all libraries by more than four standard deviations, i.e. 13%, in the non-moderated configuration. In this configuration, Pu-242 captures are few since the flux spectrum in the Pu-242 capture resonance region (between 1eV and 1keV) is small making this spectral index hard to measure. Sensitivity coefficient predictions with both MCNP6 and SERPENT2 were in good agreement.

  4. DEVELOPMENTAL EXPOSURE TO DI-N-BUTYL PHTHALATE AFFECTS CORD ORGANIZATION AND SERTOLI CELL-GONOCYTE INTERACTIONS IN THE FETAL RAT TESTIS. (R830766)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  5. Ovarian Sertoli-Leydig Cell Tumor with Elevated Inhibin B As a Cause of Secondary Amenorrhea in Adolescents with Germline DICER1 Mutation

    Science.gov (United States)

    2017-04-06

    history was significant for a right ovarian SLCT, found at age eight years which presented with ovarian torsion. The tumor was 12 cm in size, para...was International Federation of Obstetrics and Gynecology (FIGO) stage IC due to involved peritoneal washings at the pel vie entry . The patient...patient with secondary amenorrhea involves a thorough history and physical exam to look for progression of height, weight, and Tanner staging

  6. Production of Natural Gas and Fluid Flow in Tight Sand Reservoirs

    Energy Technology Data Exchange (ETDEWEB)

    Maria Cecilia Bravo

    2006-06-30

    This document reports progress of this research effort in identifying relationships and defining dependencies between macroscopic reservoir parameters strongly affected by microscopic flow dynamics and production well performance in tight gas sand reservoirs. These dependencies are investigated by identifying the main transport mechanisms at the pore scale that should affect fluids flow at the reservoir scale. A critical review of commercial reservoir simulators, used to predict tight sand gas reservoir, revealed that many are poor when used to model fluid flow through tight reservoirs. Conventional simulators ignore altogether or model incorrectly certain phenomena such as, Knudsen diffusion, electro-kinetic effects, ordinary diffusion mechanisms and water vaporization. We studied the effect of Knudsen's number in Klinkenberg's equation and evaluated the effect of different flow regimes on Klinkenberg's parameter b. We developed a model capable of explaining the pressure dependence of this parameter that has been experimentally observed, but not explained in the conventional formalisms. We demonstrated the relevance of this, so far ignored effect, in tight sands reservoir modeling. A 2-D numerical simulator based on equations that capture the above mentioned phenomena was developed. Dynamic implications of new equations are comprehensively discussed in our work and their relative contribution to the flow rate is evaluated. We performed several simulation sensitivity studies that evidenced that, in general terms, our formalism should be implemented in order to get more reliable tight sands gas reservoirs' predictions.

  7. Tight junction-associated MARVEL proteins marveld3, tricellulin, and occludin have distinct but overlapping functions.

    Science.gov (United States)

    Raleigh, David R; Marchiando, Amanda M; Zhang, Yong; Shen, Le; Sasaki, Hiroyuki; Wang, Yingmin; Long, Manyuan; Turner, Jerrold R

    2010-04-01

    In vitro studies have demonstrated that occludin and tricellulin are important for tight junction barrier function, but in vivo data suggest that loss of these proteins can be overcome. The presence of a heretofore unknown, yet related, protein could explain these observations. Here, we report marvelD3, a novel tight junction protein that, like occludin and tricellulin, contains a conserved four-transmembrane MARVEL (MAL and related proteins for vesicle trafficking and membrane link) domain. Phylogenetic tree reconstruction; analysis of RNA and protein tissue distribution; immunofluorescent and electron microscopic examination of subcellular localization; characterization of intracellular trafficking, protein interactions, dynamic behavior, and siRNA knockdown effects; and description of remodeling after in vivo immune activation show that marvelD3, occludin, and tricellulin have distinct but overlapping functions at the tight junction. Although marvelD3 is able to partially compensate for occludin or tricellulin loss, it cannot fully restore function. We conclude that marvelD3, occludin, and tricellulin define the tight junction-associated MARVEL protein family. The data further suggest that these proteins are best considered as a group with both redundant and unique contributions to epithelial function and tight junction regulation.

  8. IGF-1 decreases portal vein endotoxin via regulating intestinal tight junctions and plays a role in attenuating portal hypertension of cirrhotic rats.

    Science.gov (United States)

    Zhao, Tian-Yu; Su, Li-Ping; Ma, Chun-Ye; Zhai, Xiao-Han; Duan, Zhi-Jun; Zhu, Ying; Zhao, Gang; Li, Chun-Yan; Wang, Li-Xia; Yang, Dong

    2015-07-08

    Intestinal barrier dysfunction is not only the consequence of liver cirrhosis, but also an active participant in the development of liver cirrhosis. Previous studies showed that external administration of insulin-like growth factor 1 (IGF-1) improved intestinal barrier function in liver cirrhosis. However, the mechanism of IGF-1 on intestinal barrier in liver cirrhosis is not fully elucidated. The present study aims to investigate the mechanisms of IGF-1 improving intestinal barrier function via regulating tight junctions in intestines. We used carbon tetrachloride induced liver cirrhotic rats to investigate the effect of IGF-1 on intestinal claudin-1 and occludin expressions, serum alanine transaminase (ALT) and aspartate transaminase (AST) levels, severity of liver fibrosis, portal pressures, enterocytic apoptosis and lipopolysaccharides (LPS) levels in portal vein. The changes of IGF-1 in serum during the development of rat liver cirrhosis were also evaluated. Additionally, we assessed the effect of IGF-1 on claudin-1 and occludin expressions, changes of transepithelial electrical resistance (TEER) and apoptosis in Caco-2 cells to confirm in vivo findings. Serum IGF-1 levels were decreased in the development of rat liver cirrhosis, and external administration of IGF-1 restored serum IGF-1 levels. External administration of IGF-1 reduced serum ALT and AST levels, severity of liver fibrosis, LPS levels in portal vein, enterocytic apoptosis and portal pressure in cirrhotic rats. External administration of IGF-1 increased the expressions of claudin-1 and occludin in enterocytes, and attenuated tight junction dysfunction in intestines of cirrhotic rats. LPS decreased TEER in Caco-2 cell monolayer. LPS also decreased claudin-1 and occludin expressions and increased apoptosis in Caco-2 cells. Furthermore, IGF-1 attenuated the effect of LPS on TEER, claudin-1 expression, occludin expression and apoptosis in Caco-2 cells. Tight junction dysfunction develops during the

  9. Pressure drop characteristics in tight-lattice bundles for reduced-moderation water reactors

    International Nuclear Information System (INIS)

    Tamai, Hidesada; Kureta, Masatoshi; Yoshida, Hiroyuki; Akimoto, Hajime

    2004-01-01

    The reduced-moderation water reactor (RMWR) consists of several distinctive structures; a triangular tight-lattice configuration and a double-flat core. In order to design the RMWR core from the point of view of thermal-hydraulics, an evaluation method on pressure drop characteristics in the rod bundles at the tight-lattice configuration is required. In this study, calculated results by the Martinelli-Nelson's and Hancox's correlations were compared with experimental results in 4 x 5 rod bundles and seven-rod bundles. Consequently, the friction loss in two-phase flows becomes smaller at the tight-lattice configuration with the hydraulic diameter less than about 3 mm. This reason is due to the difference of the configuration between the multi-rod bundle and the circular tube and due to the effect of the small hydraulic diameter on the two-phase multiplier. (author)

  10. LDA+U and tight-binding electronic structure of InN nanowires

    Science.gov (United States)

    Molina-Sánchez, A.; García-Cristóbal, A.; Cantarero, A.; Terentjevs, A.; Cicero, G.

    2010-10-01

    In this paper we employ a combined ab initio and tight-binding approach to obtain the electronic and optical properties of hydrogenated Indium nitride (InN) nanowires. We first discuss InN band structure for the wurtzite structure calculated at the LDA+U level and use this information to extract the parameters needed for an empirical tight-binging implementation. These parameters are then employed to calculate the electronic and optical properties of InN nanowires in a diameter range that would not be affordable by ab initio techniques. The reliability of the large nanowires results is assessed by explicitly comparing the electronic structure of a small diameter wire studied both at LDA+U and tight-binding level.

  11. ARTHROSCOPIC TREATMENT OF ACROMIOCLAVICULAR JOINT DISLOCATION BY TIGHT ROPE TECHNIQUE (ARTHREX®)

    Science.gov (United States)

    GÓmez Vieira, Luis Alfredo; Visco, Adalberto; Daneu Fernandes, Luis Filipe; GÓmez Cordero, Nicolas Gerardo

    2015-01-01

    Presenting the arthroscopic treatment by Tight Rope - Arthrex® system for acute acromioclavicular dislocation and to evaluate results obtained with this procedure. Methods: Between August 2006 and May 2007, 10 shoulders of 10 patients with acute acromioclavicular dislocation were submitted to arthroscopic repair using the Tight Rope - Arthrex® system. Minimum follow-up was 12 months, with a mean of 15 months. Age ranged from 26 to 42, mean 34 years. All patients were male. Radiology evaluation was made by trauma series x-ray. The patients were assisted in the first month weekly and after three months after the procedure. Clinical evaluation was based on the University of California at Los Angeles (UCLA) criteria. Results: All patients were satisfied after the arthroscopic procedure and the mean UCLA score was 32,5. Conclusion: The arthroscopic treatment by Tight Rope – Arthrex® system for acute acromioclavicular dislocation showed to be an efficient technique. PMID:26998453

  12. Loose and Tight GNSS/INS Integrations: Comparison of Performance Assessed in Real Urban Scenarios.

    Science.gov (United States)

    Falco, Gianluca; Pini, Marco; Marucco, Gianluca

    2017-01-29

    Global Navigation Satellite Systems (GNSSs) remain the principal mean of positioning in many applications and systems, but in several types of environment, the performance of standalone receivers is degraded. Although many works show the benefits of the integration between GNSS and Inertial Navigation Systems (INSs), tightly-coupled architectures are mainly implemented in professional devices and are based on high-grade Inertial Measurement Units (IMUs). This paper investigates the performance improvements enabled by the tight integration, using low-cost sensors and a mass-market GNSS receiver. Performance is assessed through a series of tests carried out in real urban scenarios and is compared against commercial modules, operating in standalone mode or featuring loosely-coupled integrations. The paper describes the developed tight-integration algorithms with a terse mathematical model and assesses their efficacy from a practical perspective.

  13. An improved method for predicting brittleness of rocks via well logs in tight oil reservoirs

    Science.gov (United States)

    Wang, Zhenlin; Sun, Ting; Feng, Cheng; Wang, Wei; Han, Chuang

    2018-06-01

    There can be no industrial oil production in tight oil reservoirs until fracturing is undertaken. Under such conditions, the brittleness of the rocks is a very important factor. However, it has so far been difficult to predict. In this paper, the selected study area is the tight oil reservoirs in Lucaogou formation, Permian, Jimusaer sag, Junggar basin. According to the transformation of dynamic and static rock mechanics parameters and the correction of confining pressure, an improved method is proposed for quantitatively predicting the brittleness of rocks via well logs in tight oil reservoirs. First, 19 typical tight oil core samples are selected in the study area. Their static Young’s modulus, static Poisson’s ratio and petrophysical parameters are measured. In addition, the static brittleness indices of four other tight oil cores are measured under different confining pressure conditions. Second, the dynamic Young’s modulus, Poisson’s ratio and brittleness index are calculated using the compressional and shear wave velocity. With combination of the measured and calculated results, the transformation model of dynamic and static brittleness index is built based on the influence of porosity and clay content. The comparison of the predicted brittleness indices and measured results shows that the model has high accuracy. Third, on the basis of the experimental data under different confining pressure conditions, the amplifying factor of brittleness index is proposed to correct for the influence of confining pressure on the brittleness index. Finally, the above improved models are applied to formation evaluation via well logs. Compared with the results before correction, the results of the improved models agree better with the experimental data, which indicates that the improved models have better application effects. The brittleness index prediction method of tight oil reservoirs is improved in this research. It is of great importance in the optimization of

  14. Appraisal of the tight sands potential of the Sand Wash and Great Divide Basins

    International Nuclear Information System (INIS)

    1993-08-01

    The volume of future tight gas reserve additions is difficult to estimate because of uncertainties in the characterization and extent of the resource and the performance and cost-effectiveness of stimulation and production technologies. Ongoing R ampersand D by industry and government aims to reduce the risks and costs of producing these tight resources, increase the certainty of knowledge of their geologic characteristics and extent, and increase the efficiency of production technologies. Some basins expected to contain large volumes of tight gas are being evaluated as to their potential contribution to domestic gas supplies. This report describes the results of one such appraisal. This analysis addresses the tight portions of the Eastern Greater Green River Basin (Sand Wash and Great Divide Subbasins in Northwestern Colorado and Southwestern Wyoming, respectively), with respect to estimated gas-in-place, technical recovery, and potential reserves. Geological data were compiled from public and proprietary sources. The study estimated gas-in-place in significant (greater than 10 feet net sand thickness) tight sand intervals for six distinct vertical and 21 areal units of analysis. These units of analysis represent tight gas potential outside current areas of development. For each unit of analysis, a ''typical'' well was modeled to represent the costs, recovery and economics of near-term drilling prospects in that unit. Technically recoverable gas was calculated using reservoir properties and assumptions about current formation evaluation and extraction technology performance. Basin-specific capital and operating costs were incorporated along with taxes, royalties and current regulations to estimate the minimum required wellhead gas price required to make the typical well in each of unit of analysis economic

  15. Development of a general-purpose method for cell purification using Cre/loxP-mediated recombination.

    Science.gov (United States)

    Kuroki, Shunsuke; Akiyoshi, Mika; Ideguchi, Ko; Kitano, Satsuki; Miyachi, Hitoshi; Hirose, Michiko; Mise, Nathan; Abe, Kuniya; Ogura, Atsuo; Tachibana, Makoto

    2015-06-01

    A mammalian body is composed of more than 200 different types of cells. The purification of a certain cell type from tissues/organs enables a wide variety of studies. One popular cell purification method is immunological isolation, using antibodies against specific cell surface antigens. However, this is not a general-purpose method, since suitable antigens have not been found in certain cell types, including embryonic gonadal somatic cells and Sertoli cells. To address this issue, we established a knock-in mouse line, named R26 KI, designed to express the human cell surface antigen hCD271 through Cre/loxP-mediated recombination. First, we used the R26 Kl mouse line to purify embryonic gonadal somatic cells. Gonadal somatic cells were purified from the R26 KI; Nr5a1-Cre-transgenic (tg) embryos almost equally as efficiently as from Nr5a1-hCD271-tg embryos. Second, we used the R26 KI mouse line to purify Sertoli cells successfully from R26 KI; Amh-Cre-tg testes. In summary, we propose that the R26 KI mouse line is a powerful tool for the purification of various cell types. © 2015 Wiley Periodicals, Inc.

  16. CHARACTERIZATION OF TIGHTLY-ASSOCIATED SMOOTH MUSCLE MYOSIN-MYOSIN LIGHT CHAIN KINASE-CALMODULIN COMPLEXES*

    OpenAIRE

    Hong, Feng; Haldeman, Brian D.; John, Olivia A.; Brewer, Paul D.; Wu, Yi-Ying; Ni, Shaowei; Wilson, David P.; Walsh, Michael P.; Baker, Jonathan E.; Cremo, Christine R.

    2009-01-01

    A current popular model to explain phosphorylation of smooth muscle myosin (SMM) by smooth muscle myosin light chain kinase (MLCK) proposes that MLCK is bound tightly to actin but weakly to SMM. We found that MLCK and calmodulin (CaM) co-purify with unphosphorylated SMM (up-SMM) from chicken gizzard, suggesting that they are tightly bound. Although the MLCK:SMM molar ratio in SMM preparations was well below stoichiometric (1:73 ± 9), the ratio was ~ 23–37% of that in gizzard tissue. Fifteen t...

  17. FDTD approach to optical forces of tightly focused vector beams on metal particles.

    Science.gov (United States)

    Qin, Jian-Qi; Wang, Xi-Lin; Jia, Ding; Chen, Jing; Fan, Ya-Xian; Ding, Jianping; Wang, Hui-Tian

    2009-05-11

    We propose an improved FDTD method to calculate the optical forces of tightly focused beams on microscopic metal particles. Comparison study on different kinds of tightly focused beams indicates that trapping efficiency can be altered by adjusting the polarization of the incident field. The results also show the size-dependence of trapping forces exerted on metal particles. Transverse tapping forces produced by different illumination wavelengths are also evaluated. The numeric simulation demonstrates the possibility of trapping moderate-sized metal particles whose radii are comparable to wavelength.

  18. An efficient magnetic tight-binding method for transition metals and alloys

    DEFF Research Database (Denmark)

    Barreteau, Cyrille; Spanjaard, Daniel; Desjonquères, Marie-Catherine

    2016-01-01

    that does not necessitate any further fitting is proposed to deal with systems made of several chemical elements. This model is extended to spin (and orbital) polarized materials by adding Stoner-like and spin–orbit interactions. Collinear and non-collinear magnetism as well as spin-spirals are considered......An efficient parameterized self-consistent tight-binding model for transition metals using s, p and d valence atomic orbitals as a basis set is presented. The parameters of our tight-binding model for pure elements are determined from a fit to bulk ab-initio calculations. A very simple procedure...

  19. Device for providing a leak-tight penetration for electric cables through a reactor vault roof

    International Nuclear Information System (INIS)

    Eyral, M.; Mahe, A.

    1979-01-01

    The device for providing a cable penetration through the vault roof of a liquid sodium cooled fast reactor comprises a vertical tube closed at the top end by a flange-plate. Electric cables connected to measuring and detecting instruments are passed through the flange-plate which is joined to the reactor vault roof in leak-tight manner and enclosed within a removable hood. At least one horizontal plate is mounted within the vertical tube and provided with orifices for the leak-tight passage of the cables. Cable storage reels are placed within the tube and can be locked in position or released by controlled mechanical means

  20. The roles of loosely-bound and tightly-bound extracellular polymer substances in enhanced biological phosphorus removal.

    Science.gov (United States)

    Long, Xiangyu; Tang, Ran; Fang, Zhendong; Xie, Chaoxin; Li, Yongqin; Xian, Guang

    2017-12-01

    Extracellular polymeric substances (EPS) have be founded to participate in the process of enhanced biological phosphorus removal (EBPR), but the exact role of EPS in EBPR process is unclear. In this work, the roles of loosely-bound EPS (LB-EPS), tightly-bound EPS (TB-EPS) and microbial cell in EBPR were explored, taking the activated sludge from 4 lab-scale A/O-SBR reactors with different temperatures and organic substrates as objects. It was founded that the P of EBPR activated sludge was mainly stored in TB-EPS, but the P of non-EBPR activated sludge was primarily located in microbial cell. The P release and uptake of EBPR activated sludge was attributed to the combined action of TB-EPS and microbial cell. Furthermore, TB-EPS played an more important role than microbial cell in EBPR process. With the analysis of 31 P NMR spectroscopy, both polyP and orthoP were the main phosphorus species of TB-EPS in EBPR sludge, but only orthoP was the main phosphorus species of LB-EPS and microbial cell. During the anaerobic-aerobic cycle, the roles of LB-EPS, TB-EPS and microbial cell in transfer and transformation of P in EBPR sludge were obviously different. LB-EPS transported and retained orthoP, and microbial cell directly anaerobically released or aerobically absorbed orthoP. Importantly, TB-EPS not only transported and retained orthoP, but also participated in biological phosphorus accumulation. The EBPR performance of sludge was closely related with the polyp in TB-EPS, which might be synthesized and decomposed by extracellular enzyme. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. A new water permeability measurement method for unsaturated tight materials using saline solutions

    International Nuclear Information System (INIS)

    Malinsky, Laurent; Talandier, Jean

    2012-01-01

    Document available in extended abstract form only. Relative water permeability of material in a radioactive waste disposal is a key parameter to simulate and predict saturation state evolution. In this paper we present a new measurement method and the results obtained for Callovo-Oxfordian (Cox) clay-stone, host rock of the underground Andra laboratory at Bure (Meuse/Haute-Marne). Relative water permeability of such a low permeability rock as Cox clay-stone has been measured up to now by an indirect method. It consists in submitting a rock sample to successive relative humidity steps imposed by saline solutions. The transient mass variation during each step and the mass at hydric equilibrium are interpreted generally by using an inverse analysis method. The water relative permeability function of water saturation is derived from water diffusion coefficient evolution and water retention curve. The proposed new method consists in directly measuring the water flux across a flat cylindrical submitted to a relative humidity gradient. Two special cells have been developed. The tightness of the lateral sample surface is insured by crushing a polyurethane ring surrounding the sample set in an aluminium device placed over a Plexiglas vessel filled with a saline solution. One of the cells is designed to allow humidity measurement in the cell. These cells can also be used to measure the relative humidity produced by a saline solution or by an unsaturated material. During a permeability measurement, the cell with the sample to be tested is continuously weighted in a Plexiglas box in which a saline solution imposes a different relative humidity at the upper sample face. The experimental set-up is shown on Figure 1. The mean permeability of the sample is proportional to the rate of mass variation when steady state is reached. The result of one test is shown on Figure 2(a). Twenty four permeability measurements have been performed on four argillite samples of 15 mm in height and

  2. Tight valve

    International Nuclear Information System (INIS)

    Guedj, F.

    1987-01-01

    This sealed valve is made with a valve seat, an axial valve with a rod fixed to its upper end, a thick bell surrounding the rod and welded by a thin join on the valve casing, a threated ring screwed onto the upper end of the rod and a magnet or electromagnet rotating the ring outside the bell [fr

  3. Water tight.

    Science.gov (United States)

    Postel, S

    1993-01-01

    Many cities worldwide have gone beyond the limits of their water supply. Growing urban populations increase their demand for water, thereby straining local water supplies and requiring engineers to seek our even more distant water sources. It is costly to build and maintain reservoirs, canals, pumping stations, pipes, sewers, and treatment plants. Water supply activities require much energy and chemicals, thereby contributing to environmental pollution. Many cities are beginning to manage the water supply rather than trying to keep up with demand. Pumping ground water for Mexico City's 18 million residents (500,000 people added/year) surpasses natural replenishment by 50% to 80%, resulting in falling water tables and compressed aquifers. Mexico City now ambitiously promotes replacement of conventional toilets with 1.6 gallon toilets (by late 1991, this had saved almost 7.4 billion gallons of water/year). Continued high rural-urban migration and high birth rates could negate any savings, however. Waterloo, Ontario, has also used conservation efforts to manage water demand. These efforts include retrofit kits to make plumbing fixtures more efficient, efficiency standards for plumbing fixtures, and reduction of water use outdoors. San Jose, California, has distributed water savings devices to about 220,000 households with a 90% cooperation rate. Boston, Massachusetts, not only promoted water saving devices but also repaired leaks and had an information campaign. Increasing water rates to actually reflect true costs also leads to water conservation, but not all cities in developing countries use water meters. All households in Edmonton, Alberta, are metered and its water use is 1/2 of that of Calgary, where only some households are metered. Tucson, Arizona, reduced per capita water use 16% by raising water rates and curbing water use on hot days. Bogor, Indonesia, reduced water use almost 30% by increasing water rates. In the US, more and more states are mandating use of water-efficient plumbing fixtures. Multilateral development agencies have identified some developing country cities as demonstrated sites for urban water conservation.

  4. Thermodynamic studies of a series of homologous HIV-1 TAR RNA ligands reveal that loose binders are stronger Tat competitors than tight ones.

    Science.gov (United States)

    Pascale, Lise; Azoulay, Stéphane; Di Giorgio, Audrey; Zenacker, Laura; Gaysinski, Marc; Clayette, Pascal; Patino, Nadia

    2013-06-01

    RNA is a major drug target, but the design of small molecules that modulate RNA function remains a great challenge. In this context, a series of structurally homologous 'polyamide amino acids' (PAA) was studied as HIV-1 trans-activating response (TAR) RNA ligands. An extensive thermodynamic study revealed the occurence of an enthalpy-entropy compensation phenomenon resulting in very close TAR affinities for all PAA. However, their binding modes and their ability to compete with the Tat fragment strongly differ according to their structure. Surprisingly, PAA that form loose complexes with TAR were shown to be stronger Tat competitors than those forming tight ones, and thermal denaturation studies demonstrated that loose complexes are more stable than tight ones. This could be correlated to the fact that loose and tight ligands induce distinct RNA conformational changes as revealed by circular dichroism experiments, although nuclear magnetic resonance (NMR) experiments showed that the TAR binding site is the same in all cases. Finally, some loose PAA also display promising inhibitory activities on HIV-infected cells. Altogether, these results lead to a better understanding of RNA interaction modes that could be very useful for devising new ligands of relevant RNA targets.

  5. Intraoperative tight glucose control using hyperinsulinemic normoglycemia increases delirium after cardiac surgery.

    Science.gov (United States)

    Saager, Leif; Duncan, Andra E; Yared, Jean-Pierre; Hesler, Brian D; You, Jing; Deogaonkar, Anupa; Sessler, Daniel I; Kurz, Andrea

    2015-06-01

    Postoperative delirium is common in patients recovering from cardiac surgery. Tight glucose control has been shown to reduce mortality and morbidity. Therefore, the authors sought to determine the effect of tight intraoperative glucose control using a hyperinsulinemic-normoglycemic clamp approach on postoperative delirium in patients undergoing cardiac surgery. The authors enrolled 198 adult patients having cardiac surgery in this randomized, double-blind, single-center trial. Patients were randomly assigned to either tight intraoperative glucose control with a hyperinsulinemic-normoglycemic clamp (target blood glucose, 80 to 110 mg/dl) or standard therapy (conventional insulin administration with blood glucose target, battery. The authors considered patients to have experienced postoperative delirium when Confusion Assessment Method testing was positive at any assessment. A positive Confusion Assessment Method was defined by the presence of features 1 (acute onset and fluctuating course) and 2 (inattention) and either 3 (disorganized thinking) or 4 (altered consciousness). Patients randomized to tight glucose control were more likely to be diagnosed as being delirious than those assigned to routine glucose control (26 of 93 vs. 15 of 105; relative risk, 1.89; 95% CI, 1.06 to 3.37; P = 0.03), after adjusting for preoperative usage of calcium channel blocker and American Society of Anesthesiologist physical status. Delirium severity, among patients with delirium, was comparable with each glucose management strategy. Intraoperative hyperinsulinemic-normoglycemia augments the risk of delirium after cardiac surgery, but not its severity.

  6. Subchannel analysis of 37-rod tight-lattice bundle experiments for reduced-moderation water reactor

    International Nuclear Information System (INIS)

    Nakatsuka, Toru; Tamai, Hidesada; Akimoto, Hajime

    2005-01-01

    R and D project to investigate thermal-hydraulic performance of tight-lattice fuel bundles for Reduced-Moderation Water Reactor (RMWR) started at Japan Atomic Energy Research Institute (JAERI) in collaboration with utilities, reactor vendors and universities from 2002. The RMWR realizes a high conversion ratio larger than 0.1 for sustainable energy supply through plutonium multiple recycling based on the well-experienced LWR technologies. The reactor core comprises tight-lattice fuel assemblies with gap clearance of around 1.0 mm to reduce the water volume ratio to achieve the high conversion ratio. A problem of utmost importance from a thermal-hydraulic point of view is the coolability of the tight-lattice assembly with such a small gap width. JAERI has been carrying out experimental study to investigate the system parameter effects on the thermal-hydraulic performance and to confirm the feasibility of the core. In the present study, the subchannel analysis code NASCA was applied to 37-rod tight-lattice bundle experiments. The NASCA can give good predictions of critical power for the gap width of 1.3 mm while the prediction accuracy decreases for the gap width of 1.0 mm. To improve the prediction accuracy, the code will be modified to take the effect of film thickness distribution around fuel rods on boiling transition. (author)

  7. Vibrationally resolved UV/Vis spectroscopy with time-dependent density functional based tight binding

    NARCIS (Netherlands)

    Ruger, R.; Niehaus, T.; van Lenthe, E.; Heine, T.; Visscher, L.

    2016-01-01

    We report a time-dependent density functional based tight-binding (TD-DFTB) scheme for the calculation of UV/Vis spectra, explicitly taking into account the excitation of nuclear vibrations via the adiabatic Hessian Franck-Condon method with a harmonic approximation for the nu- clear wavefunction.

  8. Quantum confined Stark effect in Gaussian quantum wells: A tight-binding study

    International Nuclear Information System (INIS)

    Ramírez-Morales, A.; Martínez-Orozco, J. C.; Rodríguez-Vargas, I.

    2014-01-01

    The main characteristics of the quantum confined Stark effect (QCSE) are studied theoretically in quantum wells of Gaussian profile. The semi-empirical tight-binding model and the Green function formalism are applied in the numerical calculations. A comparison of the QCSE in quantum wells with different kinds of confining potential is presented

  9. Quantum confined Stark effect in Gaussian quantum wells: A tight-binding study

    Energy Technology Data Exchange (ETDEWEB)

    Ramírez-Morales, A.; Martínez-Orozco, J. C.; Rodríguez-Vargas, I. [Unidad Académica de Física, Universidad Autónoma de Zacatecas, Calzada Solidaridad Esquina Con Paseo La Bufa S/N, 98060 Zacatecas, Zac. (Mexico)

    2014-05-15

    The main characteristics of the quantum confined Stark effect (QCSE) are studied theoretically in quantum wells of Gaussian profile. The semi-empirical tight-binding model and the Green function formalism are applied in the numerical calculations. A comparison of the QCSE in quantum wells with different kinds of confining potential is presented.

  10. Results from Tight and Loose Coupled Multiphysics in Nuclear Fuels Performance Simulations using BISON

    Energy Technology Data Exchange (ETDEWEB)

    S. R. Novascone; B. W. Spencer; D. Andrs; R. L. Williamson; J. D. Hales; D. M. Perez

    2013-05-01

    The behavior of nuclear fuel in the reactor environment is affected by multiple physics, most notably heat conduction and solid mechanics, which can have a strong influence on each other. To provide credible solutions, a fuel performance simulation code must have the ability to obtain solutions for each of the physics, including coupling between them. Solution strategies for solving systems of coupled equations can be categorized as loosely-coupled, where the individual physics are solved separately, keeping the solutions for the other physics fixed at each iteration, or tightly coupled, where the nonlinear solver simultaneously drives down the residual for each physics, taking into account the coupling between the physics in each nonlinear iteration. In this paper, we compare the performance of loosely and tightly coupled solution algorithms for thermomechanical problems involving coupled thermal and mechanical contact, which is a primary source of interdependence between thermal and mechanical solutions in fuel performance models. The results indicate that loosely-coupled simulations require significantly more nonlinear iterations, and may lead to convergence trouble when the thermal conductivity of the gap is too small. We also apply the tightly coupled solution strategy to a nuclear fuel simulation of an experiment in a test reactor. Studying the results from these simulations indicates that perhaps convergence for either approach may be problem dependent, i.e., there may be problems for which a loose coupled approach converges, where tightly coupled won’t converge and vice versa.

  11. Third nearest neighbor parameterized tight binding model for graphene nano-ribbons

    Directory of Open Access Journals (Sweden)

    Van-Truong Tran

    2017-07-01

    Full Text Available The existing tight binding models can very well reproduce the ab initio band structure of a 2D graphene sheet. For graphene nano-ribbons (GNRs, the current sets of tight binding parameters can successfully describe the semi-conducting behavior of all armchair GNRs. However, they are still failing in reproducing accurately the slope of the bands that is directly associated with the group velocity and the effective mass of electrons. In this work, both density functional theory and tight binding calculations were performed and a new set of tight binding parameters up to the third nearest neighbors including overlap terms is introduced. The results obtained with this model offer excellent agreement with the predictions of the density functional theory in most cases of ribbon structures, even in the high-energy region. Moreover, this set can induce electron-hole asymmetry as manifested in results from density functional theory. Relevant outcomes are also achieved for armchair ribbons of various widths as well as for zigzag structures, thus opening a route for multi-scale atomistic simulation of large systems that cannot be considered using density functional theory.

  12. MRI tight posterior fossa sign for prenatal diagnosis of Chiari type II malformation

    Energy Technology Data Exchange (ETDEWEB)

    Ando, Kumiko; Ishikura, Reiichi; Ogawa, Masayo; Takada, Yoshihiro; Yamamoto, Satoshi; Fujiwara, Masayuki; Hirota, Shozo [Hyogo College of Medicine, Department of Radiology, Nishinomiya, Hyogo (Japan); Shakudo, Miyuki [Osaka City General Hospital, Department of Radiology, Osaka (Japan); Tanaka, Hiroyuki [Hyogo College of Medicine, Department of Gynecology, Nishinomiya (Japan); Minagawa, Kyoko [Hyogo College of Medicine, Department of Pediatrics, Nishinomiya (Japan)

    2007-12-15

    Chiari type II malformation (CMII) is one of three hindbrain malformations that display hydrocephalus. We have observed that cerebrospinal fluid (CSF) signal in the posterior fossa, which is always apparent on normal fetal MR images, is not visible in a fetus with CMII. We use the term 'tight posterior fossa' for this MR imaging finding, and evaluate the diagnostic value of this finding on fetal MR images. Included in the study were 21 fetuses which underwent brain MR imaging at 1.5 T using two-dimensional balanced turbo-field-echo (2-D balanced-TFE) in the axial and sagittal planes. Postnatal diagnoses were CMII (n=5), CNS abnormalities other than CMII (n=8), and no abnormality (n=8). A tight posterior fossa was defined as an absent or slit-like water signal space around the hindbrain in the posterior fossa on both sagittal and axial MR images. All CMII fetuses displayed a tight posterior fossa on MR images. Hydrocephalus was visualized in all CMII fetuses and myelomeningocele in four fetuses, but hindbrain herniation was visualized only in two of five fetuses. The CSF signal surrounding the hindbrain was clearly visible in all the other 16 fetuses, including five with hydrocephalus not associated with CMII, although it was slightly narrower in a fetus with a cloverleaf skull than in the normal fetuses. Tight posterior fossa in the presence of hydrocephalus is a useful and characteristic finding of CMII on fetal MRI. (orig.)

  13. MRI tight posterior fossa sign for prenatal diagnosis of Chiari type II malformation

    International Nuclear Information System (INIS)

    Ando, Kumiko; Ishikura, Reiichi; Ogawa, Masayo; Takada, Yoshihiro; Yamamoto, Satoshi; Fujiwara, Masayuki; Hirota, Shozo; Shakudo, Miyuki; Tanaka, Hiroyuki; Minagawa, Kyoko

    2007-01-01

    Chiari type II malformation (CMII) is one of three hindbrain malformations that display hydrocephalus. We have observed that cerebrospinal fluid (CSF) signal in the posterior fossa, which is always apparent on normal fetal MR images, is not visible in a fetus with CMII. We use the term 'tight posterior fossa' for this MR imaging finding, and evaluate the diagnostic value of this finding on fetal MR images. Included in the study were 21 fetuses which underwent brain MR imaging at 1.5 T using two-dimensional balanced turbo-field-echo (2-D balanced-TFE) in the axial and sagittal planes. Postnatal diagnoses were CMII (n=5), CNS abnormalities other than CMII (n=8), and no abnormality (n=8). A tight posterior fossa was defined as an absent or slit-like water signal space around the hindbrain in the posterior fossa on both sagittal and axial MR images. All CMII fetuses displayed a tight posterior fossa on MR images. Hydrocephalus was visualized in all CMII fetuses and myelomeningocele in four fetuses, but hindbrain herniation was visualized only in two of five fetuses. The CSF signal surrounding the hindbrain was clearly visible in all the other 16 fetuses, including five with hydrocephalus not associated with CMII, although it was slightly narrower in a fetus with a cloverleaf skull than in the normal fetuses. Tight posterior fossa in the presence of hydrocephalus is a useful and characteristic finding of CMII on fetal MRI. (orig.)

  14. Loose and Tight Coupling in Educational Organizations--An Integrative Literature Review

    Science.gov (United States)

    Hautala, Tanja; Helander, Jaakko; Korhonen, Vesa

    2018-01-01

    Purpose: The purpose of this paper is to review and synthesize the attributes of loose and tight coupling in educational organizations. In addition, it is aimed to determine whether this phenomenon has value and strategies to offer for the current educational administration and research. Design/methodology/approach: Integrative literature review…

  15. Experience in North America Tight Oil Reserves Development. Horizontal Wells and Multistage Hydraulic Fracturing

    Directory of Open Access Journals (Sweden)

    R.R. Ibatullin

    2017-09-01

    Full Text Available The accelerated development of horizontal drilling technology in combination with the multistage hydraulic fracturing of the reservoir has expanded the geological conditions for commercial oil production from tight reservoirs in North America. Geological and physical characteristics of tight reservoirs in North America are presented, as well as a comparison of the geological and physical properties of the reservoirs of the Western Canadian Sedimentary Basin and the Volga-Ural oil and gas province, in particular, in the territory of Tatarstan. The similarity of these basins is shown in terms of formation and deposition. New drilling technologies for horizontal wells (HW and multistage hydraulic fracturing are considered. The drilling in tight reservoirs is carried out exclusively on hydrocarbon-based muds The multi-stage fracturing technology with the use of sliding sleeves, and also slick water – a low-viscous carrier for proppant is the most effective solution for conditions similar to tight reservoirs in the Devonian formation of Tatarstan. Tax incentives which are actively used for the development of HW and multistage fracturing technologies in Canada are described. wells, multistage fracturing

  16. Microwave emulations and tight-binding calculations of transport in polyacetylene

    International Nuclear Information System (INIS)

    Stegmann, Thomas; Franco-Villafañe, John A.; Ortiz, Yenni P.; Kuhl, Ulrich; Mortessagne, Fabrice; Seligman, Thomas H.

    2017-01-01

    A novel approach to investigate the electron transport of cis- and trans-polyacetylene chains in the single-electron approximation is presented by using microwave emulation measurements and tight-binding calculations. In the emulation we take into account the different electronic couplings due to the double bonds leading to coupled dimer chains. The relative coupling constants are adjusted by DFT calculations. For sufficiently long chains a transport band gap is observed if the double bonds are present, whereas for identical couplings no band gap opens. The band gap can be observed also in relatively short chains, if additional edge atoms are absent, which cause strong resonance peaks within the band gap. The experimental results are in agreement with our tight-binding calculations using the nonequilibrium Green's function method. The tight-binding calculations show that it is crucial to include third nearest neighbor couplings to obtain the gap in the cis-polyacetylene. - Highlights: • Electronic transport in individual polyacetylene chains is studied. • Microwave emulation experiments and tight-binding calculations agree well. • In long chains a band-gap opens due the dimerization of the chain. • In short chains edge atoms cause strong resonance peaks in the center of the band-gap.

  17. Universality of energy conversion efficiency for optimal tight-coupling heat engines and refrigerators

    International Nuclear Information System (INIS)

    Sheng, Shiqi; Tu, Z C

    2013-01-01

    A unified χ-criterion for heat devices (including heat engines and refrigerators), which is defined as the product of the energy conversion efficiency and the heat absorbed per unit time by the working substance (de Tomás et al 2012 Phys. Rev. E 85 010104), is optimized for tight-coupling heat engines and refrigerators operating between two heat baths at temperatures T c and T h ( > T c ). By taking a new convention on the thermodynamic flux related to the heat transfer between two baths, we find that for a refrigerator tightly and symmetrically coupled with two heat baths, the coefficient of performance (i.e., the energy conversion efficiency of refrigerators) at maximum χ asymptotically approaches √(ε C ) when the relative temperature difference between two heat baths ε C -1 ≡(T h -T c )/T c is sufficiently small. Correspondingly, the efficiency at maximum χ (equivalent to maximum power) for a heat engine tightly and symmetrically coupled with two heat baths is proved to be η C /2+η C 2 /8 up to the second order term of η C ≡ (T h − T c )/T h , which reverts to the universal efficiency at maximum power for tight-coupling heat engines operating between two heat baths at small temperature difference in the presence of left–right symmetry (Esposito et al 2009 Phys. Rev. Lett. 102 130602). (fast track communication)

  18. Oxytocin injections in the postpartal period affect mammary tight junctions in sows

    DEFF Research Database (Denmark)

    Farmer, C.; Lessard, M.; Knight, C. H.

    2017-01-01

    The potential impacts of injecting oxytocin (OXY) to sows in the early postpartum period on the quality of mammary tight junctions, milk composition, and immune status of sows and piglets were studied. Postparturient sows received i.m. injections of either saline (control [CTL]; n = 10) or 75 IU ...

  19. Microwave emulations and tight-binding calculations of transport in polyacetylene

    Energy Technology Data Exchange (ETDEWEB)

    Stegmann, Thomas, E-mail: stegmann@icf.unam.mx [Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n, 62210 Cuernavaca (Mexico); Franco-Villafañe, John A., E-mail: jofravil@fis.unam.mx [Instituto de Física, Benemérita Universidad Autónoma de Puebla, Apartado Postal J-48, 72570 Puebla (Mexico); Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n, 62210 Cuernavaca (Mexico); Ortiz, Yenni P. [Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n, 62210 Cuernavaca (Mexico); Kuhl, Ulrich [Université de Nice – Sophia Antipolis, Laboratoire de la Physique de la Matière Condensée, CNRS, Parc Valrose, 06108 Nice (France); Mortessagne, Fabrice, E-mail: fabrice.mortessagne@unice.fr [Université de Nice – Sophia Antipolis, Laboratoire de la Physique de la Matière Condensée, CNRS, Parc Valrose, 06108 Nice (France); Seligman, Thomas H. [Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Avenida Universidad s/n, 62210 Cuernavaca (Mexico); Centro Internacional de Ciencias, 62210 Cuernavaca (Mexico)

    2017-01-05

    A novel approach to investigate the electron transport of cis- and trans-polyacetylene chains in the single-electron approximation is presented by using microwave emulation measurements and tight-binding calculations. In the emulation we take into account the different electronic couplings due to the double bonds leading to coupled dimer chains. The relative coupling constants are adjusted by DFT calculations. For sufficiently long chains a transport band gap is observed if the double bonds are present, whereas for identical couplings no band gap opens. The band gap can be observed also in relatively short chains, if additional edge atoms are absent, which cause strong resonance peaks within the band gap. The experimental results are in agreement with our tight-binding calculations using the nonequilibrium Green's function method. The tight-binding calculations show that it is crucial to include third nearest neighbor couplings to obtain the gap in the cis-polyacetylene. - Highlights: • Electronic transport in individual polyacetylene chains is studied. • Microwave emulation experiments and tight-binding calculations agree well. • In long chains a band-gap opens due the dimerization of the chain. • In short chains edge atoms cause strong resonance peaks in the center of the band-gap.

  20. Leak testing of bubble-tight dampers using tracer gas techniques

    Energy Technology Data Exchange (ETDEWEB)

    Lagus, P.L. [Lagus Applied Technology, Inc., San Diego, CA (United States); DuBois, L.J. [Commonwealth Edison, Zion, IL (United States); Fleming, K.M. [NCS Corporation, Columbus, OH (United States)] [and others

    1995-02-01

    Recently tracer gas techniques have been applied to the problem of measuring the leakage across an installed bubble-tight damper. A significant advantage of using a tracer gas technique is that quantitative leakage data are obtained under actual operating differential pressure conditions. Another advantage is that leakage data can be obtained using relatively simple test setups that utilize inexpensive materials without the need to tear ducts apart, fabricate expensive blank-off plates, and install test connections. Also, a tracer gas technique can be used to provide an accurate field evaluation of the performance of installed bubble-tight dampers on a periodic basis. Actual leakage flowrates were obtained at Zion Generating Station on four installed bubble-tight dampers using a tracer gas technique. Measured leakage rates ranged from 0.01 CFM to 21 CFM. After adjustment and subsequent retesting, the 21 CFM damper leakage was reduced to a leakage of 3.8 CFM. In light of the current regulatory climate and the interest in Control Room Habitability issues, imprecise estimates of critical air boundary leakage rates--such as through bubble-tight dampers--are not acceptable. These imprecise estimates can skew radioactive dose assessments as well as chemical contaminant exposure calculations. Using a tracer gas technique, the actual leakage rate can be determined. This knowledge eliminates a significant source of uncertainty in both radioactive dose and/or chemical exposure assessments.

  1. The Passions of Learning in Tight Circumstances: Toward a Political Economy of the Mind

    Science.gov (United States)

    McDermott, Ray

    2010-01-01

    Economies make their demands, and by necessity, people adjust, learn, and survive. People adjust to tight circumstances with passion and ingenuity. Necessity and its passions are the stuff of reality and generally more than schools or educational research can handle. Mainstream theories of learning have captured economic constraints only…

  2. Results from tight and loose coupled multiphysics in nuclear fuels performance simulations using BISON

    International Nuclear Information System (INIS)

    Novascone, S. R.; Spencer, B. W.; Andrs, D.; Williamson, R. L.; Hales, J. D.; Perez, D. M.

    2013-01-01

    The behavior of nuclear fuel in the reactor environment is affected by multiple physics, most notably heat conduction and solid mechanics, which can have a strong influence on each other. To provide credible solutions, a fuel performance simulation code must have the ability to obtain solutions for each of the physics, including coupling between them. Solution strategies for solving systems of coupled equations can be categorized as loosely-coupled, where the individual physics are solved separately, keeping the solutions for the other physics fixed at each iteration, or tightly coupled, where the nonlinear solver simultaneously drives down the residual for each physics, taking into account the coupling between the physics in each nonlinear iteration. In this paper, we compare the performance of loosely and tightly coupled solution algorithms for thermomechanical problems involving coupled thermal and mechanical contact, which is a primary source of interdependence between thermal and mechanical solutions in fuel performance models. The results indicate that loosely-coupled simulations require significantly more nonlinear iterations, and may lead to convergence trouble when the thermal conductivity of the gap is too small. We also apply the tightly coupled solution strategy to a nuclear fuel simulation of an experiment in a test reactor. Studying the results from these simulations indicates that perhaps convergence for either approach may be problem dependent, i.e., there may be problems for which a loose coupled approach converges, where tightly coupled won't converge and vice versa. (authors)

  3. KIDNEY SIZE IN INFANTS OF TIGHTLY CONTROLLED INSULIN-DEPENDENT DIABETIC MOTHERS

    NARCIS (Netherlands)

    BOS, AF; AALDERS, AL; VANDOORMAAL, JJ; MARTIJN, A; OKKEN, A

    The aim of this study was to evaluate the influence of insulin-dependent diabetes mellitus in pregnant women on the kidney size of their infants. We measured kidney length in the first week of life using ultrasonography in 20 infants of tightly controlled insulin-dependent diabetic mothers and 20

  4. Evaluation of proximal contact tightness of Class II resin composite restorations.

    NARCIS (Netherlands)

    Saber, M.H.; Loomans, B.A.C.; Zohairy, A. El; Dorfer, C.E.; El-Badrawy, W.

    2010-01-01

    OBJECTIVE: The objective of the current study was to compare in-vitro the proximal contact tightness (PCT) of Class II resin composite restorations (RCR) placed with different established and new placement techniques. METHODS: 105 ivorine lower left first molars with standardized MO cavities were

  5. Nonlinear Filtering with IMM Algorithm for Ultra-Tight GPS/INS Integration

    Directory of Open Access Journals (Sweden)

    Dah-Jing Jwo

    2013-05-01

    Full Text Available Abstract This paper conducts a performance evaluation for the ultra-tight integration of a Global positioning system (GPS and an inertial navigation system (INS, using nonlinear filtering approaches with an interacting multiple model (IMM algorithm. An ultra-tight GPS/INS architecture involves the integration of in-phase and quadrature components from the correlator of a GPS receiver with INS data. An unscented Kalman filter (UKF, which employs a set of sigma points by deterministic sampling, avoids the error caused by linearization as in an extended Kalman filter (EKF. Based on the filter structural adaptation for describing various dynamic behaviours, the IMM nonlinear filtering provides an alternative for designing the adaptive filter in the ultra-tight GPS/INS integration. The use of IMM enables tuning of an appropriate value for the process of noise covariance so as to maintain good estimation accuracy and tracking capability. Two examples are provided to illustrate the effectiveness of the design and demonstrate the effective improvement in navigation estimation accuracy. A performance comparison among various filtering methods for ultra-tight integration of GPS and INS is also presented. The IMM based nonlinear filtering approach demonstrates the effectiveness of the algorithm for improved positioning performance.

  6. A fast simulation tool for evaluation of novel well stimulation techniques for tight gas reservoirs

    NARCIS (Netherlands)

    Egberts, P.J.P.; Peters, E.

    2015-01-01

    For stimulation of tight fields, alternatives to hydraulic fracturing based on hydraulic jetting are becoming available. With hydraulic jetting many (10 to 20) laterals can be created in a (sub-) vertical well. The laterals are 100 to 200 m long, typically 4 laterals are applied with a small

  7. Effect of Glucagon-like Peptide 2 on Tight Junction in Jejunal Epithelium of Weaned Pigs though MAPK Signaling Pathway

    Directory of Open Access Journals (Sweden)

    Changsong Yu

    2014-05-01

    Full Text Available The glucagon-like peptide 2 (GLP-2 that is expressed in intestine epithelial cells of mammals, is important for intestinal barrier function and regulation of tight junction (TJ proteins. However, there is little known about the intracellular mechanisms of GLP-2 in the regulation of TJ proteins in piglets’ intestinal epithelial cells. The purpose of this study is to test the hypothesis that GLP-2 regulates the expressions of TJ proteins in the mitogen-activated protein kinase (MAPK signaling pathway in piglets’ intestinal epithelial cells. The jejunal tissues were cultured in a Dulbecco’s modified Eagle’s medium/high glucose medium containing supplemental 0 to 100 nmol/L GLP-2. At 72 h after the treatment with the appropriate concentrations of GLP-2, the mRNA and protein expressions of zonula occludens-1 (ZO-1, occludin and claudin-1 were increased (p<0.05. U0126, an MAPK kinase inhibitor, prevented the mRNA and protein expressions of ZO-1, occludin, claudin-1 increase induced by GLP-2 (p<0.05. In conclusion, these results indicated that GLP-2 could improve the expression of TJ proteins in weaned pigs’ jejunal epithelium, and the underlying mechanism may due to the MAPK signaling pathway.

  8. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

    Science.gov (United States)

    Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

    2008-03-01

    Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

  9. Jack-knife stretching promotes flexibility of tight hamstrings after 4 weeks: a pilot study.

    Science.gov (United States)

    Sairyo, Koichi; Kawamura, Takeshi; Mase, Yasuyoshi; Hada, Yasushi; Sakai, Toshinori; Hasebe, Kiyotaka; Dezawa, Akira

    2013-08-01

    Tight hamstrings are reported to be one of the causes of low back pain. However, there have been few reports on effective stretching procedures for the tight hamstrings. The so-called jack-knife stretch, an active-static type of stretching, can efficiently increase the flexibility of tight hamstrings. To evaluate hamstring tightness before and after the 4-week stretching protocol in healthy volunteer adults and patients aged under 18 years with low back pain. For understanding the hamstrings tightness, we measured two parameters including (1) finger to floor distance (FFD) and (2) pelvis forward inclination angle (PFIA). Eight healthy adult volunteers who had no lumbar or hip problems participated in this study (mean age: 26.8 years). All lacked flexibility and their FFD were positive before the experiment. Subjects performed 2 sets of the jack-knife stretch every day for 4 weeks. One set consisted of 5 repetitions, each held for 5 s. Before and during the 4-week experiment, the FFD and PFIA of toe-touching tests were measured weekly. For 17 of the sports players aged under 18, only FFD was measured. In adult volunteers, FFD was 14.1 ± 6.1 cm before the experiment and decreased to -8.1 ± 3.7 cm by the end of week 4, indicating a gain in flexibility of 22.2 cm. PFIA was 50.6 ± 8.2 before the experiment and 83.8 ± 5.8 degrees after. Before and after the experiment, the differences were significant (p hamstrings.

  10. Leak tight sealants and joint details for concrete structure in RAPP

    International Nuclear Information System (INIS)

    Singha Roy, P.K.; Baste, M.S.

    1975-01-01

    Leak tightness may pertain to either air or water and in extreme cases each will require separate consideration based on general basic requirements. Leak-tight sealants against air pressure are required in the construction joints and around penetrations in the concrete containment structures. The containment structures should be able to withstand the maximum anticipated design pressure during the incident of a MCA with only minimal leakage (0.1% of bldg. volume per day in RAPP) which is mostly through these joints. Apart from proper joint design and preparation the sealant itself must have superb adhesion to the concrete surface and integrify throughout its service life to prevent any rupture or micro-cracks at any section of the joint. Leak tightness pertains to water tightness as well. A critical water-tight joint at the bottom dome of the prestressed concrete dousing tank at its junction with the 36 inches dia dousing water pipes constructed in RAPP-2, which should be able to withstand the water pressure, continuous submergence in the water of the tank and the longitudinal and lateral movement of the water pipes during opening and closure of the dousing valves, has been made and hydrostatically tested when not even the slight sweating was found. The construction and materials of the above joints and the sealant along with the properties and performance observed during testing/use are described. As the sealant used is an imported poly-sulphide caulking compound suggestions have also been made, which may be kept in mind while developing an Indian substitute. (author)

  11. Outcome of tight versus standard glycemic control in coronary artery bypass patients

    International Nuclear Information System (INIS)

    Subhani, H.

    2012-01-01

    Objectives: To compare the outcome of tight versus standard glycemic control and its impact on post operative morbidity and short term mortality in patients undergoing Coronary Artery Bypass Grafting (CA-BG). Patients and Methods: A prospective surveillance of 124 patients undergoing isolated CABG surgery (on pump) was included in the study, 62 patients in each group were randomly assigned to tight and standard glucose control group. The main exposure was insulin in respect to level of blood glucose and the primary outcome measures were Sternotomy wound infection, Leg wound infection and new Myocardial Infarction. Surgical Site infection was assessed on a daily basis during the patient's stay in the Department of Cardio-thoracic Surgery, Sheikh Zayed Hospital, Lahore or within 30 days of operation prompting the patient to return to the hospital. Chi-square test or test was used to identify the significance of various short term morbidities and mortality. Results: In this study, 12 patients in the standard group and 4 patients in the tightly controlled group developed Sternal wound infection (p value 0.046). Similarly, 9 versus 2 patients in the standard and tight group respectively developed Leg wound infection (p-value 0.035). Test of proportion was applied and it was found that there was significant difference in the pro-portion of infection in the two groups (p value 0.05). However, there were no significant differences in other morbidities and the short term mortality. Conclusion: Study confirmed that tight glucose con-trol post operatively in CABG patient's results in reduced sternal and leg wound infection rates; however, there was no effect on other morbidities and short term mortality. (author)

  12. Cell adhesion molecules expression pattern indicates that somatic cells arbitrate gonadal sex of differentiating bipotential fetal mouse gonad.

    Science.gov (United States)

    Piprek, Rafal P; Kolasa, Michal; Podkowa, Dagmara; Kloc, Malgorzata; Kubiak, Jacek Z

    2017-10-01

    Unlike other organ anlagens, the primordial gonad is sexually bipotential in all animals. In mouse, the bipotential gonad differentiates into testis or ovary depending on the genetic sex (XY or XX) of the fetus. During gonad development cells segregate, depending on genetic sex, into distinct compartments: testis cords and interstitium form in XY gonad, and germ cell cysts and stroma in XX gonad. However, our knowledge of mechanisms governing gonadal sex differentiation remains very vague. Because it is known that adhesion molecules (CAMs) play a key role in organogenesis, we suspected that diversified expression of CAMs should also play a crucial role in gonad development. Using microarray analysis we identified 129 CAMs and factors regulating cell adhesion during sexual differentiation of mouse gonad. To identify genes expressed differentially in three cell lines in XY and XX gonads: i) supporting (Sertoli or follicular cells), ii) interstitial or stromal cells, and iii) germ cells, we used transgenic mice expressing EGFP reporter gene and FACS cell sorting. Although a large number of CAMs expressed ubiquitously, expression of certain genes was cell line- and genetic sex-specific. The sets of CAMs differentially expressed in supporting versus interstitial/stromal cells may be responsible for segregation of these two cell lines during gonadal development. There was also a significant difference in CAMs expression pattern between XY supporting (Sertoli) and XX supporting (follicular) cells but not between XY and XX germ cells. This indicates that differential CAMs expression pattern in the somatic cells but not in the germ line arbitrates structural organization of gonadal anlagen into testis or ovary. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. TRPA1-dependent reversible opening of tight junction by natural compounds with an α,β-unsaturated moiety and capsaicin.

    Science.gov (United States)

    Kanda, Yusuke; Yamasaki, Youhei; Sasaki-Yamaguchi, Yoshie; Ida-Koga, Noriko; Kamisuki, Shinji; Sugawara, Fumio; Nagumo, Yoko; Usui, Takeo

    2018-02-02

    The delivery of hydrophilic macromolecules runs into difficulties such as penetration of the cell membrane lipid bilayer. Our prior experiment demonstrated that capsaicin induces the reversible opening of tight junctions (TJs) and enhances the delivery of hydrophilic macromolecules through a paracellular route. Herein, we screened paracellular permeability enhancers other than capsaicin. As TJ opening by capsaicin is associated with Ca 2+ influx, we first screened the compounds that induce Ca 2+ influx in layered MDCK II cells, and then we determined the compounds' abilities to open TJs. Our results identified several natural compounds with α,β-unsaturated moiety. A structure-activity relationship (SAR) analysis and the results of pretreatment with reducing reagent DTT suggested the importance of α,β-unsaturated moiety. We also examined the underlying mechanisms, and our findings suggest that the actin reorganization seen in capsaicin treatment is important for the reversibility of TJ opening. Furthermore, our analyses revealed that TRPA1 is involved in the Ca 2+ influx and TJ permeability increase not only by an α,β-unsaturated compound but also by capsaicin. Our results indicate that the α,β-unsaturated moiety can be a potent pharmacophore for TJ opening.

  14. Attenuated expression of the tight junction proteins is involved in clopidogrel-induced gastric injury through p38 MAPK activation

    International Nuclear Information System (INIS)

    Wu, Hai-Lu; Gao, Xin; Jiang, Zong-Dan; Duan, Zhao-Tao; Wang, Shu-Kui; He, Bang-Shun; Zhang, Zhen-Yu; Xie, Hong-Guang

    2013-01-01

    Highlights: ► Clopidogrel suppressed GES-1 cell viability in a concentration- and time-dependent manner. ► Clopidogrel significantly increased dextran permeability, reduced occludin and ZO-1 expression, and induced cell apoptosis. ► Clopidogrel activated p38 MAPK signaling pathway. ► Activation of p38 activity was involved in clopidogrel-induced increase in gastric epithelial cells permeability and disruption of TJ. -- Abstract: Bleeding complications and delayed healing of gastric ulcer associated with use of clopidogrel is a common clinical concern; however, the underlying mechanisms remain to be determined. This study aimed to clarify whether clopidogrel could cause the damage of the human gastric epithelial cells and to further elucidate the mechanisms involved. After human gastric epithelial cell line GES-1 had been treated with clopidogrel (0.5–2.5 mM), the cell proliferation was examined by MTT assay, apoptosis was measured with DAPI staining and flow cytometry analysis, and the barrier function of the tight junctions (TJ) was evaluated by permeability measurement and transmission electron microscopy. Moreover, expression of the TJ proteins occludin and ZO-1 and the phosphorylation of the mitogen-activated protein kinases (MAPK) p38, ERK, and JNK were examined by western blot. In addition, three MAPK inhibitors specific to p38, ERK and JNK were used, respectively, to verify the signaling pathways responsible for regulating the expression of the TJ proteins being tested. Results showed that clopidogrel significantly increased dextran permeability, induced apoptosis, suppressed GES-1 cell viability, and reduced the expression of the TJ proteins (occludin and ZO-1), acting through p38 MAPK phosphorylation. Furthermore, these observed effects were partially abolished by SB-203580 (a p38 MAPK inhibitor), rather than by either U-0126 (an ERK inhibitor) or SP-600125 (a JNK inhibitor), suggesting that clopidogrel-induced disruption in the gastric

  15. The tightness of the globe valves in the exploitations practice of the gas pipe-lines

    International Nuclear Information System (INIS)

    Pietrak, T.; Rudzki, Z.; Surmacz, W.

    2006-01-01

    Technological units of the Transit Gas Pipeline (i.e. Compressor Stations, Valve Stations, Stations or National Network Service Installations) have been fitted with Ball Valves as shut-off devices (block valves). Internal tightness of the valves' seat becomes major factor in securing proper service conditions during normal pipeline operation as well as for isolating of pipeline sections in emergency situations (loss of pipeline integrity or uncontrolled gas escape). Internal tightness of the valves is being inspected during scheduled maintenance of the pipeline units. Any leak revealed during inspection is being repaired, following instructions provided in the Manufacturer's Valve Manual. After a time, some cases have been identified, when repair of the revealed leak was found to be difficult, despite close following of the repair manuals. The paper presents analysis of the issue and corrective actions taken accordingly. (authors)

  16. Relevant multi-setting tight Bell inequalities for qubits and qutrits

    International Nuclear Information System (INIS)

    Deng Dongling; Zhou Zisui; Chen Jingling

    2009-01-01

    In the celebrated paper [D. Collins, N. Gisin, J. Phys. A Math. Gen. 37 (2004) 1775], Collins and Gisin presented for the first time a three-setting Bell inequality (here we call it CG inequality for simplicity) which is relevant to the Clauser-Horne-Shimony-Holt (CHSH) inequality. Inspired by their brilliant ideas, we obtained some multi-setting tight Bell inequalities, which are relevant to the CHSH inequality and the CG inequality. Moreover, we generalized the method in the paper [J.L. Chen, D.L. Deng, Phys. Rev. A 79 (2009) 012115] to construct Bell inequality for qubits to higher dimensional system. Based on the generalized method, we present, for the first time, a three-setting tight Bell inequality for two qutrits, which is maximally violated by nonmaximally entangled states and relevant to the Collins-Gisin-Linden-Massar-Popescu inequality.

  17. Nonlinear Thomson scattering of a relativistically strong tightly focused ultrashort laser pulse

    Energy Technology Data Exchange (ETDEWEB)

    Vais, O. E.; Bochkarev, S. G., E-mail: bochkar@sci.lebedev.ru; Bychenkov, V. Yu. [Russian Academy of Sciences, Lebedev Physical Institute (Russian Federation)

    2016-09-15

    The problem of nonlinear Thomson scattering of a relativistically strong linearly polarized ultrashort laser pulse tightly focused into a spot with a diameter of D{sub F} ≳ λ (where λ is the laser wavelength) is solved. The energy, spectral, and angular distributions of radiation generated due to Thomson scattering from test electrons located in the focal region are found. The characteristics of scattered radiation are studied as functions of the tightness of laser focusing and the initial position of test particles relative to the center of the focal region for a given laser pulse energy. It is demonstrated that the ultratight focusing is not optimal for obtaining the brightest and hardest source of secondary electromagnetic radiation. The hardest and shortest radiation pulse is generated when the beam waist diameter is ≃10λ.

  18. Transit Duration Variations due to Secular Interactions in Systems with Tightly-packed Inner Planets

    Science.gov (United States)

    Boley, Aaron; Van Laerhoven, Christa; Granados Contreras, A. Paula

    2018-04-01

    Secular interactions among planets in multi-planet systems will lead to variations in orbital inclinations and to the precession of orbital nodes. Taking known system architectures at face value, we calculate orbital precession rates for planets in tightly-packed systems using classical second-order secular theory, in which the orientation of the orbits can be described as a vector sum of eigenmodes and the eigenstructure is determined only by the masses and semi-major axes of the planets. Using this framework, we identify systems that have fast precession frequencies, and use those systems to explore the range of transit duration variation that could occur using amplitudes that are consistent with tightly-packed planetary systems. We then further assess how transit duration variations could be used in practice.

  19. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids

    International Nuclear Information System (INIS)

    Aradi, Balint; Frauenheim, Thomas

    2015-01-01

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born-Oppenheimer molecular dynamics. Furthermore, for systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can also be applied to a broad range of problems in materials science, chemistry, and biology

  20. Study of minor actinides transmutation in heavy water cooled tight-pitch lattice

    International Nuclear Information System (INIS)

    Xu Xiaoqin; Shiroya, S.

    2002-01-01

    Minor actinides inhere long half-life and high toxicity. It is an alternative technical pathway and helpful for reducing environmental impact to incinerate minor actinides in spent fuel of nuclear power plants. Because of its high neutron, γ and β emitting rates and heat generation rate, it is necessary to imply more severe control and shielding techniques in the chemical treatment and fabrication. From economic view-point, it is suitable to transmute minor actinides in concentrated way. A technique for MA transmutation by heavy water cooled tight-pitch lattice system is proposed, and calculated with SRAC95 code system. It is shown that tight-pitch heavy water lattice can transmute MA effectively. The accelerator-driven subcritical system is practical for MA transmutation because of its low fraction of effective delay neutrons

  1. Gate dielectric strength dependent performance of CNT MOSFET and CNT TFET: A tight binding study

    Directory of Open Access Journals (Sweden)

    Md. Shamim Sarker

    Full Text Available This paper presents a comparative study between CNT MOSFET and CNT TFET taking into account of different dielectric strength of gate oxide materials. Here we have studied the transfer characteristics, on/off current (ION/IOFF ratio and subthreshold slope of the device using Non Equilibrium Greens Function (NEGF formalism in tight binding frameworks. The results are obtained by solving the NEGF and Poisson’s equation self-consistently in NanoTCADViDES environment and found that the ON state performance of CNT MOSFET and CNT TFET have significant dependency on the dielectric strength of the gate oxide materials. The figure of merits of the devices also demonstrates that the CNT TFET is promising for high-speed and low-power logic applications. Keywords: CNT TFET, Subthreshold slop, Barrier width, Conduction band (C.B and Valance band (V.B, Oxide dielectric strength, Tight binding approach

  2. Long-Term Leak Tightness Of O-Ring Seals In The 9975 Shipping Package

    International Nuclear Information System (INIS)

    Hoffman, E.; Skidmore, E.; Daugherty, W.

    2010-01-01

    O-ring seals in the 9975 shipping package containment vessels are fabricated from a Viton GLT or GLT-S compound. Long-term testing of these O-rings has been performed to support service life predictions for packages used for long-term storage. Since the only criterion for O-ring performance is to maintain a leak-tight seal, leak testing is the primary indicator of service life. Fixtures have been aging at elevated temperatures to provide data for service life predictions. Limited leak test failures have been observed at the higher temperatures. This provides the opportunity for comparison to trends based on other O-ring properties, such as compression stress relaxation. Initial data suggest that the CSR data have some predictive value for a leak-tight service life, but other factors can complicate efforts to draw definitive conclusions.

  3. Tight binding electronic band structure calculation of achiral boron nitride single wall nanotubes

    International Nuclear Information System (INIS)

    Saxena, Prapti; Sanyal, Sankar P

    2006-01-01

    In this paper we report the Tight-Binding method, for the electronic structure calculations of achiral single wall Boron Nitride nanotubes. We have used the contribution of π electron only to define the electronic band structure for the solid. The Zone-folding method is used for the Brillouin Zone definition. Calculation of tight binding model parameters is done by fitting them to available experimental results of two-dimensional hexagonal monolayers of Boron Nitride. It has been found that all the boron nitride nanotubes (both zigzag and armchair) are constant gap semiconductors with a band gap of 5.27eV. All zigzag BNNTs are found to be direct gap semiconductors while all armchair nanotubes are indirect gap semiconductors. (author)

  4. Bulk and interface dielectric functions: New results within the tight-binding approximation

    International Nuclear Information System (INIS)

    Elvira, V.D.; Duran, J.C.

    1991-01-01

    A tight-binding approach is used to analyze the dielectric behaviour of bulk semiconductors and semiconductor interfaces. This time interactions between second nearest neighbours are taken into account and several electrostatic models are proposed for the induced charge density around the atoms. The bulk dielectric function of different semiconductors (Si, Ge, GaAs and AlAs) are obtained and compared with other theoretical and experimental results. Finally, the energy band offset for GaAs-AlAs(1,0,0) interface is obtained and related to bulk properties of both semiconductors. The results presented in this paper show how the use of very simple but more realistic electrostatic models improve the analysis of the screening properties in semiconductors, giving a new support to the consistent tight-binding method for studying characteristics related to those properties. (Author)

  5. Headache under simulated microgravity is related to endocrine, fluid distribution, and tight junction changes.

    Science.gov (United States)

    Feuerecker, Matthias; van Oosterhout, Willebrordus P J; Feuerecker, Benedikt; Matzel, Sandra; Schelling, Gustav; Rehm, Markus; Vein, Alla A; Choukèr, Alexander

    2016-05-01

    Head-down-tilted bed rest (HDTBR) induces headaches similar to headaches during space flights. The objective of this investigation was to study hematological, endocrinological, fluid changes and tight junctions in HDTBR-induced headaches as a proxy for space headache. The randomized crossover HDTBR design by the European Space Agency included 12 healthy, nonheadache male subjects. Before, during, and after confined HDTBR periods, epinephrine (urine), cortisol (saliva), hematological, endothelium markers, and fluid distribution parameters were measured. Headaches were assessed with a validated headache questionnaire. Compared with baseline, HDTBR in all subjects was associated with higher hematocrit, hemoglobin, and epinephrine levels, higher erythrocyte counts, and lower relative plasma volumes (all P zonulin was elevated (vs headache-free subjects in HDTBR days 1, 3, 5; P < 0.05). HDTBR induces hemoconcentration and fluid redistribution in all subjects. During headache episodes, endocrinological changes, fluid distribution, and tight junctions were more pronounced, suggesting an additional role in headache pathophysiology.

  6. Study on the pressure self-adaptive water-tight junction box in underwater vehicle

    Directory of Open Access Journals (Sweden)

    Haocai Huang

    2012-09-01

    Full Text Available Underwater vehicles play a very important role in underwater engineering. Water-tight junction box (WJB is one of the key components in underwater vehicle. This paper puts forward a pressure self-adaptive water-tight junction box (PSAWJB which improves the reliability of the WJB significantly by solving the sealing and pressure problems in conventional WJB design. By redundancy design method, the pressure self-adaptive equalizer (PSAE is designed in such a way that it consists of a piston pressure-adaptive compensator (PPAC and a titanium film pressure-adaptive compensator (TFPAC. According to hydro-mechanical simulations, the operating volume of the PSAE is more than or equal to 11.6 % of the volume of WJB liquid system. Furthermore, the required operating volume of the PSAE also increases as the gas content of oil, hydrostatic pressure or temperature difference increases. The reliability of the PSAWJB is proved by hyperbaric chamber tests.

  7. Tight upper bound for the maximal quantum value of the Svetlichny operators

    Science.gov (United States)

    Li, Ming; Shen, Shuqian; Jing, Naihuan; Fei, Shao-Ming; Li-Jost, Xianqing

    2017-10-01

    It is a challenging task to detect genuine multipartite nonlocality (GMNL). In this paper, the problem is considered via computing the maximal quantum value of Svetlichny operators for three-qubit systems and a tight upper bound is obtained. The constraints on the quantum states for the tightness of the bound are also presented. The approach enables us to give the necessary and sufficient conditions of violating the Svetlichny inequality (SI) for several quantum states, including the white and color noised Greenberger-Horne-Zeilinger (GHZ) states. The relation between the genuine multipartite entanglement concurrence and the maximal quantum value of the Svetlichny operators for mixed GHZ class states is also discussed. As the SI is useful for the investigation of GMNL, our results give an effective and operational method to detect the GMNL for three-qubit mixed states.

  8. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

    Science.gov (United States)

    Colombel, Jean-Frederic; Panaccione, Remo; Bossuyt, Peter; Lukas, Milan; Baert, Filip; Vaňásek, Tomas; Danalioglu, Ahmet; Novacek, Gottfried; Armuzzi, Alessandro; Hébuterne, Xavier; Travis, Simon; Danese, Silvio; Reinisch, Walter; Sandborn, William J; Rutgeerts, Paul; Hommes, Daniel; Schreiber, Stefan; Neimark, Ezequiel; Huang, Bidan; Zhou, Qian; Mendez, Paloma; Petersson, Joel; Wallace, Kori; Robinson, Anne M; Thakkar, Roopal B; D'Haens, Geert

    2018-12-23

    Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of 200; clinical management group after random assignment: CDAI decrease of management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group

  9. Extended Lagrangian Density Functional Tight-Binding Molecular Dynamics for Molecules and Solids.

    Science.gov (United States)

    Aradi, Bálint; Niklasson, Anders M N; Frauenheim, Thomas

    2015-07-14

    A computationally fast quantum mechanical molecular dynamics scheme using an extended Lagrangian density functional tight-binding formulation has been developed and implemented in the DFTB+ electronic structure program package for simulations of solids and molecular systems. The scheme combines the computational speed of self-consistent density functional tight-binding theory with the efficiency and long-term accuracy of extended Lagrangian Born-Oppenheimer molecular dynamics. For systems without self-consistent charge instabilities, only a single diagonalization or construction of the single-particle density matrix is required in each time step. The molecular dynamics simulation scheme can be applied to a broad range of problems in materials science, chemistry, and biology.

  10. Novel Implementations of Wideband Tightly Coupled Dipole Arrays for Wide-Angle Scanning

    Science.gov (United States)

    Yetisir, Ersin

    Ultra-wideband (UWB) antennas and arrays are essential for high data rate communications and for addressing spectrum congestion. Tightly coupled dipole arrays (TCDAs) are of particular interest due to their low-profile, bandwidth and scanning range. But existing UWB (>3:1 bandwidth) arrays still suffer from limited scanning, particularly at angles beyond 45° from broadside. Almost all previous wideband TCDAs have employed dielectric layers above the antenna aperture to improve scanning while maintaining impedance bandwidth. But even so, these UWB arrays have been limited to no more than 60° away from broadside. In this work, we propose to replace the dielectric superstrate with frequency selective surfaces (FSS). In effect, the FSS is used to create an effective dielectric layer placed over the antenna array. FSS also enables anisotropic responses and more design freedom than conventional isotropic dielectric substrates. Another important aspect of the FSS is its ease of fabrication and low weight, both critical for mobile platforms (e.g. unmanned air vehicles), especially at lower microwave frequencies. Specifically, it can be fabricated using standard printed circuit technology and integrated on a single board with active radiating elements and feed lines. In addition to the FSS superstrate, a modified version of the stripline-based folded Marchand balun is presented. As usual the balun serves to match the 50Ω coaxial cable to the high input impedance ( 200Ω) at the terminals of array elements. Doing so, earlier Wilkinson power dividers, which degrade efficiency during E-plane scanning, are eliminated. To verify the proposed array concept, 12x12 TCDA prototype was fabricated using the modified balun and the new FSS superstrate layer. The design and experimental data showed an impedance bandwidth of 6.1:1 with VSWR<3.2. The latter VSWR was achieved even when scanning down to +/-60° in the H-plane, +/-70° in the D-plane and +/-75° in the E-plane. All array

  11. A Tightly Coupled Non-Equilibrium Magneto-Hydrodynamic Model for Inductively Coupled RF Plasmas

    Science.gov (United States)

    2016-02-29

    development a tightly coupled magneto-hydrodynamic model for Inductively Coupled Radio- Frequency (RF) Plasmas. Non Local Thermodynamic Equilibrium (NLTE...for Inductively Coupled Radio-Frequency (RF) Plasmas. Non Local Thermodynamic Equilibrium (NLTE) effects are described based on a hybrid State-to-State...Inductively Coupled Plasma (ICP) torches have wide range of possible applications which include deposition of metal coatings, synthesis of ultra-fine powders

  12. Loose and Tight GNSS/INS Integrations: Comparison of Performance Assessed in Real Urban Scenarios

    OpenAIRE

    Falco, Gianluca; Pini, Marco; Marucco, Gianluca

    2017-01-01

    Global Navigation Satellite Systems (GNSSs) remain the principal mean of positioning in many applications and systems, but in several types of environment, the performance of standalone receivers is degraded. Although many works show the benefits of the integration between GNSS and Inertial Navigation Systems (INSs), tightly-coupled architectures are mainly implemented in professional devices and are based on high-grade Inertial Measurement Units (IMUs). This paper investigates the performanc...

  13. Rate concept and retarded master equations for dissipative tight-binding models

    International Nuclear Information System (INIS)

    Egger, R.; Mak, C.H.; Weiss, U.

    1994-01-01

    Employing a ''noninteracting-cluster approximation,'' the dynamics of multistate dissipative tight-binding models has been formulated in terms of a set of generalized retarded master equations. The rates for the various pathways are expressed as power series in the intersite couplings. We apply this to the superexchange mechanism, which is relevant for bacterial photosynthesis and bridged electron transfer systems. This approach provides a general and unified description of both incoherent and coherent transport

  14. A dynamic traction splint for the management of extrinsic tendon tightness.

    Science.gov (United States)

    Dovelle, S; Heeter, P K; Phillips, P D

    1987-02-01

    The dynamic traction splint designed by therapists at Walter Reed Army Medical Center is used for the management of extrinsic extensor tendon tightness commonly seen in brachial plexus injuries and traumatic soft tissue injuries of the upper extremity. The two components of the splint allow for simultaneous maximum flexion of the MCP and IP joints. This simple and economical splint provides an additional modality to any occupational therapy service involved in the management of upper extremity disorders.

  15. Air tightness of new houses in the U.S.: A preliminary report; TOPICAL

    International Nuclear Information System (INIS)

    Sherman, Max H.; Matson, Nance E.

    2002-01-01

    Most dwellings in the United States are ventilated primarily through leaks in the building shell (i.e., infiltration) rather than by whole-house mechanical ventilation systems. Consequently, quantification of envelope air-tightness is critical to determining how much energy is being lost through infiltration and how much infiltration is contributing toward ventilation requirements. Envelope air tightness and air leakage can be determined from fan pressurization measurements with a blower door. Tens of thousands of unique fan pressurization measurements have been made of U.S. dwellings over the past decades. LBNL has collected the available data on residential infiltration into its Residential Diagnostics Database, with support from the U.S. Department of Energy. This report documents the envelope air leakage section of the LBNL database, with particular emphasis on new construction. The work reported here is an update of similar efforts carried out a decade ago, which used available data largely focused on the housing stock, rather than on new construction. The current effort emphasizes shell tightness measurements made on houses soon after they are built. These newer data come from over two dozen datasets, including over 73,000 measurements spread throughout a majority of the U.S. Roughly one-third of the measurements are for houses identified as energy-efficient through participation in a government or utility program. As a result, the characteristics reported here provide a quantitative estimate of the impact that energy-efficiency programs have on envelope tightness in the US, as well as on trends in construction

  16. Nanometric locking of the tight focus for optical microscopy and tip-enhanced microscopy

    International Nuclear Information System (INIS)

    Hayazawa, N; Furusawa, K; Kawata, S

    2012-01-01

    We have successfully stabilized the tight focus onto the sample surface of an optical microscope within ±1.0 nm for a virtually unlimited time duration. The time-dependent thermal drift of the tight focus and the mechanical tilt of the sample surface were simultaneously sensed by a non-optical means based on a capacitive sensor and were compensated for in real-time. This non-optical scheme is promising for the suppression of background light sources for optical microscopy. The focus stabilization is crucial for microscopic measurement at an interface, particularly when scanning a large surface area, because there is always a certain amount of mechanical tilt of the sample substrate, which degrades the contrast of the image. When imaging nanoscopic materials such as carbon nanotubes or silicon nanowires, more stringent nanometric stabilization of the focus position relative to such samples is required, otherwise it is often difficult to interpret the results from the observations. Moreover, the smaller the sample volume is, the smaller the signal becomes, resulting in a long exposure time at each position. In this sense, long-term stability of the tight focus is essential for both microscopic large area scanning and nanosized sample scanning (high-resolution/large-area imaging). In addition, the recently developed tip-enhanced microscopy requires long-term stability of the relative position of the tip, sample and focus position. We were able to successfully demonstrate a stability improvement for tip-enhanced microscopy in the same manner. The stabilization of the tight focus enables us to perform long-term and robust measurements without any degradation of optical signal, resulting in the capability of true nanometric optical imaging with good reproducibility and high precision. The technique presented is a simple add-on for any kind of optical microscope. (paper)

  17. A Fuzzy Adaptive Tightly-Coupled Integration Method for Mobile Target Localization Using SINS/WSN

    Directory of Open Access Journals (Sweden)

    Wei Li

    2016-11-01

    Full Text Available In recent years, mobile target localization for enclosed environments has been a growing interest. In this paper, we have proposed a fuzzy adaptive tightly-coupled integration (FATCI method for positioning and tracking applications using strapdown inertial navigation system (SINS and wireless sensor network (WSN. The wireless signal outage and severe multipath propagation of WSN often influence the accuracy of measured distance and lead to difficulties with the WSN positioning. Note also that the SINS are known for their drifted error over time. Using as a base the well-known loosely-coupled integration method, we have built a tightly-coupled integrated positioning system for SINS/WSN based on the measured distances between anchor nodes and mobile node. The measured distance value of WSN is corrected with a least squares regression (LSR algorithm, with the aim of decreasing the systematic error for measured distance. Additionally, the statistical covariance of measured distance value is used to adjust the observation covariance matrix of a Kalman filter using a fuzzy inference system (FIS, based on the statistical characteristics. Then the tightly-coupled integration model can adaptively adjust the confidence level for measurement according to the different measured accuracies of distance measurements. Hence the FATCI system is achieved using SINS/WSN. This innovative approach is verified in real scenarios. Experimental results show that the proposed positioning system has better accuracy and stability compared with the loosely-coupled and traditional tightly-coupled integration model for WSN short-term failure or normal conditions.

  18. Experimental Air-Tightness Analysis in Mediterranean Buildings after Windows Retrofit

    Directory of Open Access Journals (Sweden)

    Francesca Romana d’Ambrosio Alfano

    2016-09-01

    Full Text Available Energy saving and Indoor Air Quality (IAQ in buildings are strongly affected by air leakages. Several studies reveal that the energy loss owing to leaky windows can account for up to 40% of the total building energy demand. Furthermore, at the design stage, the possible infiltration of outdoor air through windows is not taken into account when determin