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Sample records for jacques baudry claudine

  1. French payload specialist Patrick Baudry prepares a meal

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Payload specialist Patrick Baudry, representing the Centre National d'Etudes Spatiales of France, prepares to open a can of lobster. The bag attached to the nearby middeck locker door appears to contain several other French snacks. His food tray is also attached to the middeck lockers. Behind his head are other food trays attached to the shuttle rehydration unit. A roll of duct tape floats in space to one side of Baudry.

  2. Payload specialists Baudry and Al-Saud in the middeck

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The two payload specialists for the STS 51-G flight share a middeck scene on Discovery. Sultan Salman Abdelazize Al-Saud (left) is in the midst of a meal while Patrick Baudry conducts a phase of the French Postural Experiment (FPE) on himself. Sleep restraints are in the background.

  3. Payload specialists Baudry and Al-Saud conduct Postural experiment

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Payload specialists Patrick Baudry (left) and Sultan Salman Abdelazize Al-Saud team up to conduct a French Postural Experement (FPE) on the middeck of the Space shuttle Discovery during the STS 51-G flight. Behind them on the middeck walls are two sleep restraints.

  4. Payload specialists Baudry and Chretien in the Shuttle full fuselage trainer

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Payload specialists Patrick Baudry (left) and Jean Loup Chretien are seated at the commander and pilot stations on the Shuttle full fuselage trainer. In this view they are looking at the camera over the backs of the shuttle seats.

  5. Jacques Cousteau

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Jacques Cousteau, the French undersea researcher, is shown addressing members of the press on his experiences during an Antarctic expedition with the oceanographic ship, Calypso. The Calypso used satellite communication and weather equipment provided by NASA to test the accuracy of satellite observations in relation to the ship's surface observations. Calypso used satellite observation information to navigate into safe waters after getting hit by an iceberg. Cousteau was born in Saint-Andre-de-Cubzac, France on June 11, 1910. He died on June 25, 1997, after contributing various books and hundreds of documents on the chartless realms that make up the planet's oceans. In 1956, with the help of Calypso and her crew, Cousteau received an Academy award for his undersea documentary, The Silent World, and cemented his position as one of the world's most famous marine biologists.

  6. Claudins and Ki-67

    PubMed Central

    Törzsök, Péter; Riesz, Péter; Kenessey, István; Székely, Eszter; Somorácz, Áron; Nyirády, Péter; Romics, Imre; Schaff, Zsuzsa; Lotz, Gábor

    2011-01-01

    Updated classification of urothelial cell cancer differentiates low-grade and high-grade cancers, which determines potential clinical outcome. Substantial interobserver variability necessitates new biomarkers to ensure classification. Claudins’ specific expression pattern characterizes normal tissues, different tumor types, and defined grades of tumor differentiation. The aim of this study was to examine the expression pattern of claudins and proliferation marker Ki-67 in low-grade and high-grade urothelial cell cancers compared with independent control samples of non-tumorous urothelium, as well as to reveal the predictive usefulness of claudins. The expression of claudins-1, -2, -3, -4, -5, -7, and -10 and Ki-67 was studied with quantitative immunohistochemistry and real-time RT-PCR with relative quantification in 103 samples: 86 urothelial cell cancers (27 low grade, 59 high grade) and 17 non-tumorous urothelia. Results were analyzed regarding overall survival and recurrence-free period as well. High-grade tumors overall showed significantly higher claudin-4 and Ki-67 and significantly lower claudin-7 expression when compared with low-grade ones. High-grade tumors revealed significantly shorter overall survival in Kaplan-Meier analysis. Claudin-4, claudin-7, and Ki-67 might be used as potential markers to differentiate low-grade and high-grade urothelial cell cancers, thereby possibly enhancing accuracy of pathological diagnosis and adding further information to clinical outcome. PMID:22043024

  7. The Claudin Megatrachea Protein Complex*

    PubMed Central

    Jaspers, Martin H. J.; Nolde, Kai; Behr, Matthias; Joo, Seol-hee; Plessmann, Uwe; Nikolov, Miroslav; Urlaub, Henning; Schuh, Reinhard

    2012-01-01

    Claudins are integral transmembrane components of the tight junctions forming trans-epithelial barriers in many organs, such as the nervous system, lung, and epidermis. In Drosophila three claudins have been identified that are required for forming the tight junctions analogous structure, the septate junctions (SJs). The lack of claudins results in a disruption of SJ integrity leading to a breakdown of the trans-epithelial barrier and to disturbed epithelial morphogenesis. However, little is known about claudin partners for transport mechanisms and membrane organization. Here we present a comprehensive analysis of the claudin proteome in Drosophila by combining biochemical and physiological approaches. Using specific antibodies against the claudin Megatrachea for immunoprecipitation and mass spectrometry, we identified 142 proteins associated with Megatrachea in embryos. The Megatrachea interacting proteins were analyzed in vivo by tissue-specific knockdown of the corresponding genes using RNA interference. We identified known and novel putative SJ components, such as the gene product of CG3921. Furthermore, our data suggest that the control of secretion processes specific to SJs and dependent on Sec61p may involve Megatrachea interaction with Sec61 subunits. Also, our findings suggest that clathrin-coated vesicles may regulate Megatrachea turnover at the plasma membrane similar to human claudins. As claudins are conserved both in structure and function, our findings offer novel candidate proteins involved in the claudin interactome of vertebrates and invertebrates. PMID:22930751

  8. Claudins in teleost fishes

    PubMed Central

    Kolosov, Dennis; Bui, Phuong; Chasiotis, Helen; Kelly, Scott P

    2013-01-01

    Teleost fishes are a large and diverse animal group that represent close to 50% of all described vertebrate species. This review consolidates what is known about the claudin (Cldn) family of tight junction (TJ) proteins in teleosts. Cldns are transmembrane proteins of the vertebrate epithelial/endothelial TJ complex that largely determine TJ permeability. Cldns achieve this by expressing barrier or pore forming properties and by exhibiting distinct tissue distribution patterns. So far, ~63 genes encoding for Cldn TJ proteins have been reported in 16 teleost species. Collectively, cldns (or Cldns) are found in a broad array of teleost fish tissues, but select genes exhibit restricted expression patterns. Evidence to date strongly supports the view that Cldns play a vital role in the embryonic development of teleost fishes and in the physiology of tissues and organ systems studied thus far. PMID:24665402

  9. Role of claudins in renal calcium handling.

    PubMed

    Negri, Armando Luis

    2015-01-01

    Paracellular channels occurring in tight junctions play a major role in transepithelial ionic flows. This pathway includes a high number of proteins, such as claudins. Within renal epithelium, claudins result in an ionic selectivity in tight junctions. Ascending thick limb of loop of Henle (ATLH) is the most important segment for calcium reabsorption in renal tubules. Its cells create a water-proof barrier, actively transport sodium and chlorine through a transcellular pathway, and provide a paracellular pathway for selective calcium reabsorption. Several studies have led to a model of paracellular channel consisting of various claudins, particularly claudin-16 and 19. Claudin-16 mediates cationic paracellular permeability in ATLH, whereas claudin-19 increases cationic selectivity of claudin-16 by blocking anionic permeability. Recent studies have shown that claudin-14 promoting activity is only located in ATLH. When co-expressed with claudin-16, claudin-14 inhibits the permeability of claudin-16 and reduces paracellular permeability to calcium. Calcium reabsorption process in ATLH is closely regulated by calcium sensor receptor (CaSR), which monitors circulating Ca levels and adjusts renal excretion rate accordingly. Two microRNA, miR-9 and miR-374, are directly regulated by CaSR. Thus, miR-9 and miR-374 suppress mRNA translation for claudin-14 and induce claudin-14 decline.

  10. Regulation of claudin/zonula occludens-1 complexes by hetero-claudin interactions

    PubMed Central

    Schlingmann, Barbara; Overgaard, Christian E.; Molina, Samuel A.; Lynn, K. Sabrina; Mitchell, Leslie A.; Dorsainvil White, StevenClaude; Mattheyses, Alexa L.; Guidot, David M.; Capaldo, Christopher T.; Koval, Michael

    2016-01-01

    Claudins are tetraspan transmembrane tight-junction proteins that regulate epithelial barriers. In the distal airspaces of the lung, alveolar epithelial tight junctions are crucial to regulate airspace fluid. Chronic alcohol abuse weakens alveolar tight junctions, priming the lung for acute respiratory distress syndrome, a frequently lethal condition caused by airspace flooding. Here we demonstrate that in response to alcohol, increased claudin-5 paradoxically accompanies an increase in paracellular leak and rearrangement of alveolar tight junctions. Claudin-5 is necessary and sufficient to diminish alveolar epithelial barrier function by impairing the ability of claudin-18 to interact with a scaffold protein, zonula occludens 1 (ZO-1), demonstrating that one claudin affects the ability of another claudin to interact with the tight-junction scaffold. Critically, a claudin-5 peptide mimetic reverses the deleterious effects of alcohol on alveolar barrier function. Thus, claudin controlled claudin-scaffold protein interactions are a novel target to regulate tight-junction permeability. PMID:27452368

  11. Regulation of claudin/zonula occludens-1 complexes by hetero-claudin interactions.

    PubMed

    Schlingmann, Barbara; Overgaard, Christian E; Molina, Samuel A; Lynn, K Sabrina; Mitchell, Leslie A; Dorsainvil White, StevenClaude; Mattheyses, Alexa L; Guidot, David M; Capaldo, Christopher T; Koval, Michael

    2016-01-01

    Claudins are tetraspan transmembrane tight-junction proteins that regulate epithelial barriers. In the distal airspaces of the lung, alveolar epithelial tight junctions are crucial to regulate airspace fluid. Chronic alcohol abuse weakens alveolar tight junctions, priming the lung for acute respiratory distress syndrome, a frequently lethal condition caused by airspace flooding. Here we demonstrate that in response to alcohol, increased claudin-5 paradoxically accompanies an increase in paracellular leak and rearrangement of alveolar tight junctions. Claudin-5 is necessary and sufficient to diminish alveolar epithelial barrier function by impairing the ability of claudin-18 to interact with a scaffold protein, zonula occludens 1 (ZO-1), demonstrating that one claudin affects the ability of another claudin to interact with the tight-junction scaffold. Critically, a claudin-5 peptide mimetic reverses the deleterious effects of alcohol on alveolar barrier function. Thus, claudin controlled claudin-scaffold protein interactions are a novel target to regulate tight-junction permeability. PMID:27452368

  12. The significance of Jacques Lacan.

    PubMed

    Leavy, S A

    1977-01-01

    The contemporary French psychoanalyst, Jacques Lacan, has offered a reinterpretation of basic Freudian concepts that is to a great extent based on the structural linguistics of F. de Saussure. Certain fundamental ideas of Lacan, such as his views that "the unconscious is structured like a language" and that "the unconscious is the discourse of the Other" are examined here, and an attempt is made to place them in perspective in psychoanalysis.

  13. Biochemical and biophysical analyses of tight junction permeability made of claudin-16 and claudin-19 dimerization

    PubMed Central

    Gong, Yongfeng; Renigunta, Vijayaram; Zhou, Yi; Sunq, Abby; Wang, Jinzhi; Yang, Jing; Renigunta, Aparna; Baker, Lane A.; Hou, Jianghui

    2015-01-01

    The molecular nature of tight junction architecture and permeability is a long-standing mystery. Here, by comprehensive biochemical, biophysical, genetic, and electron microscopic analyses of claudin-16 and -19 interactions—two claudins that play key polygenic roles in fatal human renal disease, FHHNC—we found that 1) claudin-16 and -19 form a stable dimer through cis association of transmembrane domains 3 and 4; 2) mutations disrupting the claudin-16 and -19 cis interaction increase tight junction ultrastructural complexity but reduce tight junction permeability; and 3) no claudin hemichannel or heterotypic channel made of claudin-16 and -19 trans interaction can exist. These principles can be used to artificially alter tight junction permeabilities in various epithelia by manipulating selective claudin interactions. Our study also emphasizes the use of a novel recording approach based on scanning ion conductance microscopy to resolve tight junction permeabilities with submicrometer precision. PMID:26446843

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

    PubMed Central

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

    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. PMID:26729464

  15. Claudins reign: The claudin/EMP/PMP22/γ channel protein family in C. elegans.

    PubMed

    Simske, Jeffrey S

    2013-07-01

    The claudin family of integral membrane proteins was identified as the major protein component of the tight junctions in all vertebrates. Since their identification, claudins, and their associated pfam00822 superfamily of proteins have been implicated in a wide variety of cellular processes. Claudin homologs have been identified in invertebrates as well, including Drosophila and C. elegans. Recent studies demonstrate that the C. elegans claudins, clc-1-clc- 5, and similar proteins in the greater PMP22/EMP/claudin/voltage-gated calcium channel γ subunit family, including nsy-4, and vab-9, while highly divergent at a sequence level from each other and from the vertebrate claudins, in many cases play roles similar to those traditionally assigned to their vertebrate homologs. These include regulating cell adhesion and passage of small molecules through the paracellular space, channel activity, protein aggregation, sensitivity to pore-forming toxins, intercellular signaling, cell fate specification and dynamic changes in cell morphology. Study of claudin superfamily proteins in C. elegans should continue to provide clues as to how claudin family protein function has been adapted to perform diverse functions at specialized cell-cell contacts in metazoans.

  16. Expression of claudin-5, claudin-7 and occludin in oral squamous cell carcinoma and their clinico-pathological significance

    PubMed Central

    Phattarataratip, Ekarat

    2016-01-01

    Background Claudin and occludin are the important tight junctions protein in human. The downregulation or upregulation of claudins and occludin might have a role in cancer development. The objective of this study was to investigate the expression of claudin-5, claudin-7 and occludin in oral squamous cell carcinoma (OSCC) and their relationships with the prognostically-related clinico-pathologic features. Material and Methods Standard indirect immunohistochemical technique using anti-claudin-5, anti-claudin-7 and anti-occludin was performed in formalin-fixed paraffin-embedded tissue sections of 66 OSCC samples from Faculty of Dentistry, Chulalongkorn University. The positive cases were divided into 2 groups, the low expression group (cases with less than 50% of positive cancer cells) and the high expression group for statistical analysis. Categorical analysis of the clinico-pathologic parameters together with univariate analysis using the Kaplan-Meier method and the log rank test were performed. Results There were 22 male and 23 female patients enrolled in this study, with a mean age of 65.82+12.10 years. The claudin-5 immunoreactivity was observed in 26.6% of cases. The positive immunoreactivity of claudin-7 is more noted (93.3%). Only 4 cases showed occludin immunoreactivity (8.9%) and all of them show positivity less than 25% of cancer cells. Only loss of claudin-7 expression was associated with the high pathologic grade, advanced TNM staging, large tumor size, the presence of microscopic perineural, vascular invasions and regional lymph node involvement. There is a tendency towards the association of the higher claudin-7 expression and a longer survival time (P=0.012). Conclusions The results showed expression of claudin-5, claudin-7 and low expression of occludin in OSCC. Only claudin-7 expression showed impact on clinic-pathological parameter of OSCC. Key words:Claudin, occludin, oral squamous cell carcinoma, tight junctions, oral cancer. PMID:27398181

  17. Claudin-1, but not claudin-4, exhibits differential expression patterns between well- to moderately-differentiated and poorly-differentiated gastric adenocarcinoma

    PubMed Central

    TOKUHARA, YASUNORI; MORINISHI, TATSUYA; MATSUNAGA, TORU; OHSAKI, HIROYUKI; KUSHIDA, YOSHIO; HABA, REIJI; HIRAKAWA, EIICHIRO

    2015-01-01

    Claudins are members of a large family of transmembrane proteins, which are essential in the formation of tight junctions and have previously been associated with the process of tumor progression. Studies have reported the aberrant expression of claudin-1 and claudin-4 in numerous types of cancer. The present study aimed to investigate the expression of claudin-1 and claudin-4 in gastric adenocarcinoma tissue. Surgically resected gastric adenocarcinoma tissue specimens were obtained from 94 patients. Protein expression levels of claudin-1 and claudin-4 were determined using immunohistochemical staining; the association between claudin-1 or claudin-4 expression and various clinicopathological parameters were then analyzed. In gastric adenocarcinoma specimens, the expression rates of claudin-1 and claudin-4 were 43.6 and 87.2%, respectively. Claudin-1 expression demonstrated a significant correlation with histological type (P<0.01) and was significantly higher in well- to moderately-differentiated gastric adenocarcinomas compared with poorly-differentiated tumors. However, no correlation was observed between claudin-4 expression in adenocarcinoma and clinicopathological parameters. In conclusion, downregulation of claudin-1 expression in poorly-differentiated gastric adenocarcinoma may be involved in the biological transformation of tumors. The present findings suggested that claudin-1 may be an important protein associated with histological type and therefore may have potential for use as a prognostic marker for gastric adenocarcinoma. Further studies are required to elucidate the precise mechanism of claudin expression and its involvement in tumor progression. PMID:26170982

  18. Ochratoxin A displaces claudins from detergent resistant membrane microdomains.

    PubMed

    Lambert, Daniel; Padfield, Philip J; McLaughlin, John; Cannell, Stephanie; O'Neill, Catherine A

    2007-06-29

    Ochratoxin A (OchA) is a food-borne mycotoxin with multiple effects in vivo. Previously, we have demonstrated that the toxin can significantly impair the barrier function of the gut epithelial cell line, Caco-2. Barrier disruption involved loss of claudins 3 and 4, but not claudin 1 from the tight junction complex. In this study, we demonstrate for the first time, that OchA is able to remove claudins 3 and 4 from the detergent insoluble membrane microdomains associated with the tight junctions. However, cholesterol distribution within the microdomain was unaffected by the toxin. In addition, the thiol antioxidant, N-acetyl cysteine, preserved the microdomain localisation of claudins and also the barrier function of Caco-2 cells. This work suggests that OchA-mediated barrier toxicity is due to removal of claudins from detergent insoluble membrane microdomains. Moreover, loss of microdomain association may be due to oxidative events.

  19. Claudin-3, claudin-7, and claudin-10 show different distribution patterns during decidualization and trophoblast invasion in mouse and human.

    PubMed

    Schumann, S; Buck, V U; Classen-Linke, I; Wennemuth, G; Grümmer, R

    2015-12-01

    Implantation of the mammalian embryo requires profound endometrial changes for successful pregnancy, including epithelial-mesenchymal transition of the luminal epithelium and stromal-epithelial transition of the stromal cells resulting in decidualization. Claudins (Cldn) determine the variability in tight junction paracellular permeability and may play a role during these epithelial and decidual changes. We here localized Cldn3, Cldn7 and Cldn10 proteins in the different compartments of murine endometrium up to day 8.5 of pregnancy (dpc) as well as in human endometrium and first trimester decidua. In murine estrous endometrium, luminal and glandular epithelium exhibited Cldn3 and Cldn7, whereas Cldn10 was only detectable in glandular epithelium. At 4.5 dpc, Cldn3 protein shifted to an apical localization, whereas Cldn7 vanished in the epithelium of the implantation chamber. At this stage, there was no stromal signal for Cldn3 and Cldn7, but a strong induction of Cldn10 in the primary decidual zone. Cldn3 proteins emerged at 5.5 dpc spreading considerably from 6.5 dpc onward in the endothelial cells of the decidual blood sinusoids and in the decidual cells of the compact antimesometrial region. In addition to Cldn3, Cldn10 was identified in human endometrial epithelia. Both proteins were not detected in human first trimester decidual cells. Cldn3 was shown in murine trophoblast giant cells as well as in human extravillous trophoblast cells and thus may have an impact on trophoblast invasion in both species. We here showed a specific claudin signature during early decidualization pointing to a role in decidual angiogenesis and regulation of trophoblast invasion. PMID:26340953

  20. Claudin-4 forms a paracellular barrier, revealing the interdependence of claudin expression in the loose epithelial cell culture model opossum kidney cells.

    PubMed

    Borovac, Jelena; Barker, Reid S; Rievaj, Juraj; Rasmussen, Andrew; Pan, Wanling; Wevrick, Rachel; Alexander, R Todd

    2012-12-15

    The effect of claudins on paracellular fluxes has been predominantly studied in either Madin-Darby canine kidney (MDCK) or LLCPK cells. Neither model system has a very low transepithelial resistance (TER) as observed in leaky epithelia. Moreover, results from one model system are not always consistent with another. Opossum kidney (OK) cells form tight junctions yet have a very low TER. We therefore set out to characterize the paracellular transport properties of this cell culture model. Ussing chamber dilution potential measurements revealed that OK cells exhibit a very low TER (11.7 ± 1.4 Ω·cm(2)), slight cation selectivity (P(Na)/P(Cl) = 1.10 ± 0.01), and the Eisenman permeability sequence IV; the permeability of monovalent cations ranking K(+) > Cs(+) > Rb(+) > Na(+) > Li(+). Quantitative real-time PCR studies found that OK cells endogenously express claudin-4 > -1 > -6 > -20 > -9 > -12 > -11 > -15. Overexpression of claudin-4 significantly increased TER, decreased Na(+) and Cl(-) permeability, and increased levels of claudin-1, -6, and -9 mRNA. Knockdown of claudin-4 in the overexpressing cells significantly decreased TER without altering claudin expression; thus claudin-4 forms a barrier in OK cells. Knockdown of endogenous claudin-4 decreased claudin-1, -9, and -12 expression without altering TER. Claudin-2 overexpression decreased TER, significantly increased Na(+) and Cl(-) permeability, and decreased claudin-12 and -6 expression. Together these results demonstrate that claudin expression is tightly coupled in OK cells.

  1. Did Jacques Lacan say anything new?

    PubMed

    Gazzola, Luiz

    2005-01-01

    The late French psychoanalyst Jacques Lacan is an important theoretician, well known in Europe and South America, whose work is rapidly gaining recognition in other countries. However, Lacan is still poorly known in the United States except in academic departments of philosophy, linguistics, and literature. Psychoanalytic clinicians and even many training analysts often find it difficult to approach Lacan's complex theory, and his reputation in the U.S. has suffered from a number of misunderstandings. Nevertheless, judging by his worldwide influence, he has clearly made original contributions to psychoanalytic theory and technique. A biographical sketch of Lacan's life, paired with a brief overview of his writings and seminars, helps to indicate some of the reasons for both the difficulty and the misunderstandings. A flavor of Lacan's works can be achieved through a more detailed look at one of his major concepts: the use of logical time in analysis, which is the origin of the controversial (so-called) "short sessions."

  2. Jacques Monod and Chance and Necessity.

    PubMed

    Ribatti, Domenico

    2015-01-01

    Charles Darwin proposed the theory that evolution of live organisms is based on random variation and natural selection. Jacques Monod, in his classic book Chance and Necessity, published 45 years ago, presented his thesis that the biosphere does not contain a predictable class of objects or events, but constitutes a particular occurrence, compatible indeed with the first principles but not deducible from those principles. The biosphere is therefore essentially unpredictable. In his book, Monod expounded at length on the conflict between science and religion. He saw religion as a collection of primitive myths that had been blown to shreds by science. At every turn, Monod emphasized the role of chance in human existence, an idea that is antithetical to essentially every religious doctrine that places humans as some inevitable intention of a Creator.

  3. Mode of action of claudin peptidomimetics in the transient opening of cellular tight junction barriers.

    PubMed

    Staat, Christian; Coisne, Caroline; Dabrowski, Sebastian; Stamatovic, Svetlana M; Andjelkovic, Anuska V; Wolburg, Hartwig; Engelhardt, Britta; Blasig, Ingolf E

    2015-06-01

    In epithelial/endothelial barriers, claudins form tight junctions, seal the paracellular cleft, and limit the uptake of solutes and drugs. The peptidomimetic C1C2 from the C-terminal half of claudin-1's first extracellular loop increases drug delivery through epithelial claudin-1 barriers. However, its molecular and structural mode of action remains unknown. In the present study, >100 μM C1C2 caused paracellular opening of various barriers with different claudin compositions, ranging from epithelial to endothelial cells, preferentially modulating claudin-1 and claudin-5. After 6 h incubation, C1C2 reversibly increased the permeability to molecules of different sizes; this was accompanied by redistribution of claudins and occludin from junctions to cytosol. Internalization of C1C2 in epithelial cells depended on claudin-1 expression and clathrin pathway, whereby most C1C2 was retained in recyclosomes >2 h. In freeze-fracture electron microscopy, C1C2 changed claudin-1 tight junction strands to a more parallel arrangement and claudin-5 strands from E-face to P-face association - drastic and novel effects. In conclusion, C1C2 is largely recycled in the presence of a claudin, which explains the delayed onset of barrier and junction loss, the high peptide concentration required and the long-lasting effect. Epithelial/endothelial barriers are specifically modulated via claudin-1/claudin-5, which can be targeted to improve drug delivery. PMID:25907035

  4. Jacques Joseph: Father of modern aesthetic surgery

    PubMed Central

    Bhattacharya, Surajit

    2008-01-01

    When we review the history of modern aesthetic surgery, a name that stands out as bright as a beacon and precious as gold is undoubtedly that of Jacques Joseph. A surgeon, par excellence, far ahead of his time, who chose to think out of the box, Joseph, despite all odds set out to give respectability to Aesthetic Surgery without depriving it of any scientific core values. By his words and deeds proved beyond doubt that only the very best in the field of reconstructive surgery, can visualize the hidden perfection in imperfection and formulate a treatment plan and a surgical strategy to achieve that elusive perfection. The rich surgical literature that he has left behind, the wealth of surgical instruments that he had designed and above all a way of thinking that he propagated, that aesthetic surgery is not frivolous but very serious endeavor, and treating the psychology of the patient is as important as treating his disease, undoubtedly makes him the revered ‘Father of Modern Aesthetic Surgery’. PMID:20174541

  5. Jacques Joseph: Father of modern aesthetic surgery.

    PubMed

    Bhattacharya, Surajit

    2008-10-01

    When we review the history of modern aesthetic surgery, a name that stands out as bright as a beacon and precious as gold is undoubtedly that of Jacques Joseph. A surgeon, par excellence, far ahead of his time, who chose to think out of the box, Joseph, despite all odds set out to give respectability to Aesthetic Surgery without depriving it of any scientific core values. By his words and deeds proved beyond doubt that only the very best in the field of reconstructive surgery, can visualize the hidden perfection in imperfection and formulate a treatment plan and a surgical strategy to achieve that elusive perfection. The rich surgical literature that he has left behind, the wealth of surgical instruments that he had designed and above all a way of thinking that he propagated, that aesthetic surgery is not frivolous but very serious endeavor, and treating the psychology of the patient is as important as treating his disease, undoubtedly makes him the revered 'Father of Modern Aesthetic Surgery'.

  6. Structural basis for disruption of claudin assembly in tight junctions by an enterotoxin

    PubMed Central

    Shinoda, Takehiro; Shinya, Naoko; Ito, Kaori; Ohsawa, Noboru; Terada, Takaho; Hirata, Kunio; Kawano, Yoshiaki; Yamamoto, Masaki; Kimura-Someya, Tomomi; Yokoyama, Shigeyuki; Shirouzu, Mikako

    2016-01-01

    The food-poisoning bacterium Clostridium perfringens produces an enterotoxin (~35 kDa) that specifically targets human claudin-4, among the 26 human claudin proteins, and causes diarrhea by fluid accumulation in the intestinal cavity. The C-terminal domain of the Clostridium perfringens enterotoxin (C-CPE, ~15 kDa) binds tightly to claudin-4, and disrupts the intestinal tight junction barriers. In this study, we determined the 3.5-Å resolution crystal structure of the cell-free synthesized human claudin-4•C-CPE complex, which is significantly different from the structure of the off-target complex of an engineered C-CPE with mouse claudin-19. The claudin-4•C-CPE complex structure demonstrated the mechanism underlying claudin assembly disruption. A comparison of the present C-CPE-bound structure of claudin-4 with the enterotoxin-free claudin-15 structure revealed sophisticated C-CPE-induced conformation changes of the extracellular segments, induced on the foundation of the rigid four-transmembrane-helix bundle structure. These conformation changes provide a mechanistic model for the disruption of the lateral assembly of claudin molecules. Furthermore, the present novel structural mechanism for selecting a specific member of the claudin family can be used as the foundation to develop novel medically important technologies to selectively regulate the tight junctions formed by claudin family members in different organs. PMID:27647526

  7. Structural basis for disruption of claudin assembly in tight junctions by an enterotoxin.

    PubMed

    Shinoda, Takehiro; Shinya, Naoko; Ito, Kaori; Ohsawa, Noboru; Terada, Takaho; Hirata, Kunio; Kawano, Yoshiaki; Yamamoto, Masaki; Kimura-Someya, Tomomi; Yokoyama, Shigeyuki; Shirouzu, Mikako

    2016-01-01

    The food-poisoning bacterium Clostridium perfringens produces an enterotoxin (~35 kDa) that specifically targets human claudin-4, among the 26 human claudin proteins, and causes diarrhea by fluid accumulation in the intestinal cavity. The C-terminal domain of the Clostridium perfringens enterotoxin (C-CPE, ~15 kDa) binds tightly to claudin-4, and disrupts the intestinal tight junction barriers. In this study, we determined the 3.5-Å resolution crystal structure of the cell-free synthesized human claudin-4•C-CPE complex, which is significantly different from the structure of the off-target complex of an engineered C-CPE with mouse claudin-19. The claudin-4•C-CPE complex structure demonstrated the mechanism underlying claudin assembly disruption. A comparison of the present C-CPE-bound structure of claudin-4 with the enterotoxin-free claudin-15 structure revealed sophisticated C-CPE-induced conformation changes of the extracellular segments, induced on the foundation of the rigid four-transmembrane-helix bundle structure. These conformation changes provide a mechanistic model for the disruption of the lateral assembly of claudin molecules. Furthermore, the present novel structural mechanism for selecting a specific member of the claudin family can be used as the foundation to develop novel medically important technologies to selectively regulate the tight junctions formed by claudin family members in different organs. PMID:27647526

  8. Claudin immunolocalization in neonatal mouse epithelial tissues.

    PubMed

    Troy, Tammy-Claire; Arabzadeh, Azadeh; Yerlikaya, Seda; Turksen, Kursad

    2007-11-01

    Emerging evidence supports the notion that claudins (Cldns) are dynamically regulated under normal conditions to respond to the selective permeability requirements of various tissues, and that their expression is developmentally controlled. We describe the localization of those Cldns that we have previously demonstrated to be functionally important in epidermal differentiation and the formation of the epidermal permeability barrier, e.g., Cldn1, Cldn6, Cldn11, and Cldn18, and the presence of Cldn3 and Cldn5 in various neonatal mouse epithelia including the epidermis, nail, oral mucosa, tongue, and stomach. Cldn1 is localized in the differentiated and/or undifferentiated compartments of the epidermis and nail and in the dorsal surface of the tongue and glandular compartment of the stomach but is absent from the oral mucosa and the keratinized compartment of the stomach. Cldn3 is present in the basal cells of the nail matrix and both compartments of the murine stomach but not in the epidermis, oral mucosa, or tongue. Cldn5 is found in the glandular compartment of the stomach but not in the epidermis, nail unit, oral mucosa, forestomach, and tongue. Cldn6, Cldn11, and Cldn18 occur in the differentiating suprabasal compartment of the epidermis, nail, and oral mucosa and in the dorsal and ventral surfaces of the tongue and the keratinized squamous epithelium of the stomach. The simple columnar epithelium of the glandular stomach stains for Cldn18 and reveals a non-membranous pattern for Cldn6 and Cldn11 expression. Our results demonstrate differential Cldn protein profiles in various epithelial tissues and their differentiation stages. Although the molecular mechanisms regulating Cldn expression are unknown, elucidation of their differential localization patterns in tissues with diverse permeability requirements should provide a better understanding of the role of tight junctions in tissue function. PMID:17828607

  9. Expression of claudins and their prognostic significance in noninvasive urothelial neoplasms of the human urinary bladder.

    PubMed

    Székely, Eszter; Törzsök, Péter; Riesz, Péter; Korompay, Anna; Fintha, Attila; Székely, Tamás; Lotz, Gábor; Nyirády, Péter; Romics, Imre; Tímár, József; Schaff, Zsuzsa; Kiss, András

    2011-10-01

    The members of the claudin family are major integral transmembrane protein constituents of tight junctions. Normal and neoplastic tissues can be characterized by unique qualitative and quantitative distribution of claudin subtypes, which may be related to clinicopathological features. Differential diagnosis and prognosis of nonmuscle invasive tumor entities of urinary bladder epithelium are often challenging. The aim was to investigate the expression profile of claudins in inverted urothelial papillomas (IUPs), urothelial papillomas (UPs), papillary urothelial neoplasms of low malignant potential (PUNLMPs), and intraepithelial (Ta), low-grade urothelial cell carcinomas (LG-UCCs) in order to reveal potential prognostic and differential diagnostic values of certain claudins. Claudin-1, -2, -4, and -7 protein expressions detected by immunohistochemistry and clinical data were analyzed in 15 IUPs, 20 UPs, 20 PUNLMPs, and 20 LG-UCCs. UPs, PUNLMPs, and LG-UCCs showed significantly decreased claudin-1 expression in comparison to IUPs. LG-UCCs expressing claudin-4 over the median were associated with significantly shorter recurrence-free survival. PUNLMPs expressing claudin-1 over the median revealed significantly longer recurrence-free survival. High claudin-1 protein expression might help to differentiate IUP from UPs, PUNLMPs, and LG-UCCs. High claudin-4 expression may determine an unfavorable clinical course of LG-UCCs, while high claudin-1 expression in PUNLMP was associated with markedly better clinical outcome.

  10. Expression of Claudins and Their Prognostic Significance in Noninvasive Urothelial Neoplasms of the Human Urinary Bladder

    PubMed Central

    Székely, Eszter; Törzsök, Péter; Riesz, Péter; Korompay, Anna; Fintha, Attila; Székely, Tamás; Lotz, Gábor; Nyirády, Péter; Romics, Imre; Tímár, József; Schaff, Zsuzsa; Kiss, András

    2011-01-01

    The members of the claudin family are major integral transmembrane protein constituents of tight junctions. Normal and neoplastic tissues can be characterized by unique qualitative and quantitative distribution of claudin subtypes, which may be related to clinicopathological features. Differential diagnosis and prognosis of nonmuscle invasive tumor entities of urinary bladder epithelium are often challenging. The aim was to investigate the expression profile of claudins in inverted urothelial papillomas (IUPs), urothelial papillomas (UPs), papillary urothelial neoplasms of low malignant potential (PUNLMPs), and intraepithelial (Ta), low-grade urothelial cell carcinomas (LG-UCCs) in order to reveal potential prognostic and differential diagnostic values of certain claudins. Claudin-1, -2, -4, and -7 protein expressions detected by immunohistochemistry and clinical data were analyzed in 15 IUPs, 20 UPs, 20 PUNLMPs, and 20 LG-UCCs. UPs, PUNLMPs, and LG-UCCs showed significantly decreased claudin-1 expression in comparison to IUPs. LG-UCCs expressing claudin-4 over the median were associated with significantly shorter recurrence-free survival. PUNLMPs expressing claudin-1 over the median revealed significantly longer recurrence-free survival. High claudin-1 protein expression might help to differentiate IUP from UPs, PUNLMPs, and LG-UCCs. High claudin-4 expression may determine an unfavorable clinical course of LG-UCCs, while high claudin-1 expression in PUNLMP was associated with markedly better clinical outcome. PMID:21832144

  11. Claudins and the Modulation of Tight Junction Permeability

    PubMed Central

    Günzel, Dorothee

    2013-01-01

    Claudins are tight junction membrane proteins that are expressed in epithelia and endothelia and form paracellular barriers and pores that determine tight junction permeability. This review summarizes our current knowledge of this large protein family and discusses recent advances in our understanding of their structure and physiological functions. PMID:23589827

  12. CXCR4 Antagonist AMD3100 Modulates Claudin Expression and Intestinal Barrier Function in Experimental Colitis

    PubMed Central

    Xia, Xian-Ming; Wang, Fang-Yu; Zhou, Ju; Hu, Kai-Feng; Li, Su-Wen; Zou, Bing-Bing

    2011-01-01

    Ulcerative colitis is a gastrointestinal disorder characterized by local inflammation and impaired epithelial barrier. Previous studies demonstrated that CXC chemokine receptor 4 (CXCR4) antagonists could reduce colonic inflammation and mucosal damage in dextran sulfate sodium (DSS)-induced colitis. Whether CXCR4 antagonist has action on intestinal barrier and the possible mechanism, is largely undefined. In the present study, the experimental colitis was induced by administration of 5% DSS for 7 days, and CXCR4 antagonist AMD3100 was administered intraperitoneally once daily during the study period. For in vitro study, HT-29/B6 colonic cells were treated with cytokines or AMD3100 for 24 h until assay. DSS-induced colitis was characterized by morphologic changes in mice. In AMD3100-treated mice, epithelial destruction, inflammatory infiltration, and submucosal edema were markedly reduced, and the disease activity index was also significantly decreased. Increased intestinal permeability in DSS-induced colitis was also significantly reduced by AMD3100. The expressions of colonic claudin-1, claudin-3, claudin-5, claudin-7 and claudin-8 were markedly decreased after DSS administration, whereas colonic claudin-2 expression was significantly decreased. Treatment with AMD3100 prevented all these changes. However, AMD3100 had no influence on claudin-3, claudin-5, claudin-7 and claudin-8 expression in HT-29/B6 cells. Cytokines as TNF-α, IL-6, and IFN-γ increased apoptosis and monolayer permeability, inhibited the wound-healing and the claudin-3, claudin-7 and claudin-8 expression in HT-29/B6 cells. We suggest that AMD3100 acted on colonic claudin expression and intestinal barrier function, at least partly, in a cytokine-dependent pathway. PMID:22073304

  13. Expression of claudin-1 and -11 in immature and mature pheasant (Phasianus colchicus) testes.

    PubMed

    Park, C J; Lee, J E; Oh, Y S; Shim, S; Nah, W H; Choi, K J; Gye, M C

    2011-02-01

    The expression of claudin-1 and -11, tight junctions (TJs) proteins was examined in immature and adult pheasant (Phasianus colchicus) testes. Claudin-1 and -11 cDNA were highly similar to those of human, mice, and chicken. Claudin-1 mRNA and protein (21 kDa) levels in immature testes were higher than those of adult testis. In immature testes until 6 weeks of age, Claudin-1 was found at contacts between adjacent Sertoli cells and between Sertoli cells and germ cells. In adult testis, Claudin-1 was found in early spermatocytes migrating the blood testis barrier (BTB). Blood vessels were positive for claudin-1. Claudin-11 mRNA and protein (21 kDa) increased during adulthood development of testis. In immature testis, Claudin-11 was found in apicolateral contacts between adjacent Sertoli cells, indicating its involvement in cell adhesion in immature testis. In adult testis, strong wavy Claudin-11 immunoreactivity was parallel to basal lamina at the basal part of seminiferous epithelium, indicating that Claudin-11 at the inter-Sertoli TJs may act as a structural element of the BTB. Weak Claudin-1 and -11 immunoreactivity at contacts between Sertoli cells to elongating/elongated spermatids, meiotic germ cells, and basal lamina suggests that they also participate in the cell-cell and cell-extracellular matrix adhesion in pheasant testis. Testosterone increased claudin-11 mRNA in testis organ culture and Sertoli cell primary culture, suggesting positive regulation of claudin-11 gene by androgen in Sertoli cells of pheasant testis. This is the first report on the claudins expression at BTB in avian testis.

  14. Controlling life: from Jacques Loeb to regenerative medicine.

    PubMed

    Maienschein, Jane

    2009-01-01

    In his 1987 book Controlling Life: Jacques Loeb and the Engineering Ideal in Biology, Philip Pauly presented his readers with the biologist Jacques Loeb and his role in developing an emphasis on control of life processes. Loeb's work on artificial parthenogenesis, for example, provided an example of bioengineering at work. This paper revisits Pauly's study of Loeb and explores the way current research in regenerative medicine reflects the same tradition. A history of regeneration research reveals patterns of thinking and research methods that both echo Loeb's ideology and point the way to modern studies. Pauly's work revealed far more than we readers realized at the time of its publication.

  15. Nuclear distribution of claudin-2 increases cell proliferation in human lung adenocarcinoma cells.

    PubMed

    Ikari, Akira; Watanabe, Ryo; Sato, Tomonari; Taga, Saeko; Shimobaba, Shun; Yamaguchi, Masahiko; Yamazaki, Yasuhiro; Endo, Satoshi; Matsunaga, Toshiyuki; Sugatani, Junko

    2014-09-01

    Claudin-2 is expressed in human lung adenocarcinoma tissue and cell lines, although it is absent in normal lung tissue. However, the role of claudin-2 in cell proliferation and the regulatory mechanism of intracellular distribution remain undefined. Proliferation of human adenocarcinoma A549 cells was decreased by claudin-2 knockdown together with a decrease in the percentage of S phase cells. This knockdown decreased the expression levels of ZONAB and cell cycle regulators. Claudin-2 was distributed in the nucleus in human adenocarcinoma tissues and proliferating A549 cells. The nuclear distribution of ZONAB and percentage of S phase cells were higher in cells exogenously expressing claudin-2 with a nuclear localization signal than in cells expressing claudin-2 with a nuclear export signal. Nuclear claudin-2 formed a complex with ZO-1, ZONAB, and cyclin D1. Nuclear distribution of S208A mutant, a dephosphorylated form of claudin-2, was higher than that of wild type. We suggest that nuclear distribution of claudin-2 is up-regulated by dephosphorylation and claudin-2 serves to retain ZONAB and cyclin D1 in the nucleus, resulting in the enhancement of cell proliferation in lung adenocarcinoma cells.

  16. Redistributing the Sensory: The Critical Pedagogy of Jacques Ranciere

    ERIC Educational Resources Information Center

    Lambert, Cath

    2012-01-01

    Jacques Ranciere remains neglected within educational debates. In this paper I examine the potential of his philosophies for enacting critical interventions in relation to contemporary (higher) educational concerns. Ranciere argues against the progressive temporality of pedagogic relations and provides an alternative thesis that equality is a…

  17. Under the Name of Method: On Jacques Ranciere's Presumptive Tautology

    ERIC Educational Resources Information Center

    Bingham, Charles

    2009-01-01

    This paper investigates the philosophical method of Jacques Ranciere, with special attention to use of the "presumptive tautology". It distinguishes between the Enlightenment conception of method as universally applicable technique, and the philosophical conception of method as a certain style that has been invented by a certain person.…

  18. Education as the Possibility of Justice: Jacques Derrida.

    ERIC Educational Resources Information Center

    Biesta, Gert J. J.

    This paper is an analysis of the ongoing work of philosopher Jacques Derrida and the immense body of work associated with him. Derrida's copious work is difficult to categorize since Derrida challenges the very concept that meaning can be grasped in its original moment or that meaning can be represented in the form of some proper, self-identical…

  19. Jacques Maritain and John Dewey on Education: A Reconsideration

    ERIC Educational Resources Information Center

    Gutek, Gerald L.

    2005-01-01

    Jacques Maritain and John Dewey were two of the towering figures in philosophy of education. Maritain led an international revival of Aristotelian and Thomist philosophies known as Integral Humanism. Dewey, a founding figure of Pragmatism, exercised a significant influence on American education. Originating in very different philosophical…

  20. The Humanities, Social Justice, and Reconceptualization: Jacques Maritain Revisited.

    ERIC Educational Resources Information Center

    Wolff, Richard J.; Miller, Janet L.

    1984-01-01

    Examines the educational thought of Jacques Maritain (1882-1973), the French Catholic philosopher, in terms of its similarity to other recent philosophies of education. Points out the common themes of social transformation in Maritain's work, in the "reconceptualist" movement, and in the proposals of a group of Catholic theorists. (AYC)

  1. Jacques Ranciere, Education, and the Art of Citizenship

    ERIC Educational Resources Information Center

    Means, Alex

    2011-01-01

    This article is part of a broader effort recently undertaken by educational theorists to verify the implications of Jacques Ranciere's work for the field of educational studies. Rather than attempting to fashion productive linkages between Ranciere and other critical pedagogues, to render a "new logic of emancipation," or explore the political…

  2. Use the Good Mind! An Interview with Freida Jacques.

    ERIC Educational Resources Information Center

    Simonelli, Richard

    1997-01-01

    Freida Jacques, Onondaga clan mother, discusses the discipline of the "good mind," which involves becoming aware of your thoughts, examining the intent of your actions, and deciding whether your intent is based on love or fear and anger. Peace and healing must be achieved through forgiveness and respect. Sidebars discuss Native American healing…

  3. [Jacques Monod: some unpublished pages of his life].

    PubMed

    Gilgenkrantz, Simone

    2015-01-01

    The friendship and affinity of thought between Albert Camus and Jacques Monod were little highlighted in France. A book published in the U.S. in 2013 over the period of the Second World War in France shows their importance. It seemed useful to collect the elements of correspondence and writings reflecting their common concerns,frequent meetings and friendship.

  4. Lipopolysaccharide disrupts the milk-blood barrier by modulating claudins in mammary alveolar tight junctions.

    PubMed

    Kobayashi, Ken; Oyama, Shoko; Numata, Atsushi; Rahman, Md Morshedur; Kumura, Haruto

    2013-01-01

    Mastitis, inflammation of the mammary gland, is the most costly common disease in the dairy industry, and is caused by mammary pathogenic bacteria, including Escherichia coli. The bacteria invade the mammary alveolar lumen and disrupt the blood-milk barrier. In normal mammary gland, alveolar epithelial tight junctions (TJs) contribute the blood-milk barrier of alveolar epithelium by blocking the leakage of milk components from the luminal side into the blood serum. In this study, we focused on claudin subtypes that participate in the alveolar epithelial TJs, because the composition of claudins is an important factor that affects TJ permeability. In normal mouse lactating mammary glands, alveolar TJs consist of claudin-3 without claudin-1, -4, and -7. In lipopolysaccharide (LPS)-induced mastitis, alveolar TJs showed 2-staged compositional changes in claudins. First, a qualitative change in claudin-3, presumably caused by phosphorylation and participation of claudin-7 in alveolar TJs, was recognized in parallel with the leakage of fluorescein isothiocyanate-conjugated albumin (FITC-albumin) via the alveolar epithelium. Second, claudin-4 participated in alveolar TJs with claudin-3 and claudin-7 12 h after LPS injection. The partial localization of claudin-1 was also observed by immunostaining. Coinciding with the second change of alveolar TJs, the severe disruption of the blood-milk barrier was recognized by ectopic localization of β-casein and much leakage of FITC-albumin. Furthermore, the localization of toll-like receptor 4 (TLR4) on the luminal side and NFκB activation by LPS was observed in the alveolar epithelial cells. We suggest that the weakening and disruption of the blood-milk barrier are caused by compositional changes of claudins in alveolar epithelial TJs through LPS/TLR4 signaling.

  5. Highly Conserved Testicular Localization of Claudin-11 in Normal and Impaired Spermatogenesis

    PubMed Central

    Stammler, Angelika; Lüftner, Benjamin Udo; Kliesch, Sabine; Weidner, Wolfgang; Bergmann, Martin; Middendorff, Ralf; Konrad, Lutz

    2016-01-01

    In this study we tested expression of tight junction proteins in human, mouse and rat and analyzed the localization of claudin-11 in testis of patients with normal and impaired spermatogenesis. Recent concepts generated in mice suggest that the stage-specifically expressed claudin-3 acts as a basal barrier, sealing the seminiferous epithelium during migration of spermatocytes. Corresponding mechanisms have never been demonstrated in humans. Testicular biopsies (n = 103) from five distinct groups were analyzed: normal spermatogenesis (NSP, n = 28), hypospermatogenesis (Hyp, n = 24), maturation arrest at the level of primary spermatocytes (MA, n = 24), Sertoli cell only syndrome (SCO, n = 19), and spermatogonial arrest (SGA, n = 8). Protein expression of claudin-3, -11 and occludin was analyzed. Human, mice and rat testis robustly express claudin-11 protein. Occludin was detected in mouse and rat and claudin-3 was found only in mice. Thus, we selected claudin-11 for further analysis of localization. In NSP, claudin-11 is located at Sertoli-Sertoli junctions and in Sertoli cell contacts towards spermatogonia. Typically, claudin-11 patches do not reach the basal membrane, unless flanked by the Sertoli cell body or patches between two Sertoli cell bodies. The amount of basal claudin-11 patches was found to be increased in impaired spermatogenesis. Only claudin-11 is expressed in all three species examined. The claudin-11 pattern is robust in man with impaired spermatogenesis, but the proportion of localization is altered in SCO and MA. We conclude that claudin-11 might represent the essential component of the BTB in human. PMID:27486954

  6. Aspirin inhibits hepatitis C virus entry by downregulating claudin-1.

    PubMed

    Yin, P; Zhang, L

    2016-01-01

    Aspirin has previously been reported to inhibit hepatitis C virus (HCV) replication. The aim of this study was to investigate whether aspirin is involved in blocking HCV entry. We found that aspirin inhibits the entry of HCVpp and infectious HCV. The level of claudin-1, an HCV receptor, is reduced by aspirin. Our results extend the anti-HCV effect of aspirin to the HCV entry step and further reinforce the anti-HCV role of aspirin.

  7. Analysis of changes in the expression pattern of claudins using salivary acinar cells in primary culture.

    PubMed

    Fujita-Yoshigaki, Junko

    2011-01-01

    Primary saliva is produced from blood plasma in the acini of salivary glands and is modified by ion adsorption and secretion as the saliva passes through the ducts. In rodents, acinar cells of salivary glands express claudin-3 but not claudin-4, whereas duct cells express both claudins-3 and -4. The distinct claudin expression patterns may reflect differences in the permeability of tight junctions between acinar and duct cells. To analyze the role of claudins in salivary glands, we established a system for the primary culture of parotid acinar cells, where the expression patterns of claudins are remarkably changed. Real-time RT-PCR and immunoblot analyses reveal that the expression levels of claudins-4 and -6 increased, whereas claudins-3 and -10 decreased. We found that the signal to induce those changes is triggered during cell isolation and is mediated by Src and p38 MAP kinase. Here, we introduce the methods used to determine the signal pathway that induces the change in claudin expression.

  8. Jacques Ranciere's Lesson on the Lesson

    ERIC Educational Resources Information Center

    Chambers, Samuel A.

    2013-01-01

    This article examines the significance of Jacques Ranciere's work on pedagogy, and argues that to make sense of Ranciere's "lesson on the lesson" one must do more but also less than merely explicate Ranciere's texts. It steadfastly refuses to draw out the lessons of Ranciere's writings in the manner of a series of…

  9. Chronic alcohol ingestion alters claudin expression in the alveolar epithelium of rats.

    PubMed

    Fernandez, Alberto L; Koval, Michael; Fan, Xian; Guidot, David M

    2007-08-01

    Previously we determined that chronic alcohol ingestion (6 weeks) in rats increases lung epithelial permeability in vivo approximately 5-6-fold and promotes flooding of the alveolar airspaces with proteinaceous fluid in response to stresses such as sepsis. In parallel, alveolar epithelial cells isolated from alcohol-fed rats fail to form tight monolayers in vitro, even when cultured for up to 8 days in the absence of alcohol. However, the molecular mechanisms underlying alcohol-induced permeability are unknown. Claudins are key components of tight junctions that restrict the paracellular movement of water, proteins, and solutes across cellular barriers including the alveolar epithelium. In this study, we examined the expression of multiple members of the claudin protein family in the lungs of alcohol-fed versus control-fed rats (Lieber-DeCarli liquid diet with either 36% of calories as alcohol or an isocaloric substitution with maltin-dextrin for 6 weeks). We determined that chronic alcohol ingestion affected the expression of multiple claudins; most striking were decreases in claudin-1 and claudin-7, and an increase in claudin-5, in the whole lung and in alveolar epithelial monolayers derived from alcohol-fed rats. In parallel, immunocytochemistry of alveolar epithelial monolayers from alcohol-fed rats revealed abnormal intracellular accumulation of claudin-7 protein and relatively decreased localization to cell membranes. Claudin-1 and claudin-7 are relatively specific to alveolar epithelial type I pneumocytes that form the vast majority of the alveolar epithelial barrier in vivo, and increases in claudin-5 have been associated with increased epithelial permeability in other systems. Therefore, these findings suggest that changes in claudin expression in the alveolar epithelium produce a "leakier" phenotype that renders the alcoholic lung susceptible to alveolar flooding during acute inflammatory stresses.

  10. Claudin-4 is required for vasculogenic mimicry formation in human breast cancer cells.

    PubMed

    Cui, Yong-Feng; Liu, An-Heng; An, Dai-Zhi; Sun, Ru-Bao; Shi, Yun; Shi, Yun-Xiang; Shi, Miao; Zhang, Qiang; Wang, Li-Li; Feng, Qiong; Pan, Gui-Lan; Wang, Qiang

    2015-05-10

    Vasculogenic mimicry (VM) refers to the unique capability of aggressive tumor cells to mimic the pattern of embryonic vasculogenic networks. Claudins are aberrantly expressed in aggressive breast cancer. However, the relationship between claudins and VM formation is not clear. We examined VM in two human breast cancer cell lines with different aggressive capabilities (MDA-MB-231 and MCF-7 cells) and one human umbilical vein endothelial cell line (HUVEC). Both HUVEC and MDA-MB-231 cells formed vascular channels in Matrigel cultures, while MCF-7 cells did not. Western blot analysis revealed a possible correlation between claudin-4 and -6 expression in breast cancer cell lines and tumor aggressiveness, with protein levels correlating with the ability to form vascular channels. Treatment of MDA-MB-231 and HUVEC cells with claudin-4 monoclonal antibodies completely inhibited the ability of cells to form vascular channels. Moreover, knockdown of claudin-4 by short hairpin RNA completely inhibited tubule formation in MDA-MB-231 cells. Overexpression of claudin-4 in MCF-7 cells induced formation of vascular channels. Immunocytochemistry revealed that membranous claudin-4 protein was significantly associated with vascular channel formation. Collectively, these results indicate that claudin-4 may play a critical role in VM in human breast cancer cells, opening new opportunities to improve aggressive breast cancer therapy. PMID:25871476

  11. Claudin 4 knockout mice: normal physiological phenotype with increased susceptibility to lung injury

    PubMed Central

    Kage, Hidenori; Flodby, Per; Gao, Danping; Kim, Yong Ho; Marconett, Crystal N.; DeMaio, Lucas; Kim, Kwang-Jin; Crandall, Edward D.

    2014-01-01

    Claudins are tight junction proteins that regulate paracellular ion permeability of epithelium and endothelium. Claudin 4 has been reported to function as a paracellular sodium barrier and is one of three major claudins expressed in lung alveolar epithelial cells (AEC). To directly assess the role of claudin 4 in regulation of alveolar epithelial barrier function and fluid homeostasis in vivo, we generated claudin 4 knockout (Cldn4 KO) mice. Unexpectedly, Cldn4 KO mice exhibited normal physiological phenotype although increased permeability to 5-carboxyfluorescein and decreased alveolar fluid clearance were noted. Cldn4 KO AEC monolayers exhibited unchanged ion permeability, higher solute permeability, and lower short-circuit current compared with monolayers from wild-type mice. Claudin 3 and 18 expression was similar between wild-type and Cldn4 KO alveolar epithelial type II cells. In response to either ventilator-induced lung injury or hyperoxia, claudin 4 expression was markedly upregulated in wild-type mice, whereas Cldn4 KO mice showed greater degrees of lung injury. RNA sequencing, in conjunction with differential expression and upstream analysis after ventilator-induced lung injury, suggested Egr1, Tnf, and Il1b as potential mediators of increased lung injury in Cldn4 KO mice. These results demonstrate that claudin 4 has little effect on normal lung physiology but may function to protect against acute lung injury. PMID:25106430

  12. Claudin-2 promotes breast cancer liver metastasis by facilitating tumor cell interactions with hepatocytes.

    PubMed

    Tabariès, Sébastien; Dupuy, Fanny; Dong, Zhifeng; Monast, Anie; Annis, Matthew G; Spicer, Jonathan; Ferri, Lorenzo E; Omeroglu, Atilla; Basik, Mark; Amir, Eitan; Clemons, Mark; Siegel, Peter M

    2012-08-01

    We previously identified claudin-2 as a functional mediator of breast cancer liver metastasis. We now confirm that claudin-2 levels are elevated in liver metastases, but not in skin metastases, compared to levels in their matched primary tumors in patients with breast cancer. Moreover, claudin-2 is specifically expressed in liver-metastatic breast cancer cells compared to populations derived from bone or lung metastases. The increased liver tropism exhibited by claudin-2-expressing breast cancer cells requires claudin-2-mediated interactions between breast cancer cells and primary hepatocytes. Furthermore, the reduction of the claudin-2 expression level, either in cancer cells or in primary hepatocytes, diminishes these heterotypic cell-cell interactions. Finally, we demonstrate that the first claudin-2 extracellular loop is essential for mediating tumor cell-hepatocyte interactions and the ability of breast cancer cells to form liver metastases in vivo. Thus, during breast cancer liver metastasis, claudin-2 shifts from acting within tight-junctional complexes to functioning as an adhesion molecule between breast cancer cells and hepatocytes.

  13. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    SciTech Connect

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum; Jang, Won-Suk; Lee, Sun-Joo; Lee, Seung-Sook; Park, Sunhoo

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  14. Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel

    SciTech Connect

    Wilmes, Anja Aschauer, Lydia; Limonciel, Alice; Pfaller, Walter; Jennings, Paul

    2014-09-01

    Claudins are the major proteins of the tight junctions and the composition of claudin subtypes is decisive for the selective permeability of the paracellular route and thus tissue specific function. Their regulation is complex and subject to interference by several factors, including oxidative stress. Here we show that exposure of cultured human proximal tubule cells (RPTEC/TERT1) to the immunosuppressive drug cyclosporine A (CsA) induces an increase in transepithelial electrical resistance (TEER), a decrease in dome formation (on solid growth supports) and a decrease in water transport (on microporous growth supports). In addition, CsA induced a dramatic decrease in the mRNA for the pore forming claudins -2 and -10, and the main subunits of the Na{sup +}/K{sup +} ATPase. Knock down of claudin 2 by shRNA had no discernable effect on TEER or dome formation but severely attenuated apical to basolateral water reabsorption when cultured on microporous filters. Generation of an osmotic gradient in the basolateral compartment rescued water transport in claudin 2 knock down cells. Inhibition of Na{sup +}/K{sup +} ATPase with ouabain prevented dome formation in both cell types. Taken together these results provide strong evidence that dome formation is primarily due to transcellular water transport following a solute osmotic gradient. However, in RPTEC/TERT1 cells cultured on filters under iso-osmotic conditions, water transport is primarily paracellular, most likely due to local increases in osmolarity in the intercellular space. In conclusion, this study provides strong evidence that claudin 2 is involved in paracellular water transport and that claudin 2 expression is sensitive to compound induced cellular stress. - Highlights: • Cyclosporine A increased TEER and decreased water transport in RPTEC/TERT1 cells. • Claudins 2 and 10 were decreased in response to cyclosporine A. • Knock down of claudin 2 inhibited water transport in proximal tubular cells. • We

  15. Structural constraints for the binding of short peptides to claudin-4 revealed by surface plasmon resonance.

    PubMed

    Ling, Jun; Liao, Hailing; Clark, Robin; Wong, Mandy Sze Man; Lo, David D

    2008-11-01

    Claudin family transmembrane proteins play an important role in tight junction structure and function in epithelial cells. Among the 24 isoforms identified in mice and humans, claudin-4 and -3 serve as the receptor for Clostridium perfringens enterotoxin (Cpe). The second extracellular loop (Ecl2) of claudin-4 is responsible for the binding to the C-terminal 30 amino acids of Cpe (Cpe30). To define the structural constraints for the claudin-4/Cpe30 interaction, a surface plasmon resonance (SPR) method was developed. GST fusions with claudin-4 revealed that Ecl2 with the downstream transmembrane domain of claudin-4 reconstituted the basic structural requirement for optimal binding activity to Cpe30, with affinity in the nanomolar range. Two 12-mer peptides selected by phage display against claudin-4-transfected CHO cells and a 12-mer Cpe mutant peptide also showed significant affinity for claudin-4 with this SPR assay, suggesting that a short peptide can establish stable contact with Ecl2 with nanomolar affinity. Alignment of these short peptides unveiled a common Ecl2 binding motif: . Whereas the short peptides bound native claudin-4 on transfected CHO cells in pull-down assays, only the larger Cpe30 peptide affected trans-epithelial electrical resistance (TER) in peptide-treated Caco-2BBe monolayers. Importantly, Cpe30 retained its binding to claudin-4 when fused to the C terminus of influenza hemagglutinin, demonstrating that its binding activity can be maintained in a different biochemical context. These studies may help in the design of assays for membrane receptor interactions with soluble ligands, and in applying new targeting ligands to delivering attached "cargo" proteins. PMID:18782762

  16. Knockout Mice Reveal Key Roles for Claudin 18 in Alveolar Barrier Properties and Fluid Homeostasis

    PubMed Central

    Li, Guanglei; Flodby, Per; Luo, Jiao; Kage, Hidenori; Sipos, Arnold; Gao, Danping; Ji, Yanbin; Beard, LaMonta L.; Marconett, Crystal N.; DeMaio, Lucas; Kim, Yong Ho; Kim, Kwang-Jin; Laird-Offringa, Ite A.; Minoo, Parviz; Liebler, Janice M.; Zhou, Beiyun; Crandall, Edward D.

    2014-01-01

    Claudin proteins are major constituents of epithelial and endothelial tight junctions (TJs) that regulate paracellular permeability to ions and solutes. Claudin 18, a member of the large claudin family, is highly expressed in lung alveolar epithelium. To elucidate the role of claudin 18 in alveolar epithelial barrier function, we generated claudin 18 knockout (C18 KO) mice. C18 KO mice exhibited increased solute permeability and alveolar fluid clearance (AFC) compared with wild-type control mice. Increased AFC in C18 KO mice was associated with increased β-adrenergic receptor signaling together with activation of cystic fibrosis transmembrane conductance regulator, higher epithelial sodium channel, and Na-K-ATPase (Na pump) activity and increased Na-K-ATPase β1 subunit expression. Consistent with in vivo findings, C18 KO alveolar epithelial cell (AEC) monolayers exhibited lower transepithelial electrical resistance and increased solute and ion permeability with unchanged ion selectivity. Claudin 3 and claudin 4 expression was markedly increased in C18 KO mice, whereas claudin 5 expression was unchanged and occludin significantly decreased. Microarray analysis revealed changes in cytoskeleton-associated gene expression in C18 KO mice, consistent with observed F-actin cytoskeletal rearrangement in AEC monolayers. These findings demonstrate a crucial nonredundant role for claudin 18 in the regulation of alveolar epithelial TJ composition and permeability properties. Increased AFC in C18 KO mice identifies a role for claudin 18 in alveolar fluid homeostasis beyond its direct contributions to barrier properties that may, at least in part, compensate for increased permeability. PMID:24588076

  17. Mechanisms of transcriptional activation of the mouse claudin-5 promoter by estrogen receptor alpha and beta.

    PubMed

    Burek, Malgorzata; Steinberg, Katrin; Förster, Carola Y

    2014-07-01

    Claudin-5 is an integral membrane protein and a critical component of endothelial tight junctions that control paracellular permeability. Claudin-5 is expressed at high levels in the brain vascular endothelium. Estrogens have multiple effects on vascular physiology and function. The biological actions of estrogens are mediated by two different estrogen receptor (ER) subtypes, ER alpha and ER beta. Estrogens have beneficial effects in several vascular disorders. Recently we have cloned and characterized a murine claudin-5 promoter and demonstrated 17beta-estradiol (E2)-mediated regulation of claudin-5 in brain and heart microvascular endothelium on promoter, mRNA and protein level. Sequence analysis revealed a putative estrogen response element (ERE) and a putative Sp1 transcription factor binding site in the claudin-5 promoter. The aim of the present study was to further characterize the estrogen-responsive elements of claudin-5 promoter. First, we introduced point mutations in ERE or Sp1 site in -500/+111 or in Sp1 site of -268/+111 claudin-5 promoter construct, respectively. Basal and E2-mediated transcriptional activation of mutated constructs was abrogated in the luciferase reporter gene assay. Next, we examined whether estrogen receptor subtypes bind to the claudin-5 promoter region. For this purpose we performed chromatin immunoprecipitation assays using anti-estrogen receptor antibodies and cellular lysates of E2-treated endothelial cells followed by quantitative PCR analysis. We show enrichment of claudin-5 promoter fragments containing the ERE- and Sp1-binding site in immunoprecipitates after E2 treatment. Finally, in a gel mobility shift assay, we demonstrated DNA-protein interaction of both ER subtypes at ERE. In summary, this study provides evidence that both a non-consensus ERE and a Sp1 site in the claudin-5 promoter are functional and necessary for the basal and E2-mediated activation of the promoter.

  18. Chronic inflammatory demyelinating polyneuropathy: decreased claudin-5 and relocated ZO-1

    PubMed Central

    Kanda, T; Numata, Y; Mizusawa, H

    2004-01-01

    Objectives: To clarify the dynamics of molecules composing the blood–nerve barrier (BNB) in inflammatory neuropathies. Methods: The expression of four tight junction (TJ) proteins—claudin-1, claudin-5, occludin, and ZO-1—was analysed immunohistochemically in sural nerve biopsy specimens obtained from patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Results: Claudin-1 was detected only in perineurial cells, whereas claudin-5 was present in endothelial cells, irrespective of vessel location or size. Occludin and ZO-1 were found in perineurial cells, in addition to some epineurial and endoneurial endothelial cells. In CIDP, percentages of endoneurial small vessels immunoreactive for claudin-5 were significantly decreased, as were ZO-1 immunoreactive endoneurial small vessels, with staining localised to interfaces between cells. Claudin-1 and occludin immunoreactivity did not differ appreciably between the neuropathies examined. Conclusions: The downregulation of claudin-5 and altered localisation of ZO-1 seen in CIDP specimens may indicate that BNB derangement occurs in inflammatory neuropathies. Further investigation of TJ molecules may suggest new treatments based on properties of the BNB. PMID:15090575

  19. Lyn modulates Claudin-2 expression and is a therapeutic target for breast cancer liver metastasis

    PubMed Central

    Tabariès, Sébastien; Annis, Matthew G.; Hsu, Brian E.; Tam, Christine E.; Savage, Paul; Park, Morag; Siegel, Peter M.

    2015-01-01

    Claudin-2 enhances breast cancer liver metastasis and promotes the development of colorectal cancers. The objective of our current study is to define the regulatory mechanisms controlling Claudin-2 expression in breast cancer cells. We evaluated the effect of several Src Family Kinase (SFK) inhibitors or knockdown of individual SFK members on Claudin-2 expression in breast cancer cells. We also assessed the potential effects of pan-SFK and SFK-selective inhibitors on the formation of breast cancer liver metastases. This study reveals that pan inhibition of SFK signaling pathways significantly elevated Claudin-2 expression levels in breast cancer cells. In addition, our data demonstrate that pan-SFK inhibitors can enhance breast cancer metastasis to the liver. Knockdown of individual SFK members reveals that loss of Yes or Fyn induces Claudin-2 expression; whereas, diminished Lyn levels impairs Claudin-2 expression in breast cancer cells. The Lyn-selective kinase inhibitor, Bafetinib (INNO-406), acts to reduce Claudin-2 expression and suppress breast cancer liver metastasis. Our findings may have major clinical implications and advise against the treatment of breast cancer patients with broad-acting SFK inhibitors and support the use of Lyn-specific inhibitors. PMID:25823815

  20. Lyn modulates Claudin-2 expression and is a therapeutic target for breast cancer liver metastasis.

    PubMed

    Tabariès, Sébastien; Annis, Matthew G; Hsu, Brian E; Tam, Christine E; Savage, Paul; Park, Morag; Siegel, Peter M

    2015-04-20

    Claudin-2 enhances breast cancer liver metastasis and promotes the development of colorectal cancers. The objective of our current study is to define the regulatory mechanisms controlling Claudin-2 expression in breast cancer cells. We evaluated the effect of several Src Family Kinase (SFK) inhibitors or knockdown of individual SFK members on Claudin-2 expression in breast cancer cells. We also assessed the potential effects of pan-SFK and SFK-selective inhibitors on the formation of breast cancer liver metastases. This study reveals that pan inhibition of SFK signaling pathways significantly elevated Claudin-2 expression levels in breast cancer cells. In addition, our data demonstrate that pan-SFK inhibitors can enhance breast cancer metastasis to the liver. Knockdown of individual SFK members reveals that loss of Yes or Fyn induces Claudin-2 expression; whereas, diminished Lyn levels impairs Claudin-2 expression in breast cancer cells. The Lyn-selective kinase inhibitor, Bafetinib (INNO-406), acts to reduce Claudin-2 expression and suppress breast cancer liver metastasis. Our findings may have major clinical implications and advise against the treatment of breast cancer patients with broad-acting SFK inhibitors and support the use of Lyn-specific inhibitors.

  1. HNF4α Regulates Claudin-7 Protein Expression during Intestinal Epithelial Differentiation

    PubMed Central

    Farkas, Attila E.; Hilgarth, Roland S.; Capaldo, Christopher T.; Gerner-Smidt, Christian; Powell, Doris R.; Vertino, Paula M.; Koval, Michael; Parkos, Charles A.; Nusrat, Asma

    2016-01-01

    The intestinal epithelium is a dynamic barrier that maintains the distinct environments of intestinal tissue and lumen. Epithelial barrier function is defined principally by tight junctions, which, in turn, depend on the regulated expression of claudin family proteins. Claudins are expressed differentially during intestinal epithelial cell (IEC) differentiation. However, regulatory mechanisms governing claudin expression during epithelial differentiation are incompletely understood. We investigated the molecular mechanisms regulating claudin-7 during IEC differentiation. Claudin-7 expression is increased as epithelial cells differentiate along the intestinal crypt–luminal axis. By using model IECs we observed increased claudin-7 mRNA and nascent heteronuclear RNA levels during differentiation. A screen for potential regulators of the CLDN7 gene during IEC differentiation was performed using a transcription factor/DNA binding array, CLDN7 luciferase reporters, and in silico promoter analysis. We identified hepatocyte nuclear factor 4α as a regulatory factor that bound endogenous CLDN7 promoter in differentiating IECs and stimulated CLDN7 promoter activity. These findings support a role of hepatocyte nuclear factor 4α in controlling claudin-7 expression during IEC differentiation. PMID:26216285

  2. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer

    PubMed Central

    2010-01-01

    Introduction In breast cancer, gene expression analyses have defined five tumor subtypes (luminal A, luminal B, HER2-enriched, basal-like and claudin-low), each of which has unique biologic and prognostic features. Here, we comprehensively characterize the recently identified claudin-low tumor subtype. Methods The clinical, pathological and biological features of claudin-low tumors were compared to the other tumor subtypes using an updated human tumor database and multiple independent data sets. These main features of claudin-low tumors were also evaluated in a panel of breast cancer cell lines and genetically engineered mouse models. Results Claudin-low tumors are characterized by the low to absent expression of luminal differentiation markers, high enrichment for epithelial-to-mesenchymal transition markers, immune response genes and cancer stem cell-like features. Clinically, the majority of claudin-low tumors are poor prognosis estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and epidermal growth factor receptor 2 (HER2)-negative (triple negative) invasive ductal carcinomas with a high frequency of metaplastic and medullary differentiation. They also have a response rate to standard preoperative chemotherapy that is intermediate between that of basal-like and luminal tumors. Interestingly, we show that a group of highly utilized breast cancer cell lines, and several genetically engineered mouse models, express the claudin-low phenotype. Finally, we confirm that a prognostically relevant differentiation hierarchy exists across all breast cancers in which the claudin-low subtype most closely resembles the mammary epithelial stem cell. Conclusions These results should help to improve our understanding of the biologic heterogeneity of breast cancer and provide tools for the further evaluation of the unique biology of claudin-low tumors and cell lines. PMID:20813035

  3. A Claudin-9–Based Ion Permeability Barrier Is Essential for Hearing

    PubMed Central

    Nakano, Yoko; Kim, Sung H.; Kim, Hyoung-Mi; Sanneman, Joel D.; Zhang, Yuzhou; Smith, Richard J. H.; Marcus, Daniel C.; Wangemann, Philine; Nessler, Randy A.; Bánfi, Botond

    2009-01-01

    Hereditary hearing loss is one of the most common birth defects, yet the majority of genes required for audition is thought to remain unidentified. Ethylnitrosourea (ENU)–mutagenesis has been a valuable approach for generating new animal models of deafness and discovering previously unrecognized gene functions. Here we report on the characterization of a new ENU–induced mouse mutant (nmf329) that exhibits recessively inherited deafness. We found a widespread loss of sensory hair cells in the hearing organs of nmf329 mice after the second week of life. Positional cloning revealed that the nmf329 strain carries a missense mutation in the claudin-9 gene, which encodes a tight junction protein with unknown biological function. In an epithelial cell line, heterologous expression of wild-type claudin-9 reduced the paracellular permeability to Na+ and K+, and the nmf329 mutation eliminated this ion barrier function without affecting the plasma membrane localization of claudin-9. In the nmf329 mouse line, the perilymphatic K+ concentration was found to be elevated, suggesting that the cochlear tight junctions were dysfunctional. Furthermore, the hair-cell loss in the claudin-9–defective cochlea was rescued in vitro when the explanted hearing organs were cultured in a low-K+ milieu and in vivo when the endocochlear K+-driving force was diminished by deletion of the pou3f4 gene. Overall, our data indicate that claudin-9 is required for the preservation of sensory cells in the hearing organ because claudin-9–defective tight junctions fail to shield the basolateral side of hair cells from the K+-rich endolymph. In the tight-junction complexes of hair cells, claudin-9 is localized specifically to a subdomain that is underneath more apical tight-junction strands formed by other claudins. Thus, the analysis of claudin-9 mutant mice suggests that even the deeper (subapical) tight-junction strands have biologically important ion barrier function. PMID:19696885

  4. [Saint-Jacques de Besançon Hospital].

    PubMed

    Deridder, Annick

    2007-01-01

    The first plan (1670) was carried out by Archbishop Antoine Pierre 1st de Grammont under the Spanish administration, with the aid of the Community Saint Marthe whose Congregation was at the start of a new monastic order and whose last members left Besançon a few years ago. At the beginning King Louis XIVth supported the building of the new hospital (1865) which was intended to shelter numerous soldiers like some other hospitals of the time. The main walls were ended in 1701 and the garden in 1702. The first patients were received in 1691. The cross-shaped Italian building is centred on a chapel and looks like many other buildings such as "La Salpêtriere" in Paris. It superseded the ancient medieval building "Saint-Jacques des Arènes" vowed to the travellers and pilgrims, the site of which was on the main crossing roads but on too small a space. The main architect was Canon Jacques Magnin, the material was found in the country and the gorgeous railings were forged by a local craftsman Chappuis. A local practitioner Gabriel Gascon bequeathed his sumptuous apothecary's shop. Some extensions of the building occured during the following centuries: a wing towards the garden, the "Couvent du Refuge" and its brilliant baroque chapel allowed the whole building to have a praise worthy chapel. At last the "Hôtel de Mont martin" initially built for Cardinal Granvelle was joined to the main hospital and became the Maternity Hospital. PMID:18175607

  5. Oncostatin M induces upregulation of claudin-2 in rodent hepatocytes coinciding with changes in morphology and function of tight junctions

    SciTech Connect

    Imamura, Masafumi; Kojima, Takashi . E-mail: ktakashi@sapmed.ac.jp; Lan, Mengdong; Son, Seiichi; Murata, Masaki; Osanai, Makoto; Chiba, Hideki; Hirata, Koichi; Sawada, Norimasa

    2007-05-15

    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.

  6. Longitudinal Claudin Gene Expression Analyses in Canine Mammary Tissues and Thereof Derived Primary Cultures and Cell Lines

    PubMed Central

    Hammer, Susanne C.; Becker, Annegret; Rateitschak, Katja; Mohr, Annika; Lüder Ripoli, Florenza; Hennecke, Silvia; Junginger, Johannes; Hewicker-Trautwein, Marion; Brenig, Bertram; Ngezahayo, Anaclet; Nolte, Ingo; Murua Escobar, Hugo

    2016-01-01

    Human and canine mammary tumours show partial claudin expression deregulations. Further, claudins have been used for directed therapeutic approaches. However, the development of claudin targeting approaches requires stable claudin expressing cell lines. This study reports the establishment and characterisation of canine mammary tissue derived cell lines, analysing longitudinally the claudin-1, -3, -4 and -7 expressions in original tissue samples, primary cultures and developed cell lines. Primary cultures were derived from 17 canine mammary tissues: healthy, lobular hyperplasia, simple adenoma, complex adenoma, simple tubular carcinoma, complex carcinoma, carcinoma arising in a benign mixed tumour and benign mixed tissue. Cultivation was performed, if possible, until passage 30. Claudin mRNA and protein expressions were analysed by PCR, QuantiGene Plex Assay, immunocytochemistry and immunofluorescence. Further, cytokeratin expression was analysed immunocytochemically. Cultivation resulted in 11 established cell lines, eight showing epithelial character. In five of the early passages the claudin expressions decreased compared to the original tissues. In general, claudin expressions were diminished during cultivation. Three cell lines kept longitudinally claudin, as well as epithelial marker expressions, representing valuable tools for the development of claudin targeted anti-tumour therapies. PMID:27690019

  7. Claudin-4 expression in gastric cancer cells enhances the invasion and is associated with the increased level of matrix metalloproteinase-2 and -9 expression

    PubMed Central

    HWANG, TSANN-LONG; CHANGCHIEN, TZU-TSUNG; WANG, CHEE-CHAN; WU, CHI-MING

    2014-01-01

    Claudin-4 is a member of a large family of transmembrane proteins known as claudins, which are essential for the formation and maintenance of tight junctions. Our previous studies have revealed that claudin-4 proteins are overexpressed in metastatic gastric cancer. To clarify the roles of claudin-4 in gastric cancer metastasis, human gastric adenocarcinoma (AGS) cells constitutively expressing wild-type claudin-4 were generated. Expression of claudin-4 in AGS cells was found to increase cell invasion and migration, as measured by Boyden invasion chamber assays. Moreover, the claudin-4-expressing AGS cells were found to have increased matrix metalloproteinase (MMP)-2 and -9 expression, indicating that claudin-mediated increased invasion may be mediated through the activation of the MMP protein. Overall, the results suggest that claudin-4 overexpression may promote gastric cancer metastasis through the increased invasion of gastric cancer cells. PMID:25120725

  8. Jacques Guillemeau's 16th-century account of ophthalmoplegia.

    PubMed

    Domínguez-Rodríguez, M Victoria; González-Hernández, Ayoze N

    2013-07-01

    In 1585, the renowned French royal surgeon Jacques Guillemeau published his Traité des maladies de l'oeil. The book is divided into 9 unequal sections devoted to the description of eye anatomy and ophthalmological diseases including muscle, membrane, and humor disorders; optic nerve damage; and eyelid affections. Section 3, in particular, focuses on a form of ophthalmoplegia involving progressive paralysis of extraocular muscles. Here we describe and discuss Guillemeau's theoretical framework and practical approach to this ophthalmological disorder. To determine whether this physician was possibly influenced by the thought of antique and contemporary learned men, we reviewed some fundamental ideas on cranial nerves and their paralysis as presented by authors such as Herophilus of Chalcedon, Erasistratus of Ceos, Claudius Galen, Andreas Vesalius, and Leonhard Fuchs. PMID:23700141

  9. Enzymatic cybernetics: an unpublished work by Jacques Monod.

    PubMed

    Gayon, Jean

    2015-06-01

    In 1959, Jacques Monod wrote a manuscript entitled Cybernétique enzymatique [Enzymatic cybernetics]. Never published, this unpublished manuscript presents a synthesis of how Monod interpreted enzymatic adaptation just before the publication of the famous papers of the 1960s on the operon. In addition, Monod offers an example of a philosophy of biology immersed in scientific investigation. Monod's philosophical thoughts are classified into two categories, methodological and ontological. On the methodological side, Monod explicitly hints at his preferences regarding the scientific method in general: hypothetical-deductive method, and use of theoretical models. He also makes heuristic proposals regarding molecular biology: the need to analyse the phenomena in question at the level of individual cells, and the dual aspect of all biological explanation, functional and evolutionary. Ontological issues deal with the notions of information and genetic determinism, "cellular memory", the irrelevance of the notion of "living matter", and the usefulness of a cybernetic comprehension of molecular biology.

  10. Why did Jacques Monod make the choice of mechanistic determinism?

    PubMed

    Loison, Laurent

    2015-06-01

    The development of molecular biology placed in the foreground a mechanistic and deterministic conception of the functioning of macromolecules. In this article, I show that this conception was neither obvious, nor necessary. Taking Jacques Monod as a case study, I detail the way he gradually came loose from a statistical understanding of determinism to finally support a mechanistic understanding. The reasons of the choice made by Monod at the beginning of the 1950s can be understood only in the light of the general theoretical schema supported by the concept of mechanistic determinism. This schema articulates three fundamental notions for Monod, namely that of the rigidity of the sequence of the genetic program, that of the intrinsic stability of macromolecules (DNA and proteins), and that of the specificity of molecular interactions.

  11. PKCι interacts with Rab14 and modulates epithelial barrier function through regulation of claudin-2 levels

    PubMed Central

    Lu, Ruifeng; Dalgalan, Dogukan; Mandell, Edward K.; Parker, Sara S.; Ghosh, Sourav; Wilson, Jean M.

    2015-01-01

    PKCι is essential for the establishment of epithelial polarity and the normal assembly of tight junctions. We find that PKCι knockdown does not compromise the steady-state distribution of most tight junction proteins but results in increased transepithelial resistance (TER) and decreased paracellular permeability. Analysis of the levels of tight junction components demonstrates that claudin-2 protein levels are decreased. However, other tight junction proteins, such as claudin-1, ZO-1, and occludin, are unchanged. Incubation with an aPKC pseudosubstrate recapitulates the phenotype of PKCι knockdown, including increased TER and decreased levels of claudin-2. In addition, overexpression of PKCι results in increased claudin-2 levels. ELISA and coimmunoprecipitation show that the TGN/endosomal small GTPase Rab14 and PKCι interact directly. Immunolabeling shows that PKCι and Rab14 colocalize in both intracellular puncta and at the plasma membrane and that Rab14 expression is required for normal PKCι distribution in cysts in 3D culture. We showed previously that knockdown of Rab14 results in increased TER and decreased claudin-2. Our results suggest that Rab14 and aPKC interact to regulate trafficking of claudin-2 out of the lysosome-directed pathway. PMID:25694446

  12. Urinary Claudin-2 Measurements as a Predictor of Necrotizing Enterocolitis: A Pilot Study

    PubMed Central

    P Blackwood M.D., Brian; R Wood B.S., Douglas; Y Yuan B.S., Carrie; D Nicolas, Joseph; Griffiths M.D., Anne; Mestan M.D., Karen; J Hunter M.D., Catherine

    2015-01-01

    Background: Necrotizing Enterocolitis (NEC) affects 5-10% of NICU patients where initially patients may have only nonspecific clinical findings. A noninvasive tool for detection would aid in diagnosis. Increased urinary claudins have been associated with active adult inflammatory bowel disease. Methods: Institutional Review Board approval was obtained. Neonatal intestinal tissue samples were obtained from patients with and without NEC. Immunofluorescence analysis of claudin-2 was performed on the intestinal tissue. Thirty two urine samples were collected from 6 NICU patients. Proteins were extracted and urinary claudin-2 expression was measured using Western Blot Analysis. All sample concentrations were normalized to urinary creatinine. Differences were analyzed with ANOVA or Student’s T-test. Findings were correlated to the patient’s clinical status. Results: Neonatal intestinal immunofluorescence analysis revealed that claudin-2 is present in healthy intestinal epithelium and is decreased in NEC intestinal tissue (p=0.0001). Of the six patients evaluated, three patients had NEC. All 3 patients with NEC had spikes in urinary claudin-2 levels (p<0.001, p<0.001, p 0.0598 respectively). Spikes did not appear to correlate with other etiologies of neonatal sepsis, medication use or need for mechanical ventilation. Levels during active NEC were almost twice that of NEC-free periods (p<0.0001). Conclusion: A tool for early detection would facilitate early intervention and potential prevention of severe NEC. Preliminary findings indicate that urinary claudin-2 may represent a potential biomarker for NEC worth further investigation. PMID:26500853

  13. Evidence for a role of claudin 2 as a proximal tubular stress responsive paracellular water channel.

    PubMed

    Wilmes, Anja; Aschauer, Lydia; Limonciel, Alice; Pfaller, Walter; Jennings, Paul

    2014-09-01

    Claudins are the major proteins of the tight junctions and the composition of claudin subtypes is decisive for the selective permeability of the paracellular route and thus tissue specific function. Their regulation is complex and subject to interference by several factors, including oxidative stress. Here we show that exposure of cultured human proximal tubule cells (RPTEC/TERT1) to the immunosuppressive drug cyclosporine A (CsA) induces an increase in transepithelial electrical resistance (TEER), a decrease in dome formation (on solid growth supports) and a decrease in water transport (on microporous growth supports). In addition, CsA induced a dramatic decrease in the mRNA for the pore forming claudins -2 and -10, and the main subunits of the Na(+)/K(+) ATPase. Knock down of claudin 2 by shRNA had no discernable effect on TEER or dome formation but severely attenuated apical to basolateral water reabsorption when cultured on microporous filters. Generation of an osmotic gradient in the basolateral compartment rescued water transport in claudin 2 knock down cells. Inhibition of Na(+)/K(+) ATPase with ouabain prevented dome formation in both cell types. Taken together these results provide strong evidence that dome formation is primarily due to transcellular water transport following a solute osmotic gradient. However, in RPTEC/TERT1 cells cultured on filters under iso-osmotic conditions, water transport is primarily paracellular, most likely due to local increases in osmolarity in the intercellular space. In conclusion, this study provides strong evidence that claudin 2 is involved in paracellular water transport and that claudin 2 expression is sensitive to compound induced cellular stress.

  14. Escherichia coli STb enterotoxin dislodges claudin-1 from epithelial tight junctions.

    PubMed

    Nassour, Hassan; Dubreuil, J Daniel

    2014-01-01

    Enterotoxigenic Escherichia coli produce various heat-labile and heat-stable enterotoxins. STb is a low molecular weight heat-resistant toxin responsible for diarrhea in farm animals, mainly young pigs. A previous study demonstrated that cells having internalized STb toxin induce epithelial barrier dysfunction through changes in tight junction (TJ) proteins. These modifications contribute probably to the diarrhea observed. To gain insight into the mechanism of increased intestinal permeability following STb exposure we treated human colon cells (T84) with purified STb toxin after which cells were harvested and proteins extracted. Using a 1% Nonidet P-40-containing solution we investigated the distribution of claudin-1, a major structural and functional TJ protein responsible for the epithelium impermeability, between membrane (NP40-insoluble) and the cytoplasmic (NP-40 soluble) location. Using immunoblot and confocal microscopy, we observed that treatment of T84 cell monolayers with STb induced redistribution of claudin-1. After 24 h, cells grown in Ca++-free medium treated with STb showed about 40% more claudin-1 in the cytoplasm compare to the control. Switching from Ca++-free to Ca++-enriched medium (1.8 mM) increased the dislodgement rate of claudin-1 as comparable quantitative delocalization was observed after only 6 h. Medium supplemented with the same concentration of Mg++ or Zn++ did not affect the dislodgement rate compared to the Ca++-free medium. Using anti-phosphoserine and anti-phosphothreonine antibodies, we observed that the loss of membrane claudin-1 was accompanied by dephosphorylation of this TJ protein. Overall, our findings showed an important redistribution of claudin-1 in cells treated with STb toxin. The loss of phosphorylated TJ membrane claudin-1 is likely to be involved in the increased permeability observed. The mechanisms by which these changes are brought about remain to be elucidated.

  15. Claudin-11 Tight Junctions in Myelin Are a Barrier to Diffusion and Lack Strong Adhesive Properties

    PubMed Central

    Denninger, Andrew R.; Breglio, Andrew; Maheras, Kathleen J.; LeDuc, Geraldine; Cristiglio, Viviana; Demé, Bruno; Gow, Alexander; Kirschner, Daniel A.

    2015-01-01

    The radial component is a network of interlamellar tight junctions (TJs) unique to central nervous system myelin. Ablation of claudin-11, a TJ protein, results in the absence of the radial component and compromises the passive electrical properties of myelin. Although TJs are known to regulate paracellular diffusion, this barrier function has not been directly demonstrated for the radial component, and some evidence suggests that the radial component may also mediate adhesion between myelin membranes. To investigate the physical properties of claudin-11 TJs, we compared fresh, unfixed Claudin 11-null and control nerves using x-ray and neutron diffraction. In Claudin 11-null tissue, we detected no changes in myelin structure, stability, or membrane interactions, which argues against the notion that myelin TJs exhibit significant adhesive properties. Moreover, our osmotic stressing and D2O-H2O exchange experiments demonstrate that myelin lacking claudin-11 is more permeable to water and small osmolytes. Thus, our data indicate that the radial component serves primarily as a diffusion barrier and elucidate the mechanism by which TJs govern myelin function. PMID:26445439

  16. Claudin-11 Tight Junctions in Myelin Are a Barrier to Diffusion and Lack Strong Adhesive Properties.

    PubMed

    Denninger, Andrew R; Breglio, Andrew; Maheras, Kathleen J; LeDuc, Geraldine; Cristiglio, Viviana; Demé, Bruno; Gow, Alexander; Kirschner, Daniel A

    2015-10-01

    The radial component is a network of interlamellar tight junctions (TJs) unique to central nervous system myelin. Ablation of claudin-11, a TJ protein, results in the absence of the radial component and compromises the passive electrical properties of myelin. Although TJs are known to regulate paracellular diffusion, this barrier function has not been directly demonstrated for the radial component, and some evidence suggests that the radial component may also mediate adhesion between myelin membranes. To investigate the physical properties of claudin-11 TJs, we compared fresh, unfixed Claudin 11-null and control nerves using x-ray and neutron diffraction. In Claudin 11-null tissue, we detected no changes in myelin structure, stability, or membrane interactions, which argues against the notion that myelin TJs exhibit significant adhesive properties. Moreover, our osmotic stressing and D2O-H2O exchange experiments demonstrate that myelin lacking claudin-11 is more permeable to water and small osmolytes. Thus, our data indicate that the radial component serves primarily as a diffusion barrier and elucidate the mechanism by which TJs govern myelin function.

  17. From Mephistopheles to Isaiah: Jacques Loeb, technical biology and war.

    PubMed

    Fangerau, Heiner

    2009-04-01

    In 1917, the German-American scientist Jacques Loeb (1859-1924) published a short essay, entitled 'Biology and War', that summarized his disagreement with World War I. He was deeply saddened by the break-up of the international scientific community as a consequence of the actions of bellicose politicians. These actions were in direct opposition to his efforts to promote social reform, mechanistic biology and scientific internationalism. The aim of this paper is to examine Loeb's activities aimed at these efforts before, during and after the war. It attempts to explain how Loeb's scientific work was formed, what was special about it and why it was both successful and attacked. Particular emphasis is placed on how Loeb reacted to the War and the subsequent forced disintegration of his international scientific network. Loeb's attempts to integrate his interpretation of biology into post-war Europe's approach to the life sciences is analysed in connection with his social commitment. It is argued that his emigration to the USA, the circumstances of World War I, the reaction of his German colleagues to it and the demolition of the international scientific community changed: (1) Loeb's feelings towards his old home; (2) the direction of his scientific endeavours; and (3) his engagement in science politics. His correspondence with eminent scientists from all over the world serves as a key to Loeb's efforts in the context of the social elements of scientific networks and perceptions.

  18. Claudin-18 inhibits cell proliferation and motility mediated by inhibition of phosphorylation of PDK1 and Akt in human lung adenocarcinoma A549 cells.

    PubMed

    Shimobaba, Shun; Taga, Saeko; Akizuki, Risa; Hichino, Asami; Endo, Satoshi; Matsunaga, Toshiyuki; Watanabe, Ryo; Yamaguchi, Masahiko; Yamazaki, Yasuhiro; Sugatani, Junko; Ikari, Akira

    2016-06-01

    Abnormal expression of claudin subtypes has been reported in various cancers. However, the pathological role of each claudin has not been clarified in detail. Claudin-18 was absent in human non-small cell and small cell lung cancers, although it is expressed in normal lung tissues. Here, we examined the effect of claudin-18 expression on the expression of junctional proteins, cell proliferation, and cell motility using human lung adenocarcinoma A549 cells. Real-time PCR and western blotting showed that exogenous expression of claudin-18 had no effect on the expression of junctional proteins including claudin-1, zonula occludens-1 (ZO-1), occludin, and E-cadherin. Claudin-18 was mainly distributed in cell-cell contact areas concomitant with ZO-1. Cell proliferation was significantly decreased at 48 and 72h after seeding of claudin 18-expressing cells. Claudin-18 suppressed cell motility, whereas it increased cell death in anoikis. Claudin-18 decreased phosphorylated (p)-3-phosphoinositide-dependent protein kinase-1 (PDK1) and p-Akt levels without affecting p-epidermal growth factor receptor and p-phosphatidylinositol-3 kinase (PI3K) levels. Furthermore, claudin-18 was bound with PDK1 and suppressed the nuclear localization of PDK1. We suggest that claudin-18 suppresses the abnormal proliferation and motility of lung epithelial cells mediated by inhibition of the PI3K/PDK1/Akt signaling pathway.

  19. Claudin-low bladder tumors are immune infiltrated and actively immune suppressed

    PubMed Central

    Kardos, Jordan; Chai, Shengjie; Mose, Lisle E.; Selitsky, Sara R.; Krishnan, Bhavani; Saito, Ryoichi; Iglesia, Michael D.; Milowsky, Matthew I.; Parker, Joel S.; Kim, William Y.; Vincent, Benjamin G.

    2016-01-01

    We report the discovery of a claudin-low molecular subtype of high-grade bladder cancer that shares characteristics with the homonymous subtype of breast cancer. Claudin-low bladder tumors were enriched for multiple genetic features including increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased frequency of PPARG amplification. While claudin-low tumors showed the highest expression of immune gene signatures, they also demonstrated gene expression patterns consistent with those observed in active immunosuppression. This did not appear to be due to differences in predicted neoantigen burden, but rather was associated with broad upregulation of cytokine and chemokine levels from low PPARG activity, allowing unopposed NFKB activity. Taken together, these results define a molecular subtype of bladder cancer with distinct molecular features and an immunologic profile that would, in theory, be primed for immunotherapeutic response.

  20. Claudin-low bladder tumors are immune infiltrated and actively immune suppressed

    PubMed Central

    Kardos, Jordan; Chai, Shengjie; Mose, Lisle E.; Selitsky, Sara R.; Krishnan, Bhavani; Saito, Ryoichi; Iglesia, Michael D.; Milowsky, Matthew I.; Parker, Joel S.; Kim, William Y.; Vincent, Benjamin G.

    2016-01-01

    We report the discovery of a claudin-low molecular subtype of high-grade bladder cancer that shares characteristics with the homonymous subtype of breast cancer. Claudin-low bladder tumors were enriched for multiple genetic features including increased rates of RB1, EP300, and NCOR1 mutations; increased frequency of EGFR amplification; decreased rates of FGFR3, ELF3, and KDM6A mutations; and decreased frequency of PPARG amplification. While claudin-low tumors showed the highest expression of immune gene signatures, they also demonstrated gene expression patterns consistent with those observed in active immunosuppression. This did not appear to be due to differences in predicted neoantigen burden, but rather was associated with broad upregulation of cytokine and chemokine levels from low PPARG activity, allowing unopposed NFKB activity. Taken together, these results define a molecular subtype of bladder cancer with distinct molecular features and an immunologic profile that would, in theory, be primed for immunotherapeutic response. PMID:27699256

  1. Claudin-1 expression confers resistance to anoikis in colon cancer cells in a Src-dependent manner

    PubMed Central

    Singh, Amar B.; Sharma, Ashok; Dhawan, Punita

    2012-01-01

    Denial of the appropriate cell-matrix interaction in epithelial cells induces apoptosis and is called ‘anoikis’. Cancer cells are resistant to anoikis and it is believed that the resistance to anoikis helps promote tumor malignancy especially metastasis. We and others have demonstrated that the expression of tight junction protein claudin-1 is highly upregulated in colorectal cancer (CRC) and helps promote tumor progression and metastasis. However, molecular mechanism/s underlying claudin-1-dependent regulation of CRC progression remains poorly understood. In current study, we have determined that claudin-1 expression modulates anoikis in colon cancer cells to influence colon cancer invasion and thus metastasis. We have further provided data that claudin-1 modulates anoikis in a Src-Akt-Bcl-2-dependent manner. Importantly, claudin-1 physically associates with Src/p-Src in a multiprotein complex that also includes ZO-1, a PDZ-binding tight junction protein. Taken together, our data support the role of claudin-1 in the regulation of CRC progression and suggest that the regulation of anoikis may serve as a key regulatory mechanism in claudin-1-dependent regulation of CRC progression. Our findings are of direct clinical relevance and may open new therapeutic opportunity in colon cancer treatment and/or management. PMID:22941059

  2. Interendothelial claudin-5 expression depends on cerebral endothelial cell–matrix adhesion by β1-integrins

    PubMed Central

    Osada, Takashi; Gu, Yu-Huan; Kanazawa, Masato; Tsubota, Yoshiaki; Hawkins, Brian T; Spatz, Maria; Milner, Richard; del Zoppo, Gregory J

    2011-01-01

    The hypothesis tested by these studies states that in addition to interendothelial cell tight junction proteins, matrix adhesion by β1-integrin receptors expressed by endothelial cells have an important role in maintaining the cerebral microvessel permeability barrier. Primary brain endothelial cells from C57 BL/6 mice were incubated with β1-integrin function-blocking antibody (Ha2/5) or isotype control and the impacts on claudin-5 expression and microvessel permeability were quantified. Both flow cytometry and immunofluorescence studies demonstrated that the interendothelial claudin-5 expression by confluent endothelial cells was significantly decreased in a time-dependent manner by Ha2/5 exposure relative to isotype. Furthermore, to assess the barrier properties, transendothelial electrical resistance and permeability measurements of the monolayer, and stereotaxic injection into the striatum of mice were performed. Ha2/5 incubation reduced the resistance of endothelial cell monolayers significantly, and significantly increased permeability to 40 and 150 kDa dextrans. Ha2/5 injection into mouse striatum produced significantly greater IgG extravasation than the isotype or the control injections. This study demonstrates that blockade of β1-integrin function changes interendothelial claudin-5 expression and increases microvessel permeability. Hence, endothelial cell–matrix interactions via β1-integrin directly affect interendothelial cell tight junction claudin-5 expression and brain microvascular permeability. PMID:21772312

  3. Claudin gene expression patterns do not associate with interspecific differences in paracellular nutrient absorption.

    PubMed

    Price, Edwin R; Rott, Katherine H; Caviedes-Vidal, Enrique; Karasov, William H

    2016-01-01

    Bats exhibit higher paracellular absorption of glucose-sized molecules than non-flying mammals, a phenomenon that may be driven by higher permeability of the intestinal tight junctions. The various claudins, occludin, and other proteins making up the tight junctions are thought to determine their permeability properties. Here we show that absorption of the paracellular probe l-arabinose is higher in a bat (Eptesicus fuscus) than in a vole (Microtus pennsylvanicus) or a hedgehog (Atelerix albiventris). Furthermore, histological measurements demonstrated that hedgehogs have many more enterocytes in their intestines, suggesting that bats cannot have higher absorption of arabinose simply by having more tight junctions. We therefore investigated the mRNA levels of several claudins and occludin, because these proteins may affect permeability of tight junctions to macronutrients. To assess the expression levels of claudins per tight junction, we normalized the mRNA levels of the claudins to the constitutively expressed tight junction protein ZO-1, and combined these with measurements previously made in a bat and a rodent to determine if there were among-species differences. Although expression ratios of several genes varied among species, there was not a consistent difference between bats and non-flyers in the expression ratio of any particular gene. Protein expression patterns may differ from mRNA expression patterns, and might better explain differences among species in arabinose absorption. PMID:26393434

  4. Claudin gene expression patterns do not associate with interspecific differences in paracellular nutrient absorption.

    PubMed

    Price, Edwin R; Rott, Katherine H; Caviedes-Vidal, Enrique; Karasov, William H

    2016-01-01

    Bats exhibit higher paracellular absorption of glucose-sized molecules than non-flying mammals, a phenomenon that may be driven by higher permeability of the intestinal tight junctions. The various claudins, occludin, and other proteins making up the tight junctions are thought to determine their permeability properties. Here we show that absorption of the paracellular probe l-arabinose is higher in a bat (Eptesicus fuscus) than in a vole (Microtus pennsylvanicus) or a hedgehog (Atelerix albiventris). Furthermore, histological measurements demonstrated that hedgehogs have many more enterocytes in their intestines, suggesting that bats cannot have higher absorption of arabinose simply by having more tight junctions. We therefore investigated the mRNA levels of several claudins and occludin, because these proteins may affect permeability of tight junctions to macronutrients. To assess the expression levels of claudins per tight junction, we normalized the mRNA levels of the claudins to the constitutively expressed tight junction protein ZO-1, and combined these with measurements previously made in a bat and a rodent to determine if there were among-species differences. Although expression ratios of several genes varied among species, there was not a consistent difference between bats and non-flyers in the expression ratio of any particular gene. Protein expression patterns may differ from mRNA expression patterns, and might better explain differences among species in arabinose absorption.

  5. Claudin 4 expression in triple-negative breast cancer: correlation with androgen receptors and Ki-67 expression.

    PubMed

    Abd-Elazeem, Mona A; Abd-Elazeem, Marwa A

    2015-02-01

    Breast cancer is the most common malignancy in women and the leading cause of cancer mortality worldwide. Triple-negative breast cancer (TNBC) is an important phenotype of breast cancer that accounts for a relatively small number of breast cancer cases but still represent a focus of increasing interest at the clinical, biological, and epidemiological level. Claudins are the major component of the tight junction, and only a few studies have addressed the role of claudins in breast cancer, especially TNBC. Androgen receptors (ARs), as members of the nuclear receptor superfamily, are known to be involved in a complex network of signaling pathways that collectively regulate cell proliferation. However, roles of AR in breast cancer development and progression have not been very clearly understood. The proliferation marker Ki-67 has been confirmed as an independent predictive and prognostic factor in early breast cancer. The aims of this study are to identify the clinicopathologic associations and prognostic value of claudin 4 expression in TNBC and to correlate claudin 4 expression with AR status and Ki-67 expression. Paraffin blocks obtained from 56 female patients with triple-negative primary invasive ductal breast carcinomas were analyzed for claudin 4, AR, and Ki-67 immunohistochemical expression. High levels of claudin 4 expression were detected in 66.1% of TNBC cases. There was a significant positive correlation with age, tumor size, grade, nodal status, metastasis, and Ki-67 expression (all P < .05) and negative correlation with AR status (P < .001). Androgen receptor showed positivity in 29 cases (51.78%). There was a statistical negative correlation with the all the studied clinicopathologic parameters, claudin 4 and Ki-67 expression. High claudin 4 expression, negative AR expression, and high Ki-67 index would provide a strong prognostic power to differentiate the patients with worse outcome among TNBC patients. Moreover, target treatment for TNBC cells

  6. Acid modulates the squamous epithelial barrier function by modulating the localization of claudins in the superficial layers.

    PubMed

    Oshima, Tadayuki; Koseki, Junichi; Chen, Xin; Matsumoto, Takayuki; Miwa, Hiroto

    2012-01-01

    Acid is a major cause of gastro-esophageal reflux disease. However, the influence of acid on the esophageal stratified epithelial barrier function and tight junction (TJ) proteins is not fully understood. Here, we explore the influence of acid on barrier function and TJ proteins using a newly developed model of the esophageal-like squamous epithelial cell layers that employs an air-liquid interface (ALI) system. Barrier function was determined by measuring trans-epithelial electrical resistance (TEER) and diffusion of paracellular tracers. TJ-related protein (claudin-1, claudin-4, occludin and ZO-1) expression and localization was examined by immunofluorescent staining, and by western blotting of 1% NP-40 soluble and insoluble fractions. We also examined the influence of acid (pH 2-4) on the barrier created by these cells. The in vitro ALI culture system showed a tight barrier (1500-2500 Ω·cm(2)) with the expression of claudin-1, claudin-4, occludin and ZO-1 in the superficial layers. Claudin-1, claudin-4, occludin and ZO-1 were detected as dots and whisker-like lines in the superficial layers, and as a broad line in the suprabasal layers. These localization patterns are similar to those in the human esophagus. On day 7 under ALI culture, TJ proteins were detected in the superficial layers with functional properties, including decreased permeability and increased TEER. Dilated intercellular spaces were detected at the suprabasal cell layers even under the control conditions of ALI cells. pH 2 acid on the apical side significantly reduced the TEER in ALI-cultured cells. This decrease in TEER by the acid was in parallel with the decreased amount of detergent-insoluble claudin-4. Claudin-4 delocalization was confirmed by immunofluorescent staining. In conclusion, TJs are located in the superficial layers of the esophagus, and acid stimulation disrupts barrier function, at least in part by modulating the amount and localization of claudin-4 in the superficial layers.

  7. Condensed matter physics in the 21st century: The legacy of Jacques Friedel

    NASA Astrophysics Data System (ADS)

    Bouchiat, Hélène; Villain, Jacques

    2016-03-01

    The purpose of this dossier of Comptes rendus Physique devoted to the memory of Jacques Friedel is to give a panorama of his exceptional and numerous contributions to modern condensed matter physics. Since it is not possible to cover all the domains he investigated in a single volume, we have selected only a limited number of topics. We have tried, when possible, to present a juxtaposition of articles written by his former students or colleagues with others written instead by younger researchers whose work is inspired by important concepts originating from the work of Jacques Friedel, but who may have never met him.

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

    PubMed Central

    McCabe, Mark J; Foo, Caroline FH; Dinger, Marcel E; Smooker, Peter M; Stanton, Peter G

    2016-01-01

    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. PMID:26585695

  9. A scientist born in amiens : jacques rohault (1620-1672) (French Title: Un savant amiénois : jacques rohault (1620-1672))

    NASA Astrophysics Data System (ADS)

    Le Boeuffle, A.

    2004-12-01

    Jacques Rohault is born in Amiens town at the beginning of the seventeen century. After the Middle Ages, science try to use nex methods and want to abandon Greek's dogmas. Rohault came to Paris to continue his studies and met J.B. Poquelin (Molière). He became a friend an a supporter of René Descartes. He was a very popular scientist. He practised many experiments in public and writed the book La physique to popularize science.

  10. Role of TGF-β-induced Claudin-4 expression through c-Jun signaling in non-small cell lung cancer.

    PubMed

    Rachakonda, Girish; Vu, Trung; Jin, Lin; Samanta, Debangshu; Datta, Pran K

    2016-10-01

    Claudin-4 has been identified as an integral member of tight junctions and has been found to be upregulated in various types of cancers especially in metastatic cancers. However, the molecular mechanism of the upregulation of Claudin-4 and its role in lung tumorigenesis are unknown. The aim of the present study is to investigate the role of Claudin-4 on migration and tumorigenicity of lung cancer cells and to examine the regulatory effects of TGF-β on Claudin-4 expression. We have observed that TGF-β induces the expression of Claudin-4 dramatically in lung cell lines in a time dependent manner. TGF-β-induced Smad signaling is important for enhancing Claudin-4 mRNA level through inducing its promoter activity. Treatment with curcumin, a c-Jun inhibitor, or stable knockdown of c-Jun abrogates TGF-β-induced Claudin-4 expression suggesting an involvement of the c-Jun pathway. Notably, TGF-β-induced Claudin-4 expression through c-Jun pathway plays a role in TGF-β-mediated motility and tumorigenicity of these cells. In support of these observations, we have uncovered that Claudin-4 is upregulated in 14 of 24 (58%) lung tumors when compared with normal lung tissue. This is the first study to show how TGF-β regulates the expression of Claudin-4 through c-Jun signaling and how this pathway contributes to the migratory and tumorigenic phenotype of lung tumor cells. PMID:27424491

  11. Role of TGF-β-induced Claudin-4 expression through c-Jun signaling in non-small cell lung cancer.

    PubMed

    Rachakonda, Girish; Vu, Trung; Jin, Lin; Samanta, Debangshu; Datta, Pran K

    2016-10-01

    Claudin-4 has been identified as an integral member of tight junctions and has been found to be upregulated in various types of cancers especially in metastatic cancers. However, the molecular mechanism of the upregulation of Claudin-4 and its role in lung tumorigenesis are unknown. The aim of the present study is to investigate the role of Claudin-4 on migration and tumorigenicity of lung cancer cells and to examine the regulatory effects of TGF-β on Claudin-4 expression. We have observed that TGF-β induces the expression of Claudin-4 dramatically in lung cell lines in a time dependent manner. TGF-β-induced Smad signaling is important for enhancing Claudin-4 mRNA level through inducing its promoter activity. Treatment with curcumin, a c-Jun inhibitor, or stable knockdown of c-Jun abrogates TGF-β-induced Claudin-4 expression suggesting an involvement of the c-Jun pathway. Notably, TGF-β-induced Claudin-4 expression through c-Jun pathway plays a role in TGF-β-mediated motility and tumorigenicity of these cells. In support of these observations, we have uncovered that Claudin-4 is upregulated in 14 of 24 (58%) lung tumors when compared with normal lung tissue. This is the first study to show how TGF-β regulates the expression of Claudin-4 through c-Jun signaling and how this pathway contributes to the migratory and tumorigenic phenotype of lung tumor cells.

  12. Educational Research and "Human Techniques" in the Global Technological System: The Theory of Jacques Ellul.

    ERIC Educational Resources Information Center

    Waks, Leonard J.

    The French sociologist Jacques Ellul has had great influence on contemporary thought about the role of science and technology in the emerging global society. His books "The Technological Society" (1954) and "The Technological System" (1980) characterize the new social context as a tightly interlocked global technological system increasingly…

  13. Initiating "The Methodology of Jacques Ranciere": How Does It All Start?

    ERIC Educational Resources Information Center

    Mercieca, Duncan P.

    2012-01-01

    Educationalists are currently engaging with Jacques Ranciere's thought on emancipation and equality. The focus of this paper is on what initiates the process that starts emancipation. With reference to teachers the question is: how do teachers become emancipated? This paper discusses how the teacher's life is made "sensible" and how sense is…

  14. Jacques Cousteau's Living Sea: A Museum of the Mind and the Senses

    ERIC Educational Resources Information Center

    Riddle, Jan

    1973-01-01

    Describes the major exhibits to be found in Jacques Cousteau's Living Sea Museum, which is located aboard the Queen Mary at Long Beach, California. It is described as a museum of the mind and senses, since the exhibits demand imagination and the use of sight, hearing, touch, and smell. (JR)

  15. A Portrait of the Teacher as Friend and Artist: The Example of Jean-Jacques Rousseau

    ERIC Educational Resources Information Center

    McEwan, Hunter

    2011-01-01

    The following is a reflection on the possibility of teaching by example, and especially as the idea of teaching by example is developed in the work of Jean-Jacques Rousseau. My thesis is that Rousseau created a literary version of himself in his writings as an embodiment of his philosophy, rather in the same way and with the same purpose that…

  16. The Meaning of the Global City: Jacques Ellul's Continued Relevance to 21st-Century Urbanism

    ERIC Educational Resources Information Center

    Toly, Noah

    2012-01-01

    Jacques Ellul's book, "The Meaning of the City," widely recognized as one of the most important twentieth century theological reflections on the city, was also one of his most controversial scholarly contributions. Many urbanists interpreted the book as demeaning the city and diminishing the importance of urban policy, planning, design,…

  17. Emancipating Subjects in Science Education: Taking a Lesson from Patti Lather and Jacques Ranciere

    ERIC Educational Resources Information Center

    Bazzul, Jesse

    2013-01-01

    This paper extends the conversation started by Patti Lather in her forum response to "Neoliberal ideology, global capitalism, and science education: engaging the question of subjectivity", in terms of engaging the thought of Jacques Ranciere. Ranciere can offer (science) educators a more definitive example of (possible) emancipatory political…

  18. Jacques Prevert: "Modernism"--Conception and Perception of His Contemporary Society through His Poetry.

    ERIC Educational Resources Information Center

    Buzash, Michael D.

    Born in 1900, Jacques Prevert was destined to become one of the most popular poets of the twentieth century. After spending his young adulthood with artists linked with the surrealist movement, Prevert became a satirist, social critic, songwriter, writer of children's stories and television programs, and poet. Prevert's interests in the visual…

  19. The Essential Connection Between the Two Parts of the Work of Jacques Ellul

    ERIC Educational Resources Information Center

    Vanderburg, Willem H.

    2004-01-01

    Almost without exception, interpretations of Jacques Ellul's work focus either on his sociopolitical thought or on his Christian reflections. However, each one drives the other, thereby exposing how we collectively journey through time and reality on a magic carpet of myths (in the sense of cultural anthropology). Ellul challenges us to give up…

  20. Can You Hear Me Now? Jean-Jacques Rousseau on Listening Education

    ERIC Educational Resources Information Center

    Laverty, Megan J.

    2011-01-01

    In this essay Megan J. Laverty argues that Jean-Jacques Rousseau's conception of humane communication and his proposal for teaching it have implications for our understanding of the role of listening in education. She develops this argument through a close reading of Rousseau's most substantial work on education, "Emile: Or, On Education". Laverty…

  1. The Autodidact in Defense of Himself: Jean-Jacques Rousseau and Knut Hamsun.

    ERIC Educational Resources Information Center

    Buttry, Dolores

    1980-01-01

    Describes Jean-Jacques Rousseau and Knut Hamsun as self-educated men who never ceased to warn of the evils of formal education. Quoting from their works, considers their feelings toward education as revealed in Rousseau's "Emile," with its description of ideal education, and in the ill effects of education on Hamsun's characters. (AYC)

  2. Curing Provincialism: Why We Educate the Way We Do. A Conversation with Jacques Barzun.

    ERIC Educational Resources Information Center

    American Educator, 2002

    2002-01-01

    This interview with author and cultural historian Jacques Barzun discusses the origins of history, science, art, literature, and math, calling them the core of intellectual inheritance. Notes how the frameworks they provide enable people to extend their understanding of the world and reach beyond natural, human parochialism. Discusses the…

  3. Reconsidering Emancipatory Education: Staging a Conversation between Paulo Freire and Jacques Ranciere

    ERIC Educational Resources Information Center

    Galloway, Sarah

    2012-01-01

    In this essay Sarah Galloway considers emancipation as a purpose for education through examining the theories of Paulo Freire and Jacques Ranciere. Both theorists are concerned with the prospect of distinguishing between education that might socialize people into what is taken to be an inherently oppressive society and education with emancipation…

  4. Jacques Maritain's Philosophy of History and Philosophy of Education: A Relationship Secured Through Experience and Reason.

    ERIC Educational Resources Information Center

    D'Souza, Mario

    1997-01-01

    Jacques Maritain's philosophy of history and philosophy of education both deal with the singularity of experience and the universality of reason. The philosophy of history is subordinated to moral philosophy; the philosophy of education is subordinated to metaphysics. Although Maritain's philosophies reflect a Christian world view, they can make a…

  5. The Drosophila Claudin Kune-kune is required for septate junction organization and tracheal tube size control.

    PubMed

    Nelson, Kevin S; Furuse, Mikio; Beitel, Greg J

    2010-07-01

    The vertebrate tight junction is a critical claudin-based cell-cell junction that functions to prevent free paracellular diffusion between epithelial cells. In Drosophila, this barrier is provided by the septate junction, which, despite being ultrastructurally distinct from the vertebrate tight junction, also contains the claudin-family proteins Megatrachea and Sinuous. Here we identify a third Drosophila claudin, Kune-kune, that localizes to septate junctions and is required for junction organization and paracellular barrier function, but not for apical-basal polarity. In the tracheal system, septate junctions have a barrier-independent function that promotes lumenal secretion of Vermiform and Serpentine, extracellular matrix modifier proteins that are required to restrict tube length. As with Sinuous and Megatrachea, loss of Kune-kune prevents this secretion and results in overly elongated tubes. Embryos lacking all three characterized claudins have tracheal phenotypes similar to any single mutant, indicating that these claudins act in the same pathway controlling tracheal tube length. However, we find that there are distinct requirements for these claudins in epithelial septate junction formation. Megatrachea is predominantly required for correct localization of septate junction components, while Sinuous is predominantly required for maintaining normal levels of septate junction proteins. Kune-kune is required for both localization and levels. Double- and triple-mutant combinations of Sinuous and Megatrachea with Kune-kune resemble the Kune-kune single mutant, suggesting that Kune-kune has a more central role in septate junction formation than either Sinuous or Megatrachea.

  6. Claudin-3 Overexpression Increases the Malignant Potential of Colorectal Cancer Cells: Roles of ERK1/2 and PI3K-Akt as Modulators of EGFR signaling

    PubMed Central

    de Souza, Waldemir F.; Fortunato-Miranda, Natalia; Robbs, Bruno K.; de Araujo, Wallace M.; de-Freitas-Junior, Julio C.; Bastos, Lilian G.; Viola, João P. B.; Morgado-Díaz, José A.

    2013-01-01

    The altered expressions of claudin proteins have been reported during the tumorigenesis of colorectal cancer. However, the molecular mechanisms that regulate these events in this cancer type are poorly understood. Here, we report that epidermal growth factor (EGF) increases the expression of claudin-3 in human colorectal adenocarcinoma HT-29 cells. This increase was related to increased cell migration and the formation of anchorage-dependent and anchorage-independent colonies. We further showed that the ERK1/2 and PI3K-Akt pathways were involved in the regulation of these effects because specific pharmacological inhibition blocked these events. Genetic manipulation of claudin-1 and claudin-3 in HT-29 cells showed that the overexpression of claudin-1 resulted in decreased cell migration; however, migration was not altered in cells that overexpressed claudin-3. Furthermore, the overexpression of claudin-3, but not that of claudin-1, increased the tight junction-related paracellular flux of macromolecules. Additionally, an increased formation of anchorage-dependent and anchorage-independent colonies were observed in cells that overexpressed claudin-3, while no such changes were observed when claudin-1 was overexpressed. Finally, claudin-3 silencing alone despite induce increase proliferation, and the formation of anchoragedependent and -independent colonies, it was able to prevent the EGF-induced increased malignant potential. In conclusion, our results show a novel role for claudin-3 overexpression in promoting the malignant potential of colorectal cancer cells, which is potentially regulated by the EGF-activated ERK1/2 and PI3K-Akt pathways. PMID:24069372

  7. Structure-Function Studies of Claudin Extracellular Domains by Cysteine-scanning Mutagenesis*

    PubMed Central

    Angelow, Susanne; Yu, Alan S. L.

    2009-01-01

    Claudins form size- and charge-selective pores in the tight junction that control the paracellular flux of inorganic ions and small molecules. However, the structural basis for ion selectivity of paracellular pores is poorly understood. Here we applied cysteine scanning to map the paracellular pathway of ion permeation across claudin-2-transfected Madin-Darby canine kidney type I cells. Four potential pore-lining amino acid residues in the first extracellular loop were mutated to cysteine and screened for their accessibility to thiol-reactive reagents. All mutants were functional except D65C, which formed dimers by intermolecular disulfide bonding, leading to a loss of charge and size selectivity. This suggests that claudin-2 pores are multimeric and that Asp65 lies close to a protein-protein interface. Methanethiosulfonate reagents of different size and charge and the organic mercury derivate, p-(chloromercuri)benzenesulfonic acid, significantly decreased paracellular ion permeation across I66C-transfected cells by a mechanism that suggests steric blocking of the pore. The conductance of wild-type claudin-2 and the other cysteine mutants was only weakly affected. The rate of reaction with I66C decreased dramatically with increasing size of the reagent, suggesting that Ile66 is buried deep within a narrow segment of the pore with its side group facing into the lumen. Furthermore, labeling with N-biotinoylaminoethyl methanethiosulfonate showed that I66C was weakly reactive, whereas Y35C was strongly reactive, suggesting that Tyr35 is located at the protein surface outside of the pore. PMID:19690347

  8. Claudin-2 Expression Levels in Ulcerative Colitis: Development and Validation of an In-Situ Hybridisation Assay for Therapeutic Studies

    PubMed Central

    Randall, Kevin; Reens, Jaimini; Eckersley, Sonia; Nyström, Ann-Christin; South, Marie C.; Balendran, Clare A.; Böttcher, Gerhard; Hughes, Glen; Price, Sally A.

    2016-01-01

    Ulcerative colitis is a chronic inflammatory disease affecting the colon and is characterized by epithelial damage and barrier dysfunction. Upregulation of the tight junction protein claudin-2 by cytokines is hypothesized to contribute to the dysregulation of the epithelial barrier. New therapeutic agents which block the action of cytokines are being investigated in patients with ulcerative colitis. In order to understand the potential of these therapies, it is important to have reliable assays that can assess downstream endpoints that reflect drug mechanism of action. The aim of the current study was therefore to establish & validate an assay to reproducibly assess the expression and distribution of claudin-2 in human colon biopsy samples. Initially, the potential to measure claudin-2 protein by immunohistochemistry (IHC) was investigated. To identify suitable reagents to develop an IHC assay, pre-established criteria were used to screen five commercial antibodies by Western blotting, immunofluorescence and immunohistochemistry on claudin-2 positive and negative cells and healthy and ulcerative colitis colon tissue. Despite some of these antibodies specifically detecting claudin-2 using some of these techniques, none of the antibodies showed the expected specific staining pattern in formalin fixed human colon samples. As an alternative method to detect claudin-2 expression and distribution in formalin fixed biopsy sections, an in situ hybridization assay was developed. This assay underwent a novel tiered approach of validation to establish that it was fit-for-purpose, and suitable for clinical deployment. In addition, to understand the possible relationship of claudin-2 in the context of disease severity, expression was compared to the Geboes score. Overall, the microscopical Geboes score correlated with the claudin-2 biomarker score for samples that retained crypt morphology; samples with the highest Geboes score were not specifically distinguished, probably due

  9. Claudin-2 Expression Levels in Ulcerative Colitis: Development and Validation of an In-Situ Hybridisation Assay for Therapeutic Studies.

    PubMed

    Randall, Kevin; Henderson, Neil; Reens, Jaimini; Eckersley, Sonia; Nyström, Ann-Christin; South, Marie C; Balendran, Clare A; Böttcher, Gerhard; Hughes, Glen; Price, Sally A

    2016-01-01

    Ulcerative colitis is a chronic inflammatory disease affecting the colon and is characterized by epithelial damage and barrier dysfunction. Upregulation of the tight junction protein claudin-2 by cytokines is hypothesized to contribute to the dysregulation of the epithelial barrier. New therapeutic agents which block the action of cytokines are being investigated in patients with ulcerative colitis. In order to understand the potential of these therapies, it is important to have reliable assays that can assess downstream endpoints that reflect drug mechanism of action. The aim of the current study was therefore to establish & validate an assay to reproducibly assess the expression and distribution of claudin-2 in human colon biopsy samples. Initially, the potential to measure claudin-2 protein by immunohistochemistry (IHC) was investigated. To identify suitable reagents to develop an IHC assay, pre-established criteria were used to screen five commercial antibodies by Western blotting, immunofluorescence and immunohistochemistry on claudin-2 positive and negative cells and healthy and ulcerative colitis colon tissue. Despite some of these antibodies specifically detecting claudin-2 using some of these techniques, none of the antibodies showed the expected specific staining pattern in formalin fixed human colon samples. As an alternative method to detect claudin-2 expression and distribution in formalin fixed biopsy sections, an in situ hybridization assay was developed. This assay underwent a novel tiered approach of validation to establish that it was fit-for-purpose, and suitable for clinical deployment. In addition, to understand the possible relationship of claudin-2 in the context of disease severity, expression was compared to the Geboes score. Overall, the microscopical Geboes score correlated with the claudin-2 biomarker score for samples that retained crypt morphology; samples with the highest Geboes score were not specifically distinguished, probably due

  10. Methods to analyze subcellular localization and intracellular trafficking of Claudin-16.

    PubMed

    Kausalya, P Jaya; Hunziker, Walter

    2011-01-01

    The integral tight junction protein Claudin-16 (Cldn16) is predominantly expressed in renal epithelial cells of the thick ascending limb of Henle's loop where, together with claudin-19, it forms a cation-selective pore that allows influx of Na+ from the interstitial fluid into the lumen of the kidney tubule. This leads to an electrochemical gradient that drives the reabsorbtion of Mg2+ and Ca2+ ions from the renal filtrate. Mutations in the Cldn16 gene have been identified in patients suffering from familial hypomagnesemia with hypercalciuria and nephrocalcinosis, with excessive renal wastage of Mg2+ and Ca2+ being a hallmark of this condition. Studies into the mechanism by which mutations impair Cldn16 function have shown that although several mutations affect paracellular ion transport, many interfere with intracellular trafficking of Cldn16, ultimately compromising its localization to TJs. Here, we describe the experimental approaches that can be used to monitor intracellular localization and trafficking of Cldn16. These methods can easily be adapted to study other claudins, provided suitable antibodies are available.

  11. Autophagy enhances intestinal epithelial tight junction barrier function by targeting claudin-2 protein degradation.

    PubMed

    Nighot, Prashant K; Hu, Chien-An Andy; Ma, Thomas Y

    2015-03-13

    Autophagy is an intracellular degradation pathway and is considered to be an essential cell survival mechanism. Defects in autophagy are implicated in many pathological processes, including inflammatory bowel disease. Among the innate defense mechanisms of intestinal mucosa, a defective tight junction (TJ) barrier has been postulated as a key pathogenic factor in the causation and progression of inflammatory bowel disease by allowing increased antigenic permeation. The cross-talk between autophagy and the TJ barrier has not yet been described. In this study, we present the novel finding that autophagy enhances TJ barrier function in Caco-2 intestinal epithelial cells. Nutrient starvation-induced autophagy significantly increased transepithelial electrical resistance and reduced the ratio of sodium/chloride paracellular permeability. Nutrient starvation reduced the paracellular permeability of small-sized urea but not larger molecules. The role of autophagy in the modulation of paracellular permeability was confirmed by pharmacological induction as well as pharmacological and genetic inhibition of autophagy. Consistent with the autophagy-induced reduction in paracellular permeability, a marked decrease in the level of the cation-selective, pore-forming TJ protein claudin-2 was observed after cell starvation. Starvation reduced the membrane presence of claudin-2 and increased its cytoplasmic, lysosomal localization. Therefore, our data show that autophagy selectively reduces epithelial TJ permeability of ions and small molecules by lysosomal degradation of the TJ protein claudin-2.

  12. Autophagy Enhances Intestinal Epithelial Tight Junction Barrier Function by Targeting Claudin-2 Protein Degradation*

    PubMed Central

    Nighot, Prashant K.; Hu, Chien-An Andy; Ma, Thomas Y.

    2015-01-01

    Autophagy is an intracellular degradation pathway and is considered to be an essential cell survival mechanism. Defects in autophagy are implicated in many pathological processes, including inflammatory bowel disease. Among the innate defense mechanisms of intestinal mucosa, a defective tight junction (TJ) barrier has been postulated as a key pathogenic factor in the causation and progression of inflammatory bowel disease by allowing increased antigenic permeation. The cross-talk between autophagy and the TJ barrier has not yet been described. In this study, we present the novel finding that autophagy enhances TJ barrier function in Caco-2 intestinal epithelial cells. Nutrient starvation-induced autophagy significantly increased transepithelial electrical resistance and reduced the ratio of sodium/chloride paracellular permeability. Nutrient starvation reduced the paracellular permeability of small-sized urea but not larger molecules. The role of autophagy in the modulation of paracellular permeability was confirmed by pharmacological induction as well as pharmacological and genetic inhibition of autophagy. Consistent with the autophagy-induced reduction in paracellular permeability, a marked decrease in the level of the cation-selective, pore-forming TJ protein claudin-2 was observed after cell starvation. Starvation reduced the membrane presence of claudin-2 and increased its cytoplasmic, lysosomal localization. Therefore, our data show that autophagy selectively reduces epithelial TJ permeability of ions and small molecules by lysosomal degradation of the TJ protein claudin-2. PMID:25616664

  13. Checkpoint Kinase 1 Activation Enhances Intestinal Epithelial Barrier Function via Regulation of Claudin-5 Expression

    PubMed Central

    Watari, Akihiro; Hasegawa, Maki; Yagi, Kiyohito; Kondoh, Masuo

    2016-01-01

    Several stressors are known to influence epithelial tight junction (TJ) integrity, but the association between DNA damage and TJ integrity remains unclear. Here we examined the effects of daunorubicin and rebeccamycin, two anti-tumor chemicals that induce DNA damage, on TJ integrity in human intestinal epithelial cells. Daunorubicin and rebeccamycin dose-dependently enhanced transepithelial electrical resistance (TER) and decreased flux of the 4 kDa FITC-dextran in Caco-2 cell monolayer. Daunorubicin- or rebeccamycin-induced enhancement of the TJ barrier function partly rescued attenuation of the barrier function by the inflammatory cytokines TNF-α and IFN-γ. Daunorubicin and rebeccamycin increased claudin-5 expression and the product was distributed in the actin cytoskeleton fraction, which was enriched with TJ proteins. Caffeine, which is an inhibitor of ataxia telangiectasia mutated protein (ATM) and ataxia telangiectasia mutated and Rad3-related protein (ATR), and the Chk1 inhibitor inhibited the TER increases induced by daunorubicin and rebeccamycin, whereas a Chk2 inhibitor did not. Treatment with Chk1 siRNA also significantly inhibited the TER increases. Induction of claudin-5 expression was inhibited by Chk1 inhibitor and by siRNA treatment. Our results suggest that Chk1 activation by daunorubicin and rebeccamycin induced claudin-5 expression and enhanced TJ barrier function in Caco-2 cell monolayer, which suggests a link between DNA damage and TJ integrity in the human intestine. PMID:26727128

  14. Claudin multigene family in channel catfish and their expression profiles in response to bacterial infection and hypoxia as revealed by meta-analysis of RNA-Seq datasets.

    PubMed

    Sun, Luyang; Liu, Shikai; Bao, Lisui; Li, Yun; Feng, Jianbin; Liu, Zhanjiang

    2015-03-01

    Claudins are one of the major groups of transmembrane proteins that play crucial roles in tight junctions. In addition to their function in the regulation of paracellular permeability, claudins are also involved in a number of biological processes related to pathogen infection, embryonic development, organ development and hypoxia response. Despite its importance, analyses of claudin genes in channel catfish have not been systematically performed. In this study, a total of 52 claudin genes were identified and characterized in channel catfish. Phylogenetic analyses were conducted to determine their identities and identify a number of lineage-specific claudin gene duplications in channel catfish. Expression profiles of catfish claudin genes in response to enteric septicemia of catfish (ESC) disease and hypoxia stress were determined by analyzing existing RNA-Seq datasets. Claudin genes were significantly down-regulated in the intestine at 3h post-infection, indicating that pathogens may disrupt the mucosal barrier by suppressing the expression of claudin genes. A total of six claudin genes were significantly regulated in the gill after hypoxia stress. Among them, the expressions of cldn-11b and cldn-10d were dramatically altered when comparing hypoxia tolerant fish with intolerant fish, though their specific roles involved in response to hypoxia stress remained unknown.

  15. Claudin-1, -2 and -3 Are Selectively Expressed in the Epithelia of the Choroid Plexus of the Mouse from Early Development and into Adulthood While Claudin-5 is Restricted to Endothelial Cells

    PubMed Central

    Steinemann, Alexandra; Galm, Isabel; Chip, Sophorn; Nitsch, Cordula; Maly, Ireneusz Piotr

    2016-01-01

    A primary function of epithelial and endothelial monolayers is the formation of barriers that separate tissues into functional compartments. Tight junctions (TJs) seal the intercellular space between the single cells of a monolayer. TJs thus contribute importantly to the homeostasis of the cerebrospinal fluid as they help in maintaining the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (CSF). The composition of TJs differs by its localization as well as the stage of development according to its respective function. Claudin-3 is typically present in the epithelia and has been claimed to be a constituent of the BBB. It is, however, notoriously difficult to demonstrate its expression in endothelial cells of the brain vasculature at the morphological level by means of immunohistochemical techniques. Using an improved fixation strategy (4% paraformaldehyde at pH 11, in the presence of EDTA) and the sensitive alkaline phosphatase as a detection system, we show that claudin-3 is present in mouse epithelia from embryonic day 14 onwards. In brain, it is restricted to the anlage of choroid plexus in the ventricles, together with claudin-1 and -2. In adult mice, it is clearly delineating the epithelium of the choroid plexus in the lateral and fourth ventricles. In contrast, in cerebral blood vessels claudin-3 as well as claudin-1 and -2 are absent in cerebral blood vessels during all developmental stages up to adulthood. Rather, the BBB is characterized by the presence of claudin-5, ZO-1 and occludin. Thus, in mice claudin-3 is an important constituent of TJ in the embryonic and in the adult choroid plexus. PMID:26941614

  16. Ensaio de Pedagogia Comparada: Jean Jacques Rousseau (1712-1778) X Immanuel Kant (1724-1804) (Essay on Compared Pedagogy: Jean Jacques Rousseau (1712-1778) X Immanuel Kant (1724-1804).

    ERIC Educational Resources Information Center

    Fontanella, Francisco Cock

    2000-01-01

    Finds that, although the thought of Jean Jacques Rousseau is frequently cited as an influence on Immanuel Kant, this has no basis regarding pedagogical influence. Compares the "Projecto" and "Emilio" of Rousseau with Kant's "Pedagogia." (BT)

  17. Mutations in the Tight-Junction Gene Claudin 19 (CLDN19) Are Associated with Renal Magnesium Wasting, Renal Failure, and Severe Ocular Involvement

    PubMed Central

    Konrad, Martin; Schaller, André; Seelow, Dominik; Pandey, Amit V.; Waldegger, Siegfried; Lesslauer, Annegret; Vitzthum, Helga; Suzuki, Yoshiro; Luk, John M.; Becker, Christian; Schlingmann, Karl P.; Schmid, Marcel; Rodriguez-Soriano, Juan; Ariceta, Gema; Cano, Francisco; Enriquez, Ricardo; Jüppner, Harald; Bakkaloglu, Sevcan A.; Hediger, Matthias A.; Gallati, Sabina; Neuhauss, Stephan C. F.; Nürnberg, Peter; Weber, Stefanie

    2006-01-01

    Claudins are major components of tight junctions and contribute to the epithelial-barrier function by restricting free diffusion of solutes through the paracellular pathway. We have mapped a new locus for recessive renal magnesium loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of the claudin multigene family, in patients affected by hypomagnesemia, renal failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules and the retina. The identified mutations interfere severely with either cell-membrane trafficking or the assembly of the claudin-19 protein. The identification of CLDN19 mutations in patients with chronic renal failure and severe visual impairment supports the fundamental role of claudin-19 for normal renal tubular function and undisturbed organization and development of the retina. PMID:17033971

  18. Identification of Claudin 1 Transcript Variants in Human Invasive Breast Cancer

    PubMed Central

    Zelinski, Teresa; Xie, Jiuyong; Cooper, Steven; Penner, Carla; Leygue, Etienne; Myal, Yvonne

    2016-01-01

    Background The claudin 1 tight junction protein, solely responsible for the barrier function of epithelial cells, is frequently down regulated in invasive human breast cancer. The underlying mechanism is largely unknown, and no obvious mutations in the claudin 1 gene (CLDN1) have been identified to date in breast cancer. Since many genes have been shown to undergo deregulation through splicing and mis-splicing events in cancer, the current study was undertaken to investigate the occurrence of transcript variants for CLDN1 in human invasive breast cancer. Methods RT-PCR analysis of CLDN1 transcripts was conducted on RNA isolated from 12 human invasive breast tumors. The PCR products from each tumor were resolved by agarose gel electrophoresis, cloned and sequenced. Genomic DNA was also isolated from each of the 12 tumors and amplified using PCR CLDN1 specific primers. Sanger sequencing and single nucleotide polymorphism (SNP) analyses were conducted. Results A number of CLDN1 transcript variants were identified in these breast tumors. All variants were shorter than the classical CLDN1 transcript. Sequence analysis of the PCR products revealed several splice variants, primarily in exon 1 of CLDN1; resulting in truncated proteins. One variant, V1, resulted in a premature stop codon and thus likely led to nonsense mediated decay. Interestingly, another transcript variant, V2, was not detected in normal breast tissue samples. Further, sequence analysis of the tumor genomic DNA revealed SNPs in 3 of the 4 coding exons, including a rare missense SNP (rs140846629) in exon 2 which represents an Ala124Thr substitution. To our knowledge this is the first report of CLDN1 transcript variants in human invasive breast cancer. These studies suggest that alternate splicing may also be a mechanism by which claudin 1 is down regulated at both the mRNA and protein levels in invasive breast cancer and may provide novel insights into how CLDN1 is reduced or silenced in human breast

  19. Cellular zinc is required for intestinal epithelial barrier maintenance via the regulation of claudin-3 and occludin expression.

    PubMed

    Miyoshi, Yuka; Tanabe, Soichi; Suzuki, Takuya

    2016-07-01

    Intracellular zinc is required for a variety of cell functions, but its precise roles in the maintenance of the intestinal tight junction (TJ) barrier remain unclear. The present study investigated the essential roles of intracellular zinc in the preservation of intestinal TJ integrity and the underlying molecular mechanisms. Depletion of intracellular zinc in both intestinal Caco-2 cells and mouse colons through the application of a cell-permeable zinc chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induced a disruption of the TJ barrier, as indicated by increased FITC-labeled dextran flux and decreased transepithelial electrical resistance. The TPEN-induced TJ disruption is associated with downregulation of two TJ proteins, occludin and claudin-3. Biotinylation of cell surface proteins revealed that the zinc depletion induced the proteolysis of occludin but not claudin-3. Occludin proteolysis was sensitive to the inhibition of calpain activity, and increased calpain activity was observed in the zinc-depleted cells. Although quantitative PCR analysis and promoter reporter assay have demonstrated that the zinc depletion-induced claudin-3 downregulation occurred at transcriptional levels, a site-directed mutation in the egr1 binding site in the claudin-3 promoter sequence induced loss of both the basal promoter activity and the TPEN-induced decreases. Reduced egr1 expression by a specific siRNA also inhibited claudin-3 expression and transepithelial electrical resistance maintenance in cells. This study shows that intracellular zinc has an essential role in the maintenance of the intestinal epithelial TJ barrier through regulation of occludin proteolysis and claudin-3 transcription. PMID:27151944

  20. Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation.

    PubMed

    Bardet, Claire; Courson, Frédéric; Wu, Yong; Khaddam, Mayssam; Salmon, Benjamin; Ribes, Sandy; Thumfart, Julia; Yamaguti, Paulo M; Rochefort, Gael Y; Figueres, Marie-Lucile; Breiderhoff, Tilman; Garcia-Castaño, Alejandro; Vallée, Benoit; Le Denmat, Dominique; Baroukh, Brigitte; Guilbert, Thomas; Schmitt, Alain; Massé, Jean-Marc; Bazin, Dominique; Lorenz, Georg; Morawietz, Maria; Hou, Jianghui; Carvalho-Lobato, Patricia; Manzanares, Maria Cristina; Fricain, Jean-Christophe; Talmud, Deborah; Demontis, Renato; Neves, Francisco; Zenaty, Delphine; Berdal, Ariane; Kiesow, Andreas; Petzold, Matthias; Menashi, Suzanne; Linglart, Agnes; Acevedo, Ana Carolina; Vargas-Poussou, Rosa; Müller, Dominik; Houillier, Pascal; Chaussain, Catherine

    2016-03-01

    Claudin-16 protein (CLDN16) is a component of tight junctions (TJ) with a restrictive distribution so far demonstrated mainly in the kidney. Here, we demonstrate the expression of CLDN16 also in the tooth germ and show that claudin-16 gene (CLDN16) mutations result in amelogenesis imperfecta (AI) in the 5 studied patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). To investigate the role of CLDN16 in tooth formation, we studied a murine model of FHHNC and showed that CLDN16 deficiency led to altered secretory ameloblast TJ structure, lowering of extracellular pH in the forming enamel matrix, and abnormal enamel matrix protein processing, resulting in an enamel phenotype closely resembling human AI. This study unravels an association of FHHNC owing to CLDN16 mutations with AI, which is directly related to the loss of function of CLDN16 during amelogenesis. Overall, this study indicates for the first time the importance of a TJ protein in tooth formation and underlines the need to establish a specific dental follow-up for these patients.

  1. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression.

    PubMed

    Pinton, Philippe; Nougayrède, Jean-Philippe; Del Rio, Juan-Carlos; Moreno, Carolina; Marin, Daniela E; Ferrier, Laurent; Bracarense, Ana-Paula; Kolf-Clauw, Martine; Oswald, Isabelle P

    2009-05-15

    'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.

  2. Adaptive evolution of tight junction protein claudin-14 in echolocating whales.

    PubMed

    Xu, Huihui; Liu, Yang; He, Guimei; Rossiter, Stephen J; Zhang, Shuyi

    2013-11-10

    Toothed whales and bats have independently evolved specialized ultrasonic hearing for echolocation. Recent findings have suggested that several genes including Prestin, Tmc1, Pjvk and KCNQ4 appear to have undergone molecular adaptations associated with the evolution of this ultrasonic hearing in mammals. Here we studied the hearing gene Cldn14, which encodes the claudin-14 protein and is a member of tight junction proteins that functions in the organ of Corti in the inner ear to maintain a cationic gradient between endolymph and perilymph. Particular mutations in human claudin-14 give rise to non-syndromic deafness, suggesting an essential role in hearing. Our results uncovered two bursts of positive selection, one in the ancestral branch of all toothed whales and a second in the branch leading to the delphinid, phocoenid and ziphiid whales. These two branches are the same as those previously reported to show positive selection in the Prestin gene. Furthermore, as with Prestin, the estimated hearing frequencies of whales significantly correlate with numbers of branch-wise non-synonymous substitutions in Cldn14, but not with synonymous changes. However, in contrast to Prestin, we found no evidence of positive selection in bats. Our findings from Cldn14, and comparisons with Prestin, strongly implicate multiple loci in the acquisition of echolocation in cetaceans, but also highlight possible differences in the evolutionary route to echolocation taken by whales and bats.

  3. The food contaminant deoxynivalenol, decreases intestinal barrier permeability and reduces claudin expression

    SciTech Connect

    Pinton, Philippe; Nougayrede, Jean-Philippe; Del Rio, Juan-Carlos; Moreno, Carolina; Marin, Daniela E.; Ferrier, Laurent; Bracarense, Ana-Paula; Kolf-Clauw, Martine; Oswald, Isabelle P.

    2009-05-15

    'The gastrointestinal tract represents the first barrier against food contaminants as well as the first target for these toxicants. Deoxynivalenol (DON) is a mycotoxin that commonly contaminates cereals and causes various toxicological effects. Through consumption of contaminated cereals and cereal products, human and pigs are exposed to this mycotoxin. Using in vitro, ex vivo and in vivo approaches, we investigated the effects of DON on the intestinal epithelium. We demonstrated that, in intestinal epithelial cell lines from porcine (IPEC-1) or human (Caco-2) origin, DON decreases trans-epithelial electrical resistance (TEER) and increases in a time and dose-dependent manner the paracellular permeability to 4 kDa dextran and to pathogenic Escherichia coli across intestinal cell monolayers. In pig explants treated with DON, we also observed an increased permeability of intestinal tissue. These alterations of barrier function were associated with a specific reduction in the expression of claudins, which was also seen in vivo in the jejunum of piglets exposed to DON-contaminated feed. In conclusion, DON alters claudin expression and decreases the barrier function of the intestinal epithelium. Considering that high levels of DON may be present in food or feed, consumption of DON-contaminated food/feed may induce intestinal damage and has consequences for human and animal health.

  4. Changes in the expression profiles of claudins during gonocyte differentiation and in seminomas.

    PubMed

    Manku, G; Hueso, A; Brimo, F; Chan, P; Gonzalez-Peramato, P; Jabado, N; Gayden, T; Bourgey, M; Riazalhosseini, Y; Culty, M

    2016-01-01

    Testicular germ cell tumors (TGCTs) are the most common type of cancer in young men and their incidence has been steadily increasing for the past decades. TGCTs and their precursor carcinoma in situ (CIS) are thought to arise from the deficient differentiation of gonocytes, precursors of spermatogonial stem cells. However, the mechanisms relating failed gonocyte differentiation to CIS formation remain unknown. The goal of this study was to uncover genes regulated during gonocyte development that would show abnormal patterns of expression in testicular tumors, as prospective links between failed gonocyte development and TGCT. To identify common gene and protein signatures between gonocytes and seminomas, we first performed gene expression analyses of transitional rat gonocytes, spermatogonia, human normal testicular, and TGCT specimens. Gene expression arrays, pathway analysis, and quantitative real-time PCR analysis identified cell adhesion molecules as a functional gene category including genes downregulated during gonocyte differentiation and highly expressed in seminomas. In particular, the mRNA and protein expressions of claudins 6 and 7 were found to decrease during gonocyte transition to spermatogonia, and to be abnormally elevated in seminomas. The dynamic changes in these genes suggest that they may play important physiological roles during gonocyte development. Moreover, our findings support the idea that TGCTs arise from a disruption of gonocyte differentiation, and position claudins as interesting genes to further study in relation to testicular cancer. PMID:26588606

  5. Claudin-4 Overexpression in Epithelial Ovarian Cancer Is Associated with Hypomethylation and Is a Potential Target for Modulation of Tight Junction Barrier Function Using a C-Terminal Fragment of Clostridium perfringens Enterotoxin1

    PubMed Central

    Litkouhi, Babak; Kwong, Joseph; Lo, Chun-Min; Smedley, James G; McClane, Bruce A; Aponte, Margarita; Gao, Zhijian; Sarno, Jennifer L; Hinners, Jennifer; Welch, William R; Berkowitz, Ross S; Mok, Samuel C; Garner, Elizabeth I O

    2007-01-01

    Background Claudin-4, a tight junction (TJ) protein and receptor for the C-terminal fragment of Clostridium perfringens enterotoxin (C-CPE), is overexpressed in epithelial ovarian cancer (EOC). Previous research suggests DNA methylation is a mechanism for claudin-4 overexpression in cancer and that C-CPE acts as an absorption-enhancing agent in claudin-4-expressing cells. We sought to correlate claudin-4 overexpression in EOC with clinical outcomes and TJ barrier function, investigate DNA methylation as a mechanism for overexpression, and evaluate the effect of C-CPE on the TJ. Methods Claudin-4 expression in EOC was quantified and correlated with clinical outcomes. Claudin-4 methylation status was determined, and claudin-4-negative cell lines were treated with a demethylating agent. Electric cell-substrate impedance sensing was used to calculate junctional (paracellular) resistance (Rb) in EOC cells after claudin-4 silencing and after C-CPE treatment. Results Claudin-4 overexpression in EOC does not correlate with survival or other clinical endpoints and is associated with hypomethylation. Claudin-4 overexpression correlates with Rb and C-CPE treatment of EOC cells significantly decreased Rb in a dose- and claudin-4-dependent noncytotoxic manner. Conclusions C-CPE treatment of EOC cells leads to altered TJ function. Further research is needed to determine the potential clinical applications of C-CPE in EOC drug delivery strategies. PMID:17460774

  6. [Jacques Cassard and the military pharmacy on the Island of Curaçao in 1713].

    PubMed

    Rutten, A M

    1998-01-01

    In the month of February 1713, Curacaoan militia tried in vain to stop an invasion of French troops under leading of their commander Jacques Cassard. The battle was fought near the strategically situated country house called Malpais. Several surgeons in charge of the Dutch West India Company were called to take care of the sick and wounded French and Curacaoan people. The medicines and other supplies were available from army medicine chests. The content of those chests is described and explained in this article.

  7. [Jacques Cassard and military pharmacy on the island of Curaçao in 1713].

    PubMed

    Rutten, A

    1996-01-01

    In the month of february 1713, Curaçaoan militia tried in vain to stop an invasion of French troops under leading of their commander Jacques Cassard. The battle was fought near the strategically situated country house called Malpais. Several surgeons in charge of the Dutch West India Company were called to take care for the sick and wounded French and Curaçaoan people. The medicines and other supplies were available from army medicine chests. The content of those chests is described and explained in this article.

  8. Payload specialist Jean-Jacques Favier, representing the French Space Agency (CNES), and astronaut

    NASA Technical Reports Server (NTRS)

    1996-01-01

    STS-78 ONBOARD VIEW --- Payload specialist Jean-Jacques Favier, representing the French Space Agency (CNES), and astronaut Kevin R. Kregel, pilot, perform a successful Inflight Maintenance (IFM) on the Bubble Drop Particle Unit (BDPU). The IFM technique was performed initially on the ground at the Marshall Space Flight Center (MSFC) by alternate payload specialist Pedro Duque of the European Space Agency (ESA), with the procedure being recorded on video and uplinked to the crew of the Space Shuttle Columbia to aid in the repair.

  9. [Jean-Jacques Lefrère: A miscarried ambition for blood safety in francophone Africa].

    PubMed

    Tayou Tagny, C; Laperche, S; Murphy, E

    2016-02-01

    The announcement of the death of Professor Jean-Jacques Lefrère caused considerable emotion and surprise within the francophone Africa blood transfusion research network. The group was created in 2007 in Paris. Each member that works within this group wanted to pay their last respects through dedicated publication for a brilliant researcher and writer. The tribute describes the creation of the group, its goals, its operations, its achievements and the prospects of its activities while emphasizing the essential role that Professor Lefrère played within the group. PMID:26762688

  10. Proteomic Analysis of Proteins Surrounding Occludin and Claudin-4 Reveals Their Proximity to Signaling and Trafficking Networks

    PubMed Central

    Fredriksson, Karin; Van Itallie, Christina M.; Aponte, Angel; Gucek, Marjan; Tietgens, Amber J.; Anderson, James M.

    2015-01-01

    Tight junctions are complex membrane structures that regulate paracellular movement of material across epithelia and play a role in cell polarity, signaling and cytoskeletal organization. In order to expand knowledge of the tight junction proteome, we used biotin ligase (BioID) fused to occludin and claudin-4 to biotinylate their proximal proteins in cultured MDCK II epithelial cells. We then purified the biotinylated proteins on streptavidin resin and identified them by mass spectrometry. Proteins were ranked by relative abundance of recovery by mass spectrometry, placed in functional categories, and compared not only among the N- and C- termini of occludin and the N-terminus of claudin-4, but also with our published inventory of proteins proximal to the adherens junction protein E-cadherin and the tight junction protein ZO-1. When proteomic results were analyzed, the relative distribution among functional categories was similar between occludin and claudin-4 proximal proteins. Apart from already known tight junction- proteins, occludin and claudin-4 proximal proteins were enriched in signaling and trafficking proteins, especially endocytic trafficking proteins. However there were significant differences in the specific proteins comprising the functional categories near each of the tagging proteins, revealing spatial compartmentalization within the junction complex. Taken together, these results expand the inventory of known and unknown proteins at the tight junction to inform future studies of the organization and physiology of this complex structure. PMID:25789658

  11. Poly(I:C) Induces Human Lung Endothelial Barrier Dysfunction by Disrupting Tight Junction Expression of Claudin-5

    PubMed Central

    Huang, Li-Yun; Stuart, Christine; Takeda, Kazuyo; D’Agnillo, Felice; Golding, Basil

    2016-01-01

    Viral infections are often accompanied by pulmonary microvascular leakage and vascular endothelial dysfunction via mechanisms that are not completely defined. Here, we investigated the effect of the Toll-like receptor 3 (TLR3) ligand polyinosinic-polycytidylic acid [Poly(I:C)], a synthetic analog of viral double-stranded RNA (dsRNA) commonly used to simulate viral infections, on the barrier function and tight junction integrity of primary human lung microvascular endothelial cells. Poly(I:C) stimulated IL-6, IL-8, TNFα, and IFNβ production in conjunction with the activation of NF-κB and IRF3 confirming the Poly(I:C)-responsiveness of these cells. Poly(I:C) increased endothelial monolayer permeability with a corresponding dose- and time-dependent decrease in the expression of claudin-5, a transmembrane tight junction protein and reduction of CLDN5 mRNA levels. Immunofluorescence experiments revealed disappearance of membrane-associated claudin-5 and co-localization of cytoplasmic claudin-5 with lysosomal-associated membrane protein 1. Chloroquine and Bay11-7082, inhibitors of TLR3 and NF-κB signaling, respectively, protected against the loss of claudin-5. Together, these findings provide new insight on how dsRNA-activated signaling pathways may disrupt vascular endothelial function and contribute to vascular leakage pathologies. PMID:27504984

  12. Science and the applications of science from Louis Pasteur to Jacques Monod.

    PubMed

    Schwartz, Maxime

    2015-06-01

    Jacques Monod's ideas on the applications of science came within the scope of a long tradition at the Institut Pasteur. Louis Pasteur, whose scientific career was characterized by a permanent come and go between science and its applications, long opposed the idea of getting any income from his research, until the financial needs of the Institut Pasteur made him change his mind. As for Jacques Monod, he remained a fervent supporter of basic science during his whole scientific career. However, once he became director of the Institut Pasteur, he realized that the applications of research had to be developed to support the institute from a financial point of view. Thus, he reorganized the valorization of research in the institute, through an incitation of scientists to develop projects with possible applications, and by creating a company, Institut Pasteur Production, for which he had a factory built, and which was in charge of producing and commercializing the vaccines and reagents stemming from the research at the Institut Pasteur.

  13. Expression of claudins, occludin, junction adhesion molecule A and zona occludens 1 in canine organs.

    PubMed

    Ahn, Changhwan; Shin, Da-Hye; Lee, Dongoh; Kang, Su-Myung; Seok, Ju-Hyung; Kang, Hee Young; Jeung, Eui-Bae

    2016-10-01

    Tight junctions are the outermost structures of intercellular junctions and are classified as transmembrane proteins. These factors form selective permeability barriers between cells, act as paracellular transporters and regulate structural and functional polarity of cells. Although tight junctions have been previously studied, comparison of the transcriptional‑translational levels of these molecules in canine organs remains to be investigated. In the present study, organ‑specific expression of the tight junction proteins, claudin, occludin, junction adhesion molecule A and zona occludens 1 was examined in the canine duodenum, lung, liver and kidney. Results of immunohistochemistry analysis demonstrated that the tight junctions were localized in intestinal villi and glands of the duodenum, bronchiolar epithelia and alveolar walls of the lung, endometrium and myometrium of the hepatocytes, and the distal tubules and glomeruli of the kidney. These results suggest that tight junctions are differently expressed in organs, and therefore may be involved in organ‑specific functions to maintain physiological homeostasis. PMID:27600198

  14. Clearance of persistent hepatitis C virus infection using a claudin-1-targeting monoclonal antibody

    PubMed Central

    Mailly, Laurent; Wilson, Garrick K.; Aubert, Philippe; Duong, François H. T.; Calabrese, Diego; Leboeuf, Céline; Fofana, Isabel; Thumann, Christine; Bandiera, Simonetta; Lütgehetmann, Marc; Volz, Tassilo; Davis, Christopher; Harris, Helen J.; Mee, Christopher J.; Girardi, Erika; Chane-Woon-Ming, Béatrice; Ericsson, Maria; Fletcher, Nicola; Bartenschlager, Ralf; Pessaux, Patrick; Vercauteren, Koen; Meuleman, Philip; Villa, Pascal; Kaderali, Lars; Pfeffer, Sébastien; Heim, Markus H.; Neunlist, Michel; Zeisel, Mirjam B.; Dandri, Maura; McKeating, Jane A.; Robinet, Eric; Baumert, Thomas F.

    2015-01-01

    Hepatitis C virus (HCV) infection is a leading cause of liver cirrhosis and cancer1. Cell entry of HCV2 and other pathogens3-5 is mediated by tight junction (TJ) proteins, but successful therapeutic targeting of TJ proteins has not been reported yet. Using a human liver-chimeric mouse model6 we show that a monoclonal antibody specific for TJ protein claudin-17 eliminates chronic HCV infection without detectable toxicity. This antibody inhibits HCV entry, cell-cell transmission and virus-induced signaling events. Antibody treatment reduces the number of HCV-infected hepatocytes in vivo, highlighting the need for de novo infection via host entry factors to maintain chronic infection. In summary, we demonstrate that an antibody targeting a virus receptor can cure chronic viral infection and uncover TJ proteins as targets for antiviral therapy. PMID:25798937

  15. Expression of claudins, occludin, junction adhesion molecule A and zona occludens 1 in canine organs

    PubMed Central

    Ahn, Changhwan; Shin, Da-Hye; Lee, Dongoh; Kang, Su-Myung; Seok, Ju-Hyung; Kang, Hee Young; Jeung, Eui-Bae

    2016-01-01

    Tight junctions are the outermost structures of intercellular junctions and are classified as transmembrane proteins. These factors form selective permeability barriers between cells, act as paracellular transporters and regulate structural and functional polarity of cells. Although tight junctions have been previously studied, comparison of the transcriptional-translational levels of these molecules in canine organs remains to be investigated. In the present study, organ-specific expression of the tight junction proteins, claudin, occludin, junction adhesion molecule A and zona occludens 1 was examined in the canine duodenum, lung, liver and kidney. Results of immunohistochemistry analysis demonstrated that the tight junctions were localized in intestinal villi and glands of the duodenum, bronchiolar epithelia and alveolar walls of the lung, endometrium and myometrium of the hepatocytes, and the distal tubules and glomeruli of the kidney. These results suggest that tight junctions are differently expressed in organs, and therefore may be involved in organ-specific functions to maintain physiological homeostasis. PMID:27600198

  16. Claudin-7 indirectly regulates the integrin/FAK signaling pathway in human colon cancer tissue.

    PubMed

    Ding, Lei; Wang, Liyong; Sui, Leiming; Zhao, Huanying; Xu, Xiaoxue; Li, Tengyan; Wang, Xiaonan; Li, Wenjing; Zhou, Ping; Kong, Lu

    2016-08-01

    The claudin family of proteins is integral to the structure and function of tight junctions. The role of claudin-7 (Cldn-7, CLDN7) in regulating the integrin/focal adhesion kinase (FAK)/ERK signaling pathway remains poorly understood. Therefore, we investigated differences in gene expression, primarily focusing on CLDN7 and integrin/FAK/ERK signaling pathway genes, between colon cancer and adjacent normal tissues. Quantitative real-time reverse transcription-PCR and immunohistochemistry were utilized to verify the results of mRNA and protein expression, respectively. In silico analysis was used to predict co-regulation between Cldn-7 and integrin/FAK/ERK signaling pathway components, and the STRING database was used to analyze protein-protein interaction pairs among these proteins. Meta-analysis of expression microarrays in The Cancer Genome Atlas (TCGA) database was used to identify significant correlations between Cldn-7 and components of predicted genes in the integrin/FAK/ERK signaling pathway. Our results showed marked cancer stage-specific decreases in the protein expression of Cldn-7, Gelsolin, MAPK1 and MAPK3 in colon cancer samples, and the observed changes for all proteins except Cldn-7 were in agreement with changes in the corresponding mRNA levels. Cldn-7 might indirectly regulate MAPK3 via KRT8 due to KRT8 co-expression with MAPK3 or CLDN7. Our bioinformatics methods supported the hypothesis that Cldn-7 does not directly regulate any genes in the integrin/FAK/ERK signaling pathway. These factors may participate in a common network that regulates cancer progression in which the MAPK pathway serves as the central node.

  17. Moments with Jacques Rancière: Sketches from a Lived Pedagogical Experiment in an Elementary Science Classroom

    ERIC Educational Resources Information Center

    Otoide, Lorraine; Alsop, Steve

    2015-01-01

    The work of Jacques Rancière has become rather popular of late, with a series of high-profile advocates. In this article, we reflect on an elementary classroom and an experiment with pedagogy inspired by Rancière's (1991) text, The "Ignorant Schoolmaster." The authors discuss the text, outline a 20-lesson response that emerged from the…

  18. Jean-Jacques Rousseau on Adult Education and Revolution. Paradigma of Radical, Pedagogical Thought. 2nd Revised Edition.

    ERIC Educational Resources Information Center

    Dame, Frederick William

    This book explores Jean-Jacques Rousseau's educational philosophy, as expressed in his key works, and applies that philosophy to adult education and revolution. The titles and topics of the book's seven chapters are as follows: (1) "L'Invitation: Raison d'Etre" (prelude, statement, significance, the process, assumptions and limitations); (2) "Le…

  19. How the Science versus Religion Debate Has Missed the Point of Genesis 1 and 2: Jacques Ellul (1912-1994)

    ERIC Educational Resources Information Center

    Vanderburg, Willem H.

    2010-01-01

    From a social and historical perspective, the conflict between science and religion regarding the opening chapters of Genesis in the Jewish and Christian Bibles may have more to do with uncritically reading these texts through our "cultural glasses" than with what these texts actually say. Within the context of his work, Jacques Ellul read these…

  20. Extracellular signal-regulated kinases 1/2 control claudin-2 expression in Madin-Darby canine kidney strain I and II cells.

    PubMed

    Lipschutz, Joshua H; Li, Shixiong; Arisco, Amy; Balkovetz, Daniel F

    2005-02-01

    The tight junction of the epithelial cell determines the characteristics of paracellular permeability across epithelium. Recent work points toward the claudin family of tight junction proteins as leading candidates for the molecular components that regulate paracellular permeability properties in epithelial tissues. Madin-Darby canine kidney (MDCK) strain I and II cells are models for the study of tight junctions and based on transepithelial electrical resistance (TER) contain "tight" and "leaky" tight junctions, respectively. Overexpression studies suggest that tight junction leakiness in these two strains of MDCK cells is conferred by expression of the tight junction protein claudin-2. Extracellular signal-regulated kinase (ERK) 1/2 activation by hepatocyte growth factor treatment of MDCK strain II cells inhibited claudin-2 expression and transiently increased TER. This process was blocked by the ERK 1/2 inhibitor U0126. Transfection of constitutively active mitogen-activated protein kinase/extracellular signal-regulated kinase kinase into MDCK strain II cells also inhibited claudin-2 expression and increased TER. MDCK strain I cells have higher levels of active ERK 1/2 than do MDCK strain II cells. U0126 treatment of MDCK strain I cells decreased active ERK 1/2 levels, induced expression of claudin-2 protein, and decreased TER by approximately 20-fold. U0126 treatment also induced claudin-2 expression and decreased TER in a high resistance mouse cortical collecting duct cell line (94D). These data show for the first time that the ERK 1/2 signaling pathway negatively controls claudin-2 expression in mammalian renal epithelial cells and provide evidence for regulation of tight junction paracellular transport by alterations in claudin composition within tight junction complexes.

  1. Claudin-based barrier differentiation in the colonic epithelial crypt niche involves Hopx/Klf4 and Tcf7l2/Hnf4-α cascades.

    PubMed

    Lili, Loukia N; Farkas, Attila E; Gerner-Smidt, Christian; Overgaard, Christian E; Moreno, Carlos S; Parkos, Charles A; Capaldo, Christopher T; Nusrat, Asma

    2016-01-01

    Colonic enterocytes form a rapidly renewing epithelium and barrier to luminal antigens. During renewal, coordinated expression of the claudin family of genes is vital to maintain the epithelial barrier. Disruption of this process contributes to barrier compromise and mucosal inflammatory diseases. However, little is known about the regulation of this critical aspect of epithelial cell differentiation. In order to identify claudin regulatory factors we utilized high-throughput gene microarrays and correlation analyses. We identified complex expression gradients for the transcription factors Hopx, Hnf4a, Klf4 and Tcf7l2, as well as 12 claudins, during differentiation. In vitro confirmatory methods identified 2 pathways that stimulate claudin expression; Hopx/Klf4 activation of Cldn4, 7 and 15, and Tcf7l2/Hnf4a up-regulation of Cldn23. Chromatin immunoprecipitation confirmed a Tcf7l2/Hnf4a/Claudin23 cascade. Furthermore, Hnf4a conditional knockout mice fail to induce Cldn23 during colonocyte differentiation. In conclusion, we report a comprehensive screen of colonic claudin gene expression and discover spatiotemporal Hopx/Klf4 and Tcf7l2/Hnf4a signaling as stimulators of colonic epithelial barrier differentiation. PMID:27583195

  2. Jacques Bénigne Winslow (1669-1760) and the misnomer cavernous sinus.

    PubMed

    Thakur, Jai Deep; Sonig, Ashish; Khan, Imad Saeed; Connor, David E; Pait, T Glenn; Nanda, Anil

    2014-01-01

    Sinus cavernosi, or the cavernous sinus, was coined by Jacques Bénigne Winslow in the 18th century. Among the neurosurgeons and the modern-day neuroanatomists, Winslow is mainly known for erroneously using the term cavernous sinus. As the anatomical understanding of the parasellar space advanced during the next 200 years, it was unclear as to why Winslow compared this space in the brain with that of a male reproductive organ (corpus cavernosum). Our primary objective was to study the historical treatise on anatomy written by Winslow in the 18th century and analyze his anatomical dissections and nomenclature for the parasellar compartment. In addition, his pertinent contributions to neuroscience are highlighted in this vignette.

  3. Jean-Jacques Rousseau's copy of Albrecht von Haller's Historia stirpium indigenarum Helvetiae inchoata (1768).

    PubMed

    Cook, A

    2003-04-01

    Jean-Jacques Rousseau sold his botanical texts to Daniel Malthus (father of Thomas Malthus) about 1775. Two of these are now in the Old Library, Jesus College, Cambridge, but all the rest have long been thought lost. However, a copy of Albrecht von Haller's Historia stirpium indigenarum Helvetiae inchoata (1768) in the Lindley Library, Royal Horticultural Society, London, bears Rousseau's name and seems to have been annotated by him. The volume contains the bookplate of Jane Dalton, a cousin to whom Malthus willed "all[his] Botanical Books in which the name of Rousseau is written". Haller was well-known to Rousseau, who while in exile in the Swiss Jura (1763-1765), studied under one of Haller's collaborators, Abraham Gagnebin. Rousseau cited Haller's entry 762 when describing a species of Seseli to the Duchess of Portland.

  4. Consciousness eclipsed: Jacques Loeb, Ivan P. Pavlov, and the rise of reductionistic biology after 1900.

    PubMed

    Greenspan, Ralph J; Baars, Bernard J

    2005-03-01

    The life sciences in the 20th century were guided to a large extent by a reductionist program seeking to explain biological phenomena in terms of physics and chemistry. Two scientists who figured prominently in the establishment and dissemination of this program were Jacques Loeb in biology and Ivan P. Pavlov in psychological behaviorism. While neither succeeded in accounting for higher mental functions in physical-chemical terms, both adopted positions that reduced the problem of consciousness to the level of reflexes and associations. The intellectual origins of this view and the impediment to the study of consciousness as an object of inquiry in its own right that it may have imposed on peers, students, and those who followed is explored. PMID:15766898

  5. Consciousness eclipsed: Jacques Loeb, Ivan P. Pavlov, and the rise of reductionistic biology after 1900.

    PubMed

    Greenspan, Ralph J; Baars, Bernard J

    2005-03-01

    The life sciences in the 20th century were guided to a large extent by a reductionist program seeking to explain biological phenomena in terms of physics and chemistry. Two scientists who figured prominently in the establishment and dissemination of this program were Jacques Loeb in biology and Ivan P. Pavlov in psychological behaviorism. While neither succeeded in accounting for higher mental functions in physical-chemical terms, both adopted positions that reduced the problem of consciousness to the level of reflexes and associations. The intellectual origins of this view and the impediment to the study of consciousness as an object of inquiry in its own right that it may have imposed on peers, students, and those who followed is explored.

  6. Payload specialist Jean-Jacques Favier, representing the French Space Agency (CNES), prepares a

    NASA Technical Reports Server (NTRS)

    1996-01-01

    STS-78 ONBOARD VIEW --- Payload specialist Jean-Jacques Favier, representing the French Space Agency (CNES), prepares a sample for the Advanced Gradient Heating Facility (AGHF) while wearing instruments that measure upper body movement. The Torso Rotation Experiment (TRE) complements other vestibular studies that measure differences in the way human beings react physically to their surroundings in microgravity. This is a typical Life and Microgravity Spacelab (LMS-1) mission scene, with several experiments being performed. Astronaut Susan J. Helms, payload commander, assists Favier in the AGHF preparations. Astronaut Richard M. Linnehan (bottom right), mission specialist, tests his muscle response with the Handgrip Dynamometer. Astronaut Thomas T. (Tom) Henricks (far background), mission commander, offers assistance.

  7. [Jean-Jacques Rosseau the vitalist. The moralization of medical hygiene between diet and ethical food].

    PubMed

    Menin, Marco

    2012-01-01

    The historiographical prejudice that sees in Jean-Jacques Rousseau an implacable opponent of scientific knowledge has long prevented an objective evaluation of the important influence that medical thought exerted over his philosophy. The aim of this paper is to show not only Rousseau's familiarity with the most important expressions of eighteenth-century medical literature, but also his willingness to incorporate some medical suggestions in his philosophical and literary production. In the first part of this article, I try to show how Rousseau's sensibility theory presupposes precise medical ideals, related to Montpellier School of vitalism. In the second part, I stress how Rousseau's philosophy of alimentation (which has clear anthropological and political implications) can be regarded as a genuine application of an ambition typical of vitalism: to use medical hygiene, also and above all, for moral purpose.

  8. [Jean-Jacques Rosseau the vitalist. The moralization of medical hygiene between diet and ethical food].

    PubMed

    Menin, Marco

    2012-01-01

    The historiographical prejudice that sees in Jean-Jacques Rousseau an implacable opponent of scientific knowledge has long prevented an objective evaluation of the important influence that medical thought exerted over his philosophy. The aim of this paper is to show not only Rousseau's familiarity with the most important expressions of eighteenth-century medical literature, but also his willingness to incorporate some medical suggestions in his philosophical and literary production. In the first part of this article, I try to show how Rousseau's sensibility theory presupposes precise medical ideals, related to Montpellier School of vitalism. In the second part, I stress how Rousseau's philosophy of alimentation (which has clear anthropological and political implications) can be regarded as a genuine application of an ambition typical of vitalism: to use medical hygiene, also and above all, for moral purpose. PMID:23035396

  9. Salt and acid-base metabolism in claudin-16 knockdown mice: impact for the pathophysiology of FHHNC patients.

    PubMed

    Himmerkus, Nina; Shan, Qixian; Goerke, Boeren; Hou, Jianghui; Goodenough, Daniel A; Bleich, Markus

    2008-12-01

    Claudin-16 is defective in familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC). Claudin-16 knockdown (CLDN16 KD) mice show reduced cation selectivity in the thick ascending limb. The defect leads to a collapse of the lumen-positive diffusion voltage, which drives Ca(2+) and Mg(2+) absorption. Because of the reduced tight junction permeability ratio for Na(+) over Cl(-), we proposed a backleak of NaCl into the lumen. Systemic analysis had revealed lower blood pressure and a moderately increased plasma aldosterone concentration. In this study, we measured the amiloride-sensitive equivalent short-circuit current in isolated, perfused collecting ducts and found it increased by fivefold in CLDN16 KD mice compared with wild-type (WT) mice. Amiloride treatment unmasked renal Na(+) loss in the thick ascending limb of the nephron. Under amiloride treatment, CLDN16 KD mice developed hyponatremia and the renal fractional excretion of Na(+) was twofold higher in CLDN16 KD compared with WT mice. The loss of claudin-16 also resulted in increased urinary flow, reduced HCO(3)(-) excretion, and lower urine pH. We conclude that perturbation in salt and acid-base metabolism in CLDN16 KD mice has its origin in the defective cation permselectivity of the thick ascending limb of the nephron. This study has contributed to the still incomplete understanding of the symptoms of FHHNC patients.

  10. Expression of growth differentiation factor 9 (GDF9), ALK5, and claudin-11 in adult alpaca testis.

    PubMed

    Guo, Qing Yun; Gao, Zhen Zhen; Zhao, Li; He, Jun Ping; Dong, Cheng Sheng

    2013-01-01

    Growth differentiation factor 9 (GDF9) is an oocyte-derived factor critical for folliculogenesis. Recently, in vitro data showed that GDF9 inhibited the localization of tight junction (TJ) proteins, suggesting that GDF9 could potentially regulate spermatogenesis in vivo, via inhibition of Sertoli cell TJ function. The purpose of the present study was to determine the expression and localization of GDF9, its receptor, ALK5, and its latent target protein, claudin-11 (one of TJ proteins) in adult alpaca testis using Western blot and immunohistochemistry. Western blotting results demonstrated that GDF9, ALK5 and claudin-11 were expressed in the adult alpaca testis. Immunohistochemistry revealed that GDF9 was expressed stage-specifically in the cytoplasm of pachytene spermatocytes and round spermatids of the adult alpaca seminiferous epithelium. Type I receptor, ALK5 was mainly localized in the cytoplasm of round spermatids and Leydig cells, and to a lesser extent in the cytoplasm of pachytene spermatocytes and Sertoli cells. Its latent target protein, claudin-11, was perpendicular or parallel to the basal lamina in the basal part of Sertoli cells. These results indicated that GDF9, as a paracrine and autocrine growth factor derived from round spermatids and pachytene spermatocytes, is involved in regulating spermatogenesis via action on germ cells or somatic cells (i.e. Leydig cells, Sertoli cells).

  11. Tumor Necrosis Factor Disrupts Claudin-5 Endothelial Tight Junction Barriers in Two Distinct NF-κB-Dependent Phases

    PubMed Central

    Clark, Paul R.; Kim, Richard K.; Pober, Jordan S.; Kluger, Martin S.

    2015-01-01

    Capillary leak in severe sepsis involves disruption of endothelial cell tight junctions. We modeled this process by TNF treatment of cultured human dermal microvascular endothelial cell (HDMEC) monolayers, which unlike human umbilical vein endothelial cells form claudin-5-dependent tight junctions and a high-resistance permeability barrier. Continuous monitoring with electrical cell-substrate impedance sensing revealed that TNF disrupts tight junction-dependent HDMEC barriers in discrete steps: an ~5% increase in transendothelial electrical resistance over 40 minutes; a decrease to ~10% below basal levels over 2 hours (phase 1 leak); an interphase plateau of 1 hour; and a major fall in transendothelial electrical resistance to < 70% of basal levels by 8–10 hours (phase 2 leak), with EC50 values of TNF for phase 1 and 2 leak of ~30 and ~150 pg/ml, respectively. TNF leak is reversible and independent of cell death. Leak correlates with disruption of continuous claudin-5 immunofluorescence staining, myosin light chain phosphorylation and loss of claudin-5 co-localization with cortical actin. All these responses require NF-κB signaling, shown by inhibition with Bay 11 or overexpression of IκB super-repressor, and are blocked by H-1152 or Y-27632, selective inhibitors of Rho-associated kinase that do not block other NF-κB-dependent responses. siRNA combined knockdown of Rho-associated kinase-1 and -2 also prevents myosin light chain phosphorylation, loss of claudin-5/actin co-localization, claudin-5 reorganization and reduces phase 1 leak. However, unlike H-1152 and Y-27632, combined Rho-associated kinase-1/2 siRNA knockdown does not reduce the magnitude of phase 2 leak, suggesting that H-1152 and Y-27632 have targets beyond Rho-associated kinases that regulate endothelial barrier function. We conclude that TNF disrupts TJs in HDMECs in two distinct NF-κB-dependent steps, the first involving Rho-associated kinase and the second likely to involve an as yet

  12. Claudin 28b and F-actin are involved in rainbow trout gill pavement cell tight junction remodeling under osmotic stress.

    PubMed

    Sandbichler, Adolf Michael; Egg, Margit; Schwerte, Thorsten; Pelster, Bernd

    2011-05-01

    Permeability of rainbow trout gill pavement cells cultured on permeable supports (single seeded inserts) changes upon exposure to freshwater or treatment with cortisol. The molecular components of this change are largely unknown, but tight junctions that regulate the paracellular pathway are prime candidates in this adaptational process. Using differential display polymerase chain reaction we found a set of 17 differentially regulated genes in trout pavement cells that had been exposed to freshwater apically for 24 h. Five genes were related to the cell-cell contact. One of these genes was isolated and identified as encoding claudin 28b, an integral component of the tight junction. Immunohistochemical reactivity to claudin 28b protein was concentrated in a circumferential ring colocalized to the cortical F-actin ring. To study the contribution of this isoform to changes in transepithelial resistance and Phenol Red diffusion under apical hypo-or hyperosmotic exposure we quantified the fluorescence signal of this claudin isoform in immunohistochemical stainings together with the fluorescence of phalloidin-probed F-actin. Upon hypo-osmotic stress claudin 28b fluorescence and epithelial tightness remained stable. Under hyperosmotic stress, the presence of claudin 28b at the junction significantly decreased, and epithelial tightness was severely reduced. Cortical F-actin fluorescence increased upon hypo-osmotic stress, whereas hyperosmotic stress led to a separation of cortical F-actin rings and the number of apical crypt-like pores increased. Addition of cortisol to the basolateral medium attenuated cortical F-actin separation and pore formation during hyperosmotic stress and reduced claudin 28b in junctions except after recovery of cells from exposure to freshwater. Our results showed that short-term salinity stress response in cultured trout gill cells was dependent on a dynamic remodeling of tight junctions, which involves claudin 28b and the supporting F-actin ring.

  13. Involvement of claudin-7 in HIV infection of CD4(-) cells

    PubMed Central

    Zheng, Junying; Xie, Yiming; Campbell, Richard; Song, Jun; Massachi, Samira; Razi, Miriam; Chiu, Robert; Berenson, James; Yang, Otto O; Chen, Irvin SY; Pang, Shen

    2005-01-01

    Background Human immunodeficiency virus (HIV) infection of CD4(-) cells has been demonstrated, and this may be an important mechanism for HIV transmission. Results We demonstrated that a membrane protein, claudin-7 (CLDN-7), is involved in HIV infection of CD4(-) cells. A significant increase in HIV susceptibility (2- to 100-fold) was demonstrated when CLDN-7 was transfected into a CD4(-) cell line, 293T. In addition, antibodies against CLDN-7 significantly decreased HIV infection of CD4(-) cells. Furthermore, HIV virions expressing CLDN-7 on their envelopes had a much higher infectivity for 293T CD4(-) cells than the parental HIV with no CLDN-7. RT-PCR results demonstrated that CLDN-7 is expressed in both macrophages and stimulated peripheral blood leukocytes, suggesting that most HIV virions generated in infected individuals have CLDN-7 on their envelopes. We also found that CLDN-7 is highly expressed in urogenital and gastrointestinal tissues. Conclusion Together these results suggest that CLDN-7 may play an important role in HIV infection of CD4(-) cells. PMID:16368003

  14. Claudin 4-targeted protein incorporated into PLGA nanoparticles can mediate M cell targeted delivery

    PubMed Central

    Rajapaksa, Thejani E.; Stover-Hamer, Mary; Fernandez, Xiomara; Eckelhoefer, Holly A.; Lo, David D.

    2009-01-01

    Polymer-based microparticles are in clinical use mainly for their ability to provide controlled release of peptides and compounds, but they are also being explored for their potential to deliver vaccines and drugs as suspensions directly into mucosal sites. It is generally assumed that uptake is mediated by epithelial M cells, but this is often not directly measured. To study the potential for optimizing M cell uptake of polymer microparticles in vivo, we produced sub-micron size PLGA particles incorporating a recombinant protein. This recombinant protein was produced with or without a c-terminal peptide previously shown to have high affinity binding to Claudin 4, a protein associated with M cell endocytosis. While the PLGA nanoparticles incorporate the protein throughout the matrix, much of the protein was also displayed on the surface, allowing us to take advantage of the binding activity of the targeting peptide. Accordingly, we found that instillation of these nanoparticles into the nasal passages or stomach of mice was found to significantly enhance their uptake by upper airway and intestinal M cells. Our results suggest that a reasonably simple nanoparticle manufacture method can provide insight into developing an effective needle-free delivery system. PMID:19896996

  15. Claudin-1 enhances tumor proliferation and metastasis by regulating cell anoikis in gastric cancer

    PubMed Central

    Huang, Jie; Zhang, Li; He, Changyu; Qu, Ying; Li, Jianfang; Zhang, Jianian; Du, Tao; Chen, Xuehua; Yu, Yingyan; Liu, Bingya; Zhu, Zhenggang

    2015-01-01

    Claudin-1 (CLDN1) is overexpressed in gastric cancer and correlated with tumor invasion, metastasis and poor outcome. Here, we both down and up regulated CLDN1 expression in gastric cancer cells to elucidate its role in gastric carcinogenesis and tumor progression. We found that deficiency of CLDN1 inhibited cells migration, invasion, and colony formation in vitro and tumorigenicity, metastasis in vivo. Also, CLDN1 promoted cell aggregation and increased anoikis resistance. Down or up regulation of CLDN1 was accompanied with changes of membrane β-catenin expression as well as Akt and Src activities. When β-catenin was up-regulated in CLDN1-KD cells, cell aggregation and anoikis resistance were restored, and Akt and Src signal pathways were re-activated. Taken together, these findings suggest that CLDN1 is oncogenic in gastric cancer and its malignant potential may be attributed in part to regulation of anoikis, by mediating membrane β-catenin-regulated cell-cell adhesion and cell survival. PMID:25544763

  16. Autocrine CSF1R signaling mediates switching between invasion and proliferation downstream of TGFβ in claudin-low breast tumor cells.

    PubMed

    Patsialou, A; Wang, Y; Pignatelli, J; Chen, X; Entenberg, D; Oktay, M; Condeelis, J S

    2015-05-21

    Patient data suggest that colony-stimulating factor-1 (CSF1) and its receptor (CSF1R) have critical roles during breast cancer progression. We have previously shown that in human breast tumors expressing both CSF1 and CSF1R, invasion in vivo is dependent both on a paracrine interaction with tumor-associated macrophages and an autocrine regulation of CSF1R in the tumor cells themselves. Although the role of the paracrine interaction between tumor cells and macrophages has been extensively studied, very little is known about the mechanism by which the autocrine CSF1R signaling contributes to tumor progression. We show here that breast cancer patients of the claudin-low subtype have significantly increased expression of CSF1R. Using a panel of breast cancer cell lines, we confirm that CSF1R expression is elevated and regulated by TGFβ specifically in claudin-low cell lines. Abrogation of autocrine CSF1R signaling in MDA-MB-231 xenografts (a claudin-low cell line) leads to increased tumor size by enhanced proliferation, but significantly reduced invasion, dissemination and metastasis. Indeed, we show that proliferation and invasion are oppositely regulated by CSF1R downstream of TGFβ only in claudin-low cell lines. Intravital multiphoton imaging revealed that inhibition of CSF1R in the tumor cells leads to decreased in vivo motility and a more cohesive morphology. We show that, both in vitro and in vivo, CSF1R inhibition results in a reversal of claudin-low marker expression by significant upregulation of luminal keratins and tight-junction proteins such as claudins. Finally, we show that artificial overexpression of claudins in MDA-MB-231 cells is sufficient to tip the cells from an invasive state to a proliferative state. Our results suggest that autocrine CSF1R signaling is essential in maintaining low claudin expression and that it mediates a switch between the proliferative and the invasive state in claudin-low tumor cells downstream of TGFβ.

  17. Bovine colostrum increases pore-forming claudin-2 protein expression but paradoxically not ion permeability possibly by a change of the intestinal cytokine milieu.

    PubMed

    Bodammer, Peggy; Kerkhoff, Claus; Maletzki, Claudia; Lamprecht, Georg

    2013-01-01

    An impaired intestinal barrier function is involved in the pathogenesis of inflammatory bowel disease (IBD). Several nutritional factors are supposed to be effective in IBD treatment but scientific data about the effects on the intestinal integrity remain scarce. Bovine colostrum was shown to exert beneficial effects in DSS-induced murine colitis, and the present study was undertaken to explore the underlying molecular mechanisms. Western blot revealed increased claudin-2 expression in the distal ileum of healthy mice after feeding with colostrum for 14 days, whereas other tight junction proteins (claudin-3, 4, 10, 15) remained unchanged. The colostrum-induced claudin-2 induction was confirmed in differentiated Caco-2 cells after culture with colostrum for 48 h. Paradoxically, the elevation of claudin-2, which forms a cation-selective pore, was neither accompanied by increased ion permeability nor impaired barrier function. In an in situ perfusion model, 1 h exposure of the colonic mucosa to colostrum induced significantly increased mRNA levels of barrier-strengthening cytokine transforming growth factor-β, while interleukine-2, interleukine-6, interleukine-10, interleukine-13, and tumor-necrosis factor-α remained unchanged. Thus, modulation of the intestinal transforming growth factor-β expression might have compensated the claudin-2 increase and contributed to the observed barrier strengthening effects of colostrum in vivo and in vitro. PMID:23717570

  18. Bovine Colostrum Increases Pore-Forming Claudin-2 Protein Expression but Paradoxically Not Ion Permeability Possibly by a Change of the Intestinal Cytokine Milieu

    PubMed Central

    Maletzki, Claudia; Lamprecht, Georg

    2013-01-01

    An impaired intestinal barrier function is involved in the pathogenesis of inflammatory bowel disease (IBD). Several nutritional factors are supposed to be effective in IBD treatment but scientific data about the effects on the intestinal integrity remain scarce. Bovine colostrum was shown to exert beneficial effects in DSS-induced murine colitis, and the present study was undertaken to explore the underlying molecular mechanisms. Western blot revealed increased claudin-2 expression in the distal ileum of healthy mice after feeding with colostrum for 14 days, whereas other tight junction proteins (claudin-3, 4, 10, 15) remained unchanged. The colostrum-induced claudin-2 induction was confirmed in differentiated Caco-2 cells after culture with colostrum for 48 h. Paradoxically, the elevation of claudin-2, which forms a cation-selective pore, was neither accompanied by increased ion permeability nor impaired barrier function. In an in situ perfusion model, 1 h exposure of the colonic mucosa to colostrum induced significantly increased mRNA levels of barrier-strengthening cytokine transforming growth factor-β, while interleukine-2, interleukine-6, interleukine-10, interleukine-13, and tumor-necrosis factor-α remained unchanged. Thus, modulation of the intestinal transforming growth factor-β expression might have compensated the claudin-2 increase and contributed to the observed barrier strengthening effects of colostrum in vivo and in vitro. PMID:23717570

  19. Jacques Loeb, B. F. Skinner, and the legacy of prediction and control.

    PubMed

    Hackenberg, T D

    1995-01-01

    The biologist Jacques Loeb is an important figure in the history of behavior analysis. Between 1890 and 1915, Loeb championed an approach to experimental biology that would later exert substantial influence on the work of B. F. Skinner and behavior analysis. This paper examines some of these sources of influence, with a particular emphasis on Loeb's firm commitment to prediction and control as fundamental goals of an experimental life science, and how these goals were extended and broadened by Skinner. Both Loeb and Skinner adopted a pragmatic approach to science that put practical control of their subject matter above formal theory testing, both based their research programs on analyses of reproducible units involving the intact organism, and both strongly endorsed technological applications of basic laboratory science. For Loeb, but especially for Skinner, control came to mean something more than mere experimental or technological control for its own sake; it became synonomous with scientific understanding. This view follows from (a) the successful working model of science Loeb and Skinner inherited from Ernst Mach, in which science is viewed as human social activity, and effective practical action is taken as the basis of scientific knowledge, and (b) Skinner's analysis of scientific activity, situated in the world of direct experience and related to practices arranged by scientific verbal communities. From this perspective, prediction and control are human acts that arise from and are maintained by social circumstances in which such acts meet with effective consequences.

  20. Broca and Charcot's research on Jacques Inaudi: the psychological and anthropological study of a mental calculator.

    PubMed

    Nicolas, Serge; Guida, Alessandro; Levine, Zachary

    2014-01-01

    In the nineteenth century, French scientific institutions became interested in young "mental calculators," arithmetical prodigies able to quickly and accurately perform complex mental calculations. The first scientists to study mental calculators were phrenologists who sought to prove the existence of a calculating organ in the frontal lobe. Paul Broca introduced one such mental calculator, Jacques Inaudi, to the Anthropological Society of Paris in 1880. Broca attributed extraordinary faculty for mental calculation to memory functioning (the psychological hypothesis) rather than physiological difference (the phrenological hypothesis). In 1892, prominent French Academy of Sciences member Jean-Martin Charcot produced a noteworthy study of Inaudi on the organization's behalf. Charcot observed that Inaudi called upon auditory memory rather than visual memory in his mental calculations, unlike most mental calculators who preceded him. Like Broca, Charcot was skeptical of the phrenological hypothesis, though he noted that Inaudi's skull was markedly plagiocephalic. Interestingly, anthropological examination of Inaudi is consistent with the themes of modern cognitive neuroscience. Thus, Charcot seems to have anticipated present research on the localization of mental calculation and memory for numbers. 1. (1)The Academy of Sciences, founded in 1666 by Louis XIV (1638-1715) with the goal of contributing to the advancement and application of the sciences in France, was one of the earliest European scientific institutions. As a prestigious society, it played an active role in defining scientific and technological research policy as well as drafting and publishing official reports.

  1. Broca and Charcot's research on Jacques Inaudi: the psychological and anthropological study of a mental calculator.

    PubMed

    Nicolas, Serge; Guida, Alessandro; Levine, Zachary

    2014-01-01

    In the nineteenth century, French scientific institutions became interested in young "mental calculators," arithmetical prodigies able to quickly and accurately perform complex mental calculations. The first scientists to study mental calculators were phrenologists who sought to prove the existence of a calculating organ in the frontal lobe. Paul Broca introduced one such mental calculator, Jacques Inaudi, to the Anthropological Society of Paris in 1880. Broca attributed extraordinary faculty for mental calculation to memory functioning (the psychological hypothesis) rather than physiological difference (the phrenological hypothesis). In 1892, prominent French Academy of Sciences member Jean-Martin Charcot produced a noteworthy study of Inaudi on the organization's behalf. Charcot observed that Inaudi called upon auditory memory rather than visual memory in his mental calculations, unlike most mental calculators who preceded him. Like Broca, Charcot was skeptical of the phrenological hypothesis, though he noted that Inaudi's skull was markedly plagiocephalic. Interestingly, anthropological examination of Inaudi is consistent with the themes of modern cognitive neuroscience. Thus, Charcot seems to have anticipated present research on the localization of mental calculation and memory for numbers. 1. (1)The Academy of Sciences, founded in 1666 by Louis XIV (1638-1715) with the goal of contributing to the advancement and application of the sciences in France, was one of the earliest European scientific institutions. As a prestigious society, it played an active role in defining scientific and technological research policy as well as drafting and publishing official reports. PMID:24697632

  2. Tight junctions in differentiating ameloblasts and odontoblasts differentially express ZO-1, occludin, and claudin-1 in early odontogenesis of rat molars.

    PubMed

    João, Silvia M A; Arana-Chavez, Victor E

    2004-04-01

    Little is known about the expression of associated proteins during the assembly of tight junctions (TJs). We studied the distribution of ZO-1, occludin, and claudin-1 between differentiating ameloblasts and odontoblasts in molar tooth germs from 1- to 3-day-old rats by confocal laser scanning microscopy. Immunoreactivity for ZO-1 was strong at proximal and distal junctional complexes of differentiating ameloblasts, while it was weak and punctuate at the distal region of differentiating odontoblasts. Occludin was immunoreactive at distal and proximal complexes of early differentiating ameloblasts and at distal regions of differentiating odontoblasts. However, in more advanced stages, occludin was only evident at the proximal complex of ameloblasts. Claudin-1 was strongly detected at the proximal complex but it was weak at distal complex of late differentiating ameloblasts. Thus, our results showed that ZO-1, occludin, and claudin-1 are differentially expressed as TJs assemble for regulating polarity and/or paracellular permeability in differentiating ameloblasts and odontoblasts.

  3. Probing effects of pH change on dynamic response of Claudin-2 mediated adhesion using single molecule force spectroscopy

    SciTech Connect

    Lim, Tong Seng; Vedula, Sri Ram Krishna; Hui Shi; Kausalya, P. Jaya; Hunziker, Walter; Lim, Chwee Teck

    2008-08-15

    Claudins belong to a large family of transmembrane proteins that localize at tight junctions (TJs) where they play a central role in regulating paracellular transport of solutes and nutrients across epithelial monolayers. Their ability to regulate the paracellular pathway is highly influenced by changes in extracellular pH. However, the effect of changes in pH on the strength and kinetics of claudin mediated adhesion is poorly understood. Using atomic force microscopy, we characterized the kinetic properties of homophilic trans-interactions between full length recombinant GST tagged Claudin-2 (Cldn2) under different pH conditions. In measurements covering three orders of magnitude change in force loading rate of 10{sup 2}-10{sup 4} pN/s, the Cldn2/Cldn2 force spectrum (i.e., unbinding force versus loading rate) revealed a fast and a slow loading regime that characterized a steep inner activation barrier and a wide outer activation barrier throughout pH range of 4.5-8. Comparing to the neutral condition (pH 6.9), differences in the inner energy barriers for the dissociation of Cldn2/Cldn2 mediated interactions at acidic and alkaline environments were found to be < 0.65 k{sub B}T, which is much lower than the outer dissociation energy barrier (> 1.37 k{sub B}T). The relatively stable interaction of Cldn2/Cldn2 in neutral environment suggests that electrostatic interactions may contribute to the overall adhesion strength of Cldn2 interactions. Our results provide an insight into the changes in the inter-molecular forces and adhesion kinetics of Cldn2 mediated interactions in acidic, neutral and alkaline environments.

  4. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    PubMed

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD.

  5. Fluid reabsorption in proximal convoluted tubules of mice with gene deletions of claudin-2 and/or aquaporin1

    PubMed Central

    Huang, Yuning; Mizel, Diane

    2013-01-01

    Deletions of claudin-2 (Cldn2) and aquaporin1 (AQP1) reduce proximal fluid reabsorption (PFR) by about 30% and 50%, respectively. Experiments were done to replicate these observations and to determine in AQP1/claudin-2 double knockout mice (DKO) if the effects of deletions of these established water pores are additive. PFR was determined in inactin/ketamine-anesthetized mice by free-flow micropuncture using single-nephron I125-iothalamate (io) clearance. Animal means of PFR [% of glomerular filtration rate (GFR)] derived from TF/Piothalamate ratios in 12 mice in each of four groups [wild type (WT), Cldn2−/−, AQP1−/−, and DKO) were 45.8 ± 0.85 (51 tubules), 35.4 ± 1 (54 tubules; P < 0.01 vs. WT), 36.8 ± 1 (63 tubules; P < 0.05 vs. WT), and 33.9 ± 1.4 (69 tubules; P < 0.01 vs. WT). Kidney and single-nephron GFRs (SNGFR) were significantly reduced in all mutant strains. The direct relationship between PFR and SNGFR was maintained in mutant mice, but the slope of this relationship was reduced in the absence of Cldn2 and/or AQP1. Transtubular osmotic pressure differences were not different between WT and Cldn2−/− mice, but markedly increased in DKO. In conclusion, the deletion of Cldn2, AQP1, or of both Cldn2 and AQP1 reduces PFR by 22.7%, 19.6%, and 26%, respectively. Our data are consistent with an up to 25% paracellular contribution to PFR. The reduced osmotic water permeability caused by absence of AQP1 augments luminal hypotonicity. Aided by a fall in filtered load, the capacity of non-AQP1-dependent transcellular reabsorption is sufficient to maintain PFR without AQP1 and claudin-2 at 75% of control. PMID:24049145

  6. Interferon-gamma increased epithelial barrier function via upregulating claudin-7 expression in human submandibular gland duct epithelium.

    PubMed

    Abe, Ayumi; Takano, Kenichi; Kojima, Takashi; Nomura, Kazuaki; Kakuki, Takuya; Kaneko, Yakuto; Yamamoto, Motohisa; Takahashi, Hiroki; Himi, Tetsuo

    2016-06-01

    Tight junctions (TJs) are necessary for salivary gland function and may serve as indicators of salivary gland epithelial dysfunction. IgG4-related disease (IgG4-RD) is a newly recognized fibro-inflammatory condition which disrupts the TJ associated epithelial barrier. The salivary glands are one of the most frequently involved organs in IgG4-RD, however, changes of the TJ associated epithelial barrier in salivary gland duct epithelium is poorly understood. Here, we investigated the regulation and function of TJs in human submandibular gland ductal epithelial cells (HSDECs) in normal and IgG4-RD. We examined submandibular gland (SMG) tissue from eight control individuals and 22 patients with IgG4-RD and established an HSDEC culture system. Immunohistochemistry, immunocytochemistry, western blotting, and measurement of transepithelial electrical resistance (TER) were performed. Claudin-4, claudin-7, occludin, and JAM-A were expressed at the apical side of the duct epithelium in submandibular gland (SMG) tissue and at the cell borders in HSDECs of normal and IgG4-RD. The expression and distribution of TJs in SMG tissue were not different in control individuals and patients with IgG4-RD in vivo and in vitro. Although interferon-gamma (IFNγ) generally disrupts the integrity and function of TJs, as manifested by decreased epithelial barrier function, IFNγ markedly increased the epithelial barrier function of HSDECs via upregulation of claudin-7 expression in HSDECs from patients with IgG4-RD. This is the first report showing an IFNγ-dependent increase in epithelial barrier function in the salivary gland duct epithelium. Our results provide insights into the functional significance of TJs in salivary gland duct epithelium in physiological and pathological conditions, including IgG4-RD. PMID:26956365

  7. Insilico modeling and molecular dynamic simulation of claudin-1 point mutations in HCV infection.

    PubMed

    Vipperla, Bhavaniprasad; Dass, J Febin Prabhu; Jayanthi, S

    2014-01-01

    Claudin-1 (CLDN1) in association with envelope glycoprotein (CD81) mediates the fusion of HCV into the cytosol. Recent studies have indicated that point mutations in CLDN1 are important for the entry of hepatitis C virus (HCV). To validate these findings, we employed a computational platform to investigate the structural effect of two point mutations (I32M and E48K). Initially, three-dimensional co-ordinates for CLDN1 receptor sequence were generated. Then, three mutant models were built using the point mutation including a double mutant (I32M/E48K) model from the native model structure. Finally, all the four model structures including the native and three mutant models were subjected to molecular dynamics (MD) simulation for a period of 25 ns to appreciate their dynamic behavior. The MD trajectory files were analyzed using cluster and principal component method. The analysis suggested that either of the single mutation has negligible effect on the overall structure of CLDN1 compared to the double mutant form. However, the double mutant model of CLDN1 shows significant negative impact through the impairment of H-bonds and the simultaneous increase in solvent accessible surface area. Our simulation results are visibly consistent with the experimental report suggesting that the CLDN1 receptor distortion is prominent due to the double mutation with large surface accessibility. This increase in accessible surface area due to the coexistence of double mutation may be presumed as one of the key factor that results in permissive action of HCV attachment and infection. PMID:23914916

  8. Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5.

    PubMed

    Inamura, Akinori; Adachi, Yasuhiro; Inoue, Takao; He, Yeting; Tokuda, Nobuko; Nawata, Takashi; Shirao, Satoshi; Nomura, Sadahiro; Fujii, Masami; Ikeda, Eiji; Owada, Yuji; Suzuki, Michiyasu

    2013-08-01

    The blood-brain-barrier (BBB) is formed by different cell types, of which brain microvascular endothelial cells are major structural constituents. The goal of this study was to examine the effects of cooling on the permeability of the BBB with reference to tight junction formation of brain microendothelial cells. The sensorimotor cortex above the dura mater in adult male Wistar rats was focally cooled to a temperature of 5 °C for 1 h, then immunostaining for immunoglobulin G (IgG) was performed to evaluate the permeability of the BBB. Permeability produced by cooling was also evaluated in cultured murine brain endothelial cells (bEnd3) based on measurement of trans-epithelial electric resistance (TEER). Immunocytochemistry and Western blotting of proteins associated with tight junctions in bEnd3 were performed to determine protein distribution before and after cooling. After focal cooling of the rat brain cortex, diffuse immunostaining for IgG was observed primarily around the small vasculature and in the extracellular spaces of parenchyma of the cortex. In cultured bEnd3, TEER significantly decreased during cooling (15 °C) and recovered to normal levels after rewarming to 37 °C. Immunocytochemistry and Western blotting showed that claudin-5, a critical regulatory protein for tight junctions, was translocated from the membrane to the cytoplasm after cooling in cultured bEnd3 cells. These results suggest that focal brain cooling may open the BBB transiently through an effect on tight junctions of brain microendothelial cells, and that therapeutically this approach may allow control of BBB function and drug delivery through the BBB.

  9. Cooling treatment transiently increases the permeability of brain capillary endothelial cells through translocation of claudin-5.

    PubMed

    Inamura, Akinori; Adachi, Yasuhiro; Inoue, Takao; He, Yeting; Tokuda, Nobuko; Nawata, Takashi; Shirao, Satoshi; Nomura, Sadahiro; Fujii, Masami; Ikeda, Eiji; Owada, Yuji; Suzuki, Michiyasu

    2013-08-01

    The blood-brain-barrier (BBB) is formed by different cell types, of which brain microvascular endothelial cells are major structural constituents. The goal of this study was to examine the effects of cooling on the permeability of the BBB with reference to tight junction formation of brain microendothelial cells. The sensorimotor cortex above the dura mater in adult male Wistar rats was focally cooled to a temperature of 5 °C for 1 h, then immunostaining for immunoglobulin G (IgG) was performed to evaluate the permeability of the BBB. Permeability produced by cooling was also evaluated in cultured murine brain endothelial cells (bEnd3) based on measurement of trans-epithelial electric resistance (TEER). Immunocytochemistry and Western blotting of proteins associated with tight junctions in bEnd3 were performed to determine protein distribution before and after cooling. After focal cooling of the rat brain cortex, diffuse immunostaining for IgG was observed primarily around the small vasculature and in the extracellular spaces of parenchyma of the cortex. In cultured bEnd3, TEER significantly decreased during cooling (15 °C) and recovered to normal levels after rewarming to 37 °C. Immunocytochemistry and Western blotting showed that claudin-5, a critical regulatory protein for tight junctions, was translocated from the membrane to the cytoplasm after cooling in cultured bEnd3 cells. These results suggest that focal brain cooling may open the BBB transiently through an effect on tight junctions of brain microendothelial cells, and that therapeutically this approach may allow control of BBB function and drug delivery through the BBB. PMID:23653089

  10. Regulation of gill claudin paralogs by salinity, cortisol and prolactin in Mozambique tilapia (Oreochromis mossambicus).

    PubMed

    Tipsmark, Christian K; Breves, Jason P; Rabeneck, D Brett; Trubitt, Rebecca T; Lerner, Darren T; Grau, E Gordon

    2016-09-01

    In euryhaline teleosts, reorganization of gill tight junctions during salinity acclimation involves dynamic expression of specific claudin (Cldn) paralogs. We identified four transcripts encoding Cldn tight junction proteins in the tilapia gill transcriptome: cldn10c, cldn10e, cldn28a and cldn30. A tissue distribution experiment found cldn10c and cldn10e expression levels in the gill to be 100-fold higher than any other tissues examined. cldn28a and cldn30 levels in the gill were 10-fold greater than levels in other tissues. Expression of these genes in Mozambique tilapia was examined during acclimation to fresh water (FW), seawater (SW), and in response to hormone treatments. Transfer of tilapia from FW to SW elevated cldn10c and cldn10e, while cldn28a and cldn30 were stimulated following transfer from SW to FW. In hypophysectomized tilapia transferred to FW, pituitary extirpation induced reduced expression of cldn10c, cldn10e and cldn28a; these effects were mitigated equally by either prolactin or cortisol replacement. In vitro experiments with gill filaments showed that cortisol stimulated expression of all four cldns examined, suggesting a direct action of cortisol in situ. Our data indicate that elevated cldn10c and cldn10e expression is important during acclimation of tilapia to SW possibly by conferring ion specific paracellular permeability. On the other hand, expression of cldn28a and cldn30 appears to contribute to reorganization of branchial epithelium during FW acclimation. Hormone treatment experiments showed that particular FW- and SW-induced cldns are controlled by cortisol and prolactin. PMID:27210417

  11. Clinicopathological significance of claudin 4 expression in gastric carcinoma: a systematic review and meta-analysis

    PubMed Central

    Chen, Xiaowan; Zhao, Junhua; Li, Ailin; Gao, Peng; Sun, Jingxu; Song, Yongxi; Liu, Jingjing; Chen, Ping; Wang, Zhenning

    2016-01-01

    Background The prognostic significance of claudin 4 (CLDN4) in patients with gastric cancer (GC) is controversial. This meta-analysis aims to assess the correlation between CLDN4 expression and clinicopathological characteristics and assess the prognostic significance of CLDN4 in GC. Methods We searched the PubMed and Embase databases. We performed the meta-analysis with odds ratio (OR), hazard ratio (HR), and 95% confidence interval (CI) as effect values. Results Fourteen studies containing 2,106 patients with GC were analyzed. The overall analysis showed that CLDN4 expression was associated with increasing pT category, tumor size, and lymph node metastasis in patients with GC (pT3–T4 vs pT1–T2: OR =1.56, 95% CI =1.13–2.16; P<0.01; large tumor size vs small tumor size: OR =1.64, 95% CI =1.15–2.34; P<0.01; positive lymph node metastasis vs negative lymph node metastasis: OR =1.49, 95% CI =1.12–1.97; P<0.01). CLDN4 expression was associated with histological differentiation (differentiated type vs undifferentiated type: OR =2.90, 95% CI =1.32–6.37; P=0.01; Lauren intestinal type vs diffuse type: OR =3.51, 95% CI =1.48–8.28; P<0.01). CLDN4 expression was also strongly associated with sex and age. This meta-analysis found no significant association between CLDN4 expression and prognosis for overall survival in patients with GC (HR =0.74, 95% CI =0.43–1.27; P=0.28). Conclusion Present study indicates that aberrant CLDN4 expression plays an important role in the clinicopathological characteristics of GC. PMID:27313466

  12. Regulation of tight junction proteins occludin and claudin 5 in the primate ovary during the ovulatory cycle and after inhibition of vascular endothelial growth factor.

    PubMed

    Rodewald, M; Herr, D; Fraser, H M; Hack, G; Kreienberg, R; Wulff, C

    2007-11-01

    Ovarian follicular and corpus luteum development, including angiogenesis, are characterized by cell-cell rearrangements that may require dynamic changes in cell-cell adhesion. The present study investigates the expression of tight junction proteins occludin and claudin 5 during follicular and luteal development in the primate ovary and after inhibition of vascular endothelial growth factor (VEGF) by VEGF trap treatment. Occludin was localized to the plasma membrane of granulosa cells. During follicular development occludin staining decreased significantly (P < 0.05) and disappeared completely by the ovulatory stage. After inhibition of VEGF, occludin staining was significantly (P < 0.05) higher in the granulosa of secondary and tertiary follicles compared with controls. Claudin 5 was exclusively localized to the theca vasculature. A significant (P < 0.05) increase in staining was detected from the pre-antral to the antral and ovulatory stage. However, dual staining with CD31 revealed that within the theca endothelium the amount of claudin 5 remained constant during follicular development. Treatment with VEGF trap throughout the follicular phase revealed a lack of claudin 5 staining in the theca interna but no difference was observed in the remaining theca externa vasculature. In the corpus luteum, claudin 5 was also localized in the vasculature. Treatment with VEGF trap in the mid-luteal phase resulted in a significant increase in staining (P < 0.05). These results led us to hypothesize that tight junctions are involved in regulation of follicular growth, antrum transition and follicular angiogenesis which is compromised by VEGF inhibition. VEGF may influence luteal vascular permeability by regulation of the endothelial specific tight junction protein claudin 5.

  13. EMT Inducers Catalyze Malignant Transformation of Mammary Epithelial Cells and Drive Tumorigenesis towards Claudin-Low Tumors in Transgenic Mice

    PubMed Central

    Fauvet, Frédérique; Courtois-Cox, Stéphanie; Wierinckx, Anne; Devouassoux-Shisheboran, Mojgan; Treilleux, Isabelle; Tissier, Agnès; Gras, Baptiste; Pourchet, Julie; Puisieux, Isabelle; Browne, Gareth J.; Spicer, Douglas B.; Lachuer, Joël; Ansieau, Stéphane; Puisieux, Alain

    2012-01-01

    The epithelial-mesenchymal transition (EMT) is an embryonic transdifferentiation process consisting of conversion of polarized epithelial cells to motile mesenchymal ones. EMT–inducing transcription factors are aberrantly expressed in multiple tumor types and are known to favor the metastatic dissemination process. Supporting oncogenic activity within primary lesions, the TWIST and ZEB proteins can prevent cells from undergoing oncogene-induced senescence and apoptosis by abolishing both p53- and RB-dependent pathways. Here we show that they also downregulate PP2A phosphatase activity and efficiently cooperate with an oncogenic version of H-RAS in malignant transformation of human mammary epithelial cells. Thus, by down-regulating crucial tumor suppressor functions, EMT inducers make cells particularly prone to malignant conversion. Importantly, by analyzing transformed cells generated in vitro and by characterizing novel transgenic mouse models, we further demonstrate that cooperation between an EMT inducer and an active form of RAS is sufficient to trigger transformation of mammary epithelial cells into malignant cells exhibiting all the characteristic features of claudin-low tumors, including low expression of tight and adherens junction genes, EMT traits, and stem cell–like characteristics. Claudin-low tumors are believed to be the most primitive breast malignancies, having arisen through transformation of an early epithelial precursor with inherent stemness properties and metaplastic features. Challenging this prevailing view, we propose that these aggressive tumors arise from cells committed to luminal differentiation, through a process driven by EMT inducers and combining malignant transformation and transdifferentiation. PMID:22654675

  14. Glycogen Synthase Kinase 3 (GSK-3) influences epithelial barrier function by regulating Occludin, Claudin-1 and E-cadherin expression

    SciTech Connect

    Severson, Eric A.; Kwon, Mike; Hilgarth, Roland S.; Parkos, Charles A.; Nusrat, Asma

    2010-07-02

    The Apical Junctional Complex (AJC) encompassing the tight junction (TJ) and adherens junction (AJ) plays a pivotal role in regulating epithelial barrier function and epithelial cell proliferative processes through signaling events that remain poorly characterized. A potential regulator of AJC protein expression is Glycogen Synthase Kinase-3 (GSK-3). GSK-3 is a constitutively active kinase that is repressed during epithelial-mesenchymal transition (EMT). In the present study, we report that GSK-3 activity regulates the structure and function of the AJC in polarized model intestinal (SK-CO15) and kidney (Madin-Darby Canine Kidney (MDCK)) epithelial cells. Reduction of GSK-3 activity, either by small molecule inhibitors or siRNA targeting GSK-3 alpha and beta mRNA, resulted in increased permeability to both ions and bulk solutes. Immunofluorescence labeling and immunoblot analyses revealed that the barrier defects correlated with decreased protein expression of AJC transmembrane proteins Occludin, Claudin-1 and E-cadherin without influencing other TJ proteins, Zonula Occludens-1 (ZO-1) and Junctional Adhesion Molecule A (JAM-A). The decrease in Occludin and E-cadherin protein expression correlated with downregulation of the corresponding mRNA levels for these respective proteins following GSK-3 inhibition. These observations implicate an important role of GSK-3 in the regulation of the structure and function of the AJC that is mediated by differential modulation of mRNA transcription of key AJC proteins, Occludin, Claudin-1 and E-cadherin.

  15. [A inspection in the pharmacy belonging to Jacques François Cordier in Commercy on 1752 December 9th].

    PubMed

    Labrude, Pierre

    2012-02-01

    The respect of regulation in pharmaceutical activity was ever a preoccupation for the legal powers. When the Royal College of Medicine was created in Nancy in 1752, this institution received some prerogatives in this field. The report studied here shows how such a survey is conducted in the pharmacy of a practitioner recently settled in Commercy. We are also informed of current human, hierarchal and social relations. Jacques François Cordier, whose biography is presented, was the introducer and the "godfather" of two famous pharmacists: Jean-Nicolas Trusson in Paris, and Henri Braconnot in Nancy.

  16. Jacques-Louis David's tumour: an opportunity to study the natural history of a pleomorphic adenoma of the parotid gland.

    PubMed

    Wine, Humphrey; Baum, Michael

    2008-12-01

    The great artist and one-time revolutionary, Jacques-Louis David died in 1825. The cause of his death has been open to speculation. An extraordinary sequence of portraits of the artist describes his transition from handsome middle age to a deformed old man. During this phase a swelling appears at the angle of his left jaw and over a period of 20 years a facial palsy can be diagnosed. We submit that this evidence suggests that malignant transformation of a pleomorphic adenoma of the parotid gland was the proximal cause of his death.

  17. Emancipating subjects in science education: taking a lesson from Patti Lather and Jacques Rancière

    NASA Astrophysics Data System (ADS)

    Bazzul, Jesse

    2013-03-01

    This paper extends the conversation started by Patti Lather in her forum response to "Neoliberal ideology, global capitalism, and science education: engaging the question of subjectivity", in terms of engaging the thought of Jacques Rancière. Rancière can offer (science) educators a more definitive example of (possible) emancipatory political subjectivities. His notion of radical equality can also aid in developing new pedagogical spaces in science education. This latter point is taken up in the concluding sections of this short essay.

  18. Up-Regulation of Claudin-6 in the Distal Lung Impacts Secondhand Smoke-Induced Inflammation

    PubMed Central

    Lewis, Joshua B.; Milner, Dallin C.; Lewis, Adam L.; Dunaway, Todd M.; Egbert, Kaleb M.; Albright, Scott C.; Merrell, Brigham J.; Monson, Troy D.; Broberg, Dallin S.; Gassman, Jason R.; Thomas, Daniel B.; Arroyo, Juan A.; Reynolds, Paul R.

    2016-01-01

    It has long been understood that increased epithelial permeability contributes to inflammation observed in many respiratory diseases. Recently, evidence has revealed that environmental exposure to noxious material such as cigarette smoke reduces tight junction barrier integrity, thus enhancing inflammatory conditions. Claudin-6 (Cldn6) is a tetraspanin transmembrane protein found within the tight junctional complex and is implicated in maintaining lung epithelial barriers. To test the hypothesis that increased Cldn6 ameliorates inflammation at the respiratory barrier, we utilized the Tet-On inducible transgenic system to conditionally over-express Clnd6 in the distal lung. Cldn6 transgenic (TG) and control mice were continuously provided doxycycline from postnatal day (PN) 30 until euthanasia date at PN90. A subset of Cldn6 TG and control mice were also subjected to daily secondhand tobacco smoke (SHS) via a nose only inhalation system from PN30-90 and compared to room air (RA) controls. Animals were euthanized on PN90 and lungs were harvested for histological and molecular characterization. Bronchoalveolar lavage fluid (BALF) was procured for the assessment of inflammatory cells and molecules. Quantitative RT-PCR and immunoblotting revealed increased Cldn6 expression in TG vs. control animals and SHS decreased Cldn6 expression regardless of genetic up-regulation. Histological evaluations revealed no adverse pulmonary remodeling via Hematoxylin and Eosin (H&E) staining or any qualitative alterations in the abundance of type II pneumocytes or proximal non-ciliated epithelial cells via staining for cell specific propeptide of Surfactant Protein-C (proSP-C) or Club Cell Secretory Protein (CCSP), respectively. Immunoblotting and qRT-PCR confirmed the differential expression of Cldn6 and the pro-inflammatory cytokines TNF-α and IL-1β. As a general theme, inflammation induced by SHS exposure was influenced by the availability of Cldn6. These data reveal captivating

  19. Protective effect of bone marrow derived mesenchymal stem cells in lipopolysaccharide-induced acute lung injury mediated by claudin-4 in a rat model

    PubMed Central

    Zheng, Yueliang; Cai, Wenwei; Zhou, Shengang; Xu, Liming; Jiang, Chengxing

    2016-01-01

    Our study aims to investigate the effects of bone marrow derived mesenchymal stem cells (BM-MSCs) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) as well as the underlying mechanism. In our study, Wistar rats were randomly divided into four groups: control group; ALI group; ALI+MSCs group and ALI+MSCs claudin-4 siRNA group. MRC-5 and BEAS-2B cell lines were used for in vitro assay. Flow cytometry, western blot, hematoxylin and eosin (H&E) staining, CCK-8 assay, enzyme-linked immunosorbent assay (ELISA) were involved to measure the pathological changes in lung tissues. Results showed that in vivo MSCs administration significantly attenuated pulmonary edema (wet/dry ratio), inflammation cytokines levels (TGF-α), pathological alternations and cell apoptosis which were mediated by claudin-4 in LPS-induced acute lung injury in rats. In vitro experiment showed that hypoxia could induce the expression of claudin-4 in MSCs, and MSCs treatment showed significantly enhanced cell viability (by CCK-8 assay) and reduced cell apoptosis. In conclusion, the present study demonstrated that BM-MSCs can protect against LPS-induced ALI in vivo and in vitro, at least partly mediated by claudin-4. PMID:27725857

  20. Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay.

    PubMed

    Romero, Alejandro; Ares, Irma; Ramos, Eva; Castellano, Víctor; Martínez, Marta; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Martínez, María-Aránzazu

    2016-04-15

    Aflatoxin B1 (AFB1), fumonisin B1 (FB1), ochratoxin A (OTA) and T-2 toxin (T2) are mycotoxins that commonly contaminate the food chain and cause various toxicological effects. Their global occurrence is regarded as an important risk factor for human and animal health. In this study, the results demonstrate that, in human Caco-2 cells, AFB1, FB1, OTA and T2 origin cytotoxic effects, determining cell viability through MTT assay and LDH leakage, and decrease trans-epithelial electrical resistance (TEER). The decrease in barrier properties is concomitant with a reduction in the expression levels of the tight junction constituents claudin-3, claudin-4 and occludin. The protective effect of mineral clays (diosmectite, montmorillonite and illite) on alterations in cell viability and epithelial barrier function induced by the mycotoxins was also evaluated. Illite was the best clay to prevent the mycotoxin effects. Illite plus mycotoxin co-treatment completely abolished AFB1 and FB1-induced cytotoxicity. Also, the decreases in the gene expression of claudins and the reduction of TEER induced by mycotoxins were reversed by the illite plus mycotoxin co-treatment. In conclusion, these results demonstrated that mycotoxins AFB1, FB1, T2 and OTA disrupt the intestinal barrier permeability by a mechanism involving reduction of claudin isoform expressions, and illite counteracts this disruption. PMID:27153755

  1. Mycotoxins modify the barrier function of Caco-2 cells through differential gene expression of specific claudin isoforms: Protective effect of illite mineral clay.

    PubMed

    Romero, Alejandro; Ares, Irma; Ramos, Eva; Castellano, Víctor; Martínez, Marta; Martínez-Larrañaga, María-Rosa; Anadón, Arturo; Martínez, María-Aránzazu

    2016-04-15

    Aflatoxin B1 (AFB1), fumonisin B1 (FB1), ochratoxin A (OTA) and T-2 toxin (T2) are mycotoxins that commonly contaminate the food chain and cause various toxicological effects. Their global occurrence is regarded as an important risk factor for human and animal health. In this study, the results demonstrate that, in human Caco-2 cells, AFB1, FB1, OTA and T2 origin cytotoxic effects, determining cell viability through MTT assay and LDH leakage, and decrease trans-epithelial electrical resistance (TEER). The decrease in barrier properties is concomitant with a reduction in the expression levels of the tight junction constituents claudin-3, claudin-4 and occludin. The protective effect of mineral clays (diosmectite, montmorillonite and illite) on alterations in cell viability and epithelial barrier function induced by the mycotoxins was also evaluated. Illite was the best clay to prevent the mycotoxin effects. Illite plus mycotoxin co-treatment completely abolished AFB1 and FB1-induced cytotoxicity. Also, the decreases in the gene expression of claudins and the reduction of TEER induced by mycotoxins were reversed by the illite plus mycotoxin co-treatment. In conclusion, these results demonstrated that mycotoxins AFB1, FB1, T2 and OTA disrupt the intestinal barrier permeability by a mechanism involving reduction of claudin isoform expressions, and illite counteracts this disruption.

  2. Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage.

    PubMed

    Liu, Jie; Jin, Xinchun; Liu, Ke J; Liu, Wenlan

    2012-02-29

    Blood-brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here, we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran and promoted the secretion of metalloproteinase-2 and -9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT (2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane) or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity, and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2 h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis.

  3. Matrix metalloproteinase-2-mediated occludin degradation and caveolin-1-mediated claudin-5 redistribution contribute to blood-brain barrier damage in early ischemic stroke stage.

    PubMed

    Liu, Jie; Jin, Xinchun; Liu, Ke J; Liu, Wenlan

    2012-02-29

    Blood-brain barrier (BBB) disruption occurs early enough to be within the thrombolytic time window, and this early ischemic BBB damage is closely associated with hemorrhagic transformation and thus emerging as a promising target for reducing the hemorrhagic complications of thrombolytic stroke therapy. However, the mechanisms underlying early ischemic BBB damage remain poorly understood. Here, we investigated the early molecular events of ischemic BBB damage using in vitro oxygen-glucose deprivation (OGD) and in vivo rat middle cerebral artery occlusion (MCAO) models. Exposure of bEND3 monolayer to OGD for 2 h significantly increased its permeability to FITC-labeled dextran and promoted the secretion of metalloproteinase-2 and -9 (MMP-2/9) and cytosolic translocation of caveolin-1 (Cav-1). This same OGD treatment also led to rapid degradation of tight junction protein occludin and dissociation of claudin-5 from the cytoskeleton, which contributed to OGD-induced endothelial barrier disruption. Using selective MMP-2/9 inhibitor SB-3CT (2-[[(4-phenoxyphenyl)sulfonyl]methyl]-thiirane) or their neutralizing antibodies or Cav-1 siRNA, we found that MMP-2 was the major enzyme mediating OGD-induced occludin degradation, while Cav-1 was responsible for claudin-5 redistribution. The interaction between Cav-1 and claudin-5 was further confirmed by coimmunoprecipitation. Consistent with these in vitro findings, we observed fluorescence tracer extravasation, increased gelatinolytic activity, and elevated interstitial MMP-2 levels in ischemic subcortical tissue after 2 h MCAO. Moreover, occludin protein loss and claudin-5 redistribution were detected in ischemic cerebromicrovessels. These data indicate that cerebral ischemia initiates two rapid parallel processes, MMP-2-mediated occludin degradation and Cav-1-mediated claudin-5 redistribution, to cause BBB disruption at early stroke stages relevant to acute thrombolysis. PMID:22378877

  4. The Effects of Alcohol Intoxication and Burn Injury on the Expression of Claudins and Mucins in the Small and Large Intestines.

    PubMed

    Hammer, Adam M; Khan, Omair M; Morris, Niya L; Li, Xiaoling; Movtchan, Nellie V; Cannon, Abigail R; Choudhry, Mashkoor A

    2016-01-01

    Alcohol intoxication at the time of burn injury exacerbates postburn pathogenesis. Recent findings suggest gut barrier integrity is compromised after combined alcohol and burn insult, which could contribute to these complications. Tight junction proteins and mucins play critical roles in keeping the gut barrier intact. Therefore, the goal of this study was to examine the effects of alcohol and burn injury on claudin and mucin expression in the intestines. We also evaluated if the combined insult differentially influences their expression in the small and large intestines. Male C57BL/6 mice were given a single dose of 2.9 g/kg ethanol before an approximately 12.5% body area burn. One and three days after injury, we profiled expression of several tight junction proteins, mucin, and bacterial 16S rRNA genes in the small and large intestines, using qPCR. We observed >50% decrease in claudin-4 and claudin-8 genes in both ileal and colonic epithelial cells 1 day after injury. Claudin-2 was significantly upregulated, and occludin was downregulated in the small intestine 1 day after injury. Mucin-3 expression was substantially elevated (>50%) in the small intestine, whereas mucin-2 and mucin-4 were considerably diminished in the colon (>50%) 1 day after injury. Most of the parameters were normalized to sham levels on day 3, except for mucin-3 and claudin-8, which remained decreased in the large intestine. Neither alcohol nor burn alone resulted in changes in junction or mucin gene expression compared to shams. This was accompanied with increases in the family of Gram-negative bacteria, Enterobacteriaceae, in both the small and the large intestines 1 day after injury. These findings suggest that alcohol and burn injury disrupts the normal gut microbiota and alters tight junction and mucin expression in the small and large intestines.

  5. Biphasic Modulation of Paracellular Claudin-5 Expression in Mouse Brain Endothelial Cells Is Mediated through the Phosphoinositide-3-Kinase/AKT Pathway

    PubMed Central

    Camire, Ryan B.; Beaulac, Holly J.; Brule, Stephanie A.; McGregor, Annie I.; Lauria, Emily E.

    2014-01-01

    Blood-brain barrier (BBB) integrity is compromised in many central nervous system disorders. Complex astrocyte and vascular endothelial cell interactions that regulate BBB integrity may be disturbed in these disorders. We previously showed that systemic administration of 3-chloropropanediol [(S)-(+)-3-chloro-1,2-propanediol] induces a transitory glial fibrillary acidic protein-astrocyte loss, reversible loss of tight junction complexes, and BBB integrity disruption. However, the intracellular signaling mechanisms that induce BBB integrity marker loss are unclear. We hypothesize that 3-chloropropanediol–induced modulation of tight junction protein expression is mediated through the phosphoinositide-3-kinase (PI3K)/AKT pathway. To test this hypothesis, we used a mouse brain endothelial cell line (bEnd.3) exposed to 3-chloropropanediol for up to 3 days. Results showed early reversible loss of sharp paracellular claudin-5 expression 90, 105, and 120 minutes after 3-chloropropanediol (500 μM) treatment. Sharp paracellular claudin-5 profiles were later restored, but lost again by 2 and 3 days after 3-chloropropanediol treatment. Western blot and immunofluorescence studies showed increased p85-PI3K expression and transitory increased AKT (Thr308) phosphorylation at 15 and 30 minutes after 3-chloropropanediol administration. PI3K inhibitors LY294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one hydrochloride; 2.5–25 μM] and PI-828 [2-(4-morpholinyl)-8-(4-aminopheny)l-4H-1-benzopyran-4-one; 0.1–10 μM] prevented the 3-chloropropanediol–induced AKT (Thr308) phosphorylation and both early and late loss of paracellular claudin-5. However, AKT inhibitors only prevented the early changes in claudin-5 expression. This mechanistic study provides a greater understanding of the intracellular signaling pathways mediating tight junction protein expression and supports a hypothesis that two independent pathways triggered by PI3K mediate early and late loss of paracellular

  6. Sirolimus and cyclosporine A alter barrier function in renal proximal tubular cells through stimulation of ERK1/2 signaling and claudin-1 expression.

    PubMed

    Martin-Martin, Natalia; Ryan, Gavin; McMorrow, Tara; Ryan, Michael P

    2010-03-01

    Alteration of the tight junction complex in renal epithelial cells can affect renal barrier function and perturb normal kidney homeostasis. The immunosuppressant drugs cyclosporine A (CsA) and sirolimus (SRL) used in combination demonstrated beneficial effects in organ transplantation but this combination can also result in increased adverse effects. We previously showed that CsA treatment alone caused an alteration of the tight junction complex, resulting in changes in transepithelial permeability in Madin-Darby canine kidney distal tubular/collecting duct cells. The potential effect of SRL on transepithelial permeability in kidney cells is unknown. In this study, subcytotoxic doses of SRL or CsA were found to decrease the paracellular permeability of the porcine proximal tubular epithelial cells, LLC-PK1 cell monolayers, which was detected as an increase in transepithelial electrical resistance (TER). The cotreatment with SRL and CsA was found to increase TER in a synergistic manner. CsA treatment increased total cellular expression and membrane localization of the tight junction protein claudin-1 and this further increased with the combination of SRL/CsA. SRL and CsA treatment alone or in combination stimulated the phosphorylation of ERK1/2. The MEK-ERK1/2 pathway inhibitor, U0126, reduced the SRL, CsA, and CsA/SRL-induced increase in TER. U0126 also reduced the CsA and CsA/SRL-induced increase in the membrane localization of claudin-1. Alterations in claudin-2 and claudin-4 were also detected. However, the results suggest that the modulation in expression and localization of claudin-1 appears to be pivotal in the SRL- and CsA-induced modulation of the epithelial barrier function and that modulation is regulated by ERK1/2 signaling pathway. PMID:19955189

  7. Scientific exchange: Jacques Loeb (1859-1924) and Emil Godlewski (1875-1944) as representatives of a transatlantic developmental biology.

    PubMed

    Fangerau, Heiner; Müller, Irmgard

    2007-09-01

    The German-American physiologist Jacques Loeb (1859-1924) and the Polish embryologist Emil Godlewski, jr. (1875-1944) contributed many valuable works to the body of developmental biology. Jacques Loeb was world famous at the beginning of the twentieth century for his development and demonstration of artificial parthenogenesis in 1899 and his experiments on regeneration. He served as a role model for the younger Polish experimenter Emil Godlewski, who began his career as a researcher like Loeb at the Zoological Station in Naples. Following Godlewski's first visit to Naples in 1901 a close relationship between the two scientists developed. Until Loeb's death in 1924 the two exchanged ideas via correspondence that was only interrupted during the First World War. The aim of the paper is to examine the transatlantic transfer of knowledge in the field of biological experimentation that was fostered by these two protagonists. Using a modification of Bruno Latour's model of the 'Circulatory System of Science' as a heuristic tool, different mechanisms of scientific exchange are displayed. With the help of Loeb's and Godlewski's correspondence the role of scientific communities, methods, allies, the public and institutions in the process of knowledge transfer are analysed. Preconditions for success and failure in transferring science are examined.

  8. Suicides associated with the Jacques Cartier Bridge, Montreal, Quebec 1988-1993: descriptive analysis and intervention proposal.

    PubMed

    Prévost, C; Julien, M; Brown, B P

    1996-01-01

    Falls from heights represent an uncommon means of suicide. Regional variations are attributable to the presence of particular sites which attract suicidal individuals. The Jacques Cartier Bridge in Montreal is one such site, though less well known than North American sites such as the Golden Gate Bridge or Niagara Falls. According to Coroner's records, 54 suicides were associated with the bridge for the period 1988 to 1993. All but one of the suicides were the result of jumps from the bridge. The median age of victims was 30 years, and 46 of the victims were male. Bridge-specific verbalization of suicidal intent and prior history of medically diagnosed psychiatric disorders are frequently noted. Based on a review of the effectiveness of preventive measures, we propose limiting access to jumping by means of a fence along the bridge railing. PMID:9009392

  9. H. pylori-encoded CagA disrupts tight junctions and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2.

    PubMed

    Song, Xin; Chen, Hui-Xin; Wang, Xiao-Yan; Deng, Xi-Yun; Xi, Yin-Xue; He, Qing; Peng, Tie-Li; Chen, Jie; Chen, Wei; Wong, Benjamin Chun-Yu; Chen, Min-Hu

    2013-01-01

    Helicobacter pylori encoded CagA is presently the only known virulence factor that is injected into gastric epithelial cells where it destroys apical junctional complexes and induces dedifferentiation of gastric epithelial cells, leading to H. pylori-related gastric carcinogensis. However, little is known about the molecular mechanisms by which CagA mediates these changes. Caudal-related homeobox 2 (Cdx2) is an intestine-specific transcription factor highly expressed in multistage tissues of dysplasia and cancer. One specific target of Cdx2, Claudin-2, is involved in the regulation of tight junction (TJ) permeability. In this study, our findings showed that the activity of Cdx2 binding to Cdx binding sites of CdxA (GTTTATG) and CdxB (TTTTAGG) of probes corresponding to claudin-2 flanking region increased in AGS cells, infected with CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic mutant-type strain. Moreover, Cdx2 upregulated claudin-2 expression at transcriptional level and translational level. In the meantime, we found that TJs of AGS cells, infected with CagA positive wild-type strain of H. pylori, compared to CagA negative isogenic mutant-type strain, were more severely destroyed, leading to wider cell gap, interference of contact, scattering and highly elevated migration of cells. Herein, this study is firstly demonstrated that H. pylori-encoded CagA disrupts TJs and induces invasiveness of AGS gastric carcinoma cells via Cdx2-dependent targeting of Claudin-2. This provides a new mechanism whereby CagA induced dedifferentiation of AGS cells, leading to malignant behavior of biology. PMID:24287273

  10. Bradykinin increases blood-tumor barrier permeability by down-regulating the expression levels of ZO-1, occludin, and claudin-5 and rearranging actin cytoskeleton.

    PubMed

    Liu, Li-Bo; Xue, Yi-Xue; Liu, Yun-Hui; Wang, Yi-Bao

    2008-04-01

    Bradykinin (BK) has been shown to open blood-tumor barrier (BTB) selectively and to increase permeability of the BTB transiently, but the mechanism is unclear. This study was performed to determine whether BK opens the BTB by affecting the tight junction (TJ)-associated proteins zonula occluden-1 (ZO-1), occludin, and caludin-5 and cytoskeleton protein filamentous actin (F-actin). In rat brain glioma model and BTB model in vitro, we find that the protein expression levels of ZO-1, occludin, and claudin-5 are attenuated by BK induction. Immunohistochemistry and immunofluorescence assays show that the attenuated expression of ZO-1, occludin, and claudin-5 and F-actin is most obvious in the smaller tumor capillaries (<20 microm) after BK infusion, and there is no change in the larger tumor capillaries (>20 microm). The redistribution of ZO-1, occludin, and claudin-5 and rearrangement of F-actin in brain microvascular endothelial cells are observed at the same time. Meanwhile, Evans blue assay shows that the permeability of BTB increases after BK infusion. Transmission electron microscopy indicates that TJ is opened and that pinocytotic vesicular density is increased. Transendothelial electrical resistance (TEER) and horseradish peroxidase flux assays also reveal that TJ is opened by BK induction. In addition, radioimmunity and Western blot assay reveal a significant decrease in expression levels of cAMP and catalytic subunit of protien kinase A (PKAcs) of tumor tissue. This study demonstrates that the increase of BK-mediated BTB permeability is associated with the down-regulation of ZO-1, occludin, and claudin-5 and the rearrangement of F-actin and that cAMP/PKA signal transduction system might be involved in the modulating process.

  11. TGFβ1 exacerbates blood-brain barrier permeability in a mouse model of hepatic encephalopathy via upregulation of MMP9 and downregulation of claudin-5

    PubMed Central

    McMillin, Matthew; Frampton, Gabriel; Seiwell, Andrew; Patel, Nisha; Jacobs, Amber; DeMorrow, Sharon

    2016-01-01

    Recent studies have found that vasogenic brain edema is present during hepatic encephalopathy following acute liver failure and is dependent upon increased matrix metalloproteinase 9 (MMP9) activity and downregulation of tight junction proteins. Furthermore, circulating transforming growth factor β1 (TGFβ1) is increased following liver damage and may promote endothelial cell permeability. This study aimed to assess if increased circulating TGFβ1 drives changes in tight junction protein expression and MMP9 activity following acute liver failure. Blood-brain barrier permeability was assessed in azoxymethane (AOM)-treated mice at 6, 12, and 18 hours post-injection via Evan’s blue extravasation. Monolayers of immortalized mouse brain endothelial cells (bEnd.3) were treated with recombinant TGFβ1 (rTGFβ1) and permeability to fluorescein isothiocyanate-dextran (FITC-dextran), MMP9 and claudin-5 expression were assessed. Antagonism of TGFβ1 signaling was performed in vivo to determine its role in blood-brain barrier permeability. Blood-brain barrier permeability was increased in mice at 18 hours following AOM injection. Treatment of bEnd.3 cells with rTGFβ1 led to a dose-dependent increase of MMP9 expression as well as a suppression of claudin-5 expression. These effects of rTGFβ1 on MMP9 and claudin-5 expression could be reversed following treatment with a SMAD3 inhibitor. AOM-treated mice injected with neutralizing antibodies against TGFβ demonstrated significantly reduced blood-brain barrier permeability. Blood-brain barrier permeability is induced in AOM mice via a mechanism involving the TGFβ1-driven SMAD3-dependent upregulation of MMP9 expression and decrease of claudin-5 expression. Therefore, treatment modalities aimed at reducing TGFβ1 levels or SMAD3 activity may be beneficial in promoting blood-brain barrier integrity following liver failure. PMID:26006017

  12. Differences in claudin synthesis in primary cultures of acinar cells from rat salivary gland are correlated with the specific three-dimensional organization of the cells.

    PubMed

    Qi, Bing; Fujita-Yoshigaki, Junko; Michikawa, Hiromi; Satoh, Keitaro; Katsumata, Osamu; Sugiya, Hiroshi

    2007-07-01

    Tight junctions are essential for the maintenance of epithelial cell polarity. We have previously established a system for the primary culture of salivary parotid acinar cells that retain their ability to generate new secretory granules and to secrete proteins in a signal-dependent manner. Because cell polarity and cell-cell adhesion are prerequisites for the formation of epithelial tissues, we have investigated the structure of the tight junctions in these cultures. We have found two types of cellular organization in the culture: monolayers and semi-spherical clusters. Electron microscopy has revealed tight junctions near the apical region of the lateral membranes between cells in the monolayers and cells at the surface of the clusters. The cells in the interior of the clusters also have tight junctions and are organized around a central lumen. These interior cells retain more secretory granules than the surface or monolayer cells, suggesting that they maintain their original character as acinar cells. The synthesis of claudin-4 increases during culture, although it is not detectable in the cells immediately after isolation from the glands. Immunofluorescence microscopy has shown that claudin-4 is synthesized in the monolayers and at the surface of the clusters, but not inside the clusters. Only claudin-3, which is present in the original acinar cells following isolation and in the intact gland, has been detected inside the clusters. These results suggest that differences in claudin expression are related to the three-dimensional structures of the cell cultures and reflect their ability to function as acinar cells.

  13. Toll-like receptor 2 regulates the barrier function of human bronchial epithelial monolayers through atypical protein kinase C zeta, and an increase in expression of claudin-1

    PubMed Central

    Ragupathy, Sakthikumar; Esmaeili, Farnaz; Paschoud, Serge; Sublet, Emmanuelle; Citi, Sandra; Borchard, Gerrit

    2014-01-01

    We investigated the role of Toll-like receptor (TLR) 2 in maintaining the integrity of the airway epithelial barrier using the human bronchial epithelial cell line Calu-3. Activation of TLR2 by its ligands, Pam3CysSK4 and Peptidoglycan showed a concentration dependent increase in epithelial barrier function, as measured by transepithelial electrical resistance (TEER). This was confirmed by a decrease in paracellular flux of fluorescein sodium. This TLR2 induced increase in TEER was significantly reduced by pretreatment with polyclonal anti-human TLR2-neutralizing antibody. TLR2 stimulation in Calu-3 cell monolayers resulted in an increased expression of the tight junction proteins claudin-1 and ZO-1, and a decreased expression of occludin, at both the mRNA and protein levels. A pseudosubstrate inhibitor to PKCζ significantly prevented the TLR2 mediated increase in barrier function. It also prevented the increase in claudin-1 in a concentration dependent manner up to 1 µM. TLR2 stimulation led to an increase in phosphorylation of atypical PKC ζ, which was prevented by the pseudosubstrate inhibitor in a concentration dependent manner. Taken together, our observations support a model whereby increased tight junction barrier function induced by activation of TLR2 occurs through increased expression of claudin-1, and through modulation of PKC ζ activity. PMID:25101232

  14. The targeted overexpression of a Claudin mutant in the epidermis of transgenic mice elicits striking epidermal and hair follicle abnormalities.

    PubMed

    Troy, Tammy-Claire; Turksen, Kursad

    2007-06-01

    Skin is one of the largest organs of the body, and is formed during development through a highly orchestrated process involving mesenchymal-epithelial interactions, cell commitment, and terminal differentiation. It protects against microorganism invasion and UV irradiation, inhibits water loss, regulates body temperature, and is an important part of the immune system. Using transgenic mouse technology, we have demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are intricately involved in cell signaling during epidermal differentiation and that an epidermal suprabasal overexpression of Cldn6 results in a perturbed epidermal terminal differentiation program with distinct phenotypic abnormalities. To delineate the role of the Cldn cytoplasmic tail domain in epidermal differentiation, we engineered transgenic mice targeting the overexpression of a Cldn6 cytoplasmic tail-truncation mutant in the epidermis. Transgenic mice were characterized by a lethal barrier dysfunction in addition to the existence of hyperproliferative squamous invaginations/cysts replacing hair follicles. Immunohistochemical analysis revealed an epidermal cytoplasmic accumulation of Cldn6, Cldn11, Cldn12, and Cldn18, downregulation of Cldn1 and aberrant expression of various classical markers of epidermal differentiation; namely the basal keratins as well as K1, involucrin, loricrin, and filaggrin. Collectively these studies suggest an important role for Cldns in epidermal/hair follicle differentiation programs likely involving cross talk to signaling pathways (e.g., Notch) directing cell fate selection and differentiation.

  15. The targeted overexpression of a Claudin mutant in the epidermis of transgenic mice elicits striking epidermal and hair follicle abnormalities.

    PubMed

    Troy, Tammy-Claire; Turksen, Kursad

    2007-06-01

    Skin is one of the largest organs of the body, and is formed during development through a highly orchestrated process involving mesenchymal-epithelial interactions, cell commitment, and terminal differentiation. It protects against microorganism invasion and UV irradiation, inhibits water loss, regulates body temperature, and is an important part of the immune system. Using transgenic mouse technology, we have demonstrated that Claudin (Cldn)-containing tight junctions (TJs) are intricately involved in cell signaling during epidermal differentiation and that an epidermal suprabasal overexpression of Cldn6 results in a perturbed epidermal terminal differentiation program with distinct phenotypic abnormalities. To delineate the role of the Cldn cytoplasmic tail domain in epidermal differentiation, we engineered transgenic mice targeting the overexpression of a Cldn6 cytoplasmic tail-truncation mutant in the epidermis. Transgenic mice were characterized by a lethal barrier dysfunction in addition to the existence of hyperproliferative squamous invaginations/cysts replacing hair follicles. Immunohistochemical analysis revealed an epidermal cytoplasmic accumulation of Cldn6, Cldn11, Cldn12, and Cldn18, downregulation of Cldn1 and aberrant expression of various classical markers of epidermal differentiation; namely the basal keratins as well as K1, involucrin, loricrin, and filaggrin. Collectively these studies suggest an important role for Cldns in epidermal/hair follicle differentiation programs likely involving cross talk to signaling pathways (e.g., Notch) directing cell fate selection and differentiation. PMID:17914196

  16. Molecular pathology of brain matrix metalloproteases, claudin5, and aquaporins in forensic autopsy cases with special regard to methamphetamine intoxication.

    PubMed

    Wang, Qi; Ishikawa, Takaki; Michiue, Tomomi; Zhu, Bao-Li; Guan, Da-Wei; Maeda, Hitoshi

    2014-05-01

    Methamphetamine (METH) is a highly addictive drug of abuse and toxic to the brain. Recent studies indicated that besides direct damage to dopamine and 5-HT terminals, neurotoxicity of METH may also result from its ability to modify the structure of blood-brain barrier (BBB). The present study investigated the postmortem brain mRNA and immunohistochemical expressions of matrix metalloproteases (MMPs), claudin5 (CLDN5), and aquaporins (AQPs) in forensic autopsy cases of carbon monoxide (n = 14), METH (n = 21), and phenobarbital (n = 17) intoxication, compared with mechanical asphyxia (n = 15), brain injury (n = 11), non-brain injury (n = 21), and sharp instrument injury (n = 15) cases. Relative mRNA quantification using Taqman real-time PCR assay demonstrated higher expression of AQP4 and MMP9, lower expression of CLDN5 in METH intoxication cases and lower expression of MMP2 in phenobarbital intoxication cases. Immunostaining results showed substantial interindividual variations in each group, showing no evident differences in distribution or intensity among all the causes of death. These findings suggest that METH may increase BBB permeability by altering CLDN5 and MMP9, and the self-protective system maybe activated to eliminate accumulating water from the extracellular space of the brain by up-regulating AQP4. Systematic analysis of gene expressions using real-time PCR may be a useful procedure in forensic death investigation.

  17. MMP-Mediated Disruption of Claudin-5 in the Blood–Brain Barrier of Rat Brain After Cerebral Ischemia

    PubMed Central

    Yang, Yi; Rosenberg, Gary A.

    2016-01-01

    The blood–brain barrier (BBB) has become a major focus of attention in cerebral pathophysiology and disease progression in the central nervous system. Endothelial tight junctions, the basal lamina, and perivascular astrocytes are jointly referred to as BBB or neurovascular unit. Around the cerebral endothelial cells is the basal lamina composed primarily of laminin, fibronectin, and heparan sulfate. The basal lamina provides a structural barrier to extravasation of cellular blood elements and anchors endothelial cells to astrocytes. Barriers limiting transport into and out of the brain are found at the tight junction proteins and at the basal lamina. The relative contribution of these two sites has not been studied, but it is likely that both are disrupted to some extent in various injury scenarios. We have shown that activation of matrix metalloproteinases (MMPs) opens the BBB by degrading tight junction proteins (claudin-5 and occludin) and increases BBB permeability after stroke, and that an MMP inhibitor prevents degradation of tight junction proteins and attenuates BBB disruption. PMID:21717368

  18. Nurses as 'guests'--a study of a concept in light of Jacques Derrida's philosophy of hospitality.

    PubMed

    Oresland, Stina; Lutzén, Kim; Norberg, Astrid; Rasmussen, Birgit H; Määttä, Sylvia

    2013-04-01

    As revealed in previous empirical research, nurses describe their position in home-based nursing care (HBNC) as that of 'guests' in the patient's home. Such a description is problematic as 'guests' might not be considered to belong to the realm of professionalism. As Jacques Derrida's work on hospitality has received wide publicity, sparking theoretical and philosophical discussion about host and guest, the aim of this study was to explore how the concept 'guests' can be understood in the light of Derrida's philosophy of hospitality. The study revealed that (a) guest must be considered a binary concept; and (b) hospitality should be regarded as an exchange of giving and receiving between a host and a guest. The present study demonstrated that it is important to reflect on the meaning of the concepts used by nurses in HBNC. Further theoretical and empirical exploration of the concept 'hospitality' would be fruitful, i.e. what is patients' understanding of 'hospitality' and 'hostility' related to nurses' descriptions of themselves as 'guests' in the patient's home.

  19. Metformin attenuates transforming growth factor beta (TGF-β) mediated oncogenesis in mesenchymal stem-like/claudin-low triple negative breast cancer.

    PubMed

    Wahdan-Alaswad, Reema; Harrell, J Chuck; Fan, Zeying; Edgerton, Susan M; Liu, Bolin; Thor, Ann D

    2016-01-01

    Mesenchymal stem-like/claudin-low (MSL/CL) breast cancers are highly aggressive, express low cell-cell adhesion cluster containing claudins (CLDN3/CLDN4/CLDN7) with enrichment of epithelial-to-mesenchymal transition (EMT), immunomodulatory, and transforming growth factor-β (TGF-β) genes. We examined the biological, molecular and prognostic impact of TGF-β upregulation and/or inhibition using in vivo and in vitro methods. Using publically available breast cancer gene expression databases, we show that upregulation and enrichment of a TGF-β gene signature is most frequent in MSL/CL breast cancers and is associated with a worse outcome. Using several MSL/CL breast cancer cell lines, we show that TGF-β elicits significant increases in cellular proliferation, migration, invasion, and motility, whereas these effects can be abrogated by a specific inhibitor against TGF-β receptor I and the anti-diabetic agent metformin, alone or in combination. Prior reports from our lab show that TNBC is exquisitely sensitive to metformin treatment. Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-β-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level. We report the use of ID1 and ID3 as clinical surrogate markers, where high expression of these TGF-β target genes was correlated to poor prognosis in claudin-low patients. Given TGF-β's role in tumorigenesis and immunomodulation, blockade of this pathway using direct kinase inhibitors or more broadly acting inhibitors may dampen or abolish pro-carcinogenic and metastatic signaling in patients with MCL/CL TNBC. Metformin therapy (with or without other agents) may be a heretofore unrecognized approach to reduce the oncogenic activities associated with TGF-β mediated oncogenesis. PMID:26919310

  20. Metformin attenuates transforming growth factor beta (TGF-β) mediated oncogenesis in mesenchymal stem-like/claudin-low triple negative breast cancer.

    PubMed

    Wahdan-Alaswad, Reema; Harrell, J Chuck; Fan, Zeying; Edgerton, Susan M; Liu, Bolin; Thor, Ann D

    2016-01-01

    Mesenchymal stem-like/claudin-low (MSL/CL) breast cancers are highly aggressive, express low cell-cell adhesion cluster containing claudins (CLDN3/CLDN4/CLDN7) with enrichment of epithelial-to-mesenchymal transition (EMT), immunomodulatory, and transforming growth factor-β (TGF-β) genes. We examined the biological, molecular and prognostic impact of TGF-β upregulation and/or inhibition using in vivo and in vitro methods. Using publically available breast cancer gene expression databases, we show that upregulation and enrichment of a TGF-β gene signature is most frequent in MSL/CL breast cancers and is associated with a worse outcome. Using several MSL/CL breast cancer cell lines, we show that TGF-β elicits significant increases in cellular proliferation, migration, invasion, and motility, whereas these effects can be abrogated by a specific inhibitor against TGF-β receptor I and the anti-diabetic agent metformin, alone or in combination. Prior reports from our lab show that TNBC is exquisitely sensitive to metformin treatment. Mechanistically, metformin blocks endogenous activation of Smad2 and Smad3 and dampens TGF-β-mediated activation of Smad2, Smad3, and ID1 both at the transcriptional and translational level. We report the use of ID1 and ID3 as clinical surrogate markers, where high expression of these TGF-β target genes was correlated to poor prognosis in claudin-low patients. Given TGF-β's role in tumorigenesis and immunomodulation, blockade of this pathway using direct kinase inhibitors or more broadly acting inhibitors may dampen or abolish pro-carcinogenic and metastatic signaling in patients with MCL/CL TNBC. Metformin therapy (with or without other agents) may be a heretofore unrecognized approach to reduce the oncogenic activities associated with TGF-β mediated oncogenesis.

  1. Claudin 11 inter-sertoli tight junctions in the testis of the korean soft-shelled turtle (Pelodiscus maackii).

    PubMed

    Park, Chan Jin; Ha, Cheol Min; Lee, Jae Eun; Gye, Myung Chan

    2015-04-01

    Expression of claudin 11 (CLDN11), a tight junction (TJ) protein, was examined in the Korean soft-shelled turtle (Pelodiscus maackii) testis. Spermatogenesis began during the breeding season and peaked at the end of the breeding season. Spermiation started in summer and peaked in autumn. The deduced amino acid sequence of P. maackii CLDN11 was similar to those of avian and mammalian species. During the nonbreeding season when spermatogenesis and testosterone production were active, testicular Cldn11 levels were high. In the seminiferous epithelium, strong, wavy CLDN11 strands parallel to the basement membrane delaminate the spermatogonia, and early spermatocytes are in the open compartment. Otherwise, CLDN11 was found beneath the early spermatocytes and in the Sertoli cell cytoplasm. Punctate zonula occludens 1 (ZO-1) immunoreactivity was found within the CLDN11 strands parallel to the basement membrane or at the outermost periphery of the seminiferous epithelium close to the basal lamina. During the breeding season, when circulating testosterone levels and spermatogenic activity was low, testicular CLDN11 level was lower than those during the nonbreeding season. CLDN11 was found at apicolateral contact sites between adjacent Sertoli cells devoid of the postmeiotic germ cells. At this time, lanthanum tracer diffused to the adluminal compartment of seminiferous epithelium. In cultured testis tissues, testosterone propionate significantly increased the level of Cldn11 mRNA. In P. maackii testis, CLDN11 participates in the development of the blood-testis barrier (BTB), where the CLDN11 expression was coupled with spermatogenic activity and circulating androgen levels, indicating the conserved nature of TJs expressing CLDN11 at the BTB in amniotes.

  2. Transepithelial resistance and claudin expression in trout RTgill-W1 cell line: effects of osmoregulatory hormones.

    PubMed

    Trubitt, Rebecca T; Rabeneck, D Brett; Bujak, Joanna K; Bossus, Maryline C; Madsen, Steffen S; Tipsmark, Christian K

    2015-04-01

    In the present study, we examined the trout gill cell line RTgill-W1 as a possible tool for in vitro investigation of epithelial gill function in fish. After seeding in transwells, transepithelial resistance (TER) increased until reaching a plateau after 1-2 days (20-80Ω⋅cm(2)), which was then maintained for more than 6 days. Tetrabromocinnamic acid, a known stimulator of TER via casein kinase II inhibition, elevated TER in the cell line to 125% of control values after 2 and 6h. Treatment with ethylenediaminetetraacetic acid induced a decrease in TER to <15% of pre-treatment level. Cortisol elevated TER after 12-72 h in a concentration-dependent manner, and this increase was antagonized by growth hormone (Gh). The effects of three osmoregulatory hormones, Gh, prolactin, and cortisol, on the mRNA expression of three tight junction proteins were examined: claudin-10e (Cldn-10e), Cldn-30, and zonula occludens-1 (Zo-1). The expression of cldn-10e was stimulated by all three hormones but with the strongest effect of Gh (50-fold). cldn-30 expression was stimulated especially by cortisol (20-fold) and also by Gh (4-fold). Finally, zo-1 was unresponsive to hormone treatment. Western blot analysis detected Cldn-10e and Cldn-30 immunoreactive proteins of expected molecular weight in samples from rainbow trout gills but not from RTgill-W1 cultures, possibly due to low expression levels. Collectively, these results show that the RTgill-W1 cell layers have tight junctions between cells, are sensitive to hormone treatments, and may provide a useful model for in vitro study of some in vivo gill phenomena.

  3. Claudins in a primary cultured puffer fish (Tetraodon nigroviridis) gill epithelium model alter in response to acute seawater exposure.

    PubMed

    Bui, Phuong; Kelly, Scott P

    2015-11-01

    Gill epithelium permeability and qualitative/quantitative aspects of gill claudin (cldn) tight junction (TJ) protein transcriptomics were examined with a primary cultured model gill epithelium developed using euryhaline puffer fish (Tetraodon nigroviridis) gills. The model was prepared using seawater-acclimated fish gills and was cultured on permeable cell culture filter supports. The model is composed of 1-2 confluent layers of gill pavement cells (PVCs), with the outer layer exhibiting prominent apical surface microridges and TJs between adjacent cells. During development of electrophysiological characteristics, the model exhibits a sigmoidal increase in transpithelial resistance (TER) and plateaus around 30 kΩcm(2). At this point paracellular movement of [(3)H]polyethylene glycol (PEG) 4000 was low at ~1.75 cm s(-1)×10(-7). When exposed to apical seawater (SW) epithelia exhibit a marked decrease in TER while PEG flux remained unchanged for at least 6 h. In association with this, transcript encoding cldn TJ proteins cldn3c, -23b, -27a, -27c, -32a and -33b increased during the first 6 h while cldn11a decreased. This suggests that these proteins are involved in maintaining barrier properties between gill PVCs of SW fishes. Gill cldn mRNA abundance also altered 6 and 12 h following abrupt SW exposure of puffer fish, but in a manner that differed qualitatively and quantitatively from the cultured model. This most likely reflects the cellular heterogeneity of whole tissue and/or the contribution of the endocrine system in intact fish. The current study provides insight into the physiological and transcriptomic response of euryhaline fish gill cells to a hyperosmotic environment.

  4. Claudins in a primary cultured puffer fish (Tetraodon nigroviridis) gill epithelium model alter in response to acute seawater exposure.

    PubMed

    Bui, Phuong; Kelly, Scott P

    2015-11-01

    Gill epithelium permeability and qualitative/quantitative aspects of gill claudin (cldn) tight junction (TJ) protein transcriptomics were examined with a primary cultured model gill epithelium developed using euryhaline puffer fish (Tetraodon nigroviridis) gills. The model was prepared using seawater-acclimated fish gills and was cultured on permeable cell culture filter supports. The model is composed of 1-2 confluent layers of gill pavement cells (PVCs), with the outer layer exhibiting prominent apical surface microridges and TJs between adjacent cells. During development of electrophysiological characteristics, the model exhibits a sigmoidal increase in transpithelial resistance (TER) and plateaus around 30 kΩcm(2). At this point paracellular movement of [(3)H]polyethylene glycol (PEG) 4000 was low at ~1.75 cm s(-1)×10(-7). When exposed to apical seawater (SW) epithelia exhibit a marked decrease in TER while PEG flux remained unchanged for at least 6 h. In association with this, transcript encoding cldn TJ proteins cldn3c, -23b, -27a, -27c, -32a and -33b increased during the first 6 h while cldn11a decreased. This suggests that these proteins are involved in maintaining barrier properties between gill PVCs of SW fishes. Gill cldn mRNA abundance also altered 6 and 12 h following abrupt SW exposure of puffer fish, but in a manner that differed qualitatively and quantitatively from the cultured model. This most likely reflects the cellular heterogeneity of whole tissue and/or the contribution of the endocrine system in intact fish. The current study provides insight into the physiological and transcriptomic response of euryhaline fish gill cells to a hyperosmotic environment. PMID:26239219

  5. Generation of specific monoclonal antibodies against the extracellular loops of human claudin-3 by immunizing mice with target-expressing cells.

    PubMed

    Ando, Hiroshi; Suzuki, Masayo; Kato-Nakano, Mariko; Kawamoto, Shinobu; Misaka, Hirofumi; Kimoto, Naoya; Furuya, Akiko; Nakamura, Kazuyasu

    2015-01-01

    Human claudin-3 (CLDN3) is a tetraspanin transmembrane protein of tight junction structures and is known to be over-expressed in some malignant tumors. Although a specific monoclonal antibody (MAb) against the extracellular domains of CLDN3 would be a valuable tool, generation of such MAbs has been regarded as difficult using traditional hybridoma techniques, because of the conserved sequence homology of CLDN3s among various species. In addition, high sequence similarity is shared among claudin family members, and potential cross-reactivity of MAb should be evaluated carefully. To overcome these difficulties, we generated CLDN3-expressing Chinese hamster ovary and Sf9 cells to use an immunogens and performed cell-based screening to eliminate cross-reactive antibodies. As a result, we generated MAbs that recognized the extracellular loops of CLDN3 but not those of CLDN4, 5, 6, or 9. Further in vitro studies suggested that the isolated MAbs possessed the desired binding properties for the detection or targeting of CLDN3. PMID:25744656

  6. MicroRNA 29 Targets Nuclear Factor-κB–Repressing Factor and Claudin 1 to Increase Intestinal Permeability

    PubMed Central

    Zhou, QiQi; Costinean, Stefan; Croce, Carlo M.; Brasier, Alan R.; Merwat, Shehzad; Larson, Scott A.; Basra, Sarpreet; Verne, G. Nicholas

    2014-01-01

    BACKGROUND & AIMS Some patients with irritable bowel syndrome with diarrhea (IBS-D) have intestinal hyperpermeability, which contributes to their diarrhea and abdominal pain. MicroRNA 29 (MIR29) regulates intestinal permeability in patients with IBS-D. We investigated and searched for targets of MIR29 and investigated the effects of disrupting Mir29 in mice. METHODS We investigated expression MIR29A and B in intestinal biopsies collected during endoscopy from patients with IBS (n = 183) and without IBS (controls) (n = 36). Levels were correlated with disease phenotype. We also generated and studied Mir29−/− mice, in which expression of Mir29a and b, but not c, is lost. Colitis was induced by administration of 2,4,6-trinitrobenzenesulfonic acid; intestinal tissues were collected and permeability was assessed. Microarray analysis was performed using tissues from Mir29−/− mice. Changes in levels of target genes were measured in human colonic epithelial cells and small intestinal epithelial cells after knockdown of MIR29 with anti-MIRs. RESULTS Intestinal tissues from patients with IBS-D (but not IBS with constipation or controls) had increased levels of MIR29A and B, but reduced levels of Claudin-1 (CLDN1) and nuclear factor-κB–repressing factor (NKRF). Induction of colitis and water avoidance stress increased levels of Mir29a and Mir29b and intestinal permeability in wild-type mice; these increased intestinal permeability in colons of far fewer Mir29−/− mice. In microarray and knockdown experiments, MIR29A and B were found to reduce levels of NKRF and CLDN1 messenger RNA, and alter levels of other messenger RNAs that regulate intestinal permeability. CONCLUSIONS Based on experiments in knockout mice and analyses of intestinal tissue samples from patients with IBS-D, MIR29 targets and reduces expression of CLDN1 and NKRF to increase intestinal permeability. Strategies to block MIR29 might be developed to restore intestinal permeability in patients with

  7. Effects of lactadherin on plasma D-lactic acid and small intestinal MUC2 and claudin-1 expression levels in rats with rotavirus-induced diarrhea

    PubMed Central

    XU, RUI; LEI, YI-HUI; SHI, JUN; ZHOU, YI-JUN; CHEN, YING-WEI; HE, ZHEN-JUAN

    2016-01-01

    The aim of the present study was to investigate the effects of lactadherin on plasma D-lactic acid and small intestinal mucin (MUC) 2 and claudin-1 expression levels in rats with diarrhea induced by rotavirus (RV) infection. A total of 75 seven-day-old healthy Sprague-Dawley rats were randomly divided into the following five groups: Control (C), RV infection (RVI), lactadherin before rotavirus infection (LBRI), lactadherin after rotavirus infection (LARI), and blank (B). On day 4 of artificial feeding, the rats in groups RVI, LBRI and LARI were intragastric administered 1×106 PFU RV; whereas the rats in groups C and B were intragastrically administered an equal volume of maintenance solution from the RV supernatant and normal saline, respectively. In the LBRI and LARI groups, rats received daily intragastric administration of 0.25 mg lactadherin for three days prior to and following infection with RV, respectively. The course of diarrheal symptoms was observed in each group and samples were collected on days 1, 4, and 7 post-infection in order to determine the mucosal morphology, plasma D-lactic acid levels and the expression levels of MUC2 and the intracellular junction protein, claudin-1, in the small intestine. On day 4 post-infection, the rats in group RVI demonstrated severely damaged small intestines and typical diarrheal characteristics, as detected by light microscopy; whereas rats in groups LBRI and LARI demonstrated intact small intestinal villi with partial vacuolation of epithelial cells and changes in the position of their nuclei. Electron microscopy demonstrated that the rats in the RVI group had sparse, shortened, disordered intestinal microvilli and widened intercellular junctions; whereas those in groups LBRI and LARI had long intestinal microvilli sparser compared with groups B and C and slightly widened intercellular junctions. Plasma D-lactic acid levels were increased in groups RVI, LBRI and LARI, as compared with groups B and C, and the

  8. Connexins, E-cadherin, Claudin-7 and β-catenin transiently form junctional nexuses during the post-natal mammary gland development.

    PubMed

    Dianati, Elham; Poiraud, Jérémy; Weber-Ouellette, Anne; Plante, Isabelle

    2016-08-01

    Gap junctions are intercellular channels made of connexins (Cxs) that allow direct communication between adjacent cells. Modulation of Cxs has been associated with abnormal development and function of the mammary gland and breast cancer. However, the mechanisms underlying their expression during normal mammary gland are not yet known. Cxs interact with components of tight and adherens junctions. Thus, we hypothesized that the expression levels of Cxs vary during mammary gland development and are regulated through stage-dependent interactions with members of the tight and adherens junctions. Our specific objectives were to: 1) determine the expression of Cxs and tight and adherens junction proteins throughout development and 2) characterize Cxs interactions with components of tight and adherens junctions. Murine mammary glands were sampled at various developmental stages (pre-pubescent to post-weaning). RT-qPCR and western-blot analyses demonstrated differential expression patterns for all gap (Cx43, Cx32, Cx26, Cx30), tight (Claudin-1, -3, -4, -7) and adherens (β-catenin, E- and P-cadherins) junctions throughout development. Interestingly, co-immunoprecipitation demonstrated interactions between these different types of junctions. Cx30 interacted with Cx26 just at the late pregnancy stage. While Cx43 showed a persistent interaction with β-catenin from virginity to post-weaning, its interactions with E-cadherin and Claudin-7 were transient. Cx32 interacted with Cx26, E-cadherin and β-catenin during lactation. Immunofluorescence results confirmed the existence of a junctional nexus that remodeled during mammary gland development. Together, our results confirm that the expression levels of Cxs vary concomitantly and that Cxs form junctional nexuses with tight and adherens junctions, suggesting the existence of common regulatory pathways.

  9. Expression of TM4SF10, a Claudin/EMP/PMP22 family cell junction protein, during mouse kidney development and podocyte differentiation.

    PubMed

    Bruggeman, Leslie A; Martinka, Scott; Simske, Jeffrey S

    2007-02-01

    Cell junctions in the nephron are highly specialized to perform specific and distinct filtration and reabsorption functions. The mature kidney forms complex cell junctions including slit diaphragms that prevent the passage of serum proteins into the filtrate, and tubule cell junctions that regulate specific paracellular ion reuptake. We have investigated the expression of TM4SF10 (Trans-Membrane tetra(4)-Span Family 10) in mouse kidneys. TM4SF10 is the vertebrate orthologue of Caenorhabditis elegans VAB-9, a tetraspan adherens junction protein in the PMP22/EMP/Claudin family of proteins. We found that TM4SF10 localizes at the basal-most region of podocyte precursors before the capillary loop stage, at some tubule precursors, and at the ureteric bud junction with S-shaped bodies. Overall expression of TM4SF10 peaked at postnatal day 4 and was virtually absent in adult kidneys. The very limited expression of TM4SF10 protein that persisted into adulthood was restricted to a few tubule segments but remained localized to the basal region of lateral membranes. In undifferentiated cultured podocytes, TM4SF10 localized to the perinuclear region and translocated to the cell membrane after Cadherin appearance at cell-cell contacts. TM4SF10 colocalized with ZO1 and p120ctn in undifferentiated confluent podocytes and also colocalized with the tips of actin filaments at cell contacts. Upon differentiation of cultured podocytes, TM4SF10 protein disappeared from cell contacts and expression ceased. These results suggest that TM4SF10 functions during differentiation of podocytes and may participate in the maturation of cell junctions from simple adherens junctions to elaborate slit diaphragms. TM4SF10 may define a new class of Claudin-like proteins that function during junctional development.

  10. Métallurgie fondamentale et métallurgie numérique : l'héritage de Jacques Friedel dans la théorie de la plasticité des métaux et alliages

    NASA Astrophysics Data System (ADS)

    Bréchet, Yves

    2016-03-01

    Jacques Friedel's contribution to the theory of plasticity is described, as well as the more recent developments it inspired. It involves the microscopic properties of dislocations as well as macroscopic effects. The evolution of fundamental metallurgy toward numerical metallurgy is discussed, and Friedel's point of view on numerical methods is analyzed.

  11. The novel Arrowsmith, Paul de Kruif (1890-1971) and Jacques Loeb (1859-1924): a literary portrait of "medical science".

    PubMed

    Fangerau, H M

    2006-12-01

    Shortly after bacteriologist Paul de Kruif had been dismissed from a research position at the Rockefeller Institute for Medical Research, he started contributing to a novel in collaboration with the future Nobel laureate Sinclair Lewis. The novel, Arrowsmith, would become one of the most famous satires on medicine and science. Using de Kruif's correspondence with his idol Jacques Loeb, this paper describes the many ways in which medical science is depicted in Arrowsmith. This article compares the novel with de Kruif's and Loeb's biographies, and (1) focuses on the struggles of the main character, Martin Arrowsmith, as an allegory of the institutionalisation of medical research in the US, (2) shows that (influenced by de Kruif) Sinclair's purpose is to caricaturise scientific work in modern medical research institutions anywhere and (3) shows that the novel depicts a reductionist philosophy of research that seems to contradict the "messiness" of medical practice.

  12. Jacques Loeb (1859-1924) and His Forgotten Contributions to Electrolyte and Acid-Base Physiology in The Organism as a Whole.

    PubMed

    Sgambato, Francesco; Sgambato, Ester; De Santo, Natale Gaspare

    2016-02-01

    Jacques Loeb (1859-1924) was the founder of the Journal of General Physiology which he co-directed in association with W.J.V. Osterhout in the years 1918-1924. Having worked (1889-1891)at the Marine Zoological Station of Naples, newly founded by Anton Dohrn, he was imprinted for life. A strong investigator used to perform the experiments personally. Loeb was engaged lifelong in the explanation of life on physico-chemical basis. He touched various fields (being a creative scientist full of ideas), and centered on the exchanges of electrolytes, acids and bases between the body and sea water in fish. He identified two equations: {[K+]+[Na+]}: {[Ca++]+[Mg++]} (Loebs 1st equation) {[K+]+[Na+]}: {[H+]+[Ca++]+[Mg++]} (Loebs final equation) Even nowadays these equations may have applications in a wide list of electrolyte and acid-base disturbances. Unfortunately his heredity has been dissipated.

  13. Dehydroepiandrosterone Sulfate Stimulates Expression of Blood-Testis-Barrier Proteins Claudin-3 and -5 and Tight Junction Formation via a Gnα11-Coupled Receptor in Sertoli Cells

    PubMed Central

    Papadopoulos, Dimitrios; Dietze, Raimund; Shihan, Mazen; Kirch, Ulrike; Scheiner-Bobis, Georgios

    2016-01-01

    Dehydroepiandrosterone sulfate (DHEAS) is a circulating sulfated steroid considered to be a pro-androgen in mammalian physiology. Here we show that at a physiological concentration (1 μM), DHEAS induces the phosphorylation of the kinase Erk1/2 and of the transcription factors CREB and ATF-1 in the murine Sertoli cell line TM4. This signaling cascade stimulates the expression of the tight junction (TJ) proteins claudin-3 and claudin-5. As a consequence of the increased expression, tight junction connections between neighboring Sertoli cells are augmented, as demonstrated by measurements of transepithelial resistance. Phosphorylation of Erk1/2, CREB, or ATF-1 is not affected by the presence of the steroid sulfatase inhibitor STX64. Erk1/2 phosphorylation was not observed when dehydroepiandrosterone (DHEA) was used instead of DHEAS. Abrogation of androgen receptor (AR) expression by siRNA did not affect DHEAS-stimulated Erk1/2 phosphorylation, nor did it change DHEAS-induced stimulation of claudin-3 and claudin-5 expression. All of the above indicate that desulfation and conversion of DHEAS into a different steroid hormone is not required to trigger the DHEAS-induced signaling cascade. All activating effects of DHEAS, however, are abolished when the expression of the G-protein Gnα11 is suppressed by siRNA, including claudin-3 and -5 expression and TJ formation between neighboring Sertoli cells as indicated by reduced transepithelial resistance. Taken together, these results are consistent with the effects of DHEAS being mediated through a membrane-bound G-protein-coupled receptor interacting with Gnα11 in a signaling pathway that resembles the non-classical signaling pathways of steroid hormones. Considering the fact that DHEAS is produced in reproductive organs, these findings also suggest that DHEAS, by acting as an autonomous steroid hormone and influencing the formation and dynamics of the TJ at the blood-testis barrier, might play a crucial role for the

  14. Keratin 8 and 18 Loss in Epithelial Cancer Cells Increases Collective Cell Migration and Cisplatin Sensitivity through Claudin1 Up-regulation*

    PubMed Central

    Fortier, Anne-Marie; Asselin, Eric; Cadrin, Monique

    2013-01-01

    Keratins 8 and 18 (K8/18) are simple epithelial cell-specific intermediate filament proteins. Keratins are essential for tissue integrity and are involved in intracellular signaling pathways that regulate cell response to injuries, cell growth, and death. K8/18 expression is maintained during tumorigenesis; hence, they are used as a diagnostic marker in tumor pathology. In recent years, studies have provided evidence that keratins should be considered not only as markers but also as regulators of cancer cell signaling. The loss of K8/18 expression during epithelial-mesenchymal transition (EMT) is associated with metastasis and chemoresistance. In the present study, we investigated whether K8/18 expression plays an active role in EMT. We show that K8/18 stable knockdown using shRNA increased collective migration and invasiveness of epithelial cancer cells without modulating EMT markers. K8/18-depleted cells showed PI3K/Akt/NF-κB hyperactivation and increased MMP2 and MMP9 expression. K8/18 deletion also increased cisplatin-induced apoptosis. Increased Fas receptor membrane targeting suggests that apoptosis is enhanced via the extrinsic pathway. Interestingly, we identified the tight junction protein claudin1 as a regulator of these processes. This is the first indication that modulation of K8/18 expression can influence the phenotype of epithelial cancer cells at a transcriptional level and supports the hypothesis that keratins play an active role in cancer progression. PMID:23449973

  15. Prostaglandin E2 Produced by Entamoeba histolytica Signals via EP4 Receptor and Alters Claudin-4 to Increase Ion Permeability of Tight Junctions

    PubMed Central

    Lejeune, Manigandan; Moreau, France; Chadee, Kris

    2011-01-01

    Entamoeba histolytica is a protozoan parasite that causes amebic dysentery characterized by severe watery diarrhea. Unfortunately, the parasitic factors involved in the pathogenesis of diarrhea are poorly defined. Prostaglandin E2 (PGE2) is a host lipid mediator associated with diarrheal diseases. Intriguingly, E. histolytica produces and secretes this inflammatory molecule. We investigated the mechanism whereby ameba-derived PGE2 induces the onset of diarrhea by altering ion permeability of paracellular tight junctions (TJs) in colonic epithelia. PGE2 decreased barrier integrity of TJs in a dose- and time-dependent manner, as measured by transepithelial resistance. PGE2 signals were selectively transduced via the EP4 receptor. Furthermore, PGE2 signaling decreased TJ integrity, as revealed by EP receptor-specific agonist and antagonist studies. Loss of mucosal barrier integrity corresponded with increased ion permeability across TJs. Subcellular fractionation and confocal microscopy studies highlighted a significant spatial alteration of an important TJ protein, claudin-4, that corresponded with increased sodium ion permeability through TJs toward the lumen. Moreover, PGE2-induced luminal chloride secretion was a prerequisite for alterations at TJs. Thus, the gradient of NaCl created across epithelia could serve as a trigger for osmotic water flow that leads to diarrhea. Our results highlight a pathological role for E. histolytica-derived PGE2 in the onset of diarrhea. PMID:21683675

  16. Jacques Forestier's vanished bowstring sign in ankylosing spondylitis: a call to test its validity and possible relation to spinal myofascial hypertonicity.

    PubMed

    Masi, A T; Sierakowski, S; Kim, J M

    2005-01-01

    Jacques Forestier's bowstring sign (signe de la "corde de l'arc") in ankylosing spondylitis (AS) was described by him in his 1951 book (French). In free lateral bending, the early AS patient has palpably firm, contracted dorsolumbar muscles on the concave side, opposite to the findings in normals. Forestier described this sign as a common and characteristic finding in AS. Perplexingly, the sign is essentially unknown in the rheumatologic field. A single report (Polish) on electromyographic (EMG) findings in AS and control subjects documented the electromotor component of the bowstring sign as well as its diagnostic utility in early AS patients. In this paper, the literature on EMG studies in series of AS patients is reviewed as well as kinesiologic EMG studies of normals in lateral bending. Paravertebral and other muscle pathology in AS was reviewed in relation to the EMG findings. Critical, controlled assessment of Forestier's bowstring sign and biomechanical investigations of the dorsolumbar muscles in AS promise to offer new insights into the early physiopathogenesis of this unique disease.

  17. 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

    SciTech Connect

    Carette, Diane; Perrard, Marie-Hélène; Prisant, Nadia; Gilleron, Jérome; Pointis, Georges; Segretain, Dominique; Durand, Philippe

    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.

  18. Comparable mRNA expression of inflammatory markers but lower claudin-1 mRNA levels in foreskin tissue of HSV-2 seropositive versus seronegative asymptomatic Kenyan young men

    PubMed Central

    Röhl, Maria; Tjernlund, Annelie; Mehta, Supriya D; Pettersson, Pernilla; Bailey, Robert C; Broliden, Kristina

    2015-01-01

    Objectives Skin biopsies from local sites of herpes simplex virus 2 (HSV-2)-induced ulcers can show infiltrates of inflammatory cells several months after macroscopic healing. We hypothesise that foreskin tissue samples of asymptomatic HSV-2 seropositive men had remaining signs of inflammation at the molecular level. Even in the absence of clinical lesions, genital inflammation may contribute to increased HIV susceptibility on sexual exposure to the virus. Setting Foreskin tissue samples were collected from men undergoing elective circumcision in Kisumu, Kenya. Participants The foreskin tissue samples (n=86) were stratified into study groups based on HSV-2 serology and assessed for mRNA expression of inflammatory markers. Markers of interest were further assessed by immunohistochemical staining within the tissue samples. Results The two study groups had comparable levels of all molecular markers (CD3, CD4, CD8, CD69, CCR5, HLA-DR, Langerin, DC-SIGN, Mannose Receptor 1, IL-1, IL-6, TNF-α, β7, IgA, IFN-α, CCL5, E-cadherin, ZO-1 and occludin), except for lower mRNA levels of the epithelial junction protein claudin-1 in the HSV-2 seropositive group (p=0.008). Although mRNA levels of claudin-1 were lower in HSV-2 seropositive individuals, the corresponding protein could be visualised in the foreskin epithelium of all samples tested. Conclusions Whereas no general inflammation was demonstrated in the foreskin of asymptomatic HSV-2 seropositive individuals, a decreased expression of claudin-1 indicates a less robust genital epithelial barrier. An intact epithelial barrier is essential for blocking mucosal entry of genital infections, including HIV. PMID:25694458

  19. Genome-wide DNA methylation identifies trophoblast invasion-related genes: Claudin-4 and Fucosyltransferase IV control mobility via altering matrix metalloproteinase activity.

    PubMed

    Hu, Yuxiang; Blair, John D; Yuen, Ryan K C; Robinson, Wendy P; von Dadelszen, Peter

    2015-05-01

    Previously we showed that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were affected by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450 K array). We identified 444 differentially methylated CpG loci in dNK-treated EVT compared with medium control (P < 0.05). The genes associated with these loci had critical biological roles in cellular development, cellular growth and proliferation, cell signaling, cellular assembly and organization by Ingenuity Pathway Analysis (IPA). Furthermore, 23 mobility-related genes were identified by IPA from dNK-treated EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltransferase IV) were chosen for follow-up studies because of their biological relevance from research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced compared with control (P < 0.01 for both CLDN4 and FUT4 mRNA expression; P < 0.001 for CLDN4 and P < 0.01 for FUT4 protein expression), and were inversely correlated with DNA methylation. Knocking down CLDN4 and FUT4 by small interfering RNA reduced trophoblast invasion, possibly through the altered matrix metalloproteinase (MMP)-2 and/or MMP-9 expression and activity. Taken together, dNK alter EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduces protein expression. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility. PMID:25697377

  20. Mitochondrial Respiratory Dysfunction Induces Claudin-1 Expression via Reactive Oxygen Species-mediated Heat Shock Factor 1 Activation, Leading to Hepatoma Cell Invasiveness*

    PubMed Central

    Lee, Jong-Hyuk; Lee, Young-Kyoung; Lim, Jin J.; Byun, Hae-Ok; Park, Imkyong; Kim, Gyeong-Hyeon; Xu, Wei Guang; Wang, Hee-Jung; Yoon, Gyesoon

    2015-01-01

    Although mitochondrial dysfunction has been implicated in tumor metastasis, it is unclear how it regulates tumor cell aggressiveness. We have reported previously that human hepatoma cells harboring mitochondrial defects have high tumor cell invasion activity via increased claudin-1 (Cln-1) expression. In this study, we demonstrated that mitochondrial respiratory defects induced Cln-1 transcription via reactive oxygen species (ROS)-mediated heat shock factor 1 (HSF1) activation, which contributed to hepatoma invasiveness. We first confirmed the inverse relationship between mitochondrial defects and Cln-1 induction in SNU hepatoma cells and hepatocellular carcinoma tissues. We then examined five different respiratory complex inhibitors, and complex I inhibition by rotenone most effectively induced Cln-1 at the transcriptional level. Rotenone increased both mitochondrial and cytosolic ROS. In addition, rotenone-induced Cln-1 expression was attenuated by N-acetylcysteine, an antioxidant, and exogenous H2O2 treatment was enough to increase Cln-1 transcription, implying the involvement of ROS. Next we found that ROS-mediated HSF1 activation via hyperphosphorylation was the key event for Cln-1 transcription. Moreover, the Cln-1 promoter region (from −529 to +53) possesses several HSF1 binding elements, and this region showed increased promoter activity and HSF1 binding affinity in response to rotenone treatment. Finally, we demonstrated that the invasion activity of SNU449 cells, which harbor mitochondrial defects, was blocked by siRNA-mediated HSF1 knockdown. Taken together, these results indicate that mitochondrial respiratory defects enhance Cln-1-mediated hepatoma cell invasiveness via mitochondrial ROS-mediated HSF1 activation, presenting a potential role for HSF1 as a novel mitochondrial retrograde signal-responsive transcription factor to control hepatoma cell invasiveness. PMID:26157141

  1. Omega-3-Acid Ethyl Esters Block the Pro-tumorigenic Effects of Obesity in Mouse Models of Postmenopausal Basal-Like and Claudin-Low Breast Cancer

    PubMed Central

    Ford, Nikki A.; Rossi, Emily L.; Barnett, Kelsey; Yang, Peiying; Bowers, Laura W.; Hidaka, Brandon H.; Kimler, Bruce F.; Carlson, Susan E.; Shureiqi, Imad; deGraffenried, Linda A.; Fabian, Carol J.; Hursting, Stephen D.

    2015-01-01

    Obesity induces chronic inflammation and is an established risk and progression factor for triple-negative breast cancers, including basal-like (BL) and claudin-low (CL) subtypes. We tested the effects of dietary supplementation with ethyl esters of the marine-derived anti-inflammatory omega-3 fatty acids eicosapentaenoic and docosahexaenoic acid (EPA+DHA; Lovaza®) on growth of murine BL and CL mammary tumors. Female ovariectomized C57BL/6 mice were fed a control diet or a diet-induced obesity (DIO) diet with or without EPA+DHA (0.025%, resulting in blood levels of EPA and DHA comparable to women taking Lovaza 4 g/day) for 6 weeks. All mice were then orthotopically injected with Wnt-1 cells (a BL tumor cell suspension derived from MMTV-Wnt-1 transgenic mouse mammary tumors) or M-Wnt cells (a CL tumor cell line cloned from the Wnt-1 tumor cell suspension). Mice were killed when tumors were 1 cm in diameter. EPA+DHA supplementation did not significantly impact Wnt-1 or M-Wnt mammary tumor growth in normoweight control mice. However, EPA+DHA supplementation in DIO mice reduced growth of Wnt-1 and M-Wnt tumors; reduced leptin:adiponectin ratio and pro-inflammatory eicosanoids in the serum; improved insulin sensitivity; and decreased tumoral expression of cyclooxygenase-2 and phospho-p65. Thus, EPA+DHA supplementation in mouse models of postmenopausal BL and CL breast cancer offsets many of the pro-tumorigenic effects of obesity. These preclinical findings, in combination with results from parallel biomarker studies in women, suggest EPA+DHA supplementation may reduce the burden of BL and CL breast cancer in obese women. PMID:26100521

  2. Genome-wide DNA methylation identifies trophoblast invasion-related genes: Claudin-4 and Fucosyltransferase IV control mobility via altering matrix metalloproteinase activity

    PubMed Central

    Hu, Yuxiang; Blair, John D.; Yuen, Ryan K.C.; Robinson, Wendy P.; von Dadelszen, Peter

    2015-01-01

    Previously we showed that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were affected by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450 K array). We identified 444 differentially methylated CpG loci in dNK-treated EVT compared with medium control (P < 0.05). The genes associated with these loci had critical biological roles in cellular development, cellular growth and proliferation, cell signaling, cellular assembly and organization by Ingenuity Pathway Analysis (IPA). Furthermore, 23 mobility-related genes were identified by IPA from dNK-treated EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltransferase IV) were chosen for follow-up studies because of their biological relevance from research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced compared with control (P < 0.01 for both CLDN4 and FUT4 mRNA expression; P < 0.001 for CLDN4 and P < 0.01 for FUT4 protein expression), and were inversely correlated with DNA methylation. Knocking down CLDN4 and FUT4 by small interfering RNA reduced trophoblast invasion, possibly through the altered matrix metalloproteinase (MMP)-2 and/or MMP-9 expression and activity. Taken together, dNK alter EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduces protein expression. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility. PMID:25697377

  3. Genome-wide DNA methylation identifies trophoblast invasion-related genes: Claudin-4 and Fucosyltransferase IV control mobility via altering matrix metalloproteinase activity.

    PubMed

    Hu, Yuxiang; Blair, John D; Yuen, Ryan K C; Robinson, Wendy P; von Dadelszen, Peter

    2015-05-01

    Previously we showed that extravillous cytotrophoblast (EVT) outgrowth and migration on a collagen gel explant model were affected by exposure to decidual natural killer cells (dNK). This study investigates the molecular causes behind this phenomenon. Genome wide DNA methylation of exposed and unexposed EVT was assessed using the Illumina Infinium HumanMethylation450 BeadChip array (450 K array). We identified 444 differentially methylated CpG loci in dNK-treated EVT compared with medium control (P < 0.05). The genes associated with these loci had critical biological roles in cellular development, cellular growth and proliferation, cell signaling, cellular assembly and organization by Ingenuity Pathway Analysis (IPA). Furthermore, 23 mobility-related genes were identified by IPA from dNK-treated EVT. Among these genes, CLDN4 (encoding claudin-4) and FUT4 (encoding fucosyltransferase IV) were chosen for follow-up studies because of their biological relevance from research on tumor cells. The results showed that the mRNA and protein expressions of both CLDN4 and FUT4 in dNK-treated EVT were significantly reduced compared with control (P < 0.01 for both CLDN4 and FUT4 mRNA expression; P < 0.001 for CLDN4 and P < 0.01 for FUT4 protein expression), and were inversely correlated with DNA methylation. Knocking down CLDN4 and FUT4 by small interfering RNA reduced trophoblast invasion, possibly through the altered matrix metalloproteinase (MMP)-2 and/or MMP-9 expression and activity. Taken together, dNK alter EVT mobility at least partially in association with an alteration of DNA methylation profile. Hypermethylation of CLDN4 and FUT4 reduces protein expression. CLDN4 and FUT4 are representative genes that participate in modulating trophoblast mobility.

  4. Expression of claudins -2 and -4 and cingulin is coordinated with the start of stratification and differentiation in corneal epithelial cells: retinoic acid reversibly disrupts epithelial barrier

    PubMed Central

    Ortiz-Melo, María Teresa; Sánchez-Guzmán, Erika; González-Robles, Arturo; Valdés, Jesús; Gómez-Flores, Eber; Castro-Muñozledo, Federico

    2013-01-01

    Summary Although tight junctions (TJ) have been extensively studied in simple epithelial cells, it is still unknown whether their organization is coupled to cell differentiation in stratified epithelia. We studied the expression of TJ in RCE1(5T5) cells, an in vitro model which mimics the sequential steps of rabbit corneal epithelial differentiation. RCE1(5T5) cells expressed TJ components which were assembled once cells constituted differentiated epithelia, as suggested by the increase of transepithelial electrical resistance (TER) which followed a similar kinetic to the expression of the early differentiation marker Pax-6. TJ were functional as indicated by the establishment of an epithelial barrier nonpermeable to ruthenium red or a biotin tracer. In immunostaining experiments, TJ were located at the superficial cells from the suprabasal layers; Western blot and RT-PCR suggested that TJ were composed of claudins (cldn) -1, -2, -4, cingulin (cgn), occludin (ocln) and ZO-1. Semi-quantitative RT-PCR and TER measurements showed that TJ became organized when cells began to form a 3–5 layers stratified epithelium; TER increased once cells reached confluence, with a time course comparable to the raise in the expression of cgn, cldn-2 and -4. Nevertheless, cldn-1, -2, ZO-1 and ocln were present in the cells from the beginning of cultivation, suggesting that TER increases mainly depend on TJ assembly. While EGF increased epithelial barrier strength, retinoic acid disrupted it, increasing paracellular flux about 2-fold; this effect was concentration dependent and completely reversible. Our results suggest that TJ assembly is tightly linked to the expression of corneal epithelial terminal phenotype. PMID:23429425

  5. miR-7 and miR-218 epigenetically control tumor suppressor genes RASSF1A and Claudin-6 by targeting HoxB3 in breast cancer

    SciTech Connect

    Li, Qiaoyan; Zhu, Fufan; Chen, Puxiang

    2012-07-20

    Highlights: Black-Right-Pointing-Pointer Both miR-7 and miR-218 down-regulates HoxB3 expression by targeting the 3 Prime -UTR of HoxB3 mRNA. Black-Right-Pointing-Pointer A reverse correlation between the levels of endogenous miR-7, miR218 and HoxB3 expression. Black-Right-Pointing-Pointer Epigenetic changes involve in the reactivation of HoxB3. Black-Right-Pointing-Pointer Both miRNAs inhibits the cell cycle and clone formation of breast cancer cells. -- Abstract: Many microRNAs have been implicated as key regulators of cellular growth and differentiation and have been found to dysregulate proliferation in human tumors, including breast cancer. Cancer-linked microRNAs also alter the epigenetic landscape by way of DNA methylation and post-translational modifications of histones. Aberrations in Hox gene expression are important for oncogene or tumor suppressor during abnormal development and malignancy. Although recent studies suggest that HoxB3 is critical in breast cancer, the putative role(s) of microRNAs impinging on HoxB3 is not yet fully understood. In this study, we found that the expression levels of miR-7 and miR-218 were strongly and reversely associated with HoxB3 expression. Stable overexpression of miR-7 and miR-218 was accompanied by reactivation of tumor suppressor genes including RASSF1A and Claudin-6 by means of epigenetic switches in DNA methylation and histone modification, giving rise to inhibition of the cell cycle and clone formation of breast cancer cells. The current study provides a novel link between overexpression of collinear Hox genes and multiple microRNAs in human breast malignancy.

  6. A study protocol for quantitative targeted absolute proteomics (QTAP) by LC-MS/MS: application for inter-strain differences in protein expression levels of transporters, receptors, claudin-5, and marker proteins at the blood–brain barrier in ddY, FVB, and C57BL/6J mice

    PubMed Central

    2013-01-01

    Proteomics has opened a new horizon in biological sciences. Global proteomic analysis is a promising technology for the discovery of thousands of proteins, post-translational modifications, polymorphisms, and molecular interactions in a variety of biological systems. The activities and roles of the identified proteins must also be elucidated, but this is complicated by the inability of conventional proteomic methods to yield quantitative information for protein expression. Thus, a variety of biological systems remain “black boxes”. Quantitative targeted absolute proteomics (QTAP) enables the determination of absolute expression levels (mol) of any target protein, including low-abundance functional proteins, such as transporters and receptors. Therefore, QTAP will be useful for understanding the activities and roles of individual proteins and their differences, including normal/disease, human/animal, or in vitro/in vivo. Here, we describe the study protocols and precautions for QTAP experiments including in silico target peptide selection, determination of peptide concentration by amino acid analysis, setup of selected/multiple reaction monitoring (SRM/MRM) analysis in liquid chromatography–tandem mass spectrometry, preparation of protein samples (brain capillaries and plasma membrane fractions) followed by the preparation of peptide samples, simultaneous absolute quantification of target proteins by SRM/MRM analysis, data analysis, and troubleshooting. An application of QTAP in biological sciences was introduced that utilizes data from inter-strain differences in the protein expression levels of transporters, receptors, tight junction proteins and marker proteins at the blood–brain barrier in ddY, FVB, and C57BL/6J mice. Among 18 molecules, 13 (abcb1a/mdr1a/P-gp, abcc4/mrp4, abcg2/bcrp, slc2a1/glut1, slc7a5/lat1, slc16a1/mct1, slc22a8/oat3, insr, lrp1, tfr1, claudin-5, Na+/K+-ATPase, and γ-gtp) were detected in the isolated brain capillaries, and their

  7. A New Logic of Emancipation: The Methodology of Jacques Ranciere

    ERIC Educational Resources Information Center

    Biesta, Gert

    2010-01-01

    The idea of emancipation plays a central role in modern educational theories and practices. The emancipatory impetus is particularly prominent in critical traditions and approaches where the aim of education is conceived as that of emancipating students from oppressive structures in the name of social justice and human freedom. What is needed to…

  8. Jacques Friedel and the physics of metals and alloys

    NASA Astrophysics Data System (ADS)

    Villain, Jacques; Lavagna, Mireille; Bruno, Patrick

    2016-03-01

    This is an introduction to the theoretical physics of metals for students and physicists from other specialities. Certain simple consequences of the Fermi statistics in pure metals are first addressed, namely the Peierls distortion, Kohn anomalies and the Labbé-Friedel distortion. Then the physics of dilute alloys is discussed. The analogy with nuclear collisions was a fruitful starting point, which suggested one should analyze the effects of impurities in terms of a scattering problem with the introduction of phase shifts. Starting from these concepts, Friedel derived a theory of the resistivity of alloys, and a celebrated sum rule relating the phase shifts at the Fermi level to the number of electrons in the impurity, which turned out to play a prominent role later in the context of correlated impurities, as for instance in the Kondo effect. Friedel oscillations are also an important result, related to incommensurate magnetic structures. It is shown how they can be derived in various ways: from collision theory, perturbation theory, self-consistent approximations and Green's function methods. While collision theory does not permit to take the crystal structure into account, which is responsible for electronic bands, those effects can be included in other descriptions, using for instance the tight binding approximation. xml:lang="fr"

  9. Alain Badiou, Jacques Lacan and the Ethics of Teaching

    ERIC Educational Resources Information Center

    Taubman, Peter M.

    2010-01-01

    This paper argues that Badiou's and Lacan's theorizations of ethics offer a way to formulate an ethics of teaching and to explore what such an ethics might look like when teachers encounter events that disrupt their quotidian lives. Relying on the work of Badiou and Lacan, the paper critiques mainstream approaches to the ethics of teaching and…

  10. Jean-Jacques Rousseau's views on adult education

    NASA Astrophysics Data System (ADS)

    Dame, Frederick William

    1996-01-01

    Although Rousseau describes in Émile only his scheme for childhood education, he presents us in this work with some direct statements which can be applied to explain more fully the nature of adult education. The author surveys Rousseau's ideas on the role of the general will in adult educational philosophy, subject matter, methodology and negative education, as well as the relationships between the family, student, teacher, community and the state. He concludes that the modern Rousseau would not limit education to males and would recognize that the four Rousseauian periods of educational development — infancy, childhood, youngster, adolescence — is followed by a fifth: adulthood. Adult education is the logical continuation of the four previous phases. Throughout each phase education must permit intellectual and moral growth and always allow for creativity and diversity. Only then can adults become positive contributors to their society.

  11. Crew training in weightless environment on the KC-135

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Payload specialists Patrick Baudry (right) and Jean Loup Chretien are floating over the aircraft seats in weightlessness provided by the KC-135 (26145); Baudry, center right, and Chretien are pictured between sessions of weightlessness provided by a parabolic pattern flown by the KC-135. The two watch technicians prepare an experiment to be monitored during an upcoming session of weightlessness (26146); Baudry floating in weighlessnes provided by the KC-135 (26147).

  12. Education in the Realm of the Senses: Understanding Paulo Freire's Aesthetic Unconscious through Jacques Ranciere

    ERIC Educational Resources Information Center

    Lewis, Tyson Edward

    2009-01-01

    In this article I re-examine the role that aesthetics play in Paulo Freire's pedagogy of the oppressed. As opposed to the vast majority of scholarship in this area, I suggest that aesthetics play a more centralised role in pedagogy above and beyond arts-based curricula. To help clarify Freire's position, I will argue that underlying the linguistic…

  13. [Jacques Clarion (1776-1844), professor of l'Ecole de pharmacie de Paris].

    PubMed

    Trépardoux, Francis

    2006-11-01

    Engaged in military campaigns from 1793 to 1797, he then studied medicine in Paris, as well as pharmacy, specialised in chemistry and botany. Supported by Deyeux and Corvisart, he was nominated as pharmacist of the emperor. From 1819 to 1844, he taught botany at the School of pharmacy of Paris. In 1823, the authority gave him a second chair for the medical botany at the Faculty of medicine, but after the 1830 revolution, he was dismissed. He mainly worked in taxonomy, contributing to several publications with Palisot and de Candolle for Graminaceae. He was a member of the academy of medicine.

  14. [Jacques Lacan: The turn of the Obligado or the return of the unavoidable].

    PubMed

    Harari, R

    1976-09-01

    "La Vuelta de Obligado" (Obligado bend of Paraná river) is the name of a battle fought by local rebels against the colonial invading navy. The victory was due to a witty device: the patriots stretched a cable across the river and succeded in stopping the foreign float. The event is the paradigm of the everlasting fight of under-developped countries against powerful colonial metropolis. The author examines the conditions of local fight against colonizing cultural and scientific ideas, being his main content that scientific advancement needs not be an instrument of scientific imperialism. He analyzes in detail several factors currently impeding the use of scientific discoveries and improvements, focusing into concrete "obstacles" (in Bachelard's meaning) to betterment of Psychoanalytic knowledge. The obstacles are: 1. All-pervading transference. The rule adapted from Melanie Klein theories emphasizing hic et nunc validity of materials from the patient, neglects the fact that the analyst is also moved by desire, and that the patient's productions are not fragments of behavior able to be reduced to the present situation, but vectorial motions, always open and always re-opening into something defined since the beginning as forever lost. 2. Increasing activity for the analyst. The current hypothesis concerning the possibility of analyzing everything, encouraging the analyst's hyperactivity, does not allow for theoretical evaluation of the means and ways of manifestation of unconscious drives through gaps in the discourse. 3. Pan-counter-transference. The conception of counter-transference as an instrument is against Freud's contention, defining it as a reciprocal transference that must be fought in the same way as the patient's. 4. Belittling of theory. The thesis against theory, on the grounds that Psychoanalysis deals with affects and the affective life of patients, forgets that there is always some system for understanding the world and, for want of a theory, an ideological system is always ready to provide the grid underlying all concepts used. 5. Not-analyzing. The automatic "translation", lacking the search for new links to replace the ones that analysis dismantles, leads to denaturalizing the practice and keeping intact the patient's imaginary consistent universe. 6. Intergrationism. Other theories cannot be integrated to Psychoanalysis as they have different objects and different frameworks. Conversely, Psychoanalitic concepts cannot be formulated in other theories conceptual corpus for the same reason. The exception are the sciences having similar fields and methods of analysis, such as Semiotics or Linguistics. In their case the articulation of concepts becomes possible, but still requires the previous command of Psychoanalytic Theory in its full depth. 7. Communicationalism. The most common of all integrations with other sciences is the one linking Psychoanalysis with Communications Theory...

  15. [Mirror image of the ego. On Jacques Lacan's theory of the imaginary].

    PubMed

    Gekle, H

    1995-08-01

    Lacan places the concept of the imaginary alongside the categories of the real and the symbolic. This concept plays a highly prominent role in his thinking, given that the essential determination of the imaginary is the primary relation of the ego to the image of the similar. Thus it is not surprising that unlike Freud the early Lacan acceded to the status of theoretician of surrealism, his decentralization of the cogito having a profound effect on Dalí in particular. The author shows that non-identity and paranoic anamorphosis are only conceivable as the forms of the imaginary absolutised by Lacan if they are seen in relation to an Oedipally constructed cogito--just as mannerism regularly follows classicism and cannot be conceived of separately from it. If Freud was a classicist, Lacan was the mannerist who came after him--except that the latter refused to countenance this connection. PMID:7676068

  16. Jacques Maritain and Some Christian Suggestions for the Education of Teachers

    ERIC Educational Resources Information Center

    Carpenter, Wade A.

    2005-01-01

    "What indeed has Athens to do with Jerusalem? What concord is there between the Academy and the Church?" According to third-century Christian apologist Tertullian, not much. From precisely the opposite perspective, the twentieth-century "secular humanist" John Dewey would have echoed Tertullian, although he was as greatly indebted to Christian…

  17. Jean-Jacques Is Alive and Well: Rousseau and Contemporary Sociobiology

    ERIC Educational Resources Information Center

    Masters, Roger D.

    1978-01-01

    A description of the author's personal fascination with and study of Rousseau's life. Discusses Rousseau's many questions that are relevant to evolutionary biology, sociobiology, anthropology, and ethology. Questions concern the nature of human nature, the origin of human society, nurture-nature influences on humans, and the nature of male-female…

  18. Jean-Jacques Rousseau among the Footnotes: Mapping Interdisciplinary Research in Social Science Citation Index.

    ERIC Educational Resources Information Center

    Herubel, Jean-Pierre V. M.; Buchanan, Anne L.

    1994-01-01

    Examination of citations indexed in Social Science Citation Index (SSCI) reveals salient patterns which can be helpful in determining interdisciplinarity and/or disciplinarity. Collection development efforts can be enhanced by examination of citation patterns of published research related to a classical social science author such as Jean-Jacques…

  19. Paulo Freire's Last Laugh: Rethinking Critical Pedagogy's Funny Bone through Jacques Ranciere

    ERIC Educational Resources Information Center

    Lewis, Tyson Edward

    2010-01-01

    In several enigmatic passages, Paulo Freire describes the pedagogy of the oppressed as a "pedagogy of laughter". The inclusion of laughter alongside problem-posing dialogue might strike some as ambiguous, considering that the global exploitation of the poor is no laughing matter. And yet, laughter seems to be an important aspect of the pedagogy of…

  20. Human Unity and the Catholic University: Some Notes from the Philosophy of Jacques Maritain

    ERIC Educational Resources Information Center

    D'Souza, Mario O.

    2008-01-01

    While focusing on the nature and mission of Catholic higher education, "Ex Corde Ecclesiae: The Apostolic Constitution on Catholic Universities and The Presence of the Church in the University and University Culture" are also interested in the relationship between the mission of the Catholic university and the nature of the student as a person.…

  1. [Еxpression of claudin-1, 3, and 4 in colorectal cancer and polyps].

    PubMed

    Nefedova, N A; Kharlova, O A; Mal'kov, P G

    2016-01-01

    Клаудины — семейство трансмембранных белков, относящихся к белкам плотных контактов. Доказано, что в злокачественных клетках происходят структурные и функциональные изменения этих белков, однако работы, посвященные изучению аномалий экспрессии клаудинов в новообразованиях толстой кишки, крайне немногочисленны, данные различных авторов противоречивы. Цель — изучение экспрессии белков плотных контактов в раке и доброкачественных полипах толстой кишки. Материал и методы. Были отобраны образцы 32 аденокарцином толстой кишки и биоптаты 86 полипов толстой кишки, из которых сформировано шесть групп в соответствии с классификацией ВОЗ предопухолевых поражений толстой кишки 2010 г. Во всех случаях проведено иммуногистохимическое исследование с антителами к клаудинам-1, 3 и 4. В каждом случае экспрессия маркеров оценивалась по системе, предложенной G. Sheehan и соавт. (2007) как в новообразованиях, так и в прилежащей слизистой оболочке. Результаты. Иммуногистохимическая реакция с антителами к клаудинам имеет мембранный характер; экспрессия клаудинов в прилежащей к новообразованиям слизистой оболочке во всех случаях приближалась к максимальной. В зубчатых образованиях выявлен самый низкий уровень клаудина-1 (p<0,05) по сравнению с другими группами. В группе «рак» наблюдалась умеренная отрицательная взаимосвязь уровня экспрессии клаудина-1 и степени злокачественности аденокарциномы. Уровень клаудина-3 достоверно выше в раке по сравнению с зубчатыми образованиями (p=0,034) и в классических аденомах по сравнению с зубчатыми образованиями (p=0,025). Экспрессия клаудина-4 была выраженной в большинстве случаев, за исключением группы тубулярных аденом, в которой преобладала умеренная экспрессия. Заключение. Отсутствие статистически значимой разницы в уровнях экспрессии клаудинов-1, 3 и 4 между раком, гиперпластическими полипами, зубчатыми аденомами на широком основании, традиционными зубчатыми аденомами, тубулярными и тубуловорсинчатыми аденомами, но появление достоверных различий после укрупнения групп может свидетельствовать об общем пути развития у гиперпластических полипов и зубчатых аденом на широком основании, а также у тубулярных и тубуловорсинчатых аденом. Экспрессия клаудинов-1 и 3 указывает на отличие зубчатых образований от классических аденом и рака, что подтверждает концепцию собственного «зубчатого» пути канцерогенеза зубчатых образований.

  2. Portraits of payload specialists for STS 51-G

    NASA Technical Reports Server (NTRS)

    1984-01-01

    Portraits of payload specialists for STS 51-G. Group photo includes (l.-r.) Payload specialists Patrick Baudry and backup Payload Specialist Jean-Loup Chretien, both wearing blue shuttle flight suits and standing in front of a model of the shuttle orbiter. Baudry carries his helmet (43892); Portrait of payload specialist Jean-Loup Chretien wearing blue shuttle flight suit and carring helmet. A model of the shuttle in launch position is behind him (43893); Portrait of Payload Specialist Patrick Baudry in blue shuttle flight suit and carrying his helmet. A model of the shuttle in launch position is behind him (43894).

  3. Using Chinese Knowledge in Internationalising Research Education: Jacques Ranciere, an Ignorant Supervisor and Doctoral Students from China

    ERIC Educational Resources Information Center

    Singh, Michael

    2009-01-01

    The problematic of the research reported in this paper, namely the place of Chinese knowledge in educational research in Australia provides an opportunity to use Rancire's work to rethink the place of ignorance in the supervisory pedagogies used in internationalising education. Because its scope and character is quite variable, consideration is…

  4. STS 51-G simulate meal session on orbiter's middeck

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Three members of the STS 51-G crew simulate a meal session on the orbiter's middeck during training in the crew compartment trainer at JSC's shuttle mockup and integration facility. Pictured (l.-r.) are Sultan Salman Abdelzize Al-Saud, John N. Fabian and Patrick Baudry. Fabian is a mission specialist and the other two men are payload specialists.

  5. STS 51-G crew photo on the flight deck

    NASA Technical Reports Server (NTRS)

    1985-01-01

    STS 51-G crew photo on the flight deck. Left to right in the front are John O. Creighton, Shannon W. Lucid, Daniel C. Brandenstein; and in the back row are Sultan Salman Abdelazize Al-Saud, Steven R. Nagel, John N. Fabian and Patrick Baudry.

  6. Portrait of STS 51-G Payload Specialists

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Portrait of STS 51-G Payload specialists. Left to right are Patrick Baudry, for the Centre National d'Etudes Spatiales of France; Abdulmohsen Hamad Al-Bassan, backup payload specialist to Sultan Salman Abdelazize Al-Saud of Saudi Arabia. They are standing in front of a small table containing a model of the Space Shuttle.

  7. Portrait of STS 51-G crew

    NASA Technical Reports Server (NTRS)

    1985-01-01

    Portrait of STS 51-G crew. Kneeling in front are Astronauts Daniel C. Brandenstein (left) and John O. Creighton, commander and pilot, respectively. Astronauts Shannon W. Lucid, Steven R. Nagel, and John M. Fabian, mission specialist (l.-r.) joing Payload specialists Sultan Salman Abdelazize Al-Saud (second right) and Patrick Baudry on the back row.

  8. Pierre Bourdieu and Jacques Rancière on art/aesthetics and politics: the origins of disagreement, 1963-1985.

    PubMed

    Robbins, Derek

    2015-12-01

    Rancière published two substantial criticisms of the work of Bourdieu in the early 1980s. It is possible that these were provoked by his sense that he needed to oppose what he considered to be the sociological reduction of aesthetic taste offered by Bourdieu in Distinction (Bourdieu 1986 [1979]) at precisely the moment when he (Rancière) was beginning to articulate his commitment to the potential of aesthetic expression as a mode of political resistance. Except in so far as it draws upon some of the retrospective reflections offered by Rancière in his introductions to the re-issues of his early texts, this paper examines the parallel development of the thinking of the two men up to the mid-1980s--but not beyond. The discussion is situated socio-historically and, by definition, does not seek to offer comparatively any transhistorical assessment of the values of the positions adopted by the two men. I argue that Rancière misrepresented the character of Bourdieu's sociological work by failing to recognize the underlying phenomenological orientation of his thinking. Bourdieu suppressed this orientation in the 1960s but, after the May events of 1968, it enabled him to expose the extent to which the practices of both science and art operate within constructed 'fields' in strategic distinction from popular primary experience. The challenge is to introduce an ongoing dialogue between primary and constructed cultures rather than to suppose that either social science or art possesses intrinsic autonomy. PMID:26455436

  9. The need for true controversies in psychoanalysis: the debates on Melanie Klein and Jacques Lacan in the Rio de la Plata.

    PubMed

    Bernardi, Ricardo

    2002-08-01

    Controversies are part of the process of scientific knowing. In psychoanalysis, the diversity of theoretical, technical and epistemological positions makes the debate particularly necessary and by the same token difficult. In this paper, the author examines the function of controversies and the obstacles to their development, taking as examples the debates held in the Río de la Plata (Buenos Aires and Montevideo) during the nineteen seventies, when the dominant Kleinian ideas came into contact with Lacanian thought. The author examines different examples of argumentative discourses, using concepts taken from the theory of argumentation. The major difficulties encountered did not hinge on characteristics pertaining to psychoanalytic theories (i.e. the lack of commensurability between them), but on the defensive strategies aimed at keeping each theory's premises safe from the opposing party's arguments. A true debate implies the construction of a shared argumentative field that makes it possible to lay out the different positions and see some interaction between them and is guided by the search for the best argument. When this occurs, controversies promote the discipline's development, even when they fail to reach any consensus.

  10. Jacques Lacan's theory of the subject as real, symbolic and imaginary: how can Lacanian theory be of help to mental health nursing practice?

    PubMed

    McSherry, A

    2013-11-01

    This paper presents an outline of Lacan's theory of the human subject, in particular focusing on Lacan's concepts of the real, symbolic and imaginary registers, and how an understanding of these can inform change and practice in mental health nursing. Mental health nursing is under pressure to define itself as a practice distinct from other professions in the field, and to respond in new ways to promoting mental health to the individual and a wider public. Lacan's theory of the subject is of particular relevance to mental health nurses working with mental distress but has received little attention in mental health nursing literature. Six implications for practice are outlined in terms of: against normalization, the importance of the function of the symptom, what cannot be known, meaning as ever-changing, against empathy and against holistic ideas of the self.

  11. Pierre Bourdieu and Jacques Rancière on art/aesthetics and politics: the origins of disagreement, 1963-1985.

    PubMed

    Robbins, Derek

    2015-12-01

    Rancière published two substantial criticisms of the work of Bourdieu in the early 1980s. It is possible that these were provoked by his sense that he needed to oppose what he considered to be the sociological reduction of aesthetic taste offered by Bourdieu in Distinction (Bourdieu 1986 [1979]) at precisely the moment when he (Rancière) was beginning to articulate his commitment to the potential of aesthetic expression as a mode of political resistance. Except in so far as it draws upon some of the retrospective reflections offered by Rancière in his introductions to the re-issues of his early texts, this paper examines the parallel development of the thinking of the two men up to the mid-1980s--but not beyond. The discussion is situated socio-historically and, by definition, does not seek to offer comparatively any transhistorical assessment of the values of the positions adopted by the two men. I argue that Rancière misrepresented the character of Bourdieu's sociological work by failing to recognize the underlying phenomenological orientation of his thinking. Bourdieu suppressed this orientation in the 1960s but, after the May events of 1968, it enabled him to expose the extent to which the practices of both science and art operate within constructed 'fields' in strategic distinction from popular primary experience. The challenge is to introduce an ongoing dialogue between primary and constructed cultures rather than to suppose that either social science or art possesses intrinsic autonomy.

  12. The need for true controversies in psychoanalysis: the debates on Melanie Klein and Jacques Lacan in the Rio de la Plata.

    PubMed

    Bernardi, Ricardo

    2002-08-01

    Controversies are part of the process of scientific knowing. In psychoanalysis, the diversity of theoretical, technical and epistemological positions makes the debate particularly necessary and by the same token difficult. In this paper, the author examines the function of controversies and the obstacles to their development, taking as examples the debates held in the Río de la Plata (Buenos Aires and Montevideo) during the nineteen seventies, when the dominant Kleinian ideas came into contact with Lacanian thought. The author examines different examples of argumentative discourses, using concepts taken from the theory of argumentation. The major difficulties encountered did not hinge on characteristics pertaining to psychoanalytic theories (i.e. the lack of commensurability between them), but on the defensive strategies aimed at keeping each theory's premises safe from the opposing party's arguments. A true debate implies the construction of a shared argumentative field that makes it possible to lay out the different positions and see some interaction between them and is guided by the search for the best argument. When this occurs, controversies promote the discipline's development, even when they fail to reach any consensus. PMID:12204169

  13. Conceptual barriers to understanding physical barriers

    PubMed Central

    Lingaraju, Amulya; Long, Tiha M.; Wang, Yitang; Austin, Jotham R.; Turner, Jerrold R.

    2015-01-01

    The members of the large family of claudin proteins regulate ion and water flux across the tight junction. Many claudins, e.g. claudins 2 and 15, accomplish this by forming size- and charge-selective paracellular channels. Claudins also appear to be essential for genesis of tight junction strands and recruitment of other proteins to these sites. What is less clear is whether claudins also form the paracellular seal. While this seal is defective when claudins are disrupted, some results, including ultrastructural and biochemical data, suggest that lipid structures are an important component of tight junction strands and may be responsible for the paracellular seal. This review highlights the current knowledge of claudins to barrier function and tight junction structure and suggests a model by which claudins and other tight junction proteins can drive assembly and stabilization of a lipid-based strand structure. PMID:26003050

  14. STS 51-G crewmembers depart KSC's operations and checkout building

    NASA Technical Reports Server (NTRS)

    1985-01-01

    STS 51-G crewmembers depart the Kennedy Space Center's operations and checkout building on their way to the launch pad for the launch of the Discovery. Leading the seven are Daniel C. Brandenstein, commander; and John O. Creighton, pilot. Following are Payload specialist Sultan Salman Abdelazize Al-Saud; John M. Fabian, mission specialist; Patrick Baudry, payload specialist; Shannon Lucid and Steven R. Nagel, mission specialists.

  15. Crew of the STS 51-G Discovery egress the orbiter in California

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The crew of the STS 51-G Discovery egress the orbiter in California at the end of the mission. Astronaut Danel C. Brandenstein, crew commander, shakes hands with George W.S. Abbey, Director of Flight Crew Operations at JSC. Behind Brandenstein are (bottom to top) John O. Creighton, John M. Fabian, Shannon W. Lucid, Sultan Salman Abdelazize Al-Saud, Patrick Baudry and Steven R. Nagel.

  16. Data set of the protein expression profiles of Luminal A, Claudin-low and overexpressing HER2(+) breast cancer cell lines by iTRAQ labelling and tandem mass spectrometry.

    PubMed

    Calderón-González, Karla Grisel; Valero Rustarazo, Ma Luz; Labra-Barrios, Maria Luisa; Bazán-Méndez, César Isaac; Tavera-Tapia, Alejandra; Herrera-Aguirre, Marí aEsther; Sánchez Del Pino, Manuel M; Gallegos-Pérez, José Luis; González-Márquez, Humberto; Hernández-Hernández, Jose Manuel; León-Ávila, Gloria; Rodríguez-Cuevas, Sergio; Guisa-Hohenstein, Fernando; Luna-Arias, Juan Pedro

    2015-09-01

    Breast cancer is the most common and the leading cause of mortality in women worldwide. There is a dire necessity of the identification of novel molecules useful in diagnosis and prognosis. In this work we determined the differentially expression profiles of four breast cancer cell lines compared to a control cell line. We identified 1020 polypeptides labelled with iTRAQ with more than 95% in confidence. We analysed the common proteins in all breast cancer cell lines through IPA software (IPA core and Biomarkers). In addition, we selected the specific overexpressed and subexpressed proteins of the different molecular classes of breast cancer cell lines, and classified them according to protein class and biological process. Data in this article is related to the research article "Determination of the protein expression profiles of breast cancer cell lines by Quantitative Proteomics using iTRAQ Labelling and Tandem Mass Spectrometry" (Calderón-González et al. [1] in press). PMID:26217805

  17. Data set of the protein expression profiles of Luminal A, Claudin-low and overexpressing HER2+ breast cancer cell lines by iTRAQ labelling and tandem mass spectrometry

    PubMed Central

    Calderón-González, Karla Grisel; Valero Rustarazo, Ma Luz; Labra-Barrios, Maria Luisa; Bazán-Méndez, César Isaac; Tavera-Tapia, Alejandra; Herrera-Aguirre, Marí;aEsther; Sánchez del Pino, Manuel M.; Gallegos-Pérez, José Luis; González-Márquez, Humberto; Hernández-Hernández, Jose Manuel; León-Ávila, Gloria; Rodríguez-Cuevas, Sergio; Guisa-Hohenstein, Fernando; Luna-Arias, Juan Pedro

    2015-01-01

    Breast cancer is the most common and the leading cause of mortality in women worldwide. There is a dire necessity of the identification of novel molecules useful in diagnosis and prognosis. In this work we determined the differentially expression profiles of four breast cancer cell lines compared to a control cell line. We identified 1020 polypeptides labelled with iTRAQ with more than 95% in confidence. We analysed the common proteins in all breast cancer cell lines through IPA software (IPA core and Biomarkers). In addition, we selected the specific overexpressed and subexpressed proteins of the different molecular classes of breast cancer cell lines, and classified them according to protein class and biological process. Data in this article is related to the research article “Determination of the protein expression profiles of breast cancer cell lines by Quantitative Proteomics using iTRAQ Labelling and Tandem Mass Spectrometry” (Calderón-González et al. [1] in press). PMID:26217805

  18. Data set of the protein expression profiles of Luminal A, Claudin-low and overexpressing HER2(+) breast cancer cell lines by iTRAQ labelling and tandem mass spectrometry.

    PubMed

    Calderón-González, Karla Grisel; Valero Rustarazo, Ma Luz; Labra-Barrios, Maria Luisa; Bazán-Méndez, César Isaac; Tavera-Tapia, Alejandra; Herrera-Aguirre, Marí aEsther; Sánchez Del Pino, Manuel M; Gallegos-Pérez, José Luis; González-Márquez, Humberto; Hernández-Hernández, Jose Manuel; León-Ávila, Gloria; Rodríguez-Cuevas, Sergio; Guisa-Hohenstein, Fernando; Luna-Arias, Juan Pedro

    2015-09-01

    Breast cancer is the most common and the leading cause of mortality in women worldwide. There is a dire necessity of the identification of novel molecules useful in diagnosis and prognosis. In this work we determined the differentially expression profiles of four breast cancer cell lines compared to a control cell line. We identified 1020 polypeptides labelled with iTRAQ with more than 95% in confidence. We analysed the common proteins in all breast cancer cell lines through IPA software (IPA core and Biomarkers). In addition, we selected the specific overexpressed and subexpressed proteins of the different molecular classes of breast cancer cell lines, and classified them according to protein class and biological process. Data in this article is related to the research article "Determination of the protein expression profiles of breast cancer cell lines by Quantitative Proteomics using iTRAQ Labelling and Tandem Mass Spectrometry" (Calderón-González et al. [1] in press).

  19. View of the STS 51-L Memorial service on JSC's main mall

    NASA Technical Reports Server (NTRS)

    1986-01-01

    Memorial services for the Challenger Seven were conducted on the morning of Jan. 31, 1986 at JSC's main mall. Among those in attendance were former and present astronauts and Space Shuttle payload specialists (PS). U.S. Sen. Jake Garn (R., Utah) vists at center with Sultan Salman Abdelazize Al-Saud of Saudi Arabia. Others pictured include German PS Ulf Merbold, French PS Patrick Baudry and NASA Astronauts Robert L. Stewart, Marsha S. Ivins, David C. Leestma and C. Gordon Fullerton, along with former astronaut Eugene A. Cernan.

  20. Comparative analysis of theophylline and cholera toxin in rat colon reveals an induction of sealing tight junction proteins.

    PubMed

    Markov, Alexander G; Falchuk, Evgeny L; Kruglova, Natalia M; Rybalchenko, Oksana V; Fromm, Michael; Amasheh, Salah

    2014-11-01

    Claudin tight junction proteins have been identified to primarily determine intestinal epithelial barrier properties. While functional contribution of single claudins has been characterized in detail, information on the interplay with secretory mechanisms in native intestinal epithelium is scarce. Therefore, effects of cholera toxin and theophylline on rat colon were analyzed, including detection of sealing claudins. Tissue specimens were stripped off submucosal tissue layers and mounted in Ussing chambers, and short-circuit current (ISC) and transepithelial resistance (TER) were recorded. In parallel, expression and localization of claudins was analyzed and histological studies were performed employing hematoxylin-eosin staining and light and electron microscopy. Theophylline induced a strong increase of ISC in colon tissue specimens. In parallel, a decrease of TER was observed. In contrast, cholera toxin did not induce a significant increase of ISC, whereas an increase of TER was detected after 120 min. Western blots of membrane fractions revealed an increase of claudin-3 and -4 after incubation with cholera toxin, and theophylline induced an increase of claudin-4. In accordance, confocal laser-scanning microscopy exhibited increased signals of claudin-3 and -4 after incubation with cholera toxin, and increased signals of claudin-4 after incubation with theophylline, within tight junction complexes. Morphological analyses revealed no general changes of tight junction complexes, but intercellular spaces were markedly widened after incubation with cholera toxin and theophylline. We conclude that cholera toxin and theophylline have different effects on sealing tight junction proteins in native colon preparations, which may synergistically contribute to transport functions, in vitro.

  1. 75 FR 6398 - Ocean Transportation Intermediary License Applicants

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-09

    ..., IN 46805, Officers, Tonya R. Watson, Vice President, (Qualifying Individual), Sabah A. Qiyas..., COO, (Qualifying Individual), Jean Jacques Lalou, CEO. Geevee Enterprises Inc. dba Aerosend, 245...

  2. Dewey, Derrida, and "The Double Bind"

    ERIC Educational Resources Information Center

    Garrison, Jim

    2003-01-01

    In this article, the author talks about the texts of Jacques Derrida and Dewey. The texts of Jacques Derrida seem inextricably connected to the word deconstruction, yet, Derrida insists, "The word "deconstruction," like all other words, acquires its value only from its inscription in a chain of possible substitutions." The author argues that…

  3. Literary Theory and the Notion of Difficulty. Report Series 4.7.

    ERIC Educational Resources Information Center

    Touponce, William

    The works of French literary theorists Jacques Lacan, Jacques Derrida, and Roland Barthes reflect a view of the text as the primary object of investigation for any discipline in the human sciences. Each of the three has been involved with pedagogical reforms within French cultural institutions: Derrida with the teaching of philosophy, Lacan with…

  4. Languages in a Globalising World.

    ERIC Educational Resources Information Center

    Maurais, Jacques, Ed.; Morris, Michael A., Ed.

    This book offers 21 papers in three parts. After (1) "Introduction" (Jacques Maurais and Michael A. Morris), Part 1, "Global Communication Challenges," includes (2) "Towards a New Global Linguistic Order?" (Jacques Maurais); (3) "The Geostrategies of Interlingualism" (Mark Fettes); (4) "Language Policy and Linguistic Theory" (Douglas A Kibbee);…

  5. Moliere: A Collection of Critical Essays. Twentieth Century Views Series.

    ERIC Educational Resources Information Center

    Guicharnaud, Jacques, Ed.

    One of a series of works aimed at presenting contemporary critical opinion on major authors, this collection includes essays by Jacques Guicharnaud, Rene Bray, Gustave Lanson, Alfred Simon, Will G. Moore, Ramon Fernandez, Paul Benichou, Lionel Gossman, Andre Villiers, James Doolittle, H. Gaston Hall, Robert J. Nelson, Jacques Copeau, Charles…

  6. Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network

    PubMed Central

    Springler, Alexandra; Hessenberger, Sabine; Schatzmayr, Gerd; Mayer, Elisabeth

    2016-01-01

    Deoxynivalenol (DON), produced by the plant pathogens Fusarium graminearum and Fusarium culmorum, is one of the most common mycotoxins, contaminating cereal and cereal-derived products. Although worldwide contamination of food and feed poses health threats to humans and animals, pigs are particularly susceptible to this mycotoxin. DON derivatives, such as deepoxy-deoxynivalenol (DOM-1), are produced by bacterial transformation of certain intestinal bacteria, which are naturally occurring or applied as feed additives. Intestinal epithelial cells are the initial barrier against these food- and feed-borne toxins. The present study confirms DON-induced activation of MAPK p44/42 and inhibition of p44/42 by MAPK-inhibitor U0126 monoethanolate. Influence of DON and DOM-1 on transepithelial electrical resistance (TEER), viability and expression of seven tight junction proteins (TJ), as well as the potential of U0126 to counteract DON-induced effects, was assessed. While DOM-1 showed no effect, DON significantly reduced TEER of differentiated IPEC-J2 and decreased expression of claudin-1 and -3, while leaving claudin-4; ZO-1, -2, and -3 and occludin unaffected. Inhibition of p44/42 counteracted DON-induced TEER decrease and restored claudin-3, but not claudin-1 expression. Therefore, effects of DON on TEER and claudin-3 are at least partially p44/42 mediated, while effects on viability and claudin-1 are likely mediated via alternative pathways. PMID:27618100

  7. Tight junction CLDN2 gene is a direct target of the vitamin D receptor.

    PubMed

    Zhang, Yong-guo; Wu, Shaoping; Lu, Rong; Zhou, David; Zhou, Jingsong; Carmeliet, Geert; Petrof, Elaine; Claud, Erika C; Sun, Jun

    2015-01-01

    The breakdown of the intestinal barrier is a common manifestation of many diseases. Recent evidence suggests that vitamin D and its receptor VDR may regulate intestinal barrier function. Claudin-2 is a tight junction protein that mediates paracellular water transport in intestinal epithelia, rendering them "leaky". Using whole body VDR(-/-) mice, intestinal epithelial VDR conditional knockout (VDR(ΔIEC)) mice, and cultured human intestinal epithelial cells, we demonstrate here that the CLDN2 gene is a direct target of the transcription factor VDR. The Caudal-Related Homeobox (Cdx) protein family is a group of the transcription factor proteins which bind to DNA to regulate the expression of genes. Our data showed that VDR-enhances Claudin-2 promoter activity in a Cdx1 binding site-dependent manner. We further identify a functional vitamin D response element (VDRE) 5΄-AGATAACAAAGGTCA-3΄ in the Cdx1 site of the Claudin-2 promoter. It is a VDRE required for the regulation of Claudin-2 by vitamin D. Absence of VDR decreased Claudin-2 expression by abolishing VDR/promoter binding. In vivo, VDR deletion in intestinal epithelial cells led to significant decreased Claudin-2 in VDR(-/-) and VDR(ΔIEC) mice. The current study reveals an important and novel mechanism for VDR by regulation of epithelial barriers. PMID:26212084

  8. Paracellular epithelial sodium transport maximizes energy efficiency in the kidney.

    PubMed

    Pei, Lei; Solis, Glenn; Nguyen, Mien T X; Kamat, Nikhil; Magenheimer, Lynn; Zhuo, Min; Li, Jiahua; Curry, Joshua; McDonough, Alicia A; Fields, Timothy A; Welch, William J; Yu, Alan S L

    2016-07-01

    Efficient oxygen utilization in the kidney may be supported by paracellular epithelial transport, a form of passive diffusion that is driven by preexisting transepithelial electrochemical gradients. Claudins are tight-junction transmembrane proteins that act as paracellular ion channels in epithelial cells. In the proximal tubule (PT) of the kidney, claudin-2 mediates paracellular sodium reabsorption. Here, we used murine models to investigate the role of claudin-2 in maintaining energy efficiency in the kidney. We found that claudin-2-null mice conserve sodium to the same extent as WT mice, even during profound dietary sodium depletion, as a result of the upregulation of transcellular Na-K-2Cl transport activity in the thick ascending limb of Henle. We hypothesized that shifting sodium transport to transcellular pathways would lead to increased whole-kidney oxygen consumption. Indeed, compared with control animals, oxygen consumption in the kidneys of claudin-2-null mice was markedly increased, resulting in medullary hypoxia. Furthermore, tubular injury in kidneys subjected to bilateral renal ischemia-reperfusion injury was more severe in the absence of claudin-2. Our results indicate that paracellular transport in the PT is required for efficient utilization of oxygen in the service of sodium transport. We speculate that paracellular permeability may have evolved as a general strategy in epithelial tissues to maximize energy efficiency.

  9. Paracellular epithelial sodium transport maximizes energy efficiency in the kidney

    PubMed Central

    Pei, Lei; Nguyen, Mien T.X.; Kamat, Nikhil; Magenheimer, Lynn; Zhuo, Min; Li, Jiahua; McDonough, Alicia A.; Fields, Timothy A.; Welch, William J.; Yu, Alan S.L.

    2016-01-01

    Efficient oxygen utilization in the kidney may be supported by paracellular epithelial transport, a form of passive diffusion that is driven by preexisting transepithelial electrochemical gradients. Claudins are tight-junction transmembrane proteins that act as paracellular ion channels in epithelial cells. In the proximal tubule (PT) of the kidney, claudin-2 mediates paracellular sodium reabsorption. Here, we used murine models to investigate the role of claudin-2 in maintaining energy efficiency in the kidney. We found that claudin-2–null mice conserve sodium to the same extent as WT mice, even during profound dietary sodium depletion, as a result of the upregulation of transcellular Na-K-2Cl transport activity in the thick ascending limb of Henle. We hypothesized that shifting sodium transport to transcellular pathways would lead to increased whole-kidney oxygen consumption. Indeed, compared with control animals, oxygen consumption in the kidneys of claudin-2–null mice was markedly increased, resulting in medullary hypoxia. Furthermore, tubular injury in kidneys subjected to bilateral renal ischemia-reperfusion injury was more severe in the absence of claudin-2. Our results indicate that paracellular transport in the PT is required for efficient utilization of oxygen in the service of sodium transport. We speculate that paracellular permeability may have evolved as a general strategy in epithelial tissues to maximize energy efficiency. PMID:27214555

  10. Early Activation of MAPK p44/42 Is Partially Involved in DON-Induced Disruption of the Intestinal Barrier Function and Tight Junction Network.

    PubMed

    Springler, Alexandra; Hessenberger, Sabine; Schatzmayr, Gerd; Mayer, Elisabeth

    2016-01-01

    Deoxynivalenol (DON), produced by the plant pathogens Fusarium graminearum and Fusarium culmorum, is one of the most common mycotoxins, contaminating cereal and cereal-derived products. Although worldwide contamination of food and feed poses health threats to humans and animals, pigs are particularly susceptible to this mycotoxin. DON derivatives, such as deepoxy-deoxynivalenol (DOM-1), are produced by bacterial transformation of certain intestinal bacteria, which are naturally occurring or applied as feed additives. Intestinal epithelial cells are the initial barrier against these food- and feed-borne toxins. The present study confirms DON-induced activation of MAPK p44/42 and inhibition of p44/42 by MAPK-inhibitor U0126 monoethanolate. Influence of DON and DOM-1 on transepithelial electrical resistance (TEER), viability and expression of seven tight junction proteins (TJ), as well as the potential of U0126 to counteract DON-induced effects, was assessed. While DOM-1 showed no effect, DON significantly reduced TEER of differentiated IPEC-J2 and decreased expression of claudin-1 and -3, while leaving claudin-4; ZO-1, -2, and -3 and occludin unaffected. Inhibition of p44/42 counteracted DON-induced TEER decrease and restored claudin-3, but not claudin-1 expression. Therefore, effects of DON on TEER and claudin-3 are at least partially p44/42 mediated, while effects on viability and claudin-1 are likely mediated via alternative pathways. PMID:27618100

  11. Plato's Pharmacy and Derrida's Drugstore.

    ERIC Educational Resources Information Center

    Mortensen, Chris

    2000-01-01

    In a long essay titled "Plato's Pharmacy, Jacques Derrida attacked Western metaphysics. This article undertakes to defend Western philosophy from Derrida's arguments. It is shown that Derrida's arguments are very unsatisfactory. (Author/VWL)

  12. The Jouissance of English Department Politics: A Tale of Shem and Shaun.

    ERIC Educational Resources Information Center

    Harrington, Henry R.

    1993-01-01

    Considers the role of the English department malcontent, who constantly seems to spoil any chance of departmental consensus. Discusses the typical life of the English department. Analyzes departmental disputes with the aid of Jacques Lacan's notion of "jouissance." (HB)

  13. 78 FR 24288 - Culturally Significant Objects Imported for Exhibition Determinations: “Frida Kahlo, Diego Rivera...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF STATE Culturally Significant Objects Imported for Exhibition Determinations: ``Frida Kahlo, Diego Rivera, and... included in the exhibition ``Frida Kahlo, Diego Rivera, and Masterpieces of Modern Mexico: The Jacques...

  14. Toward a 'Nouveau Emile.'

    ERIC Educational Resources Information Center

    Meyerson, Martin

    1979-01-01

    The author notes that the questions raised in Torsten Husen's book, "The School in Question," are the same raised by the eighteenth-century philosopher Jean Jacques Rousseau. Specifically, problems inherent in the concept of equal education are considered. (KC)

  15. Nigeria, Alienation, and The Novels of Chinua Achebe

    ERIC Educational Resources Information Center

    Leslie, Omolara

    1973-01-01

    Examines the novels of Chinua Achebe in the light of Jean Jacques Rousseau's definition of political alienation as the political process of representation whereby a community allows its interests to be represented by a smaller group. (Author/JM)

  16. Natural Freedom and Wilderness Survival

    ERIC Educational Resources Information Center

    Welton, George E.

    1978-01-01

    The "naturalism" of Jean Jacques Rousseau offers a philosophical base for wilderness survival: the renewal of participants in nature so that they can reenter civilization with a proper balance of natural and civil liberty. (MJB)

  17. Deconstruction and Linguistic Analysis.

    ERIC Educational Resources Information Center

    Schleifer, Ronald

    1987-01-01

    Challenges a number of concepts in classical continental linguistics. Argues that a direct relationship exists between Jacques Derrida's procedures of deconstruction and the methods of linguistic analysis. Claims that deconstruction is the negation or denial of linguistic neutralization. (JD)

  18. The Integrin β1 Subunit Regulates Paracellular Permeability of Kidney Proximal Tubule Cells*

    PubMed Central

    Elias, Bertha C.; Mathew, Sijo; Srichai, Manakan B.; Palamuttam, Riya; Bulus, Nada; Mernaugh, Glenda; Singh, Amar B.; Sanders, Charles R.; Harris, Raymond C.; Pozzi, Ambra; Zent, Roy

    2014-01-01

    Epithelial cells lining the gastrointestinal tract and kidney have different abilities to facilitate paracellular and transcellular transport of water and solutes. In the kidney, the proximal tubule allows both transcellular and paracellular transport, while the collecting duct primarily facilitates transcellular transport. The claudins and E-cadherin are major structural and functional components regulating paracellular transport. In this study we present the novel finding that the transmembrane matrix receptors, integrins, play a role in regulating paracellular transport of renal proximal tubule cells. Deleting the integrin β1 subunit in these cells converts them from a “loose” epithelium, characterized by low expression of E-cadherin and claudin-7 and high expression of claudin-2, to a “tight” epithelium with increased E-cadherin and claudin-7 expression and decreased claudin-2 expression. This effect is mediated by the integrin β1 cytoplasmic tail and does not entail β1 heterodimerization with an α-subunit or its localization to the cell surface. In addition, we demonstrate that deleting the β1 subunit in the proximal tubule of the kidney results in a major urine-concentrating defect. Thus, the integrin β1 tail plays a key role in regulating the composition and function of tight and adherens junctions that define paracellular transport properties of terminally differentiated renal proximal tubule epithelial cells. PMID:24509849

  19. A microwave antigen retrieval method using two heating steps for enhanced immunostaining on aldehyde-fixed paraffin-embedded tissue sections.

    PubMed

    Gu, Ling; Cong, Jing; Zhang, Jie; Tian, Ying-Ying; Zhai, Xiao-Yue

    2016-06-01

    Antigen retrieval is an immunohistochemical procedure that results in better exposure of target antigens in aldehyde-fixed, paraffin-embedded tissue sections to antibodies. However, the commercially recommended or conventional protocols for antigen retrieval do not always succeed in expressing the target antigen. Here, an improved method was developed for antigen retrieval from aldehyde-fixed, paraffin-embedded histological sections. Proliferating cell nuclear antigen (PCNA), tight junction proteins Claudin-2 and Claudin-7, and water channel aquaporins in kidney tissue were selected as test antigens. Typically, PCNA and Claudin-2 and Claudin-7 show negative, weak, or nonspecific immunoreactions with conventional antigen retrieval methods using microwave heating. In the present study, microwave heating was performed twice with an interval of 30 min between the two steps to allow the buffer solution to cool. Sodium citrate buffer (10 mM sodium citrate, pH 6.0) was used for PCNA, and Tris-EDTA buffer (10 mM Tris, 1 mM EDTA, pH 9.0) was used for the Claudins. Compared with conventionally prepared tissues, the tissues exhibited both enhanced and specific immunostaining, and well-preserved morphology. In conclusion, the conventional protocol could be supplemented with a second microwave heating step to improve the expression of antigens that do not respond well to the conventional method. PMID:27002723

  20. Proteopolymersomes: in vitro production of a membrane protein in polymersome membranes.

    PubMed

    Nallani, Madhavan; Andreasson-Ochsner, Mirjam; Tan, Cherng-Wen Darren; Sinner, Eva-Kathrin; Wisantoso, Yudi; Geifman-Shochat, Susana; Hunziker, Walter

    2011-12-01

    Polymersomes are stable self-assembled architectures which mimic cell membranes. For characterization, membrane proteins can be incorporated into such bio-mimetic membranes by reconstitution methods, leading to so-called proteopolymersomes. In this work, we demonstrate the direct incorporation of a membrane protein into polymersome membranes by a cell-free expression system. Firstly, we demonstrate pore formation in the preformed polymersome membrane using α-hemolysin. Secondly, we use claudin-2, a protein involved in cell-cell interactions, to demonstrate the in vitro expression of a membrane protein into these polymersomes. Surface plasmon resonance (Biacore) binding studies with the claudin-2 proteopolymersomes and claudin-2 specific antibodies are performed to show the presence of the in vitro expressed protein in polymersome membranes.

  1. The Role of Lipolysis Stimulated Lipoprotein Receptor in Breast Cancer and Directing Breast Cancer Cell Behavior

    PubMed Central

    Reaves, Denise K.; Fagan-Solis, Katerina D.; Dunphy, Karen; Oliver, Shannon D.; Scott, David W.; Fleming, Jodie M.

    2014-01-01

    The claudin-low molecular subtype of breast cancer is of particular interest for clinically the majority of these tumors are poor prognosis, triple negative, invasive ductal carcinomas. Claudin-low tumors are characterized by cancer stem cell-like features and low expression of cell junction and adhesion proteins. Herein, we sought to define the role of lipolysis stimulated lipoprotein receptor (LSR) in breast cancer and cancer cell behavior as LSR was recently correlated with tumor-initiating features. We show that LSR was expressed in epithelium, endothelium, and stromal cells within the healthy breast tissue, as well as in tumor epithelium. In primary breast tumor bioposies, LSR expression was significantly correlated with invasive ductal carcinomas compared to invasive lobular carcinomas, as well as ERα positive tumors and breast cancer cell lines. LSR levels were significantly reduced in claudin-low breast cancer cell lines and functional studies illustrated that re-introduction of LSR into a claudin-low cell line suppressed the EMT phenotype and reduced individual cell migration. However, our data suggest that LSR may promote collective cell migration. Re-introduction of LSR in claudin-low breast cancer cell lines reestablished tight junction protein expression and correlated with transepithelial electrical resistance, thereby reverting claudin-low lines to other intrinsic molecular subtypes. Moreover, overexpression of LSR altered gene expression of pathways involved in transformation and tumorigenesis as well as enhanced proliferation and survival in anchorage independent conditions, highlighting that reestablishment of LSR signaling promotes aggressive/tumor initiating cell behaviors. Collectively, these data highlight a direct role for LSR in driving aggressive breast cancer behavior. PMID:24637461

  2. Controlling Cancer: Choices for a Healthy Life. Hearing before the Select Committee on Aging. House of Representatives, Ninety-Ninth Congress, First Session (Cranston, RI).

    ERIC Educational Resources Information Center

    Congress of the U.S., Washington, DC. House Select Committee on Aging.

    This paper contains testimony and prepared statements from the Congressional hearing called to examine ways of controlling cancer. Opening statements are included from Representatives Claudine Schneider, Jim Lightfoot, and Ben Blaz. Testimonies are given by Rosemarie Lindgren, a homemaker and former cancer patient, and by Jules Cardin, a patient…

  3. Junctional Adhesion Molecule A Promotes Epithelial Tight Junction Assembly to Augment Lung Barrier Function

    PubMed Central

    Mitchell, Leslie A.; Ward, Christina; Kwon, Mike; Mitchell, Patrick O.; Quintero, David A.; Nusrat, Asma; Parkos, Charles A.; Koval, Michael

    2016-01-01

    Epithelial barrier function is maintained by tight junction proteins that control paracellular fluid flux. Among these proteins is junctional adhesion molecule A (JAM-A), an Ig fold transmembrane protein. To assess JAM-A function in the lung, we depleted JAM-A in primary alveolar epithelial cells using shRNA. In cultured cells, loss of JAM-A caused an approximately 30% decrease in transepithelial resistance, decreased expression of the tight junction scaffold protein zonula occludens 1, and disrupted junctional localization of the structural transmembrane protein claudin-18. Consistent with findings in other organs, loss of JAM-A decreased β1 integrin expression and impaired filamentous actin formation. Using a model of mild systemic endoxotemia induced by i.p. injection of lipopolysaccharide, we report that JAM-A−/− mice showed increased susceptibility to pulmonary edema. On injury, the enhanced susceptibility of JAM-A−/− mice to edema correlated with increased, transient disruption of claudin-18, zonula occludens 1, and zonula occludens 2 localization to lung tight junctions in situ along with a delay in up-regulation of claudin-4. In contrast, wild-type mice showed no change in lung tight junction morphologic features in response to mild systemic endotoxemia. These findings support a key role of JAM-A in promoting tight junction homeostasis and lung barrier function by coordinating interactions among claudins, the tight junction scaffold, and the cytoskeleton. PMID:25438062

  4. Estrogen Modulates Expression of Tight Junction Proteins in Rat Vagina

    PubMed Central

    Oh, Kyung-Jin; Ahn, Kyuyoun

    2016-01-01

    Background. The objectives of this study were to investigate the localization of tight junctions and the modulation of zonula occludens- (ZO-) 1, occludin and claudin-1 expression by estrogen in castrated female rat vagina. Female Sprague-Dawley rats (230–240 g, n = 45) were divided into three groups and subjected to a sham operation (control group, n = 15), bilateral ovariectomy (Ovx group, n = 15), or bilateral ovariectomy followed by daily subcutaneous injection of 17β-estradiol (50 μg/kg/day, Ovx + Est group, n = 15). The cellular localization and expression of ZO-1, occludin, and claudin-1 were determined in each group by immunohistochemistry and western blot. Results. Expression of ZO-1 was diffuse in all groups, with the highest intensity in the superficial epithelium in the control group. Occludin was localized in the intermediate and basal epithelium. Claudin-1 was most intense in the superficial layer of the vaginal epithelium in the control group. Expression of ZO-1, occludin, and claudin-1 was significantly decreased after ovariectomy and was restored to the level of the control after estrogen replacement. Conclusions. Tight junctions are distinctly localized in rat vagina, and estrogen modulates the expression of tight junctions. Further researches are needed to clarify the functional role of tight junctions in vaginal lubrication. PMID:27127786

  5. 76 FR 65728 - Advisory Committee on Childhood Lead Poisoning Prevention (ACCLPP)

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-24

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention (CDC) Advisory Committee on Childhood Lead... INFORMATION: Claudine Johnson, Program Operation Assistant or Tiffany Turner, Healthy Homes and Lead...

  6. Identification of Variants of Hepatitis C Virus (HCV) Entry Factors in Patients Highly Exposed to HCV but Remaining Uninfected: An ANRS Case-Control Study.

    PubMed

    Fouquet, Baptiste; Ghosn, Jade; Quertainmont, Yann; Salmon, Dominique; Rioux, Christophe; Duvivier, Claudine; Delfraissy, Jean-François; Misrahi, Micheline

    2015-01-01

    Hepatitis C virus (HCV) causes persistent infection in 75% of cases and is a major public health problem worldwide. More than 92% of intravenous drug users (IDU) infected by human immunodeficiency virus type 1 (HIV-1) are seropositive for HCV, and it is conceivable that some HIV-1-infected IDU who remain uninfected by HCV may be genetically resistant.Here we conducted a case-control study to identify mutations in HCV entry coreceptors in HIV-infected IDU who remained uninfected by HCV. We recruited 138 patients, comprising 22 HIV+ HCV- case IDU and 116 HIV+ HCV+ control IDU. We focused on coreceptors in which point mutations are known to abolish HCV infectivity in vitro. Our previous study of the Claudin-1 gene revealed no specific variants in the same case population. Here we performed direct genomic sequencing of the Claudin-6, Claudin-9, Occludin and Scavenger receptor-B1 (SCARB1) gene coding regions. Most HIV+ HCV- IDU had no mutations in HCV coreceptors. However, two HIV+ HCV- patients harbored a total of four specific mutations/variants of HCV entry factors that were not found in the HIV+ HCV+ controls. One case patient harbored heterozygous variants of both Claudin-6 and Occludin, and the other case patient harbored two heterozygous variants of SCARB1. This suggests that HCV resistance might involve complex genetic events and factors other than coreceptors, a situation similar to that reported for HIV-1 resistance. PMID:26571379

  7. Tight junctions and human diseases.

    PubMed

    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.

  8. Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier.

    PubMed

    Caron, Tyler J; Scott, Kathleen E; Fox, James G; Hagen, Susan J

    2015-10-28

    Long-term chronic infection with Helicobacter pylori (H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer, tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach, or dysfunction in the infected stomach, however, are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells, claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules, each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging, because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore, the role of H. pylori virulence factors, such as cytotoxin-associated gene A and vacoulating cytotoxin, in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo, likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study, as well, is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions, normally and in H. pylori infection, and make predictions about the consequences of claudin reorganization during H. pylori infection.

  9. The impaired intestinal mucosal immune system by valine deficiency for young grass carp (Ctenopharyngodon idella) is associated with decreasing immune status and regulating tight junction proteins transcript abundance in the intestine.

    PubMed

    Luo, Jian-Bo; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu

    2014-09-01

    This study investigated the effects of dietary valine on the growth, intestinal immune response, tight junction proteins transcript abundance and gene expression of immune-related signaling molecules in the intestine of young grass carp (Ctenopharyngodon idella). Six iso-nitrogenous diets containing graded levels of valine (4.3-19.1 g kg(-)(1) diet) were fed to the fish for 8 weeks. The results showed that percentage weight gain (PWG), feed intake and feed efficiency of fish were the lowest in fish fed the valine-deficient diet (P < 0.05). In addition, valine deficiency decreased lysozyme, acid phosphatase activities and complement 3 content in the intestine (P < 0.05), down-regulated mRNA levels of interleukin 10, transforming growth factor β1, IκBα and target of rapamycin (TOR) (P < 0.05), and up-regulated tumor necrosis factor α, interleukin 8 and nuclear factor κB P65 (NF-κB P65) gene expression (P < 0.05). Additionally, valine deficiency significantly decreased transcript of Occludin, Claudin b, Claudin c, Claudin 3, and ZO-1 (P < 0.05), and improved Claudin 15 expression in the fish intestine (P < 0.05). However, valine did not have a significant effect on expression of Claudin 12 in the intestine of grass carp (P > 0.05). In conclusion, valine deficiency decreased fish growth and intestinal immune status, as well as regulated gene expression of tight junction proteins, NF-κB P65, IκBα and TOR in the fish intestine. Based on the quadratic regression analysis of lysozyme activity or PWG, the dietary valine requirement of young grass carp (268-679 g) were established to be 14.47 g kg(-1) diet (4.82 g 100 g(-1) CP) or 14.00 g kg(-1) diet (4.77 g 100 g(-1) CP), respectively.

  10. Endotoxemia alters tight junction gene and protein expression in the kidney.

    PubMed

    Eadon, Michael T; Hack, Bradley K; Xu, Chang; Ko, Benjamin; Toback, F Gary; Cunningham, Patrick N

    2012-09-15

    Intact tight junctional (TJ) proteins are required for tubular ion transport and waste excretion. Disruption of TJs may contribute to a decreased glomerular filtration rate in acute kidney injury (AKI) via tubular backleak. The effect of LPS-mediated AKI on murine TJs has not been studied extensively. We hypothesized LPS endotoxin administration to mice would disrupt tubular TJ proteins including zonula occludens-1 (ZO-1), occludin, and claudins. ZO-1 and occludin immunofluorescence 24 h post-LPS revealed a marked change in localization from the usual circumferential fencework pattern to one with substantial fragmentation. Renal ZO-1 expression was significantly reduced 24 h after LPS (decrease of 56.1 ± 7.4%, P < 0.001), with subsequent recovery. ZO-1 mRNA expression was increased 24 h post-LPS (4.34 ± 0.87-fold, P = 0.0019), suggesting disruption of ZO-1 protein is not mediated by transcriptional regulation, but rather by degradation or changes in translation. Similarly, claudin-4 protein expression was decreased despite elevated mRNA. LPS administration resulted in dephosphorylation of occludin and fragmented tubular redistribution. Protein expression of claudin-1, and -3 was increased after LPS. ZO-1, occludin, and claudin-1, -3, and -4 gene expression were increased 48 h after LPS, suggesting a renal response to strengthen TJs following injury. Interestingly, reduced mRNA expression was found only for claudin-8. This study provides further support that LPS-induced AKI is associated with structural injury and is not merely due to hemodynamic changes.

  11. Tight Junction Defects in Atopic Dermatitis

    PubMed Central

    De Benedetto, Anna; Rafaels, Nicholas M.; McGirt, Laura Y.; Ivanov, Andrei I.; Georas, Steve N.; Cheadle, Chris; Berger, Alan E.; Zhang, Kunzhong; Vidyasagar, Sadasivan; Yoshida, Takeshi; Boguniewicz, Mark; Hata, Tissa; Schneider, Lynda C.; Hanifin, Jon M.; Gallo, Richard L.; Novak, Natalija; Weidinger, Stephan; Beaty, Terri H.; Leung, Donald Y.; Barnes, Kathleen C.; Beck, Lisa A.

    2010-01-01

    Background Atopic dermatitis (AD) is characterized by dry skin and a hyperreactive immune response to allergens, two cardinal features that are caused in part by epidermal barrier defects. Tight junctions (TJ) reside immediately below the stratum corneum and regulate the selective permeability of the paracellular pathway. Objective We evaluated the expression/function of the TJ protein, claudin-1 in epithelium from AD and nonatopic (NA) subjects and screened two American populations for SNPs in CLDN1. Methods Expression profiles of nonlesional epithelium from extrinsic AD, NA and psoriasis subjects were generated using Illumina’s BeadChips. Dysregulated intercellular proteins were validated by tissue staining and qPCR. Bioelectric properties of epithelium were measured in Ussing chambers. Functional relevance of claudin-1 was assessed using a knockdown approach in primary human keratinocytes (PHK). Twenty seven haplotype-tagging SNPs in CLDN1 were screened in two independent AD populations. Results We observed strikingly reduced expression of the TJ proteins claudin-1 and -23 only in AD, which were validated at the mRNA and protein levels. Claudin-1 expression inversely correlated with Th2 biomarkers. We observed a remarkable impairment of the bioelectric barrier function in AD epidermis. In vitro, we confirmed that silencing claudin-1 expression in human keratinocytes diminishes TJ function while enhancing keratinocyte proliferation. Finally, CLDN1 haplotype-tagging single nucleotide polymorphisms revealed associations with AD in two North American populations. Conclusion Taken together, these data suggest that an impaired epidermal TJ is a novel feature of skin barrier dysfunction and immune dysregulation observed in AD, and that CLDN1 may be a new susceptibility gene in this disease. PMID:21163515

  12. Epigenetic Regulation of MicroRNAs Controlling CLDN14 Expression as a Mechanism for Renal Calcium Handling

    PubMed Central

    Gong, Yongfeng; Himmerkus, Nina; Plain, Allein; Bleich, Markus

    2015-01-01

    The kidney has a major role in extracellular calcium homeostasis. Multiple genetic linkage and association studies identified three tight junction genes from the kidney—claudin-14, -16, and -19—as critical for calcium imbalance diseases. Despite the compelling biologic evidence that the claudin-14/16/19 proteins form a regulated paracellular pathway for calcium reabsorption, approaches to regulate this transport pathway are largely unavailable, hindering the development of therapies to correct calcium transport abnormalities. Here, we report that treatment with histone deacetylase (HDAC) inhibitors downregulates renal CLDN14 mRNA and dramatically reduces urinary calcium excretion in mice. Furthermore, treatment of mice with HDAC inhibitors stimulated the transcription of renal microRNA-9 (miR-9) and miR-374 genes, which have been shown to repress the expression of claudin-14, the negative regulator of the paracellular pathway. With renal clearance and tubule perfusion techniques, we showed that HDAC inhibitors transiently increase the paracellular cation conductance in the thick ascending limb. Genetic ablation of claudin-14 or the use of a loop diuretic in mice abrogated HDAC inhibitor-induced hypocalciuria. The genetic mutations in the calcium-sensing receptor from patients with autosomal dominant hypocalcemia (ADH) repressed the transcription of miR-9 and miR-374 genes, and treatment with an HDAC inhibitor rescued the phenotypes of cell and animal models of ADH. Furthermore, systemic treatment of mice with antagomiRs against these miRs relieved claudin-14 gene silencing and caused an ADH-like phenotype. Together, our findings provide proof of concept for a novel therapeutic principle on the basis of epigenetic regulation of renal miRs to treat hypercalciuric diseases. PMID:25071082

  13. Characterization of cell lines derived from breast cancers and normal mammary tissues for the study of the intrinsic molecular subtypes.

    PubMed

    Prat, Aleix; Karginova, Olga; Parker, Joel S; Fan, Cheng; He, Xiaping; Bixby, Lisa; Harrell, J Chuck; Roman, Erick; Adamo, Barbara; Troester, Melissa; Perou, Charles M

    2013-11-01

    Five molecular subtypes (luminal A, luminal B, HER2-enriched, basal-like, and claudin-low) with clinical implications exist in breast cancer. Here, we evaluated the molecular and phenotypic relationships of (1) a large in vitro panel of human breast cancer cell lines (BCCLs), human mammary fibroblasts (HMFs), and human mammary epithelial cells (HMECs); (2) in vivo breast tumors; (3) normal breast cell subpopulations; (4) human embryonic stem cells (hESCs); and (5) bone marrow-derived mesenchymal stem cells (hMSC). First, by integrating genomic data of 337 breast tumor samples with 93 cell lines we were able to identify all the intrinsic tumor subtypes in the cell lines, except for luminal A. Secondly, we observed that the cell lines recapitulate the differentiation hierarchy detected in the normal mammary gland, with claudin-low BCCLs and HMFs cells showing a stromal phenotype, HMECs showing a mammary stem cell/bipotent progenitor phenotype, basal-like cells showing a luminal progenitor phenotype, and luminal B cell lines showing a mature luminal phenotype. Thirdly, we identified basal-like and highly migratory claudin-low subpopulations of cells within a subset of triple-negative BCCLs (SUM149PT, HCC1143, and HCC38). Interestingly, both subpopulations within SUM149PT were enriched for tumor-initiating cells, but the basal-like subpopulation grew tumors faster than the claudin-low subpopulation. Finally, claudin-low BCCLs resembled the phenotype of hMSCs, whereas hESCs cells showed an epithelial phenotype without basal or luminal differentiation. The results presented here help to improve our understanding of the wide range of breast cancer cell line models through the appropriate pairing of cell lines with relevant in vivo tumor and normal cell counterparts.

  14. Intestinal barrier analysis by assessment of mucins, tight junctions, and α-defensins in healthy C57BL/6J and BALB/cJ mice.

    PubMed

    Volynets, Valentina; Rings, Andreas; Bárdos, Gyöngyi; Ostaff, Maureen J; Wehkamp, Jan; Bischoff, Stephan C

    2016-01-01

    The intestinal barrier is gaining increasing attention because it is related to intestinal homeostasis and disease. Different parameters have been used in the past to assess intestinal barrier functions in experimental studies; however most of them are poorly defined in healthy mice. Here, we compared a number of barrier markers in healthy mice, established normal values and correlations. In 48 mice (24 C57BL/6J, 24 BALB/cJ background), we measured mucus thickness, and expression of mucin-2, α-defensin-1 and -4, zonula occludens-1, occludin, junctional adhesion molecule-A, claudin-1, 2 and -5. We also analyzed claudin-3 and fatty acid binding protein-2 in urine and plasma, respectively. A higher expression of mucin-2 protein was found in the colon compared to the ileum. In contrast, the α-defensins-1 and -4 were expressed almost exclusively in the ileum. The protein expression of the tight junction molecules claudin-1, occludin and zonula occludens-1 did not differ between colon and ileum, although some differences occurred at the mRNA level. No age- or gender-related differences were found. Differences between C57BL/6J and BALB/cJ mice were found for α-defensin-1 and -4 mRNA expression, and for urine and plasma marker concentrations. The α-defensin-1 mRNA correlated with claudin-5 mRNA, whereas α-defensin-4 mRNA correlated with claudin-3 concentrations in urine. In conclusion, we identified a number of murine intestinal barrier markers requiring tissue analyses or measurable in urine or plasma. We provide normal values for these markers in mice of different genetic background. Such data might be helpful for future animal studies in which the intestinal barrier is of interest. PMID:27583194

  15. Tight junction disruption: Helicobacter pylori and dysregulation of the gastric mucosal barrier

    PubMed Central

    Caron, Tyler J; Scott, Kathleen E; Fox, James G; Hagen, Susan J

    2015-01-01

    Long-term chronic infection with Helicobacter pylori (H. pylori) is a risk factor for gastric cancer development. In the multi-step process that leads to gastric cancer, tight junction dysfunction is thought to occur and serve as a risk factor by permitting the permeation of luminal contents across an otherwise tight mucosa. Mechanisms that regulate tight junction function and structure in the normal stomach, or dysfunction in the infected stomach, however, are largely unknown. Although conventional tight junction components are expressed in gastric epithelial cells, claudins regulate paracellular permeability and are likely the target of inflammation or H. pylori itself. There are 27 different claudin molecules, each with unique properties that render the mucosa an intact barrier that is permselective in a way that is consistent with cell physiology. Understanding the architecture of tight junctions in the normal stomach and then changes that occur during infection is important but challenging, because most of the reports that catalog claudin expression in gastric cancer pathogenesis are contradictory. Furthermore, the role of H. pylori virulence factors, such as cytotoxin-associated gene A and vacoulating cytotoxin, in regulating tight junction dysfunction during infection is inconsistent in different gastric cell lines and in vivo, likely because non-gastric epithelial cell cultures were initially used to unravel the details of their effects on the stomach. Hampering further study, as well, is the relative lack of cultured cell models that have tight junction claudins that are consistent with native tissues. This summary will review the current state of knowledge about gastric tight junctions, normally and in H. pylori infection, and make predictions about the consequences of claudin reorganization during H. pylori infection. PMID:26523106

  16. Partial recovery of the damaged rat blood-brain barrier is mediated by adherens junction complexes, extracellular matrix remodeling and macrophage infiltration following focal astrocyte loss

    PubMed Central

    Willis, Colin L.; Camire, Ryan B.; Brule, Stephanie A.; Ray, David E.

    2013-01-01

    Blood-brain barrier (BBB) dysfunction is a feature of many neurodegenerative disorders. The mechanisms and interactions between astrocytes, extracellular matrix and vascular endothelial cells in regulating the mature BBB are poorly understood. We have previously shown that transitory GFAP-astrocyte loss, induced by systemic administration of 3-chloropropanediol, leads to reversible disruption of tight junction complexes and BBB integrity to a range of markers. However, early restoration of BBB integrity to dextran (10-70 kDa) and fibrinogen was seen in the absence of paracellular tight junction proteins claudin-5 and occludin. In the present study we show that in the GFAP-astrocyte lesioned rat inferior colliculus, paracellular expression of adherens junction proteins (VE-cadherin and β-catenin) was maintained in vascular endothelial cells that lacked paracellular claudin-5 expression and which showed reversible post-translational occludin modification. Claudin-1 expression paralleled the loss and recovery of claudin-5, while claudin -3 or -12 immunoreactivity was not detected. In addition, the extracellular matrix, as visualized by laminin and fibronectin, underwent extensive reversible remodeling and perivascular CD169 macrophages become abundant throughout the lesioned inferior colliculus. At a time that GFAP-astrocytes repopulated the lesion area and tight junction proteins were returned to paracellular domains, the extracellular matrix and leukocyte profiles normalized and resembled profiles seen in control tissue. This study supports the hypothesis that a combination of paracellular adherens junctional proteins, remodeled basement membrane and the presence perivascular leukocytes provide a temporary barrier to limit extravasation of macromolecules and potentially neurotoxic substances into the brain parenchyma until tight junction proteins are restored to paracellular domains. PMID:23845748

  17. Corticomedullary difference in the effects of dietary Ca²⁺ on tight junction properties in thick ascending limbs of Henle's loop.

    PubMed

    Plain, Allein; Wulfmeyer, Vera C; Milatz, Susanne; Klietz, Adrian; Hou, Jianghui; Bleich, Markus; Himmerkus, Nina

    2016-02-01

    The thick ascending limb of Henle's loop (TAL) drives an important part of the reabsorption of divalent cations. This reabsorption occurs via the paracellular pathway formed by the tight junction (TJ), which in the TAL shows cation selectivity. Claudins, a family of TJ proteins, determine the permeability and selectivity of this pathway. Mice were fed with normal or high-Ca(2+) diet, and effects on the reabsorptive properties of cortical and medullary TAL segments were analysed by tubule microdissection and microperfusion. Claudin expression was investigated by immunostaining and quantitative PCR. We show that the TAL adapted to high Ca(2+) load in a sub-segment-specific manner. In medullary TAL, transcellular NaCl transport was attenuated. The transepithelial voltage decreased from 10.9 ± 0.6 mV at control diet to 8.3 ± 0.5 mV at high Ca(2+) load, thereby reducing the driving force for Ca(2+) and Mg(2+) uptake. Cortical TAL showed a reduction in paracellular Ca(2+) and Mg(2+) permeabilities from 8.2 ± 0.7 to 6.2 ± 0.5 ∙ 10(-4) cm/s and from 4.8 ± 0.5 to 3.0 ± 0.2 · 10(-4) cm/s at control and high-Ca(2+) diet, respectively. Expression, localisation and regulation of claudins 10, 14, 16 and 19 differed along the corticomedullary axis: Towards the cortex, the main site of divalent cation reabsorption in TAL, high-Ca(2+) intake led to a strong upregulation of claudin-14 within TAL TJs while claudin-16 and -19 were unaltered. Towards the inner medulla, only claudin-10 was present in TAL TJ strands. In summary, high-Ca(2+) diet induced a reduction of divalent cation reabsorption via a diminution of NaCl transport and driving force in mTAL and via decreased paracellular permeabilities in cTAL. We reveal an important regulatory pattern along the corticomedullary axis and improve the understanding how the kidney disposes of detrimental excess Ca(2+).

  18. Mechanisms of Intestinal Barrier Dysfunction in Sepsis.

    PubMed

    Yoseph, Benyam P; Klingensmith, Nathan J; Liang, Zhe; Breed, Elise R; Burd, Eileen M; Mittal, Rohit; Dominguez, Jessica A; Petrie, Benjamin; Ford, Mandy L; Coopersmith, Craig M

    2016-07-01

    Intestinal barrier dysfunction is thought to contribute to the development of multiple organ dysfunction syndrome in sepsis. Although there are similarities in clinical course following sepsis, there are significant differences in the host response depending on the initiating organism and time course of the disease, and pathways of gut injury vary widely in different preclinical models of sepsis. The purpose of this study was to determine whether the timecourse and mechanisms of intestinal barrier dysfunction are similar in disparate mouse models of sepsis with similar mortalities. FVB/N mice were randomized to receive cecal ligation and puncture (CLP) or sham laparotomy, and permeability was measured to fluoresceinisothiocyanate conjugated-dextran (FD-4) six to 48 h later. Intestinal permeability was elevated following CLP at all timepoints measured, peaking at 6 to 12 h. Tight junction proteins claudin 1, 2, 3, 4, 5, 7, 8, 13, and 15, Junctional Adhesion Molecule-A (JAM-A), occludin, and ZO-1 were than assayed by Western blot, real-time polymerase chain reaction, and immunohistochemistry 12 h after CLP to determine potential mechanisms underlying increases in intestinal permeability. Claudin 2 and JAM-A were increased by sepsis, whereas claudin-5 and occludin were decreased by sepsis. All other tight junction proteins were unchanged. A further timecourse experiment demonstrated that alterations in claudin-2 and occludin were detectable as early as 1 h after the onset of sepsis. Similar experiments were then performed in a different group of mice subjected to Pseudomonas aeruginosa pneumonia. Mice with pneumonia had an increase in intestinal permeability similar in timecourse and magnitude to that seen in CLP. Similar changes in tight junction proteins were seen in both models of sepsis although mice subjected to pneumonia also had a marked decrease in ZO-1 not seen in CLP. These results indicate that two disparate, clinically relevant models of sepsis

  19. Learner, Student, Speaker: Why It Matters How We Call Those We Teach

    ERIC Educational Resources Information Center

    Biesta, Gert

    2010-01-01

    In this paper I discuss three different ways in which we can refer to those we teach: as learner, as student or as speaker. My interest is not in any aspect of teaching but in the question whether there can be such a thing as emancipatory education. Working with ideas from Jacques Ranciere I offer the suggestion that emancipatory education can be…

  20. Art, Politics, and the Pedagogical Relation

    ERIC Educational Resources Information Center

    Ruitenberg, Claudia W.

    2011-01-01

    In recent years the French philosopher Jacques Ranciere has addressed the predicament of artists and curators who, in their eagerness to convey a critical message or engage their viewers in an emancipatory process, end up predetermining the outcomes of the experience, hence blocking its critical or emancipatory potential. In this essay I consider…

  1. Emancipation, Equality and Education: Ranciere's Critique of Bourdieu and the Question of Performativity

    ERIC Educational Resources Information Center

    Pelletier, Caroline

    2009-01-01

    Jacques Rancire's work has had significant impact in philosophy and literary theory, but remains largely undiscussed in the field of education. This article is a review of the relevance of Rancire's work to education research. Rancire's argument about education emerges from his critique of Bourdieu, which states that Bourdieu reinforces inequality…

  2. What I Talk about When I Talk about Teaching and Learning

    ERIC Educational Resources Information Center

    Safstrom, Carl Anders

    2011-01-01

    In this text I discuss two events in which I learned something important about life and about education in order to formulate in a precise manner two propositions for my pedagogical creed. In focus for both are the interrelatedness of theory and life. The stories are told through the lenses of Emmanuel Levinas's and Jacques Ranciere's thinking,…

  3. Aesthetics, Affect, and Educational Politics

    ERIC Educational Resources Information Center

    Means, Alex

    2011-01-01

    This essay explores aesthetics, affect, and educational politics through the thought of Gilles Deleuze and Jacques Ranciere. It contextualizes and contrasts the theoretical valences of their ethical and democratic projects through their shared critique of Kant. It then puts Ranciere's notion of dissensus to work by exploring it in relation to a…

  4. Creative Class, Dismissed

    ERIC Educational Resources Information Center

    Fendrich, Laurie

    2008-01-01

    Recently the author has been including in her undergraduate seminars Jean-Jacques Rousseau's "Letter to d'Alembert on the Theatre" (1758), the most provocative essay on the arts ever written. It is about the unintended effects of theater--which, for Rousseau, stands in for all of the arts--on an audience. The essay is an impassioned rebuttal to…

  5. Problematizing Knowledge-Power Relationships: A Rancièrian Provocation for Music Education

    ERIC Educational Resources Information Center

    Kanellopoulos, Panagiotis A.

    2016-01-01

    This paper suggests a framework for re-thinking the relationships between power and knowledge in music education. Informed by Jacques Rancière's notion of equality it explores how a dialectic between knowledge/mastery and ignorance/equality effects a rupture in the canonical relationships between knowledge and authority. Further, and based on a…

  6. Ambitions and Responsibilities: A Textual Analysis of the Norwegian National Curriculum Regulations for Nursing Education

    ERIC Educational Resources Information Center

    Solbrekke, Tone Dyrdal; Heggen, Kristin; Engebretsen, Eivind

    2014-01-01

    Society assigns professional educational programs the responsibility to aid students in learning and dedicate expert knowledge to furthering the well-being of citizens. This demand calls for addressing the how educational policies prioritize learning professionals' responsibility. Inspired by the theory of Jacques Derrida, we deconstruct the…

  7. Installation of a Bridge Barrier as a Suicide Prevention Strategy in Montréal, Québec, Canada

    PubMed Central

    Perron, Stéphane; Fournier, Michel; Perron, Paul-André; Ouellet, Frédéric

    2013-01-01

    Objectives. We investigated whether the installation of a suicide prevention barrier on Jacques-Cartier Bridge led to displacement of suicides to other jumping sites on Montréal Island and Montérégie, Québec, the 2 regions it connects. Methods. Suicides on Montréal Island and Montérégie were extracted from chief coroners’ records. We used Poisson regression to assess changes in annual suicide rates by jumping from Jacques-Cartier Bridge and from other bridges and other sites and by other methods before (1990–June 2004) and after (2005–2009) installation of the barrier. Results. Suicide rates by jumping from Jacques-Cartier Bridge decreased after installation of the barrier (incidence rate ratio [IRR] = 0.24; 95% confidence interval [CI] = 0.13, 0.43), which persisted when all bridges (IRR = 0.39; 95% CI = 0.27, 0.55) and all jumping sites (IRR = 0.66; 95% CI = 0.54, 0.80) in the regions were considered. Conclusions. Little or no displacement to other jumping sites may occur after installation of a barrier at an iconic site such as Jacques-Cartier Bridge. A barrier’s design is important to its effectiveness and should be considered for new bridges with the potential to become symbolic suicide sites. PMID:23678905

  8. Dissenting with Queer Theory: Reading Rancière Queerly

    ERIC Educational Resources Information Center

    Greteman, Adam J.

    2014-01-01

    In this article, the author looks to the work of Jacques Rancière to engage the possibilities in dissensus in queer theory in education. Fatigued of Foucault, bored with Butler, disdainful of Derrida and dumbfounded by Deleuze and Guattari, and just generally tired of feeling bullied into citing particular people and not others, the author…

  9. Council of Europe Experimental Special Classes for Migrant Workers' Children, Academic Year 1972-73. (Vitry, France).

    ERIC Educational Resources Information Center

    Pestour, Renee; And Others

    During the 1972-73 academic year, an adaptation class for foreign pupils was conducted at the "Anatole France" Co-Educational School in Vitry, France. The class was composed of children between the ages of 6 and 10 years, mainly of Portuguese nationality. Pupils spent 27 hours per week in class. The "Frere Jacques" method, devised by the Office…

  10. The Flemish Bastard and the Former Indians: Metis and Identity in Seventeenth-Century New York

    ERIC Educational Resources Information Center

    Midtrod, Tom Arne

    2010-01-01

    This article examines the lives of three children of Dutch men and Mohawk women: the Mohawk leader Smits Jan and the siblings Jacques van Slyck and Hilletie van Olinda of the Dutch village of Schenectady. In recent years several historians have examined how cross-cultural settings enabled people to reshape their identities. William Hart sees the…

  11. Choreographing Theory: An Analysis of Edouard Lock's "Amelia" (2002) Questioning the Limits of Feminist and Poststructuralist Perspectives

    ERIC Educational Resources Information Center

    Ireland, Ruby

    2009-01-01

    Edouard Lock's dance film "Amelia" (2002) is the focus of this essay. Second-wave feminist and poststructuralist perspectives inform the analysis of this piece of contemporary dance. Laura Mulvey's male gaze theory and Julia Kristeva's theory of the semiotic and symbolic realms of representation are explored and critiqued, whilst Jacques Derrida's…

  12. Sartre: A Collection of Critical Essays. Twentieth Century Views Series.

    ERIC Educational Resources Information Center

    Kern, Edith, Ed.

    One of a series of works aimed at presenting contemporary critical opinion on major authors, this collection includes essays by Edith Kern, Claude-Edmonde Magny, Henri Peyre, Kenneth Douglas, Edmund Wilson, Theophil Spoerri, Jacques Guicharnaud, Eric Bentley, Robert Champigny, Oreste F. Pucciani, Frederic Jameson, Rene Girard, Guido…

  13. Our Brave New World Today

    ERIC Educational Resources Information Center

    Stivers, Richard

    2010-01-01

    Aldous Huxley is perhaps the only author to have written a work of science fiction and a work of nonfiction to ascertain whether fiction had become reality. Both "Brave New World" and "Brave New World Revisited" are discussed and compared with Jacques Ellul's work on technology.

  14. International Reports on Literacy Research: France, United Kingdom, Brazil

    ERIC Educational Resources Information Center

    Malloy, Jacquelynn A., Comp.; Botza, Stergios, Comp.

    2005-01-01

    This is a compilation of reports on international literacy research. The report includes 3 separate reports on France, United Kingdom and Brazil. In the first report, research correspondent Jacques Fijalkow presents research into variations of reading motivation related to students' socioeconomic status (SES), age, and gender. Three of these…

  15. AGORA--II. "The Role of the Company in Lifelong Learning" (Thessaloniki, Greece, November 17-18, 1997). CEDEFOP Panorama.

    ERIC Educational Resources Information Center

    Planas, Jordi

    This document contains the participants list, agenda, and six papers from a seminar on the role of the company in lifelong learning in the European Union. "Introductory Comment: The Role of the Company in Lifelong Learning" (Jacques Delcourt) traces the movement from training for life toward flexible training systems coupled with flexible work and…

  16. On the Borders: The Arrival of Irregular Immigrants in Malta--Some Implications for Education

    ERIC Educational Resources Information Center

    Mercieca, Duncan

    2007-01-01

    This paper concerns the issue of the continual arrival of irregular immigrants in Malta and the problems that ensue. The view generally held is that we need to respond to the needs of irregular immigrants by providing services. However, with reference to some of Jacques Derrida's ideas, I argue in this paper that the "other"/immigrant is not there…

  17. Commodification of Ghana's Volta River: An Example of Ellul's Autonomy of Technique

    ERIC Educational Resources Information Center

    Agbemabiese, Lawrence; Byrne, John

    2005-01-01

    Jacques Ellul argued that modernity's nearly exclusive reliance on science and technology to design society would threaten human freedom. Of particular concern for Ellul was the prospect of the technical milieu overwhelming culture. The commodification of the Volta River in order to modernize Ghana illustrates the Ellulian dilemma of the autonomy…

  18. Proceedings of the EMU Conference on Foreign Languages for Business and the Professions (Dearborn, Michigan, April 5-7, 1984). Part I: Business Needs/Educators Respond.

    ERIC Educational Resources Information Center

    Voght, Geoffrey M., Ed.

    Part I of the proceedings includes seven presentations. They are: "International Language Evaluation and Professional Points of View" (M. Jacques Cartier); "Foreign Languages and International Businesses in Colorado: A Report and Assessment" (Alain W. D. Ranwez and Donald Schmidt); "The Use of Foreign Languages in International Banking: A Survey…

  19. Preschoolers' Recitation versus Understanding of a Televised Song.

    ERIC Educational Resources Information Center

    Calvert, Sandra L.; And Others

    A study was conducted to determine whether children think about the verbal messages embedded in songs, or merely sing the words without thinking about them. A total of 48 preschool girls and boys viewed a televised vignette of the song "Frere Jacques" under varying conditions of language comprehensibility, rehearsal, and repetition. The visual…

  20. Quebec's Aboriginal Languages: History, Planning and Development. Multilingual Matters 107.

    ERIC Educational Resources Information Center

    Maurais, Jacques, Ed.

    This book provides an overview of the history, present circumstances, and future prospects of the native languages of Quebec: Abenaki, Algonquin, Atikamekw, Cree, Inuktitut, Micmac, Mohawk, Montagnais, and Naskapi. Chapter 1, "The Situation of Aboriginal Languages in the Americas" (Jacques Maurais), discusses the linguistic demography of American…

  1. Papers on Educational Reform, Volume IV.

    ERIC Educational Resources Information Center

    Open Court Publishing Co., La Salle, IL.

    The following nine papers were presented to the Open Court Editorial Advisory Board Meeting, 1974. In "National Assessment of Educational Progress" J. Stanley Ahmann provides an overview of assessment aims, construction, and results. Jacques Barzun discusses the history of educational theory in "The Use of Tradition in Educational Disputes". In…

  2. Music Education in the Sign of Deconstruction

    ERIC Educational Resources Information Center

    Dyndahl, Petter

    2008-01-01

    In this article, the aim is to address different forms of relationship between deconstruction, as coined by Jacques Derrida, and research perspectives on music education. Deconstruction represents a radical departure from Western ontology from Plato onward and its essentialistic notions of the metaphysics of presence. Instead, Derrida claims that…

  3. The Promise of Politics and Pedagogy in Derrida

    ERIC Educational Resources Information Center

    Peters, Michael A.

    2006-01-01

    In this article, the author profiles Jacques Derrida, whose teaching activity made an invaluable and indelible contribution to the intellectual life of the University of California, Irvine (UCI). The question of pedagogy is central for Derrida, not only in terms of teaching people to read and write differently, but as a means for appreciating the…

  4. Representational and Territorial Economies in Global Citizenship Education: Welcoming the Other at the Limit of Cosmopolitan Hospitality

    ERIC Educational Resources Information Center

    Langmann, Elisabet

    2011-01-01

    In this article, I argue that any success a discourse on cosmopolitan hospitality might have in global citizenship education depends on how it deals with its own limits, and I propose a way of responding to these limits that takes the cosmopolitan commitment to openness to the other seriously. Following Jacques Derrida, my point is that to teach…

  5. Whose Place Is This Anyway? Reflecting upon Hospitality and Higher Education

    ERIC Educational Resources Information Center

    Loewen, Nathan

    2016-01-01

    In this essay I propose that using online tools to connect geographically-separated classrooms for real-time collaborative learning experiences may effectively develop intercultural competency in the religious studies classroom. I explore personal examples from several international and inter-institutional collaborations with Jacques Derrida's…

  6. Derrida, Friendship and Responsible Teaching in Contrast to Effective Teaching

    ERIC Educational Resources Information Center

    Sinha, Shilpi

    2013-01-01

    Educational theorists working within the tradition of Jacques Derrida and Emmanuel Levinas's thought, posit teaching to be a site of implied ethics, that is, a realm in which non-violent or less violent relations to the other are possible. Derrida links ethics to the realm of friendship, enabling one to understand teaching as a site of the…

  7. Uncommon Grounds: Preparing Students in Higher Music Education for the Unpredictable

    ERIC Educational Resources Information Center

    Lapidaki, Eleni

    2016-01-01

    This article considers the contribution that Jacques Derrida's work "Of Hospitality" might make to higher music education as it unsettles the usual ascription of normative value to learning and teaching music at the university. Along these lines, what is most at issue in the encounter with Derrida's thinking is the concomitant notion of…

  8. What Kind of Deconstruction for Deconstructive Religious Education? Response to Noaparast and Khosravi

    ERIC Educational Resources Information Center

    Biesta, Gert J. J.; Miedema, Siebren

    2011-01-01

    The question whether the writings of Jacques Derrida have anything to offer for religious education is, in the authors' opinion, a very important one. In their attempts at answering the question, the authors have tried to argue that the writings of Derrida provide openings that speak to both theology and education in a way that is not only…

  9. "Technique" and Artistic Imitation and Invention

    ERIC Educational Resources Information Center

    Younes, Samir

    2012-01-01

    Contrary to the general belief that modernist art and architecture reflect the technological society, Jacques Ellul maintains in his "L'empire du non-sens" that they are justifications for the integration of humankind into what he called the technicist complex. Modernism in art and architecture meant that every product must be qualified by a…

  10. Inventing the Educational Subject in the "Information Age"

    ERIC Educational Resources Information Center

    Bojesen, Emile

    2016-01-01

    This paper asks the question of how we can situate the educational subject in what Luciano Floridi has defined as an "informational ontology" (Floridi in "The philosophy of information." Oxford University Press, Oxford, 2011a). It will suggest that Jacques Derrida and Bernard Stiegler offer paths toward rethinking the…

  11. Pedagogies of Hauntology in History Education: Learning to Live with the Ghosts of Disappeared Victims of War and Dictatorship

    ERIC Educational Resources Information Center

    Zembylas, Michalinos

    2013-01-01

    Michalinos Zembylas examines how history education can be reconceived in terms of Jacques Derrida's notion of "hauntology," that is, as an ongoing conversation with the "ghost"--in the case of this essay, the ghosts of disappeared victims of war and dictatorship. Here, Zembylas uses hauntology as both metaphor and pedagogical methodology for…

  12. Affordances of Equality: Rancière, Emerging Media, and the New Amateur

    ERIC Educational Resources Information Center

    Thumlert, Kurt

    2015-01-01

    This article extends a recent educational engagement with the work of Jacques Rancière by linking his meditations on 19th-century worker emancipation to present cultural contexts and media forms. Taking Nick Prior's (2010) notion of the "new amateur" as point of departure, I argue that new media and attendant production contexts offer an…

  13. "Listen Then, Or, Rather, Answer": Contemporary Challenges to Socratic Education

    ERIC Educational Resources Information Center

    Fullam, Jordan

    2015-01-01

    The popularity of Jacques Rancière in recent work in educational philosophy has rejuvenated discussion of the merits and weaknesses of Socratic education, both in Plato's dialogues and in invocations of Socrates in contemporary educational practice. In this essay Jordan Fullam explores the implications of this trend through comparing…

  14. East Siberia and Bering Sea, Russia

    NASA Technical Reports Server (NTRS)

    2002-01-01

    On June 5, 2001 MODIS captured this true-color image of Eastern Siberia and the Bering Strait. To the right of the image is the western tip of Alaska's St. Lawrence Island. Credit: Jacques Descloitres, MODIS Land Rapid Response Team

  15. [The sense of the senseless, psychoanalytic aspects of delusion in psychosis].

    PubMed

    Chaperot, Christophe

    2011-01-01

    The psychoanalytic approach to delusion in psychosis leads us to examine the function of a "furrow". It is necessary to remain in the furrow in order not to become delusional. References to Sigmund Freud, Jacques Lacan, Mélanie Klein and Jean-Claude Maleval enlighten us as to the origin and the function of delusion as an attempt to give meaning.

  16. Opening Philosophy to the World: Derrida and Education in Philosophy

    ERIC Educational Resources Information Center

    Burik, Steven

    2009-01-01

    In this essay, Steven Burik discusses Jacques Derrida's position with regard to the place of education in philosophy within the university system, and then relates these thoughts to comparative philosophy. Philosophers find themselves constantly having to defend philosophy and the importance of teaching philosophy against pressure from the powers…

  17. Annals of Community-Oriented Education, Volume 3, Part I, 1990.

    ERIC Educational Resources Information Center

    Engel, C., Ed.; And Others

    This collection gathers together several papers reflecting the state of the art in the development of community-based programs in health sciences education. Titles and authors are as follows: "Issues in Implementing a Problem-Based Learning Curriculum at the University of Sherbrooke" (Jacques E. Des Marchais; Bertrand Dumais); "Students'…

  18. Language and Being Human in Technology

    ERIC Educational Resources Information Center

    van der Laan, J. M.

    2012-01-01

    This essay considers the analysis Jacques Ellul carried out about the devaluation of language. This investigation also explores the consequences of that devaluation (or humiliation as Ellul called it) wrought by our orientation to technology. Our existence in technology transforms language and our use of it, shifting emphasis as well to the visual…

  19. Lacan, Subjectivity and the Task of Mathematics Education Research

    ERIC Educational Resources Information Center

    Brown, Tony

    2008-01-01

    This paper addresses the issue of subjectivity in the context of mathematics education research. It introduces the psychoanalyst and theorist Jacques Lacan whose work on subjectivity combined Freud's psychoanalytic theory with processes of signification as developed in the work of de Saussure and Peirce. The paper positions Lacan's subjectivity…

  20. Two Cultures, Two Dialogists and Two Intersecting Theories

    ERIC Educational Resources Information Center

    Ravenscroft, Lesley

    2012-01-01

    This paper presents some possibilities for applying the linguistic and psychological theories of two dialogists, Mikhail Bakhtin and Jacques Lacan, to the classroom. There is a short summary of how the two theories may interact with each other and then a discussion of their two opposing views of identity formation. Bakhtin was a Russian, coming…

  1. Don't Fence Me In: The Liberation of Undomesticated Critique

    ERIC Educational Resources Information Center

    Ruitenberg, Claudia

    2004-01-01

    In response to Helmut Heid's critique of domesticated philosophical critique, I focus on the metaphor of domestication, which is central to his article. Drawing on the work of Jacques Derrida, I offer a deconstructive critique of the opposition between domesticated and undomesticated critique, arguing that a clear conceptual demarcation between…

  2. Thanatos and Civilization: Lacan, Marcuse, and the Death Drive

    ERIC Educational Resources Information Center

    Cho, Daniel

    2006-01-01

    During the 1950s and 1960s two thinkers, Herbert Marcuse and Jacques Lacan, were conducting a "return to Freud" for very similar reasons. If the differences between them are often advertised, their affinities are less so. In this article, I examine how their "return to Freud" and fidelity to psychoanalysis serves as a common ground to read each in…

  3. Why Ranciere Now?

    ERIC Educational Resources Information Center

    Tanke, Joseph J.

    2010-01-01

    This essay introduces readers to the work of Jacques Ranciere and demonstrates how his thinking on art and politics can help alleviate certain impasses within contemporary aesthetic and political theory. Exploiting untranslated sources, I present Ranciere's recent work as responding to predispositions within the theory and practice of art that…

  4. 'Administering the Medicine': Progressive Education, Colonialism, and the State.

    ERIC Educational Resources Information Center

    Cote, Joost

    2001-01-01

    Draws comparisons between the Australian education directors, Frank Tate and Jacques Henry Abendanon. Discusses educational reform issues based on racial contexts and social, political, and cultural aspects in the British colony of Victoria and the Dutch colony of Java. Concludes that, though their politcal contexts are different, their views are…

  5. Eyeless in America, the Sequel: Hollywood and Indiewood's Iraq War on Film

    ERIC Educational Resources Information Center

    Blackmore, Tim

    2012-01-01

    This article builds on conclusions drawn in the article "Eyeless in America," by the same author and considers how 50 American films about the wars in Iraq and Afghanistan intended to function as what Jacques Ellul called "integration propaganda" fared. This article considers and rejects a number of theories about why most feature war films failed…

  6. "The Treasure Within: Learning to Know, Learning to Do, Learning to Live Together and Learning to Be." What Is the Value of that Treasure 15 Years after Its Publication?

    ERIC Educational Resources Information Center

    Delors, Jacques

    2013-01-01

    This is an English translation of a speech held by French economist and politician Jacques Delors, former President of the European Commission, on 7 November 2011 at the opening of the International Congress on Lifelong Learning in Donostia/San Sebastián, Spain. Fifteen years after the International Commission on Education for the Twenty-first…

  7. Rousseau's "Emile" and its Contribution to the Development of Educational Theory.

    ERIC Educational Resources Information Center

    Oliver, R. Graham

    1982-01-01

    Jean-Jacques Rousseau's educational and political thought is compared to that of John Locke. Rousseau's theories, as expressed in "Emile," are placed in the context of some of that author's other works to show how his educational theories can seem practical in terms of his views on social and political inequality. (PP)

  8. In the Shadow of "Emile": Pedagogues, Pediatricians, Physical Education, 1686-1762

    ERIC Educational Resources Information Center

    Tosato-Rigo, Daniele

    2012-01-01

    This article takes as its starting point the commonplace that Rousseau's "Emile" enabled his contemporaries to discover not only childhood but physical education. Focused on what the pedestal erected for Jean-Jacques somewhat overshadows, a brief historiographic overview and a survey of some major writings on education before Rousseau (by the…

  9. The Growth of Democratic Tradition: The Age of Enlightenment. Tenth Grade Lesson. Schools of California Online Resources for Education (SCORE): Connecting California's Classrooms to the World.

    ERIC Educational Resources Information Center

    Rosa, Marie A.

    This lesson plan begins with an overview of the age of enlightenment and those ideas that influenced the founders of the United States. The lesson plan provides information sheets about five enlightenment thinkers: John Locke (1632-1704), Mary Wolstonecraft (1759-1898), Baron de Montesquieu (1689-1755), Jean Jacques Rousseau (1712-1788), and John…

  10. The Writing Cure: Psychoanalysis, Composition, and the Aims of Education.

    ERIC Educational Resources Information Center

    Bracher, Mark

    Asserting that psychoanalysis and writing instruction have much to offer each other, this book examines the intersection between these two fields and proposes pedagogical uses of psychoanalytic technique for writing instruction. Articulating an approach based on the work of Jacques Lacan, the book shows how a psychoanalytic perspective can offer…

  11. Metaphor and Metonymy.

    ERIC Educational Resources Information Center

    Grigg, Russell

    1994-01-01

    Describes in some detail the structure of metaphor and metonymy, reviewing three main structures of metaphor--supposition, extension, and apposition--and proposing a comprehensive definition of metaphor taking all three structures into account. Draws on Roman Jakobson when explaining Jacques Lacan's claim that condensation is metaphor and…

  12. Subjectivity as an Unlimited Semiosis: Lacan and Peirce

    ERIC Educational Resources Information Center

    Nordtug, Birgit

    2004-01-01

    The discussion on subjectivity is based on the psychoanalyst Jacques Lacan's understanding of subjectivity as constructed in and through language, and the philosopher Charles Sanders Peirce's general ideas of signifying construction as an unlimited sign-exchanging process--the idea of the unlimited semiosis. The article advocates combining…

  13. Aborigines of the Imaginary: Applying Lacan to Aboriginal Education

    ERIC Educational Resources Information Center

    Harrison, Neil

    2012-01-01

    This paper applies the work of Jacques Lacan, a French psychoanalyst, to decipher the desire of the teacher in Aboriginal education. It argues that the images of Aboriginal people represented in Australian classrooms are effects of the teacher's Imaginary, the Imaginary being one of the three psychoanalytic domains theorised by Lacan over a period…

  14. The Ethics of the "Real" In Levinas, Lacan, and Buddhism: Pedagogical Implications.

    ERIC Educational Resources Information Center

    Jagodzinski, Jan

    2002-01-01

    Explores the unstated ethics that exist in the silent space between teacher and students, highlighting Emmanuel Levinas, Jacques Lacan, and Buddhism. The paper uses the juxtaposition of west and east to help illuminate ethical pedagogy, and it argues that there is an unknowable dimension which raises the question of ethics in human relations that…

  15. At the Intersection between the Subject and the Political: A Contribution to an Ongoing Discussion

    ERIC Educational Resources Information Center

    Pais, Alexandre

    2016-01-01

    The issue of subjectivity has recently occasioned a lively discussion in this journal opposing socioculturalism and Lacanian psychoanalysis. By confronting Luis Radford's cultural theory with Jacques Lacan's psychoanalysis, Tony Brown sought to show the limitations of socioculturalism. This article takes advantage of that discussion to develop a…

  16. Burke, Nietzsche, Lacan: Three Perspectives on the Rhetoric of Order.

    ERIC Educational Resources Information Center

    Thomas, Douglas

    1993-01-01

    Examines the complex relationship between rhetoric and order in the works of Kenneth Burke, Friedrich Nietzsche, and Jacques Lacan. Argues for three differing, yet complementary, views of rhetoric and order, each having a corresponding epistemology and axiology. Concludes with an analysis of the construction of order in Thomas Hobbe's "Leviathan."…

  17. Enjoying God's Death: "The Passion of the Christ" and the Practices of an Evangelical Public

    ERIC Educational Resources Information Center

    Lundberg, Christian

    2009-01-01

    Publics are not simply a product of common attention to texts, but are also animated by an economy of tropes and affects that relies on processes of metonymic connection, metaphorical condensation, and affective investment. Drawing on Jacques Lacan's theory of enjoyment and his treatments of metaphor and metonymy as rhetorical forms, this essay…

  18. Psychologizing and the Anti-Psychologist: Dewey, Lacan, and Contemporary Art Education

    ERIC Educational Resources Information Center

    Thomas, Beth A.

    2012-01-01

    Art education throughout the 20th and into the 21st century has drawn on both psychology and psychoanalysis to support approaches to teaching and learning in the arts. This article examines the concept of "psychologizing" as it appears in the writing of psychologist/philosopher John Dewey (1859-1952) and psychiatrist/psychoanalyst Jacques Lacan…

  19. Antihumanism in the Humanities.

    ERIC Educational Resources Information Center

    Schwartz, Joel

    1990-01-01

    Analyzes the antihumanistic elements of Jacques Derrida's theory of deconstruction. Argues that the modern French intellectuals, including Foucault, Derrida, and Lacan, have had an antihumanistic effect on the American social sciences and humanities by rejecting the existence of truth, morality, and rationality. (FMW)

  20. "The Ignorant Schoolmaster": Jacotot/Rancière on Equality, Emancipation and Education

    ERIC Educational Resources Information Center

    Mukhopadhyay, Rahul; Narayanan, Varadarajan

    2014-01-01

    Jacques Rancière (born 1940), much like his contemporary Michel Foucault, has an academic oeuvre that defies neat classification within established disciplinary boundaries. This is due to the cross-disciplinary nature of his work, with a strong orientation towards history and philosophy. Although he trained as a philosopher (studying with Louis…

  1. An Examination of Prepropaganda and Political Change in Afghanistan during a National Crisis--September, 1979-January, 1980.

    ERIC Educational Resources Information Center

    Logan, Robert; Hayes, James

    Jacques Ellul defined "prepropaganda" as the subtle and sophisticated use of news services to improve an authoritarian government's public image. Because its value is directly related to its being used sparingly, he predicted that prepropaganda would increase when an authoritarian government felt threatened and decrease when it once more felt…

  2. Derridean Justice and the DJ: A Classroom Impossibility?

    ERIC Educational Resources Information Center

    Dale, Peter

    2012-01-01

    In recent years, researchers and theorists of music education have taken a stronger interest in questions of justice. Meanwhile, in educational research more broadly, there has been a simultaneous growth in efforts to bring deconstruction and the theories of Jacques Derrida to bear upon philosophies of education. One significant difficulty with…

  3. "Remediating Childhood Recollection": Facilitating Intermedial Theatre Based on Lived-Experience, Recollection and Remediation of Digital Video

    ERIC Educational Resources Information Center

    Kelly, Jem

    2016-01-01

    This paper reports on an intermedial pedagogy informed by Jacques Rancière's "Ignorant Schoolmaster" (1991). Two case studies interrogate the creative application of notions found in intermedial practice, hypersurface and palimpsest, discussing student agency as rigorous, innovative and research-led. The emerging status of pedagogy in…

  4. A history of research on yeasts 3: Emil Fischer, Eduard Buchner and their contemporaries, 1880-1900.

    PubMed

    Barnett, J A; Lichtenthaler, F W

    2001-03-15

    Through the discovery of Buchner, Biology was relieved of another fragment of mysticism. The splitting up of sugar into CO2 and alcohol is no more the effect of a "vital principle" than the splitting up of cane sugar by invertase. (Jacques Loeb 1906 [138] p.22.)

  5. International Reports on Literacy Research: France and Argentina

    ERIC Educational Resources Information Center

    Malloy, Jacquelynn A., Comp.; Botzakis, Stergios, Comp.

    2006-01-01

    This is a compilation of two separate reports on international literacy research from France and Argentina. In the reports from France, research correspondent Jacques Fijalkow detailed three research projects that included the following: (1) A description of adult literacy skills; (2) An investigation of how study-abroad students were integrated…

  6. Behind the School Walls: The School Community in French and English Boarding Schools for Girls, 1810-1867

    ERIC Educational Resources Information Center

    de Bellaigue, Christina

    2004-01-01

    This article develops a comparative analysis of lay boarding schools for girls in France and England in the first part of the nineteenth century, demonstrating that the character of school life in the two countries differed markedly. Contemporary observers such as Matthew Arnold, Henry Montucci and Jacques Demogeot visited boys' schools on either…

  7. [The union of three families of apothecaries in Paris in the 17th and 18th centuries--The apothecaries François Pihoué, François Regnault, Henry Charas and Marie Fourneau].

    PubMed

    Warolin, Christian

    2015-06-01

    The family network started with Marie Fourneau, daughter of the apothecary Jacques Fourneau, married successively two apothecaries first François Pihoué and then François Regnault and whose only daughter Marie Anne married the apothecary Henry Charas grandson of the famous apothecary Moyse Charas.

  8. The Public Library, Democracy and Rancière's Poetics of Politics

    ERIC Educational Resources Information Center

    Huzar, Timothy Jozef

    2013-01-01

    Introduction: This paper applies the thought of Jacques Rancière to the concept of democracy as it is traditionally understood in library studies literature. Methods: The paper reviews a cross-section of instances of the link between democracy and the public library in library studies literature. It offers a close textual analysis of Michael…

  9. Pedagogy of Ignorance

    ERIC Educational Resources Information Center

    Anwaruddin, Sardar M.

    2015-01-01

    In this article I discuss how Jacques Rancière's thought invites us to re-conceptualize the education-emancipation nexus. The primary goal of traditional approaches to emancipatory and anti-oppressive education has been to empower the oppressed so that the latter can (re)gain their voice and transform their situations. Building on Rancière's…

  10. Les observateurs

    NASA Astrophysics Data System (ADS)

    Ponsard, P.

    2014-09-01

    Nore observatoire de Nandrin vous attend - Comète Jacques (C/2014 E2) - Nuages noctulescents - L’observatoire de Cointe vu du monument interalliés - Orage sur la province de Liège - La police de Liège à l’heure des rendez-vous célestes

  11. Perpetuating the Technological Ideology: An Ellulian Critique of Feenberg's Democratized Rationalization

    ERIC Educational Resources Information Center

    Garrison, Kevin

    2010-01-01

    Andrew Feenberg, in his book "Questioning Technology", offers his theory of "democratized rationalization" as a critical alternative to Jacques Ellul's essentialist perspective. Feenberg argues that Ellul has confused the tendency toward efficiency in technological discourse with the essence of technology, thereby disallowing for a "positive…

  12. Surrealism and Film.

    ERIC Educational Resources Information Center

    Matthews, J. H.

    This book is a critical, genre study of surrealist films including a general discussion of the backgrounds, influences, and overall traits of surrealism as a mode of artistic response to an absurdist world. Citing the impetus of Jacques Vache and Andre Breton as the originators of surrealism, the work expands upon the themes of fractured realism…

  13. D&D of the French High Enrichment Gaseous Diffusion Plant

    SciTech Connect

    BEHAR, Christophe; GUIBERTEAU, Philippe; DUPERRET, Bernard; TAUZIN, Claude

    2003-02-27

    This paper describes the D&D program that is being implemented at France's High Enrichment Gaseous Diffusion Plant, which was designed to supply France's Military with Highly Enriched Uranium. This plant was definitively shut down in June 1996, following French President Jacques Chirac's decision to end production of Highly Enriched Uranium and dismantle the corresponding facilities.

  14. Postmodern Philosophical Critique and the Pursuit of Knowledge in Higher Education. Critical Studies in Education and Culture Series.

    ERIC Educational Resources Information Center

    Mourad, Roger P., Jr.

    This book explores postmodern critique in scholarly inquiry in the context of the philosophies of Jean-Francois Lyotard, Michel Foucault, Jacques Derrida, Richard Rorty, and Calvin Schrag. Claiming that the overall course of inquiry is characterized by basic theoretical deficiencies, postmodern critique suggests a rethinking of the nature and aims…

  15. [Not Available].

    PubMed

    Gourevitch, Danielle

    2016-01-01

    After a paper by Jacques Chevallier (Histoire des sciences médicales, XLIX, 2015, 179-188), the author presents two unpublished letters from Engène Brieux, a popular write, and amateur of cruises, to Dr. Édouard Toulouse, a famous psychiatrist. PMID:27349129

  16. The History of the Present: Towards a Contemporary Phenomenology of the School.

    ERIC Educational Resources Information Center

    Peim, Nick

    2001-01-01

    Discusses phenomenology as it relates to the theory that radical distinction cannot be sustained for subject and object, based on our perceptions of the factors involved. Focuses on Michel Foucault's philosophy and Jacques Derrida's anti-essentialist phenomenology. States that potential exists for rethinking the politics of theory in education.…

  17. Why Man Explores.

    ERIC Educational Resources Information Center

    California Inst. of Tech., Pasadena.

    This document presents a transcript of a National Aeronautics and Space Administration panel discussion held on July 2, 1976, in conjunction with the Viking Mission to Mars. The panel consisted of Norman Cousins, Ray Bradbury, Jacques Cousteau, James Michener, and Philip Morrison, and the principal topic was a philosophical discussion of the…

  18. Open File: Education in Asia.

    ERIC Educational Resources Information Center

    Ordonez, Victor, Ed.; Maclean, Rupert, Ed.

    2000-01-01

    This collection of scholarly essays on comparative education is divided into four sections. The first section, Viewpoints/Controversies, contains the essay "Educational Policies and Contents in Developing Countries" (Jacques Hallak). The second section, Open File: Education in Asia, contains the following essays: "Some Current Issues, Concerns and…

  19. Freeze, Wait, Reanimate: Cryonic Suspension and Science Fiction

    ERIC Educational Resources Information Center

    Shoffstall, Grant

    2010-01-01

    This essay takes as its chief point of departure Jacques Ellul's contention that imaginative treatments of malevolent technology in antitechnological science fiction, by way of inviting rejection, refusal, dismissal, or condemnation, conspire in facilitating human acceptance of and adjustment to technology as it otherwise presently is. The author…

  20. 75 FR 36774 - Qualification of Drivers; Exemption Renewals; Vision

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-06-28

    ... FURTHER INFORMATION CONTACT: Dr. Mary D. Gunnels, Director, Medical Programs, (202)-366-4001, fmcsamedical... 23, 2010 (75 FR 20881). Conclusion The Agency has not received any adverse evidence on any of these..., Laurent G. Jacques, Lucio Leal, Earl R. Mark, Douglas A. Mendoza, Michael R. Moore, Richard W....

  1. Teaching Rousseau: Natural Man and Present Existence.

    ERIC Educational Resources Information Center

    Rice, Daryl H.

    1989-01-01

    Offers an interpretation of Jean-Jacques Rousseau's "Discourse on the Origin and Foundations of Inequality" and provides examples of classroom exercises designed to make Rousseau's ideas and writings accessible to undergraduates. Stresses Rousseau's philosophy on natural man, language, ethics, and society. Includes interpretive references to…

  2. Education's Three Old Ideas, and a Better Idea.

    ERIC Educational Resources Information Center

    Egan, Kieran

    1999-01-01

    Discusses three educational ideas, demonstrating their incompatibility: (1) a focus on socialization; (2) Plato's notion that education is the process of seeking truth about reality; and (3) Jean-Jacques Rousseau's idea that the mind undergoes a developmental process and education furthers its development. Argues that education is learning to use…

  3. The Primary Aim of Speech Communication Education: Some Potential Concerns for Members of the Discipline.

    ERIC Educational Resources Information Center

    Hudson, David D.

    Following a brief discussion of the works of the philosopher Jacques Maritain, who viewed the educational process as the art of helping individuals to realize the nature of that which is inherent in them, this paper analyzes the implications of Maritain's views for the discipline of speech communication. The paper suggests that education in speech…

  4. Technological Nihilism vs. Natural Law: Science, Morality, and the Law Today

    ERIC Educational Resources Information Center

    Lawler, Peter Augustine

    2005-01-01

    The conflict between the followers of Jacques Maritain and the followers of John Dewey seems to amount to this: each group accuses the other of promoting education for tyranny. Pragmatism, for the Deweyans, frees human beings from the idea of a fixed human nature to pursue freely their ever-evolving ideas of happiness or fulfillment. According to…

  5. DEFECTS IN CERVICAL VERTEBRAE IN BORIC ACID-EXPOSED RAT EMBRYOS ARE ASSOCIATED WITH ANTERIOR SHIFTS OF HOX GENE EXPRESSION DOMAINS

    EPA Science Inventory

    Defects in cervical vertebrae in boric acid-exposed rat embryos are associated with anterior shifts of hox gene expression domains

    Nathalie Wery,1 Michael G. Narotsky,2 Nathalie Pacico,1 Robert J. Kavlock,2 Jacques J. Picard,1 AND Francoise Gofflot,1*
    1Unit of Developme...

  6. Rousseau and the Fable: Rethinking the Fabulous Nature of Educational Philosophy

    ERIC Educational Resources Information Center

    Lewis, Tyson E.

    2012-01-01

    In this essay Tyson Lewis reevaluates Jean-Jacques Rousseau's assessment of the pedagogical value of fables in Emile's education using Giorgio Agamben's theory of poetic production and Thomas Keenan's theory of the inherent ambiguity of the fable. From this perspective, the "unreadable" nature of the fable that Rousseau exposed is not simply the…

  7. Who Won the Debate in Women Education? Rousseau or Wollstonecraft?

    ERIC Educational Resources Information Center

    Owusu-Gyamfi, Clifford

    2016-01-01

    Curriculum framework in the education of children became debatable during the enlightenment. Jean-Jacque Rousseau's treatise, "Emile," outlined an educational curriculum based on natural rights. Rousseau thought education should be based on espousing and exploring the natural abilities of a person. Therefore, since women have a natural…

  8. Thinking about the Nature and Role of Authority in Democratic Education with Rousseau's "Emile"

    ERIC Educational Resources Information Center

    Michaud, Olivier

    2012-01-01

    Educational authority is an issue in contemporary democracies. Surprisingly, little attention has been given to the problem of authority in Jean-Jacques Rousseau's "Emile" and his work has not been addressed in the contemporary debate on the issue of authority in democratic education. Olivier Michaud's goals are, first, to address both of these…

  9. Rousseau's Imaginary Friend: Childhood, Play, and Suspicion of the Imagination in "Emile"

    ERIC Educational Resources Information Center

    Shuffelton, Amy B.

    2012-01-01

    In this essay Amy Shuffelton considers Jean-Jacques Rousseau's suspicion of imagination, which is, paradoxically, offered in the context of an imaginative construction of a child's upbringing. First, Shuffelton articulates Rousseau's reasons for opposing children's development of imagination and their engagement in the sort of imaginative play…

  10. Exploring Fear: Rousseau, Dewey, and Freire on Fear and Learning

    ERIC Educational Resources Information Center

    English, Andrea; Stengel, Barbara

    2010-01-01

    Fear is not the first feature of educational experience associated with the best-known progressive educational theorists--Jean-Jacques Rousseau, John Dewey, and Paolo Freire. But each of these important thinkers did, in fact, have something substantive to say about how fear functions in the processes of learning and growth. Andrea English and…

  11. Realizing the Natural Self: Rousseau and the Current System of Education

    ERIC Educational Resources Information Center

    Peckover, Christopher

    2012-01-01

    Jean-Jacques Rousseau believed that Nature is master. Children acknowledge this truth perhaps better than most adults. Nature gives life to humanity and provides humans with the tools necessary to survive. Even as an infant, Nature urges the child to scream for nourishment. As children, humans trust their master. The idea of resisting their human…

  12. The Wish for the End of Education and the Myth of Paradise: The Impact of Rousseauism on the Development of a Radical Critique of Education.

    ERIC Educational Resources Information Center

    Ruder, Georg

    1989-01-01

    Inquires into the question of how the necessity for a radical critique of education is justified, based on a comparative analysis of the argumentational structures used by Alice Miller and Jean Jacques Rousseau. Hypothesizes that both approaches are based on a concept of the origin of human societies based on the modern version of "the myth of…

  13. Alexander Meiklejohn in Search of Freedom and Dignity.

    ERIC Educational Resources Information Center

    Johnson, Tony W.

    1982-01-01

    Assesses the contributions of the philosopher/educator Alexander Meiklejohn. Discusses the influences of Jean-Jacques Rousseau, Immanuel Kant, and the U.S. Constitution on Meiklejohn's educational theories, which stressed that human freedom and dignity can be enhanced by rigorous examination of U.S. Supreme Court decisions and the meaning of…

  14. Political and Cultural Nationalism in Education. The Ideas of Rousseau and Herder Concerning National Education.

    ERIC Educational Resources Information Center

    Wiborg, Susanne

    2000-01-01

    Jean Jacques Rousseau in France and Johann Gottfied Herder in Germany both emphasized the role of education in building the nation-state. However, Rousseau focused on shaping the national character through citizenship education and political socialization in public schools, while Herder saw a national identity evolving from a common culture and…

  15. A Contrast in Schooling: The Natural Education of Emile vs. Giroux's Radical Education.

    ERIC Educational Resources Information Center

    Sigmon, Scott B.

    Jean-Jacques Rousseau's classic work "Emile" of 1762 is contrasted with Henry G. Giroux's 1981 book "Ideology Culture and the Process of Schooling." Although both Giroux and Rousseau are social critics, their notions about education and its outcome are contrary and not due to historical time alone. This comparative analysis characterizes…

  16. Young Mary Wollstonecraft's Schooling and Its Influence on Her Future Pioneering Agenda for the Rational Education of Women.

    ERIC Educational Resources Information Center

    Roberts, Leonard H.

    This paper presents biographical information about Mary Wollstonecraft (1759-1797), focusing especially on her education. The paper begins with an overview of the status of women's education, or lack of it, in 18th century England. It then describes Wollstonecraft's reaction to Jean Jacques Rousseau's views on women's education and the influence…

  17. Rousseau, Happiness, and the Economic Approach to Education

    ERIC Educational Resources Information Center

    Gilead, Tal

    2012-01-01

    Since the 1960s, the influence of economic thought on education has been steadily increasing. Taking Jean-Jacques Rousseau's educational thought as a point of departure, Tal Gilead critically inquires into the philosophical foundations of what can be termed the economic approach to education. Gilead's focus in this essay is on happiness and the…

  18. Outdoor Education--The Past Is Prologue to the Future.

    ERIC Educational Resources Information Center

    Rillo, Thomas J.

    Although educators and philosophers such as Johann Amos Comenius, Jean Jacques Rousseau, Pestalozzi, and Froebel stressed the study of nature, outdoor education really began with the first teaching-learning act which occurred outdoors. The human being, physiologically and psychologically adapted for outdoor existence, has only been indoors for…

  19. Rosseau Revisited: Gender as a Category in the History of Education.

    ERIC Educational Resources Information Center

    Schmid, Pia

    1992-01-01

    Reviews research on the impact of Jean Jacques Rousseau on educational history. Discusses the effects of either integrating or omitting gender as a research category. Concludes with a review of feminist research on Rousseau within the framework of educational history. (CFR)

  20. Master Teachers at the Carnegie.

    ERIC Educational Resources Information Center

    Judson, Bay Hallowell

    1989-01-01

    Describes children's art education at Pittsburgh's Carnegie Museum of Art from 1928-1975. Discusses how the educational philosophy was influenced by Jean-Jacques Rousseau, John Dewey, and Franz Cizek, stating that the goal of art education was to build character, transmit culture, promote healthy competition, and develop moral values and…

  1. The Happy and Suffering Student? Rousseau's "Emile" and the Path Not Taken in Progressive Educational Thought

    ERIC Educational Resources Information Center

    Mintz, Avi I.

    2012-01-01

    One of the mantras of progressive education is that genuine learning ought to be exciting and pleasurable, rather than joyless and painful. To a significant extent, Jean-Jacques Rousseau is associated with this mantra. In a theme of "Emile" that is often neglected in the educational literature, however, Rousseau stated that "to suffer is the first…

  2. History and the Curriculum in Rousseau's "Emile."

    ERIC Educational Resources Information Center

    Owen, David B.

    1982-01-01

    This essay considers Jean Jacques Rousseau's conception of history in "Emile" and its relationship to Rousseau's educational curriculum. History is, for Rousseau, at the heart of the curriculum and is one of the chief instruments for imparting knowledge of the world and encouraging moral behavior. (PP)

  3. L2 Reading Research and Pedagogical Considerations in the Teaching of French and Francophone Theater

    ERIC Educational Resources Information Center

    Edwards, Carole; Taylor, Alan M.

    2012-01-01

    Little research on improving second language (L2) reading comprehension of French and francophone theater has been conducted. This study provides insight into enhancing L2 comprehension of drama by combining L2 research with examples from L'accent grave by Jacques Prevert, Ton beau capitaine by Simone Schwarz-Bart (1987), Un Touareg s'est marie a…

  4. The Question in Educational Leadership: For Whom and for What Are We Responsible?

    ERIC Educational Resources Information Center

    Carlson, Dennis

    2010-01-01

    Jacques Derrida wrote about democratic leadership in educational institutions throughout his later work, but in this article the author notes the importance of Derrida's essays published as "Eyes of the University" (2004). Derrida begins by returning to questions raised by Immanuel Kant two centuries earlier with regard to the founding of the…

  5. Settling No Conflict in the Public Place: Truth in Education, and in Rancierean Scholarship

    ERIC Educational Resources Information Center

    Bingham, Charles

    2010-01-01

    This essay offers an educational understanding of truth deriving from the work of Jacques Ranciere. Unlike other educational accounts--the traditional, progressive, and critical accounts--of truth that take education as a way of approaching pre-existing truths (or lack of pre-existing truths), this essay establishes an account of truth that is…

  6. The Humanities without Condition: Derrida and the Singular "Oeuvre"

    ERIC Educational Resources Information Center

    Attridge, Derek

    2014-01-01

    In an important lecture on the function of the Humanities, "The University without Condition", Jacques Derrida asks what it means to "profess" the truth and advocates a commitment to the "oeuvre"--the work that constitutes an event rather than just a contribution to knowledge. I examine a few phrases from the lecture,…

  7. Contemporary Art and Art in Education: The New, Emancipation and Truth

    ERIC Educational Resources Information Center

    Atkinson, Dennis

    2012-01-01

    This article assembles some ideas on equality and learning in relation to the notions of truth and emancipation. It considers learning as a political act, as defined by Jacques Ranciere and Alain Badiou, rather than, for example, an incremental process of psychological or sociological development. Practical exemplifications will be taken from…

  8. Out of the Ordinary: Incorporating Limits with Austin and Derrida

    ERIC Educational Resources Information Center

    Williams, Emma

    2014-01-01

    This article seeks to open up a re-examination of the relationship between thought and language by reference to two philosophers: John Austin and Jacques Derrida. While in traditional philosophical terms these thinkers stand far apart, recent work in the philosophy of education has highlighted the importance of Austin's work in a way that has…

  9. An Act of Methodology: A Document in Madness--Writing Ophelia

    ERIC Educational Resources Information Center

    Steinnes, Jenny

    2012-01-01

    This paper is an attempt to stage some questions concerning methodology and education, inspired by Ophelia in Shakespeare's "Hamlet" and by Jacques Derrida's poetic philosophical oeuvres. What are at stake are the long traditions of preferences of sanity over madness, friend over enemy, male over female and of clean, unambiguous univocal language…

  10. Educational Technology: A Presupposition of Equality?

    ERIC Educational Resources Information Center

    Orlando, Joanne

    2014-01-01

    The work of philosopher Jacques Rancière is used conceptually and methodologically to frame an exploration of the driving interests in educational technology policy and the sanctioning of particular discursive constructions of pedagogy that result. In line with Rancière's thinking, the starting point for this analysis is that of…

  11. [The union of three families of apothecaries in Paris in the 17th and 18th centuries--The apothecaries François Pihoué, François Regnault, Henry Charas and Marie Fourneau].

    PubMed

    Warolin, Christian

    2015-06-01

    The family network started with Marie Fourneau, daughter of the apothecary Jacques Fourneau, married successively two apothecaries first François Pihoué and then François Regnault and whose only daughter Marie Anne married the apothecary Henry Charas grandson of the famous apothecary Moyse Charas. PMID:26189312

  12. Educational Neocolonialism and the World Bank: A Rancièrean Reading

    ERIC Educational Resources Information Center

    Anwaruddin, Sardar M.

    2014-01-01

    In this article, I employ Jacques Rancière's conception of an explicative order to explore how the World Bank contributes to the global project of educational neocolonialism. I argue that the Bank operates as a Master Explicator who taps into students' "inability" to learn by themselves. It explicates concepts such as…

  13. Towards a Politicized Notion of Citizenship for Science Education: Engaging the Social through Dissensus

    ERIC Educational Resources Information Center

    Bazzul, Jesse

    2015-01-01

    This theoretical article draws from the political thought of Jacques Rancière to trouble some taken-for-granted conceptions of citizenship education. Rancière's notion of politics and dissensus (as opposed to consensus) can lay the groundwork for a version of citizenship that challenges what is deemed sensible, visible, who is counted in…

  14. Knowledge and the Curriculum: Derrida, Deconstruction and "Sustainable Development"

    ERIC Educational Resources Information Center

    Winter, Christine

    2007-01-01

    This paper enquires into curriculum knowledge about sustainable development at advanced level in geography in English schools through a critical look at two concepts. The deconstructive perspective used is drawn from Jacques Derrida. The focus is on school knowledge and responsibility to other ways of knowing that may be neglected within…

  15. Best Practices in Marine and Coastal Science Education: Lessons Learned from a National Estuarine Research Reserve.

    ERIC Educational Resources Information Center

    McDonnell, Janice D.

    The Jacques Cousteau National Estuarine Research Reserve (JC NERR) program has successfully capitalized on human fascination with the ocean by using the marine environment to develop interest and capability in science. The Institute of Marine & Coastal Sciences, as the managing agency of the JC NERR, makes its faculty, staff resources, and…

  16. 1. Historic American Buildings Survey Original Water Color in Wells ...

    Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

    1. Historic American Buildings Survey Original Water Color in Wells Fargo Bank Historical Museum Capt. Jean Jacques Vioget, Artist Spring of 1837 FIRST WATER COLOR OF SAN FRANCISCO (JACOB LEESE HOUSE IN CENTER) - San Francisco, Historic View, 1837, San Francisco, San Francisco County, CA

  17. Education as Humanism of the Other

    ERIC Educational Resources Information Center

    Tarc, Aparna Mishra

    2005-01-01

    This paper explores how educators might intervene in canonized texts of the human subject on which a particular and exclusive kind of humanism rests. In imagining possible interventions educators might make, I turn to and trace Jacques Derrida's on-going deconstruction of the philosophical texts of subjectivity. In his body of work, Derrida…

  18. Education as Seance: Specters, Spirits, and the Expansion of Memory

    ERIC Educational Resources Information Center

    Ruitenberg, Claudia

    2009-01-01

    In this essay I propose that education be conceived as seance: a place where ghosts are summoned in order that we may come to (speaking) terms with them. Against the backdrop of my own summoning of the ghosts haunting my childhood visits to a nearby castle, I draw on the work of Jacques Derrida to provide a theoretical rationale for the importance…

  19. Scenes of Aesthetic Education: Ranciere, Oedipus, and "Notre Musique"

    ERIC Educational Resources Information Center

    De Boever, Arne

    2012-01-01

    In an interview titled "The Janus-Face of Politicized Art," Jacques Ranciere describes his methodology as follows: "I always try to think in terms of horizontal distributions, combinations between systems of possibilities, not in terms of surface and substratum. Where one searches for the hidden beneath the apparent, a position of mastery is…

  20. Acceptance, Resistance and Educational Transformation: A Taoist Reading of "The First Man"

    ERIC Educational Resources Information Center

    Roberts, Peter

    2013-01-01

    This article provides a Taoist reading of Camus' posthumously published novel, "The first man". With its focus on the early life of the central character, Jacques Cormery, "The first man" is a semi-autobiographical account of learning and transformation, but it is, like so many other stories of its kind, one sustained by…

  1. Thinking about Women's History, Part Two.

    ERIC Educational Resources Information Center

    Pope, Barbara Corrado

    1993-01-01

    Reviews eight European histories by Dorothy O. Helly, Ed., and Susan M. Reverby, Ed. (1992); Joy Wiltenburg (1992); Margaret L. King (1991); Joan DeJean (1991); Jacques Gelis (1991); Barbara Duden (1991); Jane Lewis (1991); and Sheila Rowbotham (1989). This sampling shows women's historians use an interdisciplinary approach and consistently deal…

  2. Google™ underwater

    NASA Astrophysics Data System (ADS)

    Showstack, Randy

    2012-10-01

    The first underwater panoramic images were added to Google Maps™, the company announced on 25 September. This first “underwater Street View collection,” launched in partnership with the Caitlin Seaview Survey, provides people with the opportunity to “become the next virtual Jacques Cousteau.” For more information, see: maps.google.com/ocean.

  3. Rival Visions: J.J. Rousseau and T.H. Huxley on the Nature (or Nurture) of Inequality and What It Means for Education

    ERIC Educational Resources Information Center

    Currie-Knight, Kevin

    2011-01-01

    Jean-Jacques Rousseau (1712-1778) and Thomas Huxley (1852-1895) had different, but substantial, effects on the history of education. Rousseau's educational theories supplied the intellectual foundation for pedagogical progressivism. Huxley's educational writings helped to enlarge the scope of the British curriculum to include such things as…

  4. Lifelong Learning in the European Union: Whither the Lisbon Strategy?

    ERIC Educational Resources Information Center

    Jones, Hywel Ceri

    2005-01-01

    This article traces the Lisbon strategy back to the White Paper issued by President Jacques Delors in 1993 on "Growth, Competitiveness, and Jobs" as the launching point for the structural reform agenda needed to turn around the massive unemployment crisis and proposing a combination of policies for the structural reform of the labour market and…

  5. Ranciere and the Poetics of the Social Sciences

    ERIC Educational Resources Information Center

    Pelletier, Caroline

    2009-01-01

    This article reviews the significance of Jacques Ranciere's work for methodological debates in the social sciences, and education specifically. It explores the implications of constructing research as an aesthetic, rather than primarily a methodological, endeavour. What is at stake in this distinction is the means by which research intervenes in…

  6. Critical Thinking and the Question of Critique: Some Lessons from Deconstruction.

    ERIC Educational Resources Information Center

    Biesta, Gert J. J.; Stams, Geert Jan J. M.

    2001-01-01

    Provides some philosophical groundwork for contemporary debates about the idea of critical thinking. Discusses three styles of critique: critical dogmatism, transcendental critique (Karl-Otto Apel), and deconstruction (Jacques Derrida). Argues that while transcendental critique is able to solve some of the problems of the dogmatic approach to…

  7. In Search of the Modern Hero.

    ERIC Educational Resources Information Center

    Shugar, Carol E.

    1988-01-01

    Provides profiles of contemporary figures who can serve as appropriate role models (heroes and heroines) for today's young people. Profiled are Desmond Tutu, Neil Armstrong, Mother Teresa, Lech Walesa, Jesse Jackson, Jacques Cousteau, Sharon Christa McAuliffe, and Anatoly Shcharansky. (SKC)

  8. Derrida's Right to Philosophy, Then and Now

    ERIC Educational Resources Information Center

    Willinsky, John

    2009-01-01

    In this essay, a tribute to Jacques Derrida's educational efforts at expanding access to current work in philosophy, John Willinsky examines his efforts as both a public right and an element of academic freedom that bear on the open access movement today. Willinsky covers Derrida's extension and outreach work with the Groupe de Recherches pour…

  9. Temptation and Seduction in the Technological Milieu

    ERIC Educational Resources Information Center

    van der Laan, J. M.

    2004-01-01

    Jacques Ellul's work on propaganda provides the basis for this analysis of life in technology. Advertising and the mass media rely on temptation and seduction and create a constant flow of propaganda, all of which serve the technological system. Propaganda aims to condition and regulate us so that we participate in and adapt ourselves to a desired…

  10. Eyeless in America: Hollywood and Indiewood's Iraq War on Film

    ERIC Educational Resources Information Center

    Blackmore, Tim

    2012-01-01

    This article examines 50 films produced and released between the years 2001 and 2012 that are concerned with the American wars in Iraq and Afghanistan. Using Jacques Ellul's theories set out in his book "Propaganda," the article argues that while the films have failed at the box office, they were intended to function as integration propaganda. The…

  11. Aporias, Responsibility, and the Im/possibility of Teaching Multicultural Education

    ERIC Educational Resources Information Center

    Wang, Hongyu

    2005-01-01

    Drawing upon Jacques Derrida's notions of aporia and responsibility, this essay discusses the dilemmas of multicultural education and the pedagogical responsibility of multicultural educators. Derrida emphasizes that there is no responsibility without experiencing aporia as the possibility of the impossible. To promote personal transformation and…

  12. "Hospes": The Wabash Center as a Site of Transformative Hospitality

    ERIC Educational Resources Information Center

    Jones, Carolyn M.

    2007-01-01

    The Wabash Center for Teaching and Learning in Theology and Religion is a place of hospitality and its staff the epitome of the "good host." This essay explores the meaning of hospitality, including its problematic dimensions, drawing on a number of voices and texts: Jacques Derrida's "Of Hospitality"; Henri M. Nouwen's "Reaching Out: The Three…

  13. Papers on Education Reform, Volume II.

    ERIC Educational Resources Information Center

    Open Court Publishing Co., La Salle, IL.

    The following ten papers were presented to the Open Court Editorial Advisory Board in 1971. "Where Educational Nonsense Comes From" by Jacques Barzun focuses on education as the removal of ignorance. "The Importance of Teaching Poetry" by Cleanth Brooks discusses the powers of poetry in the instruction of yound children. In "Educating the…

  14. [The sense of the senseless, psychoanalytic aspects of delusion in psychosis].

    PubMed

    Chaperot, Christophe

    2011-01-01

    The psychoanalytic approach to delusion in psychosis leads us to examine the function of a "furrow". It is necessary to remain in the furrow in order not to become delusional. References to Sigmund Freud, Jacques Lacan, Mélanie Klein and Jean-Claude Maleval enlighten us as to the origin and the function of delusion as an attempt to give meaning. PMID:21416882

  15. Nifedipine prevents sodium caprate-induced barrier dysfunction in human epidermal keratinocyte cultures.

    PubMed

    Uchino, Yoshihiro; Matsumoto, Junichi; Watanabe, Takuya; Hamabashiri, Masato; Tsuchiya, Takashi; Kimura, Ikuya; Yamauchi, Atsushi; Kataoka, Yasufumi

    2015-01-01

    Tight junctions (TJs) of the epidermis play an important role in maintaining the epidermal barrier. TJ breakdown is associated with skin problems, such as wrinkles and transepidermal water loss (TEWL). Clinical studies have reported that topical nifedipine is effective in reducing the depth of wrinkles and improving TEWL. However, it remains unknown whether nifedipine influences the TJ function in the epidermis. In the present study, we investigated the effect of nifedipine on epidermal barrier dysfunction in normal human epidermal keratinocytes (NHEKs) treated with sodium caprate (C10), a TJ inhibitor. Nifedipine reversed the C10-decreased transepithelial electrical resistance values as a measure of disruption of the epidermal barrier. Immunocytochemical observations revealed that nifedipine improved the C10-induced irregular arrangement of claudin-1, a key protein in TJs. Taken together, these findings suggest that nifedipine prevents epidermal barrier dysfunction, at least in part, by reconstituting the irregular claudin-1 localization at TJs in C10-treated NHEKs. PMID:26027835

  16. Genes Regulating Epithelial Polarity Are Critical Suppressors of Esophageal Oncogenesis

    PubMed Central

    Li, Xiu-Min; Wang, Hui; Zhu, Li-Li; Zhao, Run-Zhen; Ji, Hong-Long

    2015-01-01

    Esophageal cancer is an aggressive disease featured by early lymphatic and hematogenous dissemination, and is the sixth leading cause of cancer-related deaths worldwide. The proper formation of apicobasal polarity is essential for normal epithelium physiology and tissue homeostasis, while loss of polarity is a hallmark of cancer development including esophageal oncogenesis. In this review, we summarized the stages of esophageal cancer development associated with the loss or deregulation of epithelial cell apicobasal polarity. Loss of epithelial apicobasal polarity exerts an indispensable role in the initiation of esophageal oncogenesis, tumor progression, and the advancement of tumors from benign to malignant. In particular, we reviewed the involvement of several critical genes, including Lkb1, claudin-4, claudin-7, Par3, Lgl1, E-cadherin, and the Scnn1 gene family. Understanding the role of apicobasal regulators may lead to new paradigms for treatment of esophageal tumors, including improvement of prognostication, early diagnosis, and individually tailored therapeutic interventions in esophageal oncology. PMID:26185530

  17. Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level.

    PubMed

    Price, Edwin R; Rott, Katherine H; Caviedes-Vidal, Enrique; Karasov, William H

    2014-10-01

    Flying vertebrates have been hypothesized to rely heavily on paracellular absorption of nutrients to compensate for having smaller intestines than non-flyers. We tested this hypothesis in an insectivorous bat (Myotis lucifugus) and two insect-eating rodents (Onychomys leucogaster and Peromyscus leucopus). In intact animals, the fractional absorption of orally dosed l-arabinose (Mr 150) was 82% in M. lucifugus, which was more than twice that of the rodents. Absorption of creatinine (Mr 113) was greater than 50% for all species and did not differ between M. lucifugus and the rodents. We also conducted intestinal luminal perfusions on anesthetized animals. Absorption of l-arabinose per nominal surface area in M. lucifugus was nearly double that of the rodents, while absorption of creatinine was not different among species. Using an everted sleeve preparation, we demonstrated that high concentrations of l-arabinose and creatinine did not inhibit their own uptake, validating their use as passive, paracellular probes. Histological measurements indicated that M. lucifugus has more cells, and presumably more tight junctions, per nominal surface area than P. leucopus. This seems unlikely to explain entirely the higher absorption of l-arabinose in M. lucifugus during perfusions, because l-arabinose absorption normalized to the number of enterocytes was still double that of P. leucopus. As an alternative, we investigated tight junction gene expression. M. lucifugus had higher expression of claudin-1 and claudin-15, and lower expression of claudin-2 relative to P. leucopus. Expression of claudin-7 and occludin did not differ among species. Taken together, our results support the hypothesis that bats have evolved higher paracellular nutrient absorption than non-flying animals, and that this phenomenon might be driven by both histological characteristics and differences in tight junction gene expression. PMID:25063860

  18. CHOLESTEROL DEPLETION ALTERS DETERGENT-SPECIFIC SOLUBILITY PROFILES OF SELECTED TIGHT JUNCTION PROTEINS AND THE PHOSPHORYLATION OF OCCLUDIN

    PubMed Central

    Lynch, Robert D.; Francis, Stacy A.; McCarthy, Karin M.; Casas, Elizabeth; Thiele, Christoph; Schneeberger, Eveline E.

    2007-01-01

    Differential centrifugation of Triton X-100 or CHAPS lysates from control and cholesterol (CH) depleted MDCK II cells, segregated integral tight junction (TJ) proteins associated with detergent resistant membranes (DRMs) into two groups. Group A proteins (occludin, claudin-2 and -3) were detected in large, intermediate and small aggregates in both detergents, whereas group B proteins (claudin-1, -4 and -7) were observed in small aggregates in TX-100 and in intermediate and small aggregates in CHAPS. Depletion of CH altered the distribution of group A and B proteins among the three size categories in a detergent-specific manner. In lysates produced with octyl glucoside, a detergent that selectively extracts proteins from DRMs, group A proteins were undetectable in large aggregates and CH depletion did not alter the distribution of either group A or B proteins in intermediate or small aggregates. Neither occludin (group A) nor claudin-1 (group B) was in intimate enough contact with CH to be cross-linked to [3H]-photo-cholesterol. However, antibodies to either TJ protein co-immunoprecipitated caveolin-1, a CH-binding protein. Unlike claudins, occludin’s presence in TJs and DRMs did not require palmitoylation. Equilibrium density centrifugation on discontinuous OptiPrep gradients revealed detergent-related differences in the densities of TJ-bearing DRMs. There was little or no change in those densities after CH depletion. Removing CH from the plasma membrane increased tyrosine and threonine phosphorylation of occludin, and transepithelial electrical resistance (TER) within 30 min. After 2 h of CH efflux, phospho-occludin levels and TER fell below control values. We conclude that the association of integral TJ proteins with DRMS, pelleted at low speeds, is partially CH dependent. However, the buoyant density of TJ-associated DRMs is a function of the detergent used and is insensitive to decreases in CH. PMID:17574235

  19. Characterization of a naturally occurring breast cancer subset enriched in EMT and stem cell characteristics

    SciTech Connect

    Hennessy, Bryan T.; Gonzalez-Angulo, Ana-Maria; Stemke-Hale, Katherine; Gilcrease, Michael Z.; Krishnamurthy, Savitri; Lee, Ju-Seog; Fridlyand, Jane; Sahin, Aysegul; Agarwal, Roshan; Joy, Corwin; Liu, Wenbin; Stivers, David; Baggerly, Keith; Carey, Mark; Lluch, Ana; Monteagudo, Carlos; He, Xiaping; Weigman, Victor; Fan, Cheng; Palazzo, Juan; Hortobagyi, Gabriel N.; Nolden, Laura K.; Wang, Nicholas J.; Valero, Vicente; Gray, Joe W.; Perou, Charles M.; Mills, Gordon B.

    2009-05-19

    Metaplastic breast cancers (MBC) are aggressive, chemoresistant tumors characterized by lineage plasticity. To advance understanding of their pathogenesis and relatedness to other breast cancer subtypes, 28 MBCs were compared with common breast cancers using comparative genomic hybridization, transcriptional profiling, and reverse-phase protein arrays and by sequencing for common breast cancer mutations. MBCs showed unique DNA copy number aberrations compared with common breast cancers. PIK3CA mutations were detected in 9 of 19 MBCs (47.4%) versus 80 of 232 hormone receptor-positive cancers (34.5%; P = 0.32), 17 of 75 HER-2-positive samples (22.7%; P = 0.04), 20 of 240 basal-like cancers (8.3%; P < 0.0001), and 0 of 14 claudin-low tumors (P = 0.004). Of 7 phosphatidylinositol 3-kinase/AKT pathway phosphorylation sites, 6 were more highly phosphorylated in MBCs than in other breast tumor subtypes. The majority of MBCs displayed mRNA profiles different from those of the most common, including basal-like cancers. By transcriptional profiling, MBCs and the recently identified claudin-low breast cancer subset constitute related receptor-negative subgroups characterized by low expression of GATA3-regulated genes and of genes responsible for cell-cell adhesion with enrichment for markers linked to stem cell function and epithelial-to-mesenchymal transition (EMT). In contrast to other breast cancers, claudin-low tumors and most MBCs showed a significant similarity to a 'tumorigenic' signature defined using CD44{sup +}/CD24{sup -} breast tumor-initiating stem cell-like cells. MBCs and claudin-low tumors are thus enriched in EMT and stem cell-like features, and may arise from an earlier, more chemoresistant breast epithelial precursor than basal-like or luminal cancers. PIK3CA mutations, EMT, and stem cell-like characteristics likely contribute to the poor outcomes of MBC and suggest novel therapeutic targets.

  20. Defective Barrier Function in Neosquamous Epithelium

    PubMed Central

    Jovov, Biljana; Shaheen, Nicholas J; Orlando, Geraldine S.; Djukic, Zorka; Orlando, Roy C.

    2013-01-01

    BACKGROUND Radiofrequency ablation (RFA) of Barrett’s esophagus (BE) is a common strategy for the prevention of esophageal adenocarcinoma (EAC). After RFA, the ablated esophagus heals on acid suppressive therapy, and is re-populated with a stratified squamous epithelium, referred to as ‘neosquamous epithelium (NSE).’ Because the ability of the NSE to protect the underlying tissue from recurrent insult by reflux is unclear, we assessed the barrier function of NSE by comparing it to that of the native upper squamous epithelium (USE) in subjects having undergone RFA. METHODS At varying intervals following RFA, the barrier function of NSE and USE were assessed in endoscopic biopsies by light and electron microscopy, and by measurement of electrical resistance (RT) and fluorescein flux in mini-Ussing chambers. Chamber results were further compared with results from control biopsies (healthy distal esophagus). A claudin expression profile in the tight junctions (TJ) of NSE and USE was determined using qRT-PCR. Differential expression of claudin 4 between NSE and USE was assayed by immunoblots. RESULTS USE was histologically normal while NSE showed dilated intercellular spaces and marked eosinophilia. NSE was also more permeable than USE and healthy controls, having lower mean RT and higher fluorescein fluxes. Abnormally low RT values for NSE were unrelated to the time period following RFA (or number of prior RFA sessions), being abnormal even 26 months after RFA. Abnormal permeability in NSE was associated with significantly lower values for claudin-4 and claudin-10 than in USE. CONCLUSIONS NSE commonly exhibits defective barrier function. Since this defect will make it vulnerable to injury, inflammation and destruction by acidic and weakly acidic refluxates, it may in part explain incidences of recurrence of BE following ablation. PMID:23318477

  1. IL-1β and TSH disturb thyroid epithelium integrity in autoimmune thyroid diseases.

    PubMed

    Rebuffat, Sandra A; Kammoun-Krichen, Maha; Charfeddine, Ilhem; Ayadi, Hammadi; Bougacha-Elleuch, Noura; Peraldi-Roux, Sylvie

    2013-03-01

    Pro-inflammatory cytokines such as IL-1β and TNFα are known to affect thyroid function. They stimulate IL-6 secretion and modify epithelium integrity by altering junction proteins. To study the role of cytokines on thyroid epithelia tightness in autoimmune thyroid diseases (AITD), we analyzed the expression profiles of junction proteins (ZO-1, Claudin, JAM-A) and cytokines in human thyroid slices and also investigated the effect of IL-1β on the epithelium integrity in primary cultures of human thyrocytes. Junction proteins expression (ZO-1, Claudin, JAM-A) has been analyzed by immunohistochemistry on thyroid slices and by Western blot on membrane proteins extracted from thyrocytes of patients suffering from Graves and Hashimoto diseases. The high expression of junction proteins we found on Graves' disease thyroid slices as well as in cell membrane extracts acknowledges the tightness of thyroid follicular cells in this AITD. In contrast, the reduced expression of JAM and ZO-1 in thyroid cells from patients suffering from Hashimoto thyroiditis is in agreement with the loss of thyroid follicular cell integrity that occurs in this pathology. Concerning the effects on epithelium integrity of TSH and of the pro-inflammatory cytokine IL-1β in primary cultures of human thyroid cells, TSH appeared able to modify JAM-A localization but without any change in the expression levels of JAM-A, Claudin and ZO-1. Inversely, IL-1β provoked a decrease in the expression of- and a redistribution of both, Claudin and ZO-1 without modifying the expression and sub-cellular distribution patterns of JAM-A in thyroid cells. These results demonstrate (i) that Hashimoto's- and Graves' diseases display different junction proteins expression patterns with a loss of epithelium integrity in the former and (ii) that IL-1β modifies thyroid epithelial tightness of human thyrocytes by altering the expression and localization of junction proteins. Therefore, IL-1β could play a role in the

  2. Podoplanin-mediated TGF-β-induced epithelial-mesenchymal transition and its correlation with bHLH transcription factor DEC in TE-11 cells.

    PubMed

    Wu, Yunyan; Liu, Qiang; Yan, Xu; Kato, Yukio; Tanaka, Makiko; Inokuchi, Sadaki; Yoshizawa, Tadashi; Morohashi, Satoko; Kijima, Hiroshi

    2016-06-01

    Podoplanin is reported involved in the collective cell invasion, another tumor invasion style which is distinct from the single cell invasion, so-called epithelial-mesenchymal transition (EMT). In this study, we investigated the correlation between podoplanin and EMT-related markers in esophageal squamous cell carcinoma (ESCC), and evaluated its linkage with the basic helix-loop-helix (bHLH) transcription factor differentiated embryonic chondrocyte (DEC) 1 and DEC2. Three ESCC cell lines and human squamous cell carcinoma A431 cells were subjected to western blot analyses for podoplanin and EMT markers, as well as the expression of DEC1 and DEC2. By RT-qPCR and western blotting, we found that TGF-β increased the expression of podoplanin and mensenchymal markers (e.g., N-cadherin and vimentin), while decreased the expression of epithelial markers (e.g., Claudin-4 and E-cadherin), accompanied by Smad2 phosphorylation and slug activation. Moreover, TGF-β has different effects on the expression of DEC1 and DEC2, that is, it upregulates DEC1, but downregulates DEC2. Capability of cell proliferation, invasion and migration were further analyzed using CCK-8 assay, Matrigel-invasion assay, and the wound-healing assay, respectively. The proliferation, invasion and migration ability were significantly lost in podoplanin-knockdown cells when compared with the scrambled siRNA group. In addition to these changes, the expression of Claudin-4, but not that of Claudin-1 or E-cadherin, was induced by the siRNA against podoplanin. On the contrary, overexpression of DEC1 and DEC2 exhibits opposite effects on podoplanin, but only slight effect on Claudin-4 was detected. These data indicated that podoplanin is significantly associated with EMT of TE-11 cells, and may be directly or indirectly regulated by bHLH transcription factors DEC1 and DEC2.

  3. Effects of Maternal Treatment with Corticosteroids on Tight Junction Protein Expression in the Cerebral Cortex of the Ovine Fetus with and without Exposure to In-Utero Brain Ischemia

    PubMed Central

    Malaeb, Shadi N; Sadowska, Grazyna B; Stonestreet, Barbara S

    2007-01-01

    Maternal treatment with corticosteroids reduces blood-brain barrier permeability in premature ovine fetuses and the incidence of intraventricular hemorrhage in premature infants. We tested the hypothesis that maternally administered corticosteroids increase the expression of tight junction (TJ) proteins in the cerebral cortex of ovine fetuses with and without exposure to in-utero brain ischemia. Fetuses at 80% of gestation were studied 18 h after the last of four 4−6 mg dexamethasone or placebo injections were given over 48 h to ewes. Groups were placebo/control, dexamethasone/control, placebo/ischemic, and dexamethasone/ischemic. Ischemia consisted of 30 min of fetal carotid artery occlusion and 72 h of reperfusion. Cerebral cortex was snap frozen. Western immunoblot was used to measure the protein expression of occludin, claudin-1, claudin-5, zonula occludens (ZO)-1, and ZO-2, and a TJ accessory protein annexin II. Occludin and annexin II protein expression were 48% and 58% higher (P<0.05) in the dexamethasone/ischemic than placebo/control group, respectively. Claudin-5 protein expression was 69% and 73% higher (P<0.05) in the placebo/ischemic and dexamethasone/ischemic than placebo/control group. Claudin-1 expression did not differ among groups. ZO-1 protein expression was 25%, 40%, and 55% lower in the dexamethasone/control, placebo/ischemic and dexamethasone/ischemic than placebo/control group, respectively. ZO-2 expression was 45% and 70% lower (P<0.01) in the placebo/ischemic and dexamethasone/ischemic than placebo/control group. We conclude that maternal corticosteroid treatment differentially regulates the expression of component proteins of TJs in the cerebral cortex of fetuses exposed to brain ischemia. The functional significance of this differential regulation warrants further investigation. PMID:17583681

  4. Sox18 preserves the pulmonary endothelial barrier under conditions of increased shear stress.

    PubMed

    Gross, Christine M; Aggarwal, Saurabh; Kumar, Sanjiv; Tian, Jing; Kasa, Anita; Bogatcheva, Natalia; Datar, Sanjeev A; Verin, Alexander D; Fineman, Jeffrey R; Black, Stephen M

    2014-11-01

    Shear stress secondary to increased pulmonary blood flow (PBF) is elevated in some children born with congenital cardiac abnormalities. However, the majority of these patients do not develop pulmonary edema, despite high levels of permeability inducing factors. Previous studies have suggested that laminar fluid shear stress can enhance pulmonary vascular barrier integrity. However, little is known about the mechanisms by which this occurs. Using microarray analysis, we have previously shown that Sox18, a transcription factor involved in blood vessel development and endothelial barrier integrity, is up-regulated in an ovine model of congenital heart disease with increased PBF (shunt). By subjecting ovine pulmonary arterial endothelial cells (PAEC) to laminar flow (20 dyn/cm(2) ), we identified an increase in trans-endothelial resistance (TER) across the PAEC monolayer that correlated with an increase in Sox18 expression. Further, the TER was also enhanced when Sox18 was over-expressed and attenuated when Sox18 expression was reduced, suggesting that Sox18 maintains the endothelial barrier integrity in response to shear stress. Further, we found that shear stress up-regulates the cellular tight junction protein, Claudin-5, in a Sox18 dependent manner, and Claudin-5 depletion abolished the Sox18 mediated increase in TER in response to shear stress. Finally, utilizing peripheral lung tissue of 4 week old shunt lambs with increased PBF, we found that both Sox18 and Claudin-5 mRNA and protein levels were elevated. In conclusion, these novel findings suggest that increased laminar flow protects endothelial barrier function via Sox18 dependent up-regulation of Claudin-5 expression. PMID:24677020

  5. Sox18 preserves the pulmonary endothelial barrier under conditions of increased shear stress

    PubMed Central

    Gross, Christine M.; Aggarwal, Saurabh; Kumar, Sanjiv; Tian, Jing; Kasa, Anita; Bogatcheva, Natalia; Datar, Sanjeev A.; Verin, Alexander D.; Fineman, Jeffrey R.; Black, Stephen M.

    2014-01-01

    Shear stress secondary to increased pulmonary blood flow (PBF) is elevated in some children born with congenital cardiac abnormalities. However, the majority of these patients do not develop pulmonary edema, despite high levels of permeability inducing factors. Previous studies have suggested that laminar fluid shear stress can enhance pulmonary vascular barrier integrity. However, little is known about the mechanisms by which this occurs. Using microarray analysis, we have previously shown that Sox18, a transcription factor involved in blood vessel development and endothelial barrier integrity, is up-regulated in an ovine model of congenital heart disease with increased PBF (shunt). By subjecting ovine pulmonary arterial endothelial cells (PAEC) to laminar flow (20 dyn/cm2), we identified an increase in trans-endothelial resistance (TER) across the PAEC monolayer that correlated with an increase in Sox18 expression. Further, the TER was also enhanced when Sox18 was over-expressed and attenuated when Sox18 expression was reduced, suggesting that Sox18 maintains the endothelial barrier integrity in response to shear stress. Further, we found that shear stress up-regulates the cellular tight junction protein, Claudin-5, in a Sox18 dependent manner, and Claudin-5 depletion abolished the Sox18 mediated increase in TER in response to shear stress. Finally, utilizing peripheral lung tissue of 4 week old shunt lambs with increased PBF, we found that both Sox18 and Claudin-5 mRNA and protein levels were elevated. In conclusion, these novel findings suggest that increased laminar flow protects endothelial barrier function via Sox18 dependent up-regulation of Claudin-5 expression. PMID:24677020

  6. Paracellular nutrient absorption is higher in bats than rodents: integrating from intact animals to the molecular level.

    PubMed

    Price, Edwin R; Rott, Katherine H; Caviedes-Vidal, Enrique; Karasov, William H

    2014-10-01

    Flying vertebrates have been hypothesized to rely heavily on paracellular absorption of nutrients to compensate for having smaller intestines than non-flyers. We tested this hypothesis in an insectivorous bat (Myotis lucifugus) and two insect-eating rodents (Onychomys leucogaster and Peromyscus leucopus). In intact animals, the fractional absorption of orally dosed l-arabinose (Mr 150) was 82% in M. lucifugus, which was more than twice that of the rodents. Absorption of creatinine (Mr 113) was greater than 50% for all species and did not differ between M. lucifugus and the rodents. We also conducted intestinal luminal perfusions on anesthetized animals. Absorption of l-arabinose per nominal surface area in M. lucifugus was nearly double that of the rodents, while absorption of creatinine was not different among species. Using an everted sleeve preparation, we demonstrated that high concentrations of l-arabinose and creatinine did not inhibit their own uptake, validating their use as passive, paracellular probes. Histological measurements indicated that M. lucifugus has more cells, and presumably more tight junctions, per nominal surface area than P. leucopus. This seems unlikely to explain entirely the higher absorption of l-arabinose in M. lucifugus during perfusions, because l-arabinose absorption normalized to the number of enterocytes was still double that of P. leucopus. As an alternative, we investigated tight junction gene expression. M. lucifugus had higher expression of claudin-1 and claudin-15, and lower expression of claudin-2 relative to P. leucopus. Expression of claudin-7 and occludin did not differ among species. Taken together, our results support the hypothesis that bats have evolved higher paracellular nutrient absorption than non-flying animals, and that this phenomenon might be driven by both histological characteristics and differences in tight junction gene expression.

  7. TcpC protein from E. coli Nissle improves epithelial barrier function involving PKCζ and ERK1/2 signaling in HT-29/B6 cells.

    PubMed

    Hering, N A; Richter, J F; Fromm, A; Wieser, A; Hartmann, S; Günzel, D; Bücker, R; Fromm, M; Schulzke, J D; Troeger, H

    2014-03-01

    The probiotic Escherichia coli Nissle 1917 (EcN) is widely used to maintain remission in ulcerative colitis. This is thought to be mediated by various immunomodulatory and barrier-stabilizing effects in the intestine. In this study, the mechanisms of barrier modulation by EcN were studied in the human epithelial HT-29/B6 cell culture model.EcN supernatant increased transepithelial resistance (TER) and reduced permeability to mannitol because of sealing of the paracellular passage pathway as revealed by two-path impedance spectroscopy. This increase in TER was attributed to the TcpC protein of EcN. TcpC induced protein kinase C-ζ (PKCζ) and extracellular-signal-regulated kinase 1/2 (ERK1/2) phosphorylation, which in turn resulted in upregulation of the barrier-forming tight junction protein claudin-14. By specific silencing of protein expression by small interfering RNA (siRNA), the sealing function of claudin-14 was confirmed. In conclusion, the TcpC protein of EcN affects innate immunity by improving intestinal barrier function through upregulation of claudin-14 via PKCζ and ERK1/2 signaling. PMID:23900194

  8. Acute regulation of tight junction ion selectivity in human airway epithelia

    PubMed Central

    Flynn, Andrea N.; Itani, Omar A.; Moninger, Thomas O.; Welsh, Michael J.

    2009-01-01

    Electrolyte transport through and between airway epithelial cells controls the quantity and composition of the overlying liquid. Many studies have shown acute regulation of transcellular ion transport in airway epithelia. However, whether ion transport through tight junctions can also be acutely regulated is poorly understood both in airway and other epithelia. To investigate the paracellular pathway, we used primary cultures of differentiated human airway epithelia and assessed expression of claudins, the primary determinants of paracellular permeability, and measured transepithelial electrical properties, ion fluxes, and La3+ movement. Like many other tissues, airway epithelia expressed multiple claudins. Moreover, different cell types in the epithelium expressed the same pattern of claudins. To evaluate tight junction regulation, we examined the response to histamine, an acute regulator of airway function. Histamine stimulated a rapid and transient increase in the paracellular Na+ conductance, with a smaller increase in Cl− conductance. The increase was mediated by histamine H1 receptors and depended on an increase in intracellular Ca2+ concentration. These results suggest that ion flow through the paracellular pathway can be acutely regulated. Such regulation could facilitate coupling of the passive flow of counter ions to active transcellular transport, thereby controlling net transepithelial salt and water transport. PMID:19208806

  9. Zona occludens-2 is critical for blood-testis barrier integrity and male fertility.

    PubMed

    Xu, Jianliang; Anuar, Farhana; Ali, Safiah Mohamed; Ng, Mei Yong; Phua, Dominic C Y; Hunziker, Walter

    2009-10-01

    Tight junction integral membrane proteins such as claudins and occludin are tethered to the actin cytoskeleton by adaptor proteins, notably the closely related zonula occludens (ZO) proteins ZO-1, ZO-2, and ZO-3. All three ZO proteins have recently been inactivated in mice. Although ZO-3 knockout mice lack an obvious phenotype, animals deficient in ZO-1 or ZO-2 show early embryonic lethality. Here, we rescue the embryonic lethality of ZO-2 knockout mice by injecting ZO-2(-/-) embryonic stem (ES) cells into wild-type blastocysts to generate viable ZO-2 chimera. ZO-2(-/-) ES cells contribute extensively to different tissues of the chimera, consistent with an extraembryonic requirement for ZO-2 rather than a critical role in epiblast development. Adult chimera present a set of phenotypes in different organs. In particular, male ZO-2 chimeras show reduced fertility and pathological changes in the testis. Lanthanum tracer experiments show a compromised blood-testis barrier. Expression levels of ZO-1, ZO-3, claudin-11, and occludin are not apparently affected. ZO-1 and occludin still localize to the blood-testis barrier region, but claudin-11 is less well restricted and the localization of connexin-43 is perturbed. The critical role of ZO-2 for male fertility and blood-testis barrier integrity thus provides a first example for a nonredundant role of an individual ZO protein in adult mice.

  10. Sebaceous Gland, Hair Shaft, and Epidermal Barrier Abnormalities in Keratosis Pilaris with and without Filaggrin Deficiency

    PubMed Central

    Gruber, Robert; Sugarman, Jeffrey L.; Crumrine, Debra; Hupe, Melanie; Mauro, Theodora M.; Mauldin, Elizabeth A.; Thyssen, Jacob P.; Brandner, Johanna M.; Hennies, Hans-Christian; Schmuth, Matthias; Elias, Peter M.

    2016-01-01

    Although keratosis pilaris (KP) is common, its etiopathogenesis remains unknown. KP is associated clinically with ichthyosis vulgaris and atopic dermatitis and molecular genetically with filaggrin-null mutations. In 20 KP patients and 20 matched controls, we assessed the filaggrin and claudin 1 genotypes, the phenotypes by dermatoscopy, and the morphology by light and transmission electron microscopy. Thirty-five percent of KP patients displayed filaggrin mutations, demonstrating that filaggrin mutations only partially account for the KP phenotype. Major histologic and dermatoscopic findings of KP were hyperkeratosis, hypergranulosis, mild T helper cell type 1-dominant lymphocytic inflammation, plugging of follicular orifices, striking absence of sebaceous glands, and hair shaft abnormalities in KP lesions but not in unaffected skin sites. Changes in barrier function and abnormal paracellular permeability were found in both interfollicular and follicular stratum corneum of lesional KP, which correlated ultrastructurally with impaired extracellular lamellar bilayer maturation and organization. All these features were independent of filaggrin genotype. Moreover, ultrastructure of corneodesmosomes and tight junctions appeared normal, immunohistochemistry for claudin 1 showed no reduction in protein amounts, and molecular analysis of claudin 1 was unremarkable. Our findings suggest that absence of sebaceous glands is an early step in KP pathogenesis, resulting in downstream hair shaft and epithelial barrier abnormalities. PMID:25660180

  11. Combined deletion of Pten and p53 in mammary epithelium accelerates triple-negative breast cancer with dependency on eEF2K

    PubMed Central

    Liu, Jeff C; Voisin, Veronique; Wang, Sharon; Wang, Dong-Yu; Jones, Robert A; Datti, Alessandro; Uehling, David; Al-awar, Rima; Egan, Sean E; Bader, Gary D; Tsao, Ming; Mak, Tak W; Zacksenhaus, Eldad

    2014-01-01

    The tumor suppressors Pten and p53 are frequently lost in breast cancer, yet the consequences of their combined inactivation are poorly understood. Here, we show that mammary-specific deletion of Pten via WAP-Cre, which targets alveolar progenitors, induced tumors with shortened latency compared to those induced by MMTV-Cre, which targets basal/luminal progenitors. Combined Pten-p53 mutations accelerated formation of claudin-low, triple-negative-like breast cancer (TNBC) that exhibited hyper-activated AKT signaling and more mesenchymal features relative to Pten or p53 single-mutant tumors. Twenty-four genes that were significantly and differentially expressed between WAP-Cre:Pten/p53 and MMTV-Cre:Pten/p53 tumors predicted poor survival for claudin-low patients. Kinome screens identified eukaryotic elongation factor-2 kinase (eEF2K) inhibitors as more potent than PI3K/AKT/mTOR inhibitors on both mouse and human Pten/p53-deficient TNBC cells. Sensitivity to eEF2K inhibition correlated with AKT pathway activity. eEF2K monotherapy suppressed growth of Pten/p53-deficient TNBC xenografts in vivo and cooperated with doxorubicin to efficiently kill tumor cells in vitro. Our results identify a prognostic signature for claudin-low patients and provide a rationale for using eEF2K inhibitors for treatment of TNBC with elevated AKT signaling. PMID:25330770

  12. Transmigration of Neural Stem Cells across the Blood Brain Barrier Induced by Glioma Cells

    PubMed Central

    Díaz-Coránguez, Mónica; Segovia, José; López-Ornelas, Adolfo; Puerta-Guardo, Henry; Ludert, Juan; Chávez, Bibiana; Meraz-Cruz, Noemi; González-Mariscal, Lorenza

    2013-01-01

    Transit of human neural stem cells, ReNcell CX, through the blood brain barrier (BBB) was evaluated in an in vitro model of BBB and in nude mice. The BBB model was based on rat brain microvascular endothelial cells (RBMECs) cultured on Millicell inserts bathed from the basolateral side with conditioned media (CM) from astrocytes or glioma C6 cells. Glioma C6 CM induced a significant transendothelial migration of ReNcells CX in comparison to astrocyte CM. The presence in glioma C6 CM of high amounts of HGF, VEGF, zonulin and PGE2, together with the low abundance of EGF, promoted ReNcells CX transmigration. In contrast cytokines IFN-α, TNF-α, IL-12p70, IL-1β, IL-6, IL-8 and IL-10, as well as metalloproteinases -2 and -9 were present in equal amounts in glioma C6 and astrocyte CMs. ReNcells expressed the tight junction proteins occludin and claudins 1, 3 and 4, and the cell adhesion molecule CRTAM, while RBMECs expressed occludin, claudins 1 and 5 and CRTAM. Competing CRTAM mediated adhesion with soluble CRTAM, inhibited ReNcells CX transmigration, and at the sites of transmigration, the expression of occludin and claudin-5 diminished in RBMECs. In nude mice we found that ReNcells CX injected into systemic circulation passed the BBB and reached intracranial gliomas, which overexpressed HGF, VEGF and zonulin/prehaptoglobin 2. PMID:23637756

  13. Chronic type 2 diabetes reduces the integrity of the blood-brain barrier by reducing tight junction proteins in the hippocampus

    PubMed Central

    YOO, Dae Young; YIM, Hee Sun; JUNG, Hyo Young; NAM, Sung Min; KIM, Jong Whi; CHOI, Jung Hoon; SEONG, Je Kyung; YOON, Yeo Sung; KIM, Dae Won; HWANG, In Koo

    2016-01-01

    In the present study, we investigated the effects of type 2 diabetes-induced hyperglycemia on the integrity of the blood–brain barrier and tight junction markers in the rat hippocampus. Forty-week-old diabetic (Zucker diabetic fatty, ZDF) rats and littermate control (Zucker lean control, ZLC) rats were used in this study. We evaluated the integrity of the blood–brain barrier by measuring sodium fluorescein extravasation and blood vessel ultrastructure. In addition, tight junction markers, such as zona occludens-1, occludin and claudin-5, were quantified by western blot analysis. ZDF rats showed significantly increased sodium fluorescein leakage in the hippocampus. Tight junction markers, such as occludin and claudin-5, were significantly decreased in the hippocampi of ZDF rats compared to those of ZLC rats. In addition, ZDF rats showed ultrastructural changes with phagocytic findings in the blood vessels. These results suggest that chronic untreated diabetes impairs the permeability of the hippocampal blood–brain barrier by down-regulating occludin and claudin-5, indicating that chronic untreated diabetes may cause hippocampus-dependent dysfunction. PMID:26876499

  14. Rapid remodeling of tight junctions during paracellular diapedesis in a human model of the blood-brain barrier.

    PubMed

    Winger, Ryan C; Koblinski, Jennifer E; Kanda, Takashi; Ransohoff, Richard M; Muller, William A

    2014-09-01

    Leukocyte transendothelial migration (TEM; diapedesis) is a critical event in immune surveillance and inflammation. Most TEM occurs at endothelial cell borders (paracellular). However, there is indirect evidence to suggest that, at the tight junctions of the blood-brain barrier (BBB), leukocytes migrate directly through the endothelial cell body (transcellular). Why leukocytes migrate through the endothelial cell body rather than the cell borders is unknown. To test the hypothesis that the tightness of endothelial cell junctions influences the pathway of diapedesis, we developed an in vitro model of the BBB that possessed 10-fold higher electrical resistance than standard culture conditions and strongly expressed the BBB tight junction proteins claudin-5 and claudin-3. We found that paracellular TEM was still the predominant pathway (≥98%) and TEM was dependent on PECAM-1 and CD99. We show that endothelial tight junctions expressing claudin-5 are dynamic and undergo rapid remodeling during TEM. Membrane from the endothelial lateral border recycling compartment is mobilized to the exact site of tight junction remodeling. This preserves the endothelial barrier by sealing the intercellular gaps with membrane and engaging the migrating leukocyte with unligated adhesion molecules (PECAM-1 and CD99) as it crosses the cell border. These findings provide new insights into leukocyte-endothelial interactions at the BBB and suggest that tight junctions are more dynamic than previously appreciated. PMID:25063869

  15. Ouabain modulates epithelial cell tight junction

    PubMed Central

    Larre, Isabel; Lazaro, Amparo; Contreras, Ruben G.; Balda, Maria S.; Matter, Karl; Flores-Maldonado, Catalina; Ponce, Arturo; Flores-Benitez, David; Rincon-Heredia, Ruth; Padilla-Benavides, Teresita; Castillo, Aída; Shoshani, Liora; Cereijido, Marcelino

    2010-01-01

    Epithelial cells treated with high concentrations of ouabain (e.g., 1 μM) retrieve molecules involved in cell contacts from the plasma membrane and detach from one another and their substrates. On the basis of this observation, we suggested that ouabain might also modulate cell contacts at low, nontoxic levels (10 or 50 nM). To test this possibility, we analyzed its effect on a particular type of cell–cell contact: the tight junction (TJ). We demonstrate that at concentrations that neither inhibit K+ pumping nor disturb the K+ balance of the cell, ouabain modulates the degree of sealing of the TJ as measured by transepithelial electrical resistance (TER) and the flux of neutral 3 kDa dextran (JDEX). This modulation is accompanied by changes in the levels and distribution patterns of claudins 1, 2, and 4. Interestingly, changes in TER, JDEX, and claudins behavior are mediated through signal pathways containing ERK1/2 and c-Src, which have distinct effects on each physiological parameter and claudin type. These observations support the theory that at low concentrations, ouabain acts as a modulator of cell–cell contacts. PMID:20534449

  16. Changes in barrier health status of the gill for grass carp (Ctenopharyngodon idella) during valine deficiency: Regulation of tight junction protein transcript, antioxidant status and apoptosis-related gene expression.

    PubMed

    Feng, Lin; Luo, Jian-Bo; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu

    2015-08-01

    This study investigated the effects of dietary valine on tight junction protein transcription, antioxidant status and apoptosis on grass carp gills (Ctenopharyngodon idella). Fish were fed six different experimental diets containing graded levels of valine (4.3, 8.0, 10.6, 13.1, 16.7, 19.1 g/kg). The results indicated that valine deficiency decreased Claudin b, Claudin 3, Occludin and ZO-1 transcription and increased Claudin 15 expression in the fish gill (P < 0.05). These effects were partly due to the down-regulation of interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and IκB α and the up-regulation of relative mRNA expression of interleukin 1β (IL-1β), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α) and nuclear factor κB P65 (NF-κB P65) (P < 0.05). However, valine deficiency and valine supplementation did not have a significant effect on Claudin c and Claudin 12 expression in grass carp gills (P > 0.05). Valine deficiency also disrupted antioxidant status in the gill by decreasing anti-superoxide radicals and hydroxyl radical capacity, glutathione contents and the activities and mRNA levels of Cu/Zn superoxide dismutase (SOD1), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione-S-transferase (GST) (P < 0.05). These results may be ascribed to the down-regulation of NF-E2-related factor 2 (Nrf2), target of rapamycin (TOR) and ribosomal protein S6 kinase 1 (S6K1) and the up-regulation of Kelch-like-ECH-associated protein 1 (Keap1) (P < 0.05). Additionally, valine deficiency induced DNA fragmentation via the up-regulation of Caspase 3, Caspase 8 and Caspase 9 expressions (P < 0.05). These results may be ascribed to the improvement in ROS levels in the fish gill (P < 0.05). Taken together, the results showed that valine deficiency impaired the structural integrity of fish gill by disrupted fish antioxidant defenses and regulating the expression of tight junction protein, cytokines, antioxidant

  17. Changes in integrity of the gill during histidine deficiency or excess due to depression of cellular anti-oxidative ability, induction of apoptosis, inflammation and impair of cell-cell tight junctions related to Nrf2, TOR and NF-κB signaling in fish.

    PubMed

    Jiang, Wei-Dan; Feng, Lin; Qu, Biao; Wu, Pei; Kuang, Sheng-Yao; Jiang, Jun; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2016-09-01

    This study firstly explored the possible effects of dietary histidine on structural integrity and the related signaling factor gene expression in the gills of fish. Young grass carp (Ctenopharyngodon idella) were fed with six diets containing gradual levels of histidine for 8 weeks. The results firstly demonstrated that histidine deficiency caused increases in reactive oxygen species (ROS) contents, and severe oxidative damage (lipid peroxidation and protein oxidation) in the gills of fish, which was partially due to the decreased glutathione (GSH) content and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)]. Further investigations indicated that histidine deficiency caused depressions of those antioxidant enzyme activities are related to the down-regulation of corresponding antioxidant enzyme genes and the related signaling factor Nrf2 mRNA levels. Meanwhile, histidine deficiency induced DNA fragmentation via up-regulation of caspase-3, caspase-8 and caspase-9 expressions that referring to the down-regulation of TOR and S6K mRNA levels. Furthermore, His deficiency down-regulated claudin-b, claudin-c, claudin-3, claudin-12, claudin-15, occludin and ZO-1 transcription in fish gills. These effects were partially related to the up-regulation of pro-inflammatory cytokines, interleukin 1β (IL-1β), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α) and related signaling factor nuclear factor κB P65 (NF-κB P65) mRNA levels, and the down-regulation of anti-inflammatory cytokines, interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and related signaling factor IκBα mRNA levels. Excessive histidine exhibited negative effects that were similar to histidine deficiency, whereas the optimal histidine levels reversed those negative effects. Taken together, our results showed that histidine deficiency or excess impaired the structural

  18. Folic acid deficiency impairs the gill health status associated with the NF-κB, MLCK and Nrf2 signaling pathways in the gills of young grass carp (Ctenopharyngodon idella).

    PubMed

    Shi, Lei; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu

    2015-11-01

    The aim of this study was to investigate the effect of dietary folic acid on fish growth, the immune and barrier functions of fish gills, and the potential mechanisms of these effects. Young grass carp (Ctenopharyngodon idella) were fed diets containing graded levels of folic acid at 0.10 (basal diet), 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results showed that acid phosphatase and lysozyme activities and the complement component 3 content in fish gills decreased with folic acid deficiency (P < 0.05). Folic acid deficiency up-regulated liver-expressed antimicrobial peptide 1, interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65, IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression. Folic acid deficiency down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in fish gills (P < 0.05). These results showed that limited folic acid decreased fish gill immune status. Furthermore, folic acid deficiency down-regulated claudin-b, claudin-c, claudin-3, occludin and zonula occludens 1 gene expression, whereas folic acid deficiency up-regulated claudin-12, claudin-15, myosin light chain kinase and p38 mitogen activated protein kinase gene expression in fish gills (P < 0.05). These results suggested that folic acid deficiency disrupted tight junction-mediated fish gill barrier function. Additionally, folic acid deficiency increased the content of reactive oxygen species, protein carbonyl and malondialdehyde (MDA); Mn superoxide dismutase activity and gene expression; and Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression (P < 0.05). Conversely, folic acid deficiency decreased Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase activities and gene expression as well as NF-E2-related factor 2 gene expression in fish gills (P < 0.05). All of these results indicated that folic acid

  19. Clostridium perfringens enterotoxin as a potential drug for intravesical treatment of bladder cancer.

    PubMed

    Gabig, Theodore G; Waltzer, Wayne C; Whyard, Terry; Romanov, Victor

    2016-09-16

    The current intravesical treatment of bladder cancer (BC) is limited to a few chemotherapeutics that show imperfect effectiveness and are associated with some serious complications. Thus, there is an urgent need for alternative therapies, especially for patients with high-risk non-muscle invasive (NMIBC). Clostridium perfringens enterotoxin (CPE), cytolytic protein binds to its receptors: claudin 3 and 4 that are expressed in epithelial cells. This binding is followed by rapid cell death. Claudin 4 is present in several epithelial tissue including bladder urothelium and its expression is elevated in some forms of BC. In addition to directly targeting BC cells, binding of CPE to claudins increases urothelium permeability that creates conditions for better accession of the tumor. Therefore, we evaluated CPE as a candidate for intravesical treatment of BC using a cellular model. We examined cytotoxicity of CPE against BC cells lines and 3D cultures of cells derived from surgical samples. To better elucidate cellular mechanisms, activated by CPE and to consider the use of CPE non-toxic fragment (C-CPE) for combination treatment with other drugs we synthesized C-CPE, compared its cytotoxic activity with CPE and examined claudin 4 expression and intracellular localization after C-CPE treatment. CPE induced cell death after 1 h in low aggressive RT4 cells, in moderately aggressive 5637 cells and in the primary 3D cultures of BC cells derived from NMIBC. Conversely, non-transformed urothelial cells and cells derived from highly aggressive tumor (T24) survived this treatment. The reason for this resistance to CPE might be the lower expression of CLDNs or their inaccessibility for CPE in these cells. C-CPE treatment for 48 h did not affect cell viability in tested cells, but declined expression of CLDN4 in RT4 cells. C-CPE increased sensitivity of RT4 cells to Mitommycin C and Dasatinib. To better understand mechanisms of this effect we examined expression and

  20. Changes in integrity of the gill during histidine deficiency or excess due to depression of cellular anti-oxidative ability, induction of apoptosis, inflammation and impair of cell-cell tight junctions related to Nrf2, TOR and NF-κB signaling in fish.

    PubMed

    Jiang, Wei-Dan; Feng, Lin; Qu, Biao; Wu, Pei; Kuang, Sheng-Yao; Jiang, Jun; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2016-09-01

    This study firstly explored the possible effects of dietary histidine on structural integrity and the related signaling factor gene expression in the gills of fish. Young grass carp (Ctenopharyngodon idella) were fed with six diets containing gradual levels of histidine for 8 weeks. The results firstly demonstrated that histidine deficiency caused increases in reactive oxygen species (ROS) contents, and severe oxidative damage (lipid peroxidation and protein oxidation) in the gills of fish, which was partially due to the decreased glutathione (GSH) content and antioxidant enzyme activities [superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione-S-transferase (GST) and glutathione reductase (GR)]. Further investigations indicated that histidine deficiency caused depressions of those antioxidant enzyme activities are related to the down-regulation of corresponding antioxidant enzyme genes and the related signaling factor Nrf2 mRNA levels. Meanwhile, histidine deficiency induced DNA fragmentation via up-regulation of caspase-3, caspase-8 and caspase-9 expressions that referring to the down-regulation of TOR and S6K mRNA levels. Furthermore, His deficiency down-regulated claudin-b, claudin-c, claudin-3, claudin-12, claudin-15, occludin and ZO-1 transcription in fish gills. These effects were partially related to the up-regulation of pro-inflammatory cytokines, interleukin 1β (IL-1β), interleukin 8 (IL-8), tumor necrosis factor-α (TNF-α) and related signaling factor nuclear factor κB P65 (NF-κB P65) mRNA levels, and the down-regulation of anti-inflammatory cytokines, interleukin 10 (IL-10), transforming growth factor β1 (TGF-β1) and related signaling factor IκBα mRNA levels. Excessive histidine exhibited negative effects that were similar to histidine deficiency, whereas the optimal histidine levels reversed those negative effects. Taken together, our results showed that histidine deficiency or excess impaired the structural

  1. Dietary pantothenic acid deficiency and excess depress the growth, intestinal mucosal immune and physical functions by regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in grass carp (Ctenopharyngodon idella).

    PubMed

    Li, Li; Feng, Lin; Jiang, Wei-Dan; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2015-08-01

    This study investigated the effects of dietary pantothenic acid (PA) on the growth, intestinal mucosal immune and physical barrier, and relative mRNA levels of signaling molecules in the intestine of grass carp (Ctenopharyngodon idella). A total of 540 grass carp (253.44 ± 0.69 g) were fed six diets with graded levels of PA (PA1, PA15, PA30, PA45, PA60 and PA75 diets) for 8 weeks. The results indicated that compared with PA deficiency (PA1 diet) and excess (PA75 diet) groups, optimal PA supplementation increased (P < 0.05): (1) percent weight gain (PWG), feed intake and feed efficiency; (2) lysozyme activity, complement 3 content, liver-expressed antimicrobial peptide 2 and hepcidin, interleukin 10, transforming growth factor β1 and inhibitor of κBα mRNA levels in some intestinal segments; (3) activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione S-transferases and glutathione reductase, and NF-E2-related factor 2 (Nrf2) mRNA level in the whole intestine; (4) Claudin b, Claudin 3, Claudin c, Occludin and ZO-1 mRNA levels in some intestinal segments of grass carp. Conversely, optimal PA supplementation decreased (P < 0.05): (1) tumor necrosis factor α, interleukin 1β, interferon γ2, interleukin 8, nuclear factor κB P65 (NF-κB P65), IκB kinase α, IκB kinase β, IκB kinase γ and target of rapamycin (TOR) mRNA expression levels in some intestinal segments; (2) reactive oxygen species, malondialdehyde and protein carbonyl contents, and Kelch-like ECH-associating protein 1a, Kelch-like ECH-associating protein 1b in the intestine; (3) Claudin 12, Claudin 15a and myosin light-chain kinase (MLCK) mRNA levels in some intestinal segments of grass carp. In conclusion, optimum PA promoted growth, intestinal mucosal immune and physical function, as well as regulated mRNA levels of signaling molecules NF-κB P65, TOR, Nrf2 and MLCK in grass carp intestine. Based on the quadratic

  2. Toward the sociopolitical in science education

    NASA Astrophysics Data System (ADS)

    Tolbert, Sara; Bazzul, Jesse

    2016-07-01

    In this paper, we explore how Jacques Rancière's (The ignorant schoolmaster: five lessons in intellectual emancipation. Stanford University Press, Stanford, 1991) notions of radical equality and dissensus reveal horizons for activism and sociopolitical engagement in science education theory, research, and practice. Drawing on Rochelle Gutiérrez' (J Res Math Educ 44(1):37-68, 2013a. doi: 10.5951/jresematheduc.44.1.0037; J Urban Math Educ 6(2):7-19, b) "sociopolitical turn" for mathematics education, we identify how the field of science education can/is turning from more traditional notions of equity, achievement and access toward issues of systemic oppression, identity and power. Building on the conversation initiated by Lorraine Otoide who draws from French philosopher Jacques Rancière to experiment with a pedagogy of radical equality, we posit that a sociopolitical turn in science education is not only imminent, but necessary to meet twenty-first century crises.

  3. [Clothes of the HOUSE, or Clothes of REASON? Children's clothing during the Age of Enlightenment].

    PubMed

    Kottek, Samuel

    2014-01-01

    Children's clothing is a subject that forms part of the history of pediatrics. Many studies focus on the ideas developed by Locke and Rousseau. Here we choose to focus our study on an author who is rarely quoted: Jacques Ballexserd (1726-1774), "citizen of Geneva," who is little known to historians of pediatrics. However, George Frederic Still (1868-1941) devotes two pages to his views in his Histoire de la Pédiatrie.

  4. Ellen Weaver, Biologist

    NASA Technical Reports Server (NTRS)

    1973-01-01

    Ellen Weaver, an associate professor of biology from California State University is shown developing instrumentation to be used in satellites for ocean monitoring. In the early 1970s, NASA researchers and ocean explorer Jacques Cousteau formed a team to study productivity of the sea. The team devised a sensor system to monitor ocean temperatures and chlorophyll levels by aircraft. This sensor was used in the satellite communication and weather equipment provided by NASA to assist in the accuracy of satellite observation.

  5. The design of an enzyme: a chronology on the controversy.

    PubMed

    Buc, Henri

    2013-05-13

    After the publication of the Monod-Wyman-Changeux model, a controversy arose between Jacques Monod, Francis Crick and Jeffries Wyman about the comparison of the regulatory performances of an oligomer undergoing a concerted transition between two states and a monomer having the same composition and subjected to a similar conformational equilibrium. The controversy took place between September 1965 and March 1966. It gave rise to several unpublished notes. Numerous misunderstandings between the participants were not fully dissipated as the controversy abruptly ended.

  6. Terrorism--A (Self) Love Story: Redirecting the Significance Quest Can End Violence

    ERIC Educational Resources Information Center

    Kruglanski, Arie W.; Belanger, Jocelyn J.; Gelfand, Michele; Gunaratna, Rohan; Hettiarachchi, Malkanthi; Reinares, Fernando; Orehek, Edward; Sasota, Jo; Sharvit, Keren

    2013-01-01

    Jean-Jacques Rousseau's concepts of self-love ("amour propre") and love of self ("amour de soi meme") are applied to the psychology of terrorism. Self-love is concern with one's image in the eyes of respected others, members of one's group. It denotes one's feeling of personal significance, the sense that…

  7. Victoria Land, Ross Sea, and Ross Ice Shelf, Antarctica

    NASA Technical Reports Server (NTRS)

    2002-01-01

    On December 19, 2001, MODIS acquired data that produced this image of Antarctica's Victoria Land, Ross Ice Shelf, and the Ross Sea. The coastline that runs up and down along the left side of the image denotes where Victoria Land (left) meets the Ross Ice Shelf (right). The Ross Ice Shelf is the world's largest floating body of ice, approximately the same size as France. Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  8. Coast of the East Siberian Sea, Russia

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Sea ice is pulling away from the coastline of northeastern Siberia in the east Siberia Sea. This true-color Moderate Resolution Imaging Spectroradiometer (MODIS) image from May 26, 2002, also the thinning of ice in bays and coves, and the blue reflection of the water from beneath causes the ice to appear bright blue. Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  9. Flooding of the Ob and Irtysh Rivers, Russia

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This pair of true- and false-color images shows flooding along the Ob' (large east-west running river) and Irtysh (southern tributary of the Ob') on July 7, 2002. In the false-color image, land surfaces are orange-gold and flood waters are black or dark blue. Fires are marked with red dots in both images. Rivers Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  10. [Ethical issues in transfusion medicine].

    PubMed

    Tissot, J-D; Danic, B; Cabaud, J-J; Garraud, O

    2016-09-01

    Ethics is on the cross road of off values that are present along the ways of transfusion medicine. This is an important tool to afford opinions as well as debates that always emerge when discussing transfusion medicine. The wording is particularly important; this was one among several others that characterized the soul of Jean-Jacques Lefrère when he opened the doors of the ethical issues of transfusion medicine. PMID:27443188

  11. Jacobus Sylvius (1478-1555): physician, teacher, and anatomist.

    PubMed

    Tubbs, R Shane; Linganna, Sanjay; Loukas, Marios

    2007-11-01

    Jacques Dubois (1478-1555), better known by his Latin cognomen Jacobus Sylvius was one of the great anatomists and teachers of the Renaissance period. His legacy today, however, is marred by his feud with pupil Andreas Vesalius. The story of Sylvius's life provides the modern clinical anatomist with valuable lessons regarding the nature of orthodoxy, conflict, and the evolving nature of "truth." PMID:17948293

  12. Insulating oxide surfaces and nanostructures

    NASA Astrophysics Data System (ADS)

    Goniakowski, Jacek; Noguera, Claudine

    2016-03-01

    This contribution describes some peculiarities of the science of oxide surfaces and nanostructures and proposes a simple conceptual scheme to understand their electronic structure, in the spirit of Jacques Friedel's work. Major results on the effects of non-stoichiometry and polarity are presented, for both semi-infinite surfaces and ultra-thin films, and promising lines of research for the near future are sketched. xml:lang="fr"

  13. Lena River Delta and East Siberian Sea

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The winter sea ice in the east Siberian Sea is looking a bit like a cracked windshield in these true-color Moderate Resolution Imaging Spectroradiometer (MODIS) images from June 16 and 23, 2002. North of the thawing tundra, the sea ice takes on its cracked, bright blue appearance as it thins, which allows the reflection of the water to show through. Numerous still-frozen lakes dot the tundra. Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  14. East Siberian Sea, Russia

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The winter sea ice in the east Siberian Sea is looking a bit like a cracked windshield in these true-color Moderate Resolution Imaging Spectroradiometer (MODIS) images from June 16 and 23, 2002. North of the thawing tundra, the sea ice takes on its cracked, bright blue appearance as it thins, which allows the reflection of the water to show through. Numerous still-frozen lakes dot the tundra. Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  15. Classical music and the teeth.

    PubMed

    Eramo, Stefano; Di Biase, Mary Jo; De Carolis, Carlo

    2013-01-01

    Teeth and their pathologies are frequent themes in classical music. The teeth have inspired popular songwriters such as Thomas Crecquillon, Carl Loewe, Amilcare Ponchielli & Christian Sinding; as well as composers whose works are still played all over the world, such as Robert Schumann and Jacques Offenbach. This paper examines several selections in which the inspiring theme is the teeth and the pain they can cause, from the suffering of toothache, to the happier occasion of a baby's first tooth. PMID:23691776

  16. Lake Volta, Ghana

    NASA Technical Reports Server (NTRS)

    2002-01-01

    This true-color image of Lake Volta in Ghana was acquired March 31, 2002 by the Moderate Resolution Imaging Spectroradiometer (MODIS). Lake Volta is one of the world's largest artificially created lakes. Lake Volta is actually a reservoir formed from the damming of the Volta River, and extends 250 miles north of the Akosombo Dam. The lake covers an area of 8,482 square km. Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  17. Phytoplankton bloom all along the coast of Southeast United States

    NASA Technical Reports Server (NTRS)

    2002-01-01

    All along the eastern and southern coasts of the United States, marine plants seem impervious to the onslaught of winter weather further north. In this true-color image from January 9, 2002, phytoplankton can be seen growing in the nation's coastal waters; their characteristic blue-green swirls are especially visible off the west coast of Florida. Fire locations are marked with red dots. Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  18. Sulfur plumes off Namibia

    NASA Technical Reports Server (NTRS)

    2002-01-01

    Sulfur plumes rising up from the bottom of the ocean floor produce colorful swirls in the waters off the coast of Namibia in southern Africa. The plumes come from the breakdown of marine plant matter by anaerobic bacteria that do not need oxygen to live. This image was acquired by the Moderate Resolution Imaging Spectroradiometer (MODIS) on the Terra satellite on April 24, 2002 Credit: Jacques Descloitres, MODIS Land Rapid Response Team, NASA/GSFC

  19. In pursuit of the practice of radical equality: Rancière inspired pedagogical inquiries in elementary school science education

    NASA Astrophysics Data System (ADS)

    Otoide, Lorraine

    2016-01-01

    This article outlines a study of praxis. Inspired by my reading of Jacques Rancière's (The ignorant schoolmaster: Five lessons in intellectual emancipation, trans. K. Ross, Stanford University Press, Stanford, 1991) influential text, The Ignorant School Master, I explore the practical applications of his work for teaching and outline a pedagogical response that sought to effect educational change through a philosophically driven teacher inquiry.

  20. The semiotics of gender.

    PubMed

    Van Buren, J

    1992-01-01

    The semiotics of gender are investigated in this article for the purpose of exploring the way that deep unconscious motives in relationship to cultural biases give rise to gender concepts. Theories of semiotic processes, including Jacques Lacan's concept of the psychoanalytic signifier, are explained briefly and applied to the signs of gender. The article concludes that gender concepts develop out of biology, unconscious feelings, and social patterning, and are not given, natural, and irrevocable.

  1. Dislocations and other topological oddities

    NASA Astrophysics Data System (ADS)

    Pieranski, Pawel

    2016-03-01

    We will show that the book Dislocations by Jacques Friedel, published half a century ago, can still be recommended, in agreement with the author's intention, as a textbook "for research students at University and for students at engineering schools as well as for research engineers". Indeed, today dislocations are known to occur not only in solid crystals but also in many other systems discovered more recently such as colloidal crystals or liquid crystals having periodic structures. Moreover, the concept of dislocations is an excellent starting point for lectures on topological defects occurring in systems equipped with order parameters resulting from broken symmetries: disclinations in nematic or hexatic liquid crystals, dispirations in chiral smectics or disorientations in lyotropic liquid crystals. The discussion of dislocations in Blue Phases will give us an opportunity to call on mind Sir Charles Frank, friend of Jacques Friedel since his Bristol years, who called these ephemeral mesophases "topological oddities". Being made of networks of disclinations, Blue Phases are similar to Twist Grain Boundary (TGB) smectic phases, which are made of networks of screw dislocations and whose existence was predicted by de Gennes in 1972 on the basis of the analogy between smectics and superconductors. We will stress that the book by Jacques Friedel contains seeds of this analogy.

  2. Biology and war--American biology and international science.

    PubMed

    Fangerau, Heiner

    2007-01-01

    The German-born American scientist Jacques Loeb (1859-1924) was one of the most important promoters of experimental biology around 1900. He was best known for his physico-chemical explanations of psychological processes and his biotechnological approach to artificial parthenogenesis. At the start of the First World War, Loeb was deeply troubled by the deterioration of the international scientific community and the growing alienation of his German and American colleagues. The aim of this paper is to examine Jacques Loeb's activities aimed at advancing scientific internationalism before, during, and after the war. Loeb, for example, tried to negotiate the publication of German authors in American journals during the war, at a time when this was categorically rejected by publishers. Immediately after the war, he tried to create a specific system aimed at disseminating scientific literature and funding selected European colleagues, in order to overcome what he considered reactionary and hegemonic forces within German scientific institutions. His correspondence with eminent scientists from all over the world (amongst them Albert Einstein, Richard Goldschmidt, Otto Meyerhof, Otto Warburg, Paul Ehrlich, Wolfgang Ostwald, Wilhelm Roux, and Ross Harrison) will serve as a source for the analysis. Special emphasis will be placed on the question how Jacques Loeb integrated epistemology, his particular world view, and his social commitment into the workings of his own life and how he tried to extend his scientific goal of controlling biological systems to the sphere of international science.

  3. Autonomous cure of damaged human intestinal epithelial cells by TLR2 and TLR4-dependent production of IL-22 in response to Spirulina polysaccharides.

    PubMed

    Tominaga, Akira; Konishi, Yuko; Taguchi, Takahiro; Fukuoka, Satoshi; Kawaguchi, Tokuichi; Noda, Tetsuo; Shimizu, Keiji

    2013-12-01

    In order to analyze the damage of human epithelial cells, we used human quasi-normal FPCK-1-1 cells derived from a colonic polyp in a patient with familial adenomatous polyposis as a monolayer, which is co-cultured with peptidoglycan (PGN)-stimulated THP-1 cells. Co-cultured FPCK-1-1 cells showed a decreased transepithelial electrical resistance (TER) and the lower level of claudin-2. When Spirulina complex polysaccharides were added one day before the start of the co-culture, there was no decrease of TER and claudin-2 (early phase damage). In contrast, when Spirulina complex polysaccharides were added to FPCK-1-1 cells after the level of TER had decreased, there was no recovery at the level of claudin-2, though the TER level recovered (late phase damage). The mucosa reconstitution is suggested to be involved in the recovery from the damaged status. Interestingly, autonomous recovery of FPCK-1-1 cells from both the early and late phase damage requires the production of IL-22, because anti-IL-22 antibodies inhibited recovery in these cases. Antibodies against either TLR2 or TLR4 inhibited the production of IL-22 from FPCK-1-1 colon epithelial cells, suggesting that signals through TLR2 and TLR4 are necessary for autonomous recovery of FPCK-1-1 colon epithelial cells by producing IL-22. In conclusion, we have established a useful model for the study of intestinal damage and recovery using human colon epithelial cells and our data suggest that damage to human colon epithelial cells can, at least in part, be recovered by the autonomous production of IL-22 in response to Spirulina complex polysaccharides. PMID:24126111

  4. Mechanisms That Determine the Internal Environment of the Developing Brain: A Transcriptomic, Functional and Ultrastructural Approach

    PubMed Central

    Liddelow, Shane A.; Dziegielewska, Katarzyna M.; Ek, C. Joakim; Habgood, Mark D.; Bauer, Hannelore; Bauer, Hans-Christian; Lindsay, Helen; Wakefield, Matthew J.; Strazielle, Nathalie; Kratzer, Ingrid; Møllgård, Kjeld; Ghersi-Egea, Jean-François; Saunders, Norman R.

    2013-01-01

    We provide comprehensive identification of embryonic (E15) and adult rat lateral ventricular choroid plexus transcriptome, with focus on junction-associated proteins, ionic influx transporters and channels. Additionally, these data are related to new structural and previously published permeability studies. Results reveal that most genes associated with intercellular junctions are expressed at similar levels at both ages. In total, 32 molecules known to be associated with brain barrier interfaces were identified. Nine claudins showed unaltered expression, while two claudins (6 and 8) were expressed at higher levels in the embryo. Expression levels for most cytoplasmic/regulatory adaptors (10 of 12) were similar at the two ages. A few junctional genes displayed lower expression in embryos, including 5 claudins, occludin and one junctional adhesion molecule. Three gap junction genes were enriched in the embryo. The functional effectiveness of these junctions was assessed using blood-delivered water-soluble tracers at both the light and electron microscopic level: embryo and adult junctions halted movement of both 286Da and 3kDa molecules into the cerebrospinal fluid (CSF). The molecular identities of many ion channel and transporter genes previously reported as important for CSF formation and secretion in the adult were demonstrated in the embryonic choroid plexus (and validated with immunohistochemistry of protein products), but with some major age-related differences in expression. In addition, a large number of previously unidentified ion channel and transporter genes were identified for the first time in plexus epithelium. These results, in addition to data obtained from electron microscopical and physiological permeability experiments in immature brains, indicate that exchange between blood and CSF is mainly transcellular, as well-formed tight junctions restrict movement of small water-soluble molecules from early in development. These data strongly indicate the

  5. 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

    PubMed Central

    Yu, Changsong; Jia, Gang; Deng, Qiuhong; Zhao, Hua; Chen, Xiaoling; Liu, Guangmang; Wang, Kangning

    2016-01-01

    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. PMID:26954146

  6. Altered intracellular region of MUC1 and disrupted correlation of polarity-related molecules in breast cancer subtypes

    PubMed Central

    Iizuka, Misato; Nakanishi, Yoko; Fuchinoue, Fumi; Maeda, Tetsuyo; Murakami, Eriko; Obana, Yukari; Enomoto, Katsuhisa; Tani, Mayumi; Sakurai, Kenichi; Amano, Sadao; Masuda, Shinobu

    2015-01-01

    MUC1 glycoprotein is overexpressed and its intracellular localization altered during breast carcinoma tumorigenesis. The present study aimed to clarify the relationship of cytoplasmic localization of MUC1 with the breast cancer subtype and the correlation of 10 molecules associated with cell polarity in breast cancer subtypes. We immunostained 131 formalin-fixed and paraffin-embedded breast cancer specimens with an anti-MUC1 antibody (MUC1/CORE). For 48 of the 131 tumor specimens, laser-assisted microdissection and real-time quantitative RT-PCR were performed to analyze mRNA levels of MUC1 and 10 molecules, β-catenin, E-cadherin, claudin 3, claudin 4, claudin 7, RhoA, cdc42, Rac1, Par3 and Par6. Localization of MUC1 protein varied among breast cancer subtypes, that is, both the apical domain and cytoplasm in luminal A-like tumors (P < 0.01) and both the cytoplasm and cell membrane in luminal B-like (growth factor receptor 2 [HER2]+) tumors (P < 0.05), and no expression was found in triple negative tumors (P < 0.001). Estrogen receptor (ER)+ breast cancers showed higher MUC1 mRNA levels than ER− breast cancers (P < 0.01). The incidence of mutual correlations of expression levels between two of the 10 molecules (55 combinations) was 54.5% in normal breast tissue and 38.2% in luminal A-like specimens, 16.4% in luminal B-like (HER2+), 3.6% in HER2 and 18.2% in triple negative specimens. In conclusion, each breast cancer subtype has characteristic cytoplasmic localization patterns of MUC1 and different degrees of disrupted correlation of the expression levels between the 10 examined molecules in comparison with normal breast tissue. PMID:25556893

  7. Gene expression fingerprint of uterine serous papillary carcinoma: identification of novel molecular markers for uterine serous cancer diagnosis and therapy

    PubMed Central

    Santin, A D; Zhan, F; Cane', S; Bellone, S; Palmieri, M; Thomas, M; Burnett, A; Roman, J J; Cannon, M J; Shaughnessy, J; Pecorelli, S

    2005-01-01

    Uterine serous papillary cancer (USPC) represents a rare but highly aggressive variant of endometrial cancer, the most common gynecologic tumour in women. We used oligonucleotide microarrays that interrogate the expression of some 10 000 known genes to profile 10 highly purified primary USPC cultures and five normal endometrial cells (NEC). We report that unsupervised analysis of mRNA fingerprints readily distinguished USPC from normal endometrial epithelial cells and identified 139 and 390 genes that exhibited >5-fold upregulation and downregulation, respectively, in primary USPC when compared to NEC. Many of the genes upregulated in USPC were found to represent adhesion molecules, secreted proteins and oncogenes, such as L1 cell adhesion molecule, claudin-3 and claudin-4, kallikrein 6 (protease M) and kallikrein 10 (NES1), interleukin-6 and c-erbB2. Downregulated genes in USPC included SEMACAP3, ras homolog gene family, member I (ARHI), and differentially downregulated in ovarian carcinoma gene 1. Quantitative RT–PCR was used to validate differences in gene expression between USPC and NEC for several of these genes. Owing to its potential as a novel therapeutic marker, expression of the high-affinity epithelial receptor for Clostridium perfringens enterotoxin (CPE) claudin-4 was further validated through immunohistochemical analysis of formalin-fixed paraffin-embedded specimens from which the primary USPC cultures were obtained, as well as an independent set of archival USPC specimens. Finally, the sensitivity of primary USPC to the administration of scalar doses of CPE in vitro was also demonstrated. Our results highlight the novel molecular features of USPC and provide a foundation for the development of new type-specific therapies against this highly aggressive variant of endometrial cancer. PMID:15785748

  8. Progesterone and allopregnanolone attenuate blood-brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases.

    PubMed

    Ishrat, Tauheed; Sayeed, Iqbal; Atif, Fahim; Hua, Fang; Stein, Donald G

    2010-11-01

    Blood-brain barrier (BBB) breakdown after stroke is linked to the up-regulation of metalloproteinases (MMPs) and inflammation. This study examines the effects of progesterone (PROG) and its neuroactive metabolite allopregnanolone (ALLO) on BBB integrity following permanent middle cerebral artery occlusion (pMCAO). Rats underwent pMCAO by electro-coagulation and received intraperitoneal injections of PROG (8 mg/kg), ALLO (8 mg/kg) or vehicle at 1 h post-occlusion and then subcutaneous injections (8 mg/kg) at 6, 24, and 48 h. MMP activation and expression were analyzed by Western blot, immunohistochemistry and gelatin zymography 72 h post-pMCAO. Occludin1, claudin5, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) were analyzed at 72 h post-pMCAO with Western blots. BBB permeability was measured by Evans blue extravasation and infarct size was evaluated by cresyl violet at 72 h after pMCAO. Ischemic injury significantly (p<0.05) increased the expression of MMP-9, MMP-2, TNF-α and IL-6, and reduced the levels of occludin1 and claudin5. These changes were followed by increased infarct size (% contralateral hemisphere) and Evans blue extravasation into the brain indicating compromise of the BBB. PROG and ALLO attenuated BBB disruption and infarct size following pMCAO by reducing MMPs and the inflammatory response and by preventing the degradation of occludin1 and claudin5. We conclude that PROG and ALLO can help to protect BBB disruption following pMCAO. PMID:20816826

  9. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats

    PubMed Central

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R.; Tóth, Andrea E.; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A.

    2016-01-01

    Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and

  10. Intestinal immune function, antioxidant status and tight junction proteins mRNA expression in young grass carp (Ctenopharyngodon idella) fed riboflavin deficient diet.

    PubMed

    Chen, Liang; Feng, Lin; Jiang, Wei-Dan; Jiang, Jun; Wu, Pei; Zhao, Juan; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang

    2015-11-01

    This study investigated the effects of riboflavin on intestinal immunity, tight junctions and antioxidant status of young grass carp (Ctenopharyngodon idella). Fish were fed diets containing graded levels of riboflavin (0.63-10.04 mg/kg diet) for 8 weeks. The study indicated that riboflavin deficiency decreased lysozyme, acid phosphatase, copper/zinc superoxide dismutase, glutathione reductase and glutathione peroxidase activities, and contents of complement component 3 and reduced glutathione in the intestine of fish (P < 0.05). Meanwhile, riboflavin deficiency increased reactive oxygen species, malondialdehyde and protein carbonyl contents and catalase activity (P < 0.05) in the intestine of fish. Furthermore, real-time polymerase chain reaction analysis was used to investigate mRNA expression patterns and found that the mRNA levels of interleukin 10 and transforming growth factor β1, Occludin, zonula occludens 1, Claudin-b and Claudin-c, inhibitor protein κBα, target of rapamycin, ribosomal S6 protein kinase 1 and NF-E2-related factor 2, copper/zinc superoxide dismutase, glutathione peroxidase and glutathione reductase were decreased (P < 0.05) in the intestine of fish fed riboflavin-deficient diet. Conversely, the mRNA levels of tumor necrosis factor α, interleukin 1β, interleukin 8, nuclear factor kappa B p65, Ikappa B kinase β, Ikappa B kinase γ, Kelch-like-ECH-associated protein 1b, p38 mitogen-activated protein kinase, myosin light chain kinase and Claudin-12 were increased (P < 0.05) in the intestine of fish fed riboflavin-deficient diet. In conclusion, riboflavin deficiency decreased immunity and structural integrity of fish intestine. The optimum riboflavin level for intestinal acid phosphatase activity of young grass carp was estimated to be 6.65 mg/kg diet.

  11. Protective effects of vascular endothelial growth factor in cultured brain endothelial cells against hypoglycemia.

    PubMed

    Zhao, Fei; Deng, Jiangshan; Yu, Xiaoyan; Li, Dawei; Shi, Hong; Zhao, Yuwu

    2015-08-01

    Hypoglycemia is a common and serious problem among patients with type 1 diabetes receiving treatment with insulin. Clinical studies have demonstrated that hypoglycemic edema is involved in the initiation of hypoglycemic brain damage. However, the mechanisms of this edema are poorly understood. Vascular endothelial growth factor (VEGF), a potent regulator of blood vessel function, has been observed an important candidate hormone induced by hypoglycemia to protect neurons by restoring plasma glucose. Whether VEGF has a protective effect against hypoglycemia-induced damage in brain endothelial cells is still unknown. To investigate the effects of hypoglycemia on cerebral microvascular endothelial cells and assess the protective effect of exogenous VEGF on endothelial cells during hypoglycemia, confluent monolayers of the brain endothelial cell line bEnd.3 were treated with normal (5.5 mM glucose), hypoglycemic (0, 0.5, 1 mM glucose) medium or hypoglycemic medium in the presence of VEGF. The results clearly showed that hypoglycemia significantly downregulated the expression of claudin-5 in bEnd.3 cells, without affecting ZO-1 and occludin expression and distribution. Besides, transendothelial permeability significantly increased under hypoglycemic conditions compared to that under control conditions. Moreover, the hypoglycemic medium in presence of VEGF decreased endothelial permeability via the inhibition of claudin-5 degradation and improved hypoglycemia-induced cell toxicity. Furthermore, Glucose transporter-1 (Glut-1) and apoptosis regulator Bcl-2 expression were significantly upregulated. Taken together, hypoglycemia can significantly increase paraendocellular permeability by downregulating claudin-5 expression. We further showed that VEGF protected brain endothelial cells against hypoglycemia by enhancing glucose passage, reducing endothelial cell death, and ameliorating paraendocellular permeability.

  12. Moderate Hypothermia Provides Better Protection of the Intestinal Barrier than Deep Hypothermia during Circulatory Arrest in a Piglet Model: A Microdialysis Study

    PubMed Central

    Chen, Guangxian; Tang, Zhixian; Lin, Weibin; Rong, Jian; Wu, Zhongkai

    2016-01-01

    Introduction This study aimed to assess the effects of different temperature settings of hypothermic circulatory arrest (HCA) on intestinal barrier function in a piglet model. Methods Twenty Wuzhishan piglets were randomly assigned to 40 min of HCA at 18°C (DHCA group, n = 5), 40 min of HCA at 24°C (MHCA group, n = 5), normothermic cardiopulmonary bypass (CPB group, n = 5) or sham operation (SO group, n = 5). Serum D-lactate (SDL) and lipopolysaccharide (LPS) levels were determined. Microdialysis parameters (glucose, lactate, pyruvate and glycerol) in the intestinal dialysate were measured. After 180 min of reperfusion, intestinal samples were harvested for real-time polymerase chain reaction and western blotting measurements for E-cadherin and Claudin-1. Results Higher levels of SDL and LPS were detected in the DHCA group than in the MHCA group (P < 0.001). Both MHCA and DHCA groups exhibited lower glucose levels, higher lactate and glycerol levels and a higher lactate to pyruvate (L/P) ratio compared with the CPB group (p<0.05); the DHCA group had higher lactate and glycerol levels and a higher L/P ratio (p<0.05) but similar glucose levels compared to the MHCA group. No significant differences in E-cadherin mRNA or protein levels were noted. Upregulation of claudin-1 mRNA levels was detected in both the DHCA and MHCA animals’ intestines (P < 0.01), but only the DHCA group exhibited a decrease in claudin-1 protein expression (P < 0.01). Conclusion HCA altered the energy metabolism and expression of epithelial junctions in the intestine. Moderate hypothermia (24°C) was less detrimental to the markers of normal functioning of the intestinal barrier than deep hypothermia (18°C). PMID:27685257

  13. Evaluation the effect of thiamin deficiency on intestinal immunity of young grass carp (Ctenopharyngodon idella).

    PubMed

    Wen, Ling-Mei; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Zhao, Juan; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin

    2015-10-01

    Our study explored the effect of dietary thiamin on growth and immunity (intestine, head kidney, spleen and liver) of young grass carp (Ctenopharyngodon idella). Fish were fed diets containing six graded levels of thiamin at 0.12-2.04 mg/kg diet for 8 weeks. The percentage weight gain (PWG), feed intake and feed efficiency were lower in fish fed the 0.12 mg/kg diet. Thiamin deficiency decreased complement 3 content, lysozyme (LA) and acid phosphatase activities, mRNA levels of hepcidin and interleukin (IL) 10, elevated mRNA levels of interferon γ2, tumor necrosis factor α, IL-1β and IL-8 in intestine, head kidney, spleen and liver. The mRNA levels of inhibitor protein-κBα, target of rapamycin (TOR) and NF-E2-related factor 2 (Nrf2), the activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase were down-regulated, mRNA levels of myosin light-chain kinase (MLCK), IκB kinases (IKKβ and IKKγ), nuclear factor κB P65 (NF-κB P65) and Kelch-like-ECH-associated protein 1a (Keap1a) were up-regulated in the intestine of fish fed the thiamin-deficient diet. Additionally, thiamin deficiency decreased claudin b, c and 3, ZO-1 and occludin mRNA levels in each intestinal segment, increased claudin 12 and claudin 15a mRNA levels in distal intestine. In conclusion, thiamin deficiency decreased fish growth and immunity of intestine, head kidney, spleen and liver. The dietary thiamin requirement of young grass carp (242-742 g) based on intestinal LA activity or PWG were determined to be 1.15 or 0.90 mg/kg diet, respectively.

  14. Progesterone and allopregnanolone attenuate blood-brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases

    PubMed Central

    Ishrat, Tauheed; Sayeed, Iqbal; Atif, Fahim; Hua, Fang; Stein, Donald G.

    2010-01-01

    Blood-brain barrier (BBB) breakdown after stroke is linked to the up-regulation of metalloproteinases (MMPs) and inflammation. This study examines the effects of progesterone (PROG) and its neuroactive metabolite allopregnanolone (ALLO) on BBB integrity following permanent middle cerebral artery occlusion (pMCAO). Rats underwent pMCAO by electro-coagulation and received intraperitoneal injections of PROG (8 mg/kg), ALLO (8 mg/kg) or vehicle at 1 h post-occlusion and then subcutaneous injections (8 mg/kg) at 6, 24, and 48 h. MMP activation and expression were analyzed by Western blot, immunohistochemistry and gelatin zymography 72 h post-pMCAO. Occludin1, claudin5, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) were analyzed at 72 h post-pMCAO with Western blots. BBB permeability was measured by Evans blue extravasation and infarct size was evaluated by cresyl violet at 72 h after pMCAO. Ischemic injury significantly (p<0.05) increased the expression of MMP-9, MMP-2, TNF-α and IL-6, and reduced the level of occludin1 and claudin5. These changes were followed by increased infarct size (% contralateral hemisphere) and Evans blue extravasation into the brain indicating compromise of the BBB. PROG and ALLO attenuated BBB disruption and infarct size following pMCAO by reducing MMPs and the inflammatory response and by preventing the degradation of occludin1 and claudin5. We conclude that PROG and ALLO can help to protect BBB disruption following pMCAO. PMID:20816826

  15. Manganese deficiency or excess caused the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier, as regulated by NF-κB, TOR and Nrf2 signalling, in grass carp (Ctenopharyngodon idella).

    PubMed

    Jiang, Wei-Dan; Tang, Ren-Jun; Liu, Yang; Kuang, Sheng-Yao; Jiang, Jun; Wu, Pei; Zhao, Juan; Zhang, Yong-An; Tang, Ling; Tang, Wu-Neng; Zhou, Xiao-Qiu; Feng, Lin

    2015-10-01

    Intestinal mucosal immune components and mRNA levels of inflammatory cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules in young grass carp (Ctenopharyngodon idellus) under dietary manganese (Mn) deficiency or excess were investigated. Fish were fed the diets containing graded levels of Mn [3.65-27.86 mg Mn kg(-1) diet] for 8 weeks. The results demonstrated that Mn deficiency significantly decreased the lysozyme and acid phosphatase (ACP) activities, up-regulated tumour necrosis factor α (TNF-α), interleukin 8 and the signalling factor nuclear factor-κB p65, and down-regulated interleukin 10 (IL-10), transforming growth factor β1, inhibitor of signalling factors κB-α and target of rapamycin mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI). However, Mn deficiency did not change the C3 content in the PI, whereas it decreased the C3 contents in the MI and DI. Additionally, Mn depletion also resulted in significantly low mRNA levels for tight junction proteins (claudin-b, claudin-c, claudin-15, occludin and zonula occludens-1), antioxidant enzymes (MnSOD, GPx and CAT) and NF-E2-related factor-2 in the intestines of fish. Excessive Mn exhibited toxic effects similar to Mn deficiency, where optimal Mn contents reversed those indicators. In conclusion, Mn deficiency or excess causes the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier relating to NF-κB, TOR and Nrf2 signalling in grass carp. Furthermore, quadratic regression analysis at 95% maximum response of lysozyme and acid phosphatase activities in the distal intestine of young grass carp revealed the optimum dietary Mn levels to be 8.90 and 8.99 mg kg(-1) diet, respectively.

  16. Disruption of MDCK cell tight junctions by the free-living amoeba Naegleria fowleri.

    PubMed

    Shibayama, Mineko; Martínez-Castillo, Moisés; Silva-Olivares, Angélica; Galindo-Gómez, Silvia; Navarro-García, Fernando; Escobar-Herrera, Jaime; Sabanero, Myrna; Tsutsumi, Víctor; Serrano-Luna, Jesús

    2013-02-01

    Naegleria fowleri is the aetiological agent of primary amoebic meningoencephalitis. This parasite invades its host by penetrating the olfactory mucosa. However, the mechanism of epithelium penetration is not well understood. In the present study, we evaluated the effect of N. fowleri trophozoites and the non-pathogenic Naegleria gruberi on Madin-Darby canine kidney (MDCK) tight junction proteins, including claudin-1, occludin and ZO-1, as well as on the actin cytoskeleton. Trophozoites from each of the free-living amoeba species were co-cultured with MDCK cells in a 1 : 1 ratio for 1, 3, 6 or 10 h. Light microscopy revealed that N. fowleri caused morphological changes as early as 3 h post-infection in an epithelial MDCK monolayer. Confocal microscopy analysis revealed that after 10 h of co-culture, N. fowleri trophozoites induced epithelial cell damage, which was characterized by changes in the actin apical ring and disruption of the ZO-1 and claudin-1 proteins but not occludin. Western blot assays revealed gradual degradation of ZO-1 and claudin-1 as early as 3 h post-infection. Likewise, there was a drop in transepithelial electrical resistance that resulted in increased epithelial permeability and facilitated the invasion of N. fowleri trophozoites by a paracellular route. In contrast, N. gruberi did not induce alterations in MDCK cells even at 10 h post-infection. Based on these results, we suggest that N. fowleri trophozoites disrupt epithelial monolayers, which could enable their penetration of the olfactory epithelium and subsequent invasion of the central nervous system.

  17. Restraint Stress-Induced Morphological Changes at the Blood-Brain Barrier in Adult Rats.

    PubMed

    Sántha, Petra; Veszelka, Szilvia; Hoyk, Zsófia; Mészáros, Mária; Walter, Fruzsina R; Tóth, Andrea E; Kiss, Lóránd; Kincses, András; Oláh, Zita; Seprényi, György; Rákhely, Gábor; Dér, András; Pákáski, Magdolna; Kálmán, János; Kittel, Ágnes; Deli, Mária A

    2015-01-01

    Stress is well-known to contribute to the development of both neurological and psychiatric diseases. While the role of the blood-brain barrier is increasingly recognized in the development of neurodegenerative disorders, such as Alzheimer's disease, dysfunction of the blood-brain barrier has been linked to stress-related psychiatric diseases only recently. In the present study the effects of restraint stress with different duration (1, 3, and 21 days) were investigated on the morphology of the blood-brain barrier in male adult Wistar rats. Frontal cortex and hippocampus sections were immunostained for markers of brain endothelial cells (claudin-5, occluding, and glucose transporter-1) and astroglia (GFAP). Staining pattern and intensity were visualized by confocal microscopy and evaluated by several types of image analysis. The ultrastructure of brain capillaries was investigated by electron microscopy. Morphological changes and intensity alterations in brain endothelial tight junction proteins claudin-5 and occludin were induced by stress. Following restraint stress significant increases in the fluorescence intensity of glucose transporter-1 were detected in brain endothelial cells in the frontal cortex and hippocampus. Significant reductions in GFAP fluorescence intensity were observed in the frontal cortex in all stress groups. As observed by electron microscopy, 1-day acute stress induced morphological changes indicating damage in capillary endothelial cells in both brain regions. After 21 days of stress thicker and irregular capillary basal membranes in the hippocampus and edema in astrocytes in both regions were seen. These findings indicate that stress exerts time-dependent changes in the staining pattern of tight junction proteins occludin, claudin-5, and glucose transporter-1 at the level of brain capillaries and in the ultrastructure of brain endothelial cells and astroglial endfeet, which may contribute to neurodegenerative processes, cognitive and

  18. Blood-Brain Barrier Disruption and Oxidative Stress in Guinea Pig after Systemic Exposure to Modified Cell-Free Hemoglobin

    PubMed Central

    Butt, Omer I.; Buehler, Paul W.; D'Agnillo, Felice

    2011-01-01

    Systemic exposure to cell-free hemoglobin (Hb) or its breakdown products after hemolysis or with the use of Hb-based oxygen therapeutics may alter the function and integrity of the blood-brain barrier. Using a guinea pig exchange transfusion model, we investigated the effect of a polymerized cell-free Hb (HbG) on the expression of endothelial tight junction proteins (zonula occludens 1, claudin-5, and occludin), astrocyte activation, IgG extravasation, heme oxygenase (HO), iron deposition, oxidative end products (4-hydroxynonenal adducts and 8-hydroxydeoxyguanosine), and apoptosis (cleaved caspase 3). Reduced zonula occludens 1 expression was observed after HbG transfusion as evidenced by Western blot and confocal microscopy. Claudin-5 distribution was altered in small- to medium-sized vessels. However, total expression of claudin-5 and occludin remained unchanged except for a notable increase in occludin 72 hours after HbG transfusion. HbG-transfused animals also showed increased astrocytic glial fibrillary acidic protein expression and IgG extravasation after 72 hours. Increased HO activity and HO-1 expression with prominent enhancement of HO-1 immunoreactivity in CD163-expressing perivascular cells and infiltrating monocytes/macrophages were also observed. Consistent with oxidative stress, HbG increased iron deposition, 4-hydroxynonenal and 8-hydroxydeoxyguanosine immunoreactivity, and cleaved caspase-3 expression. Systemic exposure to an extracellular Hb triggers blood-brain barrier disruption and oxidative stress, which may have important implications for the use of Hb-based therapeutics and may provide indirect insight on the central nervous system vasculopathies associated with excessive hemolysis. PMID:21356382

  19. A high-grain diet causes massive disruption of ruminal epithelial tight junctions in goats.

    PubMed

    Liu, Jun-hua; Xu, Ting-ting; Liu, Yu-jie; Zhu, Wei-yun; Mao, Sheng-yong

    2013-08-01

    Alterations in rumen epithelial tight junctions (TJs) at the tissue and molecular levels during high-grain (HG) diet feeding are unknown. Here, 10 male goats were randomly assigned to either a hay diet (0% grain; n = 5) or HG diet group (65% grain; n = 5) to characterize the changes in ruminal epithelial structure and TJ protein expression and localization using scanning and transmission electron microscopy, quantitative real-time PCR, Western blot analysis, and immunofluorescence. After 7 wk of feeding, ruminal free LPS in HG group increased significantly (P < 0.001) compared with the hay group, and free LPS in the peripheral blood was detectable with concentrations of 0.8 ± 0.20 EU/ml, while not detectable in the control, suggesting a leakage of LPS into the blood in the HG group. Correspondingly, the HG-fed goats showed profound alterations in ruminal epithelial structure and TJ proteins, depicted by marked epithelial cellular damage and intercellular junction erosion, down-regulation of TJ proteins claudin-4, occludin, and zonula occludens-1 mRNA and protein expression, as well as redistribution of claudin-1, claudin-4, and occludin. Furthermore, these changes in TJ proteins in the HG group were coupled with the upregulation of mRNA levels for the cytokines TNF-α and IFN-γ in the ruminal epithelia. These results demonstrated for the first time that the HG diet feeding caused disruption of ruminal epithelial TJs that was associated with a local inflammatory response in the rumen epithelium. These findings may provide new insights into understanding the role of TJ proteins in the ruminal epithelial immune homeostasis of ruminants. PMID:23739344

  20. Progesterone and allopregnanolone attenuate blood-brain barrier dysfunction following permanent focal ischemia by regulating the expression of matrix metalloproteinases.

    PubMed

    Ishrat, Tauheed; Sayeed, Iqbal; Atif, Fahim; Hua, Fang; Stein, Donald G

    2010-11-01

    Blood-brain barrier (BBB) breakdown after stroke is linked to the up-regulation of metalloproteinases (MMPs) and inflammation. This study examines the effects of progesterone (PROG) and its neuroactive metabolite allopregnanolone (ALLO) on BBB integrity following permanent middle cerebral artery occlusion (pMCAO). Rats underwent pMCAO by electro-coagulation and received intraperitoneal injections of PROG (8 mg/kg), ALLO (8 mg/kg) or vehicle at 1 h post-occlusion and then subcutaneous injections (8 mg/kg) at 6, 24, and 48 h. MMP activation and expression were analyzed by Western blot, immunohistochemistry and gelatin zymography 72 h post-pMCAO. Occludin1, claudin5, tumor necrosis factor-alpha (TNF-α) and Interleukin-6 (IL-6) were analyzed at 72 h post-pMCAO with Western blots. BBB permeability was measured by Evans blue extravasation and infarct size was evaluated by cresyl violet at 72 h after pMCAO. Ischemic injury significantly (p<0.05) increased the expression of MMP-9, MMP-2, TNF-α and IL-6, and reduced the levels of occludin1 and claudin5. These changes were followed by increased infarct size (% contralateral hemisphere) and Evans blue extravasation into the brain indicating compromise of the BBB. PROG and ALLO attenuated BBB disruption and infarct size following pMCAO by reducing MMPs and the inflammatory response and by preventing the degradation of occludin1 and claudin5. We conclude that PROG and ALLO can help to protect BBB disruption following pMCAO.