R.C. Traver, Porter Zouave Band, August 1869

Sturgis' source: Mrs. A.L. Nue; Original photo by Revenaugh & Co., Photographic & Portrait Studio, No. 28 Huron St., upstairs

An examination of Commodore Porter's Exposition in which some of the errors and inaccuracies of that publication are rectified, and some of its deficiencies supplied.

Mode of access: Internet.

Carboxy terminus of glucose transporter 3 contains an apical membrane targeting domain

We previously demonstrated that distinct facilitative glucose transporter isoforms display differential sorting in polarized epithelial cells. In Madin-Darby canine kidney (MDCK) cells, glucose transporter 1 and 2 (GLUT1 and GLUT2) are localized to the basolateral cell surface whereas GLUTs 3 and 5 are targeted to the apical membrane. To explore the molecular mechanisms underlying this asymmetric distribution, we analyzed the targeting of chimeric glucose transporter proteins in MDCK cells. Replacement of the carboxy-terminal cytosolic tail of GLUT1, GLUT2, or GLUT4 with that from GLUT3 resulted in apical targeting. Conversely, a GLUT3 chimera containing the cytosolic carboxy terminus of GLUT2 was sorted to the basolateral membrane. These findings are not attributable to the presence of a basolateral signal in the tails of GLUTs 1, 2, and 4 because the basolateral targeting of GLUT1 was retained in a GLUT1 chimera containing the carboxy terminus of GLUT5. In addition, we were unable to demonstrate the presence of an autonomous basolateral sorting signal in the GLUT1 tail using the low-density lipoprotein receptor as a reporter. By examining the targeting of a series of more defined GLUT1/3 chimeras, we found evidence of an apical targeting signal involving residues 473 - 484 (DRSGKDGVMEMN) in the carboxy tail. We conclude that the targeting of GLUT3 to the apical cell surface in MDCK cells is regulated by a unique cytosolic sorting motif.

Specific modulation of airway epithelial tight junctions by apical application of an occludin peptide

Tight junctions are directly involved in regulating the passage of ions and macromolecules (gate functions) in epithelial and endothelial cells. The modulation of these gate functions to transiently regulate the paracellular permeability of large solutes and ions could increase the delivery of pharmacological agents or gene transfer vectors. To reduce the inflammatory responses caused by tight junction-regulating agents, alternative strategies directly targeting specific tight junction proteins could prove to be less toxic to airway epithelia. The apical delivery of peptides corresponding to the first extracellular loop of occludin to transiently modulate apical paracellular flux has been demonstrated in intestinal epithelia. We hypothesized that apical application of these occludin peptides could similarly modulate tight junction permeability in airway epithelia. Thus, we investigated the effects of apically applied occludin peptide on the paracellular permeability of molecular tracers and viral vectors in well differentiated human airway epithelial cells. The effects of occludin peptide on cellular toxicity, tight junction protein expression and localization, and membrane integrity were also assessed. Our data showed that apically applied occludin peptide significantly reduced transepithelial resistance in airway epithelia and altered tight junction permeability in a concentration-dependent manner. These alterations enhanced the paracellular flux of dextrans as well as gene transfer vectors. The occludin peptide redistributed occludin but did not alter the expression or distribution of ZO-1, claudin-1, or claudin-4. These data suggest that specific targeting of occludin could be a better-suited alternative strategy for tight junction modulation in airway epithelial cells compared with current agents that modulate tight junctions.

Retromer controls epithelial cell polarity by trafficking the apical determinant crumbs

The evolutionarily conserved apical determinant Crumbs (Crb) is essential for maintaining apicobasal polarity and integrity of many epithelial tissues [1]. Crb levels are crucial for cell polarity and homeostasis, yet strikingly little is known about its trafficking or the mechanism of its apical localization. Using a newly established, liposome-based system described here, we determined Crb to be an interaction partner and cargo of the retromer complex. Retromer is essential for the retrograde transport of numerous transmembrane proteins from endosomes to the trans-Golgi network (TGN) and is conserved between plants, fungi, and animals [2]. We show that loss of retromer function results in a substantial reduction of Crb in Drosophila larvae, wing discs, and the follicle epithelium. Moreover, loss of retromer phenocopies loss of crb by preventing apical localization of key polarity molecules, such as atypical protein kinase C (aPKC) and Par6 in the follicular epithelium, an effect that can be rescued by overexpression of Crb. Additionally, loss of retromer results in multilayering of the follicular epithelium, indicating that epithelial integrity is severely compromised. Our data reveal a mechanism for Crb trafficking by retromer that is vital for maintaining Crb levels and localization. We also show a novel function for retromer in maintaining epithelial cell polarity.

Competition, competitive advantage, and clusters:the ideas of Michael Porter

Comprehensive coverage of all aspects of Michael Porter's works Contributions from leading authorities across the disciplines Contains response from Porter Harvard professor, Michael Porter has been one of the most influential figures in strategic management research over the last three decades. He infused a rigorous theoretical framework of industrial organization economics with the then still embryonic field of strategic management and elevated it to its current status as an academic discipline. Porter's outstanding career is also characterized by its cross-disciplinary nature. Following his most important work on strategic management, he then made a leap to the policy side and dealt with a completely different set of analytical units. More recently he has made a foray into inner city development, environmental regulations, and health care services. Throughout these explorations Porter has maintained his integrative approach, seeking a road that links management case studies and the general model building of mainstream economics. With expert contributors from a range of disciplines including strategic management, economic development, economic geography, and planning, this book assesses the contribution Michael Porter has made to these respective disciplines. It clarifies the sources of tension and controversy relating to all the major strands of Porter's work, and provides academics, students, and practitioners with a critical guide for the application of Porter's models. The book highlights that while many of the criticisms of Porter's ideas are valid, they are almost an inevitable outcome for a scholar who has sought to build bridges across wide disciplinary valleys. His work has provided others with a set of frameworks to explore in more depth the nature of competition, competitive advantage, and clusters from a range of vantage points.

High permeability of the anionic form restricts accumulation of indomethacin by cultured gastric surface epithelial cells exposed to low apical pH

The 'ion-trapping' hypothesis suggests that the intracellular concentration of acidic non-steroidal anti-inflammatory drugs in gastric epithelial cells could be much higher than in the gastric lumen, and that such accumulation could contribute to their gastrotoxicity. Our aim was to examine the effect of the pH of the apical medium on the apical to basal transfer of the acidic drug indomethacin (pK a 4.5) across a gastric mucous epithelial cell monolayer, and to determine whether indomethacin accumulated in cells exposed to a low apical pH. Guinea-pig gastric mucous epithelial cells were grown on porous membrane culture inserts (Transwells®) for 72 h. Transfer and accumulation of [ 14C] indomethacin were assessed by scintillation counting. Transfer of [ 3H]mannitol and measurement of trans-epithelial electrical resistance were used to assess integrity of the monolayer. Distribution of [ 14C] urea was used to estimate the intracellular volume of the monolayer. The monolayer was not disrupted by exposure of the apical face to media of pH ≥ 3, or by indomethacin. Transfer of indomethacin (12 μM) to the basal medium increased with decreasing apical medium pH. The apparent permeability of the undissociated acid was estimated to be five times that of the anion. The intracellular concentration of indomethacin was respectively 5.3, 4.1 and 4.3 times that in the apical medium at pH 5.5, 4.5 and 3.0. In conclusion, this study represents the first direct demonstration that indomethacin accumulates in gastric epithelial cells exposed to low apical pH. However, accumulation of indomethacin was moderate and the predictions of the ion-trapping hypothesis were not met, probably due to the substantial permeability of anionic indomethacin across membranes. © 2006 Elsevier B.V. All rights reserved.

Apicectomías de dientes premolares y molares mandibulares en el conejo de raza neo zelandesa: estudio histológico usando distintos materiales de obturación apical

La apicectomía es una técnica de cirugía odontológica humana y veterinaria, que consiste en la amputación o resección de la porción más apical de la raíz dentaria y la retrobturación del ápice con algún material, con el objetivo de conservar el diente afectado de alguna patología apical. Se han usado gran variedad de materiales para la obturación, como amalgama, gutapercha, ionómero de vidrio, composite, MTA e hidróxido de calcio. En este estudio pretendemos comprobar la viabilidad de la técnica de la realización de la apicectomías en premolares y molares mandibulares, usando distintos materiales de retrobturación como son el iónomero de vidrio Ketac Cem μ® y el composite Tetric EvoFlow® en el conejo de experimentación de raza Neozelandesa. Realizamos las apicectomías de los dientes 407, 408 y 409 (3º premolar, 4º premolar y 1º molar inferior derecho), en una sola fase a diez animales. En el primer diente (407) solo se aplica un sellado del diente apicectomizado con hidróxido de calcio en polvo® y pasta Dycal® Dentin y no se coloca ningún material de obturación. En el segundo diente (408), se aplica un sellado con hidróxido de calcio en polvo® y pasta Dycal® Dentin y encima una retrobturación con ionómero de vidrio Ketac Cem μ® y en el tercer diente (409), se aplica un sellado con hidróxido de calcio en polvo® y pasta Dycal® Dentin y encima una retroturación con el composite Tetric EvoFlow®. A las 4 y 8 semanas se sacrificaron los animales y se realizó la toma de muestras. Estas fueron radiografiadas y posteriormente se realizaron cortes histológicos de los dientes apicectomizados y del tejido alrededor. Los cortes fueron teñidos con la tinción Levai-Laczkó y se realizó el estudio histológico cuantitativo y semicuantitativo, según la norma UNE-EN ISO 10993-6:2007, para medir la presencia de inflamación, fibrosis, infiltrados adiposos y cierre óseo del defecto...

Economist Sylvia Porter

General note: Title and date provided by Bettye Lane.

Economist Sylvia Porter

General note: Title and date provided by Bettye Lane.

Diane Porter, only female chief planning officer of a new town, shown operating tramway from Manhattan to Roosevelt Island

General note: Title and date provided by Bettye Lane.