VE-PTP maintains the endothelial barrier via plakoglobin and becomes dissociated from VE-cadherin by leukocytes and by VEGF

We have shown recently that vascular endothelial protein tyrosine phosphatase (VE-PTP), an endothelial-specific membrane protein, associates with vascular endothelial (VE)-cadherin and enhances VE-cadherin function in transfected cells (Nawroth, R., G. Poell, A. Ranft, U. Samulowitz, G. Fachinger, M. Golding, D.T. Shima, U. Deutsch, and D. Vestweber. 2002. EMBO J. 21:4885-4895). We show that VE-PTP is indeed required for endothelial cell contact integrity, because down-regulation of its expression enhanced endothelial cell permeability, augmented leukocyte transmigration, and inhibited VE-cadherin-mediated adhesion. Binding of neutrophils as well as lymphocytes to endothelial cells triggered rapid (5 min) dissociation of VE-PTP from VE-cadherin. This dissociation was only seen with tumor necrosis factor alpha-activated, but not resting, endothelial cells. Besides leukocytes, vascular endothelial growth factor also rapidly dissociated VE-PTP from VE-cadherin, indicative of a more general role of VE-PTP in the regulation of endothelial cell contacts. Dissociation of VE-PTP and VE-cadherin in endothelial cells was accompanied by tyrosine phoshorylation of VE-cadherin, beta-catenin, and plakoglobin. Surprisingly, only plakoglobin but not beta-catenin was necessary for VE-PTP to support VE-cadherin adhesion in endothelial cells. In addition, inhibiting the expression of VE-PTP preferentially increased tyrosine phosphorylation of plakoglobin but not beta-catenin. In conclusion, leukocytes interacting with endothelial cells rapidly dissociate VE-PTP from VE-cadherin, weakening endothelial cell contacts via a mechanism that requires plakoglobin but not beta-catenin.

Functions of lipid raft membrane microdomains at the blood-brain barrier

The blood-brain barrier (BBB) is a highly specialized structural and functional component of the central nervous system that separates the circulating blood from the brain and spinal cord parenchyma. Brain endothelial cells (BECs) that primarily constitute the BBB are tightly interconnected by multiprotein complexes, the adherens junctions and the tight junctions, thereby creating a highly restrictive cellular barrier. Lipid-enriched membrane microdomain compartmentalization is an inherent property of BECs and allows for the apicobasal polarity of brain endothelium, temporal and spatial coordination of cell signaling events, and actin remodeling. In this manuscript, we review the role of membrane microdomains, in particular lipid rafts, in the BBB under physiological conditions and during leukocyte transmigration/diapedesis. Furthermore, we propose a classification of endothelial membrane microdomains based on their function, or at least on the function ascribed to the molecules included in such heterogeneous rafts: (1) rafts associated with interendothelial junctions and adhesion of BECs to basal lamina (scaffolding rafts); (2) rafts involved in immune cell adhesion and migration across brain endothelium (adhesion rafts); (3) rafts associated with transendothelial transport of nutrients and ions (transporter rafts).

Slit2 prevents neutrophil recruitment and renal ischemia-reperfusion injury.

Neutrophils recruited to the postischemic kidney contribute to the pathogenesis of ischemia-reperfusion injury (IRI), which is the most common cause of renal failure among hospitalized patients. The Slit family of secreted proteins inhibits chemotaxis of leukocytes by preventing activation of Rho-family GTPases, suggesting that members of this family might modulate the recruitment of neutrophils and the resulting IRI. Here, in static and microfluidic shear assays, Slit2 inhibited multiple steps required for the infiltration of neutrophils into tissue. Specifically, Slit2 blocked the capture and firm adhesion of human neutrophils to inflamed vascular endothelial barriers as well as their subsequent transmigration. To examine whether these observations were relevant to renal IRI, we administered Slit2 to mice before bilateral clamping of the renal pedicles. Assessed at 18 hours after reperfusion, Slit2 significantly inhibited renal tubular necrosis, neutrophil and macrophage infiltration, and rise in plasma creatinine. In vitro, Slit2 did not impair the protective functions of neutrophils, including phagocytosis and superoxide production, and did not inhibit neutrophils from killing the extracellular pathogen Staphylococcus aureus. In vivo, administration of Slit2 did not attenuate neutrophil recruitment or bacterial clearance in mice with ascending Escherichia coli urinary tract infections and did not increase the bacterial load in the livers of mice infected with the intracellular pathogen Listeria monocytogenes. Collectively, these results suggest that Slit2 may hold promise as a strategy to combat renal IRI without compromising the protective innate immune response.

Wnt activation of immortalized brain endothelial cells as a tool for generating a standardized model of the blood brain barrier in vitro

Reproducing the characteristics and the functional responses of the blood-brain barrier (BBB) in vitro represents an important task for the research community, and would be a critical biotechnological breakthrough. Pharmaceutical and biotechnology industries provide strong demand for inexpensive and easy-to-handle in vitro BBB models to screen novel drug candidates. Recently, it was shown that canonical Wnt signaling is responsible for the induction of the BBB properties in the neonatal brain microvasculature in vivo. In the present study, following on from earlier observations, we have developed a novel model of the BBB in vitro that may be suitable for large scale screening assays. This model is based on immortalized endothelial cell lines derived from murine and human brain, with no need for co-culture with astrocytes. To maintain the BBB endothelial cell properties, the cell lines are cultured in the presence of Wnt3a or drugs that stabilize β-catenin, or they are infected with a transcriptionally active form of β-catenin. Upon these treatments, the cell lines maintain expression of BBB-specific markers, which results in elevated transendothelial electrical resistance and reduced cell permeability. Importantly, these properties are retained for several passages in culture, and they can be reproduced and maintained in different laboratories over time. We conclude that the brain-derived endothelial cell lines that we have investigated gain their specialized characteristics upon activation of the canonical Wnt pathway. This model may be thus suitable to test the BBB permeability to chemicals or large molecular weight proteins, transmigration of inflammatory cells, treatments with cytokines, and genetic manipulation.

Na 1 Nachlass Max Horkheimer, 7 - Korrespondenzen u.a. mit Familie Cahn (p. I 4, 1-297a)

1 Brief von Max Horkheimer an die Cadillac Motor Division, 05.06.1939; 148 Briefe zwischen Erwin Cahn, Lotte Cahn, Ilse Cahn, Max Cahn, Lilo Cahn, Lina Cahn und Max Horkheimer, 1938-1942; 10 Briefe zwischen dem Transmigration Bureau og the American Jewish Joint Distribution Committee und Friedrich Pollock, 1941-1942; 3 Briefe zwischen dem National Refugee Service und Max Horkheimer, 07.04.1941, 1941; 1 Brief von Julius S. Bach an die National City Bank of New York, 27.06.1940; 1 Brief von Julius S. Bach an den American Consul General Berlin, 15.04.1940; 1 Brief von Max Horkheimer an Julius S. Bach, 15.05.1940; 16 Briefe von Max Horkheimer an den American Consul General Stuttgart, 1938-1941; 2 Briefe zwischen der Auswandererstelle Marx und Max Horkheimer, 02.06.1941; 5 Briefe zwischen dem Reisebüro Anselm Stuttgart und Max Horkheimer, 1941; 9 Briefe zwischen der Sapt A.G und Max Horkheimer, 1940-1941; 3 Briefe zwischen Emanuel Green und Max Horkheimer, 26.09.1940, 1940; 3 Briefe zwischen der Zweigstelle Wüttemberg der Reichsvereinigung der Juden in Deutschland und Max Horkheimer, 1940, 19.09.1940; 2 Briefe zwischen der Auswandererstelle Adler und Max Horkheimer, 25.05.1940; 2 Briefe von Max Horkheimer an den American Consul General Berlin, 1939; 1 Brief von Max Horkheimer an S. Klein, 20.03.1939; 1 Brief von Max Horkheimer an den Collector of Customs, 27.02.1939; 1 Brief von Max Horkheimer an Ludwig Lewisohn,. 03.01.1939; 1 Brief von Friedlaender an Kahn, 15.12.1938; 1 Brief von Erwin Cahn an Max Horkheimer, 07.02.1935;

Some leading ideas of Hinduism,

Mode of access: Internet.

The tomorrow of death; or, The future life according to science.

Mode of access: Internet.

De palingenesia veterum seu metempsychosi sic dicta pythagorica. libri III. quibus num Pythagoras animarum humanarum de corpore uno in aliud corpus crassum vel hominis vel bruti etc. transmigrationem adseruisse: atque hinc & carnibus, & fabis abstinuisse censeatur recte disquiritur ... / Guilielmi Irhovii.

P. 218-219 misnumbered as p. 118-119.

Ceylon Buddhism : being the collected writings of Daniel John Gogerly ... edited by Arthur Stanley Bishop ...

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Magnetic nanoformulation of azidothymidine 5’-triphosphate for targeted delivery across the blood–brain barrier

Despite significant advances in highly active antiretroviral therapy (HAART), the prevalence of neuroAIDS remains high. This is mainly attributed to inability of antiretroviral therapy (ART) to cross the blood–brain barrier (BBB), thus resulting in insufficient drug concentration within the brain. Therefore, development of an active drug targeting system is an attractive strategy to increase the efficacy and delivery of ART to the brain. We report herein development of magnetic azidothymidine 5′-triphosphate (AZTTP) liposomal nanoformulation and its ability to transmigrate across an in vitro BBB model by application of an external magnetic field. We hypothesize that this magnetically guided nanoformulation can transverse the BBB by direct transport or via monocyte-mediated transport. Magnetic AZTTP liposomes were prepared using a mixture of phosphatidyl choline and cholesterol. The average size of prepared liposomes was about 150 nm with maximum drug and magnetite loading efficiency of 54.5% and 45.3%, respectively. Further, magnetic AZTTP liposomes were checked for transmigration across an in vitro BBB model using direct or monocyte-mediated transport by application of an external magnetic field. The results show that apparent permeability of magnetic AZTTP liposomes was 3-fold higher than free AZTTP. Also, the magnetic AZTTP liposomes were efficiently taken up by monocytes and these magnetic monocytes showed enhanced transendothelial migration compared to normal/non-magnetic monocytes in presence of an external magnetic field. Thus, we anticipate that the developed magnetic nanoformulation can be used for targeting active nucleotide analog reverse transcriptase inhibitors to the brain by application of an external magnetic force and thereby eliminate the brain HIV reservoir and help to treat neuroAIDS.

The Efficacy of San Lazaro and His Manifestations: Divine Mediators of Health Within Miami's Cuban-American Santeria Community.

This study explored the origins, evolution and influence of the tradition of San Lázaro as it currently pertains to the Cuban-American Santeria community in Miami. The main argument of the study is that in the context of the contemporary religious culture of Santeria in Miami, San Lázaro is a hybrid spirit. Many manifestations of healing entities have come to merge in the person of this spirit. Though practitioners identify with specific manifestations of this spirit, the processes of transmigration have blurred the lines of deep-rooted faiths and created a fusion of meanings from disparate traditions, making San Lázaro an ambivalent personality. San Lázaro’s ambivalence is the very quality that makes him such an important Orisha. As a deity whose personalities demonstrates the combination of a diversity of qualities, including those that contradict each other, San Lázaro is deployed in a very broad range of healing context, making him a versatile Orisha. This study clarified the contrasting qualities this deity embodies and traces the socio-historical context in which the deity acquires the layers of meanings it is currently associated with. Drawing on interviews with Lázaranian worshipers [Lázarenos] in Miami and engaging in Bourdieu’s concept of Habitus, the study provided a window into the nature of the tradition of San Lázaro and how its usage is linked with the African heritage of the worshipers.

'That Puissant City': John Milton's Roman Sojourns 1638-1639

John Milton’s sojourns in Rome (1638-9) are attested by his comments in Defensio Secunda, by the minutes of the English College, by Latin encomia which he received from Roman academicians, and, not least, by his Latin letter to Lucas Holstenius (19/29 March 1639), and several Latin poems which he composed in the course of his residency in the capital city: Ad Salsillum, and three Latin epigrams extolling the praises of the virtuosa soprano, Leonora Baroni. Read together, these texts serve to reveal much about Milton’s participation in, and reaction to, the ‘Puissant City’, (History of Britain, Bk 2).

The present monograph presents fresh evidence of Milton's integration into the academic and cultural life of seventeenth-century Rome. It argues that his links with two Roman academies: the Accademia dei Fantastici and Accademia degli Umoristi constitute a sustained participation in an academic community paralleling that of his independently attested performance in Florentine academies (on which I have published extensively). It also investigates his links with Alessandro Cherubini, David Codner, Giovanni Batista Doni, and the Baroni circle hymned in three published anthologies.

Chapter 1: Milton and the Accademia dei Fantastici investigates the cultural climate surrounding Milton's Ad Salsillum by examining two of that academy's publications: the Poesie dei Signori Accademici Fantastici di Roma (Rome, 1637) and the Academia Tenuta da Fantastici a. 12 di Maggio 1655 (Rome, 1655), the latter celebrating the creation of Fabio Chigi as Pope Alexander VII on 5 April 1655. Read in a new light, Milton’s self-fashioning, it is argued, takes its place not only alongside Salzilli’s encomium in Milton's honour, and his Italian sonnets in the 1637 Poesie, but also in relation to other poems in that collection, and the academy's essentially Catholic eulogistic trend. The chapter also provides fresh evidence of Salzilli’s survival of the illness described in Milton’s poem by his epistolary correspondence with Tomaso Stigliani.

Chapter 2: Milton and the Vatican argues for links between Milton’s Latin letter to Holstenius and a range of Holstenius’ published works: his edition of the axioms of the later Pythagoreans gifted by him to Milton, and his published neo-Platonic works. This is achieved by mutual appropriation of Similitudes in a series of Miltonic similes, the anabasis/katabasis motifs in a reworking of the Platonic theory of the transmigration of souls, and allusion to etymological details highlighted in Holstenius’ published editions. The chapter also reveals Milton’s alertness to typographical procedures and, by association, to Holstenius’ recent role (1638) as Director of the press of the Biblioteca Vaticana.

Chapter 3: Milton and the Accademia degli Umoristi argues for Milton’s likely participation in this Roman academy, as suggested by his links with its members. His three Latin epigrams in praise of Leonora Baroni, the only female member of the Umoristi, have hitherto been studied in relation to the 1639 Applausi in her honour. In a new reading, Milton, it is suggested, invokes and interrogates Catholic doctrine before a Catholic audience only to view the whole through the lens of a neo-Platonic Hermeticism (by echoing the phraseology of the sixteenth-century Franciscan Hannibal Rosselli) that refreshingly transcends religious difference. Crucially, the hitherto neglected L’Idea della Veglia (Rome, 1640) includes further encomiastic verse, sonnets to, and by Leonora, and details of the conversazioni hosted by her family at the precise time of Milton’s Roman sojourns. Milton may well have been a participant. The chapter concludes in an assessment of his links with the youthful prodigy Alessandro Cherubini, and of his audience with Francesco Barberini.

Chapter 4: Milton at a Roman Opera analyses the potential impact of ‘Chi Soffre, Speri’, which he attended on 18/28 February 1639, mounted by Francesco Barberini to inaugurate the recently completed theatre of the Palazzo Barberini. A detailed analysis of the opera's libretto, music, and theatricality casts a backward glance to Milton's Comus, and a forward glance to Paradise Lost. It also assesses Milton’s musical interests at this time, as attested by his links with Doni, and his purchase of works by Monteverdi and others.

Chapter 5: Milton’s English Connections in Rome develops the work of Miller and Chaney by investigating Milton’s co-diners at the English College in Rome on 30 October 1638, and by analysing his links between David Codner (alias Matteo Selvaggio), and the family of Jane Savage, Marchioness of Winchester, lamented by Milton in 1631. It also assesses his potential relations with the Englishman Thomas Gawen, who ‘accidentally sometimes fell into the company of John Milton’ (Antony Wood).

Chasing butterflies: The Conception of the Soul in Plutarch’s Works

When first approaching a topic such as the concept of material or natural soul in Greek literature, the researcher might be puzzled. While in diverse contemporary cultures, numerous theriomorphic figures (bears, ravens, mice, wasps, bees, dragonflies, and dung-beetles) serve to represent the human soul in its transmigration from life to death, this is not the case in Greek culture. At least, this is what one may conclude from the monograph written by the Dutch scholar J. Bremmer, The early Greek Concept of the Soul: "importunely, there are no other indications of a possible connection between the butterfly and the soul of the living and the dead" (1987: 64). Given Plutarch’s great interest in the soul, which can be seen in a variety of texts referring to its generation, form, internal dichotomy, material substance, origin and destination, etc., the question arises as to whether Plutarch also includes such a representation of the soul when departing from the dead body. Does the corpus plutarcheum preserve and transmit such conception of the human soul? And if it does, are we dealing with survival of ancestral beliefs or motifs or is it a simple metaphor by means of which ancients intended to express the departing of the life-breath? In the following pages I will focus on three texts that allegedly include the butterfly-motif to represent the human soul, to wit, Table Talks 636C, Consolation to his Wife 611F, and the fragment 177 Sandbach.