ABCB5 Identifies Immunoregulatory Dermal Cells

Cell-based strategies represent a new frontier in the treatment of immune-mediated disorders. However, the paucity of markers for isolation of molecularly defined immunomodulatory cell populations poses a barrier to this field. Here, we show that ATP-binding cassette member B5 (ABCB5) identifies dermal immunoregulatory cells (DIRCs) capable of exerting therapeutic immunoregulatory functions through engagement of programmed cell death 1 (PD-1). Purified Abcb5(+) DIRCs suppressed T cell proliferation, evaded immune rejection, homed to recipient immune tissues, and induced Tregs in vivo. In fully major-histocompatibility-complex-mismatched cardiac allotransplantation models, allogeneic DIRCs significantly prolonged allograft survival. Blockade of DIRC-expressed PD-1 reversed the inhibitory effects of DIRCs on T cell activation, inhibited DIRC-dependent Treg induction, and attenuated DIRC-induced prolongation of cardiac allograft survival, indicating that DIRC immunoregulatory function is mediated, at least in part, through PD-1. Our results identify ABCB5(+) DIRCs as a distinct immunoregulatory cell population and suggest promising roles of this expandable cell subset in cellular immunotherapy.

Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke

Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood-brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental stroke models. This suggests that previous achievements in MS research may be relevant for stroke. Interestingly, the converse is equally true. Concepts on the neurovascular unit that were developed in a stroke context turned out to be applicable to neuroinflammatory research in MS. Examples include work on the important role of the vascular basement membrane and the BBB for the invasion of immune cells into the brain. Furthermore, tissue plasminogen activator (tPA), the only established drug treatment in acute stroke, modulates the pathogenesis of MS. Endogenous tPA is released from endothelium and astroglia and acts on the BBB, microglia and other neuroinflammatory cells. Thus, the vascular perspective of stroke research provides important input into the mechanisms on how endothelial cells and the BBB regulate inflammation in MS, particularly the invasion of immune cells into the CNS. In the current review we will first discuss pathogenesis of both diseases and current treatment regimens and will provide a detailed overview on pathways of immune cell migration across the barriers of the CNS and the role of activated astrocytes in this process. This article is part of a Special Issue entitled: Neuro inflammation: A common denominator for stroke, multiple sclerosis and Alzheimer's disease, guest edited by Helga de Vries and Markus Swaninger.

Holländische Künstler : Ed. Frankfort

Bernard de Vries

Ueber einige Ursachen der Richtung bilateralsymmetrischer Pflanzentheile

Von Dr. Hugo de Vries

Ueber das Welken abgeschnittener Sprosse

Von Dr. Hugo de Vries

Längenwachsthum der Ober- und Unterseite sich krümmender Ranken

Von Dr. Hugo de Vries

Zur Mechanik der Bewegungen von Schlingpflanzen

Von Dr. Hugo de Vries

Ueber die Dehnbarkeit wachsender Sprosse

Von Dr. Hugo de Vries

Oceanography during TYDEMAN cruise DCM (DeepChlorMax) to the Equatorial Atlantic

The cruise with RV Tydeman was devoted to study permanently stratified plankton systems in the (sub)tropical ocean, which are characterised by a deep chlorophyll peak between 80 and 150 m. To minimise lateral effects by horizontal transport of nutrients and organic matter from river outflow and upwelling regions, stations were selected in the middle of the North Atlantic Ocean between the continents of America and Africa. (5 - 35° N and 50 - 15° W). Here the vertical distributions of light and nutrients control the abundance and growth of autotrophic algae in the thermically stratified water column. This phytoplankton is numerically dominated by the prokaryotic picoplankters Synechococcus spp. and Prochlorococcus spp., which are smaller than 2 ?m. The productivity of the 100 to 150 m deep euphotic zone can be high, because a high heterotrophic/autotrophic biomass ratio induces a rapid regeneration of nutrients and inorganic carbon. Primary grazers are mainly micro-organisms such as heterotrophic nannoflagellates and ciliates, which feed on the small algae and on bacteria. Heterotrophic bacteria can outnumber the autotrophic algae, because their number is related to the substrate pools of dissolved and particulate dead organic matter. These DOC and detritus pools reach equilibrium at a concentration, where the rate of their production (proportional to algal biomass) equals their mineralisation and sinking rate (proportional to the concentration and weight of POC and detritus). At a relatively low value of the weight-specific loss rates, the equilibrium concentration of these carbon pools and their load of bacteria can be high. The bacterial productivity is proportional to the mineralisation rate, which in a steady state can never be higher than the rate of primary production. Hence the ratio in turnover rate of bacteria and autotrophs tends to be reciprocally proportional to their biomass ratio.

Matemática I - Polimodal : proyecto pedagógico con modalidad a distancia para la terminalidad de estudios de ECB3 y Educación Polimodal EDITEP

Este libro busca que el lector identifique e interprete conocimientos referidos a números reales y a sus operaciones, reconociendo los algoritmos y los procedimientos relacionados vinculándolos al cálculo de distintas medidas; que comprenda y sepa resolver problemas, seleccionando el tipo de razonamiento o argumentación que requiera la situación; que emplee sistemas de ecuaciones e inecuaciones para modelizar y resolver situaciones reales del entorno cotidiano; y que identifique, defina, grafique, describe e interprete distintos tipos de funciones asociándolas a situaciones reales. Se editó como material de aprendizaje destinado al personal de seguridad pública de la Provincia de Mendoza en el marco del proyecto pedagógico con modalidad a distancia para la terminalidad de estudios de EGB3 y Educación Polimodal –EDITEP–, implementado a partir de la firma del Convenio entre la Universidad Nacional de Cuyo y el Gobierno de la Provincia de Mendoza, en octubre de 2003.

Matemática II-EGB 3 : proyecto pedagógico con modalidad a distancia para la terminalidad de estudios de EGB3 y Educación Polimodal EDITEP

El presente libro propone profundizar lo aprendido anteriormente en el área de Matemática y avanzar en el aprendizaje de nuevos conceptos y procedimientos. Al final de este curso esperamos que el alumno pueda identificar, interpretar y utilizar, en la resolución de problemas, algunos conceptos matemáticos relacionados con: los números racionales, sus cálculos y operaciones, figuras planas y tridimensionales, las medidas y la medición, los gráficos y los distintos lenguajes matemáticos. Se editó como material de aprendizaje destinado al personal de seguridad pública de la Provincia de Mendoza en el marco del proyecto pedagógico con modalidad a distancia para la terminalidad de estudios de EGB3 y Educación Polimodal –EDITEP–, implementado a partir de la firma del Convenio entre la Universidad Nacional de Cuyo y el Gobierno de la Provincia de Mendoza, en octubre de 2003.