Inside-Out Regulation of ICAM-1 Dynamics in TNF-α-Activated Endothelium

Background: During transendothelial migration, leukocytes use adhesion molecules, such as ICAM-1, to adhere to the endothelium. ICAM-1 is a dynamic molecule that is localized in the apical membrane of the endothelium and clusters upon binding to leukocytes. However, not much is known about the regulation of ICAM-1 clustering and whether membrane dynamics are linked to the ability of ICAM-1 to cluster and bind leukocyte integrins. Therefore, we studied the dynamics of endothelial ICAM-1 under non-clustered and clustered conditions. Principal Findings: Detailed scanning electron and fluorescent microscopy showed that the apical surface of endothelial cells constitutively forms small filopodia-like protrusions that are positive for ICAM-1 and freely move within the lateral plane of the membrane. Clustering of ICAM-1, using anti-ICAM-1 antibody-coated beads, efficiently and rapidly recruits ICAM-1. Using fluorescence recovery after photo-bleaching (FRAP), we found that clustering increased the immobile fraction of ICAM-1, compared to non-clustered ICAM-1. This shift required the intracellular portion of ICAM-1. Moreover, biochemical assays showed that ICAM-1 clustering recruited beta-actin and filamin. Cytochalasin B, which interferes with actin polymerization, delayed the clustering of ICAM-1. In addition, we could show that cytochalasin B decreased the immobile fraction of clustered ICAM-1-GFP, but had no effect on non-clustered ICAM-1. Also, the motor protein myosin-II is recruited to ICAM-1 adhesion sites and its inhibition increased the immobile fraction of both non-clustered and clustered ICAM-1. Finally, blocking Rac1 activation, the formation of lipid rafts, myosin-II activity or actin polymerization, but not Src, reduced the adhesive function of ICAM-1, tested under physiological flow conditions. Conclusions: Together, these findings indicate that ICAM-1 clustering is regulated in an inside-out fashion through the actin cytoskeleton. Overall, these data indicate that signaling events within the endothelium are required for efficient ICAM-1-mediated leukocyte adhesio

Conversion in Turkish : an overview

This paper presents an overview of possible cases of conversion in Turkish. I argue that apparent cases of conversion between nouns and adjectives are cases of syntactic transposition, and apparent cases of conversion between nouns/adjectives and verbs are end products of phonological changes in the history of the language, which resulted in pairs of lexemes that are formally identical synchronically, but not historically. This does not mean that no cases of morphological conversion can be traced in the language. I will present two cases of secondary word-class conversion from derived, inflected and uninflected words to toponyms which might be taken as instances of morphological conversion or derivation by zero-affixation

Ponowne spojrzenie na ,,zepsucie języka”

In deze bijdrage staat de vraag centraal of er zoiets bestaat als “taalverloedering”. Taalkundigen bestrijden deze gedachte en nemen het standpunt in dat er enkel en alleen sprake is van taalverandering. Leken lijken veelal niet overtuigd van het gelijk van de taalkundigen. In dit artikel wordt betoogd, dat het niet verwonderlijk is dat leken niet geneigd zijn om de taalkundigen te volgen, daar taalkundigen en leken het over twee verschillende zaken hebben. Taalkundigen zijn vooral gericht op het ontstaan van de nieuwe vorm, terwijl leken vooral op de acceptatie van de nieuwe vorm gericht zijn. Daarnaast is ook cruciaal voor het niet accepteren van de nieuwe vorm, dat het huidige algemeen Nederlands vooral wordt beïnvloed door de niet-standaard variëteiten van het Nederlands, dat wil zeggen: variëteiten die door veel sprekers als niet- of weinig prestigieus worden ervaren.Artykuł podejmuje kwestię zasadności tezy o degradacji języka. Językoznawcy kwestionują taką koncepcję i przyjmują stanowisko, że można mówić jedynie o zmianach w języku. Argumenty te nie przekonują zwykłych użytkowników języka. W artykule przyjęto, że brak akceptacji poglądu językoznawców nie zaskakuje, ponieważ każda z grup, to jest językoznawcy i laicy, koncentrują się na innym zagadnieniu. Językoznawcy skupiają się głównie na powstawaniu nowej formy, podczas gdy laicy już tylko na jej akceptacji. Ponadto na brak akceptacji dla nowej formy wpływa fakt, że wspólczesny język niderlandzki pozostaje pod silnym wpływem odmian nierespektujących normy, tzn. takich, które w oczach wielu użytkowników języka są mało prestiżowe lub w ogóle są pozbawione prestiżu.This contribution focuses on the question of whether languages can become corrupted. In general, linguists take the view that there is no such thing as “language corruption”; in their opinion, languages only change. Laymen, on the other hand, are not convinced by the linguistic arguments. In this paper, the stand is taken that it is not surprising at all that laymen are not willing to accept the view taken by linguists, since linguists and laymen focus on two different issues. Linguists are primarily concerned with the linguistic development as such (and the rise of the new form), whereas laymen focus on the actual acceptability of the new form. In addition, of further importance to the resistance that many changes meet with is the fact that present-day Dutch is heavily influenced by its substandard varieties, i.e. those varieties which, in the eyes of many speakers, have little or no prestige