Cysteine Peptidase Cathepsin X as a Therapeutic Target for Simultaneous TLR3/4-mediated Microglia Activation

Microglia are resident macrophages in the central nervous system that are involved in immune responses driven by Toll-like receptors (TLRs). Microglia-mediated inflammation can lead to central nervous system disorders, and more than one TLR might be involved in these pathological processes. The cysteine peptidase cathepsin X has been recognized as a pathogenic factor for inflammation-induced neurodegeneration. Here, we hypothesized that simultaneous TLR3 and TLR4 activation induces synergized microglia responses and that these phenotype changes affect cathepsin X expression and activity. Murine microglia BV2 cells and primary murine microglia were exposed to the TLR3 ligand polyinosinic-polycytidylic acid (poly(I:C)) and the TLR4 ligand lipopolysaccharide (LPS), individually and simultaneously. TLR3 and TLR4 co-activation resulted in increased inflammatory responses compared to individual TLR activation, where poly(I:C) and LPS induced distinct patterns of proinflammatory factors together with different patterns of cathepsin X expression and activity. TLR co-activation decreased intracellular cathepsin X activity and increased cathepsin X localization at the plasma membrane with concomitant increased extracellular cathepsin X protein levels and activity. Inhibition of cathepsin X in BV2 cells by AMS36, cathepsin X inhibitor, significantly reduced the poly(I:C)- and LPS-induced production of proinflammatory cytokines as well as apoptosis. Additionally, inhibiting the TLR3 and TLR4 common signaling pathway, PI3K, with LY294002 reduced the inflammatory responses of the poly(I:C)- and LPS-activated microglia and recovered cathepsin X activity. We here provide evidence that microglial cathepsin X strengthens microglia activation and leads to subsequent inflammation-induced neurodegeneration. As such, cathepsin X represents a therapeutic target for treating neurodegenerative diseases related to excess inflammation

A Multilingual Benchmark to Capture Olfactory Situations over Time

We present a benchmark in six European languages containing manually annotated information about olfactory situations and events following a FrameNet-like approach. The documents selection covers ten domains of interest to cultural historians in the olfactory domain and includes texts published between 1620 to 1920, allowing a diachronic analysis of smell descriptions. With this work, we aim to foster the development of olfactory information extraction approaches as well as the analysis of changes in smell descriptions over time

Onkraj prešernovske strukture: Ljubav reče greva

Prispevek obravnava pesnitev Ljubav reče greva Nine Dragičević. Osnovna literarna interpretacija pesmi je razširjena v obravnavo teme pesnika in njegovega dela. Skozi to tematiko v pesnitev vstopa dejanski družbenopolitični položaj literarnega umetnika, ki je deloma še vedno ujet v nadnacionalno in nadčasovno prešernovsko strukturo. Članek zaključujeta performativna obravnava in aktivistična sinteza pesnitve.The article analyses the poem Ljubav reče greva (Luv Says Let’s Go) by Nina Dragičević. Basic literary interpretation is broadened by assessing of the role of a poet and his/her work as portrayed through the poem. By integrating this theme into the poem, I argue, the author brings about the socio-political status of literary artists, who are still to some extent entrapped within the supranational and timeless Prešeren structure. The article is concluded by an assessment through performative theory and offers a socially proactive outlook

Assessment of contemporary narratological approaches on the basis of analysis of novels Secret History, 4 3 2 1, and A Tale for Time Being

Diplomsko delo obravnava sodobne naratološke pristope ob analizi izbranih romanov. Naratologija je razmeroma mlada veja literarne vede, ki se ukvarja z vprašanjem, kaj in kako je o nečem mogoče pripovedovati v literaturi. Predklasične pristope je v največji meri oblikoval Franz K. Stanzel, na klasično naratologijo s teoretiki, kot so bili, Tzvetan Todorov, Roland Barthes, Gérard Genette, pa je v največji meri vplival strukturalizem. V sodobnosti pa se je naratologija vrnila k svojim jezikoslovnim koreninam (t. i. kognitivni obrat), kar bo prikazano prek obravnave teorije Marie-Laure Ryan in Davida Hermana. Za naratološko analizo so bili izbrani romani Skrivna zgodovina Donne Tartt, 4 3 2 1 Paula Austerja in A Tale for the Time Being Ruth Ozeki, saj je za vse tri značilna izstopajoča notranja razdeljenost. Namen diplomskega dela je z analizo izbranih romanov preveriti relevantnost klasičnih in sodobnih naratoloških pristopov na izbranih romanih. Prav slednje povzroča največjo zadrego pri nas – razen posameznih primerov do naratoloških obravnav romanov ne prihaja.Thesis analyses selected novels on the basis of classical and contemporary narratological approaches. Narratology is a relatively young subcategory in the field of literary science, that deals with the questions of what and how can something be narrated in literature. Most influential theorist in the field of protonarratological researches was Franz K. Stanzel, but classical narratology, with theorists such as Tzvetan Todorov, Roland Barthes, Gérard Genette, was based heavily on structuralist approach. Contemporary approaches returned to linguistic roots (regarding to the so-called cognitive turn), with theorists like Marie-Laure Ryan and David Herman. Novels that were chosen for narratological analysis, are: Secret History by Donna Tartt, 4 3 2 1 by Paul Auster and A Tale for the Time Being by Ruth Ozeki. What they all have in common is unusual internal structure. The aim of thesis is to test the relevancy of classical and contemporary narratological approaches on selected novels. While theoretical examination of narratological approaches is present in Slovene literary theory, narratological anaylsis themselves are not except for few cases

Comparing the Influence of Setting on the Development of Main Characters in Virginia Woolf\u27s Voyage Out and Zofka Kveder\u27s Njeno življenje (Her Life)

V magistrski nalogi analiziram dogajalni prostor z vidika prostorske literarne vede, ki razume prostor v prepletu naravno- in družbenogeografskih značilnosti. Najprej predstavim različne pristope k obravnavam dogajalnega prostora, med katerimi sta se kot najprimernejši izkazali metodologiji Barbare Piatti in Bertranda Westphala, ki sem ju uporabila za analizo romanov The Voyage Out angleške pisateljice Virginie Woolf in Njeno življenje slovenske pisateljice Zofke Kveder. V obeh romanih dogajalni prostor (in njegovo spreminjanje) predstavlja pomemben element dogajanja in ni zgolj njuno ozadje oz. kulisa. Analiza je pokazala, da družbene implikacije, vzpostavljene na naravnogeografskih danostih, pomembno vplivajo na potek zgodbe in razvoj glavne osebe v obeh romanih.In my master\u27s thesis, I analyse the setting from the perspective of spatial literary studies, which understands space in the terms of the interplay of natural and socio-geographical features. First, I present different approaches to the study of literary setting: I have focused on the research around the notion of literary geography as proposed by Barbara Piatti and the geocriticism as proposed by Bertrand Westphal, because they complement each other: while Piatti focuses on geographical aspect of the literary setting, Westphal emphasises the sociocultural aspect. Using these approaches, I analysed the novels The Voyage Out by the English writer Virginia Woolf and Her Life by the Slovenian writer Zofka Kveder. In both novels, the setting (and its changes) is an important element of the plot and does not serve only as a backdrop or background. The analysis has shown that the social implications arising from the natural geography have an important influence on the course of the story and the development of the main character in both novels

Neuroinflammation-induced upregulation of glial cathepsin X expression and activity in vivo

Neuroinflammation is an important factor in pathogenesis of neurodegenerative diseases. Microglia-derived lysosomal cathepsins have been increasingly recognized as important inflammatory mediators that trigger signalling pathways that aggravate neuroinflammation. In vitro, a contribution to neuroinflammation processes has been shown for cathepsin X, howeverthe expression patterns and functional roles of cathepsin X in neuroinflammatory brain pathology remain elusive. In this study, we analyzed the expression, activity, regional distribution and cellular localization of cathepsin X in the rat brain with neuroinflammation-induced neurodegeneration. Unilateral injection of LPS induced strong upregulation of cathepsin X expression and its activity in the ipsilateral striatum. In addition to the striatum, cathepsin X overexpression was detected in other brain areas such as cerebral cortex, corpus callosum, subventricular zone and external globus pallidus, whereas the upregulation was mainly restricted to activated microglia and reactive astrocytes. Continuous administration of the cathepsin X inhibitor AMS36 indicated protective effects against LPS-induced striatal degeneration, as seen by the attenuated the LPS-mediated dilation of the lateral ventricles and partial decreased extent of striatal lesion. Taken together, our results indicate that cathepsin X plays a role as a pathogenic factor in neuroinflammation-induced neurodegeneration and represents a potential therapeutic target for neurodegenerative diseases associated with neuroinflammation

Prevalence of the Helicobacter pylori babA2 Gene in Children Mainly Depends on the PCR Primer Set Used

Various polymerase chain reaction- (PCR-) based methods with varying positivity rates were designed to detect the Helicobacter pylori babA2 gene. To compare different primer sets, babA2 prevalence was determined in 279 H. pylori-positive pediatric samples using the 832 bp, 139 bp, and 271 bp PCR primer sets, resulting in 34.0%, 51.3%, and 79.6% prevalence of the babA2 gene, respectively. The babA2 status determined using the 832 bp and 139 bp PCR primer sets significantly correlated with bacterial density and activity of inflammation, whereas no such correlations were found using the 271 bp PCR primer set. The 139 and 832 bp PCR primer sets concordantly detected the babA2 gene in 93 cases; however, in comparison to the 832 bp PCR primer set, the 139 bp PCR primer set detected additional 50 babA2 cases, whereas only two 832 bp positive cases were missed. The 271 bp PCR primer set missed 32 babA2 cases that were 832 bp and/or 139 bp PCR positive, but tested solely positive in 109 cases. Interestingly, cloning of a subset of 271 bp PCR positive samples revealed amplification of the babA/B gene chimera. Hence, in our opinion, the 271 bp PCR protocol is not a reliable diagnostic tool for detecting the babA2 gene in children. Our results reaffirm previous observations that the use of certain babA2 PCR primer sets can significantly impact estimation of the prevalence and clinical relevance of the H. pylori babA2 gene in children, suggesting babA2 detection methods should be carefully selected

Ali in koliko poznamo izbrane neologizme, pozabnice in igre besed

V raziskovalni nalogi so združene seminarske naloge, ki so jih študentke opravljale pri predmetu Pomenoslovje in besedotvorje. Z anketami so preverjale, ali sodelujoči poznajo in uporabljajo izbrane izraze in ali predlagajo drugačna poimenovanja. Analiza je zajemala tri skupine izrazov – neologizme, pozabnice in besedne igre