Differential regulation of mast cell degranulation versus cytokine secretion by the actin regulatory proteins Coronin1a and Coronin1b

Coronin1a inhibits mast cell degranulation through actin cytoskeletal dynamics while augmenting cytokine secretion, an effect exacerbated by additional loss of Coronin1b

Modulation of Mast Cell Reactivity by Lipids: The Neglected Side of Allergic Diseases

Mast cells (MCs) have long been mainly regarded as effector cells in IgE-associated allergic disorders with potential immunoregulatory roles. Located close to the allergen entry sites in the skin and mucosa, MCs can capture foreign substances such as allergens, toxins, or noxious substances and are exposed to the danger signals produced by epithelial cells. MC reactivity shaped by tissue-specific factors is crucial for allergic responses ranging from local skin reactions to anaphylactic shock. Development of Th2 response leading to allergen-specific IgE production is a prerequisite for MC sensitization and induction of FcεRI-mediated MC degranulation. Up to now, IgE production has been mainly associated with proteins, whereas lipids present in plant pollen grains, mite fecal particles, insect venoms, or food have been largely overlooked regarding their immunostimulatory and immunomodulatory properties. Recent studies, however, have now demonstrated that lipids affect the sensitization process by modulating innate immune responses of epithelial cells, dendritic cells, and NK-T cells and thus crucially contribute to the outcome of sensitization. Whether and how lipids affect also MC effector functions in allergic reactions has not yet been fully clarified. Here, we discuss how lipids can affect MC responses in the context of allergic inflammation. Direct effects of immunomodulatory lipids on MC degranulation, changes in local lipid composition induced by allergens themselves and changes in lipid transport affecting MC reactivity are possible mechanisms by which the function of MC might be modulated

Lipid Mediators From Timothy Grass Pollen Contribute to the Effector Phase of Allergy and Prime Dendritic Cells for Glycolipid Presentation

Plant pollen are an important source of antigens that evoke allergic responses. Protein antigens have been the focus of studies aiming to elucidate the mechanisms responsible for allergic reactions to pollen. However, proteins are not the sole active agent present in pollen. It is known that pollen grains contain lipids essential for its reproduction and bioactive lipid mediators. These small molecular compounds are co-delivered with the allergens and hence have the potential to modulate the immune response of subjects by activating their innate immune cells. Previous reports showed that pollen associated lipid mediators exhibited neutrophil- and eosinophil-chemotactic activity and induced polarization of dendritic cells (DCs) toward a Th2-inducing phenotype. In our study we performed chemical analyses of the pollen associated lipids, that are rapidly released upon hydration. As main components we have identified different types of phytoprostanes (PhytoPs), and for the first time phytofurans (PhytoFs), with predominating 16-F1t-PhytoPs (PPF1-I), 9-F1t-PhytoPs (PPF1-II), 16-E1t-PhytoPs (PPE1-I) and 9-D1t-PhytoPs (PPE1-II), and 16(RS)-9-epi-ST-Δ14-10-PhytoFs. Interestingly 16-E1t-PhytoP and 9-D1t-PhytoPs were found to be bound to glycerol. Lipid-containing samples (aqueous pollen extract, APE) induced murine mast cell chemotaxis and IL-6 release, and enhanced their IgE-dependent degranulation, demonstrating a role for these lipids in the immediate effector phase of allergic inflammation. Noteworthy, mast cell degranulation seems to be dependent on glycerol-bound, but not free phytoprostanes. On murine dendritic cells, APE selectively induced the upregulation of CD1d, likely preparing lipid-antigen presentation to iNKT cells. Our report contributes to the understanding of the activity of lipid mediators in the immediate effector phase of allergic reactions but identifies a yet undescribed pathway for the recognition of pollen-derived glycolipids by iNKT cells

Eosinophils in glioblastoma biology

Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review

Practice Oriented Regional Studies in German Language Classes in Vocational School

Šajā darbā tiek aplūkots, kā svešvalodas apguve atbilst reālās dzīves izvirzītajām prasībām, cik daudz arodskolēnam ir jāzina par valsti, kura viņam ir sveša, bet kuras valodu viņš apgūst un kuru viņam ir iespēja apmeklēt, respektīvi, valsts zinību saturs vācu valodas stundās un mācību grāmatās. Tā kā zinības par valsti nav šķiramas no valodas apguves un kultūras, tām ir jāveic kāds konkrēts uzdevums mācību stundās. Kādam jābūt šo zinību saturam arodskolēniem, kuru zināšanu līmenis svešvalodā un motivācija mācīties ne vienmēr ir apmierinoši, ir aplūkojamā problēma šajā darbā. Darba mērķis ir pierādīt, ka lielāki panākumi svešvalodas apguvē var tikt sasniegti tikai saistībā ar komunikatīvi orientētām un uz ikdienas situācijām balstītām zinībām par valsti, kurām jābūt vācu valodas kā svešvalodas stundas sastāvdaļai. Jo vairāk ir sadzīviski orientētu zināšanu par valsti, kuras valoda tiek apgūta, jo intensīvāk tiks kāpināta motivācija, interese un spēja runāt šajā valodā. Darbs ir sadalīts 5 nodaļās: -teorētiskais valsts zinību pamatojums: definīcija, funkcijas, mērķi un nozīme, aktuālākais valsts zinību virzieni, to spezifika un didaktiskās iespējas arodskolā, -mācību līdzekļos iekļauto valsts zinību satura analīze, -praktiskā daļa – skolēnu aptauja, kuri ir apmeklējuši valsti, kuras valodu viņi ir mācījušies.In the present work it is a question of how the foreign language learning corresponds to the real life how much a professional pupil about a foreign country whose language he learns and to which he will surely go needs to know - therefore the regional studies contents in the DaF- instruction and in the teaching-works. She is supposed to find a role in the instruction so that the regional studies are not separable of the language acquisition and of the culture. Which regional studies contents are supposed to be with profession-oriented young people contained with their brief language level, this stands in the focus of my work. The objective of the work is to be proved, that the higher services during the foreign language learning only by means of the communicative- and orientated to the everyday life situations regional studies that is integrated in the German hour can be reached. Each more realistic regional study it gives, the more intense should the interest and the motivation, as well as the ability for the speaking climb. The work is divided into 5 chapters: -The theoretical background the regional studies: Definition, functions, objectives and significance, the most current approaches the regional studies, the Spezifik the regional studies and didactic possibilities in the professional school. -Analysis of the regional studies mediation in the teaching-works, -The practical one chapter- a questioning of the pupils that had gone to the country itself

Worthless, Priceless, Sacred. Performing state as superparent by out-of-family caregivers

Sociālā antropoloģijaSocioloģija, politoloģija un antropoloģijaSocial AnthropologySociology, Politics and AnthropologyMaģistra darbs “Nevērtīgs, nenovērtējams, svēts. Ārpusģimenes aprūpētāju prakses īstenojot valsti kā supervecāku” ir institucionalizēto bērnu un tur strādājošo valsts īstenošanas pieredzes un prakses analīze un teorētiskā interpretācija. Izmantojot Agambena kailās dzīvības un Edelmana iedomāto bērnu, darbā tiek konstruēts un dekonstruēts bērna jēdziens, kas pamatojotes uz empirisko materiālu norāda, ka valsts īstenotā biopoitiku ‘bērna labākajās interesēs’ tiek radīta un īstenota neesošam tēlam. Valsts birokrātiskie mehānismi regulē, definē un leģitimē dažādus radniecības aktus un attiecības. To darot, valsts kā aparāts sevi ierindo supervecāka (Rockhill 2010, 157) lomā visiem bērniem, jo īpaši tiem, kam nepieciešama aizstāvība, pareizā aprūpe. Šīs supervecāka lomas īstenošana tiek deleģēta institūcijām, tur strādājošajiem, kas savā saskarmē ar bērnu to īsteno balstoties uz savu izpratni, uz savu iemiesoto dzīves pieredzi. Valsts politikas virzītāji plāno un paļaujas uz cilvēku radniecību kaut vai demogrāfiskā līmenī (Žabicka 2018). Tādējādi izlemjot, kurš ar ko ir likumīgi saistīts, kā arī virza un veido arī pašas šīs attiecības. Bērnam noņem visu, atstājot kailo dzīvību, lai to normalizētu jau citā, pareizā radniecībā. Biopolitika (Bianco, Giuseppe; Miguel, de Beistegui 2015), kas novienkāršojot nozīmē regulētu dzimstību, kontrolētu mirstību, ar atļauto izvēles brīvībi, kas ir definēta pastāvošās iekārtas akceptētajā normalizācijas rāmī un pasniegta indivīdam kā nepieciešamība virzītai ekonomiskai labbūtībai un drošumspējai . Realitātē īstenotā biopolitika bērna labākajās interesēs, sabiedrībā pašu bērnu atspoguļo kā pasīvu kultūras saņēmēju, kurš “lineārā līknē dodas savā ceļā uz pilngadību” (Abella 2017, 23). Bērniem līdz pilngadības sasniegšanai nav savu politisko tiesību: “Bērni nav balsotāji, bērni par mums nebalsos” (Kalnozols 2018). Morālu un likumisku motīvu vadīti par bērniem bērna labākajās interesēs rūpējas pieaugušie. Šie aprūpes apsvērumi nekad nav tikai morāli, tie vienmēr ir apzināti/ neapzināti politiski un ekonomiski virzīti. Bērnam ir tikai kailā dzīvība (Agamben 1998), ķermenis, kas tiek pārvietots, pakļauts un veidots pēc aprūpē iesaistīto ieskatiem. Bērnība, kā kultūras projekts ar mērķiem un nozīmēm, ir pastāvīga pielāgošanās un cīņa (Weisner 2015). Lauka darba etnogrāfiskie dati ieskicē vecāku, bērnu un aprūpētāju attiecībām ar valsts iekārtā noteikto pre-institucionālajā, institucionālajā un post – institucionālajā (Rockhill 2010, 3-5) posmā, kurus interpretējot teorijā, pastiprinot ar pētījumiem un analizējot īstenotās prakses, pierādu, ka valsts kā supervecāka politika ar likumos definēto rīcības vadmotīvu “bērna [labākajās] interesēs” (Saeima 1998), tiek īstenota uz neesošu, iedomātu (Edelman 1998) bērnu.Master's thesis “Worthless, priceless, sacred. Performing state as superparent by out-of-family caregivers” is an analysis and theoretical interpretation of the experience and practice of state performing by institutionalized children and those working there. Using Agamben's bare life and Edelman's imagined child, the work constructs and deconstructs the concept of the child, which, based on empirical material, indicates that the state-implemented biopolitics in the 'best interests of the child' is created and implemented for a non-existent image in child. State bureaucratic mechanisms regulates, define and legitimize various acts and kinship relationships. In doing so, the state as an apparatus, places itself in the role of a superparent (Rockhill 2010, 157) for all children, especially for those in need of protection, proper care. The implementation of this role of superparent is delegated to institutions, to those who work there, who in their contact with the child performe this role, based on their understanding, on their embodied life experience. Public policy makers plan and rely on kinship, even more at the demographic level (Žabicka 2018). Thus, in deciding on legal terams, to whom parental relationships are allowed to perform and to whom it’s not. Everything is removed from the child, leaving it’s bare life to be normalized in another, correct kinship. Biopolitics (Bianco, Giuseppe; Miguel, de Beistegui 2015), which in simple means regulated birth, controlled mortality, with defined in the accepted normalization framework allowed freedom of choice, and presented to the individual as a necessity for directed economic well-being and security. The reality-based biopolitics in the best interests of the child, in society, portrays the child himself as a passive recipient of culture, who “goes on a linear curve on his way to adulthood” (Abella 2017, 23). Children do not have their political rights until they reach their adulthood: “Children are not voters, children do not vote for us” (Kalnozols 2018). Driven by moral and legal motives, children are cared for by adults in ‘the best interests of the child’. These care considerations are never just moral, they are always consciously / unconsciously politically and economically driven. The child has only a bare life (Agamben 1998), a body that is moved, exposed and shaped at the discretion of the caregivers. Childhood, as a cultural project with goals and meanings, is a constant adaptation and struggle (Weisner 2015). The ethnographic data of the field work outline the relations of parents, children and caregivers with the pre-institutional, institutional and post-institutional (Rockhill 2010, 3-5) stages of the state system, which, when interpreted in theory, reinforced by research and analysis, show that the state as a superparental policy with the guiding principle of action “in the best interests of the child” defined by law (Saeima 1998), is performed to a non-existent, imaginary child (E