A salsolinol dopaminerg transzmisszióban betöltött fiziológiás szerepének vizsgálata = Examination of the physiological role of salsolinol in dopaminergic neurotransmission

Korábban kimutattuk, hogy a hipofízis közti-hátsó lebenyének (NIL) prolaktin (PRL) ürítő hatásért a salsolinol (SAL) felelős. A PRL-szint emelkedéssel párhuzamosan a SAL az eminentia medianaban (ME) csökkenti, míg az elülső lebenyben (AL) növeli cAMP szintet. A SAL-nak egy szerkezeti analógja, az 1MeDIQ képes gátolni a szopási ingerre és a stresszre bekövetkező PRL szint emelkedést. Mindezek alátámasztják korábbi feltevésünket, hogy a SAL az a régóta keresett élettanilag is jelentős prolaktoliberin. Az 1MeDIQ az amfetamin (AMPH)-hoz hasonló psziho-stimuláns hatással is rendelkezik, növeli a plazma katecholamin-szinteket. A perifériás szimpatikus beidegzések műtéti vagy farmakológiás (chlorisondamine) lézióját követően fellépő változások a SAL hatásában világosan jelzik, hogy az 1MeDIQ hatásában a norepinefrin (NE)-erg rendszer kulcsszerepet játszik. A PRL felszabadító hatása mellett a SAL csökkenti a stressz és az 1MeDIQ kiváltotta plazma NE és epinefrin (E) emelkedést. Hasonló kölcsönhatást találtunk az AMPH és a SAL prolaktin elválasztásra gyakorolt hatásában is. A szimpatikus idegelemek által beidegzett szervekben, mint a pitvarban, lépben, májban, vagy az ovariumban, a SAL szelektíven csökkenti a dopamin (DA) koncentrációját. SAL-nak ez a hatása a kivédhető AMPH-előkezeléssel. Összefoglalva, a SAL és az AMPH között kölcsönhatás állapítható meg az elülső lebenyi PRL-ürítés és a szimpatikus végződésekben zajló katecholamin-metabolizmus vonatkozásában egyaránt. | We have previously shown that salsolinol (SAL) is responsible for the prolactin (PRL) releasing activity detected in the neurointermediate lobe (NIL) of the pituitary gland. SAL can induce a decrease of cAMP level in the median eminence (ME) and an increase in the anterior lobe (AL). A structural analogue of SAL, 1MeDIQ, can inhibit the elevation of plasma PRL induced by physiological stimuli like suckling or stress. All these data support our assumption that SAL may be the physiologically relevant prolactoliberin. 1MeDIQ has a psycho-stimulant action as well, which is similar to the effect of amphetamine (AMPH) i.e. induces an increase in plasma catecholamine concentrations. Surgical or pharmacological (chlorisondamine) lesions of peripheral sympathetic innervations clearly indicate that norepinephrin (NE)-erg system has pivotal role in the action of 1MeDIQ. SAL, besides its PRL releasing activity, can significantly decrease stress and 1MeDIQ induced increase in plasma NE and epinephrine (E) levels. There is an interaction between AMPH and SAL on pituitary PRL release too. SAL treatment results in a selective decrease in DA content of sympathetically innervated organs like atrium, spleen, liver, ovaries, and salivary gland. This effect of SAL is prevented by AMPH pretreatment. It is clear that there is a mutual interaction between SAL and AMPH not only on PRL release, but their interaction is obvious on the catecholamine ?metabolism? of nerve terminals as well

Macromolecular theory of solvation and structure in mixtures of colloids and polymers

The structural and thermodynamic properties of mixtures of colloidal spheres and non-adsorbing polymer chains are studied within a novel general two-component macromolecular liquid state approach applicable for all size asymmetry ratios. The dilute limits, when one of the components is at infinite dilution but the other concentrated, are presented and compared to field theory and models which replace polymer coils with spheres. Whereas the derived analytical results compare well, qualitatively and quantitatively, with mean-field scaling laws where available, important differences from ``effective sphere'' approaches are found for large polymer sizes or semi-dilute concentrations.Comment: 23 pages, 10 figure

Rhetorical-Performative Analysis of the Urban Symbolic Landscape : Populism in Action

This chapter introduces a rhetorical-performative analysis as a tool for exploring urban symbolic landscape and populism and hence deals with relationality and materiality from the postfoundational perspective. It connects the articulation theory of cultural theorists Stuart Hall or political theorists Ernesto Laclau and Chantal Mouffe and spatial analysis of cultural geographer Doreen Massey to the study of populism. The case of Hungary shows how political frontiers have been articulated in the public space, contestable interpretations of the past are deliberately used and key symbolic urban landscapes transformed radically to articulate a political ‘us’—and ‘them.’ In the 2010s, in the Hungarian capital Budapest, the top-down process transforming urban space faced bottom-up movements which reproduce the populist logic of articulation.Peer reviewe

Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the murine immunological synapse [version 1]

Background: Mutations of the common cytokine receptor gamma chain (γc) cause Severe Combined Immunodeficiency characterized by absent T and NK cell development. Although stem cell therapy restores these lineages, residual immune defects are observed that may result from selective persistence of γc-deficiency in myeloid lineages. However, little is known about the contribution of myeloid-expressed γc to protective immune responses.  Here we examine the importance of γc for myeloid dendritic cell (DC) function. Methods: We utilize a combination of in vitro DC/T-cell co-culture assays and a novel lipid bilayer system mimicking the T cell surface to delineate the role of DC-expressed γc during DC/T-cell interaction. Results: We observed that γc in DC was recruited to the contact interface following MHCII ligation, and promoted IL-15Rα colocalization with engaged MHCII. Unexpectedly, trans-presentation of IL-15 was required for optimal CD4+T cell activation by DC and depended on DC γc expression. Neither recruitment of IL-15Rα nor IL-15 trans-signaling at the DC immune synapse (IS), required γc signaling in DC, suggesting that γc facilitates IL-15 transpresentation through induced intermolecular cis associations or cytoskeletal reorganization following MHCII ligation. Conclusions: These findings show that DC-expressed γc is required for effective antigen-induced CD4+ T cell activation. We reveal a novel mechanism for recruitment of DC IL-15/IL-15Rα complexes to the IS, leading to CD4+ T cell costimulation through localized IL-15 transpresentation that is coordinated with antigen-recognition

Dendritic cell-expressed common gamma-chain recruits IL-15 for trans-presentation at the murine immunological synapse [version 2; referees: 2 approved]

BACKGROUND: Mutations of the common cytokine receptor gamma chain (γc) cause Severe Combined Immunodeficiency characterized by absent T and NK cell development. Although stem cell therapy restores these lineages, residual immune defects are observed that may result from selective persistence of γc-deficiency in myeloid lineages. However, little is known about the contribution of myeloid-expressed γc to protective immune responses.  Here we examine the importance of γc for myeloid dendritic cell (DC) function. METHODS: We utilize a combination of in vitro DC/T-cell co-culture assays and a novel lipid bilayer system mimicking the T cell surface to delineate the role of DC-expressed γc during DC/T-cell interaction. RESULTS: We observed that γc in DC was recruited to the contact interface following MHCII ligation, and promoted IL-15Rα colocalization with engaged MHCII. Unexpectedly, trans-presentation of IL-15 was required for optimal CD4+T cell activation by DC and depended on DC γc expression. Neither recruitment of IL-15Rα nor IL-15 trans-signaling at the DC immune synapse (IS), required γc signaling in DC, suggesting that γc facilitates IL-15 transpresentation through induced intermolecular cis associations or cytoskeletal reorganization following MHCII ligation. CONCLUSION: These findings show that DC-expressed γc is required for effective antigen-induced CD4+ T cell activation. We reveal a novel mechanism for recruitment of DC IL-15/IL-15Rα complexes to the IS, leading to CD4+ T cell costimulation through localized IL-15 transpresentation that is coordinated with antigen-recognition

Investigation into the formation of the scrape-off layer density shoulder in JET ITER-like wall L-mode and H-mode plasmas

The low temperature boundary layer plasma (Scrape-Off-Layer or SOL) between the hot core and the surrounding vessel determines the level of power-loading, erosion and implantation of material surfaces, and thus the viability of tokamak-based fusion as an energy source. This study explores mechanisms affecting the formation of flattened density profiles, so-called ‘density shoulders’, in the low-field side (LFS) SOL, which modify ion and neutral fluxes to surfaces – and subsequent erosion. There is evidence against local enhancement of ionization inducing shoulder formation. We find that increases in SOL parallel resistivity, Λdiv (=[L||νei Ωi ]/cs Ωe), postulated to lead to shoulder growth through changes in SOL turbulence characteristics, correlates with increases in upstream SOL shoulder amplitude, As only under a subset of conditions (D2-fuelled L-mode density scans with outer strike point on the horizontal target). Λdiv fails to correlate with As for cases of N2 seeding or during sweeping of the strike point across the horizontal target. The limited correlation of Λdiv with As was also found for H-mode discharges. Thus, while Λdiv above a threshold of ~1 may be necessary for shoulder formation and/or growth, another shoulder mechanism is required. More significantly we find that in contrast to parallel resistivity, outer divertor recycling as quantified by the total outer divertor Balmer Dα emission, I-Dα, does scale with shoulder amplitude where Λdiv does and even where Λdiv fails. Divertor recycling could lead to SOL density shoulder formation through: a) reducing the parallel to the field flow (loss) of ions out of the SOL to the divertor; and b) changes in radial electric fields which lead to ExB poloidal flows as well as potentially affecting the SOL turbulence birth characteristics. Thus changes in divertor recycling may be the sole process in bringing about SOL density shoulders or in tandem with parallel resistivity

Neutral pathways and heat flux widths in vertical- and horizontal-target EDGE2D-EIRENE simulations of JET

This paper further analyses the EDGE2D-EIRENE simulations presented by Chankin et al (2017 Nucl. Mater. Energy 12 273), of L-mode JET plasmas in vertical-vertical (VV) and Vertical-horizontal (VH) divertor configurations. As expected, the simulated outer divertor ionisation source peaks near the separatrix in VV and radially further out in VH. We identify the reflections of recycled neutrals from lower divertor tiles as the primary mechanism by which ionisation is concentrated on the outer divertor separatrix in the VV configuration. These lower tile reflection pathways (of neutrals from the outer divertor, and to an even greater extent from the inner divertor) dominate the outer divertor separatrix ionisation. In contrast, the lower-tile-reflection pathways are much weaker in the VH simulation and its outer divertor ionisation is dominated by neutrals which do not reflect from any surfaces. Interestingly, these differences in neutral pathways give rise to strong differences in the heat flux density width λq at the outer divertor entrance: λq = 3.2 mm in VH compared to λq = 11.8 mm in VV. In VH, a narrow channel exists in the near scrape-off-layer (SOL) where the convected heat flux, driven by strong Er × B flow and thermoelectric current, dominates over the conducted heat flux. The width of this channel sets λq and is determined by the radial distance between the separatrix and the ionisation peak in the outer divertor

Observations and modelling of ion cyclotron emission observed in JET plasmas using a sub-harmonic arc detection system during ion cyclotron resonance heating

Peer reviewe