LOS oligosaccharide modification enhances dendritic cell responses to meningococcal native outer membrane vesicles expressing a non toxic lipid A.

Outer membrane vesicles (OMV) are released by many bacteria, and contain immunogenic antigens in addition to harmful inflammatory factors, like lipopolysaccharides. Chemically detoxified OMV have been used in vaccines against Neisseria meningitidis (Nm), however little is known about their interaction with antigen presenting cells. In this study, we investigated the interaction of Nm OMV with human dendritic cells (DC) to gain further understanding of their biological activity. We engineered a novel serogroup B Nm that is unencapsulated (siaD), expresses pentacylated lipid A (lpxL1), hence conferring reduced toxicity, and expresses an lgtB oligosaccharide structure designed to target OMV to DC via DC-SIGN. We show that the lgtB moiety is critical for internalization of NOMV by DC. Furthermore, the lgtB moiety significantly enhances DC maturation, IL-10 and IL-23 production in the presence of a pentacylated lipid A. Whilst different DC phenotypes were observed for each NOMV, this had little effect on Th1 and Th2 cell differentiation, however lgtB significantly increased Th17 cell expansion in the presence of pentacylated lipid A. We believe that lgtB/lpxL1 NOMV should be considered further as a vaccine vector, particularly considering the importance of lgtB in antigen uptake and further human studies on antigen specific responses should be considered

Modification of hyperacute canine renal homograft and pig-to-dog heterograft rejection by the intra-arterial infusion of citrate

Hyperacute rejection was studied in seven presensitized canine recipients of renal homografts and in 22 canine recipients of pig kidneys. Under both experimental circumstances, untreated animals rejected the grafts within a few minutes. With the intra-arterial infusion of sodium citrate, hyperacute heterograft rejection was forestalled for the duration of therapy, and with homografts the benefit outlasted treatment by many hours. The protection of heterografts was not due solely to anticoagulation by the citrate, since heparin in large doses did not accomplish the same thing. A contributory factor may have been complement inhibition since removal of complement by the grafts was greatly reduced in the citrate-treated animals. © 1971

Deletion of the GABAA α2-subunit does not alter self dministration of cocaine or reinstatement of cocaine seeking

Rationale GABAA receptors containing α2-subunits are highly represented in brain areas that are involved in motivation and reward, and have been associated with addiction to several drugs, including cocaine. We have shown previously that a deletion of the α2-subunit results in an absence of sensitisation to cocaine. Objective We investigated the reinforcing properties of cocaine in GABAA α2-subunit knockout (KO) mice using an intravenous self-administration procedure. Methods α2-subunit wildtype (WT), heterozygous (HT) and KO mice were trained to lever press for a 30 % condensed milk solution. After implantation with a jugular catheter, mice were trained to lever press for cocaine (0.5 mg/kg/infusion) during ten daily sessions. Responding was extinguished and the mice tested for cue- and cocaine-primed reinstatement. Separate groups of mice were trained to respond for decreasing doses of cocaine (0.25, 0.125, 0.06 and 0.03 mg/kg). Results No differences were found in acquisition of lever pressing for milk. All genotypes acquired self-administration of cocaine and did not differ in rates of self-administration, dose dependency or reinstatement. However, whilst WT and HT mice showed a dose-dependent increase in lever pressing during the cue presentation, KO mice did not. Conclusions Despite a reported absence of sensitisation, motivation to obtain cocaine remains unchanged in KO and HT mice. Reinstatement of cocaine seeking by cocaine and cocaine-paired cues is also unaffected. We postulate that whilst not directly involved in reward perception, the α2-subunit may be involved in modulating the “energising” aspect of cocaine’s effects on reward-seeking

Deletion of the gabra2 gene results in hypersensitivity to the acute effects of ethanol but does not alter ethanol self administration

Human genetic studies have suggested that polymorphisms of the GABRA2 gene encoding the GABA(A) α2-subunit are associated with ethanol dependence. Variations in this gene also convey sensitivity to the subjective effects of ethanol, indicating a role in mediating ethanol-related behaviours. We therefore investigated the consequences of deleting the α2-subunit on the ataxic and rewarding properties of ethanol in mice. Ataxic and sedative effects of ethanol were explored in GABA(A) α2-subunit wildtype (WT) and knockout (KO) mice using a Rotarod apparatus, wire hang and the duration of loss of righting reflex. Following training, KO mice showed shorter latencies to fall than WT littermates under ethanol (2 g/kg i.p.) in both Rotarod and wire hang tests. After administration of ethanol (3.5 g/kg i.p.), KO mice took longer to regain the righting reflex than WT mice. To ensure the acute effects are not due to the gabra2 deletion affecting pharmacokinetics, blood ethanol concentrations were measured at 20 minute intervals after acute administration (2 g/kg i.p.), and did not differ between genotypes. To investigate ethanol's rewarding properties, WT and KO mice were trained to lever press to receive increasing concentrations of ethanol on an FR4 schedule of reinforcement. Both WT and KO mice self-administered ethanol at similar rates, with no differences in the numbers of reinforcers earned. These data indicate a protective role for α2-subunits, against the acute sedative and ataxic effects of ethanol. However, no change was observed in ethanol self administration, suggesting the rewarding effects of ethanol remain unchange

A Land System representation for global assessments and land-use modeling

Current global scale land-change models used for integrated assessments and climate modeling are based on classifications of land cover. However, land-use management intensity and livestock keeping are also important aspects of land use, and are an integrated part of land systems. This article aims to classify, map, and to characterize Land Systems (LS) at a global scale and analyze the spatial determinants of these systems. Besides proposing such a classification, the article tests if global assessments can be based on globally uniform allocation rules. Land cover, livestock, and agricultural intensity data are used to map LS using a hierarchical classification method. Logistic regressions are used to analyze variation in spatial determinants of LS. The analysis of the spatial determinants of LS indicates strong associations between LS and a range of socioeconomic and biophysical indicators of human-environment interactions. The set of identified spatial determinants of a LS differs among regions and scales, especially for (mosaic) cropland systems, grassland systems with livestock, and settlements. (Semi-)Natural LS have more similar spatial determinants across regions and scales. Using LS in global models is expected to result in a more accurate representation of land use capturing important aspects of land systems and land architecture: the variation in land cover and the link between land-use intensity and landscape composition. Because the set of most important spatial determinants of LS varies among regions and scales, land-change models that include the human drivers of land change are best parameterized at sub-global level, where similar biophysical, socioeconomic and cultural conditions prevail in the specific regions. © 2012 Blackwell Publishing Ltd

The relationship between structural game characteristics and gambling behavior: a population-level study

The aim of this study was to examine the relationship between the structural characteristics and gambling behavior among video lottery terminal (VLT) gamblers. The study was ecological valid, because the data consisted of actual gambling behavior registered in the participants natural gambling environment without intrusion by researchers. Online behavioral tracking data from Multix, an eight game video lottery terminal, were supplied by Norsk-Tipping (the state owned gambling company in Norway). The sample comprised the entire population of Multix gamblers (N = 31,109) who had gambled in January 2010. The individual number of bets made across games was defined as the dependent variable, reward characteristics of a game (i.e., payback percentage, hit frequency, size of winnings and size of jackpot) and bet characteristics of a game (i.e., range of betting options and availability of advanced betting options) served as the independent variables. Control variables were age and gender. Two separate cross-classified multilevel random intercepts models were used to analyze the relationship between bets made, reward characteristics and bet characteristics, where the number of bets was nested within both individuals and within games. The results show that the number of bets is positively associated with payback percentage, hit frequency, being female and age, and negatively associated with size of wins and range of available betting options. In summary, the results show that the reward characteristics and betting options explained 27 % and 15 % of the variance in the number of bets made, respectively. It is concluded that structural game characteristics affect gambling behavior. Implications of responsible gambling are discussed

Comments on Non-holomorphic Modular Forms and Non-compact Superconformal Field Theories

We extend our previous work arXiv:1012.5721 [hep-th] on the non-compact N=2 SCFT_2 defined as the supersymmetric SL(2,R)/U(1)-gauged WZW model. Starting from path-integral calculations of torus partition functions of both the axial-type (`cigar') and the vector-type (`trumpet') models, we study general models of the Z_M-orbifolds and M-fold covers with an arbitrary integer M. We then extract contributions of the degenerate representations (`discrete characters') in such a way that good modular properties are preserved. The `modular completion' of the extended discrete characters introduced in arXiv:1012.5721 [hep-th] are found to play a central role as suitable building blocks in every model of orbifolds or covering spaces. We further examine a large M-limit (the `continuum limit'), which `deconstructs' the spectral flow orbits while keeping a suitable modular behavior. The discrete part of partition function as well as the elliptic genus is then expanded by the modular completions of irreducible discrete characters, which are parameterized by both continuous and discrete quantum numbers modular transformed in a mixed way. This limit is naturally identified with the universal cover of trumpet model. We finally discuss a classification of general modular invariants based on the modular completions of irreducible characters constructed above.Comment: 1+40 pages, no figure; v2 some points are clarified with respect to the `continuum limit', typos corrected, to appear in JHEP; v3 footnotes added in pages 18, 23 for the relation with arXiv:1407.7721[hep-th