Humans Lack iGb3 Due to the Absence of Functional iGb3-Synthase: Implications for NKT Cell Development and Transplantation

The glycosphingolipid isoglobotrihexosylceramide, or isogloboside 3 (iGb3), is believed to be critical for natural killer T (NKT) cell development and self-recognition in mice and humans. Furthermore, iGb3 may represent an important obstacle in xenotransplantation, in which this lipid represents the only other form of the major xenoepitope Galα(1,3)Gal. The role of iGb3 in NKT cell development is controversial, particularly with one study that suggested that NKT cell development is normal in mice that were rendered deficient for the enzyme iGb3 synthase (iGb3S). We demonstrate that spliced iGb3S mRNA was not detected after extensive analysis of human tissues, and furthermore, the iGb3S gene contains several mutations that render this product nonfunctional. We directly tested the potential functional activity of human iGb3S by expressing chimeric molecules containing the catalytic domain of human iGb3S. These hybrid molecules were unable to synthesize iGb3, due to at least one amino acid substitution. We also demonstrate that purified normal human anti-Gal immunoglobulin G can bind iGb3 lipid and mediate complement lysis of transfected human cells expressing iGb3. Collectively, our data suggest that iGb3S is not expressed in humans, and even if it were expressed, this enzyme would be inactive. Consequently, iGb3 is unlikely to represent a primary natural ligand for NKT cells in humans. Furthermore, the absence of iGb3 in humans implies that it is another source of foreign Galα(1,3)Gal xenoantigen, with obvious significance in the field of xenotransplantation

RAPA (Polinesia Francesa) (Isla). Cartas náuticas. 1878 (1867). 1:20000

Presenta dos perspectivas de la isla de Rapa en el Polinesia Francesa se determinan los números de sonda y veriles, y fondeaderos principalesEscala gráfica en millas marinasIndica veriles y sondas batimétricas y gráfico de declinación magnéticaRelieve representado por normales y puntos acotadosEn los angulos superior e inferior derechos se señalan el número de referencia y el precio, respectivamenteCopia digital. Madrid : Ministerio de Cultura. Dirección General del Libro, Archivos y Bibliotecas, 201

Front Matter

The carbohydrate Galα1-3Galβ1-(3)4GlcNAc-R (α-Gal) is produced in all mammals except for humans, apes and old world monkeys that lost the ability to synthetize this carbohydrate. Therefore, humans can produce high antibody titers against α-Gal. Anti-α-Gal IgE antibodies have been associated with tick-induced allergy (i.e. α-Gal syndrome) and anti-α-Gal IgG/IgM antibodies may be involved in protection against malaria, leishmaniasis and Chagas disease. The α-Gal on tick salivary proteins plays an important role in the etiology of the α-Gal syndrome. However, whether ticks are able to produce endogenous α-Gal remains currently unknown. In this study, the Ixodes scapularis genome was searched for galactosyltransferases and three genes were identified as potentially involved in the synthesis of α-Gal. Heterologous gene expression in α-Gal-negative cells and gene knockdown in ticks confirmed that these genes were involved in α-Gal synthesis and are essential for tick feeding. Furthermore, these genes were shown to play an important role in tick-pathogen interactions. Results suggested that tick cells increased α-Gal levels in response to Anaplasma phagocytophilum infection to control bacterial infection. These results provided the molecular basis of endogenous α-Gal production in ticks and suggested that tick galactosyltransferases are involved in vector development, tick-pathogen interactions and possibly the etiology of α-Gal syndrome in humans.This research was supported by the Consejería de Educación, Cultura y Deportes, JCCM, Spain, project CCM17-PIC-036 (SBPLY/17/180501/000185). JJV was supported by Project FIT (Pharmacology, Immunotherapy, nanoToxicology), funded by the European Regional Development Fund.Peer Reviewe

Boomerang: Rebounding the consequences of reputation feedback on crowdsourcing platforms

Paid crowdsourcing platforms suffer from low-quality workand unfair rejections, but paradoxically, most workers and requesters have high reputation scores. These inflated scores, which make high-quality work and workers difficult to find,stem from social pressure to avoid giving negative feedback. We introduce Boomerang, a reputation system for crowdsourcing that elicits more accurate feedback by rebounding the consequences of feedback directly back onto the person who gave it. With Boomerang, requesters find that their highly rated workers gain earliest access to their future tasks, and workers find tasks from their highly-rated requesters at the top of their task feed. Field experiments verify that Boomerang causes both workers and requesters to provide feedback that is more closely aligned with their private opinions. Inspired by a game-theoretic notion of incentive-compatibility, Boomerang opens opportunities for interaction design to incentivize honest reporting over strategic dishonesty

Qualitative questionnaire for the identification of cognems (Qualiquic): an exploratory technique to identify social representation contents and relations

While the investigation of social representation contents through the analysis of word associations is convenient, it does not directly inform about the nature of relationships that representation elements maintain with the social object. This paper presents a qualitative technique, Qualiquic, that is easy and simple to administer. Qualiquic has the advantage of gathering representation contents characterized by their relationships with the representation object, based on a simplified list of descriptive, practical, and evaluative connectors of the basic cognitive schemes model. The underlying theoretical principles are explained, and empirical guidelines are provided, as well as an empirical example of use

Taxonomic and Environmental Variability in the Elemental Composition and Stoichiometry of Individual Dinoflagellate and Diatom Cells from the NW Mediterranean Sea

Here we present, for the first time, the elemental concentration, including C, N and O, of single phytoplankton cells collected from the sea. Plankton elemental concentration and stoichiometry are key variables in phytoplankton ecophysiology and ocean biogeochemistry, and are used to link cells and ecosystems. However, most field studies rely on bulk techniques that overestimate carbon and nitrogen because the samples include organic matter other than plankton organisms. Here we used X-ray microanalysis (XRMA), a technique that, unlike bulk analyses, gives simultaneous quotas of C, N, O, Mg, Si, P, and S, in single-cell organisms that can be collected directly from the sea. We analysed the elemental composition of dinoflagellates and diatoms (largely Chaetoceros spp.) collected from different sites of the Catalan coast (NW Mediterranean Sea). As expected, a lower C content is found in our cells compared to historical values of cultured cells. Our results indicate that, except for Si and O in diatoms, the mass of all elements is not a constant fraction of cell volume but rather decreases with increasing cell volume. Also, diatoms are significantly less dense in all the measured elements, except Si, compared to dinoflagellates. The N:P ratio of both groups is higher than the Redfield ratio, as it is the N:P nutrient ratio in deep NW Mediterranean Sea waters (N:P = 20–23). The results suggest that the P requirement is highest for bacterioplankton, followed by dinoflagellates, and lowest for diatoms, giving them a clear ecological advantage in P-limited environments like the Mediterranean Sea. Finally, the P concentration of cells of the same genera but growing under different nutrient conditions was the same, suggesting that the P quota of these cells is at a critical level. Our results indicate that XRMA is an accurate technique to determine single cell elemental quotas and derived conversion factors used to understand and model ocean biogeochemical cycles

Antibody Recognition of Cancer-Related Gangliosides and Their Mimics Investigated Using in silico Site Mapping

Modified gangliosides may be overexpressed in certain types of cancer, thus, they are considered a valuable target in cancer immunotherapy. Structural knowledge of their interaction with antibodies is currently limited, due to the large size and high flexibility of these ligands. In this study, we apply our previously developed site mapping technique to investigate the recognition of cancer-related gangliosides by anti-ganglioside antibodies. The results reveal a potential ganglioside-binding motif in the four antibodies studied, suggesting the possibility of structural convergence in the anti-ganglioside immune response. The structural basis of the recognition of ganglioside-mimetic peptides is also investigated using site mapping and compared to ganglioside recognition. The peptides are shown to act as structural mimics of gangliosides by interacting with many of the same binding site residues as the cognate carbohydrate epitopes. These studies provide important clues as to the structural basis of immunological mimicry of carbohydrates

La substitution dans les études de représentations sociales : quel processus impliqué ?

International audienceThis study of social representations aims at identifying the process involved in the responses produced with a substitution technique. Two alternative hypotheses are discussed: one that considers that substitution induces social comparison (Chokier and Moliner, 2006), the other suggesting that this technique leads to a reduction of normative pressures (Guimelli, 1998). In the research presented here, we studied the social representations of Drug addicts (in the tolerance towards the use of cannabis) and of Unemployed people, in order to compare the results with those obtained by Chokier and Moliner (2006) about security. With a specific population of students, these objects allowed us to manipulate two levels of distance to the object of representation. Concerning the technique of substitution, three levels of distance to the reference group (French people in general, Young people, Students) were combined into questionnaires with four types of instructions: standard, substitution, pro- and counter-normative. The PCA highlights a Guttman effect, which indicating that the responses produced with standard instruction are less normative than the responses produced with the substitution instruction to Young people. These results invalidate an explanation in terms of effect Primus Inter Pares. Globally, the results mainly show that the more the distance to the object is low and the distance to the reference group is high, the more the responses produce in substitution are seen as pro-normative and near from those produced with standard instruction. More specifically, we identified a number of inconsistencies with regard to what one could expect from an explanation of the phenomena in terms of personal versus social identity. As regards the representation of Unemployed people, the more the participants are closed to the reference group, the more the responses produced with an instruction of auto-valorization (pro-normative) are closed to those produced in substitution. However, on one hand, this result is observed only with the representation of Unemployed people, and, on the other hand, a social comparison explanation would suppose that the participants perceived the group of French people in general as homogeneous and identified themselves to this group at the same level than to the two other reference groups, which is unlikely. Finally, these results lead us to conclude that the substitution does not induce social comparison (Chokier and Moliner, 2006), but more probably reduction of normative pressures (Guimelli, 1998). It thus suggests that the study of masking effects through a substitution technique should take into account two parameters: distance to the object and distance to the reference group.Cette étude de représentations sociales permet d’identifier le processus impliqué dans les réponses produites avec une technique de substitution. Deux hypothèses alternatives sont discutées : l’une considère que la substitution induit un processus de comparaison sociale (Chokier et Moliner, 2006), l’autre suggère que cette technique entraîne une réduction des pressions normatives (Guimelli, 1998). Dans la recherche présentée ici, on étudiait les représentations sociales du Toxicomane (ici la tolérance vis-à-vis de la consommation de cannabis) et du Chômeur afin de comparer les résultats obtenus à ceux qu’obtiennent Chokier et Moliner (2006) à propos de la Sécurité. Avec une population spécifique, des Étudiants, ces objets permettent de manipuler deux niveaux de distance à l’objet de représentation. Concernant la technique de substitution, trois niveaux de distance au groupe de référence (Français en général, Jeunes, Étudiants) ont été combinés dans des questionnaires avec quatre types de consignes : standard, substitution, pro- et contre-normatives. L’ACP met en évidence un effet Guttman indiquant que les réponses en consigne standard sont moins normatives que les réponses produites en substitution aux Jeunes. On écarte ainsi une explication en termes d’effet Primus Inter Pares (PIP). De façon générale, les résultats montrent, principalement, que plus la distance à l’objet est faible et la distance au groupe de référence élevée, plus les réponses en substitution sont vues comme pro-normatives et proches des réponses standard. Le détail des résultats met quant à lui en évidence un certain nombre d’incohérences en regard de ce que l’on pourrait attendre d’une explication des phénomènes en termes d’identité sociale versus personnelle. Concernant la représentation du Chômeur, les réponses produites en consigne d’autovalorisation et celles produites en substitution sont d’autant plus proches que les groupes de références sont proches des participants, et cela quels que soient ces groupes de références. Toutefois, on constate, d’une part, que ce résultat ne s’observe qu’avec la représentation du Chômeur, et, d’autre part, qu’il faudrait alors conclure que les participants perçoivent le groupe des Français en général comme homogène et s’identifient à ce dernier au même degré qu’au deux autres groupes de référence. Finalement, ces résultats amènent à conclure que la consigne de substitution n’induit pas un processus de comparaison sociale (Chokier et Moliner, 2006), mais plus sûrement un processus de réduction des pressions normatives (Guimelli, 1998). On suggère ainsi que l’étude des effets de masquage par le biais d’une technique de substitution doit avoir pour préalable la prise en compte des deux paramètres que sont la distance à l’objet et la distance au groupe de référence

Absence du changement d’attitude consécutif à l’ajout d’une cognition consonante non justificatrice : nouvel apport pour le paradigme de la double soumission induite

International audienceIn the double forced compliance paradigm, attitude change does not appear any more after adding one cognition, which is consonant with the problematic behavior and justifies it. In our research, we have tested if adding one cognition which is only consonant with the problematic behavior affected the attitude change. Participants realized a counter-attitudinal essay in choice condition or in no-choice condition. After its completion, only half of the participants read their arguments. Reading was one cognition consonant with the problematic behavior without justifying it. In post-experimental phase, the attitude was measured. Our results showed that participants after reading their essay did not change their attitude any more. Our results specify the absence of attitude change in the paradigm of double compliance.Dans le paradigme de la double soumission induite, le changement d’attitude n’est plus observé après par l’ajout d’une cognition ayant un double statut. Elle est consonante avec le comportement problématique et justificatrice de ce dernier. Dans notre étude, nous avons testé l’effet de l’ajout d’une cognition consonante non justificatrice sur le changement d’attitude. La moitié des participants réalisaient librement un essai contre-attitudinal, l’autre pas. La moitié des participants lisaient leurs arguments, l’autre pas. La lecture des arguments constituait une cognition consonante avec l’essai contre-attitudinal, sans pour autant le justifier. En phase post-expérimentale, l’attitude envers l’essai était recueillie. Les résultats montrent que les participants n’avaient plus besoin de changer d’attitude après avoir lu leur essai contre-attitudinal. Nos résultats contribuent à préciser l’absence du changement d’attitude dans le paradigme de la double soumission induite