Optimization of sample preparation for MRI of formaldehyde-fixed brains

International audienceMagnetic resonance imaging of post-mortem brains allows long acquisition times up to several days and can be used to obtain high-resolution images at high field (7 T) which can be readily correlated with histological examination of the tissue. However, death and formaldehyde fixation are known to modify severely the relaxivity and diffusion properties of brain tissue. In particular, formaldehyde is known to shorten T2, which drastically reduces SNR.In order to counteract this effect and recover better SNR, free fixative can be washed out by soaking the sample in isotonic saline solution. This has been demonstrated in small biopsy-sized tissue samples, but little data is available concerning whole brain specimens.This study was designed to describe the kinetics of the change of relaxivity and diffusion properties of whole brain specimen at 7 T, during fixation, and during soaking in saline solution, in order to determine optimal soaking times.In the ewe brain, the fixation was found to stabilize after approximately 8 weeks, and the optimal duration of saline soaking is found to be around 3 weeks. These durations can be expected to be longer for larger specimen, such as human brains, which require longer penetration times

La sépulture collective mégalithique de Cabrials (Béziers, Hérault). Une petite allée sépulcrale enterrée du début du Néolithique final

La structure fouillée en novembre 2007 au lieu-dit « Cabrials » est un petit monument de la fin du Néolithique. Il a été installé dans une excavation oblongue d’environ 3 m par 1,50 m et se compose de 9 orthostates, tous retouchés, soigneusement ajustés et bloqués par de plus petites pierres. Tous les orthostates des parois sont des stèles frustes ou des éléments d’architecture remployés. Les dalles de couvertures ont été arrachées par les labours. Une seule a été retrouvée à proximité. Elle présente la même taille et forme que les autres. Par contre, il ne subsiste aucun indice relatif à une plausible signalisation.La chambre présente un plan rectangulaire de 1,50 m par 0,70 m et une hauteur d’environ 0,90 m. Son grand axe est orienté nord-ouest/sud-est. On entrait dans la chambre par le biais d’une fosse accolée à son petit côté nord-ouest, qui correspond à un couloir embryonnaire court ou, encore, au débouché d’un couloir en partie aérien. Cet accès et la chambre sont séparés par une dalle amovible, appuyée sur deux piliers. Cette configuration, chambre longue unique, enterrée, à laquelle on accède par un couloir frontal également excavé, se rapproche typologiquement d’une allée sépulcrale enterrée. Il s’agit en l’occurrence d’un très petit monument mais son caractère mégalithique est incontestable, de même que son fonctionnement collectif. Cette tombe concerne, en effet, 19 individus au minimum, dont les inhumations ont été échelonnées dans le temps. Les dépôts ont été remaniés de manière importante en au moins deux phases principales.La condamnation de la sépulture pose problème, car il s’agit d’une procédure réalisée longtemps après le dernier dépôt.Les jeunes immatures sont sur-représentés, ce qui est surprenant pour ce type de sépulture. Par ailleurs, la durée d’utilisation semble courte, ce que suggère aussi la forte cohérence typologique du mobilier, dont toutes les composantes se rapportent au Néolithique final 1. Les datations 14C évoquent de manière concordante une fréquentation située autour de 3300 B.C. Le mobilier se compose d’un grand vase de stockage issu de la sphère domestique, de quelques outils lithiques et de différents éléments dont la distribution est relativement conforme à celle observée pour de plus grandes sépultures collectives, notamment dans le nord de la France.Enfin, la chronologie de ce monument un peu antérieure au plein développement des sépultures collectives mégalithiques en Languedoc, sa taille modeste et son fonctionnement particulier évoquent des traits intermédiaires entre des petits coffres lithiques du Néolithique moyen et de plus grandes sépultures, plus longuement utilisées, du Néolithique final.The structure excavated in November 2007 at the locality “Cabrials” is a small monument dating from the end of the Neolithic. It is set in an oblong excavation of approximately 3 m by 1.50 m and is composed of 9 orthostats, all retouched, carefully fitted together and blocked by smaller stones. All the orthostats of the walls are made up of rough stelae and re-used architectural elements. The covering slabs were torn off by ploughing. Only one slab was found in the vicinity, showing the same size as the others. On the other hand, there is no indication of a plausible marker.The chamber has a rectangular plan of 1.50 m by 0.70 m and a height of approximately 0.90 m. The long axis is oriented north-west/south-east. The chamber is entered via by a pit backing onto the short north-western side, corresponding to a short embryonic passage or to a partly open-air passage. This access is separated from the chamber by a removable capstone, resting on two pillars. This configuration, consisting of a single long burial chamber with a frontal access that is also below ground level, is typologically very similar to an underground gallery grave. While the monument is very small, its megalithic character is undeniable, in the same way as its collective function. Indeed, this tomb concerns at least 19 individuals, whose burials were spread out over time. The deposits were significantly re-used in at least two main phases.The concealing of the burial chamber is problematic, because it involved a procedure carried out a long time after the last deposit.Immature young individuals are over-represented, which is surprising for this type of burial. In addition, the utilization period seems short, which is also suggested by the strong typological coherence of the goods, with all the components being related to the final Neolithic 1. The 14C dating consistently indicates use of the site around 3300 B.C. Burial goods are composed of a large storage vase derived from the domestic sphere, some lithic tools and various elements whose distribution is relatively consistent with that observed for larger collective burials, in particular in the north of France.Lastly, the age of this monument, which is slightly earlier than the full development of megalithic collective burials in Languedoc, along with its modest size and its particular mode of functioning, evoke features that are intermediate between the small cists of the Middle Neolithic and the larger burial structures of the Final Neolithic, which were used for longer periods of time

The political import of deconstruction—Derrida’s limits?: a forum on Jacques Derrida’s specters of Marx after 25 Years, part I

Jacques Derrida delivered the basis of The Specters of Marx: The State of the Debt, the Work of Mourning, & the New International as a plenary address at the conference ‘Whither Marxism?’ hosted by the University of California, Riverside, in 1993. The longer book version was published in French the same year and appeared in English and Portuguese the following year. In the decade after the publication of Specters, Derrida’s analyses provoked a large critical literature and invited both consternation and celebration by figures such as Antonio Negri, Wendy Brown and Frederic Jameson. This forum seeks to stimulate new reflections on Derrida, deconstruction and Specters of Marx by considering how the futures past announced by the book have fared after an eventful quarter century. Maja Zehfuss, Antonio Vázquez-Arroyo and Dan Bulley and Bal Sokhi-Bulley offer sharp, occasionally exasperated, meditations on the political import of deconstruction and the limits of Derrida’s diagnoses in Specters of Marx but also identify possible paths forward for a global politics taking inspiration in Derrida’s work of the 1990s

The Cellular Prion Protein Interacts with the Tissue Non-Specific Alkaline Phosphatase in Membrane Microdomains of Bioaminergic Neuronal Cells

BACKGROUND: The cellular prion protein, PrP(C), is GPI anchored and abundant in lipid rafts. The absolute requirement of PrP(C) in neurodegeneration associated to prion diseases is well established. However, the function of this ubiquitous protein is still puzzling. Our previous work using the 1C11 neuronal model, provided evidence that PrP(C) acts as a cell surface receptor. Besides a ubiquitous signaling function of PrP(C), we have described a neuronal specificity pointing to a role of PrP(C) in neuronal homeostasis. 1C11 cells, upon appropriate induction, engage into neuronal differentiation programs, giving rise either to serotonergic (1C11(5-HT)) or noradrenergic (1C11(NE)) derivatives. METHODOLOGY/PRINCIPAL FINDINGS: The neuronal specificity of PrP(C) signaling prompted us to search for PrP(C) partners in 1C11-derived bioaminergic neuronal cells. We show here by immunoprecipitation an association of PrP(C) with an 80 kDa protein identified by mass spectrometry as the tissue non-specific alkaline phosphatase (TNAP). This interaction occurs in lipid rafts and is restricted to 1C11-derived neuronal progenies. Our data indicate that TNAP is implemented during the differentiation programs of 1C11(5-HT) and 1C11(NE) cells and is active at their cell surface. Noteworthy, TNAP may contribute to the regulation of serotonin or catecholamine synthesis in 1C11(5-HT) and 1C11(NE) bioaminergic cells by controlling pyridoxal phosphate levels. Finally, TNAP activity is shown to modulate the phosphorylation status of laminin and thereby its interaction with PrP. CONCLUSION/SIGNIFICANCE: The identification of a novel PrP(C) partner in lipid rafts of neuronal cells favors the idea of a role of PrP in multiple functions. Because PrP(C) and laminin functionally interact to support neuronal differentiation and memory consolidation, our findings introduce TNAP as a functional protagonist in the PrP(C)-laminin interplay. The partnership between TNAP and PrP(C) in neuronal cells may provide new clues as to the neurospecificity of PrP(C) function

Present eternity : quests of temporality in the literary production of the "extrême contemporain" in France (The Writings of Dominique Fourcade and Emmanuel Hocquard)

The term \uab extr\ueame contemporain \ubb is an expression currently used by scholars to indicate the French literary production of the last 20 years. This term was used in a work of literature for the first time by the French poet Dominique Fourcade in 1986 (\uc9l\ue9gie L apostrophe E.C.) in reference to an epoch, but also to a new sense of experiencing time and space in the so-called \uab age of digital reproducibility \ubb. The aim of this paper is to consider how the change in temporal protocols due to the triumph of Big Optics (Paul Virilio) affects the sense of teleology (destiny) and the quest for experience in French contemporary poetry (in particular, in the genre of the elegy). Including both memory and anticipation, the \uab extr\ueame contemporain \ubb production seems to prefer the \u201ctime of now\u201d, Jetz-zeit in Benjamin\u2019s words, to past or testimony, and speaks to the present, whose responsibility is to give voice to a space where everything is simply allowed to happen

Disrupted lymph node and splenic stroma in mice with induced inflammatory melanomas is associated with impaired recruitment of T and dendritic cells

International audienceMigration of dendritic cells (DC) from the tumor environment to the T cell cortex in tumor-draining lymph nodes (TDLN) is essential for priming naïve T lymphocytes (TL) to tumor antigen (Ag). We used a mouse model of induced melanoma in which similar oncogenic events generate two phenotypically distinct melanomas to study the influence of tumor-associated inflammation on secondary lymphoid organ (SLO) organization. One tumor promotes inflammatory cytokines, leading to mobilization of immature myeloid cells (iMC) to the tumor and SLO; the other does not. We report that inflammatory tumors induced alterations of the stromal cell network of SLO, profoundly altering the distribution of TL and the capacity of skin-derived DC and TL to migrate or home to TDLN. These defects, which did not require tumor invasion, correlated with loss of fibroblastic reticular cells in T cell zones and in impaired production of CCL21. Infiltrating iMC accumulated in the TDLN medulla and the splenic red pulp. We propose that impaired function of the stromal cell network during chronic inflammation induced by some tumors renders spleens non-receptive to TL and TDLN non-receptive to TL and migratory DC, while the entry of iMC into these perturbed SLO is enhanced. This could constitute a mechanism by which inflammatory tumors escape immune control. If our results apply to inflammatory tumors in general, the demonstration that SLO are poorly receptive to CCR7-dependent migration of skin-derived DC and naïve TL may constitute an obstacle for proposed vaccination or adoptive TL therapies of their hosts

TSPO ligands stimulate ZnPPIX transport and ROS accumulation leading to the inhibition of P. falciparum growth in human blood

After invading red blood cells (RBCs), Plasmodium falciparum (Pf) can export its own proteins to the host membrane and activate endogenous channels that are present in the membrane of RBCs. This transport pathway involves the Voltage Dependent Anion Channel (VDAC). Moreover, ligands of the VDAC partner TranSlocator PrOtein (TSPO) were demonstrated to inhibit the growth of the parasite. We studied the expression of TSPO and VDAC isoforms in late erythroid precursors, examined the presence of these proteins in membranes of non-infected and infected human RBCs, and evaluated the efficiency of TSPO ligands in inhibiting plasmodium growth, transporting the haem analogue Zn-protoporphyrin-IX (ZnPPIX) and enhancing the accumulation of reactive oxygen species (ROS). TSPO and VDAC isoforms are differentially expressed on erythroid cells in late differentiation states. TSPO2 and VDAC are present in the membranes of mature RBCs in a unique protein complex that changes the affinity of TSPO ligands after Pf infection. TSPO ligands dose-dependently inhibited parasite growth, and this inhibition was correlated to ZnPPIX uptake and ROS accumulation in the infected RBCs. Our results demonstrate that TSPO ligands can induce Pf death by increasing the uptake of porphyrins through a TSPO2-VDAC complex, which leads to an accumulation of ROS

A many-analysts approach to the relation between religiosity and well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N=10,535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β=0.120). For the second research question, this was the case for 65% of the teams (median reported β=0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates

A Many-analysts Approach to the Relation Between Religiosity and Well-being

The relation between religiosity and well-being is one of the most researched topics in the psychology of religion, yet the directionality and robustness of the effect remains debated. Here, we adopted a many-analysts approach to assess the robustness of this relation based on a new cross-cultural dataset (N = 10, 535 participants from 24 countries). We recruited 120 analysis teams to investigate (1) whether religious people self-report higher well-being, and (2) whether the relation between religiosity and self-reported well-being depends on perceived cultural norms of religion (i.e., whether it is considered normal and desirable to be religious in a given country). In a two-stage procedure, the teams first created an analysis plan and then executed their planned analysis on the data. For the first research question, all but 3 teams reported positive effect sizes with credible/confidence intervals excluding zero (median reported β = 0.120). For the second research question, this was the case for 65% of the teams (median reported β = 0.039). While most teams applied (multilevel) linear regression models, there was considerable variability in the choice of items used to construct the independent variables, the dependent variable, and the included covariates