Search for passing-through-walls neutrons constrains hidden braneworlds

In many theoretical frameworks our visible world is a $3$-brane, embedded in a multidimensional bulk, possibly coexisting with hidden braneworlds. Some works have also shown that matter swapping between braneworlds can occur. Here we report the results of an experiment - at the Institut Laue-Langevin (Grenoble, France) - designed to detect thermal neutron swapping to and from another braneworld, thus constraining the probability $p^2$ of such an event. The limit, $p<4.6\times 10^{-10}$ at $95 \%$ C.L., is $4$ orders of magnitude better than the previous bound based on the disappearance of stored ultracold neutrons. In the simplest braneworld scenario, for two parallel Planck-scale branes separated by a distance $d$, we conclude that $d>87$ in Planck length units.Comment: 5 pages, 3 figures. Published in Physics Letters

Etude Clinique des niveaux de perturbation de la metacognition, de la cognition sociale et du contrôle exécutif dans la pathologie frontale

Recent and convergent studies in neuropsychology have suggested the importance of frontal regions to the integrity of a number of functions such as metamemory capacities, executive functions, and social skills (Theory of Mind : ToM). In this original work, following Stuss et Anderson (2004), we assume a link between disturbances of these functions. We proposed to 16 frontal patients and 20 matched healthy subjects a protocol designed to test metamemory, ToM and executive functions in order to analyze the relations between disturbances of self-awareness (metamemory) and awareness of others (ToM), and cognitive control (executive functions). Our results confirm the importance of frontal lobes on these capacities. No correlation was found between measures of metamemory, measures of ToM and executive scores. The observation of individual profiles emphasizes the existence of dissociations between self awareness and consciousness of the others, and between these two forms of metacognitive control and the executive functioning. These results confirm the importance to engage more studies combining aspects of ToM, metacognition and executive control, to better understand the organization and architecture of the functions supported by frontal lobe

Contrôle exécutif, cognition sociale, émotions et métacognition

Cette synthèse aborde la question de la cognition sociale (théorie de l’esprit en particulier), du traitement des émotions et de la métacognition dans une perspective de neuropsychologie clinique. Nous nous attardons sur les études examinant les relations qu’entretiennent ces différents aspects du comportement humain avec les fonctions exécutives et les structures frontales. Les résultats rapportés montrent que les liens potentiels entre la théorie de l’esprit et le fonctionnement exécutif font encore beaucoup débat, et que l’étude des relations entre théorie de l’esprit et lobe frontal mérite d’être affinée. Les lésions frontales perturbent le traitement des émotions, mais les relations entre perturbation des fonctions exécutives et troubles du traitement des émotions restent inexplorées. La métacognition a été peu étudiée chez les patients dysexécutifs par lésions frontales, si ce n’est au travers de quelques études sur la métamémoire qui montrent que les patients frontaux ont globalement tendance à surestimer leurs performances. Cette surestimation ne semble pas nécessairement procéder d’un déficit exécutif, d’une incapacité de jugement, ni d’une méconnaissance du fonctionnement mnésique normal et pathologique. Il ne s’agit pas non plus d’une difficulté d’utilisation de connaissances. De plus, les différentes mesures métamnésiques obtenues chez les patients frontaux corrèlent peu entre elles, indiquant qu’elles engagent probablement des processus du contrôle métamnésique relativement indépendants qu’il conviendrait de spécifier. Enfin, il faudra aussi vérifier, avec des malades porteurs de lésions frontales et/ou de syndromes dysexécutifs, les propositions théoriques les plus récentes voulant que les concepts de théorie de l’esprit et de métacognition soient finalement assez proches

Bilingualism and adult differences in inhibitory mechanisms: Evidence from a bilingual stroop task

The present investigation examined the functioning of inhibitory mechanisms in younger and older bilinguals using a bilingual version of the Stroop test. The study predicted different patterns of age related decline in inhibitory mechanisms (inter- and intralingual interference) in bilinguals depending on their level of proficiency. Consistent with expectations, older bilinguals were slower when they responded in their non-dominant language. Furthermore, older unbalanced bilinguals showed greater interlingual interference when they responded with their second language to visual stimuli written in their dominant language. Balanced bilinguals showed equivalent interference effects between all conditions. These findings suggest that manipulating two languages may enhance the efficiency of inhibitory mechanisms

Novel lines of Pax6-/- embryonic stem cells exhibit reduced neurogenic capacity without loss of viability

<p>Abstract</p> <p>Background</p> <p>Embryonic stem (ES) cells can differentiate into all cell types and have been used extensively to study factors affecting neuronal differentiation. ES cells containing mutations in known genes have the potential to provide useful in vitro models for the study of gene function during neuronal differentiation. Recently, mouse ES cell lines lacking the neurogenic transcription factor Pax6 were reported; neurons derived from these <it>Pax6</it>^-/-ES cells died rapidly after neuronal differentiation in vitro.</p> <p>Results</p> <p>Here we report the derivation of new lines of <it>Pax6</it>^-/-ES cells and the assessment of their ability to survive and differentiate both in vitro and in vivo. Neurons derived from our new <it>Pax6</it>^-/-lines were viable and continued to elaborate processes in culture under conditions that resulted in the death of neurons derived from previously reported <it>Pax6</it>^-/-ES cell lines. The new lines of <it>Pax6</it>^-/-ES cells showed reduced neurogenic potential, mimicking the effects of loss of Pax6 in vivo. We used our new lines to generate <it>Pax6</it>^-/-↔ <it>Pax6</it>^+/+chimeras in which the mutant cells survived and displayed the same phenotypes as <it>Pax6</it>^-/-cells in <it>Pax6</it>^-/-↔ <it>Pax6</it>^+/+chimeras made by embryo aggregation.</p> <p>Conclusions</p> <p>We suggest that loss of Pax6 from ES cells reduces their neurogenic capacity but does not necessarily result in the death of derived neurons. We offer these new lines as additional tools for those interested in the generation of chimeras and the analysis of in vitro ES cell models of Pax6 function during neuronal differentiation, embryonic and postnatal development.</p

Combined loss of the BH3-only proteins Bim and Bmf restores B-cell development and function in TACI-Ig transgenic mice.

Terminal differentiation of B cells depends on two interconnected survival pathways, elicited by the B-cell receptor (BCR) and the BAFF receptor (BAFF-R), respectively. Loss of either signaling pathway arrests B-cell development. Although BCR-dependent survival depends mainly on the activation of the v-AKT murine thymoma viral oncogene homolog 1 (AKT)/PI3-kinase network, BAFF/BAFF-R-mediated survival engages non-canonical NF-κB signaling as well as MAPK/extracellular-signal regulated kinase and AKT/PI3-kinase modules to allow proper B-cell development. Plasma cell survival, however, is independent of BAFF-R and regulated by APRIL that signals NF-κB activation via alternative receptors, that is, transmembrane activator and CAML interactor (TACI) or B-cell maturation (BCMA). All these complex signaling events are believed to secure survival by increased expression of anti-apoptotic B-cell lymphoma 2 (Bcl2) family proteins in developing and mature B cells. Curiously, how lack of BAFF- or APRIL-mediated signaling triggers B-cell apoptosis remains largely unexplored. Here, we show that two pro-apoptotic members of the 'Bcl2 homology domain 3-only' subgroup of the Bcl2 family, Bcl2 interacting mediator of cell death (Bim) and Bcl2 modifying factor (Bmf), mediate apoptosis in the context of TACI-Ig overexpression that effectively neutralizes BAFF as well as APRIL. Surprisingly, although Bcl2 overexpression triggers B-cell hyperplasia exceeding the one observed in Bim(-/-)Bmf(-/-) mice, Bcl2 transgenic B cells remain susceptible to the effects of TACI-Ig expression in vivo, leading to ameliorated pathology in Vav-Bcl2 transgenic mice. Together, our findings shed new light on the molecular machinery restricting B-cell survival during development, normal homeostasis and under pathological conditions. Our data further suggest that Bcl2 antagonists might improve the potency of BAFF/APRIL-depletion strategies in B-cell-driven pathologies

Cryptosporidium parvum, a potential cause of colic adenocarcinoma

<p>Abstract</p> <p>Background</p> <p>Cryptosporidiosis represents a major public health problem. This infection has been reported worldwide as a frequent cause of diarrhoea. Particularly, it remains a clinically significant opportunistic infection among immunocompromised patients, causing potentially life-threatening diarrhoea in HIV-infected persons. However, the understanding about different aspects of this infection such as invasion, transmission and pathogenesis is problematic. Additionally, it has been difficult to find suitable animal models for propagation of this parasite. Efforts are needed to develop reproducible animal models allowing both the routine passage of different species and approaching unclear aspects of <it>Cryptosporidium </it>infection, especially in the pathophysiology field.</p> <p>Results</p> <p>We developed a model using adult severe combined immunodeficiency (SCID) mice inoculated with <it>Cryptosporidium parvum </it>or <it>Cryptosporidium muris </it>while treated or not with Dexamethasone (Dex) in order to investigate divergences in prepatent period, oocyst shedding or clinical and histopathological manifestations. <it>C. muris</it>-infected mice showed high levels of oocysts excretion, whatever the chemical immunosuppression status. Pre-patent periods were 11 days and 9.7 days in average in Dex treated and untreated mice, respectively. Parasite infection was restricted to the stomach, and had a clear preferential colonization for fundic area in both groups. Among <it>C. parvum</it>-infected mice, Dex-treated SCID mice became chronic shedders with a prepatent period of 6.2 days in average. <it>C. parvum</it>-inoculated mice treated with Dex developed glandular cystic polyps with areas of intraepithelial neoplasia, and also with the presence of intramucosal adenocarcinoma.</p> <p>Conclusion</p> <p>For the first time <it>C. parvum </it>is associated with the formation of polyps and adenocarcinoma lesions in the gut of Dex-treated SCID mice. Additionally, we have developed a model to compare chronic <it>muris </it>and <it>parvum </it>cryptosporidiosis using SCID mice treated with corticoids. This reproducible model has facilitated the evaluation of clinical signs, oocyst shedding, location of the infection, pathogenicity, and histopathological changes in the gastrointestinal tract, indicating divergent effects of Dex according to <it>Cryptosporidium </it>species causing infection.</p

Alteration of Blood–Brain Barrier Integrity by Retroviral Infection

The blood–brain barrier (BBB), which forms the interface between the blood and the cerebral parenchyma, has been shown to be disrupted during retroviral-associated neuromyelopathies. Human T Lymphotropic Virus (HTLV-1) Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP) is a slowly progressive neurodegenerative disease associated with BBB breakdown. The BBB is composed of three cell types: endothelial cells, pericytes and astrocytes. Although astrocytes have been shown to be infected by HTLV-1, until now, little was known about the susceptibility of BBB endothelial cells to HTLV-1 infection and the impact of such an infection on BBB function. We first demonstrated that human cerebral endothelial cells express the receptors for HTLV-1 (GLUT-1, Neuropilin-1 and heparan sulfate proteoglycans), both in vitro, in a human cerebral endothelial cell line, and ex vivo, on spinal cord autopsy sections from HAM/TSP and non-infected control cases. In situ hybridization revealed HTLV-1 transcripts associated with the vasculature in HAM/TSP. We were able to confirm that the endothelial cells could be productively infected in vitro by HTLV-1 and that blocking of either HSPGs, Neuropilin 1 or Glut1 inhibits this process. The expression of the tight-junction proteins within the HTLV-1 infected endothelial cells was altered. These cells were no longer able to form a functional barrier, since BBB permeability and lymphocyte passage through the monolayer of endothelial cells were increased. This work constitutes the first report of susceptibility of human cerebral endothelial cells to HTLV-1 infection, with implications for HTLV-1 passage through the BBB and subsequent deregulation of the central nervous system homeostasis. We propose that the susceptibility of cerebral endothelial cells to retroviral infection and subsequent BBB dysfunction is an important aspect of HAM/TSP pathogenesis and should be considered in the design of future therapeutics strategies

Neuron-glia cross talk in rat striatum after transient forebrain ischemia

Striatum is highly vulnerable to transient forebrain ischemia induced by the 4 vessel occlusion (4V0) method (Brierley 1976. Pulsinelli et al. 1982, Zini et al. 1990a). Massive degeneration and loss of Nissl-stained neurons occur within 24 hr from an ischemia of long duration (30 min) (Pulsinelli et al. 1982). Neuronal loss is mainly restricted to the lateral part of caudate-putamen (Pulsinelli et al. 1982, Zini et al. 1990a). Cellular alterations include loss of medium-size spiny projection neurons (Pulsinelli et al. 1982, Francis and Pulsinelli 1982), largely corresponding to dopaminoceptive neurons (Benfenati et al. 1989, Zoli et al. 1989), and increase in reactive astrocytes (Pulsinelli et al. 1982, Grimaldi et al. 1990) and microglia (Gehrmann et al. 1982). On the other hand, large cholinergie (Francis and Pulsinelli 1982) and medium-size aspiny somatostatin (SS)/neuropeptide Y (NPY)-containing interneurons are resistant to the ischemic insult (Pulsinelli et al. 1982, Grimaldi et al. 1990). In a few instances, such as in the case of SS and NPY immunoreactivity (IR), the initial loss is followed by full recovery within 7 (SS) or 40 (NPY) days post-ischemia (Grimaldi et al. 1990). However, it is not known whether some kind of recovery is present for the bulk of medium-size spiny projections neurons after the first days post-ischemia