Modulation of brain activity during a Stroop inhibitory task by the kind of cognitive control required
Grandjean, Julien ; D'Ostilio, Kevin ; Phillips, Christophe et al
in PLoS ONE (2012), 7(7), 41513
This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control ... [more ▼]
This study used a proportion congruency manipulation in the Stroop task in order to investigate, at the behavioral and brain substrate levels, the predictions derived from the Dual Mechanisms of Control (DMC) account of two distinct modes of cognitive control depending on the task context. Three experimental conditions were created that varied the proportion congruency: mostly incongruent (MI), mostly congruent (MC), and mostly neutral (MN) contexts. A reactive control strategy, which corresponds to transient interference resolution processes after conflict detection, was expected for the rare conflicting stimuli in the MC context, and a proactive strategy, characterized by a sustained task-relevant focus prior to the occurrence of conflict, was expected in the MI context. Results at the behavioral level supported the proactive/reactive distinction, with the replication of the classic proportion congruent effect (i.e., less interference and facilitation effects in the MI context). fMRI data only partially supported our predictions. Whereas reactive control for incongruent trials in the MC context engaged the expected fronto-parietal network including dorsolateral prefrontal cortex (DLPFC) and anterior cingulate cortex, proactive control in the MI context was not associated with any sustained lateral prefrontal cortex activations, contrary to our hypothesis. Surprisingly, incongruent trials in the MI context elicited transient activation in common with incongruent trials in the MC context, especially in DLPFC, superior parietal lobe, and insula. This lack of sustained activity in MI is discussed in reference to the possible involvement of item-specific rather than list-wide mechanisms of control in the implementation of a high task-relevant focus. [less ▲]Detailed reference viewed: 28 (2 ULg)
Mesenchymal Stem Cell Graft Improves Recovery after Spinal Cord Injury in Adult Rats through Neurotrophic and Pro-Angiogenic Actions.
; Cantinieaux, Dorothée ; et al
in PLoS ONE (2012), 7(6), 39500
Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord ... [more ▼]
Numerous strategies have been managed to improve functional recovery after spinal cord injury (SCI) but an optimal strategy doesn't exist yet. Actually, it is the complexity of the injured spinal cord pathophysiology that begets the multifactorial approaches assessed to favour tissue protection, axonal regrowth and functional recovery. In this context, it appears that mesenchymal stem cells (MSCs) could take an interesting part. The aim of this study is to graft MSCs after a spinal cord compression injury in adult rat to assess their effect on functional recovery and to highlight their mechanisms of action. We found that in intravenously grafted animals, MSCs induce, as early as 1 week after the graft, an improvement of their open field and grid navigation scores compared to control animals. At the histological analysis of their dissected spinal cord, no MSCs were found within the host despite their BrdU labelling performed before the graft, whatever the delay observed: 7, 14 or 21 days. However, a cytokine array performed on spinal cord extracts 3 days after MSC graft reveals a significant increase of NGF expression in the injured tissue. Also, a significant tissue sparing effect of MSC graft was observed. Finally, we also show that MSCs promote vascularisation, as the density of blood vessels within the lesioned area was higher in grafted rats. In conclusion, we bring here some new evidences that MSCs most likely act throughout their secretions and not via their own integration/differentiation within the host tissue. [less ▲]Detailed reference viewed: 25 (10 ULg)
Polymorphus Minutus Affects Antitoxic Responses of Gammarus Roeseli Exposed to Cadmium
Gismondi, Eric ; ;
in PLoS ONE (2012), 7
Dre-miR-2188 Targets Nrp2a and Mediates Proper Intersegmental Vessel Development in Zebrafish Embryos.
; ; et al
in PLoS ONE (2012), 7(6), 39417
BACKGROUND: MicroRNAs (miRNAs) are a class of small RNAs that are implicated in the control of eukaryotic gene expression by binding to the 3'UTR of target mRNAs. Several algorithms have been developed ... [more ▼]
BACKGROUND: MicroRNAs (miRNAs) are a class of small RNAs that are implicated in the control of eukaryotic gene expression by binding to the 3'UTR of target mRNAs. Several algorithms have been developed for miRNA target prediction however, experimental validation is still essential for the correct identification of miRNA targets. We have recently predicted that Neuropilin2a (Nrp2a), a vascular endothelial growth factor receptor which is essential for normal developmental angiogenesis in zebrafish, is a dre-miR-2188 target. METHODOLOGY: Here we show that dre-miR-2188 targets the 3'-untranslated region (3'UTR) of Nrp2a mRNA and is implicated in proper intersegmental vessel development in vivo. Over expression of miR-2188 in zebrafish embryos down regulates Nrp2a expression and results in intersegmental vessel disruption, while its silencing increases Nrp2a expression and intersegmental vessel sprouting. An in vivo GFP sensor assay based on a fusion between the GFP coding region and the Nrp2a 3'UTR confirms that miR-2188 binds to the 3'UTR of Nrp2a and inhibits protein translation. CONCLUSIONS: We demonstrate that miR-2188 targets Nrp2a and affects intersegmental vessel development in zebrafish embryos. [less ▲]Detailed reference viewed: 15 (1 ULg)
Effect of Multiple Parasitic Infections on the Tolerance to Pollutant Contamination
Gismondi, Eric ; ; et al
in PLoS ONE (2012), 7Detailed reference viewed: 6 (0 ULg)
Phylogeography, risk factors and genetic history of hepatitis C virus in Gabon, central Africa.
; ; et al
in PLoS ONE (2012), 7(8), 42002
BACKGROUND: The epidemiological and molecular characteristics of hepatitis C virus (HCV) infection in the general population have been poorly investigated in Africa. The aim of this study was to determine ... [more ▼]
BACKGROUND: The epidemiological and molecular characteristics of hepatitis C virus (HCV) infection in the general population have been poorly investigated in Africa. The aim of this study was to determine the prevalence, genotype distribution and epidemic history of HCV in the Gabonese general population. METHODS/PRINCIPAL FINDINGS: A total of 4042 sera collected from adults in 220 villages in all nine administrative areas of the country were screened for antibodies to HCV. HCV NS5B region sequencing was performed for molecular characterization and population genetic analyses. Of 4042 tested sera, 455 (11.2%) were positive. The seroprevalence of HCV varied significantly by administrative area, with the highest rate in Ogooue-Lolo province (20.4%) and the lowest in Ogooue-Maritine province (3.7%). History of parenteral injections, past hospital admission and age over 55 years were independent risk factors for HCV infection (p<0.0001). Phylogenetic analyses showed that 91.9% of the strains were genotype 4 (HCV-4), 5.7% genotype 1 and 2.2% genotype 2. HCV-4 strains were highly heterogeneous, with more than eight subtypes; subtype 4e predominated (57.3%). Coalescence analyses indicated that subtype 4e was the oldest, with an estimated most recent common ancestor of 1702 [95% CI, 1418-1884]. The epidemic profile indicated that it spread exponentially during the first part of the 20th century, probably by iatrogenic transmission. CONCLUSIONS/SIGNIFICANCE: These results confirm the endemicity of HCV subtype 4e in Gabon and show that its spread is due to a cohort effect, with previous, possibly iatrogenic events. More extensive epidemiological studies are needed to better characterize the route of transmission and the dissemination of HCV in Gabon. [less ▲]Detailed reference viewed: 4 (0 ULg)
Decoding Semi-Constrained Brain Activity from fMRI Using Support Vector Machines and Gaussian Processes
Schrouff, Jessica ; Kussé, Caroline ; Wehenkel, Louis et al
in PLoS ONE (2012), 7(4),
Predicting a particular cognitive state from a specific pattern of fMRI voxel values is still a methodological challenge. Decoding brain activity is usually performed in highly controlled experimental ... [more ▼]
Predicting a particular cognitive state from a specific pattern of fMRI voxel values is still a methodological challenge. Decoding brain activity is usually performed in highly controlled experimental paradigms characterized by a series of distinct states induced by a temporally constrained experimental design. In more realistic conditions, the number, sequence and duration of mental states are unpredictably generated by the individual, resulting in complex and imbalanced fMRI data sets. This study tests the classification of brain activity, acquired on 16 volunteers using fMRI, during mental imagery, a condition in which the number and duration of mental events were not externally imposed but self-generated. To deal with these issues, two classification techniques were considered (Support Vector Machines, SVM, and Gaussian Processes, GP), as well as different feature extraction methods (General Linear Model, GLM and SVM). These techniques were combined in order to identify the procedures leading to the highest accuracy measures. Our results showed that 12 data sets out of 16 could be significantly modeled by either SVM or GP. Model accuracies tended to be related to the degree of imbalance between classes and to task performance of the volunteers. We also conclude that the GP technique tends to be more robust than SVM to model unbalanced data sets. [less ▲]Detailed reference viewed: 48 (16 ULg)
Decoding the folding of Burkholderia glumae lipase: folding intermediates en route to kinetic stability
; ; Feller, Georges et al
in PLoS ONE (2012), 7(5), 36999Detailed reference viewed: 22 (4 ULg)
Does pet ownership in infancy lead to asthma or allergy at school age? Pooled analysis of individual participant data from 11 European birth cohorts.
; ; et al
in PLoS ONE (2012)Detailed reference viewed: 35 (7 ULg)
Modelling temporal stability of EPI time series using magnitude images acquired with multi-channel receiver coils.
; Balteau, Evelyne ; et al
in PLoS ONE (2012), 7(12), 52075Detailed reference viewed: 7 (0 ULg)
Characterization of spontaneous bone marrow recovery after sublethal total body irradiation: importance of the osteoblastic/adipocytic balance.
Poncin, Géraldine ; Beaulieu, Aurore ; Humblet, Chantal et al
in PLoS ONE (2012), 7(2), 30818
Many studies have already examined the hematopoietic recovery after irradiation but paid with very little attention to the bone marrow microenvironment. Nonetheless previous studies in a murine model of ... [more ▼]
Many studies have already examined the hematopoietic recovery after irradiation but paid with very little attention to the bone marrow microenvironment. Nonetheless previous studies in a murine model of reversible radio-induced bone marrow aplasia have shown a significant increase in alkaline phosphatase activity (ALP) prior to hematopoietic regeneration. This increase in ALP activity was not due to cell proliferation but could be attributed to modifications of the properties of mesenchymal stem cells (MSC). We thus undertook a study to assess the kinetics of the evolution of MSC correlated to their hematopoietic supportive capacities in mice treated with sub lethal total body irradiation. In our study, colony-forming units - fibroblasts (CFU-Fs) assay showed a significant MSC rate increase in irradiated bone marrows. CFU-Fs colonies still possessed differentiation capacities of MSC but colonies from mice sacrificed 3 days after irradiation displayed high rates of ALP activity and a transient increase in osteoblastic markers expression while ppargamma and neuropilin-1 decreased. Hematopoietic supportive capacities of CFU-Fs were also modified: as compared to controls, irradiated CFU-Fs significantly increased the proliferation rate of hematopoietic precursors and accelerated the differentiation toward the granulocytic lineage. Our data provide the first evidence of the key role exerted by the balance between osteoblasts and adipocytes in spontaneous bone marrow regeneration. First, (pre)osteoblast differentiation from MSC stimulated hematopoietic precursor's proliferation and granulopoietic regeneration. Then, in a second time (pre)osteoblasts progressively disappeared in favour of adipocytic cells which down regulated the proliferation and granulocytic differentiation and then contributed to a return to pre-irradiation conditions. [less ▲]Detailed reference viewed: 18 (5 ULg)
Identification of protein networks involved in the disease course of experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis.
; ; et al
in PLoS ONE (2012), 7(4), 35544
A more detailed insight into disease mechanisms of multiple sclerosis (MS) is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the ... [more ▼]
A more detailed insight into disease mechanisms of multiple sclerosis (MS) is crucial for the development of new and more effective therapies. MS is a chronic inflammatory autoimmune disease of the central nervous system. The aim of this study is to identify novel disease associated proteins involved in the development of inflammatory brain lesions, to help unravel underlying disease processes. Brainstem proteins were obtained from rats with MBP induced acute experimental autoimmune encephalomyelitis (EAE), a well characterized disease model of MS. Samples were collected at different time points: just before onset of symptoms, at the top of the disease and following recovery. To analyze changes in the brainstem proteome during the disease course, a quantitative proteomics study was performed using two-dimensional difference in-gel electrophoresis (2D-DIGE) followed by mass spectrometry. We identified 75 unique proteins in 92 spots with a significant abundance difference between the experimental groups. To find disease-related networks, these regulated proteins were mapped to existing biological networks by Ingenuity Pathway Analysis (IPA). The analysis revealed that 70% of these proteins have been described to take part in neurological disease. Furthermore, some focus networks were created by IPA. These networks suggest an integrated regulation of the identified proteins with the addition of some putative regulators. Post-synaptic density protein 95 (DLG4), a key player in neuronal signalling and calcium-activated potassium channel alpha 1 (KCNMA1), involved in neurotransmitter release, are 2 putative regulators connecting 64% of the identified proteins. Functional blocking of the KCNMA1 in macrophages was able to alter myelin phagocytosis, a disease mechanism highly involved in EAE and MS pathology. Quantitative analysis of differentially expressed brainstem proteins in an animal model of MS is a first step to identify disease-associated proteins and networks that warrant further research to study their actual contribution to disease pathology. [less ▲]Detailed reference viewed: 33 (6 ULg)
An improved protocol for efficient engraftment in NOD/LTSZ-SCIDIL-2Rgammanull mice allows HIV replication and development of anti-HIV immune responses.
; ; et al
in PloS one (2012), 7(6), 38491
Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rgamma(null) (NSG) and NOD/SCID/IL2Rgamma(null) (NOG) mice need efficient human cell engraftment for long ... [more ▼]
Cord blood hematopoietic progenitor cells (CB-HPCs) transplanted immunodeficient NOD/LtsZ-scidIL2Rgamma(null) (NSG) and NOD/SCID/IL2Rgamma(null) (NOG) mice need efficient human cell engraftment for long-term HIV-1 replication studies. Total body irradiation (TBI) is a classical myeloablation regimen used to improve engraftment levels of human cells in these humanized mice. Some recent reports suggest the use of busulfan as a myeloablation regimen to transplant HPCs in neonatal and adult NSG mice. In the present study, we further ameliorated the busulfan myeloablation regimen with fresh CB-CD34+cell transplantation in 3-4 week old NSG mice. In this CB-CD34+transplanted NSG mice engraftment efficiency of human CD45+cell is over 90% in peripheral blood. Optimal engraftment promoted early and increased CD3+T cell levels, with better lymphoid tissue development and prolonged human cell chimerism over 300 days. These humanized NSG mice have shown long-lasting viremia after HIV-1JRCSF and HIV-1Bal inoculation through intravenous and rectal routes. We also saw a gradual decline of the CD4+T cell count, widespread immune activation, up-regulation of inflammation marker and microbial translocation after HIV-1 infection. Humanized NSG mice reconstituted according to our new protocol produced, moderate cellular and humoral immune responses to HIV-1 postinfection. We believe that NSG mice reconstituted according to our easy to use protocol will provide a better in vivo model for HIV-1 replication and anti-HIV-1 therapy trials. [less ▲]Detailed reference viewed: 20 (4 ULg)
Granger causality analysis of steady-state electroencephalographic signals during propofol-induced anaesthesia.
; ; Bruno, Marie-Aurélie et al
in PLoS ONE (2012), 7(1), 29072
Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed ... [more ▼]
Changes in conscious level have been associated with changes in dynamical integration and segregation among distributed brain regions. Recent theoretical developments emphasize changes in directed functional (i.e., causal) connectivity as reflected in quantities such as 'integrated information' and 'causal density'. Here we develop and illustrate a rigorous methodology for assessing causal connectivity from electroencephalographic (EEG) signals using Granger causality (GC). Our method addresses the challenges of non-stationarity and bias by dividing data into short segments and applying permutation analysis. We apply the method to EEG data obtained from subjects undergoing propofol-induced anaesthesia, with signals source-localized to the anterior and posterior cingulate cortices. We found significant increases in bidirectional GC in most subjects during loss-of-consciousness, especially in the beta and gamma frequency ranges. Corroborating a previous analysis we also found increases in synchrony in these ranges; importantly, the Granger causality analysis showed higher inter-subject consistency than the synchrony analysis. Finally, we validate our method using simulated data generated from a model for which GC values can be analytically derived. In summary, our findings advance the methodology of Granger causality analysis of EEG data and carry implications for integrated information and causal density theories of consciousness. [less ▲]Detailed reference viewed: 111 (5 ULg)
A novel mouse model for multiple myeloma (MOPC315.BM) that allows noninvasive spatiotemporal detection of osteolytic disease.
; ; et al
in PLoS ONE (2012), 7(12), 51892
Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always ... [more ▼]
Multiple myeloma (MM) is a lethal human cancer characterized by a clonal expansion of malignant plasma cells in bone marrow. Mouse models of human MM are technically challenging and do not always recapitulate human disease. Therefore, new mouse models for MM are needed. Mineral-oil induced plasmacytomas (MOPC) develop in the peritoneal cavity of oil-injected BALB/c mice. However, MOPC typically grow extramedullary and are considered poor models of human MM. Here we describe an in vivo-selected MOPC315 variant, called MOPC315.BM, which can be maintained in vitro. When injected i.v. into BALB/c mice, MOPC315.BM cells exhibit tropism for bone marrow. As few as 10(4) MOPC315.BM cells injected i.v. induced paraplegia, a sign of spinal cord compression, in all mice within 3-4 weeks. MOPC315.BM cells were stably transfected with either firefly luciferase (MOPC315.BM.Luc) or DsRed (MOPC315.BM.DsRed) for studies using noninvasive imaging. MOPC315.BM.Luc cells were detected in the tibiofemoral region already 1 hour after i.v. injection. Bone foci developed progressively, and as of day 5, MM cells were detected in multiple sites in the axial skeleton. Additionally, the spleen (a hematopoietic organ in the mouse) was invariably affected. Luminescent signals correlated with serum myeloma protein concentration, allowing for easy tracking of tumor load with noninvasive imaging. Affected mice developed osteolytic lesions. The MOPC315.BM model employs a common strain of immunocompetent mice (BALB/c) and replicates many characteristics of human MM. The model should be suitable for studies of bone marrow tropism, development of osteolytic lesions, drug testing, and immunotherapy in MM. [less ▲]Detailed reference viewed: 32 (1 ULg)
Oculomotor guidance and capture by irrelevant faces
Devue, Christel ; ;
in Plos ONE (2012)
Even though it is generally agreed that face stimuli constitute a special class of stimuli, which are treated preferentially by our visual system, it remains unclear whether faces can capture attention in ... [more ▼]
Even though it is generally agreed that face stimuli constitute a special class of stimuli, which are treated preferentially by our visual system, it remains unclear whether faces can capture attention in a stimulus-driven manner. Moreover, there is a long-standing debate regarding the mechanism underlying the preferential bias of selecting faces. Some claim that faces constitute a set of special low-level features to which our visual system is tuned; others claim that the visual system is capable of extracting the meaning of faces very rapidly, driving attentional selection. Those debates continue because many studies contain methodological peculiarities and manipulations that prevent a definitive conclusion. Here, we present a new visual search task in which observers had to make a saccade to a uniquely colored circle while completely irrelevant objects were also present in the visual field. The results indicate that faces capture and guide the eyes more than other animated objects and that our visual system is not only tuned to the low-level features that make up a face but also to its meaning. [less ▲]Detailed reference viewed: 24 (4 ULg)
Imatinib and Nilotinib Inhibit Hematopoietic Progenitor Cell Growth, but Do Not Prevent Adhesion, Migration and Engraftment of Human Cord Blood CD34+ Cells
Belle, Ludovic ; ; FOGUENNE, Jacques et al
in PLoS ONE (2012), 7(12), 52564
Background: The availability of tyrosine kinase inhibitors (TKIs) has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib is also known to ... [more ▼]
Background: The availability of tyrosine kinase inhibitors (TKIs) has considerably changed the management of Philadelphia chromosome positive leukemia. The BCR-ABL inhibitor imatinib is also known to inhibit the tyrosine kinase of the stem cell factor receptor, c-Kit. Nilotinib is 30 times more potent than imatinib towards BCR-ABL in vitro. Studies in healthy volunteers and patients with chronic myelogenous leukemia or gastrointestinal stromal tumors have shown that therapeutic doses of nilotinib deliver drug levels similar to those of imatinib. The aim of this study was to compare the inhibitory effects of imatinib and nilotinib on proliferation, differentiation, adhesion, migration and engraftment capacities of human cord blood CD34+ cells. Design and Methods: After a 48-hour cell culture with or without TKIs, CFC, LTC-IC, migration, adhesion and cell cycle analysis were performed. In a second time, the impact of these TKIs on engraftment was assessed in a xenotransplantation model using NOD/SCID/IL-2Rc (null) mice. <br />Results: TKIs did not affect LTC-IC frequencies despite in vitro inhibition of CFC formation due to inhibition of CD34+ cell cycle entry. Adhesion of CD34+ cells to retronectin was reduced in the presence of either imatinib or nilotinib but only at high concentrations. Migration through a SDF-1a gradient was not changed by cell culture in the presence of TKIs. Finally, bone marrow cellularity and human chimerism were not affected by daily doses of imatinib and nilotinib in a xenogenic transplantation model. No significant difference was seen between TKIs given the equivalent affinity of imatinib and nilotinib for KIT. <br />Conclusions: These data suggest that combining non-myeloablative conditioning regimen with TKIs starting the day of the transplantation could be safe. [less ▲]Detailed reference viewed: 39 (16 ULg)
Repression of floral meristem fate is crucial in shaping tomato inflorescence
; ; et al
in PLoS ONE (2012), 7(2), 31096Detailed reference viewed: 59 (15 ULg)
Fast Homozygosity Mapping and Identification of a Zebrafish ENU-Induced Mutation by Whole-Genome Sequencing.
Voz, Marianne ; Coppieters, Wouter ; Manfroid, Isabelle et al
in PLoS ONE (2012), 7(4), 34671
Forward genetics using zebrafish is a powerful tool for studying vertebrate development through large-scale mutagenesis. Nonetheless, the identification of the molecular lesion is still laborious and ... [more ▼]
Forward genetics using zebrafish is a powerful tool for studying vertebrate development through large-scale mutagenesis. Nonetheless, the identification of the molecular lesion is still laborious and involves time-consuming genetic mapping. Here, we show that high-throughput sequencing of the whole zebrafish genome can directly locate the interval carrying the causative mutation and at the same time pinpoint the molecular lesion. The feasibility of this approach was validated by sequencing the m1045 mutant line that displays a severe hypoplasia of the exocrine pancreas. We generated 13 Gb of sequence, equivalent to an eightfold genomic coverage, from a pool of 50 mutant embryos obtained from a map-cross between the AB mutant carrier and the WIK polymorphic strain. The chromosomal region carrying the causal mutation was localized based on its unique property to display high levels of homozygosity among sequence reads as it derives exclusively from the initial AB mutated allele. We developed an algorithm identifying such a region by calculating a homozygosity score along all chromosomes. This highlighted an 8-Mb window on chromosome 5 with a score close to 1 in the m1045 mutants. The sequence analysis of all genes within this interval revealed a nonsense mutation in the snapc4 gene. Knockdown experiments confirmed the assertion that snapc4 is the gene whose mutation leads to exocrine pancreas hypoplasia. In conclusion, this study constitutes a proof-of-concept that whole-genome sequencing is a fast and effective alternative to the classical positional cloning strategies in zebrafish. [less ▲]Detailed reference viewed: 22 (7 ULg)
Effects of Sublethal Cadmium Exposure on Antipredator Behavioural and Antitoxic Responses in the Invasive Amphipod Dikerogammarus villosus
; Gismondi, Eric ; et al
in PLoS ONE (2012), 7(8)Detailed reference viewed: 8 (1 ULg)