References of "PLoS ONE"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailMyelin-Derived Lipids Modulate Macrophage Activity by Liver X Receptor Activation
Bogie, Jeroen F. J.; Timmermans, Silke; Huynh-Thu, Vân Anh ULg et al

in PLoS ONE (2012), 7(9), 44998

Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. Foamy macrophages and microglia, containing ... [more ▼]

Multiple sclerosis is a chronic, inflammatory, demyelinating disease of the central nervous system in which macrophages and microglia play a central role. Foamy macrophages and microglia, containing degenerated myelin, are abundantly found in active multiple sclerosis lesions. Recent studies have described an altered macrophage phenotype after myelin internalization. However, it is unclear by which mechanisms myelin affects the phenotype of macrophages and how this phenotype can influence lesion progression. Here we demonstrate, by using genome wide gene expression analysis, that myelin-phagocytosing macrophages have an enhanced expression of genes involved in migration, phagocytosis and inflammation. Interestingly, myelin internalization also induced the expression of genes involved in liver-X-receptor signaling and cholesterol efflux. In vitro validation shows that myelin-phagocytosing macrophages indeed have an increased capacity to dispose intracellular cholesterol. In addition, myelin suppresses the secretion of the pro-inflammatory mediator IL-6 by macrophages, which was mediated by activation of liver-X-receptor b. Our data show that myelin modulates the phenotype of macrophages by nuclear receptor activation, which may subsequently affect lesion progression in demyelinating diseases such as multiple sclerosis. [less ▲]

Detailed reference viewed: 24 (5 ULg)
Full Text
Peer Reviewed
See detailGeological Substrates Shape Tree Species and Trait Distributions in African Moist Forests
Fayolle, Adeline ULg; Engelbrecht, Bettina; Freycon, Vincent et al

in PLoS ONE (2012), 7(8), 1-10

Background: Understanding the factors that shape the distribution of tropical tree species at large scales is a central issue in ecology, conservation and forest management. The aims of this study were to ... [more ▼]

Background: Understanding the factors that shape the distribution of tropical tree species at large scales is a central issue in ecology, conservation and forest management. The aims of this study were to (i) assess the importance of environmental factors relative to historical factors for tree species distributions in the semi-evergreen forests of the northern Congo basin; and to (ii) identify potential mechanisms explaining distribution patterns through a trait-based approach. Methodology/Principal Findings: We analyzed the distribution patterns of 31 common tree species in an area of more than 700,000 km² spanning the borders of Cameroon, the Central African Republic, and the Republic of Congo using forest inventory data from 56,445 0.5-ha plots. Spatial variation of environmental (climate, topography and geology) and historical factors (human disturbance) were quantified from maps and satellite records. Four key functional traits (leaf phenology, shade tolerance, wood density, and maximum growth rate) were extracted from the literature. The geological substrate was of major importance for the distribution of the focal species, while climate and past human disturbances had a significant but lesser impact. Species distribution patterns were significantly related to functional traits. Species associated with sandy soils typical of sandstone and alluvium were characterized by slow growth rates, shade tolerance, evergreen leaves, and high wood density, traits allowing persistence on resource-poor soils. In contrast, fast-growing pioneer species rarely occurred on sandy soils, except for Lophira alata. Conclusions/Significance: The results indicate strong environmental filtering due to differential soil resource availability across geological substrates. Additionally, long-term human disturbances in resource-rich areas may have accentuated the observed patterns of species and trait distributions. Trait differences across geological substrates imply pronounced differences in population and ecosystem processes, and call for different conservation and management strategies. [less ▲]

Detailed reference viewed: 61 (24 ULg)
Full Text
Peer Reviewed
See detailA novel phase portrait for neuronal excitability
Drion, Guillaume ULg; Franci, Alessio ULg; Seutin, Vincent ULg et al

in PLoS ONE (2012), 7(8),

Fifty years ago, FitzHugh introduced a phase portrait that became famous for a twofold reason: it captured in a physiological way the qualitative behavior of Hodgkin-Huxley model and it revealed the power ... [more ▼]

Fifty years ago, FitzHugh introduced a phase portrait that became famous for a twofold reason: it captured in a physiological way the qualitative behavior of Hodgkin-Huxley model and it revealed the power of simple dynamical models to unfold complex firing patterns. To date, in spite of the enormous progresses in qualitative and quantitative neural modeling, this phase portrait has remained a core picture of neuronal excitability. Yet, a major difference between the neurophysiology of 1961 and of 2011 is the recognition of the prominent role of calcium channels in firing mechanisms. We show that including this extra current in Hodgkin-Huxley dynamics leads to a revision of FitzHugh-Nagumo phase portrait that affects in a fundamental way the reduced modeling of neural excitability. The revisited model considerably enlarges the modeling power of the original one. In particular, it captures essential electrophysiological signatures that otherwise require non-physiological alteration or considerable complexification of the classical model. As a basic illustration, the new model is shown to highlight a core dynamical mechanism by which calcium channels control the two distinct firing modes of thalamocortical neurons. [less ▲]

Detailed reference viewed: 61 (9 ULg)
Full Text
Peer Reviewed
See detailEnhanced Characterization of the Smell of Death by Comprehensive Two-Dimensional Gas Chromatography-Time-of-Flight Mass Spectrometry (GCxGC-TOFMS)
Dekeirsschieter, Jessica ULg; Stefanuto, Pierre-Hugues ULg; Brasseur, Catherine ULg et al

in PLoS ONE (2012), 7(6), 39005

Soon after death, the decay process of mammalian soft tissues begins and leads to the release of cadaveric volatile compounds in the surrounding environment. The study of postmortem decomposition products ... [more ▼]

Soon after death, the decay process of mammalian soft tissues begins and leads to the release of cadaveric volatile compounds in the surrounding environment. The study of postmortem decomposition products is an emerging field of study in forensic science. However, a better knowledge of the smell of death and its volatile constituents may have many applications in forensic sciences. Domestic pigs are the most widely used human body analogues in forensic experiments, mainly due to ethical restrictions. Indeed, decomposition trials on human corpses are restricted in many countries worldwide. This article reports on the use of comprehensive two-dimensional gas chromatography coupled with time-offlight mass spectrometry (GCxGC-TOFMS) for thanatochemistry applications. A total of 832 VOCs released by a decaying pig carcass in terrestrial ecosystem, i.e. a forest biotope, were identified by GCxGC-TOFMS. These postmortem compounds belong to many kinds of chemical class, mainly oxygen compounds (alcohols, acids, ketones, aldehydes, esters), sulfur and nitrogen compounds, aromatic compounds such as phenolic molecules and hydrocarbons. The use of GCxGC-TOFMS in study of postmortem volatile compounds instead of conventional GC-MS was successful. [less ▲]

Detailed reference viewed: 177 (29 ULg)
Full Text
Peer Reviewed
See detailPhosphorylation of p65(RelA) on Ser547 by ATM represses NF-κB-dependent transcription of specific genes after genotoxic stress.
Sabatel, Hélène ULg; Di Valentin, Emmanuel ULg; Gloire, Geoffrey ULg et al

in PLoS ONE (2012)

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA ... [more ▼]

The NF-κB pathway is involved in immune and inflammation responses, proliferation, differentiation and cell death or survival. It is activated by many external stimuli including genotoxic stress. DNA double-strand breaks activate NF-κB in an ATM-dependent manner. In this manuscript, a direct interaction between p65(RelA) and the N-terminal extremity of ATM is reported. We also report that only one of the five potential ATM-(S/T)Q target sites present in p65, namely Ser547, is specifically phosphorylated by ATM in vitro. A comparative transcriptomic analysis performed in HEK-293 cells expressing either wild-type HA-p65 or a non-phosphorylatable mutant HA-p65S547A identified several differentially transcribed genes after an etoposide treatment (e.g. IL8, A20, SELE). The transcription of these genes is increased in cells expressing the mutant. Substitution of Ser547 to alanine does not affect p65 binding abilities on the κB site of the IL8 promoter but reduces p65 interaction with HDAC1. Cells expressing p65S547A have a higher level of histone H3 acetylated on Lys9 at the IL8 promoter, which is in agreement with the higher gene induction observed. These results indicate that ATM regulates a sub-set of NF-κB dependent genes after a genotoxic stress by direct phosphorylation of p65. [less ▲]

Detailed reference viewed: 46 (17 ULg)
Full Text
Peer Reviewed
See detailAuditory Resting-State Network Connectivity in Tinnitus: a Functionnal MRI Study.
MAUDOUX, Audrey ULg; LEFEBVRE, Philippe ULg; CABAY, Jean-Evrard ULg et al

in PLoS ONE (2012)

The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test ... [more ▼]

The underlying functional neuroanatomy of tinnitus remains poorly understood. Few studies have focused on functional cerebral connectivity changes in tinnitus patients. The aim of this study was to test if functional MRI ‘‘resting-state’’ connectivity patterns in auditory network differ between tinnitus patients and normal controls. Thirteen chronic tinnitus subjects and fifteen age-matched healthy controls were studied on a 3 tesla MRI. Connectivity was investigated using independent component analysis and an automated component selection approach taking into account the spatial and temporal properties of each component. Connectivity in extra-auditory regions such as brainstem, basal ganglia/NAc, cerebellum, parahippocampal, right prefrontal, parietal, and sensorimotor areas was found to be increased in tinnitus subjects. The right primary auditory cortex, left prefrontal, left fusiform gyrus, and bilateral occipital regions showed a decreased connectivity in tinnitus. These results show that there is a modification of cortical and subcortical functional connectivity in tinnitus encompassing attentional, mnemonic, and emotional networks. Our data corroborate the hypothesized implication of non-auditory regions in tinnitus physiopathology and suggest that various regions of the brain seem involved in the persistent awareness of the phenomenon as well as in the development of the associated distress. leading to disabling chronic tinnitus. [less ▲]

Detailed reference viewed: 149 (11 ULg)
Full Text
Peer Reviewed
See detailRelating the Chondrocyte Gene Network to Growth Plate Morphology: From Genes to Phenotype
Kerkhofs, Johan ULg; Roberts, Scott J; Luyten, Frank P et al

in PLoS ONE (2012)

During endochondral ossification, chondrocyte growth and differentiation is controlled by many local signalling pathways. Due to crosstalks and feedback mechanisms, these interwoven pathways display a ... [more ▼]

During endochondral ossification, chondrocyte growth and differentiation is controlled by many local signalling pathways. Due to crosstalks and feedback mechanisms, these interwoven pathways display a network like structure. In this study, a large-scale literature based logical model of the growth plate network was developed. The network is able to capture the different states (resting, proliferating and hypertrophic) that chondrocytes go through as they progress within the growth plate. In a first corroboration step, the effect of mutations in various signalling pathways of the growth plate network was investigated. [less ▲]

Detailed reference viewed: 26 (9 ULg)
Full Text
Peer Reviewed
See detailLigand Binding Study of Human PEBP1/RKIP: Interaction with Nucleotides and Raf-1 Peptides Evidenced by NMR and Mass Spectrometry
Tavel, Laurette ULg; Jaquillard, Lucie; Karsisiotis, Andreas et al

in PLoS ONE (2012), 7(4): e36187

Background Human Phosphatidylethanolamine binding protein 1 (hPEBP1) also known as Raf kinase inhibitory protein (RKIP), affects various cellular processes, and is implicated in metastasis formation and ... [more ▼]

Background Human Phosphatidylethanolamine binding protein 1 (hPEBP1) also known as Raf kinase inhibitory protein (RKIP), affects various cellular processes, and is implicated in metastasis formation and Alzheimer's disease. Human PEBP1 has also been shown to inhibit the Raf/MEK/ERK pathway. Numerous reports concern various mammalian PEBP1 binding ligands. However, since PEBP1 proteins from many different species were investigated, drawing general conclusions regarding human PEBP1 binding properties is rather difficult. Moreover, the binding site of Raf-1 on hPEBP1 is still unknown. Methods/Findings In the present study, we investigated human PEBP1 by NMR to determine the binding site of four different ligands: GTP, FMN, and one Raf-1 peptide in tri-phosphorylated and non-phosphorylated forms. The study was carried out by NMR in near physiological conditions, allowing for the identification of the binding site and the determination of the affinity constants KD for different ligands. Native mass spectrometry was used as an alternative method for measuring KD values. Conclusions/Significance Our study demonstrates and/or confirms the binding of hPEBP1 to the four studied ligands. All of them bind to the same region centered on the conserved ligand-binding pocket of hPEBP1. Although the affinities for GTP and FMN decrease as pH, salt concentration and temperature increase from pH 6.5/NaCl 0 mM/20°C to pH 7.5/NaCl 100 mM/30°C, both ligands clearly do bind under conditions similar to what is found in cells regarding pH, salt concentration and temperature. In addition, our work confirms that residues in the vicinity of the pocket rather than those within the pocket seem to be required for interaction with Raf-1. [less ▲]

Detailed reference viewed: 38 (9 ULg)
Full Text
Peer Reviewed
See detailPhysical Fitness and Mitochondrial Respiratory Capacity in Horse Skeletal Muscle
Votion, Dominique ULg; Gnaiger, Erich; Lemieux, Hélène et al

in PLoS ONE (2012), 7(4), 1-12

We applied high-resolution respirometry and multiple substrate-uncoupler-inhibitor titration protocols to study mitochondrial physiology in small (1.0–2.5 mg) permeabilized muscle fibres sampled from ... [more ▼]

We applied high-resolution respirometry and multiple substrate-uncoupler-inhibitor titration protocols to study mitochondrial physiology in small (1.0–2.5 mg) permeabilized muscle fibres sampled from triceps brachii of healthy horses. The present investigation on horse skeletal muscle has tested the methodology used to study mitochondrial function in muscle microbiopsies by high-resolution respirometry to define reference protocols for horses (from sampling procedure to data analysis). [less ▲]

Detailed reference viewed: 42 (21 ULg)
Full Text
Peer Reviewed
See detailSalivary Glucose Oxidase from Caterpillars Mediates the Induction of Rapid and Delayed-Induced Defenses in the Tomato Plant
Tian, Donglan; Peiffer, Michelle; Shoemaker, Erica et al

in PLoS ONE (2012), 7(4), 36168

Detailed reference viewed: 25 (1 ULg)
Full Text
Peer Reviewed
See detailMotor fatigue measurement by distance-induced slow down of walking speed in multiple sclerosis
PHAN BA, Remy ULg; CALAY, Philippe ULg; GRODENT, Patrick ULg et al

in PLoS ONE (2012), 7(4), 34744

Background: Motor fatigue and ambulation impairment are prominent clinical features of people with multiple sclerosis (pMS). We hypothesized that a multimodal and comparative assessment of walking speed ... [more ▼]

Background: Motor fatigue and ambulation impairment are prominent clinical features of people with multiple sclerosis (pMS). We hypothesized that a multimodal and comparative assessment of walking speed on short and long distance would allow a better delineation and quantification of gait fatigability in pMS. Objectives: To compare 4 walking paradigms: the timed 25-foot walk (T25FW), a corrected version of the T25FW with dynamic start (T25FW+), the timed 100-meter walk (T100MW) and the timed 500-meter walk (T500MW). Methods: Thirty controls and 81 pMS performed the 4 walking tests in a single study visit. Results: The 4 walking tests were performed with a slower WS in pMS compared to controls even in subgroups with minimal disability. The finishing speed of the last 100-meter of the T500MW was the slowest measurable WS whereas the T25FW+ provided the fastest measurable WS. The ratio between such slowest and fastest WS (Deceleration Index, DI) was significantly lower only in pMS with EDSS 4.0-6.0, a pyramidal or cerebellar functional system score reaching 3 or a maximum reported walking distance !4000m. Conclusion: The motor fatigue which triggers gait deceleration over a sustained effort in pMS can be measured by the WS ratio between performances on a very short distance and the finishing pace on a longer more demanding task. The absolute walking speed is abnormal early in MS whatever the distance of effort when patients are unaware of ambulation impairment. In contrast, the DI-measured ambulation fatigability appears to take place later in the disease course. [less ▲]

Detailed reference viewed: 74 (10 ULg)
Full Text
Peer Reviewed
See detailSelf-assemblage and quorum in the earthworm Eisenia fetida (Oligochaete, Lumbricidae)
Zirbes, Lara ULg; Brostaux, Yves ULg; Mescher, Mark et al

in PLoS ONE (2012), 7(3), 32564

Detailed reference viewed: 29 (6 ULg)
Full Text
Peer Reviewed
See detailDifferential expression of Vegfr-2 and its soluble form in preeclampsia.
Munaut, Carine ULg; LORQUET, Sophie ULg; Pequeux, Christel ULg et al

in PLoS ONE (2012), 7(3), 33475

Background: Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably ... [more ▼]

Background: Several studies have suggested that the main features of preeclampsia (PE) are consequences of endothelial dysfunction related to excess circulating anti-angiogenic factors, most notably, soluble sVEGFR-1 (also known as sFlt-1) and soluble endoglin (sEng), as well as to decreased PlGF. Recently, soluble VEGF type 2 receptor (sVEGFR-2) has emerged as a crucial regulator of lymphangiogenesis. To date, however, there is a paucity of information on the changes of VEGFR-2 that occur during the clinical onset of PE. Therefore, the aim of our study was to characterize the plasma levels of VEGFR-2 in PE patients and to perform VEGFR-2 immunolocalization in placenta. METHODOLOGY/PRINCIPAL FINDINGS: By ELISA, we observed that the VEGFR-2 plasma levels were reduced during PE compared with normal gestational age matched pregnancies, whereas the VEGFR-1 and Eng plasma levels were increased. The dramatic drop in the VEGFR-1 levels shortly after delivery confirmed its placental origin. In contrast, the plasma levels of Eng and VEGFR-2 decreased only moderately during the early postpartum period. An RT-PCR analysis showed that the relative levels of VEGFR-1, sVEGFR-1 and Eng mRNA were increased in the placentas of women with severe PE. The relative levels of VEGFR-2 mRNA as well as expressing cells, were similar in both groups. We also made the novel finding that a recently described alternatively spliced VEGFR-2 mRNA variant was present at lower relative levels in the preeclamptic placentas. CONCLUSIONS/SIGNIFICANCE: Our results indicate that the plasma levels of anti-angiogenic factors, particularly VEGFR-1 and VEGFR-2, behave in different ways after delivery. The rapid decrease in plasma VEGFR-1 levels appears to be a consequence of the delivery of the placenta. The persistent circulating levels of VEGFR-2 suggest a maternal endothelial origin of this peptide. The decreased VEGFR-2 plasma levels in preeclamptic women may serve as a marker of endothelial dysfunction. [less ▲]

Detailed reference viewed: 36 (7 ULg)
Full Text
Peer Reviewed
See detailLower-Order Effects Adjustment in Quantitative Traits Model-Based Multifactor Dimensionality Reduction
Mahachie John, Jestinah ULg; Cattaert, Tom ULg; Van Lishout, François ULg et al

in PLoS ONE (2012)

Identifying gene-gene interactions or gene-environment interactions in studies of human complex diseases remains a big challenge in genetic epidemiology. An additional challenge, often forgotten, is to ... [more ▼]

Identifying gene-gene interactions or gene-environment interactions in studies of human complex diseases remains a big challenge in genetic epidemiology. An additional challenge, often forgotten, is to account for important lower-order genetic effects. These may hamper the identification of genuine epistasis. If lower-order genetic effects contribute to the genetic variance of a trait, identified statistical interactions may simply be due to a signal boost of these effects. In this study, we restrict attention to quantitative traits and bi-allelic SNPs as genetic markers. Moreover, our interaction study focuses on 2- way SNP-SNP interactions. Via simulations, we assess the performance of different corrective measures for lower-order genetic effects in Model-Based Multifactor Dimensionality Reduction epistasis detection, using additive and co-dominant coding schemes. Performance is evaluated in terms of power and familywise error rate. Our simulations indicate that empirical power estimates are reduced with correction of lower-order effects, likewise familywise error rates. Easy-to-use automatic SNP selection procedures, SNP selection based on ‘‘top’’ findings, or SNP selection based on p-value criterion for interesting main effects result in reduced power but also almost zero false positive rates. Always accounting for main effects in the SNP-SNP pair under investigation during Model-Based Multifactor Dimensionality Reduction analysis adequately controls false positive epistasis findings. This is particularly true when adopting a co-dominant corrective coding scheme. In conclusion, automatic search procedures to identify lower-order effects to correct for during epistasis screening should be avoided. The same is true for procedures that adjust for lower-order effects prior to Model-Based Multifactor Dimensionality Reduction and involve using residuals as the new trait. We advocate using ‘‘on-the-fly’’ lower-order effects adjusting when screening for SNP-SNP interactions using Model-Based Multifactor Dimensionality Reduction analysis. [less ▲]

Detailed reference viewed: 63 (29 ULg)
Full Text
Peer Reviewed
See detailNew Ophthalmosaurid Ichthyosaurs from the European Lower Cretaceous Demonstrate Extensive Ichthyosaur Survival across the Jurassic–Cretaceous Boundary
Fischer, Valentin ULg; Maisch, Michael; Naish, Darren et al

in PLoS ONE (2012), 7(1), 29234

Background Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events ... [more ▼]

Background Ichthyosauria is a diverse clade of marine amniotes that spanned most of the Mesozoic. Until recently, most authors interpreted the fossil record as showing that three major extinction events affected this group during its history: one during the latest Triassic, one at the Jurassic–Cretaceous boundary (JCB), and one (resulting in total extinction) at the Cenomanian-Turonian boundary. The JCB was believed to eradicate most of the peculiar morphotypes found in the Late Jurassic, in favor of apparently less specialized forms in the Cretaceous. However, the record of ichthyosaurs from the Berriasian–Barremian interval is extremely limited, and the effects of the end-Jurassic extinction event on ichthyosaurs remains poorly understood. Methodology/Principal Findings Based on new material from the Hauterivian of England and Germany and on abundant material from the Cambridge Greensand Formation, we name a new ophthalmosaurid, Acamptonectes densus gen. et sp. nov. This taxon shares numerous features with Ophthalmosaurus, a genus now restricted to the Callovian–Berriasian interval. Our phylogenetic analysis indicates that Ophthalmosauridae diverged early in its history into two markedly distinct clades, Ophthalmosaurinae and Platypterygiinae, both of which cross the JCB and persist to the late Albian at least. To evaluate the effect of the JCB extinction event on ichthyosaurs, we calculated cladogenesis, extinction, and survival rates for each stage of the Oxfordian–Barremian interval, under different scenarios. The extinction rate during the JCB never surpasses the background extinction rate for the Oxfordian–Barremian interval and the JCB records one of the highest survival rates of the interval. Conclusions/Significance There is currently no evidence that ichthyosaurs were affected by the JCB extinction event, in contrast to many other marine groups. Ophthalmosaurid ichthyosaurs remained diverse from their rapid radiation in the Middle Jurassic to their total extinction at the beginning of the Late Cretaceous. [less ▲]

Detailed reference viewed: 71 (9 ULg)
Full Text
Peer Reviewed
See detailThe inositol phosphatase SHIP-1 inhibits NOD2-induced NF-κB activation by disturbing the interaction of XIAP with RIP2
Condé, Claude ULg; Rambout, Xavier ULg; Lebrun, Marielle ULg et al

in PLoS ONE (2012)

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a ... [more ▼]

SHIP-1 is an inositol phosphatase predominantly expressed in hematopoietic cells. Over the ten past years, SHIP-1 has been described as an important regulator of immune functions. Here, we characterize a new inhibitory function for SHIP-1 in NOD2 signaling. NOD2 is a crucial cytoplasmic bacterial sensor that activates proinflammatory and antimicrobial responses upon bacterial invasion. We observed that SHIP-1 decreases NOD2-induced NF-κB activation in macrophages. This negative regulation relies on its interaction with XIAP. Indeed, we observed that XIAP is an essential mediator of the NOD2 signaling pathway that enables proper NF-κB activation in macrophages. Upon NOD2 activation, SHIP-1 C-terminal proline rich domain (PRD) interacts with XIAP, thereby disturbing the interaction between XIAP and RIP2 in order to decrease NF-κB signaling. [less ▲]

Detailed reference viewed: 39 (16 ULg)
Full Text
Peer Reviewed
See detailFemale mice deficient in alpha-fetoprotein show female-typical neural responses to conspecific-derived pheromones.
Brock, Olivier; Keller, Matthieu; Douhard, Quentin et al

in PLoS ONE (2012), 7(6), 39204

The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP ... [more ▼]

The neural mechanisms controlling sexual behavior are sexually differentiated by the perinatal actions of sex steroid hormones. We recently observed using female mice deficient in alpha-fetoprotein (AFP-KO) and which lack the protective actions of AFP against maternal estradiol, that exposure to prenatal estradiol completely defeminized the potential to show lordosis behavior in adulthood. Furthermore, AFP-KO females failed to show any male-directed mate preferences following treatment with estradiol and progesterone, indicating a reduced sexual motivation to seek out the male. In the present study, we asked whether neural responses to male- and female-derived odors are also affected in AFP-KO female mice. Therefore, we compared patterns of Fos, the protein product of the immediate early gene, c-fos, commonly used as a marker of neuronal activation, between wild-type (WT) and AFP-KO female mice following exposure to male or estrous female urine. We also tested WT males to confirm the previously observed sex differences in neural responses to male urinary odors. Interestingly, AFP-KO females showed normal, female-like Fos responses, i.e. exposure to urinary odors from male but not estrous female mice induced equivalent levels of Fos protein in the accessory olfactory pathways (e.g. the medial part of the preoptic nucleus, the bed nucleus of the stria terminalis, the amygdala, and the lateral part of the ventromedial hypothalamic nucleus) as well as in the main olfactory pathways (e.g. the piriform cortex and the anterior cortical amygdaloid nucleus), as WT females. By contrast, WT males did not show any significant induction of Fos protein in these brain areas upon exposure to either male or estrous female urinary odors. These results thus suggest that prenatal estradiol is not involved in the sexual differentiation of neural Fos responses to male-derived odors. [less ▲]

Detailed reference viewed: 6 (0 ULg)
Full Text
Peer Reviewed
See detailReduction in inter-hemispheric connectivity in disorders of consciousness.
Ovadia-Caro, Smadar; Nir, Yuval; Soddu, Andrea ULg et al

in PLoS ONE (2012), 7(5), 37238

Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC ... [more ▼]

Clinical diagnosis of disorders of consciousness (DOC) caused by brain injury poses great challenges since patients are often behaviorally unresponsive. A promising new approach towards objective DOC diagnosis may be offered by the analysis of ultra-slow (<0.1 Hz) spontaneous brain activity fluctuations measured with functional magnetic resonance imaging (fMRI) during the resting-state. Previous work has shown reduced functional connectivity within the "default network", a subset of regions known to be deactivated during engaging tasks, which correlated with the degree of consciousness impairment. However, it remains unclear whether the breakdown of connectivity is restricted to the "default network", and to what degree changes in functional connectivity can be observed at the single subject level. Here, we analyzed resting-state inter-hemispheric connectivity in three homotopic regions of interest, which could reliably be identified based on distinct anatomical landmarks, and were part of the "Extrinsic" (externally oriented, task positive) network (pre- and postcentral gyrus, and intraparietal sulcus). Resting-state fMRI data were acquired for a group of 11 healthy subjects and 8 DOC patients. At the group level, our results indicate decreased inter-hemispheric functional connectivity in subjects with impaired awareness as compared to subjects with intact awareness. Individual connectivity scores significantly correlated with the degree of consciousness. Furthermore, a single-case statistic indicated a significant deviation from the healthy sample in 5/8 patients. Importantly, of the three patients whose connectivity indices were comparable to the healthy sample, one was diagnosed as locked-in. Taken together, our results further highlight the clinical potential of resting-state connectivity analysis and might guide the way towards a connectivity measure complementing existing DOC diagnosis. [less ▲]

Detailed reference viewed: 25 (2 ULg)