References of "PLoS ONE"
     in
Bookmark and Share    
Full Text
Peer Reviewed
See detailExploiting SNP Correlations within Random Forest for Genome-Wide Association Studies
Botta, Vincent ULg; Louppe, Gilles ULg; Geurts, Pierre ULg et al

in PLoS ONE (2014)

The primary goal of genome-wide association studies (GWAS) is to discover variants that could lead, in isolation or in combination, to a particular trait or disease. Standard approaches to GWAS, however ... [more ▼]

The primary goal of genome-wide association studies (GWAS) is to discover variants that could lead, in isolation or in combination, to a particular trait or disease. Standard approaches to GWAS, however, are usually based on univariate hypothesis tests and therefore can account neither for correlations due to linkage disequilibrium nor for combinations of several markers. To discover and leverage such potential multivariate interactions, we propose in this work an extension of the Random Forest algorithm tailored for structured GWAS data. In terms of risk prediction, we show empirically on several GWAS datasets that the proposed T-Trees method significantly outperforms both the original Random Forest algorithm and standard linear models, thereby suggesting the actual existence of multivariate non-linear effects due to the combinations of several SNPs. We also demonstrate that variable importances as derived from our method can help identify relevant loci. Finally, we highlight the strong impact that quality control procedures may have, both in terms of predictive power and loci identification. [less ▲]

Detailed reference viewed: 230 (25 ULg)
Full Text
Peer Reviewed
See detailWidespread occurrence of expressed fungal secretory peroxidases in forest soils
Kellner, Harald; Luis, Patricia; Pecyna, Marek, J. et al

in PLoS ONE (2014), 9(4),

Detailed reference viewed: 19 (11 ULg)
Full Text
Peer Reviewed
See detailInfluence of noise correction on intra- and inter-subject variability of quantitative metrics in diffusion kurtosis imaging
André, Elodie ULg; Grinberg, Farida; Farrher, Ezequiel et al

in PLoS ONE (2014)

Diffusion kurtosis imaging (DKI) is a promising extension of diffusion tensor imaging, giving new insights into the white matter microstructure and providing new biomarkers. Given the rapidly increasing ... [more ▼]

Diffusion kurtosis imaging (DKI) is a promising extension of diffusion tensor imaging, giving new insights into the white matter microstructure and providing new biomarkers. Given the rapidly increasing number of studies, DKI has a potential to establish itself as a valuable tool in brain diagnostics. However, to become a routine procedure, DKI still needs to be improved in terms of robustness, reliability, and reproducibility. As it requires acquisitions at higher diffusion31 weightings, results are more affected by noise than in diffusion tensor imaging. The lack of standard procedures for post-processing, especially for noise correction, might become a significant obstacle for the use of DKI in clinical routine limiting its application. We considered two noise correction schemes accounting for the noise properties of multichannel phased-array coils, in order to improve the data quality at signal-to-noise ratio (SNR) typical for DKI. The SNR dependence of estimated DKI metrics such as mean kurtosis (MK), mean diffusivity (MD) and fractional anisotropy (FA) is investigated for these noise correction approaches in Monte Carlo simulations and in in vivo human studies. The intra-subject reproducibility is investigated in a single subject study by varying the SNR level and SNR spatial distribution. Then the impact of the noise correction on inter-subject variability is evaluated in a homogeneous sample of 25 healthy volunteers. Results show a strong impact of noise correction on the MK estimate, while the estimation of FA and MD was affected to a lesser extent. Both intra- and inter-subject SNR related variability of the MK estimate is considerably reduced after correction for the noise bias, providing more accurate and reproducible measures. In this work, we have proposed a straightforward method that improves accuracy of DKI metrics. This should contribute to standardization of DKI applications in clinical studies and making valuable inferences in group analysis and longitudinal studies. [less ▲]

Detailed reference viewed: 133 (42 ULg)
Full Text
Peer Reviewed
See detailNIMEFI: Gene Regulatory Network Inference using Multiple Ensemble Feature Importance Algorithms
Ruyssinck, Joeri; Huynh-Thu, Vân Anh ULg; Geurts, Pierre ULg et al

in PLoS ONE (2014), 9(3), 92709

One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts ... [more ▼]

One of the long-standing open challenges in computational systems biology is the topology inference of gene regulatory networks from high-throughput omics data. Recently, two community-wide efforts, DREAM4 and DREAM5, have been established to benchmark network inference techniques using gene expression measurements. In these challenges the overall top performer was the GENIE3 algorithm. This method decomposes the network inference task into separate regression problems for each gene in the network in which the expression values of a particular target gene are predicted using all other genes as possible predictors. Next, using tree-based ensemble methods, an importance measure for each predictor gene is calculated with respect to the target gene and a high feature importance is considered as putative evidence of a regulatory link existing between both genes. The contribution of this work is twofold. First, we generalize the regression decomposition strategy of GENIE3 to other feature importance methods. We compare the performance of support vector regression, the elastic net, random forest regression, symbolic regression and their ensemble variants in this setting to the original GENIE3 algorithm. To create the ensemble variants, we propose a subsampling approach which allows us to cast any feature selection algorithm that produces a feature ranking into an ensemble feature importance algorithm. We demonstrate that the ensemble setting is key to the network inference task, as only ensemble variants achieve top performance. As second contribution, we explore the effect of using rankwise averaged predictions of multiple ensemble algorithms as opposed to only one. We name this approach NIMEFI (Network Inference using Multiple Ensemble Feature Importance algorithms) and show that this approach outperforms all individual methods in general, although on a specific network a single method can perform better. An implementation of NIMEFI has been made publicly available. [less ▲]

Detailed reference viewed: 68 (10 ULg)
Full Text
Peer Reviewed
See detailCXCR4-related increase of circulating human lymphoid progenitors after allogeneic hematopoietic stem cell transplantation
Glauzy, Salomé; André-Schmutz, I; Larghero, J et al

in PLoS ONE (2014), 9(3), 91492

Detailed reference viewed: 8 (1 ULg)
Full Text
Peer Reviewed
See detailIdentification of Metabolic Pathways Expressed by Pichia anomala KH6 in the Presence of the Pathogen Botrytis cinerea on Apple: New Possible Targets for Biocontrol Improvement
Kwasiborski, Anthony; Bajji, Mohammed; Renaut, J. et al

in PLoS ONE (2014), 9(3),

Detailed reference viewed: 40 (9 ULg)
Full Text
Peer Reviewed
See detailCombining PET images and neuropsychological test data for automatic diagnosis of Alzheimer’s disease
Segovia-Román, Fermín ULg; Bastin, Christine ULg; Salmon, Eric ULg et al

in PLoS ONE (2014), 9(2),

In recent years, several approaches to develop computer aided diagnosis (CAD) systems for dementia have been proposed. Some of these systems analyze neurological brain images by means of machine learning ... [more ▼]

In recent years, several approaches to develop computer aided diagnosis (CAD) systems for dementia have been proposed. Some of these systems analyze neurological brain images by means of machine learning algorithms in order to find the patterns that characterize the disorder, and a few combine several imaging modalities to improve the diagnostic accuracy. However, they usually do not use neuropsychological testing data in that analysis. The purpose of this work is to measure the advantages of using not only neuroimages as data source in CAD systems for dementia but also neuropsychological scores. To this aim, we compared the accuracy rates achieved by systems that use neuropsychological scores beside the imaging data in the classification step and systems that use only one of these data sources. In order to address the small sample size problem and facilitate the data combination, a dimensionality reduction step (implemented using three different algorithms) was also applied on the imaging data. After each image is summarized in a reduced set of image features, the data sources were combined and classified using three different data combination approaches and a Support Vector Machine classifier. That way, by testing different dimensionality reduction methods and several data combination approaches, we aim not only highlighting the advantages of using neuropsychological scores in the classification, but also implementing the most accurate computer system for early dementia detention. The accuracy of the CAD systems were estimated using a database with records from 46 subjects, diagnosed with MCI or AD. A peak accuracy rate of 89% was obtained. In all cases the accuracy achieved using both, neuropsychological scores and imaging data, was substantially higher than the one obtained using only the imaging data. [less ▲]

Detailed reference viewed: 154 (25 ULg)
Full Text
Peer Reviewed
See detailDo Photobiont Switch and Cephalodia Emancipation Act as Evolutionary Drivers in the Lichen Symbiosis? A Case Study in the Pannariaceae (Peltigerales)
Magain, Nicolas ULg; Sérusiaux, Emmanuël ULg

in PLoS ONE (2014), 9(2), 89876

Lichen symbioses in the Pannariaceae associate an ascomycete and either cyanobacteria alone (usually Nostoc; bipartite thalli) or green algae and cyanobacteria (cyanobacteria being located in dedicated ... [more ▼]

Lichen symbioses in the Pannariaceae associate an ascomycete and either cyanobacteria alone (usually Nostoc; bipartite thalli) or green algae and cyanobacteria (cyanobacteria being located in dedicated structures called cephalodia; tripartite thalli) as photosynthetic partners (photobionts). In bipartite thalli, cyanobacteria can either be restricted to a well-delimited layer within the thallus (‘pannarioid’ thalli) or spread over the thallus that becomes gelatinous when wet (‘collematoid’ thalli). We studied the collematoid genera Kroswia and Physma and an undescribed tripartite species along with representatives of the pannarioid genera Fuscopannaria, Pannaria and Parmeliella. Molecular inferences from 4 loci for the fungus and 1 locus for the photobiont and statistical analyses within a phylogenetic framework support the following: (a) several switches from pannarioid to collematoid thalli occured and are correlated with photobiont switches; the collematoid genus Kroswia is nested within the pannarioid genus Fuscopannaria and the collematoid genus Physma is sister to the pannarioid Parmeliella mariana group; (b) Nostoc associated with collematoid thalli in the Pannariaceae are related to that of the Collemataceae (which contains only collematoid thalli), and never associated with pannarioid thalli; Nostoc associated with pannarioid thalli also associate in other families with similar morphology; (c) ancestors of several lineages in the Pannariaceae developed tripartite thalli, bipartite thalli probably resulting from cephalodia emancipation from tripartite thalli which eventually evolved and diverged, as suggested by the same Nostoc present in the collematoid genus Physma and in the cephalodia of a closely related tripartite species; Photobiont switches and cephalodia emancipation followed by divergence are thus suspected to act as evolutionary drivers in the family Pannariaceae. [less ▲]

Detailed reference viewed: 50 (4 ULg)
Full Text
Peer Reviewed
See detailHow Does Pollen Chemistry Impact Development and Feeding Behaviour of Polylectic Bees?
Vanderplanck, Maryse ULg; Moerman, Romain; Rasmont, Pierre et al

in PLoS ONE (2014), 9(1), 9

Larvae and imagos of bees rely exclusively on floral rewards as a food source but host-plant range can vary greatly among bee species. While oligolectic species forage on pollen from a single family of ... [more ▼]

Larvae and imagos of bees rely exclusively on floral rewards as a food source but host-plant range can vary greatly among bee species. While oligolectic species forage on pollen from a single family of host plants, polylectic bees, such as bumblebees, collect pollen from many families of plants. These polylectic species contend with interspecific variability in essential nutrients of their host-plants but we have only a limited understanding of the way in which chemicals and chemical combinations influence bee development and feeding behaviour. In this paper, we investigated five different pollen diets (Calluna vulgaris, Cistus sp., Cytisus scoparius, Salix caprea and Sorbus aucuparia) to determine how their chemical content affected bumblebee colony development and pollen/syrup collection. Three compounds were used to characterise pollen content: polypeptides, amino acids and sterols. Several parameters were used to determine the impact of diet on micro-colonies: (i) Number and weight of larvae (total and mean weight of larvae), (ii) weight of pollen collected, (iii) pollen efficacy (total weight of larvae divided by weight of the pollen collected) and (iv) syrup collection. Our results show that pollen collection is similar regardless of chemical variation in pollen diet while syrup collection is variable. Micro-colonies fed on S. aucuparia and C. scoparius pollen produced larger larvae (i.e. better mates and winter survivors) and fed less on nectar compared to the other diets. Pollen from both of these species contains 24-methylenecholesterol and high concentrations of polypeptides/total amino acids. This pollen nutritional “theme” seems therefore to promote worker reproduction in B. terrestris micro-colonies and could be linked to high fitness for queenright colonies. As workers are able to selectively forage on pollen of high chemical quality, plants may be evolutionarily selected for their pollen content, which might attract and increase the degree of fidelity of generalist pollinators, such as bumblebees. [less ▲]

Detailed reference viewed: 40 (10 ULg)
Full Text
Peer Reviewed
See detailBone marrow-derived mesenchymal stem cells drive lymphangiogenesis.
Maertens, Ludovic ULg; Erpicum, Charlotte ULg; Detry, Benoît ULg et al

in PLoS ONE (2014), 9(9), 106976

It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during ... [more ▼]

It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2. [less ▲]

Detailed reference viewed: 48 (9 ULg)
Full Text
Peer Reviewed
See detailCortical response variation with different sound pressure levels: a combined event-related potentials and FMRI study.
Neuner, Irene; Kawohl, Wolfram; Arrubla Martinez, Jorge Andres ULg et al

in PLoS ONE (2014), 9(10), 109216

INTRODUCTION: Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI ... [more ▼]

INTRODUCTION: Simultaneous recording of electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) provides high spatial and temporal resolution. In this study we combined EEG and fMRI to investigate the structures involved in the processing of different sound pressure levels (SPLs). METHODS: EEG data were recorded simultaneously with fMRI from 16 healthy volunteers using MR compatible devices at 3 T. Tones with different SPLs were delivered to the volunteers and the N1/P2 amplitudes were included as covariates in the fMRI data analysis in order to compare the structures activated with high and low SPLs. Analysis of variance (ANOVA) and ROI analysis were also performed. Additionally, source localisation analysis was performed on the EEG data. RESULTS: The integration of averaged ERP parameters into the fMRI analysis showed an extended map of areas exhibiting covariation with the BOLD signal related to the auditory stimuli. The ANOVA and ROI analyses also revealed additional brain areas other than the primary auditory cortex (PAC) which were active with the auditory stimulation at different SPLs. The source localisation analyses showed additional sources apart from the PAC which were active with the high SPLs. DISCUSSION: The PAC and the insula play an important role in the processing of different SPLs. In the fMRI analysis, additional activation was found in the anterior cingulate cortex, opercular and orbito-frontal cortices with high SPLs. A strong response of the visual cortex was also found with the high SPLs, suggesting the presence of cross-modal effects. [less ▲]

Detailed reference viewed: 14 (1 ULg)
Full Text
Peer Reviewed
See detailRemoval of pulse artefact from EEG data recorded in MR environment at 3T. Setting of ICA parameters for marking artefactual components: application to resting-state data.
Maggioni, Eleonora; Arrubla Martinez, Jorge Andres ULg; Warbrick, Tracy et al

in PLoS ONE (2014), 9(11), 112147

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) allow for a non-invasive investigation of cerebral functions with high temporal and spatial resolution. The main ... [more ▼]

Simultaneous electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) allow for a non-invasive investigation of cerebral functions with high temporal and spatial resolution. The main challenge of such integration is the removal of the pulse artefact (PA) that affects EEG signals recorded in the magnetic resonance (MR) scanner. Often applied techniques for this purpose are Optimal Basis Set (OBS) and Independent Component Analysis (ICA). The combination of OBS and ICA is increasingly used, since it can potentially improve the correction performed by each technique separately. The present study is focused on the OBS-ICA combination and is aimed at providing the optimal ICA parameters for PA correction in resting-state EEG data, where the information of interest is not specified in latency and amplitude as in, for example, evoked potential. A comparison between two intervals for ICA calculation and four methods for marking artefactual components was performed. The performance of the methods was discussed in terms of their capability to 1) remove the artefact and 2) preserve the information of interest. The analysis included 12 subjects and two resting-state datasets for each of them. The results showed that none of the signal lengths for the ICA calculation was highly preferable to the other. Among the methods for the identification of PA-related components, the one based on the wavelets transform of each component emerged as the best compromise between the effectiveness in removing PA and the conservation of the physiological neuronal content. [less ▲]

Detailed reference viewed: 18 (0 ULg)
Full Text
Peer Reviewed
See detailThe default mode network and EEG regional spectral power: a simultaneous fMRI-EEG study.
Neuner, Irene; Arrubla Martinez, Jorge Andres ULg; Werner, Cornelius J. et al

in PLoS ONE (2014), 9(2), 88214

Electroencephalography (EEG) frequencies have been linked to specific functions as an "electrophysiological signature" of a function. A combination of oscillatory rhythms has also been described for ... [more ▼]

Electroencephalography (EEG) frequencies have been linked to specific functions as an "electrophysiological signature" of a function. A combination of oscillatory rhythms has also been described for specific functions, with or without predominance of one specific frequency-band. In a simultaneous fMRI-EEG study at 3 T we studied the relationship between the default mode network (DMN) and the power of EEG frequency bands. As a methodological approach, we applied Multivariate Exploratory Linear Optimized Decomposition into Independent Components (MELODIC) and dual regression analysis for fMRI resting state data. EEG power for the alpha, beta, delta and theta-bands were extracted from the structures forming the DMN in a region-of-interest approach by applying Low Resolution Electromagnetic Tomography (LORETA). A strong link between the spontaneous BOLD response of the left parahippocampal gyrus and the delta-band extracted from the anterior cingulate cortex was found. A positive correlation between the beta-1 frequency power extracted from the posterior cingulate cortex (PCC) and the spontaneous BOLD response of the right supplementary motor cortex was also established. The beta-2 frequency power extracted from the PCC and the precuneus showed a positive correlation with the BOLD response of the right frontal cortex. Our results support the notion of beta-band activity governing the "status quo" in cognitive and motor setup. The highly significant correlation found between the delta power within the DMN and the parahippocampal gyrus is in line with the association of delta frequencies with memory processes. We assumed "ongoing activity" during "resting state" in bringing events from the past to the mind, in which the parahippocampal gyrus is a relevant structure. Our data demonstrate that spontaneous BOLD fluctuations within the DMN are associated with different EEG-bands and strengthen the conclusion that this network is characterized by a specific electrophysiological signature created by combination of different brain rhythms subserving different putative functions. [less ▲]

Detailed reference viewed: 47 (1 ULg)
Full Text
Peer Reviewed
See detailGABA concentration in posterior cingulate cortex predicts putamen response during resting state fMRI.
Arrubla Martinez, Jorge Andres ULg; Tse, Desmond H. Y.; Amkreutz, Christin et al

in PLoS ONE (2014), 9(9), 106609

The role of neurotransmitters in the activity of resting state networks has been gaining attention and has become a field of research with magnetic resonance spectroscopy (MRS) being one of the key ... [more ▼]

The role of neurotransmitters in the activity of resting state networks has been gaining attention and has become a field of research with magnetic resonance spectroscopy (MRS) being one of the key techniques. MRS permits the measurement of γ-aminobutyric acid (GABA) and glutamate levels, the central biochemical constituents of the excitation-inhibition balance in vivo. The inhibitory effects of GABA in the brain have been largely investigated in relation to the activity of resting state networks in functional magnetic resonance imaging (fMRI). In this study GABA concentration in the posterior cingulate cortex (PCC) was measured using single voxel spectra acquired with standard point resolved spectroscopy (PRESS) from 20 healthy male volunteers at 3 T. Resting state fMRI was consecutively measured and the values of GABA/Creatine+Phosphocreatine ratio (GABA ratio) were included in a general linear model matrix as a step of dual regression analysis in order to identify voxels whose neuroimaging metrics during rest were related to individual levels of the GABA ratio. Our data show that the connection strength of putamen to the default-mode network during resting state has a negative linear relationship with the GABA ratio measured in the PCC. These findings highlight the role of PCC and GABA in segregation of the motor input, which is an inherent condition that characterises resting state. [less ▲]

Detailed reference viewed: 25 (2 ULg)
Full Text
Peer Reviewed
See detailPotentiated interaction between ineffective doses of budesonide and formoterol to control the inhaled cadmium-induced up-regulation of metalloproteinases and acute pulmonary inflammation in rats.
Zhang, Wenhui; Zhi, Jianming; Cui, Yongyao et al

in PloS one (2014), 9(10), 109136

The anti-inflammatory properties of glucocorticoids are well known but their protective effects exerted with a low potency against heavy metals-induced pulmonary inflammation remain unclear. In this study ... [more ▼]

The anti-inflammatory properties of glucocorticoids are well known but their protective effects exerted with a low potency against heavy metals-induced pulmonary inflammation remain unclear. In this study, a model of acute pulmonary inflammation induced by a single inhalation of cadmium in male Sprague-Dawley rats was used to investigate whether formoterol can improve the anti-inflammatory effects of budesonide. The cadmium-related inflammatory responses, including matrix metalloproteinase-9 (MMP-9) activity, were evaluated. Compared to the values obtained in rats exposed to cadmium, pretreatment of inhaled budesonide (0.5 mg/15 ml) elicited a significant decrease in total cell and neutrophil counts in bronchoalveolar lavage fluid (BALF) associated with a significant reduction of MMP-9 activity which was highly correlated with the number of inflammatory cells in BALF. Additionally, cadmium-induced lung injuries characterized by inflammatory cell infiltration within alveoli and the interstitium were attenuated by the pre-treatment of budesonide. Though the low concentration of budesonide (0.25 mg/15 ml) exerted a very limited inhibitory effects in the present rat model, its combination with an inefficient concentration of formoterol (0.5 mg/30 ml) showed an enhanced inhibitory effect on neutrophil and total cell counts as well as on the histological lung injuries associated with a potentiation of inhibition on the MMP-9 activity. In conclusion, high concentration of budesonide alone could partially protect the lungs against cadmium exposure induced-acute neutrophilic pulmonary inflammation via the inhibition of MMP-9 activity. The combination with formoterol could enhance the protective effects of both drugs, suggesting a new therapeutic strategy for the treatment of heavy metals-induced lung diseases. [less ▲]

Detailed reference viewed: 18 (1 ULg)
Full Text
Peer Reviewed
See detailEstablishment of a murine graft-versus-myeloma model using allogeneic stem cell transplantation
Binsfeld, Marilène ULg; Beguin, Yves ULg; Belle, Ludovic ULg et al

in PLoS ONE (2014), (doi:10.1371), 113764

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic ... [more ▼]

Background: Multiple myeloma (MM) is a malignant plasma cell disorder with poor long-term survival and high recurrence rates. Despite evidence of graft-versus-myeloma (GvM) effects, the use of allogeneic hematopoietic stem cell transplantation (allo-SCT) has remained controversial in MM. In the current study, we investigated the anti-myeloma effects of allo-SCT from B10.D2 mice into MHC-matched myeloma-bearing Balb/cJ mice (previously injected with the MOPC315.BM myeloma cell line), based on a chronic graft-versus-host disease (GvHD) murine model. Methods and results: Balb/cJ mice were injected intravenously with luciferase-transfected MOPC315.BM cells, and received 30 days later an allogeneic (B10.D2 donor) or autologous (Balb/cJ donor) transplantation by intravenous administration of bone marrow cells and splenocytes. We observed a graft-versus-myeloma effect in 94% of the allogeneic transplanted mice, as luciferase signal completely disappeared after transplantation, whereas all the autologous transplanted mice showed myeloma evolution. Lower serum paraprotein levels and myeloma infiltration in bone marrow and spleen in the allogeneic setting confirmed the observed GvM effect, while allogeneic mice also displayed chronic GvHD symptoms. In vivo and in vitro data suggest the involvement of effector memory CD4 and CD8 T cells in the GvM effect. The essential role of CD8 T cells was demonstrated in vivo where CD8 T-cell depletion of the graft resulted in reduced GvM effects. Finally, TCR V spectratyping analysis identified V families within CD4 and CD8 T cells which were associated with both GvM effects and GVHD, whereas other V families within CD4 T cells were associated exclusively with either GvM or GvHD responses. Conclusions: We successfully established an immunocompetent murine model of graft-versus-myeloma. This is the first immunocompetent murine model which is based on a MM model closely resembling human MM disease (bone marrow tropism, ...) and using allo-SCT after the disease establishment, as a curative treatment [less ▲]

Detailed reference viewed: 49 (21 ULg)
Full Text
Peer Reviewed
See detailGalectin Expression Profiling Identifies Galectin-1 and Galectin-9Δ5 as Prognostic Factors in Stage I/II Non-Small Cell Lung Cancer
Schulkens, Iris; Heusschen, Roy ULg; Van den boogaart, Vivianne et al

in PLoS ONE (2014), 9(9), 107988

Detailed reference viewed: 12 (2 ULg)
Full Text
Peer Reviewed
See detailCrystal structure of penicillin-binding protein 3 (PBP3) from Escherichia coli
Sauvage, Eric ULg; Derouaux, Adeline ULg; Fraipont, Claudine ULg et al

in PLoS ONE (2014)

In Escherichia coli, penicillin-binding protein 3 (PBP3), also known as FtsI, is a central component of the divisome, catalyzing cross-linking of the cell wall peptidoglycan during cell division. PBP3 is ... [more ▼]

In Escherichia coli, penicillin-binding protein 3 (PBP3), also known as FtsI, is a central component of the divisome, catalyzing cross-linking of the cell wall peptidoglycan during cell division. PBP3 is mainly periplasmic, with a 23 residues cytoplasmic tail and a single transmembrane helix. We have solved the crystal structure of a soluble form of PBP3 (PBP357-577) at 2.5 Å revealing the two modules of high molecular weight class B PBPs, a carboxy terminal module exhibiting transpeptidase activity and an amino terminal module with unknown function. To gain additional insight, the PBP3 Val88-Ser165 subdomain (PBP388-165), for which the electron density is poorly defined in the PBP3 crystal, was produced and its structure solved by SAD phasing at 2.1 Å. The structure shows a three dimensional domain swapping with a β-strand of one molecule inserted between two strands of the paired molecule, suggesting a possible role in PBP357-577 dimerization. [less ▲]

Detailed reference viewed: 49 (16 ULg)
Full Text
Peer Reviewed
See detailDiscovering main genetic interactions with LABNet LAsso-based network inference.
Gadaleta, Francesco ULg; Van Steen, Kristel ULg

in PloS one (2014), 9(11), 110451

Genome-wide association studies can potentially unravel the mechanisms behind complex traits and common genetic diseases. Despite the valuable results produced thus far, many questions remain unanswered ... [more ▼]

Genome-wide association studies can potentially unravel the mechanisms behind complex traits and common genetic diseases. Despite the valuable results produced thus far, many questions remain unanswered. For instance, which specific genetic compounds are linked to the risk of the disease under investigation; what biological mechanism do they act through; or how do they interact with environmental and other external factors? The driving force of computational biology is the constantly growing amount of big data generated by high-throughput technologies. A practical framework that can deal with this abundance of information and that consent to discovering genetic associations and interactions is provided by means of networks. Unfortunately, high dimensionality, the presence of noise and the geometry of data can make the aforementioned problem extremely challenging. We propose a penalised linear regression approach that can deal with the aforementioned issues that affect genetic data. We analyse the gene expression profiles of individuals with a common trait to infer the network structure of interactions among genes. The permutation-based approach leads to more stable and reliable networks inferred from synthetic microarray data. We show that a higher number of permutations determines the number of predicted edges, improves the overall sensitivity and controls the number of false positives. [less ▲]

Detailed reference viewed: 66 (0 ULg)