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See detailThe role of short-term memory and visuo-spatial skills in numerical magnitude processing: evidence from Turner syndrome
Attout, Lucie ULiege; Noël, Marie-Pascale; Nassogne, Marie-Cécile et al

in PLoS ONE (2017), 12(2), 0171454

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See detailStudies of HVC Plasticity in Adult Canaries Reveal Social Effects and Sex Differences as Well as Limitations of Multiple Markers Available to Assess Adult Neurogenesis.
Shevchouk, Olesya ULiege; Ball, G.F.; Cornil, Charlotte ULiege et al

in PLoS ONE (2017), 12(1), 0170938

In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new ... [more ▼]

In songbirds, neurogenesis in the song control nucleus HVC is sensitive to the hormonal and social environment but the dynamics of this process is difficult to assess with a single exogenous marker of new neurons. We simultaneously used three independent markers to investigate HVC neurogenesis in male and female canaries. Males were castrated, implanted with testosterone and housed either alone (M), with a female (M-F) or with another male (M-M) while females were implanted with 17β- estradiol and housed with a male (F-M). All subjects received injections of the two thymidine analogues, BrdU and of EdU, respectively 21 and 10 days before brain collection. Cells containing BrdU or EdU or expressing doublecortin (DCX), which labels newborn neurons, were quantified. Social context and sex differentially affected total BrdU+, EdU+, BrdU+EdU- and DCX+ populations. M-M males had a higher density of BrdU+ cells in the ventricular zone adjacent to HVC and of EdU+ in HVC than M-F males. M birds had a higher ratio of BrdU+EdU- to EdU+ cells than M-F subjects suggesting higher survival of newer neurons in the former group. Total number of HVC DCX+ cells was lower in M-F than in M-M males. Sex differences were also dependent of the type of marker used. Several technical limitations associated with the use of these multiple markers were also identified. These results indicate that proliferation, recruitment and survival of new neurons can be independently affected by environmental conditions and effects can only be fully discerned through the use of multiple neurogenesis markers. [less ▲]

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See detailMinimally invasive estimation of ventricular dead space volume through use of Frank-Starling curves.
Davidson, Shaun; Pretty, Chris; Pironet, Antoine et al

in PLoS ONE (2017), 12(4), 0176302

This paper develops a means of more easily and less invasively estimating ventricular dead space volume (Vd), an important, but difficult to measure physiological parameter. Vd represents a subject and ... [more ▼]

This paper develops a means of more easily and less invasively estimating ventricular dead space volume (Vd), an important, but difficult to measure physiological parameter. Vd represents a subject and condition dependent portion of measured ventricular volume that is not actively participating in ventricular function. It is employed in models based on the time varying elastance concept, which see widespread use in haemodynamic studies, and may have direct diagnostic use. The proposed method involves linear extrapolation of a Frank-Starling curve (stroke volume vs end-diastolic volume) and its end-systolic equivalent (stroke volume vs end-systolic volume), developed across normal clinical procedures such as recruitment manoeuvres, to their point of intersection with the y-axis (where stroke volume is 0) to determine Vd. To demonstrate the broad applicability of the method, it was validated across a cohort of six sedated and anaesthetised male Pietrain pigs, encompassing a variety of cardiac states from healthy baseline behaviour to circulatory failure due to septic shock induced by endotoxin infusion. Linear extrapolation of the curves was supported by strong linear correlation coefficients of R = 0.78 and R = 0.80 average for pre- and post- endotoxin infusion respectively, as well as good agreement between the two linearly extrapolated y-intercepts (Vd) for each subject (no more than 7.8% variation). Method validity was further supported by the physiologically reasonable Vd values produced, equivalent to 44.3-53.1% and 49.3-82.6% of baseline end-systolic volume before and after endotoxin infusion respectively. This method has the potential to allow Vd to be estimated without a particularly demanding, specialised protocol in an experimental environment. Further, due to the common use of both mechanical ventilation and recruitment manoeuvres in intensive care, this method, subject to the availability of multi-beat echocardiography, has the potential to allow for estimation of Vd in a clinical environment. [less ▲]

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See detailMaternal Nutrition during Pregnancy Affects Testicular and Bone Development, Glucose Metabolism and Response to Overnutrition in Weaned Horses Up to Two Years.
Robles, M; Gauthier, C; Mendoza García, Luis ULiege et al

in PLoS ONE (2017), 12(e0169295),

INTRODUCTION: Pregnant mares and post-weaning foals are often fed concentrates rich in soluble carbohydrates, together with forage. Recent studies suggest that the use of concentrates is linked to ... [more ▼]

INTRODUCTION: Pregnant mares and post-weaning foals are often fed concentrates rich in soluble carbohydrates, together with forage. Recent studies suggest that the use of concentrates is linked to alterations of metabolism and the development of osteochondrosis in foals. The aim of this study was to determine if broodmare diet during gestation affects metabolism, osteoarticular status and growth of yearlings overfed from 20 to 24 months of age and/or sexual maturity in prepubertal colts. MATERIAL AND METHODS: Twenty-four saddlebred mares were fed forage only (n = 12, group F) or cracked barley and forage (n = 12, group B) from mid-gestation until foaling. Colts were gelded at 12 months of age. Between 20 and 24 months of age, all yearlings were overfed (+140% of requirements) using an automatic concentrate feeder. Offspring were monitored for growth between 6 and 24 months of age, glucose homeostasis was evaluated via modified frequently sampled intra veinous glucose tolerance test (FSIGT) at 19 and 24 months of age and osteoarticular status was investigated using radiographic examinations at 24 months of age. The structure and function of testicles from prepubertal colts were analyzed using stereology and RT-qPCR. RESULTS: Post-weaning weight growth was not different between groups. Testicular maturation was delayed in F colts compared to B colts at 12 months of age. From 19 months of age, the cannon bone was wider in B vs F yearlings. F yearlings were more insulin resistant at 19 months compared to B yearlings but B yearlings were affected more severely by overnutrition with reduced insulin sensitivity. The osteoarticular status at 24 months of age was not different between groups. CONCLUSION: In conclusion, nutritional management of the pregnant broodmare and the growing foal may affect sexual maturity of colts and the metabolism of foals until 24 months of age. These effects may be deleterious for reproductive and sportive performances in older horses. [less ▲]

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See detailDevelopment and performance assessment of a luminex xMAP(R) direct hybridization assay for the detection and identification of indoor air fungal contamination.
Libert, Xavier; Packeu, Ann; Bureau, Fabrice ULiege et al

in PLoS ONE (2017), 12(3), 0173390

Considered as a public health problem, indoor fungal contamination is generally monitored using classical protocols based on culturing. However, this culture dependency could influence the ... [more ▼]

Considered as a public health problem, indoor fungal contamination is generally monitored using classical protocols based on culturing. However, this culture dependency could influence the representativeness of the fungal population detected in an analyzed sample as this includes the dead and uncultivable fraction. Moreover, culture-based protocols are often time-consuming. In this context, molecular tools are a powerful alternative, especially those allowing multiplexing. In this study a Luminex xMAP(R) assay was developed for the simultaneous detection of 10 fungal species which are most frequently in indoor air and that may cause health problems. This xMAP(R) assay was found to be sensitive, i.e. its limit of detection is ranging between 0.05 and 0.01 ng of gDNA. The assay was subsequently tested with environmental air samples which were also analyzed with a classical protocol. All the species identified with the classical method were also detected with the xMAP(R) assay, however in a shorter time frame. These results demonstrate that the Luminex xMAP(R) fungal assay developed in this study could contribute to the improvement of public health and specifically to the indoor fungal contamination treatment. [less ▲]

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See detailStructural models of the different trimers present in the core of phycobilisomes from Gracilaria chilensis based on crystal structures and sequences.
Dagnino-Leone, Jorge; Figueroa, Maximiliano; Mella, Claudia et al

in PLoS ONE (2017), 12(5), 0177540

Phycobilisomes (PBS) are accessory light harvesting protein complexes that directionally transfer energy towards photosystems. Phycobilisomes are organized in a central core and rods radiating from it ... [more ▼]

Phycobilisomes (PBS) are accessory light harvesting protein complexes that directionally transfer energy towards photosystems. Phycobilisomes are organized in a central core and rods radiating from it. Components of phycobilisomes in Gracilaria chilensis (Gch) are Phycobiliproteins (PBPs), Phycoerythrin (PE), and Phycocyanin (PC) in the rods, while Allophycocyanin (APC) is found in the core, and linker proteins (L). The function of such complexes depends on the structure of each component and their interaction. The core of PBS from cyanobacteria is mainly composed by cylinders of trimers of alpha and beta subunits forming heterodimers of Allophycocyanin, and other components of the core including subunits alphaII and beta18. As for the linkers, Linker core (LC) and Linker core membrane (LCM) are essential for the final emission towards photoreaction centers. Since we have previously focused our studies on the rods of the PBS, in the present article we investigated the components of the core in the phycobilisome from the eukaryotic algae, Gracilaria chilensis and their organization into trimers. Transmission electron microscopy provided the information for a three cylinders core, while the three dimensional structure of Allophycocyanin purified from Gch was determined by X-ray diffraction method and the biological unit was determined as a trimer by size exclusion chromatography. The protein sequences of all the components of the core were obtained by sequencing the corresponding genes and their expression confirmed by transcriptomic analysis. These subunits have seldom been reported in red algae, but not in Gracilaria chilensis. The subunits not present in the crystallographic structure were modeled to build the different composition of trimers. This article proposes structural models for the different types of trimers present in the core of phycobilisomes of Gch as a first step towards the final model for energy transfer in this system. [less ▲]

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See detailPatients' expectations impact their satisfaction following total hip or knee arthroplasty
Neuprez, Audrey ULiege; Delcour, J.-P.; Fatemi, F. et al

in PLoS ONE (2016), 11(12), 1-14

Introduction The objective of this study was to assess the number and magnitude of preoperative expectations and to correlate them with the degree of satisfaction expressed one year after Total Hip ... [more ▼]

Introduction The objective of this study was to assess the number and magnitude of preoperative expectations and to correlate them with the degree of satisfaction expressed one year after Total Hip Arthroplasty (THA) or Total Knee Arthroplasty (TKA), in patients with severe and painful osteoarthritis (OA). Materials and Methods Preoperative expectations (within 20 days prior to surgery) and postoperative satisfaction (one year after the intervention) were measured using the previously validated French version of the Hospital for Special Surgery Hip or Knee Replacement Expectations Survey. Postoperative satisfaction was measured using a specific scale, following the same methodology as that used for the assessment of expectations. Prediction of the satisfaction of the patients was performed using multivariate linear regression modelling. Results A total of 138 patients (80 THA and 58 TKA) completed the two parts of the study. The expectations score (mean ± SD) (range 0-100) was 72.58 ± 12.63 before THA and 69.10 ± 13.72 before TKA (p = 0.13). The number of expectations expressed was 14.34 ± 1.32 (out of a potential maximum of 18) before THA and 14.70 ± 2.29 (out of a potential maximum of 19) before TKA. After 1 year, THA generated a significantly higher degree of satisfaction compared to TKA (69.70 ± 14.46 v 60.44 ± 17.54, p<0.001) (range 0-100). The pre-operative expectations score was the single best positive predictor of the post-surgery satisfaction assessment both for TKA and THA. Conclusion Patients undergoing total joint arthroplasty for end-stage OA have a high level of expectations, before both THA and TKA. While both types of interventions significantly improve essential and non-essential activities, the rate of satisfaction is significantly greater post THA. Preoperative expectations are a major contributor to the final degree of satisfaction, one year after surgery. These results re-emphasize the need for an optimal preoperative interaction between health care providers and patients, to allow patients a chance to foresee a reasonable outcome after TJA. © 2016 Neuprez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. [less ▲]

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See detailLimited Impact of Imatinib in a Murine Model of Sclerodermatous Chronic Graft-versus-Host Disease
Belle, Ludovic ULiege; Fransolet, Gilles ULiege; Somja, Joan ULiege et al

in PLoS ONE (2016), 11

Background Sclerodermatous chronic Graft-versus-Host Disease (scl-cGVHD) is one of the most severe form of cGVHD. The Platelet-derived Grotwth Factor (PDGF) and the Transforming Growth Factor-β (TGF-β ... [more ▼]

Background Sclerodermatous chronic Graft-versus-Host Disease (scl-cGVHD) is one of the most severe form of cGVHD. The Platelet-derived Grotwth Factor (PDGF) and the Transforming Growth Factor-β (TGF-β) play a significant role in the fibrosing process occurring in scl-cGVHD. This prompted us to assess the impact of the PDGF-r and c-Abl tyrosine kinase inhibitor imatinib on scl-cGVHD. Methods To assess the impact of imatinib on T cell subset proliferation in vivo, Balb/cJ recipient mice were lethally (7 Gy) irradiated and then injected with 10x106 bone marrow cells from B10.D2 mice on day 0. Fourteen days later, 70x106 carboxyfluorescein succinimidyl ester (CFSE)-labeled splenocytes from B10.D2 mice were infused and imatinib or sterile water was administered for 5 days. To induce severe scl-cGVHD, Balb/cJ mice were injected i.v. with 10.106 bone marrow cells and 70.106 splenocytes from B10.D2 donor mice after 7 Gy irradiation. Mice were then given sterile water or imatinib from day +7 after transplantation to the end of the experiment (day +52). Results Imatinib decreased the proliferation of total T cells (P = 0.02), CD8+ T cells (P = 0.01), and of regulatory T cells (Tregs) (P = 0.02) in the spleen. In the severe scl-cGVHD model, imatinib-treated mice had significantly lower levels of PDGF-r phosphorylation than control mice on day 29 after transplantation (P = 0.008). However, scl-cGVHD scores were similar between vehicle- and imatinib-treated mice during the whole experiment, while there was a suggestion for less weight loss in imatinib-treated mice that reached statistical significance at day +52 following transplantation (P = 0.02). [less ▲]

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See detailA Novel Physiological Glycosaminoglycan-Deficient Splice Variant of Neuropilin-1 Is Anti-Tumorigenic In Vitro and In Vivo
Hendricks, Céline; Dubail, Johanne; Brohée, Laura ULiege et al

in PLoS ONE (2016)

Neuropilin-1 (NRP1) is a transmembrane protein acting as a co-receptor for several growth factors and interacting with other proteins such as integrins and plexins/semaphorins. It is involved in axonal ... [more ▼]

Neuropilin-1 (NRP1) is a transmembrane protein acting as a co-receptor for several growth factors and interacting with other proteins such as integrins and plexins/semaphorins. It is involved in axonal development, angiogenesis and cancer progression. Its primary mRNA is subjected to alternative splicing mechanisms generating different isoforms, some of which lack the transmembrane domain and display antagonist properties to NRP1 full size (FS). NRP1 is further post-translationally modified by the addition of glycosaminoglycans (GAG) side chains through an O-glycosylation site at serine612. Here, we characterized a novel splice variant which has never been investigated, NRP1-Δ7, differing from the NRP1-FS by a deletion of 7 amino acids occurring two residues downstream of the O-glycosylation site. This short sequence contains two aspartic residues critical for efficient glycosylation. As expected, the high molecular weight products appearing as a smear in SDS-PAGE and reflecting the presence of GAG in NRP1-FS were undetectable in the NRP1-Δ7 protein. NRP1-Δ7 mRNA was found expressed at an appreciable level, between 10 and 30% of the total NRP1, by various cells lines and tissues from human and murine origin. To investigate the biological properties of this isoform, we generated prostatic (PC3) and breast (MDA-MB-231) cancer cells able to express recombinant NRP1-FS or NRP1-Δ7 in a doxycycline-inducible manner. Cells with increased expression of NRP1-Δ7 were characterized in vitro by a significant reduction of proliferation, migration and anchorage-independent growth, while NRP1-FS had the expected opposite “pro-tumoral” effects. Upon VEGF-A165 treatment, a lower internalization rate was observed for NRP1-Δ7 than for NRP1-FS. Finally, we showed that NRP1-Δ7 inhibited growth of prostatic tumors and their vascularization in vivo. This report identifies NRP1-Δ7 as a splice variant displaying anti-tumorigenic properties in vitro and in vivo, emphasizing the need to consider this isoform in future studies. [less ▲]

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See detail68Ga and 188Re Starch-Based Microparticles as Theranostic Tool for the Hepatocellular Carcinoma: Radiolabeling and Preliminary In Vivo Rat Studies
Verger, Elise ULiege; Drion, Pierre ULiege; MEFFRE, Geneviève ULiege et al

in PLoS ONE (2016)

This work aims to develop, validate and optimize the radiolabeling of Starch-Based Microparticles (SBMP) by 188Re and 68Ga in the form of ready-to-use radiolabeling kits, the ultimate goal being to obtain ... [more ▼]

This work aims to develop, validate and optimize the radiolabeling of Starch-Based Microparticles (SBMP) by 188Re and 68Ga in the form of ready-to-use radiolabeling kits, the ultimate goal being to obtain a unique theranostic vector for the treatment of Hepatocellular Carcinoma. METHODS: Optimal labeling conditions and composition of freeze-dried kits were defined by monitoring the radiochemical purity while varying several parameters. In vitro stability studies were carried out, as well as an in vivo biodistribution as a preliminary approach with the intra-arterial injection of 68Ga radiolabeled SBMP into the hepatic artery of DENA-induced rats followed by PET/CT imaging. RESULTS: Kits were optimized for 188Re and 68Ga with high and stable radiochemical purity (>95% and >98% respectively). The in vivo preliminary study was successful with more than 95% of activity found in the liver and mostly in the tumorous part. CONCLUSION: SBMP are a promising theranostic agent for the Selective Internal Radiation Therapy of Hepatocellular carcinoma [less ▲]

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See detailNuclear Magnetic Resonance Metabolomic Profiling of Mouse Kidney, Urine and Serum Following Renal Ischemia/Reperfusion Injury.
Jouret, François ULiege; Leenders, Justine ULiege; Defraigne, Jean-Olivier ULiege et al

in PLoS ONE (2016), 11(9), 1-14

Abstract BACKGROUND: Ischemia/reperfusion (I/R) is the most common cause of acute kidney injury (AKI). Its pathophysiology remains unclear. Metabolomics is dedicated to identify metabolites involved in ... [more ▼]

Abstract BACKGROUND: Ischemia/reperfusion (I/R) is the most common cause of acute kidney injury (AKI). Its pathophysiology remains unclear. Metabolomics is dedicated to identify metabolites involved in (patho)physiological changes of integrated living systems. Here, we performed 1H-Nuclear Magnetic Resonance metabolomics using urine, serum and kidney samples from a mouse model of renal I/R. METHODS: Renal 30-min ischemia was induced in 12-week-old C57BL/6J male mice by bilaterally clamping vascular pedicles, and was followed by 6, 24 or 48-hour reperfusion (n = 12/group). Sham-operated mice were used as controls. Statistical discriminant analyses, i.e. principal component analysis and orthogonal projections to latent structures (OPLS-DA), were performed on urine, serum and kidney lysates at each time-point. Multivariate receiver operating characteristic (ROC) curves were drawn, and sensitivity and specificity were calculated from ROC confusion matrix (with averaged class probabilities across 100 cross-validations). RESULTS: Urine OPLS-DA analysis showed a net separation between I/R and sham groups, with significant variations in levels of taurine, di- and tri-methylamine, creatine and lactate. Such changes were observed as early as 6 hours post reperfusion. Major metabolome modifications occurred at 24h post reperfusion. At this time-point, correlation coefficients between urine spectra and conventional AKI biomarkers, i.e. serum creatinine and urea levels, reached 0.94 and 0.95, respectively. The area under ROC curve at 6h, 24h and 48h post surgery were 0.73, 0.98 and 0.97, respectively. Similar discriminations were found in kidney samples, with changes in levels of lactate, fatty acids, choline and taurine. By contrast, serum OPLS-DA analysis could not discriminate sham-operated from I/R-exposed animals. CONCLUSIONS: Our study demonstrates that renal I/R in mouse causes early and sustained metabolomic changes in urine and kidney composition. The most implicated pathways at 6h and 24h post reperfusion include gluconeogenesis, taurine and hypotaurine metabolism, whereas protein biosynthesis, glycolysis, and galactose and arginine metabolism are key at 48h post reperfusion. [less ▲]

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See detailThe Envelope Cytoplasmic Tail of HIV-1 Subtype C Contributes to Poor Replication Capacity through Low Viral Infectivity and Cell-to-Cell Transmission.
Santos da Silva, Eveline; Mulinge, Martin; Lemaire, Morgane et al

in PLoS ONE (2016)

The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in ... [more ▼]

The cytoplasmic tail (gp41CT) of the HIV-1 envelope (Env) mediates Env incorporation into virions and regulates Env intracellular trafficking. Little is known about the functional impact of variability in this domain. To address this issue, we compared the replication of recombinant virus pairs carrying the full Env (Env viruses) or the Env ectodomain fused to the gp41CT of NL4.3 (EnvEC viruses) (12 subtype C and 10 subtype B pairs) in primary CD4+ T-cells and monocyte-derived-macrophages (MDMs). In CD4+ T-cells, replication was as follows: B-EnvEC = B-Env>C-EnvEC>C-Env, indicating that the gp41CT of subtype C contributes to the low replicative capacity of this subtype. In MDMs, in contrast, replication capacity was comparable for all viruses regardless of subtype and of gp41CT. In CD4+ T-cells, viral entry, viral release and viral gene expression were similar. However, infectivity of free virions and cell-to-cell transmission of C-Env viruses released by CD4+ T-cells was lower, suggestive of lower Env incorporation into virions. Subtype C matrix only minimally rescued viral replication and failed to restore infectivity of free viruses and cell-to-cell transmission. Taken together, these results show that polymorphisms in the gp41CT contribute to viral replication capacity and suggest that the number of Env spikes per virion may vary across subtypes. These findings should be taken into consideration in the design of vaccines. [less ▲]

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See detailDegradation rate of 5-fluorouracil in Metastatic Colorectal Cancer: A New Predictive Outcome Biomarker?
Botticelli, Andrea; Borro, Marina; ONESTI, Concetta Elisa ULiege et al

in PLoS ONE (2016), 11(9), 0163105

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See detailAssociation of Empirically Derived Dietary Patterns with Cardiovascular Risk Factors: A Comparison of PCA and RRR Methods
Sauvageot, Nicolas ULiege; Leite, sonia; Alkerwi, Ala'a et al

in PLoS ONE (2016), 11(8),

Abstract Introduction Principal component analysis is used to determine dietary behaviors of a population whereas reduced rank regression is used to construct disease-related dietary patterns. This study ... [more ▼]

Abstract Introduction Principal component analysis is used to determine dietary behaviors of a population whereas reduced rank regression is used to construct disease-related dietary patterns. This study aimed to compare both types of DP and theirs associations with cardiovascular risk factors (CVRF). Materiel and Methods Data were derived from the cross sectional NESCAV (Nutrition, Environment and Cardiovascular Health) study, aiming to describe the cardiovascular health of the Greater region’s population (Grand duchy of Luxembourg, Wallonia (Belgium), Lorraine (France)). 2298 individuals were included for this study and dietary intake was assessed using a 134-item food frequency questionnaire. Results We found that CVRF-related patterns also reflect eating behaviours of the population. Comparing concordant food groups between both dietary pattern methods, a diet high in fruits, oleaginous and dried fruits, vegetables, olive oil, fats rich in omega 6 and tea and low in fried foods, lean and fatty meat, processed meat, ready meal, soft drink and beer was associated with lower prevalence of CVRF. In the opposite, a pattern characterized by high intakes of fried foods, meat, offal, beer, wine and aperitifs and spirits, and low intakes of cereals, sugar and sweets and soft drinks was associated with higher prevalence of CVRF. Conclusion In sum, we found that a “Prudent” and “Animal protein and alcohol” patterns were both associated with CVRF and behaviourally meaningful. Moreover, the relationships of those dietary patterns with lifestyle characteristics support the theory that food choices are part of a larger pattern of healthy lifestyle. [less ▲]

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See detailHabenular Neurogenesis in Zebrafish Is Regulated by a Hedgehog, Pax6 Proneural Gene Cascade
Halluin, Caroline; Madelaine, Romain; Naye, Francois et al

in PLoS ONE (2016), 11(7), 0158210

The habenulae are highly conserved nuclei in the dorsal diencephalon that connect the forebrain to the midbrain and hindbrain. These nuclei have been implicated in a broad variety of behaviours in humans ... [more ▼]

The habenulae are highly conserved nuclei in the dorsal diencephalon that connect the forebrain to the midbrain and hindbrain. These nuclei have been implicated in a broad variety of behaviours in humans, primates, rodents and zebrafish. Despite this, the molecular mechanisms that control the genesis and differentiation of neural progenitors in the habenulae remain relatively unknown. We have previously shown that, in zebrafish, the timing of habenular neurogenesis is left-right asymmetric and that in the absence of Nodal signalling this asymmetry is lost. Here, we show that habenular neurogenesis requires the homeobox transcription factor Pax6a and the redundant action of two proneural bHLH factors, Neurog1 and Neurod4. We present evidence that Hedgehog signalling is required for the expression of pax6a, which is in turn necessary for the expression of neurog1 and neurod4. Finally, we demonstrate by pharmacological inhibition that Hedgehog signalling is required continuously during habenular neurogenesis and by cell transplantation experiments that pathway activation is required cell autonomously. Our data sheds light on the mechanism underlying habenular development that may provide insights into how Nodal signalling imposes asymmetry on the timing of habenular neurogenesis. [less ▲]

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See detailTracing QTLs for Leaf Blast Resistance and Agronomic Performance of Finger Millet (Eleusine coracana (L.) Gaertn.) Genotypes through Association Mapping and in silico Comparative Genomics Analyses.
Ramakrishnan, M; Stanislaus, Antony Ceasar ULiege; Duraipandiyan, V. et al

in PLoS ONE (2016)

Finger millet is one of the small millets with high nutritive value. This crop is vulnerable to blast disease caused by Pyricularia grisea, which occurs annually during rainy and winter seasons. Leaf ... [more ▼]

Finger millet is one of the small millets with high nutritive value. This crop is vulnerable to blast disease caused by Pyricularia grisea, which occurs annually during rainy and winter seasons. Leaf blast occurs at early crop stage and is highly damaging. Mapping of resistance genes and other quantitative trait loci (QTLs) for agronomic performance can be of great use for improving finger millet genotypes. Evaluation of one hundred and twenty-eight finger millet genotypes in natural field conditions revealed that leaf blast caused severe setback on agronomic performance for susceptible genotypes, most significant traits being plant height and root length. Plant height was reduced under disease severity while root length was increased. Among the genotypes, IE4795 showed superior response in terms of both disease resistance and better agronomic performance. A total of seven unambiguous QTLs were found to be associated with various agronomic traits including leaf blast resistance by association mapping analysis. The markers, UGEP101 and UGEP95, were strongly associated with blast resistance. UGEP98 was associated with tiller number and UGEP9 was associated with root length and seed yield. Cross species validation of markers revealed that 12 candidate genes were associated with 8 QTLs in the genomes of grass species such as rice, foxtail millet, maize, Brachypodium stacei, B. distachyon, Panicum hallii and switchgrass. Several candidate genes were found proximal to orthologous sequences of the identified QTLs such as 1,4-β-glucanase for leaf blast resistance, cytokinin dehydrogenase (CKX) for tiller production, calmodulin (CaM) binding protein for seed yield and pectin methylesterase inhibitor (PMEI) for root growth and development. Most of these QTLs and their putatively associated candidate genes are reported for first time in finger millet. On validation, these novel QTLs may be utilized in future for marker assisted breeding for the development of fungal resistant and high yielding varieties of finger millet. [less ▲]

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See detailBenchmarking for Bayesian Reinforcement Learning
Castronovo, Michaël ULiege; Ernst, Damien ULiege; Couëtoux, Adrien ULiege et al

in PLoS ONE (2016)

In the Bayesian Reinforcement Learning (BRL) setting, agents try to maximise the col- lected rewards while interacting with their environment while using some prior knowledge that is accessed beforehand ... [more ▼]

In the Bayesian Reinforcement Learning (BRL) setting, agents try to maximise the col- lected rewards while interacting with their environment while using some prior knowledge that is accessed beforehand. Many BRL algorithms have already been proposed, but even though a few toy examples exist in the literature, there are still no extensive or rigorous benchmarks to compare them. The paper addresses this problem, and provides a new BRL comparison methodology along with the corresponding open source library. In this methodology, a comparison criterion that measures the performance of algorithms on large sets of Markov Decision Processes (MDPs) drawn from some probability distributions is defined. In order to enable the comparison of non-anytime algorithms, our methodology also includes a detailed analysis of the computation time requirement of each algorithm. Our library is released with all source code and documentation: it includes three test prob- lems, each of which has two different prior distributions, and seven state-of-the-art RL algorithms. Finally, our library is illustrated by comparing all the available algorithms and the results are discussed. [less ▲]

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