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See detailNovel perspectives in the definition of responders in trials of osteoarthritis
Bruyère, Olivier ULg

Conference (2012, March 23)

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See detailNovel perspectives in the pathogenesis of type 1 diabetes
Geenen, Vincent ULg

Conference (2005, November)

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See detailNovel pH or thermosensitive block copolymers for triggered drug-delivery systems
Jérôme, Christine ULg

Conference (2007, October 30)

Over the last decade, polymer micelles and nanoparticles have attracted an increasing interest as efficient drug delivery systems. Polymer micelles from amphiphilic block copolymers are supramolecular ... [more ▼]

Over the last decade, polymer micelles and nanoparticles have attracted an increasing interest as efficient drug delivery systems. Polymer micelles from amphiphilic block copolymers are supramolecular core-shell type assemblies of some tens of nanometers in diameter. They are highly stable in aqueous solution because of their low intrinsic critical micelle concentration, which prevents their dissociation upon dilution in the blood stream after intravenous injection. The combination of poly(ethylene oxide) (PEO) with hydrophobic aliphatic polyesters, such as poly(ε-caprolactone) (PCL) or polylactide (PLA), allows to prepare stealthy drug nanocarriers (thanks to PEO), which are biodegradable and biocompatible and capable of encapsulating a hydrophobic drug (due to the aliphatic polyester). In this field, the inclusion of an additional pH-responsive block in the supramolecular assembly is a promising strategy to improve the targeting of tumor tissues by taking advantage of the lower pH at the vicinity of tumor cells. A variety of novel amphiphilic and pH-sensitive copolymers have been synthesized and tested as building blocks for the design of smart nanocarriers able to expose selectively the targeting unit at the vicinity of tumor. Various macromolecular architectures combining PEO, PCL and P2VP have been accordingly synthesized such as linear and star shape di- and triblock copolymers. Their (co)-micellization has been studied in terms of size, particle shape (DLS, TEM) and stealth behavior. Besides, thermo-responsive copolymers combining PEO, polyacrylic acid and poly-N-isopropyl-acrylamide have been synthesized and found efficient in stabilizing stealthy magnetic nanoparticles promising for thermally triggered release of drugs during hyperthermia. [less ▲]

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See detailNovel pH responsive-copolymers for smart drug carriers
Jérôme, Christine ULg

Conference (2008, September 22)

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See detailA novel pH sensitive water soluble fluorescent nanomicellar sensor for potential biomedical applications
Georgiev, N. I.; Bryaskova, Rayne; Tzoneva, R. et al

in Bioorganic & Medicinal Chemistry (2013), 21(21), 6292-6303

Herein we report on the synthesis and sensor activity of a novel pH sensitive probe designed as highly water-soluble fluorescent micelles by grafting of 1,8-naphthalimide–rhodamine bichromophoric FRET ... [more ▼]

Herein we report on the synthesis and sensor activity of a novel pH sensitive probe designed as highly water-soluble fluorescent micelles by grafting of 1,8-naphthalimide–rhodamine bichromophoric FRET system (RNI) to the PMMA block of a well-defined amphiphilic diblock copolymer—poly(methyl methacrylate)–b-poly(methacrylic acid) (PMMA48–b-PMAA27). The RNI-PMMA48–b-PMAA27 adduct is capable of self-assembling into micelles with a hydrophobic PMMA core, containing the anchored fluorescent probe, and a hydrophilic shell composed of PMAA block. Novel fluorescent micelles are able to serve as a highly sensitive pH probe in water and to internalize successfully HeLa and HEK cells. Furthermore, they showed cell specificity and significantly higher photostability than that of a pure organic dye label such as BODIPY. The valuable properties of the newly prepared fluorescent micelles indicate the high potential of the probe for future biological and biomedical applications. [less ▲]

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See detailNovel pH-responsive copolymers for smart drug carriers
Jérôme, Christine ULg

Conference (2009, November 18)

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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 ▲]

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See detailA Novel Phase Portrait to Understand Neuronal Excitability
Drion, Guillaume ULg; Franci, Alessio ULg; Seutin, Vincent ULg et al

Conference (2012, March)

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See detailNovel phenolic glycolipids: antioxidant activity and effect on membrane models
Sainvitu, Pauline ULg; Nasir, Mehmet Nail ULg; Draguet, Florian et al

Poster (2013, May 30)

Aromatic glycolipids are of both medical as well as pharmaceutical interest. Antimicrobial, antiviraland antiinflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B ... [more ▼]

Aromatic glycolipids are of both medical as well as pharmaceutical interest. Antimicrobial, antiviraland antiinflammatory activities have been reported (Otto, 2000, Journal of Molecular Catalysis B: Enzymatic). Moreover, they are expected to have interesting antioxidant properties when they contain phenolic groups. The alkyl chain should enhance their ability to penetrate into the cellular membrane (Nicolosi, 2002, Journal of Molecular Catalysis B: Enzymatic). The presence of a sugar unit could also be useful to target specific cells. In this study, novel aromatic glycolipids were synthesized as useful models for studying the structure–activity relationship, in particular as regards to their aromatic group.Theireffect on cell viability when an oxidative stress is induced was tested. In parallel, their interaction with cell models (liposomes) was studied through membrane fusion and permeability experiments. [less ▲]

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See detailNovel photobioreactors based on microalgae immobilized in silica gels obtained by "Chimie douce" for biofuel production
Léonard, Alexandre ULg; Rooke, J.; Sarmento, H. et al

in Abstracts of Papers - American Chemical Society, National Meeting (2010)

A new generation of photobioreactors for the clean production of green biofuels is described. It is based on the smart combination of living and inanimate, namely microalgae encapsulated in porous silica ... [more ▼]

A new generation of photobioreactors for the clean production of green biofuels is described. It is based on the smart combination of living and inanimate, namely microalgae encapsulated in porous silica gels. Such hybrid materials would allow for the controlled exploitation of photosynthesis to assimilate atmospheric CO2 and convert it into useful energy sources by using sunlight. The use of biocompatible routes for the immobilization of cyanobacteria has extended the duration of survival up to 40 weeks. [less ▲]

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See detailNovel photosynthetic CO2 bioconvertor based on green algae entrapped in low-sodium silica gels
Rooke, J. C.; Léonard, Alexandre ULg; Sarmento, H. et al

in Journal of Materials Chemistry (2011), 21(4), 951-959

A photosynthetic bioreactor for CO2 assimilation has been designed using silica sol-gel immobilisation technologies with the chlorophyta Botryococcus braunii (Kützing) and Chlorella vulgaris (Beijerinck ... [more ▼]

A photosynthetic bioreactor for CO2 assimilation has been designed using silica sol-gel immobilisation technologies with the chlorophyta Botryococcus braunii (Kützing) and Chlorella vulgaris (Beijerinck). The living hybrid gels formed revealed a mesoporosity that enabled diffusion of nutrients and gases, promoting the light and dark photosynthetic reactions from within the bulk of the material. To determine the efficiency of the photosynthetic bioreactor in terms of CO 2 remediation, the activity and viability of the encapsulated cells have been monitored through oximetry, 14C assimilation, pulse amplitude modulation fluorimetry and confocal microscopy, revealing a long term productivity of living hybrid materials capable of photosynthetic processes for at least 80 days. Structural and textural properties of the gels were established through 29Si MAS-NMR and N2 physisorption respectively. © 2011 The Royal Society of Chemistry. [less ▲]

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See detailNovel plasma extraction procedure and development of a specific enzyme immunoassay of oxytocin: application to biological and clinical investigations of small-cell carcinoma of the lung
Pequeux, Christel ULg; Hendrick, Jean-Claude; Hagelstein, Marie-Thérèse ULg et al

in Scandinavian Journal of Clinical & Laboratory Investigation (2001), 61(5), 407-415

Paraneoplastic secretion of the lactation-inducing hormone oxytocin (OT) has been reported in about 30% of cases of small cell carcinoma of the lung (SCCL). In order to investigate the role of OT in the ... [more ▼]

Paraneoplastic secretion of the lactation-inducing hormone oxytocin (OT) has been reported in about 30% of cases of small cell carcinoma of the lung (SCCL). In order to investigate the role of OT in the biology of SCCL tumours, a specific enzyme-immunoassay(EIA) for OT, which can be applied to both human plasma <br />and culturemedium, has been developed. OT EIA is performed on 96-well microtiter plates coated with a rabbit polyclonal antibody (Ab) anti-OT (O4). This antibody does not exhibit any significant cross-reactivity either with vasopressin (VP) or with vasotocin (VT). The immunological reaction involving Ab anti-OT is a competition between the tracer (biotinylatedOT) and syntheticOT (standard curve) or OT present in biological samples. In order to limit interference induced by plasma proteins, plasma samples are titrated by a one-step centrifugation on centricon YM-3 (cut-oOE 3000 Da). After plasma filtration, 90.7 ± 5.1 (SD) % (n = 22) immunoreactive ( IR) OT is recovered. The sensitivity of OT EIA is 1 pmol/L, while intra- and inter-assay coefficients of variation (CV) are around 3.41% and 2.84%, respectively. In healthy volunteers, plasma IR OT is 7.28 ± 4.49 (SD) pmol/L (n = 32) with no gender diOEerence. As shown by the data both from plasma of SCCL patients and from supernatants and cell contents of SCCL cell lines, this EIA procedure offers a novel, reproducible, specific and sensitive method for the measurement of IR OT. [less ▲]

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See detailNovel post-digest isotope coded protein labeling method for phospho- and glycoproteome analysis
Fleron, Maximilien ULg; Greffe, Yannick ULg; Musmeci, Davide ULg et al

in Journal of Proteomics (2010), 73(10), 1986-2005

In the field of proteomics there is an apparent lack of reliable methodology for quantification of posttranslational modifications. Present study offers a novel post-digest ICPL quantification strategy ... [more ▼]

In the field of proteomics there is an apparent lack of reliable methodology for quantification of posttranslational modifications. Present study offers a novel post-digest ICPL quantification strategy directed towards characterization of phosphorylated and glycosylated proteins. The value of the method is demonstrated based on the comparison of two prostate related metastatic cell lines originating from two distinct metastasis sites (PC3 and LNCaP). The method consists of protein digestion, ICPL labeling, mixing of the samples, PTM enrichment and MS-analysis. Phosphorylated peptides were isolated using TiO(2), whereas the enrichment of glycosylated peptides was performed using hydrazide based chemistry. Isolated PTM peptides were analyzed along with non enriched sample using 2D-(SCX-RP)-Nano-HPLC-MS/MS instrumentation. Taken together the novel ICPL labeling method offered a significant improvement of the number of identified (∼600 individual proteins) and quantified proteins (>95%) in comparison to the classical ICPL method. The results were validated using alternative protein quantification strategies as well as label-free MS quantification method. On the biological level, the comparison of PC3 and LNCaP cells has shown specific modulation of proteins implicated in the fundamental process related to metastasis dissemination. Finally, a preliminary study involving clinically relevant autopsy cases reiterated the potential biological value of the discovered proteins. [less ▲]

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See detailA novel potassium channel gene, KCNQ2, is mutated in an inherited epilepsy of newborns.
Singh, N. A.; Charlier, Carole ULg; Stauffer, D. et al

in Nature Genetics (1998), 18(1), 25-9

Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder ... [more ▼]

Idiopathic generalized epilepsies account for about 40% of epilepsy up to age 40 and commonly have a genetic basis. One type is benign familial neonatal convulsions (BFNC), a dominantly inherited disorder of newborns. We have identified a sub-microscopic deletion of chromosome 20q13.3 that co-segregates with seizures in a BFNC family. Characterization of cDNAs spanning the deleted region identified one encoding a novel voltage-gated potassium channel, KCNQ2, which belongs to a new KQT-like class of potassium channels. Five other BFNC probands were shown to have KCNQ2 mutations, including two transmembrane missense mutations, two frameshifts and one splice-site mutation. This finding in BFNC provides additional evidence that defects in potassium channels are involved in the mammalian epilepsy phenotype. [less ▲]

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See detailA novel procedure to measure shrinkage-free tree-rings from very large wood samples combining photogrammetry, high-resolution image processing, and GIS tools
Latte, Nicolas ULg; Beeckman, Hans; Bauwens, Sébastien ULg et al

in Dendrochronologia (2015), 34

We present a new procedure for wood sampling and tree-ring measurement that can be used for dendrochronological investigation on very large trees, specifically adapted for tropical rainforest species ... [more ▼]

We present a new procedure for wood sampling and tree-ring measurement that can be used for dendrochronological investigation on very large trees, specifically adapted for tropical rainforest species. This procedure takes advantage of the technological developments in computing, image processing, and geographic information systems (GIS) to overcome the technical limitations of the currently used methods. Two types of wood samples can be used (stem disks and/or bars) depending on tree diameter, and the difficulty of ring delineation and crossdating. Bars are an effective compromise between cores and disks. We developed an application combining several programs (Excel, R, ArcGIS, and MapWinGIS) in the Windows operating system for semi-automatic measurement of tree-rings from high-resolution images of the sanded cross-section. Using an innovative method to reverse the wood shrinkage resulting from the drying process, tree-ring measurement can be performed on shrinkage-free images, thus referring to the actual growth of the tree. [less ▲]

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See detailA novel pyrid-3-yl sulfonylurea, BM 27, effective in brain edema and stroke treatment
Masereel, B.; Renard, P.; Pirotte, Bernard ULg et al

Conference (1994, September)

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See detailNovel Relative ICPL Based Quantitative Phospho- and Glycoproteome Analysis Method
Fleron, Maximilien ULg; Greffe, Yannick ULg; Massart, Anne-Cécile ULg et al

Poster (2010, April 16)

Large scale proteomic analysis remains challenging partially because proteins are inhomogeneous and often influenced by a variety of structural modifications. In particular, these specific chemical ... [more ▼]

Large scale proteomic analysis remains challenging partially because proteins are inhomogeneous and often influenced by a variety of structural modifications. In particular, these specific chemical modifications called posttranslational modifications (PTM) are crucial determinants for the protein function and biological role. Up to now there have been a growing number of studies describing the enrichment and identification of PTM. However, a significant dearth of data offering a reliable methodology for PTM quantification does exist. The present work aims at developing a label based protein PTM quantification strategy and demonstrating its value on comparative analysis of cells originating from two distinct prostate metastasis sites. PC3 and LNCaP cells isolated from bone and lymph node prostate cancer metastasis sites respectively, were lysed and spiked with three non-human proteins serving as internal standards. Following this, the samples were reduced and alkylated, digested with trypsin and subjected to peptide ICPL (isotope coded protein label) labeling. The two peptide containing samples were joined together followed by the affinity isolation of phospho- (using TiO2 metal affinity chromatography) and glycopeptides (oxidized glycans were bound on hydrazide resin). The enriched fraction as well as the flow-through were analyzed on a 2D-(SCX and C18-RP)-nano-HPLC system. The peptide identification and quantification was conducted using electrospray ion-trap mass spectrometer (Bruker, HCT-ultra). Validation of the differentially modulated proteins was conducted in several biological and technical replicates using the label free MSe based quantification strategy. This PTM based, novel relative protein quantification using post-digest ICPL has detected over 598 individual proteins. Of these more than 95 % have been successfully quantified. PTM enrichment methodologies allowed an isolation rate of 91 % and 50 % for phosphorylated and glycosylated proteins respectively. The detailed comparison of PC3 and LNCaP cells has shown specific overexpression of selected proteins indicating differences between these two prostate metastatic cell lines. Several of these modulated proteins have been previously described to be related to prostate cancer (e.g. annexin A2 and vimentin) while others could be considered as potentially novel. These proteins might be implicated in the fundamental process related to metastasis dissemination. However, because of the known discrepancy between cell systems and clinical material, the present study can be regarded only as a step towards elucidation of these complex interactions. [less ▲]

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See detailA novel renal carbonic anhydrase type III plays a role in proximal tubule dysfunction.
JOURET, François ULg; Gailly, Philippe; Martin, D. et al

in Kidney International (2008), 74(1), 52-61

Dysfunction of the proximal tubule (PT) is associated with variable degrees of solute wasting and low-molecular-weight proteinuria. We measured metabolic consequences and adaptation mechanisms in a model ... [more ▼]

Dysfunction of the proximal tubule (PT) is associated with variable degrees of solute wasting and low-molecular-weight proteinuria. We measured metabolic consequences and adaptation mechanisms in a model of inherited PT disorders using PT cells of ClC-5-deficient (Clcn5Y/-) mice, a well-established model of Dent's disease. Compared to cells taken from control mice, those from the mutant mice had increased expression of markers of proliferation (Ki67, proliferative cell nuclear antigen (PCNA), and cyclin E) and oxidative scavengers (superoxide dismutase I and thioredoxin). Transcriptome and protein analyses showed fourfold induction of type III carbonic anhydrase in a kidney-specific manner in the knockout mice located in scattered PT cells. Kidney-specific carbonic anhydrase type III (CAIII) upregulation was confirmed in other mice lacking the multiligand receptor megalin and in a patient with Dent's disease due to an inactivating CLCN5 mutation. The type III enzyme was specifically detected in the urine of mice lacking ClC-5 or megalin, patients with Dent's disease, and in PT cell lines exposed to oxidative stress. Our study shows that lack of PT ClC-5 in mice and men is associated with CAIII induction, increased cell proliferation, and oxidative stress. [less ▲]

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See detailNovel RGD-like molecules based on the tyrosine template design, synthesis, and biological evaluation on isolated integrins alpha(V)beta/alpha(IIb)beta(3) and in cellular adhesion tests
Biltresse, S.; Attolini, M.; Dive, Georges ULg et al

in Bioorganic & Medicinal Chemistry (2004), 12(20), 5379-5393

RGD (Arg-Gly-Asp) peptidomimetics have been designed for covalent anchorage on biomaterials. The tyrosine template was thus equipped with (i) a basic side chain of various flexibility, (ii) an acidic side ... [more ▼]

RGD (Arg-Gly-Asp) peptidomimetics have been designed for covalent anchorage on biomaterials. The tyrosine template was thus equipped with (i) a basic side chain of various flexibility, (ii) an acidic side chain, which incorporated the XPS fluorine tag, and (iii) a spacer-arm terminated by a primary amine for surface grafting. The most active compounds showed IC50 values in the nanomolar range versus isolated human integrins alpha(v)beta(3) and alpha(IIb)beta(3). Preincubation of CaCo2 cells with soluble peptidomimetics (2 and 19a) prevented cellular adhesion on culture plates coated with vitronectin. On the other hand, peptidomimetics (19a and 19b) immobilized on a poly(ethylene)terephthalate membrane (PET) promoted CaCo2 cells adhesion. A modeling study at the ab initio level in MINI-1' basis allowed to compare the various synthetic ligands of integrins and to propose novel pharmacophore structures. (C) 2004 Elsevier Ltd. All rights reserved. [less ▲]

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See detailNovel role for type E Immunoglobulins: host protection against venoms.
Marichal, Thomas ULg

Scientific conference (2014, October)

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