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See detailNovel nanosized water soluble fluorescent micelles with embedded perylene diimide fluorophores for potential biomedical applications: Cell permeability, localization and cytotoxicity
Bryaskova, Rayna; Georgiev, Nikolai I.; Dimov, Stefan M. et al

in Materials Science & Engineering : C (2015), 51

Novel biocompatiblewater-soluble fluorescent micelleswithembedded perylene diimides (PDI) for intracellular applications have been prepared by self assembling of amphiphilic poly(vinyl alcohol)-b-poly ... [more ▼]

Novel biocompatiblewater-soluble fluorescent micelleswithembedded perylene diimides (PDI) for intracellular applications have been prepared by self assembling of amphiphilic poly(vinyl alcohol)-b-poly(acrylonitrile) (PVA-b-PAN) copolymers in the presence of synthesized fluorophores. Amphiphilic PVA-b-PAN copolymers were obtained by selective hydrolysis of well-defined poly(vinyl acetate)-b-poly(acrylonitrile) (PVAc-b-PAN) copolymer. The preparation of the novel fluorescence micelles consisting of PVA hydrophilic shell and PAN hy- drophobic core with incorporated PDI fluorophores has been confirmed by DLS and TEManalysis. The cytotoxic- ity of the water-soluble fluorophores and their internalization into living cells depending on the micellar concentration have been tested. Itwas shown that they could successfully enter in living cellswithout destroying their morphology. The results obtained indicate that the novel water-soluble fluorescent micelles with embed- ded PDI fluorophores would be suitable for potential intracellular biomedical applications. [less ▲]

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See detailA novel neurodevelopmental syndrome responsive to 5-hydroxytryptophan and carbidopa.
RAMAEKERS, Vincent ULg; Senderek, J.; Hausler, M. et al

in Molecular genetics and metabolism (2001), 73(2), 179-87

Tryptophan hydroxylase (TPH; EC 1.14.16.4) catalyzes the first rate-limiting step of serotonin biosynthesis by converting l-tryptophan to 5-hydroxytryptophan. Serotonin controls multiple vegetative ... [more ▼]

Tryptophan hydroxylase (TPH; EC 1.14.16.4) catalyzes the first rate-limiting step of serotonin biosynthesis by converting l-tryptophan to 5-hydroxytryptophan. Serotonin controls multiple vegetative functions and modulates sensory and alpha-motor neurons at the spinal level. We report on five boys with floppiness in infancy followed by motor delay, development of a hypotonic-ataxic syndrome, learning disability, and short attention span. Cerebrospinal fluid (CSF) analysis showed a 51 to 65% reduction of the serotonin end-metabolite 5-hydroxyindoleacetic acid (5HIAA) compared to age-matched median values. In one out of five patients a low CSF 5-methyltetrahydrofolate (MTHF) was present probably due to the common C677T heterozygous mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Baseline 24-h urinary excretion showed diminished 5HIAA values, not changing after a single oral load with l-tryptophan (50-70 mg/kg), but normalizing after 5-hydroxytryptophan administration (1 mg/kg). Treatment with 5-hydroxytryptophan (4-6 mg/kg) and carbidopa (0.5-1.0 mg/kg) resulted in clinical amelioration and normalization of 5HIAA levels in CSF and urine. In the patient with additional MTHFR heterozygosity, a heterozygous missense mutation within exon 6 (G529A) of the TPH gene caused an exchange of valine by isoleucine at codon 177 (V177I). This has been interpreted as a rare DNA variant because the pedigree analysis did not provide any genotype-phenotype correlation. In the other four patients the TPH gene analysis was normal. In conclusion, this new neurodevelopmental syndrome responsive to treatment with 5-hydroxytryptophan and carbidopa might result from an overall reduced capacity of serotonin production due to a TPH gene regulatory defect, unknown factors inactivating the TPH enzyme, or selective loss of serotonergic neurons. [less ▲]

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See detailNovel norovirus recombinants and GII.4 sub-lineages associated with outbreaks between 2006 and 2010 in Belgium
Mathijs, Elisabeth ULg; Denayer, Sarah; Palmeira, Leonor et al

in Virology Journal (2011)

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See detailNovel organic solvent-tolerant esterase isolated by metagenomics: insights into the lipase/esterase classification
Berlemont, Renaud; Spee, Olivier; Delsaute, Maud et al

in Revista Argentina de Microbiologia (2013), (45), 3-12

in order to isolate novel organic solvent-tolerant (oSt) lipases, a metagenomic library was built using dna derived from a temperate forest soil sample. a two-step activity-based screening allowed the ... [more ▼]

in order to isolate novel organic solvent-tolerant (oSt) lipases, a metagenomic library was built using dna derived from a temperate forest soil sample. a two-step activity-based screening allowed the isolation of a lipolytic clone active in the presence of organic solvents. Sequencing of the plasmid pRBest recovered from the positive clone revealed the presence of a putative lipase/esterase encoding gene. the deduced amino acid sequence (RBest1) contains the conserved lipolytic enzyme signature and is related to the previously described oSt lipase from Lysinibacillus sphaericus 205y, which is the sole studied prokaryotic enzyme belonging to the 4.4 a/b hydrolase subgroup (abh04.04). Both in vivo and in vitro studies of the substrate specificity of RBest1, using triacylglycerols or nitrophenyl-esters, respectively, revealed that the enzyme is highly specific for butyrate (c4) compounds, behaving as an esterase rather than a lipase. the RBest1 esterase was purified and biochemically characterized. the optimal esterase activity was observed at ph 6.5 and at temperatures ranging from 38 to 45 °c. enzymatic activity, determined by hydrolysis of p‐nitrophenyl esters, was found to be affected by the presence of different miscible and non-miscible organic solvents, and salts. noteworthy, RBest1 remains significantly active at high ionic strength. these findings suggest that RBest1 possesses the ability of oSt enzymes to molecular adaptation in the presence of organic compounds and resistance of halophilic proteins. [less ▲]

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See detailNovel organocobalt based on acetylacetonate ligands for the precision synthesis of telechelic polymers
Demarteau, Jérémy ULg; Cordella, Daniela ULg; Kermagoret, Anthony et al

Conference (2015, December 17)

Organocobalt(III) with acetylacetonate ligands is the most representative example of R-Co bearing a weak C-Co bond that can release alkyl radicals under mild experimental conditions without requiring a ... [more ▼]

Organocobalt(III) with acetylacetonate ligands is the most representative example of R-Co bearing a weak C-Co bond that can release alkyl radicals under mild experimental conditions without requiring a photoactivation. The unique isolated specimen is a short oligo(vinyl acetate) end-capped by Co(acac)2. The high lability of the C-Co bond of this R-Co combined to the unique capacity of Co(acac)2 to reversibly trap alkyl radicals make this organocobalt unique for the precision synthesis of unprecedented polymers by the so-called Cobalt-Mediated Radical Polymerization (CMRP) technique. The growth of unstabilized and highly reactive growing radicals formed by the addition of R· to unconjugated olefins (vinyl esters, vinyl amides, vinyl imidazolium, vinyl chloride, ethylene) is controlled by the reversible formation of a weak C-Co bond at the polymer chain end. The lack of alternatives to this R-Co, especially to the structure of the alkyl group, has placed limitations on further innovation in (macro)molecular design. Other functional variants that would enable attractive chain-end derivatizations are unfortunately not available. In this communication, we will address this important challenge by describing an innovative synthetic route towards the preparation of a new functional R-Co(acac)2 that are characterized by a weak C-Co bond. We will report the conditions required for initiating and controlling the radical polymerization of various monomers from these R-Co. We will also demonstrate their utility for the production of novel telechelic polymers under mild experimental conditions, syntheses that can be carried out in water. [less ▲]

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See detailNovel organocobalt for the synthesis of functional polymers
Demarteau, Jérémy ULg; Kermagoret, Anthony; Jérôme, Christine ULg et al

Poster (2015, September 11)

Organocobalt(III) with acetylacetonate (acac) ligands is the most representative example of R-Co bearing a labile C-Co bond that can release alkyl radicals under mild experimental conditions without ... [more ▼]

Organocobalt(III) with acetylacetonate (acac) ligands is the most representative example of R-Co bearing a labile C-Co bond that can release alkyl radicals under mild experimental conditions without requiring a photoactivation. The unique isolated R-Co is a short oligo(vinyl acetate) end-capped by Co(acac)2. The high lability of its C-Co bond combined to the unique capacity of Co(acac)2 to reversibly trap alkyl radicals make this R-Co unique for the precision design of unprecedented polymers by Cobalt-Mediated Radical Polymerization (CMRP). The growth of unstabilized and highly reactive growing radicals formed by the addition of R• to unconjugated vinyl monomers (vinyl esters, vinyl amides, vinyl imidazolium, vinyl chloride, etc;) is controlled by the reversible formation of a weak C-Co bond at the polymer chain end. The lack of alternatives to this R-Co, especially to the structure of the alkyl group, has however placed limitations on post-functionalizations of end-chains. Other functional variants that would enable attractive chain-end derivatizations are unfortunately not available. In this poster, we will address this important challenge by describing an innovative synthetic route towards the preparation of new functional R-Co(acac)2 that are sources of halomethyl radicals under mild experimental conditions. The efficiency of these novel organocobalt complexes for the precision synthesis of end-functional and telechelic polymers will be described. Also, the solubility of these complexes in water enables the facile production of end-functionalized water soluble poly(ionic liquid)s. Further derivatizations of the halomethyl group at the chain-end of polymers produced by this system will be demonstrated by click reaction, largely broadening the range of possible functional groups. Finally, besides numerous applications in macromolecular engineering, this unexplored family of R-Co presents a high potential in radical reactions in organic synthesis by the facile production of halomethyl radicals. [less ▲]

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See detailA Novel Oxidizing Reagent Based on Potassium Ferrate(VI)
Delaude, Lionel ULg; Laszlo, Pierre ULg

in Journal of Organic Chemistry (1996), 61(18), 6360-6370

A new, efficient preparation has been devised for potassium ferrate(VI) (K(2)FeO(4)). The ability of this high-valent iron salt for oxidizing organic substrates in nonaqueous media was studied. Using ... [more ▼]

A new, efficient preparation has been devised for potassium ferrate(VI) (K(2)FeO(4)). The ability of this high-valent iron salt for oxidizing organic substrates in nonaqueous media was studied. Using benzyl alcohol as a model, the catalytic activity of a wide range of microporous adsorbents was ascertained. Among numerous solid supports of the aluminosilicate type, the K10 montmorillonite clay was found to be best at achieving quantitative formation of benzaldehyde, without any overoxidation to benzoic acid. The roles of the various parameters (reaction time and temperature, nature of the solvent, method of preparation of the solid reagent) were investigated. The evidence points to a polar reaction mechanism. The ensuing procedure was applied successfully, at room temperature, to oxidation of a series of alcohols to aldehydes and ketones, to oxidative coupling of thiols to disulfides, and to oxidation of nitrogen derivatives. At 75 degrees C, the reagent has the capability of oxidizing both activated and nonactivated hydrocarbons. Toluene is turned into benzyl alcohol (and benzaldehyde). Cycloalkanes are also oxidized, in significant (30-40%) yields, to the respective cycloalkanols (and cycloalkanones). Thus, potassium ferrate, used in conjunction with an appropriate heterogeneous catalyst, is a strong and environmentally friendly oxidant. [less ▲]

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See detailA novel pattern recognition approach to transient stability assessment of power systems
Belhomme, Régine; Van Cutsem, Thierry ULg; Pavella, Mania ULg

in Proc. 10th IFAC World Congress (1987)

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See detailNovel peptide inhibiting both TEM-1 beta-lactamase and penicillin-binding proteins.
Phichith, Denis; Bun, Sylvie; Padiolleau-Lefevre, Severine et al

in The FEBS journal (2010), 277(23), 4965-72

9G4H9, a catalytic antibody displaying beta-lactamase-like activity, has been developed by the anti-idiotypic approach using beta-lactamase as the first antigen. Thus 9G4H9 represents the 'internal image ... [more ▼]

9G4H9, a catalytic antibody displaying beta-lactamase-like activity, has been developed by the anti-idiotypic approach using beta-lactamase as the first antigen. Thus 9G4H9 represents the 'internal image' of beta-lactamase. We selected a cyclic peptide anchored to a bacteriophage M13 library using 9G4H9 as the target. Pep90 is a cyclic heptapeptide enclosed between two cysteine residues. We showed that Pep90 could inhibit both TEM-1 beta-lactamase (K(i) = 333 mum) and several penicillin-binding proteins (IC(5)(0) values ranging from 6-62 mum). We determined that the tryptophan residue of Pep90 is of crucial importance for its inhibitory activity. Using Pep90 as a scaffold, we generated a new class of peptidomimetics that retained inhibitory activity towards TEM-1 beta-lactamase. [less ▲]

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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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