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See detailMolecular mechanisms of glucocorticoid hormone action
Lan, N. C.; Nguyen, T.; Cathala, G. et al

in Journal of Molecular and Cellular Cardiology (1982), 14 Suppl 3

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See detailMolecular mechanisms of type I collagen-induced apoptosis in breast carcinoma cells
Maquoi, Erik ULg; Assent, Delphine ULg; Foidart, Jean-Michel ULg et al

Poster (2013, September 27)

Objective: As invading breast carcinoma cells breach the underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop ... [more ▼]

Objective: As invading breast carcinoma cells breach the underlying basement membrane, they become confronted with a dense three-dimensional reactive stroma dominated by type I collagen. To develop metastatic capabilities, invading tumour cells must acquire the capacity to negotiate this hostile microenvironment. By enmeshing cells in a dense fibrillar network, type I collagen acts as a physical barrier for cell migration as well as an endogenous antigrowth signal, partly by inducing apoptosis in epithelial cells. Aberrant cell survival resulting from an acquired resistance toward apoptosis represents a prominent hallmark of cancers. However, the molecular mechanisms implicated in collagen-induced apoptosis remain poorly defined. Here, we investigate the molecular mechanisms by which type I collagen induces apoptosis in breast carcinoma cells and identify MMP-14, a membrane-anchored matrix metalloproteinase, as a key anti-apoptotic factor. Methods: To investigate the induction of apoptosis by collagen, human breast adenocarcinoma MCF-7 cells overexpressing or not MMP-14 were plated on plastic plates or embedded within three dimensional type I collagen gels (Col3D). Cell death was evaluated by measuring cytoplasmic histone-associated DNA fragments (Cell Death Detection ELISA). The percentage of cells with an apoptotic nuclear morphology was also determined. The interactions between cancer cells and Col3D were analyzed by confocal microscopy and the impact of Col3D on the transcriptome of cancer cells was investigated using Illumina HT-12 BeadArrays. Results: When cultured within Col3D gels, MCF-7 cells displayed a round morphology and a cell death characterized by a Z-VAD-FMK-dependent chromatin condensation, nuclear segmentation and oligonucleosomal DNA fragmentation was induced. Transfection of MCF-7 cells with MMP-14 cDNA promoted the interactions between cells and collagen and prevented apoptosis. A transcriptomic analysis revealed that culturing MCF-7 cells within Col3D altered the expression of about 700 genes, irrespective of MMP-14 expression. Col3D modulated the expression of several apoptosis-related genes. Interestingly, MMP-14 activity was sufficient to prevent the Col3D-dependent induction of Bcl2-Interacting Killer (BIK), a pro-apoptotic member of the Bcl-2 family. Conclusions: Our results shed light on the molecular mechanisms by which a collagen-rich microenvironment triggers apoptosis in invading breast cancer cells. Furthermore, we demonstrate that MMP-14 promotes tumour progression by circumventing apoptosis. [less ▲]

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See detailMolecular modeling of phthalates – PPARs interactions
Kambia, Nicolas; Renault, Nicolas; Dilly, Sébastien ULg et al

in Journal of Enzyme Inhibition & Medicinal Chemistry (2008), 23(5), 611-616

Di(2-ethylhexyl) phthalate (DEHP) is the most widely plasticizer for polyvinyl chloride (PVC) that is used in plastic tubes, in medical and paramedical devices as well as in food storage packaging. The ... [more ▼]

Di(2-ethylhexyl) phthalate (DEHP) is the most widely plasticizer for polyvinyl chloride (PVC) that is used in plastic tubes, in medical and paramedical devices as well as in food storage packaging. The toxicological profile of DEHP has been evaluated in a number of experimental animal models and has been extensively documented. Its toxicity is in part linked to the activation of the peroxisome proliferator-activated receptor a (PPARa). As a response, an intensive research for a new, biologically inert plasticizer has been initiated. Among the alternative studied, tri(2-ethylhexyl) trimellitate (TEHTM) or trioctyl trimellitate (TOTM) has attracted increasing interest. However, very little information is available on their biological effects. We proceeded to dock TOTM, DEHP and its metabolites in order to identify compounds that are likely to interact with PPARa and PPARg binding sites. The results obtained hint that TOTM is not able to bind to PPARs and should therefore be safer than DEHP. [less ▲]

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See detailMolecular modeling of the amphipathic helices of the plasma apolipoproteins.
Brasseur, Robert ULg; Lins, Laurence ULg; Vanloo, B. et al

in Proteins (1992), 13(3), 246-57

In this paper we propose a classification of the amphipathic helical repeats occurring in the plasma apolipoprotein sequences. It is based upon the calculation of the molecular hydrophobicity potential ... [more ▼]

In this paper we propose a classification of the amphipathic helical repeats occurring in the plasma apolipoprotein sequences. It is based upon the calculation of the molecular hydrophobicity potential around the helical segments. The repeats were identified using a new autocorrelation matrix, based upon similarities of hydrophobic and hydrophilic properties of the amino acid residues within the apolipoprotein sequences. The helices were constructed by molecular modeling, the molecular hydrophobicity potential was calculated, and isopotential contour lines drawn around the helices yielded a three-dimensional visualization of the hydrophobicity potential. Two classes of apolipoproteins could be differentiated by comparing the hydrophobic angles obtained by projection of the isopotential contour lines on a plane perpendicular to the long axis of the helix. The isopotential contour lines around apo AI, AIV, and E are more hydrophilic than hydrophobic, whereas they are of similar intensity for apo AII, CI, and CIII. In both cases discoidal lipid-protein complexes are generated, with the amphipathic helices around the edge of the lipid core. The long axis of the helices is oriented parallel to the phospholipid acyl chains and the hydrophilic side of the helix toward the aqueous phase. As a result of the differences in hydrophobicity potential, the contact between the hydrophobic side of the helices and the phospholipid acyl chains is larger for apo AII, CI, and CIII than for the other apolipoproteins. This might account for the greater stability of the discoidal complexes generated between phospholipids and these apoproteins. [less ▲]

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See detailMolecular modeling study of 4-phenylpiperazine and 4-phenyl-1,2,3,6-tetrahydropyridine derivatives: A new step towards the design of high-affinity 5-HT1A ligands
Dilly, Sébastien ULg; Graulich, Amaury; Liégeois, Jean-François ULg

in Bioorganic & Medicinal Chemistry Letters (2010), 20(2), 1118-1123

The main feature of many drugs having a 5-HT1A affinity is the presence of an arylpiperazine moiety. Indeed, the protonated nitrogen and the aromatic ring of the arylpiperazine compounds are considered ... [more ▼]

The main feature of many drugs having a 5-HT1A affinity is the presence of an arylpiperazine moiety. Indeed, the protonated nitrogen and the aromatic ring of the arylpiperazine compounds are considered crucial for the interaction with the receptor. However, the replacement of the piperazine moiety by a 1,2,3,6-tetrahydropyridine ring in 4-arylpiperazine-ethyl carboxamide derivatives was recently shown to be highly favourable for 5-HT1A affinity. In order to better understand the favourable effect of this chemical modification, we performed a conformational analysis of these compounds mainly based on the position of the phenyl ring relative to the piperazine and tetrahydropyridine moiety. In the piperazine compounds, the phenyl ring preferentially adopts a perpendicular orientation, whereas an almost planar orientation seems to be the most favourable conformation for the tetrahydropyridine compounds. Therefore, this conformational difference appears as a key for a better interaction with the receptor binding site. This result will serve for the designing high-affinity 5-HT1A ligands. [less ▲]

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See detailMolecular Modeling Study of Beta- and Gamma-Cyclodextrin Complexes with Miconazole
Piel, Géraldine ULg; Dive, Georges ULg; Evrard, Brigitte ULg et al

in European Journal of Pharmaceutical Sciences (2001), 13(3), 271-9

Different authors have demonstrated the inclusion of miconazole in cyclodextrins (CD). Miconazole can be included in the CD cavity both in the neutral and in the ionized form. The present study tries to ... [more ▼]

Different authors have demonstrated the inclusion of miconazole in cyclodextrins (CD). Miconazole can be included in the CD cavity both in the neutral and in the ionized form. The present study tries to understand which fragment of the miconazole molecule is involved in the inclusion. Austin Model 1 approximate molecular orbital calculations have been performed on several complexes between beta-cyclodextrin (betaCD) or gamma-cyclodextrin (gammaCD) and miconazole in the ionized and the non-ionized forms of the two R and S enantiomers in three different orientations. We observed that betaCD is a good vehicle to transport miconazole which can be very easily released. The complexation energy between miconazole and betaCD is not very high but the entropic factor has a great incidence on the stability of the formed complex. The inclusion of the dichlorobenzene-CH(2)-O- and of the imidazole part of the S isomer gives rise to the most probable complex in acidic conditions (ionized miconazole). Nevertheless, the inclusion should be considered as a dynamic process in which different parts of the molecule could be alternatively included in betaCD. The present work demonstrates the high capability of deformation of betaCD which could easily accommodate several types of ligand. By opposite, the cycle extension in gammaCD leads to a more rigid vehicle with regards to miconazole. [less ▲]

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See detailMolecular modelling study of bis-isoquinolinium derivatives as small conductance Ca2+ - activated K+ channel blockers
Dilly, Sébastien ULg; Graulich, Amaury; Chavatte, Philippe et al

Poster (2008, May 30)

Small conductance calcium-activated potassium channels (SK) are widely expressed throughout the central nervous system and the periphery. Three subtypes of SK channels have been identified so far in ... [more ▼]

Small conductance calcium-activated potassium channels (SK) are widely expressed throughout the central nervous system and the periphery. Three subtypes of SK channels have been identified so far in different parts of the brain. Activation of SK channels by a rise in intracellular calcium leads to the hyperpolarisation of the membrane, hence reducing cell excitability. Blocking the SK channels might be beneficial for the treatment of depression, Parkinson’s disease and cognitive disorders. In this context, starting from the scaffold of N-methyl-laudanosine (NML) which is a known SK channel blocker (Scuvée-Moreau et al., 2002), a series of original bis-isoquinolinium derivatives were synthezised and evaluated for their affinity on the apamin-sensitive sites (Graulich et al., 2007). These quaternary compounds are powerful blockers, and the most active ones have 10 times more affinity for SK channels than dequalinium. Based on a conformational analysis, a molecular modeling study was also performed. The heads of the various conformational families were compared to a pharmacophoric model previously described (Dilly et al., 2005). The in silico results are well correlated by the in vitro binding studies. Firstly, a 6,7-dimethoxy or a 6,7,8-trimethoxy substitution is shown to be favourable. Secondly, although the length of the linker has no significant influence in the alkane derivatives, the ortho and meta linkers lead to more favourable conformations than the para linker in the xylene derivatives. [less ▲]

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See detailMolecular monitoring of the introgression in Gossypium hirsutum L. of G. sturtanium Willis genes controlling the "glanded-plant and glandless-seed" trait
Benbouza, H.; Lacape, M.; Jacquemin, J. M. et al

in World Cotton Research Conference - 3. Cotton production for the new Millenium (2004)

One hundred mapped micro-satellites markers located on the chromosomes of subgenome Ah were used to monitor the introgression of DNA fragments coming from the Australian species G. sturtianum Willis in ... [more ▼]

One hundred mapped micro-satellites markers located on the chromosomes of subgenome Ah were used to monitor the introgression of DNA fragments coming from the Australian species G. sturtianum Willis in BC1, BC2, BC2S1, BC2S2, BC2S3, BC3, BC3S1 and BC3S2 obtained from the G. hirsutum L. x G. raimondii Ulb. x G. sturtianum (HRS) trispecific hybrid. In these plants, the inhibition of the gossypol synthesis only in the seed seems to be linked to the substitution of fragments of linkage groups C2, C3, C4, C5, C6, C7 and C9 of G. hirsutum by homeologous segments of G. sturtianum chromosomes. The prospect to use these genetic stocks to develop commercial varieties is discussed according to the putative genetic determinism of the “low-gossypol seed and high-gossypol plant”-trait. [less ▲]

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See detailThe Molecular Neuron-Glia Couple and Epileptogenesis
Grisar, Thierry ULg; Lakaye, Bernard ULg; Thomas, E. et al

in Advances in Neurology (1999), 79

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See detailThe molecular neuron-glia couple and epileptogenesis
Grisar, Thierry ULg; Lakaye, Bernard ULg; Thomas, Elizabeth et al

in Delgado-Escueta, A. V.; Wilson, W. A.; Olsen, R. W. (Eds.) et al Jasper's Basic Mechanisms of the Epilepsies, 3rd edition (1999)

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See detailMolecular organization of selected prokaryotic S-Iayer proteins
Claus, Harald; Akça, Erol; Debaerdemaeker, Tony et al

in Canadian Journal of Microbiology (2005), 51

Regular crystalline surface layers (S-layers) are widespread among prokaryotes and probably represent the earliest cell wall structures. S-layer genes have been found in approximately 400 different ... [more ▼]

Regular crystalline surface layers (S-layers) are widespread among prokaryotes and probably represent the earliest cell wall structures. S-layer genes have been found in approximately 400 different species of the prokaryotic domains bacteria and archaea. S-layers usually consist of a single (glyco-rprotein species with molecular masses ranging from about 40 to 200 kDa that form lattices of oblique, tetragonal, or hexagonal architecture. The primary sequences of hyperthermophilic archaeal species exhibit some characteristic signatures, Further adaptations to their specific environments occur by various post-translational modifications, such as linkage of glycans, lipids, phosphate, and sulfate groups to the protein or by proteolytic processing. Specific domains direct the anchoring of the S-layer to the underlying cell wall components and transport across the cytoplasma memhrane. In addition to their presumptive original role as protective coats in archaea and bacteria, they have adapted new functions, e.g., as molecular sieves, attachment sites for extracellular enzymes, and virulence factors. [less ▲]

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See detailMolecular organization of surfactin-phospholipid monolayers: Effect of phospholipid chain length and polar head
Bouffioux, O.; Berquand, A.; Eeman, M. et al

in Biochimica et Biophysica Acta - Biomembranes (2007), 1768(7), 1758-1768

Mixed monolayers of the surface-active lipopeptide surfactin-C-15 and various lipids differing by their chain length (DMPC, DPPC, DSPC) and polar headgroup (DPPC, DPPE, DPPS) were investigated by atomic ... [more ▼]

Mixed monolayers of the surface-active lipopeptide surfactin-C-15 and various lipids differing by their chain length (DMPC, DPPC, DSPC) and polar headgroup (DPPC, DPPE, DPPS) were investigated by atomic force microscopy (AFM) in combination with molecular modeling (Hypermatrix procedure) and surface pressure-area isotherms. In the presence of surfactin, AFM topographic images showed phase separation for each surfactin-phospholipid system except for surfactin-DMPC, which was in good agreement with compression isotherms. On the basis of domain shape and line tension theory, we conclude that the miscibility between surfactin and phospholipids is higher for shorter chain lengths (DMPC > DPPC > DSPC) and that the polar headgroup of phospholipids influences the miscibility of surfactin in the order DPPC > DPPE > DPPS. Molecular modeling data show that mixing surfactin and DPPC has a destabilizing effect on DPPC monolayer while it has a stabilizing effect towards DPPE and DPPS molecular interactions. Our results provide valuable information on the activity mechanism of surfactin and may be useful for the design of surfactin delivery systems. (c) 2007 Elsevier B.V. All rights reserved. [less ▲]

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See detailMolecular pathways involved in apoptotic cell death in the injured cochlea: Cues to novel therapeutic strategies
Lallemend, François; Lefèbvre, Philippe ULg; Hans, Grégory ULg et al

in Current Pharmaceutical Design (2005), 11(17), 2257-2275

Most hearing loss results from lesions of the sensory cells and/or neurons of the auditory portion of the inner ear. To date, only the cochlear implantation offers long-term hearing-aid benefit, but still ... [more ▼]

Most hearing loss results from lesions of the sensory cells and/or neurons of the auditory portion of the inner ear. To date, only the cochlear implantation offers long-term hearing-aid benefit, but still with limited performance and expensive cost. While the underlying causes of deafness are not clear, the death or hair cells and/or neurons and the loss of neuronal contacts are key pathological features. Pinpointing molecular events that control cell death in the cochlea is critical for the development of new strategies to prevent and treat deafness, whether in combination or not with cochlear implant therapy. [less ▲]

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See detailMolecular pathways of angiogenesis inhibition.
Tabruyn, Sébastien ULg; Griffioen, Arjan W

in Biochemical and Biophysical Research Communications (2007), 355(1), 1-5

A large body of evidence now demonstrates that angiostatic therapy represents a promising way to fight cancer. This research recently resulted in the approval of the first angiostatic agent for clinical ... [more ▼]

A large body of evidence now demonstrates that angiostatic therapy represents a promising way to fight cancer. This research recently resulted in the approval of the first angiostatic agent for clinical treatment of cancer. Progress has been achieved in decrypting the cellular signaling in endothelial cells induced by angiostatic agents. These agents predominantly interfere with the molecular pathways involved in migration, proliferation and endothelial cell survival. In the current review, these pathways are discussed. A thorough understanding of the mechanism of action of angiostatic agents is required to develop efficient anti-tumor therapies. [less ▲]

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See detailMolecular pathways supporting the proliferation staging of malignant melanoma (review).
Quatresooz, Pascale ULg; Pierard, Gérald ULg; Franchimont, Claudine ULg et al

in International Journal of Molecular Medicine (2009), 24(3), 295-301

The clinical diagnosis of cutaneous melanoma always calls for histological confirmation. In addition to the recognition of the classic aspects of the neoplasm, immunohistochemistry is determinant, in ... [more ▼]

The clinical diagnosis of cutaneous melanoma always calls for histological confirmation. In addition to the recognition of the classic aspects of the neoplasm, immunohistochemistry is determinant, in particular in the assessment of the size of the replicative compartment. Generally, the proliferation rate is indicative of the neoplastic progression and is related to the clinical growth rate of the neoplasm. It allows to distinguish high risk melanomas showing a high growth rate from those of lower malignancy associated with a restricted growth rate. In melanoma, the recruitment and progression of neoplastic cells in the cell cycle of proliferation have lost some of their controls that are normally processed by a series of key regulatory molecules. In addition, the apoptotic pathway counteracting any hyperproliferative activity is released of the dependency of specific regulated molecular mechanisms. This review summarizes the current knowledge on key molecular components involved in the deregulation of the growth fraction, cell proliferation and apoptosis in melanocytic neoplasms. The implication of cyclins and of the mitogen-activated protein kinase pathways are scrutinized. The involvement of neoplastic stem cells in the metastatic process is also discussed. [less ▲]

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See detailMolecular phylogeny and systematics of Dipodoidea: a test of morphology-based hypotheses
Lebedev, Vladimir; Bannikova, Anna; Pagès, Marie ULg et al

in Zoologica Scripta (2013), (3),

The superfamily Dipodoidea (Rodentia, Myomorpha) in its current interpretation contains a single family subdivided into six subfamilies. Four of them include morphologically specialized bipedal arid ... [more ▼]

The superfamily Dipodoidea (Rodentia, Myomorpha) in its current interpretation contains a single family subdivided into six subfamilies. Four of them include morphologically specialized bipedal arid-dwelling jerboas (Dipodinae – three-toed jerboas, Allactaginae – fivetoed jerboas, Cardiocraniinae – pygmy jerboas and Euchoreutinae – long-eared jerboas), the other two are represented by more generalized quadrupedal taxa (Zapodinae – jumping mice and Sminthinae – birch mice). Despite considerable effort from morphologists, the taxonomy as well as the phylogeny of the Dipodoidea remains controversial. Strikingly, molecular approach has never been envisaged to investigate these questions. In this study, the phylogenetic relationships among the main dipodoid lineages were reconstructed for the first time using DNA sequence data from four nuclear genes (IRBP, GHR, BRCA1, RAG1). No evidence of conflict among genes was revealed. The same robustly supported tree topology was inferred from the concatenated alignment whatever the phylogenetic methods used (maximum parsimony, maximum-likelihood and Bayesian phylogenetic methods). Sminthinae branches basally within the dipodoids followed by Zapodinae. Monophyletic Cardiocraniinae is sister to all other jerboas. Within the latter, the monophyly of both Dipodinae and Allactaginae is highly supported. The relationships between Dipodinae, Allactaginae and Euchoreutinae should be regarded as unresolved trichotomy. Morphological hypotheses were confronted to findings based on the presented molecular data. As a result, previously proposed sister group relationships between Euchoreutes and Sicista, Paradipus and Cardiocraniinae as well as the monophyly of Cardiocaniinae + Dipodinae were rejected. However, the latter association is consistently supported by most morphological analyses. The basis of the obvious conflict between genes and morphology remains unclear. Suggested modifications to the taxonomy of Dipodoidea imply recognition of three families: Sminthidae, Zapodidae and Dipodidae, the latter including Cardiocraniinae, Euchoreutinae, Allactaginae and Dipodinae as subfamilies. [less ▲]

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See detailMolecular phylogeny in the genus Phaseolus.
Fofana, B.; Du Jardin, Patrick ULg; Baudoin, Jean-Pierre ULg

in 3rd European conference on grain legumes. Opportunities for highquality, healthy and added-value crops to meet European demands.Valladolid, Spain, 14-19 November 1998. (1998)

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