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See detailMetabolic and Structural Abnormalities in Dogs with Early Left Ventricular Dysfunction Induced by Incessant Tachycardia
Mc Entee, Kathleen ULg; Flandre, Thierry; Doizé, Cécile ULg et al

in American Journal of Veterinary Research (2001), 62(6), 889-94

OBJECTIVE: To assess morphologic and metabolic abnormalities in dogs with early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP). ANIMALS: 7 Beagles. PROCEDURE: Plasma ... [more ▼]

OBJECTIVE: To assess morphologic and metabolic abnormalities in dogs with early left ventricular dysfunction (ELVD) induced by rapid right ventricular pacing (RRVP). ANIMALS: 7 Beagles. PROCEDURE: Plasma carnitine concentrations were measured before and after development of ELVD induced by RRVP. At the same times, transvenous endomyocardial biopsy was performed, and specimens were submitted for determination of myocardial carnitine concentrations and histologic, morphometric, and ultrastructural examination. RESULTS: In 4 dogs in which baseline plasma total carnitine concentration was normal, RRVP induced a decrease in myocardial total and free carnitine concentrations and an increase in myocardial esterified carnitine concentration. In 3 dogs in which baseline plasma total carnitine concentration was low, plasma and myocardial carnitine concentrations were unchanged after pacing. Structural changes associated with pacing included perinuclear vacuolization in 3 dogs. Morphometric analyses indicated there was a decrease in myofiber cross-sectional diameter and area following pacing. Electron microscopy revealed changes in myofibrils and mitochondria following pacing. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that moderate to severe alterations in myocyte cytoarchitecture are present in dogs with ELVD induced by RRVP and that in dogs with normal plasma carnitine concentrations, myocardial carnitine deficiency may be a biochemical marker of ELVD. Results also indicated that transvenous endomyocardial biopsy can be used to evaluate biochemical and structural myocardial changes in dogs with cardiac disease. [less ▲]

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See detailMetabolic and structural connectivity within the default mode network relates to working memory performance in young healthy adults
Yakushev, Igor; Chételat, Gael; Fischer F.U. et al

in NeuroImage (2013), 79

Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes ... [more ▼]

Studies of functional connectivity suggest that the default mode network (DMN) might be relevant for cognitive functions. Here, we examined metabolic and structural connectivity between major DMN nodes, the posterior cingulate (PCC) and medial prefrontal cortex (MPFC), in relation to normal working memory (WM). DMN was captured using independent component analysis of [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) data from 35 young healthy adults (27.1±5.1 years). Metabolic connectivity, a correlation between FDG uptake in PCC and MPFC, was examined in groups of subjects with (relative to median) low (n=18) and high (n=17) performance on digit span backward test as an index of verbal WM. In addition, fiber tractography based on PCC and MPFC nodes as way points was performed in a subset of subjects. FDG uptake in the DMN nodes did not differ between high and low performers. However, significantly (p=0.01) lower metabolic connectivity was found in the group of low performers. Furthermore, as compared to high performers, low performers showed lower density of the left superior cingulate bundle. Verbal WM performance is related to metabolic and structural connectivity within the DMN in young healthy adults. Metabolic connectivity as quantified with FDG-PET might be a sensitive marker of the normal variability in some cognitive functions. [less ▲]

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See detailMetabolic cerebral correlates of conjunctive and relational memory in Alzheimer's disease
Bastin, Christine ULg; Bahri, Mohamed Ali ULg; Collette, Fabienne ULg et al

Poster (2014)

Introduction. Memory deficits are the clinical hallmark of typical Alzheimer’s disease. The precise nature of these deficits however remains to be fully characterized. In this study, we investigated ... [more ▼]

Introduction. Memory deficits are the clinical hallmark of typical Alzheimer’s disease. The precise nature of these deficits however remains to be fully characterized. In this study, we investigated binding in long-term episodic memory. Relational binding processes in memory create an associative link between independent items or between items and context into episodic memories (Cohen et al., 1999). An alternative process, conjunctive binding, allows associations to be encoded as a united representation of features into a single entity (O'Reilly and Rudy, 2001; Mayes et al., 2007). The current study (1) assessed whether Alzheimer’s disease disrupt both conjunctive and relational memory, and (2) related patients’ memory performance to cerebral metabolism. Methods. Thirty patients with mild Alzheimer’s disease and 24 healthy older adults performed a source memory task where items were associated to a background color (Diana et al., 2008, 2010). In one condition, relational binding was promoted by the instruction to associate the item with another object of the same color as the background. In the other condition, color had to be integrated as an item feature (conjunctive binding). Patients’ brain metabolic activity at rest (FDG-PET) was analysed with spatio-temporal Partial Least Squares (McIntosh et al., 1996) in order to assess the relation of behavioral performance and activity in functional cerebral networks. Results. Alzheimer’s disease patients had an impaired capacity to remember item-color associations, with deficits in both relational and conjunctive memory. However, performance in the two kinds of associative memory varied independently across patients. Partial least square analyses revealed a significant pattern of metabolic activity that correlated specifically with each condition (accounting for 76.48 % of the covariance in the data; p< .05). More specifically, poor conjunctive memory was related to hypometabolism in an anterior temporal-posterior fusiform brain network, whereas relational memory correlated with metabolism in regions of the default mode network. Conclusions. These findings support the hypothesis of distinct neural systems specialized in different types of associative memory and point to heterogeneous profiles of memory alteration in Alzheimer’s disease as a function of damage to the respective neural networks. [less ▲]

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See detailMetabolic Changes in the Spinal Cord After Brachial Plexus Root Re-implantation
Kachramanoglou, C; De Vita, E; Thomas, D et al

in Neurorehabilitation & Neural Repair (2013), 27(2), 118-124

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See detailMetabolic clearance rate of insulin in type 2 diabetic patients treated with combined insulin and sulfonylurea therapy.
Castillo, M. J.; Scheen, André ULg; Lefebvre, Pierre ULg

in Revista Espanola de Fisiologia (1994), 50(1), 27-34

The metabolic clearance rate of insulin (MCRI) in 10 non-obese type 2 diabetic patients treated with either insulin alone or combined insulin plus sulfonylurea therapy is investigated. A classical 2-hour ... [more ▼]

The metabolic clearance rate of insulin (MCRI) in 10 non-obese type 2 diabetic patients treated with either insulin alone or combined insulin plus sulfonylurea therapy is investigated. A classical 2-hour euglycaemic hyperinsulinaemic glucose clamp using the artificial pancreas was performed in a randomized order after two 6-week periods of treatment: either with subcutaneous injections of insulin alone or with insulin plus oral administration of the sulfonylurea compound glipizide at the dose of 3 x 10 mg/day. The MCRI was calculated knowing the constant insulin infusion rate (0.1 U.kg-1.h-1) and measuring basal and steady-state plasma free insulin and C-peptide levels. When the test was performed at the end of the period of treatment with insulin plus glipizide and 30 min after the ingestion of the last dose of 10 mg glipizide, plasma C-peptide levels were significantly increased and steady-state free insulin levels tended to be slightly higher whereas the metabolic clearance rate of glucose was not affected. The MCRI was significantly reduced by glipizide from 23.3 +/- 2.9 to 18.9 +/- 2.0 ml.kg-1.min-1 p < 0.05. These results demonstrate that the sulfonylurea glipizide decreases the MCRI. This effect may play a role in the hypoglycemic action of sulfonylureas. [less ▲]

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See detailMetabolic correlates of clinical heterogeneity in questionable Alzheimer’s disease
Salmon, Eric ULg; Lekeu, Françoise ULg; Garraux, Gaëtan ULg et al

in Neurobiology of Aging (2008), 29

Thirty-four subjects with questionable Alzheimer's disease (QAD) were included in a 3-year prospective study and underwent neuropsychological testing and measurement of brain metabolism using FDG-PET at ... [more ▼]

Thirty-four subjects with questionable Alzheimer's disease (QAD) were included in a 3-year prospective study and underwent neuropsychological testing and measurement of brain metabolism using FDG-PET at entry. Seventeen patients (50%) did not convert to AD during the follow-up period. Compared to elderly controls of similar age, the cerebral activity of non-converters was reduced in the dorsolateral prefrontal cortex. Moreover, the variability of metabolism in the posterior cingulate cortex was related to their visuospatial memory performance, while disparity in parietal activity was related to their verbal memory performance. These results demonstrate the cerebral metabolic heterogeneity of patients with QAD. Initial functional images of converters showed that activity was already impaired in the posterior cingulate, lateral temporal cortex, anterior cingulate and orbitofrontal cortex. This metabolic pattern is consistent with a pre-dementia stage of AD, and highlights the fact that significant frontal metabolic involvement may be associated with impaired activity in posterior associative cortices in very early AD. [less ▲]

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See detailMetabolic diversity and microbial biomass in forest soils across climatic and tree species diversity gradients
Carnol, Monique ULg; Bosman, Bernard ULg; Vanoppen, Astrid et al

Poster (2013, August)

The biogeochemical cycling in forest ecosystems is highly dependent on the interactions between plants and soil. Tree species affect element cycling through deposition in throughfall, litterfall ... [more ▼]

The biogeochemical cycling in forest ecosystems is highly dependent on the interactions between plants and soil. Tree species affect element cycling through deposition in throughfall, litterfall, microbial activities in soil and rhizosphere processes. Tree species diversification has been suggested for maintaining forest ecosystem services and combining provisioning and supporting services within multifunctional and sustainable forestry. However, the understanding of the role of biodiversity in forests is unclear, in particular concerning the microbial diversity and activity in soils. Here we synthesize results from measurements of bacterial metabolic diversity and microbial biomass in soils sampled in the 209 plots of the Exploratory Platform of the FunDivEUROPE project (http://www.fundiveurope.eu/). This Exploratory Platform is a network of comparative plots of 1-5 tree species established in existing mature forest in 6 countries. These six focal regions represent important European forest types along the gradient from boreal forest to Mediterranean forest. We analysed the impact of tree species richness and the role of other controlling factors on the metabolic diversity of soil bacteria and on microbial biomass. [less ▲]

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See detailMetabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence.
Scheen, André ULg; Paquot, Nicolas ULg

in Diabetes & metabolism (2014), 40(6 Suppl 1), 4-11

Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by ... [more ▼]

Sodium-glucose cotransporter type 2 (SGLT-2) inhibitors (canagliflozin, dapagliflozin, empagliflozin) are new glucose-lowering agents that exert their therapeutic activity independently of insulin by facilitating glucose excretion through the kidneys. However, this simple renal mechanism that results in sustained glucose urinary loss leads to more complex indirect metabolic effects. First, by reduction of chronic hyperglycaemia and attenuation of glucose toxicity, SGLT-2 inhibitors can improve both insulin secretion by beta cells and peripheraltissue insulin sensitivity. In the case of canagliflozin, because of low-potency SGLT1 inhibition, a non-renal (intestinal) effect may also be considered, which may contribute to better control of postprandial hyperglycaemia, although this contribution remains to be better analyzed in humans. Second, chronic glucose loss most probably leads to compensatory mechanisms. One of them, although not well evidenced in humans, might involve an increase in energy intake, an effect that may limit weight loss in the long run. Another could be an increase in endogenous glucose production, most probably driven by increased glucagon secretion, which may somewhat attenuate the glucoselowering effect. Nevertheless, despite these compensatory mechanisms and most probably because of the positive effects of the reduction in glucotoxicity, SGLT-2 inhibitors exert clinically relevant glucose-lowering activity while promoting weight loss, a unique dual effect among oral antidiabetic agents. Furthermore, the combination of SGLT-2 inhibitors with other drugs that either have anorectic effects (such as incretin-based therapies) or reduce hepatic glucose output (like metformin) and, thus, may dampen these two compensatory mechanisms appears appealing for the management of type 2 diabetes mellitus. [less ▲]

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See detailMetabolic enzymes from psychrophilic bacteria: Challenge of adaptation to low temperatures in ornithine carbamoyltransferase from Moritella abyssi
Xu, Y.; Feller, Georges ULg; Gerday, Charles ULg et al

in Journal of Bacteriology (2003), 185(7), 2161-2168

The enzyme ornithine carbamoyltransferase (OTCase) of Motitella abyssi (OTCase(Mab)), a new, strictly psychrophilic and piezophilic bacterial species, was purified. OTCase(Mab) displays maximal activity ... [more ▼]

The enzyme ornithine carbamoyltransferase (OTCase) of Motitella abyssi (OTCase(Mab)), a new, strictly psychrophilic and piezophilic bacterial species, was purified. OTCase(Mab) displays maximal activity at rather low temperatures (23 to 25degreesC) compared to other cold-active enzymes and is much less thermoresistant than its homologues from Escherichia coli or thermophilic procaryotes. In vitro the enzyme is in equilibrium between a trimeric state and a dodecameric, more stable state. The melting point and denaturation enthalpy changes for the two forms are considerably lower than the corresponding values for the dodecameric Pyrococcus furiosus OTCase and for a thermolabile trimeric mutant thereof. OTCase(Mab) displays higher K-m values for ornithine and carbamoyl phosphate than mesophilic and thermophilic OTCases and is only weakly inhibited by the bisubstrate analogue delta-N-phosphonoacetyl-L-ornithine (PALO). OTCase(Mab) differs from other, nonpsychrophilic OTCases by substitutions in the most conserved motifs, which probably contribute to the comparatively high K-m values and the lower sensitivity to PALO. The K. for ornithine, however, is substantially lower at low temperatures. A survey of the catalytic efficiencies (k(cat)/K-m) of OTCases adapted to different temperatures showed that OTCase(Mab) activity remains suboptimal at low temperature despite the 4.5-fold decrease in the K-m value for ornithine observed when the temperature is brought from 20 to 5degreesC. OTCase(Mab) adaptation to cold indicates a trade-off between affinity and catalytic velocity, suggesting that optimization of key metabolic enzymes at low temperatures may be constrained by natural limits. [less ▲]

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See detailMetabolic monitoring of chemosensitivity with 18FDG PET.
Jerusalem, Guy ULg; Belhocine, Tarik Z

in Methods in Molecular Medicine (2005), 111

Accurate and early evaluation of tumor response to chemotherapy is a growing clinical need for optimal management of oncology patients. This is even more warranted by the lack of appropriate response ... [more ▼]

Accurate and early evaluation of tumor response to chemotherapy is a growing clinical need for optimal management of oncology patients. This is even more warranted by the lack of appropriate response evaluation criteria to new molecularly targeted anticancer therapies. In the two last decades, new developments in the field of nuclear oncology have allowed the introduction of various radiopharmaceuticals to be used on dedicated imaging devices. In the present chapter, we report the added value that positron emission tomography (PET) with 18F-fluorodeoxyglucose (18FDG) may offer to assess tumor response to treatment. PET is a high-end imaging technology using 18FDG as metabolic tracer that mimics the biochemical behavior of the natural glucose molecule. Because most tumor types exhibit increased glucose metabolism, the imaging of 18FDG uptake within cancer tissues prior to any treatment enables the metabolic technique to follow tumor responsiveness sequentially after one or several courses of chemotherapy. Moreover, metabolic tumor response evaluated by 18FDG PET often precedes morphological tumor changes measured by computed tomography or magnetic resonance imaging. So far, the suboptimal proper ties of 18FDG tracer and the lack of standardized methodology in PET imaging remain objective limitations for qualitative and quantitative assessment of chemosensitivity using the metabolic method. [less ▲]

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See detailMetabolic Pathway Analysis and Reduction for Mammalian Cell Cultures-Towards Macroscopic Modeling
Niu, H; Amribt, Z; Fickers, Patrick ULg et al

in Chemical Engineering Science (2013), (102), 461-473

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See detailMetabolic plasticity of wild-type and AOX-deficient Chlamydomonas reinhardtii cells related to the inorganic nitrogen source (nitrate or ammonium), as revealed by a 2D-DIGE comparative proteomic analysis
Gerin, Stéphanie ULg; Mathy, Grégory; Franck, Fabrice ULg

Poster (2012, June 15)

In the model unicellular green alga Chlamydomonas reinhardtii, both nitrate and ammonium can be used as primary inorganic nitrogen sources. Interestingly, the expression of the mitochondrial alternative ... [more ▼]

In the model unicellular green alga Chlamydomonas reinhardtii, both nitrate and ammonium can be used as primary inorganic nitrogen sources. Interestingly, the expression of the mitochondrial alternative oxidase (AOX), an "energy-dissipating" ubiquinol-oxygen oxidoreductase of the mitochondrial electron transport chain, is under the control of the exogenous nitrogen source : it is activated in nitrate-grown cells and repressed in ammonium-grown cells at both transcriptional and translational levels. This regulation of AOX by nitrogen is Chlamydomonas-specific and currently its bioenergetic and metabolic significance is poorly understood. In order to get clues to this peculiar phenomenon, we characterized the global metabolic response of a wild-type strain (WT) and an AOX-deficient mutant (AOX-) obtained by RNA interference grown either on nitrate or ammonium. For this purpose, we used a highly accurate 2D electrophoresis-based comparative proteomic approach (2D-DIGE) to compare the cellular proteomes of nitrate and ammonium-grown WT and AOX- Chlamydomonas. The analysis was performed in the middle of the exponential growth phase in mixotrophic conditions. It revealed many proteomic modifications between WT and AOX- cells and a smaller number between nitrate and ammonium-grown cells. In nitrate-grown cells, we notably observed an important up-regulation of glutamine synthetase. Interestingly, in AOX- cells, we respectively detected a general down-regulation and a general up-regulation of mitochondrial and chloroplastic bioenergetic enzymes, and also an important up-regulation of glutathione-dependent oxidative stress defense systems together with a remarkable down-regulation of methionine synthase. Altogether these results and previous studies provide new features in understanding the metabolic adaptations occurring in response to the inorganic nitrogen source with emphasis on the role played by AOX. [less ▲]

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See detailMetabolic profile of mixed culture acidogenic fermentation of lignocellulosic residues and the effect of upstream substrate fractionation by steam explosion
Perimenis, Anastasios; van Aarle, Ingrid; Nicolay, Thomas et al

in Biomass Conversion and Biorefinery (in press)

Lignocellulosic biomass residues have attracted attention for the sustainable production of molecules for material and energetic use through biochemical conversion. Their recalcitrant structure prevents a ... [more ▼]

Lignocellulosic biomass residues have attracted attention for the sustainable production of molecules for material and energetic use through biochemical conversion. Their recalcitrant structure prevents a broader use and asks for the development of sustainable techniques that can efficiently separate, recover and valorize the constituting components. In a cascading concept, residual streams of such processes can be further exploited in an attempt to valorize the largest possible fraction of the initial material. Three lignocellulosic substrates, namely dried sugar beet pulp, wheat bran and miscanthus straw, were upstream fractionated by steam explosion to extract the hemicellulose fraction. This study evaluated the valorization of the residual solid fraction through mixed acidogenic fermentation for the production of volatile fatty acids (VFA) as platform chemicals. Batch experiments have been conducted for the reference material (non-treated) and the solid fraction remaining after steam explosion, with and without the addition of an external mixed inoculum. Steam explosion residues contained less hemicellulose than the initial materials. The difference in the fermentation profile between steam explosion residues and non-treated substrates is dependent on the substrate. Maximum total VFA (tVFA) concentration was 18.8 gCOD/kgmixed_liquor, and maximum yield of chemical oxygen demand (COD) conversion into tVFAwas 33 % for the case of non-treated inoculated beet pulp. [less ▲]

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See detailMetabolic profiling in pea seeds
Vigeolas, Hélène ULg

Conference (2005)

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See detailMetabolic properties of bovine muscles: regulation by genetic and nutritional factors.
Hocquette, J. F.; Cabaraux, Jean-François ULg; Jurie, C. et al

in Book of absracts of the 54th Annual Meeting of the European Association for Animal Production (2003)

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See detailMetabolic reprogramming in transformed mouse cortical astrocytes: a proteomic study.
Bentaib, Azeddine; De Tullio, Pascal ULg; Chneiweiss, Herve et al

in Journal of proteomics (2015), 113

Metabolic reprogramming is thought to play a key role in sustaining the survival and proliferation of cancer cells. These changes facilitate for example the uptake and release of nutrients required for ... [more ▼]

Metabolic reprogramming is thought to play a key role in sustaining the survival and proliferation of cancer cells. These changes facilitate for example the uptake and release of nutrients required for nucleotide, protein and lipid synthesis necessary for macromolecule assembly and tumor growth. We applied a 2D-DIGE (Two-Dimensional Differential in-Gel Electrophoresis) quantitative proteomic analysis to characterize the proteomes of mouse astrocytes that underwent in vitro cancerous transformation, and of their normal counterparts. Metabolic reprogramming effects on enzymatic and structural protein expression as well as associated metabolites abundance were quantified. Using enzymatic activity measurements and zymography, we documented and confirmed several changes in abundance and activity of various isoenzymes likely to participate in metabolic reprogramming. We found that after transformation, the cells increase their expression of glycolytic enzymes, thus augmenting their ability to use aerobic glycolysis (Warburg effect). An increased capacity to dispose of reducing equivalents through lactate production was also documented. Major effects on carbohydrates, amino acids and nucleotides metabolic enzymes were also observed. Conversely, the transformed cells reduced their enzymatic capacity for reactions of tricarboxylic acid oxidation, for neurotransmitter (glutamate) metabolism, for oxidative stress defense and their expression of astroglial markers. BIOLOGICAL SIGNIFICANCE: The use of a global approach based on a 2D DIGE analysis allows obtaining a comprehensive view of the metabolic reprogramming undergone by astrocytes upon cancerous transformation. Indeed, except for a few enzymes such as pyruvate carboxylase and glutaminase that were not detected in our initial analysis, pertinent information on the abundance of most enzymes belonging to pathways relevant to metabolic reprogramming was directly obtained. In this in vitro model, transformation causes major losses of astrocyte-specific proteins and functions and the acquisition of metabolic adaptations that favor intermediate metabolites production for increased macromolecule biosynthesis. Thus our approach appears to be readily applicable for the investigation of changes in protein abundance that determine various transformed cell phenotypes. It could similarly be applied to the evaluation of the effects of treatments aimed at correcting the consequences of cell transformation. [less ▲]

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