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See detailImpaired angiogenesis and tumor development by inhibition of the mitotic kinesin Eg5.
Exertier, Prisca; Javerzat, Sophie; Wang, Baigang et al

in Oncotarget (2013), 4(12), 2302-16

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of ... [more ▼]

Kinesin motor proteins exert essential cellular functions in all eukaryotes. They control mitosis, migration and intracellular transport through interaction with microtubules. Small molecule inhibitors of the mitotic kinesin KiF11/Eg5 are a promising new class of anti-neoplastic agents currently evaluated in clinical cancer trials for solid tumors and hematological malignancies. Here we report induction of Eg5 and four other mitotic kinesins including KIF20A/Mklp2 upon stimulation of in vivo angiogenesis with vascular endothelial growth factor-A (VEGF-A). Expression analyses indicate up-regulation of several kinesin-encoding genes predominantly in lymphoblasts and endothelial cells. Chemical blockade of Eg5 inhibits endothelial cell proliferation and migration in vitro. Mitosis-independent vascular outgrowth in aortic ring cultures is strongly impaired after Eg5 or Mklp2 protein inhibition. In vivo, interfering with KIF11/Eg5 function causes developmental and vascular defects in zebrafish and chick embryos and potent inhibition of tumor angiogenesis in experimental tumor models. Besides blocking tumor cell proliferation, impairing endothelial function is a novel mechanism of action of kinesin inhibitors. [less ▲]

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See detailImpaired automatic and unconscious motor processes in Parkinson's disease
D'Ostilio, Kevin ULg; CREMERS, Julien ULg; DELVAUX, Valérie ULg et al

in Scientific Reports (2013)

While it is increasingly recognized that voluntary movements are produced by an interaction between conscious and unconscious processes, the role of the latter in Parkinson’s disease has received little ... [more ▼]

While it is increasingly recognized that voluntary movements are produced by an interaction between conscious and unconscious processes, the role of the latter in Parkinson’s disease has received little attention to date. Here, we administered a subliminal masked prime task to 15 Parkinson’s disease patients and 15 age-matched healthy elderly subjects. Compatibility effects were examined by manipulating the direction of the arrows and the interstimuli interval. Analysis of the positive compatibility effect revealed performance differences between the most and the least affected hand in Parkinson’s disease patients. Additionally, patients did not show the same tendency toward a negative compatibility effect as compared to elderly controls. These novel findings provide evidence supporting the role of basal ganglia circuits in controlling the balance between automatic motor response facilitation and inhibition. [less ▲]

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See detailImpaired cerebral connectivity in vegetative state
Laureys, Steven ULg; Faymonville, Marie ULg; Goldman, S. et al

in Physiological imaging of the brain with PET (2000)

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See detailImpaired controlled recollection processes in depression and subjective memory complaints
Jermann, Françoise; Adam, Stéphane ULg; Ceschi, Grazia et al

Poster (2001, July 18)

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See detailImpaired diaphragmatic function in the pneumonic calf
Desmecht, Daniel ULg; Linden, Annick ULg; Amory, Hélène ULg et al

in Proceedings of the 10th Comparative Respiratory Society Meeting (1991)

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See detailImpaired effective cortical connectivity in vegetative state : Preliminary investigation using PET
Laureys, Steven ULg; Goldman, Serge; Phillips, Christophe ULg et al

in Neuroimage (1999), 9(4), 377-382

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural ... [more ▼]

Vegetative state (VS) is a condition of abolished awareness with persistence of arousal. Awareness is part of consciousness, which itself is thought to represent an emergent property of cerebral neural networks. Our hypothesis was that part of the neural correlate underlying VS is an altered connectivity, especially between the associative cortices. We assessed regional cerebral glucose metabolism (rCMRGlu) and effective cortical connectivity in four patients in VS by means of statistical parametric mapping and [F-18]fluorodeoxyglucose-positron emission tomography. Our data showed a common pattern of impaired rCMRGlu in the prefrontal, premotor, and parietotemporal association areas and posterior cingulate cortex/precuneus in VS. In a next step, we demonstrated that in VS patients various prefrontal and premotor areas have in common that they are less tightly connected with the posterior cingulate cortex than in normal controls. These results provide a strong argument for an alteration of cortical connectivity in VS patients. (C) 1999 Academic Press. [less ▲]

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See detailImpaired emotional facial expression in alcoholism compared with obsessive compulsive disorder and normal controls
Kornreich, C; Blairy, Sylvie ULg; Philippot, P et al

in Psychiatry Research (2001), 102

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See detailImpaired emotional facial expression recognition is associated with interpersonal problems in alcoholism
Kornreich, C; Philippot, P; Foisy, ML et al

in Alcohol & Alcoholism (2002), 37(4), 394-400

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See detailImpaired immune responses in diabetes mellitus: analysis of the factors and mechanisms involved. Relevance to the increased susceptibility of diabetic patients to specific infections.
Moutschen, Michel ULg; Scheen, André ULg; Lefebvre, Pierre ULg

in Diabète & Métabolisme (1992), 18(3), 187-201

The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk ... [more ▼]

The reasons why diabetic patients present with an increased susceptibility to frequent and protracted infections remain unclear. The virtual absence of epidemiological studies of the independent risk factors involved contrasts with the multitude of in vitro models focused on the metabolism and function of immune cells from diabetic patients. This review analyzes some of these models and their clinical relevance. The different levels of diabetes pathogenesis: genetic (Type 1), autoimmune (Type 1) and metabolic (Type 1 and Type 2) are responsible for immune abnormalities demonstrated in in vitro models. The participation of genetic and autoimmune factors has been mainly characterized on T lymphocyte function. The B8 DR3 haplotype is associated with several minor immunologic abnormalities in vitro. However, the high frequency of this haplotype in healthy individuals argues against its involvement in significant defects of antimicrobial immunity. Genetic deficiency of C4, present in 25% of Type 1 diabetic patients could, on the other hand, be responsible for opsonization defects against encapsulated pathogens. Several immunological abnormalities related to the autoimmune process preceding the onset of Type 1 diabetes mellitus, such as the depletion of memory CD4+ cells and the defective natural killer activity could transiently impair host defences against viral diseases. Several in vitro functional defects of the immune system have been correlated with the metabolic control of diabetic patients. This suggests the involvement of insulinopenia in some of the abnormalities observed. Insulinopenia-induced enzymatic defects have often been proposed to inhibit energy-requiring functions of phagocytes and lymphocytes. However, the relevance of this mechanism could be confined to patients with extremely severe metabolic abnormalities. The importance of systemic consequences of insulinopenia such as hyperglycaemia and ketosis has also been addressed. Usually, the defects induced in vitro by these factors are slight and require supraphysiologic concentrations of glucose or ketone bodies. Recent studies have shown abnormalities of signal transduction mechanisms in which insulinopenia itself and other factors such as circulating immune complexes could be involved. Despite numerous controversies, many in vitro studies of the immune cells of diabetic patients have demonstrated significant defects which bear quantitative similarities with abnormalities described in other immunodeficiency syndromes. Furthermore, several mechanisms have been proposed to link the different defects observed with the specific infections encountered in diabetic patients. [less ▲]

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See detailImpaired insulin-induced erythrocyte magnesium accumulation is correlated to impaired insulin-mediated glucose disposal in type 2 (non-insulin-dependent) diabetic patients.
Paolisso, G.; Sgambato, S.; Giugliano, D. et al

in Diabetologia (1988), 31(12), 910-5

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal ... [more ▼]

Plasma and erythrocyte magnesium levels were measured by atomic absorption spectrometry in 12 healthy subjects and 12 moderately obese patients with Type 2 (non-insulin-dependent) diabetes mellitus. Basal plasma and erythrocyte magnesium levels were significantly lower in diabetic patients than in control subjects. In vitro incubation in the presence of 100 mU/l insulin significantly increased magnesium erythrocyte levels in both control subjects (p less than 0.001) and patients with diabetes (p less than 0.001). However, even in the presence of 100 mU/l insulin, the erythrocyte magnesium content of patients with Type 2 diabetes was lower than that of control subjects. The in vitro dose-response curve of the effect of insulin on magnesium erythrocyte accumulation was shifted to the right when red cells of diabetic patients were used, with a highly significant reduction of the maximal effect. Such reduction of the maximal effect of insulin suggests that the impairment of insulin-induced erythrocyte magnesium accumulation observed in Type 2 diabetic patients results essentially from a post-receptor defect.(ABSTRACT TRUNCATED AT 250 WORDS) [less ▲]

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See detailImpaired iodide organification in autonomous thyroid nodules
Moreno-Reyes, Rodrigo; Tang, Bich-Ngoc-Thanh; Seret, Alain ULg et al

in Journal of Clinical Endocrinology and Metabolism (2007), 92(12), 4719-4724

Context: The clinical evolution of autonomous thyroid nodules (ATN) is unpredictable, and thyrotoxicosis is observed at variable nodule size. In vitro data suggest that hydrogen peroxide production is ... [more ▼]

Context: The clinical evolution of autonomous thyroid nodules (ATN) is unpredictable, and thyrotoxicosis is observed at variable nodule size. In vitro data suggest that hydrogen peroxide production is decreased in ATN, indicating intranodular iodide organification impairment. Objective: We aimed to determine iodide organification efficiency in ATN and its relationship with thyroid status in patients. Design: Forty-six patients with a single ATN on the I-123 thyroid scan were included in the study. Biological evaluation and iodine perchlorate (I-ClO4) discharge test were carried out in all subjects. Setting: The study took place at an academic hospital. Results: Among the 46 patients, 28 patients (61%) had a positive I-ClO4 discharge test with a mean +/- SD value of discharge of 42 +/- 13%, and 18 (39%) had a negative discharge test with mean +/- SD of 5 +/- 9%. In the group of patients with a negative discharge test but not in the group with a positive test, serum-free T-3 and free T-4 concentrations were significantly correlated with the I-123 uptake. The severity of hyperthyroidism was not different between both groups. Conclusions: Intranodular iodide organification was impaired in most patients with ATN. Whether differences in organification capability could predict the risk for evolution to overt hyperthyroidism in patients with ATN remains to be established. [less ▲]

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See detailImpaired LTP in the dentate gyrus of calretinin deficient mice
Schiffman, S. N.; Schurmans, Stéphane ULg; Gurden, H. et al

in Cell Biology International (1998), 22(5), 386-387

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See detailImpaired motor coordination and Purkinje cell excitability in mice lacking calretinin
Schiffmann, Serge N.; Cheron, Guy; Lohoff, Ann et al

in Proceedings of the National Academy of Sciences of the United States of America (1999), 96

n the cerebellum, the parallel fiber-Purkinje cell synapse can undergo long-term synaptic plasticity suggested to underlie motor learning and resulting from variations in intracellular calcium ... [more ▼]

n the cerebellum, the parallel fiber-Purkinje cell synapse can undergo long-term synaptic plasticity suggested to underlie motor learning and resulting from variations in intracellular calcium concentration ([Ca2+]i). Ca2+ binding proteins are enriched in the cerebellum, but their role in information processing is not clear. Here, we show that mice deficient in calretinin (Cr-/-) are impaired in tests of motor coordination. An impairment in Ca2+ homeostasis in Cr-/- Purkinje cells was supported by the high Ca2+-saturation of calbindin-D28k in these cells. The firing behavior of Purkinje cells is severely affected in Cr-/- alert mice, with alterations of simple spike firing rate, complex spike duration, and simple spike pause. In contrast, in slices, transmission at parallel fiber- or climbing fiber-Purkinje cell synapses is unaltered, indicating that marked modifications of the firing behavior in vivo can be undetectable in slice. Thus, these results show that calretinin plays a major role at the network level in cerebellar physiology [less ▲]

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See detailImpaired neuromuscular transmission and skeletal muscle fiber necrosis in mice lacking Na/Ca exchanger 3
Sokolow, S.; Manto, M.; Gailly, P. et al

in Journal of Clinical Investigation (2004), 113

We produced and analyzed mice deficient for Na/Ca exchanger 3 (NCX3), a protein that mediates cellular Ca(2+) efflux (forward mode) or Ca(2+) influx (reverse mode) and thus controls intracellular Ca(2 ... [more ▼]

We produced and analyzed mice deficient for Na/Ca exchanger 3 (NCX3), a protein that mediates cellular Ca(2+) efflux (forward mode) or Ca(2+) influx (reverse mode) and thus controls intracellular Ca(2+) concentration. NCX3-deficient mice (Ncx3(-/-)) present a skeletal muscle fiber necrosis and a defective neuromuscular transmission, reflecting the absence of NCX3 in the sarcolemma of the muscle fibers and at the neuromuscular junction. The defective neuromuscular transmission is characterized by the presence of electromyographic abnormalities, including low compound muscle action potential amplitude, a decremental response at low-frequency nerve stimulation, an incremental response, and a prominent postexercise facilitation at high-frequency nerve stimulation, as well as neuromuscular blocks. The analysis of quantal transmitter release in Ncx3(-/-) neuromuscular junctions revealed an important facilitation superimposed on the depression of synaptic responses and an elevated delayed release during high-frequency nerve stimulation. It is suggested that Ca(2+) entering nerve terminals is cleared relatively slowly in the absence of NCX3, thereby enhancing residual Ca(2+) and evoked and delayed quantal transmitter release during repetitive nerve stimulation. Our findings indicate that NCX3 plays an important role in vivo in the control of Ca(2+) concentrations in the skeletal muscle fibers and at the neuromuscular junction [less ▲]

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See detailImpaired respiration discloses the physiological significance of state transitions in Chlamydomonas.
Cardol, Pierre ULg; Alric, Jean; Girard-Bascou, Jacqueline et al

in Proceedings of the National Academy of Sciences of the United States of America (2009), 106(37), 15979-84

State transitions correspond to a major regulation process for photosynthesis, whereby chlorophyll protein complexes responsible for light harvesting migrate between photosystem II and photosystem I in ... [more ▼]

State transitions correspond to a major regulation process for photosynthesis, whereby chlorophyll protein complexes responsible for light harvesting migrate between photosystem II and photosystem I in response to changes in the redox poise of the intersystem electron carriers. Here we disclose their physiological significance in Chlamydomonas reinhardtii using a genetic approach. Using single and double mutants defective for state transitions and/or mitochondrial respiration, we show that photosynthetic growth, and therefore biomass production, critically depends on state transitions in respiratory-defective conditions. When extra ATP cannot be provided by respiration, enhanced photosystem I turnover elicited by transition to state 2 is required for photosynthetic activity. Concomitant impairment of state transitions and respiration decreases the overall yield of photosynthesis, ultimately leading to reduced fitness. We thus provide experimental evidence that the combined energetic contributions of state transitions and respiration are required for efficient carbon assimilation in this alga. [less ▲]

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See detailImpaired semantic knowledge underlies the reduced verbal short-term storage capacity in Alzheimer's disease.
Peters, Frederic; Majerus, Steve ULg; De Baerdemaeker, Julie et al

in Neuropsychologia (2009), 47(14), 3067-73

A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during ... [more ▼]

A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor STM performance. The aim of this study was to examine the influence of semantic knowledge on verbal short-term memory storage capacity in normal aging and in AD by exploring the impact of word imageability on STM performance. Sixteen patients suffering from mild AD, 16 healthy elderly subjects and 16 young subjects performed an immediate serial recall task using word lists containing high or low imageability words. All participant groups recalled more high imageability words than low imageability words, but the effect of word imageability on verbal STM was greater in AD patients than in both the young and the elderly control groups. More precisely, AD patients showed a marked decrease in STM performance when presented with lists of low imageability words, whereas recall of high imageability words was relatively well preserved. Furthermore, AD patients displayed an abnormal proportion of phonological errors in the low imageability condition. Overall, these results indicate that the support of semantic knowledge on STM performance was impaired for lists of low imageability words in AD patients. More generally, these findings suggest that the deterioration of semantic knowledge is partly responsible for the poor verbal short-term storage capacity observed in AD. [less ▲]

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See detailImpaired short-term memory for order in adults with dyslexia
Martinez Perez, Trecy ULg; Majerus, Steve ULg; Poncelet, Martine ULg

in Research in Developmental Disabilities (2013), 34

Verbal short-term memory (STM) deficits are consistently associated with dyslexia, but the nature of these deficits remains poorly understood. This study used the distinction between item and order ... [more ▼]

Verbal short-term memory (STM) deficits are consistently associated with dyslexia, but the nature of these deficits remains poorly understood. This study used the distinction between item and order retention processes to achieve a better understanding of STM deficits in adults with dyslexia. STM for item information has been shown to depend on the quality of underlying phonological representations, and hence should be impaired in dyslexia, which is characterized by poorly developed phonological representations. On the other hand, STM for order information is considered to reflect core STM processes, which are independent from language processing. Thirty adults with dyslexia and thirty control participants matched for age, education, vocabulary, and IQ were presented STM tasks, which distinguished item and order STM capacities. We observed not only impaired order STM in adults with dyslexia, but this impairment was independent of item STM impairment. This study shows that adults with dyslexia present a deficit in core verbal STM processes, a deficit which cannot be accounted for by the language processing difficulties that characterize dyslexia. Moreover, these results support recent theoretical accounts considering independent order STM and item STM processes, with a potentially causal involvement of order STM processes in reading acquisition. [less ▲]

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See detailImpaired verbal short-term memory for serial order information in dyslexic adults
Martinez Perez, Trecy ULg; Majerus, Steve ULg; Poncelet, Martine ULg

Poster (2010, September 10)

This study used the distinction of item and order information in verbal short-term memory (STM) to further our understanding of verbal STM impairments in dyslexia. Item STM has been shown to depend on the ... [more ▼]

This study used the distinction of item and order information in verbal short-term memory (STM) to further our understanding of verbal STM impairments in dyslexia. Item STM has been shown to depend on the quality of underlying phonological representations and hence should be impaired in dyslexic participants given their poor phonological processing abilities. On the other hand, order STM represents a specific STM capacity predicting learning capacity for new phonological and orthographic sequences (Majerus et al., 2006; Nithart et al, 2010). If STM impairments contribute to dyslexia, then especially order STM should be impaired, in addition to item STM. [less ▲]

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