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See detailOverexpression of a novel member of the mitochondrial carrier family rescues defects in both DNA and RNA metabolism in yeast mitochondria.
Van Dyck, E.; Jank, B.; Ragnini, A. et al

in Molecular & General Genetics [=MGG] (1995), 246

The PIF1 and MRS2 gene products have previously been shown to be essential for mitochondrial DNA maintenance at elevated temperatures and mitochondrial group II intron splicing, respectively, in the yeast ... [more ▼]

The PIF1 and MRS2 gene products have previously been shown to be essential for mitochondrial DNA maintenance at elevated temperatures and mitochondrial group II intron splicing, respectively, in the yeast Saccharomyces cerevisiae. A multicopy suppressor capable of rescuing the respiratory deficient phenotype associated with null alleles of either gene has been isolated. This suppressor is a nuclear gene that was called RIM2/MRS12. The RIM2/MRS12 gene encodes a predicted protein of 377 amino acids that is essential for mitochondrial DNA metabolism and proper cell growth. Inactivation of this gene causes the total loss of mitochondrial DNA and, compared to wild-type rhoo controls, a slow-growth phenotype on media containing glucose. Analysis of the RIM2/MRS12 protein sequence suggests that RIM2/MRS12 encodes a novel member of the mitochondrial carrier family. In particular, a typical triplicate structure, where each repeat consists of two putative transmembrane segments separated by a hydrophilic loop, can be deduced from amino acid sequence comparisons and the hydropathy profile of RIM2/MRS12. Antibodies directed against the aminoterminus of RIM2/MRS12 detect this protein in mitochondria. The function of the RIM2/MRS12 protein and the substrates it might transport are discussed. [less ▲]

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See detailOverexpression of CD39 in mouse airways promotes bacteria induced inflammation
Theatre, Emilie ULg; Frederix, Kim; Guilmain, William et al

in Journal of Immunology (2012), 189(4), 1966-1974

In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of ... [more ▼]

In airways, the ecto-nucleoside triphosphate diphosphohydrolase CD39 plays a central role in the regulation of physiological mucosal nucleotide concentrations and likely contributes to the control of inflammation because accelerated ATP metabolism occurs in chronic inflammatory lung diseases.We sought to determine whether constant elevated CD39 activity in lung epithelia is sufficient to cause inflammation and whether this affects the response to acute LPS or Pseudomonas aeruginosa exposure. We generated transgenic mice overexpressing human CD39 under the control of the airway-specific Clara cell 10-kDa protein gene promoter. Transgenic mice did not develop any spontaneous lung inflammation. However, intratracheal instillation of LPS resulted in accelerated recruitment of neutrophils to the airways of transgenic mice. Macrophage clearance was delayed, and the amounts of CD8+ T and B cells were augmented. Increased levels of keratinocyte chemoattractant, IL-6, and RANTES were produced in transgenic lungs. Similarly, higher numbers of neutrophils and macrophages were found in the lungs of transgenic mice infected with P. aeruginosa, which correlated with improved bacteria clearance. The transgenic phenotype was partially and differentially restored by coinstillation of P2X1 or P2X7 receptor antagonists or of caffeine with LPS. Thus, a chronic increase of epithelial CD39 expression and activity promotes airway inflammation in response to bacterial challenge by enhancing P1 and P2 receptor activation. [less ▲]

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See detailOverexpression of CD9 in human breast cancer cells promotes the development of bone metastases.
Kischel, Philippe; Bellahcene, Akeila ULg; Deux, Blandine et al

in Anticancer Research (2012), 32(12), 5211-20

BACKGROUND: Bone is a preferred target for circulating metastatic breast cancer cells. We found that the CD9 protein was up-regulated in the B02 osteotropic cell line, derived from the aggressive parental ... [more ▼]

BACKGROUND: Bone is a preferred target for circulating metastatic breast cancer cells. We found that the CD9 protein was up-regulated in the B02 osteotropic cell line, derived from the aggressive parental MDA-MB-231 breast cancer cell line. Here, we investigated the putative relationship between CD9 expression and the osteotropic phenotype. MATERIALS AND METHODS: Overexpression of CD9 was analyzed by immunoblotting in different cell lines. Immunohistochemistry was used to assess CD9 expression in primary tumors and metastatic lesions. In vivo experiments were conducted in mice using a monoclonal antibody against CD9. RESULTS: CD9 overexpression was confirmed in osteotropic cells. CD9 was significantly overexpressed in bone metastases versus primary tumors and visceral metastatic lesions. Finally, in vivo experiments showed that an antibody against CD9 delays homing of B02 cells in bone marrow, slowing down bone destruction. CONCLUSION: Our study reveals a potential implication of CD9 in the formation of bony metastases from breast cancer cells. [less ▲]

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See detailOverexpression of GRP94 in breast cancer cells resistant to oxidative stress promotes high levels of cancer cell proliferation and migration: implications for tumor recurrence.
Dejeans, Nicolas; Glorieux, Christophe; Guénin, Samuel ULg et al

in Free Radical Biology & Medicine (2012), 52(6), 993-1002

Targeting the altered redox status of cancer cells is emerging as an interesting approach to potentiate chemotherapy. However, to maximize the effectiveness of this strategy and define the correct ... [more ▼]

Targeting the altered redox status of cancer cells is emerging as an interesting approach to potentiate chemotherapy. However, to maximize the effectiveness of this strategy and define the correct chemotherapeutic associations, it is important to understand the biological consequences of chronically exposing cancer cells to reactive oxygen species (ROS). Using an H(2)O(2)-generating system, we selected a ROS-resistant MCF-7 breast cancer cell line, namely Resox cells. By exploring different survival pathways that are usually induced during oxidative stress, we identified a constitutive overexpression of the endoplasmic reticulum chaperone, GRP94, in these cells, whereas levels of its cytoplasmic homolog HSP90, or GRP78, were not modified. This overexpression was not mediated by constitutive unfolded protein response (UPR) activation. The increase in GRP94 is tightly linked to an increase in cell proliferation and migration capacities, as shown by GRP94-silencing experiments. Interestingly, we also observed that GRP94 silencing inhibits migration and proliferation of the highly aggressive MDA-MB-231 cells. By immunohistochemistry, we showed that GRP94 expression was higher in recurrent human breast cancers than in their paired primary neoplasias. Similar to the situation in the Resox cells, this increase was not associated with an increase in UPR activation in recurrent tumors. In conclusion, this study suggests that GRP94 overexpression may be a hallmark of aggressiveness and recurrence in breast cancers. [less ▲]

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See detailOverexpression of the 67-kD laminin receptor correlates with tumor progression in human prostate cancer
Waltregny, David ULg; de Leval, Laurence ULg; Ménard, Sylvie et al

in Proceedings of the American Association for Cancer Research (1997), 38

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See detailOverexpression of the 67-kD laminin receptor correlates with tumour progression in human colorectal carcinoma.
Sanjuan, X.; Fernandez, P. L.; Miquel, R. et al

in Journal of Pathology (The) (1996), 179(4), 376-80

The high affinity 67-kD laminin receptor (67LR) is a cell surface protein whose expression is increased in a number of human carcinoma models. To date, 67LR expression in colorectal carcinomas has been ... [more ▼]

The high affinity 67-kD laminin receptor (67LR) is a cell surface protein whose expression is increased in a number of human carcinoma models. To date, 67LR expression in colorectal carcinomas has been examined in a small number of cases. 67LR expression has been immunohistochemically analysed in a large series of human colorectal neoplasms, using the MLuC5 monoclonal antibody. The study included 59 samples of non-neoplastic mucosa, 45 polyps (11 hyperplastic, 34 adenomas), 196 carcinomas, and lymph node metastases of 87 carcinomas. Epithelial cells of normal mucosa and hyperplastic polyps were negative or showed weak positivity in the paranuclear and apical areas of the cytoplasm. In adenomas and carcinomas, the staining was stronger, with a membranous or cytoplasmic pattern. The expression of 67LR correlated significantly with the progression from normal mucosa (22 per cent) to adenoma (44 per cent), carcinoma (61 per cent), and lymph node metastasis (75 per cent) (P < 0.0001). Expression of the laminin receptor showed a tendency to be more frequently positive in advanced stage (III+IV; 67 (III+IV; 67 per cent) when compared with early stage (I+II) carcinomas (54 per cent). The difference, however, was not statistically significant (P = 0.058). In addition, 14 out of 28 (50 per cent) primary carcinomas without 67LR expression became positive in lymph node metastases, while most (86 per cent) of the MLuC5-positive primary carcinomas were also immunoreactive in metastases. In conclusion, these results indicate that 67LR is up-regulated in the progression of human colorectal carcinomas and may play a role in the local and metastatic progression of these tumours. [less ▲]

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See detailOverexpression of the 67-kDa laminin receptor correlates with tumor progression in human prostate cancer
Waltregny, David ULg; de Leval, Laurence ULg; Ménard, Sylvie et al

in Clinical & Experimental Metastasis (1996, March), 14(Suppl. 1), 1996

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See detailOverexpression of the homeobox gene HOXC8 in human prostate cancer correlates with loss of tumor differentiation
Waltregny, David ULg; Alami, Younes; Clausse, Nathalie et al

in Prostate (2002), 50(3), 162-169

BACKGROUND. Homeobox (HOX)-containing proteins have been identified as regulators controlling the coordinated expression of genes involved in development and differentiation. Recent data also suggest a ... [more ▼]

BACKGROUND. Homeobox (HOX)-containing proteins have been identified as regulators controlling the coordinated expression of genes involved in development and differentiation. Recent data also suggest a possible involvement of HOX genes in malignant transformation and/or progression. We have previously shown that HOXC8 expression was selectively turned on in human cervix cancer cells compared with normal keratinocytes, suggesting that HOXC8 may be involved in the process leading to the transformation of cervix keratinocytes [Alami et al.: Biochem Biophys Res Commun 257:738-745,1999]. METHODS. RT-PCR and in situ hybridization experiments were performed to investigate the expression and cell type localization of HOXC8 transcripts in human prostate cancer cell lines and tissues. In situ hybridization was performed with the use of an HOXC8 anti-sense digoxigenin-labeled probe to investigate HOXC8 mRNA expression in 27 prostate cancer tissue specimens. RESULTS. Out of the three human prostate cancer cell lines tested, DU-145 and PC3 but not LNCaP cells expressed detectable amount of HOXC8 transcripts. Results from in situ hybridization experiments demonstrated that HOXC8 gene was expressed mainly in malignant epithelial cells. Furthermore, the staining intensity in epithelial cells was significantly increased in high Gleason score carcinomas (scores 7-9, n = 12; labeling intensity 2 + to 3 +) compared with the one observed in low and intermediate Gleason score tumors (scores 3-6, n = 15; labeling intensity 0 and 1 +) (ANOVA test, P < 0.0001). CONCLUSIONS. Our data showing that HOXC8 overexpression is associated with the loss of tumor differentiation in human prostate cancer suggests that HOXC8 may play a role in the acquisition of the invasive and metastatic phenotype of this malignancy. (C) 2002 Wiley-Liss, Inc. [less ▲]

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See detailOverexpression of the platelet P2X1 ion channel in transgenic mice generates a novel prothrombotic phenotype.
Oury, Cécile ULg; Kuijpers, Marijke; Toth-Zsamboki, Emese et al

in Blood (2003)

This study describes transgenic mice overexpressing the human P2X(1) ion channel in the megakaryocytic cell lineage. Platelets from these mice display increased secretion and aggregation evoked by low ... [more ▼]

This study describes transgenic mice overexpressing the human P2X(1) ion channel in the megakaryocytic cell lineage. Platelets from these mice display increased secretion and aggregation evoked by low doses of collagen, convulxin, or the thromboxane A(2) mimetic U46619. Perfusing whole blood from transgenic mice over collagen fibers at a shear rate of 1000 seconds(-1) resulted in increased P2X(1)-dependent aggregate formation and phosphatidylserine exposure. Platelet hyperreactivity to collagen was correlated with up-regulated extracellular signal-regulated kinase 2 (ERK2) phosphorylation. In a viscometer, shear stress caused potent aggregation of transgenic platelets under conditions in which wild-type platelets did not aggregate. In an in vivo model of thromboembolism consisting of intravenous injection of a low dose of collagen plus epinephrine, transgenic mice died more readily than wild-type mice. Preinjection of U0126 not only fully protected transgenic mice against thrombosis, it also enhanced the survival of wild-type mice injected with a higher collagen dose. Hence, the platelet P2X(1) ion channel plays a role in hemostasis and thrombosis through its participation in collagen-, thromboxane A(2)-, and shear stress-triggered platelet responses. Activation of the ERK2 pathway is instrumental in these processes. [less ▲]

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See detailOverexpression of the platelet P2X1 ion channel.in transgenic mice generates a novel prothrombotic phenotype.
Oury, Cécile ULg; Kuijpers, Marijke; Toth-Zsamboki, Emese et al

in Journal of Thrombosis and Haemostasis [=JTH] (2003)

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See detailOverexpression of the soluble vascular endothelial growth factor receptor in preeclamptic patients: Pathophysiological consequences
Tsatsaris, V.; Goffin, Frédéric ULg; Munaut, Carine ULg et al

in Journal of Clinical Endocrinology and Metabolism (2003), 88(11), 5555-5563

Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in ... [more ▼]

Several growth factors such as vascular endothelial growth factor (VEGF)-A and placental growth factor (PlGF) are involved in the placental vascular development. We investigated whether dysregulation in the VEGF family may explain the defective uteroplacental vascularization characterizing preeclampsia. We compared pregnancies complicated by early onset severe preeclampsia or intrauterine growth retardation to normal pregnancies. Maternal plasma, placentas, and placental bed biopsies were collected. The mRNA levels of VEGF-A, PlGF, and their receptors were quantified in placentas and placental beds. Levels of VEGF-A, PlGF, and soluble VEGF receptor (VEGFR) were assessed in maternal plasma. In compromised pregnancies, elevated levels of VEGF-A and VEGFR-1 mRNAs may reflect the hypoxic status of the placenta. On contrast, the membrane-bound VEGFR-1 was decreased in the placental bed of preeclamptic patients. Preeclampsia was associated with low levels of circulating PlGF and increased levels of total VEGF-A and soluble VEGFR-1. Free VEGF-A was undetectable in maternal blood. Immunohistochemical studies revealed that VEGF-A and PlGF were localized in trophoblastic cells. Altogether, our results suggest two different pathophysiological mechanisms associated with preeclampsia. The first one is related to an overproduction of competitive soluble VEGFR-1 that may lead to suppression of VEGF-A and PlGF effects. The second one is the down-regulation of its membrane bound form (VEGFR-1) in the placental bed, which may result in the defective uteroplacental development. [less ▲]

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See detailOverexpression of TIMP-1 under the MMP-9 promoter interferes with wound healing in transgenic mice
Salonurmi, T.; Parikka, M.; Kontusaari, S. et al

in Cell & Tissue Research (2004), 315(1), 27-37

We have generated transgenic mice harboring the murine matrix metalloproteinase 9 (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were viable and fertile and exhibited normal ... [more ▼]

We have generated transgenic mice harboring the murine matrix metalloproteinase 9 (MMP-9) promoter cloned in front of human TIMP-1 cDNA. The transgenic mice were viable and fertile and exhibited normal growth and general development. During wound healing the mice were shown to express human TIMP-1 in keratinocytes that normally express MMP-9. However, the healing of skin wounds was significantly retarded with slow migration of keratinocytes over the wound in transgenic mice. In situ zymography carried out on wound tissues revealed total blockage of gelatinolytic activity (i.e., MMP-9 and MMP-2). The results confirm studies with MMP-9 knockout mice showing that MMP-9 is not essential for general development, but they also demonstrate an important role of keratinocyte MMP-9, as well that of other keratinocyte MMPs that are inhibited by TIMP-1, in wound healing. The transgenic mice generated in this study provide a model for the role of MMPs in MMP-9-producing cells in other challenging situations such as bone fracture recovery and cancer invasion. [less ▲]

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See detailOverexpression, purification and characterization of Mycobacterium bovis BCG alcohol dehydrogenase.
Wilkin, J. M.; Soetaert, K.; Stelandre, M. et al

in European Journal of Biochemistry (1999), 262(2), 299-307

A previous study of the effect of zinc deprivation on Mycobacterium bovis BCG pointed out the potential importance of an alcohol dehydrogenase for maintaining the hydrophobic character of the cell ... [more ▼]

A previous study of the effect of zinc deprivation on Mycobacterium bovis BCG pointed out the potential importance of an alcohol dehydrogenase for maintaining the hydrophobic character of the cell envelope. In this report, the effect of the overexpression of the M. bovis BCG alcohol dehydrogenase (ADH) in Mycobacterium smegmatis and M. bovis BCG is described. The purification of the enzyme was performed to apparent homogeneity from overexpressing M. bovis BCG cells and its kinetic parameters were determined. The enzyme showed a strong preference for both aromatic and aliphatic aldehydes while the corresponding alcohols were processed 100-1000-fold less efficiently. The best kcat/Km values were found with benzaldehyde > 3-methoxybenzaldehyde > octanal > coniferaldehyde. A phylogenetic analysis clearly revealed that the M. bovis BCG ADH together with the ADHs from Bacillus subtilis and Helicobacter pylori formed a sister group of the class C medium-chain alcohol dehydrogenases, the plant cinnamyl alcohol dehydrogenases (CADs). Comparison of the kinetic properties of our ADH with some related class C enzymes indicated that the mycobacterial enzyme substrate profile resembled that of the CADs involved in plant defence rather than those implicated in lignification. A possible role for the M. bovis BCG ADH in the biosynthesis of the lipids composing the mycobacterial cell envelope is proposed. [less ▲]

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See detailOverexpression, solubilization and refolding of a genetically engineered derivative of the penicillin-binding protein 3 of Escherichia coli K12.
Bartholomé-De Belder, J.; Nguyen-Distèche, Martine ULg; Houba-Herin, N. et al

in Molecular Microbiology (1988), 2(4), 519-525

Replacement of the amino-terminal 40-amino-acid region of the 588-amino-acid precursor of the membrane-bound penicillin-binding protein 3 (PBP3) by the decapeptide MKGKEFQAWI was carried out by altering ... [more ▼]

Replacement of the amino-terminal 40-amino-acid region of the 588-amino-acid precursor of the membrane-bound penicillin-binding protein 3 (PBP3) by the decapeptide MKGKEFQAWI was carried out by altering the amino-coding end of the ftsI gene. Insertion of the modified gene into a runaway-replication plasmid under the control of a fused lpp promoter and lac promoter/operator, resulted in the overexpression by Escherichia coli of the modified PBP3 (designated PBP3**) in the cytoplasm. About 80% of the accumulated PBP3** underwent sequestration in the form of insoluble protein granules that were isolated by cell breakage or cell lysis. After selective removal of contaminants by an EDTA-lysozyme/DNase (deoxyribonuclease)/Nonidet extraction, treatment of the granules with guanidinium chloride followed by dialysis against buffer containing 0.5 M NaCl yielded a refolded, water-soluble PBP3**, which, upon chromatography on Superose 12, exhibited the expected 60,000 molecular mass. The refolded PBP3** bound benzylpenicillin in a 1 to 1 molar ratio, was highly sensitive to aztreonam and showed the same degree of thermostability, in terms of penicillin-binding capacity, as the parent, membrane-bound PBP3, suggesting that protein refolding occurred with formation of the correct intramolecular interactions. Two to three mg of refolded PBP3** can be obtained from 1 litre of culture of the overproducing strain. [less ▲]

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See detailOvergenerality Bias and these Consequences in Borderline Personality Disorder.
Boulanger, Marie ULg; Smets, Virginie; Blairy, Sylvie ULg

Poster (2010, June)

Objective: The present study investigated the Autobiographical Memory (AM) in borderline disorder population. AM is an entity that encompasses the individuals’past personnal experiences. Previous ... [more ▼]

Objective: The present study investigated the Autobiographical Memory (AM) in borderline disorder population. AM is an entity that encompasses the individuals’past personnal experiences. Previous researches have shown disturbances in AM among several psychiatric disorders such as depression, schizophrenia and bipolar disorder. This disturbances take the overgeneral retrieving form. Thus, when patients were asked to retrieve a specific event located in time and place, they recalled an overgeneral event. This deficit is not an isolated phenomen. Indeed the researches showed that AM deficits is related to decreasing of the ability to solve interpersonnal problem (Evans et al., 1992; Goddard et al., 1996) and impairments to project onself into the specific future events (D’argembeau et al., 2008; Williams et al., 1996). Impairments to respond adequately to social problems or to concrete plans for the future create hopelessness and to contribute to suicide attempt (Arie et al., 2008). Given the high risk of suicide or suicide attempts present in the Bordeline Personnality Disorder (BPD), consideration of AM in this population is appropriate. The aim of the present study was investigate the AM, the projection into the future and the problem solving in patients suffering from BPD. Method: 21 subjects BPD and 21 healthy controls participated in this study. First, the participants were asked to complete TeMA (validated French versions of AMT by Neumann & Philippot, 2006). Participants were instructed to generate specific past and future memories in response to cues words. Secondly, they were had to complete the OTT, they were asked to yield the most solutions as possible to daily problems. Finally the depression was controlled as well as neuropsychological variables. Results: The subjects with BPD recalled less specific past events and imagined less specific future events than healthy subjects (t(40) = 2.21, p = .031; t(40) = 3.4, p = .001, respectively). In addition, the number of past and future specific events was marginally correlated (r(42) = .31, p = .051). However, no difference between two groups on OTT and no correlation between past specificity and problem solving emerged. Discussion: As other clinical populations, the subjects with a BPD encounter deficits to retrieve specific past events. Moreover, these impairments are associated with deficits to imagine specific future events. Nevertheless, the ability to generate specific events was not related to the ability to solve problem. The observation of reduced specificity in the generation of autobiographical material is particularly clinically relevant. Indeed, difficulty in imagining the future may contribute to relapse. In conclusion, more systematic measure of this ability should be taken in both research and clinical fields. [less ▲]

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See detailOvergenerality Memory Style for Past and Future Events and Emotions Related in Bipolar Disorder. What are the Links with Problem Solving and Interpersonal Relationships?
Boulanger, Marie ULg; Lejeune, Aurélie; Blairy, Sylvie ULg

in Psychiatry Research (2013), 210(3), 863-870

This study investigated patients with Bipolar Disorder’s abilities to generate specific past and future events in response to positive and negative cues words as well as emotional intensity related to ... [more ▼]

This study investigated patients with Bipolar Disorder’s abilities to generate specific past and future events in response to positive and negative cues words as well as emotional intensity related to these ones. The relationships between the number of generated specific events cognitive functioning, interpersonal problems and the ability to problem solving were investigated. Nineteen BD and nineteen healthy controls completed a French version of the AMT to evaluate the past and future events recall, in function of their valence, and emotions related. Furthermore, they completed the Optional Thinking Test, the Inventory of Interpersonal Problems and the neuropsychological measures. Compared to healthy controls, BD recollected (1) fewer specific past negative events and (2) fewer future specific positive and negative events furthermore, (3) they felt more emotional intensity related to future events. These results were explained in the light of theoretical models. Finally, specific past memories deficits in BD were linked with issues in problem solving but not with levels of distress arising from interpersonal problems. In view of AM functions in everyday life, all types of deficits should be taken into consideration, and AM remediation envisaged. [less ▲]

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See detailOverhead athletes and sports performance on the field
Forthomme, Bénédicte ULg; Crielaard, Jean-Michel ULg; Croisier, Jean-Louis ULg

in Abstract book du 11th Annual Congress of the European College of Sports Science (ECSSA) (2006)

Detailed reference viewed: 22 (7 ULg)