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See detailModulation of medial prefrontal and inferior parietal cortices when thinking about past, present, and future selves.
D'Argembeau, Arnaud ULg; Stawarczyk, David ULg; Majerus, Steve ULg et al

in Social Neuroscience (2010), 5

Recent functional neuroimaging studies have shown that reflecting on representations of the present self versus temporally distant selves is associated with higher activity in the medial prefrontal cortex ... [more ▼]

Recent functional neuroimaging studies have shown that reflecting on representations of the present self versus temporally distant selves is associated with higher activity in the medial prefrontal cortex (MPFC). In the current fMRI study, we investigated whether this effect of temporal perspective is symmetrical between the past and future. The main results revealed that the MPFC showed higher activity when reflecting on the present self than when reflecting on past and future selves, with no difference between past and future selves. Temporal perspective also modulated activity in the right inferior parietal cortex but in the opposite direction, activity in this brain region being higher when reflecting on past and future selves relative to the present self (with again no difference between past and future selves). These findings show that differences in brain activity when thinking about current versus temporally distant selves are symmetrical between the past and the future. It is suggested that by processing degrees of self-relatedness, the MPFC might sustain the process of identifying oneself with current representations of the self, whereas the right inferior parietal cortex might be involved in distinguishing the present self from temporally distant selves. [less ▲]

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See detailModulation of melanogenesis of B16 melanoma cells in culture
Gillet, Marie-Claire ULg; Bassleer, R.

Conference (1981, May)

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See detailModulation of Nod2-dependent NF-kappa B signaling by the actin cytoskeleton
Legrand, Sylvie ULg; Kustermans, Gaëlle ULg; Bex, Françoise et al

in Journal of Cell Science (2007), 120(7), 1299-1310

Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF-kappa B activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin ... [more ▼]

Actin disruption by CytochalasinD (CytD) and LatrunculinB (LatB) induced NF-kappa B activation in myelomonocytic and intestinal epithelial cells. In an attempt to elucidate the mechanism by which actin disruption induced IKK activation, we studied the human Nod2 protein, which was able to induce NF-kappa B activation and whose expression was restricted to myelomonocytic and intestinal epithelial cells. Nod2 is thought to play key roles in pathogen defence through sensing bacteria and generating an inflammatory immune response. We showed that actin disruption by CytD significantly and specifically increased Nod2-mediated NF-kappa B signaling. Nod2 was fully partitioned in the Triton-X-100-insoluble fraction but translocated into the soluble fraction after CytD treatment, demonstrating that the presence of Nod2 in the detergent-insoluble pellet was specific to actin cytoskeleton. Confocal analysis also revealed a Nod2 colocalization with membrane-associated F-actin. Colocalization and co-immunoprecipitation assays with endogenous Rac1 have shown that Nod2 associated with activated Rac1 in membrane ruffles through both its N-terminal caspase recruitment domains (CARD) and C-terminal leucine-rich repeats (LRRs). Membrane ruffle disruption by a Rac1 dominant negative form primed Nod2-dependent NF-kappa B signaling. The recruitment of Nod2 in Rac-induced dynamic cytoskeletal structures could be a strategy to both repress the Nod2-dependent NF-kappa B signaling in unstimulated cells and rapidly mobilize Nod2 during bacterial infection. [less ▲]

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See detailModulation of Proteolytic Activity During Neuritogenesis in the Pc12 Nerve Cell: Differential Control of Plasminogen Activator and Plasminogen Activator Inhibitor Activities by Nerve Growth Factor and Dibutyryl-Cyclic Amp
Leprince, Pierre ULg; Rogister, Bernard ULg; Delree, P. et al

in Journal of Neurochemistry (1991), 57(2), 665-74

Extracellular proteolysis is considered to be required during neuritic outgrowth to control the adhesiveness between the growing neurite membrane and extracellular matrix proteins. In this work, PC12 ... [more ▼]

Extracellular proteolysis is considered to be required during neuritic outgrowth to control the adhesiveness between the growing neurite membrane and extracellular matrix proteins. In this work, PC12 nerve cells were used to study the modulation of proteolytic activity during neuronal differentiation. PC12 cells were found to contain and release a 70-75-kDa tissue-type plasminogen activator (tPA) and a much less abundant 48-kDa urokinase-type plasminogen activator. A plasminogen activator inhibitor (PAI) activity with molecular sizes of 54 and 58 kDa was also detected in PC12 cell conditioned medium and formed high-molecular-mass complexes with released tPA. Release of PAI activity was dependent on treatment with nerve growth factor (NGF), whereas tPA synthesis and release were under control of a cyclic AMP-dependent mechanism and increased on treatment with dibutyryl-cyclic AMP [(But)2cAMP] or cholera toxin. Simultaneous treatment with NGF and (But)2cAMP resulted in increases of both tPA and PAI release and enhancement of tPA-PAI complex formation. The resulting plasminogen activator activity in conditioned medium was high in (But)2cAMP-treated cultures with short neuritic outgrowth but remained low in NGF- or NGF plus (But)2cAMP-treated cultures, where neurite extension was, respectively, large and very large. These results suggest that excess proteolytic activity may be detrimental to neuritic outgrowth and that not only PAI release but also tPA-PAI complex formation is associated with production of large and stable neuritic outgrowth. This can be understood as an involvement of PAI in the protection against neurite-destabilizing proteolytic activity. [less ▲]

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See detailModulation of small conductance calcium-activated potassium (SK) channels: a new challenge in medicinal chemistry.
Liégeois, Jean-François ULg; Mercier, Frédéric ULg; Graulich, Amaury et al

in Current Medicinal Chemistry (2003), 10(8), 625-47

Small conductance calcium-activated potassium (SK) channels are found in many types of neurons as well as in some other cell types. These channels are selective for K(+) and open when intracellular Ca(2 ... [more ▼]

Small conductance calcium-activated potassium (SK) channels are found in many types of neurons as well as in some other cell types. These channels are selective for K(+) and open when intracellular Ca(2+) rises to omega 500 nM. In neurons, this occurs during and after an action potential. Activation of SK channels hyperpolarizes the membrane, thus reducing cell excitability for several tens or hundreds of milliseconds. This phenomenon is called a afterhyperpolarization (AHP). Three subtypes of SK channels (SK1, SK2, SK3) have been cloned and exhibit a differential localization in the brain. SK channels may play a role in physiological and pathological conditions. They may be involved in the control of memory and cognition. Moreover, they are heavily expressed in the basal ganglia (in particular in the substantia nigra, pars compacta) and in the limbic system, suggesting that they may modulate motricity and emotional behaviour. Based on these facts, SK channel subtypes may be a suitable target for developing novel therapeutic agents, but more work is needed to validate these targets. Hence, there is a great need for selective ligands. Moreover, although the risk of peripheral side-effects for SK channel modulators appears to be low, some questions remain to be investigated. Currently, different molecules are known as SK channel modulators. Apamin is a very potent peptidic agent; it produces a strong blockade of these targets which is only very slowly reversible and it has limited selectivity. Dequalinium was found to be an effective blocker. Different chemical modulations on the dequalinium structure led to the discovery of highly potent bis-quinolinium derivatives such as UCL 1684. Other bis-(2-amino-benzimidazole) derivatives are in development. On the other hand, quaternary salts of bicuculline were reported to be effective in inhibiting AHPs. More recent developments on structurally-related molecules revealed that methyl-laudanosine is a new interesting tool for exploring SK channel pharmacology. Finally, a family of compounds has been shown to facilitate SK channel opening. Such compounds may be useful in treating disorders involving neuronal hyperexcitability. [less ▲]

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See detailModulation of steroid action: Importance of coactivators
Charlier, Thierry ULg

Scientific conference (2012)

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See detailModulation of steroid action: Importance of steroid binding globulins
Charlier, Thierry ULg

Scientific conference (2008)

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See detailModulation of steroid activity by transcription coactivators in songbirds
Charlier, Thierry ULg; Auger, Catherine J; Balthazart, Jacques ULg et al

in Hormones & Behavior (2003), 44

Songbirds have developed a specialized, steroid-dependent telencephalic vocal control system for the production of learned vocalization. Recent progress in the study of the mechanisms by which steroid ... [more ▼]

Songbirds have developed a specialized, steroid-dependent telencephalic vocal control system for the production of learned vocalization. Recent progress in the study of the mechanisms by which steroid receptors act on the eukaryotic genome has highlighted the role of a newly discovered protein family, the Nuclear Receptor Coactivators. More specifically, the CREB-binding protein (CBP) and the Steroid Receptor Coactivator-1 (SRC-1) have been shown to be actively involved in mediating steroid hormone action in the developing rat brain. The distribution of the coactivator SRC-1 was analyzed in canaries by in situ hybridization. A very broad but heterogeneous distribution of the transcript was observed, mainly in steroid-sensitive areas of the hypothalamus, the song control system and several catecholaminergic areas. The presence of SRC-1 in these regions was also confirmed by immunocytochemistry. A similar very high concentration of the coactivator CBP protein was also found in steroid-sensitive areas of the hypothalamus and in the song system. Sex differences in SRC-1 mRNA concentration were detected in HVC and in area X. Moreover, preliminary data obtained independently in starlings (CBP) and in quail (SRC-1) suggest that the expression of coactivators is regulated by steroids as well as by photoperiod. The presence of these steroid receptor coactivators in the telencephalic song control nuclei and in catecholaminergic cell groups that innervate the song system and their possible regulation by photoperiod and/or steroids support the idea that SRC-1 and CBP could play an important role in the control of singing behavior by modulating estrogen and androgen receptor action. [less ▲]

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See detailModulation of steroid-dependent male sexual behavior and neural gene expression: A role for steroid receptor co-activators
Charlier, Thierry ULg; Ball, Gregory F; Balthazart, Jacques ULg

in Trabajos del Instituto Cajal (2005), 80

One of the best-characterized actions of steroids is the regulation of brain areas involved in endocrine function and in the activation of reproductive behaviors in male and female vertebrates. Progress ... [more ▼]

One of the best-characterized actions of steroids is the regulation of brain areas involved in endocrine function and in the activation of reproductive behaviors in male and female vertebrates. Progress in the understanding of the mechanisms that control the expression of the eukaryotic genome by nuclear receptors has brought forward the importance of steroid receptor coactivators in mediating efficient gene transcription. However, little is know about the specific physiological requirements of these coactivators in vivo. In Japanese quail, testosterone treatment of castrated males restores the full copulatory behavior and increases the volume of the sexually dimorphic medial preoptic nucleus (POM) to the level observed in intact males [1]. Testosterone also affects a number of sexually dimorphic neurochemical characteristics such as the vasotocineric innervation of the septum and meadial preoptic nucleus [2]. The quail therefore provides an excellent model to study steroid-dependent sexual behavior and the associated neuroplasticity and should provide insights into the modulation of steroid action by steroid receptor coactivators. The present studies were focused on the steroid receptor co-activator-1 (SRC-1), which was already shown to be involved in the process of sexual differentiation of brain and behavior in rats [3]. We first amplified by RT-PCR from quail brains a 3,411bp fragment highly homologous with the chicken (94.5%) and mammalian (70%) SRC-1 and designed digoxigenin-labeled oligonucleotides for in situ hybridization. A broad distribution of SRC-1 transcripts was observed throughout the male quail brain. A particularly dense coactivator expression was observed in limbic (e.g. POM, nucleus striae terminalis) and mesencephalic (e.g. substantia grisea centralis) nuclei associated with the control of male sexual behavior [4]. Because male and female quail exhibit a very pronounced sexual dimorphism in the steroid-dependent mechanisms that activate male-typical copulatory behavior, we investigated the potential role of SRC-1 in the sexually differentiated responses to steroids by quantifiying the SRC-1 mRNA by real time quantitative polymerase chain reaction (qPCR) and the corresponding protein by western blot (WB). Contrary to previous results, which had identified a higher SRC-1 mRNA expression in the POM of males compared to females [4], we found in two separate experiments that sexually mature females had higher concentrations of SRC-1 in the preoptic area-hypothalamus (HPOA) compared to males. Additional studies should be carried out to identify the origins of this discrepancy but seasonality and time of the day when brains were collected are potentially involved. We also quantified the SRC-1 mRNA and protein in the preoptic area-hypothalamus (HPOA) of castrated males treated or not with testosterone. SRC-1 mRNA was increased by testosterone in two independent experiments but not in a third one. This difference is likely due to the differential manipulations of the birds during these experiments. Birds had been repeatedly handled to test their sexual behavior in the first experiment and we showed that stress tends to decrease the coactivator expression in the male HPOA. This interpretation is strengthened by recent work in rats indicating that stress regulates SRC-1 expression in hypothalamus and hippocampus [5]. More surprisingly, we found a significant correlation between the expression of SRC-1 and the time of the day when birds were killed in the optic lobes, hippocampus and hindbrain. The expression of SRC-1 in the optic lobes increased throughout the day, independently of sex, testosterone treatment or stress. In the hippocampus and hindbrain, the coactivator concentration varied in opposite directions during the morning and afternoon and reached respectively its lowest or highest concentration around the middle of the day, here again independently of sex, stress and hormonal treatment. Together, these data support the idea that SRC-1 is not constitutively expressed but regulated by steroids, stress and possibly other unidentified factors. Differential controls also appear to take place in specific brain nuclei and these differential controls should be further analyzed by immunohistochemistry and in situ hybridization. A second part of our work was dedicated to the study of the physiological significance of SRC-1 whith the use of daily intra-cerebroventricular injections of modified antisense (AS) oligonucleotides (Locked nucleic acid LNA) to disrupt SRC-1 expression in the POM. AS injections significantly reduced the expression of male copulatory behavior in response to exogenous testosterone compared to control animals (Ctrl group) that received the vehicle alone or scrambled (SC) oligonucleotides. Moreover, sexual behavior was restored and even enhanced within 48 hours after interruption of AS injection (ASSC group). Western blot analysis confirmed the decrease of SRC-1 expression in AS animals and demonstrated an over-expression of the coactivator in ASSC animals. The effects of SRC-1 knock down on behavior was related to a reduced POM volume defined by Nissl-staining and aromatase immunohistochemistry. The aromatase index, indicative of the relative amount of aromatase in the POM as well as the vasotocinergic innervation of this nucleus were higher in the Ctrl group. Taken together, these findings indicate that SRC-1 functions as a critical regulatory molecule in the brain to modulate steroid-dependent gene transcription and behavior. The study of the modulation of nuclear receptors activity by different co-regulatory proteins is still in its infancy. Abnormal co-activator expression or function is currently being linked to some endocrine/neurological disorders in humans and it is thus critical to understand how co-activator expression and function are controlled in the developing as well as in the adult brain. [less ▲]

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See detailModulation of steroid-dependent male sexual behavior and neural gene expression: a role for steroid receptor co-activators
Charlier, Thierry ULg; Ball, Gregory F.; Balthazart, Jacques ULg

in Dawson, Alister; Sharp, Peter J. (Eds.) Functional anvian endocrinology (2005)

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See detailModulation of Temporalis Muscle Exteroceptive Suppression by Limb Stimuli in Normal Man
Schoenen, Jean ULg; Wang, W.; Gérard, P.

in Brain Research (1994), 657(1-2), 214-20

The effects of noxious and non-noxious limb stimulations on the second exteroceptive suppression of voluntary temporalis muscle activity (ES2) were studied in healthy human volunteers. Duration of ... [more ▼]

The effects of noxious and non-noxious limb stimulations on the second exteroceptive suppression of voluntary temporalis muscle activity (ES2) were studied in healthy human volunteers. Duration of temporalis ES2 was measured on averaged rectified responses obtained after stimulating the labial commissure at an intensity of 25 mA. Single peripheral electrical stimuli applied over nerve trunks or over the skin before the labial stimulus decreased ES2 duration. This effect was most pronounced after cutaneous stimuli, especially of the index finger, and it was not observed when the conditioning stimulus was a 10 second, high frequency train. For stimulation at the index finger, temporalis ES2 inhibition progressively increased with intensity from 10 mA to 40 mA; it was maximal for an interstimulus interval between 50 and 140 ms. After naloxone (0.4 mg or 4 mg, i.v.) there was a partial reversal of the index-induced ES2 depression, but this effect was not significant. Immersion of one hand in water heated at 47 degrees C produced a short-lasting ES2 reduction. These results are comparable, though not similar, to the inhibition of the digastric reflex (or jaw opening reflex) observed in animals after limb stimuli and to the depression of the spinal flexion reflex reported in man after heterotopic peripheral stimuli. Although peripheral stimuli were able by themselves to suppress temporalis EMG activity in some subjects, it is likely that they reduce labial-induced ES2 via activation of brainstem structures, such as periaqueductal gray matter or raphe magnus nucleus, which are thought to inhibit the medullary inhibitory interneurons mediating ES2. [less ▲]

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See detailModulation of testosterone-dependent male sexual behavior and the associated neuroplasticity.
Charlier, Thierry; Seredynski, Aurore ULg; Niessen, Neville-Andrew ULg et al

in General and Comparative Endocrinology (2013)

Steroids modulate the transcription of a multitude of genes and ultimately influence numerous aspects of reproductive behaviors. Our research investigates how one single steroid, testosterone, is able to ... [more ▼]

Steroids modulate the transcription of a multitude of genes and ultimately influence numerous aspects of reproductive behaviors. Our research investigates how one single steroid, testosterone, is able to trigger this vast number of physiological and behavioral responses. Testosterone potency can be changed locally via aromatization into 17b-estradiol which then activates estrogen receptors of the alpha and beta subtypes. We demonstrated that the independent activation of either receptor activates different aspects of male sexual behavior in Japanese quail. In addition, several studies suggest that the specificity of testosterone action on target genes transcription is related to the recruitment of specific steroid receptor coactivators. We demonstrated that the specific down-regulation of the coactivators SRC-1 or SRC-2 in the medial preoptic nucleus by antisense techniques significantly inhibits steroid-dependent male-typical copulatory behavior and the underlying neuroplasticity. In conclusion, our results demonstrate that the interaction between several steroid metabolizing enzymes, steroid receptors and their coactivators plays a key role in the control of steroid-dependent male sexual behavior and the associated neuroplasticity in quail. [less ▲]

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See detailModulation of the 6-position of benzopyran derivatives and inhibitory effects on the insulin releasing process
Florence, Xavier; Dilly, Sébastien ULg; De Tullio, Pascal ULg et al

in Bioorganic & Medicinal Chemistry (2011)

The synthesis of different series of 4- and 6-substituted R/S-3,4-dihydro-2,2-dimethyl-2H-1- benzopyrans is described. All of these new benzopyran derivatives were bearing, at the 4- position, a ... [more ▼]

The synthesis of different series of 4- and 6-substituted R/S-3,4-dihydro-2,2-dimethyl-2H-1- benzopyrans is described. All of these new benzopyran derivatives were bearing, at the 4- position, a phenylthiourea moiety substituted on the phenyl ring by a meta or a para-electronwithdrawing group such as Cl or CN. The study aimed at exploring the influence of the nature of the substituent at the 6-position in order to develop new benzopyran-type KATP channel activators exhibiting an improved selectivity towards the insulin secreting cells. The original compounds were examined in vitro on rat pancreatic islets (inhibition of insulin release) as well as on rat aorta rings (vasorelaxant effect) and their activity was compared to that of the reference KATP channel activators (±)-cromakalim, (±)-pinacidil, diazoxide and to previously synthesized cromakalim analogues. Structure–activity relationships indicated that the inhibitory effect on the insulin secreting cells was related to the lipophilicity of the molecules and to the size of the substituent located at the 6-position. A marked inhibitory activity on the insulin secretory process was obtained with molecules bearing a bulky tertbutyloxycarbonylamino group at the 6-position (20-23). The latter compounds were found to have the same efficacy on the pancreatic endocrine tissue than some previously described molecules. Lastly, radioisotopic experiments further identified R/S-N-4-chlorophenyl-N’-(6- tert-butyloxycarbonylamino-3,4-dihydro-2,2-dimethyl-2H-1-benzopyran-4-yl)thiourea (23) as a KATP channel opener. [less ▲]

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See detailModulation of the acetylcholine- and substance P-induced pulmonary edema by calcitonin gene-related peptide in the rabbit.
Delaunois, Annie ULg; Gustin, Pascal ULg; Ansay, Michel ULg

in Journal of Pharmacology and Experimental Therapeutics (The) (1994), 270(1), 30-6

The effects of calcitonin gene-related peptide (CGRP) (6 x 10(-8) M) on hemodynamics and on pulmonary microvascular permeability were investigated in isolated, perfused rabbit lungs by measuring the ... [more ▼]

The effects of calcitonin gene-related peptide (CGRP) (6 x 10(-8) M) on hemodynamics and on pulmonary microvascular permeability were investigated in isolated, perfused rabbit lungs by measuring the arterial, capillary and venous pressures and the capillary filtration coefficient (Kf,c). CGRP was administered alone or in combination with capsaicin (10(-4) M), acetylcholine (ACh) (10(-11) M to 10(-7) M), substance P (SP) (10(-10) M to 10(-6) M) and serotonin (10(-4) M). The influence of a specific antagonist of CGRP receptors, CGRP8-37 (10(-8) M), on the pulmonary edema induced by these mediators was also considered. CGRP had no direct effect on the vascular pressures or on Kf,c. Capsaicin and serotonin induced an increase in Kf,c of 271 +/- 49% and 676 +/- 147% of base line, respectively. ACh and SP also increased the microvascular permeability, in proportion to the concentration. The effects of capsaicin, ACh and SP have been related to the activation of neurokinin NK1 receptors. Co-administration of CGRP with capsaicin and ACh enhanced the increase in Kf,c induced by these two drugs. By contrast, when co-injected with SP, CGRP inhibited the Kf,c increase induced by 10(-8) M and 10(-7) M of SP (P < .05) and significantly decreased the arterial and capillary pressures. CGRP also partly prevented the pulmonary edema induced by serotonin (P < .05). Pretreatment with CGRP8-37 partly prevented the effects of capsaicin and ACh on Kf,c but bestowed no protection against SP-induced pulmonary edema. These data suggest that CGRP is co-released with SP from the C-fibers upon the action of capsaicin and ACh in the rabbit lung. Because CGRP potentiated the pulmonary edema induced in capsaicin and ACh, but decreased the effects of SP, we hypothesize that CGRP exerts a positive retro-control on the release of neuropeptides by these fibers but can attenuate their effects on the target cells. [less ▲]

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See detailModulation of the arachidonic cascade with omega 3 fatty acids or analogues: Potential therapeutic benefits
Roland, Isabelle ULg; de Leval, X.; Evrard, Brigitte ULg et al

in Mini-Reviews in Medicinal Chemistry (2004), 4(6), 659-668

Increasing interest in the role of omega 3 fatty acids has arisen in these latest years since evidence of their implication in the cardioprotective fish based diet of the Inuit has been demonstrated ... [more ▼]

Increasing interest in the role of omega 3 fatty acids has arisen in these latest years since evidence of their implication in the cardioprotective fish based diet of the Inuit has been demonstrated. Furthermore, several in vitro, in vivo and epidemiological studies support the benefit of this fatty acids intake in various pathological states such as in the cardiovascular, cancer, inflammation, psychiatric, paediatric, pulmonary, dermatological and ophthalmologic fields. This review will focus on metabolism and pharmacological implication of w3 fatty acids intake as well as its interest in the prevention or treatment of the above-mentioned pathologies. [less ▲]

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See detail. Modulation of the biological action of bovine growth hormone by passive immunization in hypophysectomised rat
Jacqmin, Sandrine; Vleurick, Lieve; Renaville, Robert ULg et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2000), 3

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See detailModulation of the biological action of bovine growth hormone by passive immunization in hypophysectomized rat.
Jacqmin, S.; Vleurick, L.; Renaville, Robert ULg et al

in Biotechnologie, Agronomie, Société et Environnement = Biotechnology, Agronomy, Society and Environment [=BASE] (2000), 4(1),

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