160 research outputs found
Grasping Points Determination Using Visual Features
This paper discusses some issues for generating point of contact using visual features. To address these issues, the paper is divided into two sections: visual features extraction and grasp planning. In order to provide a suitable description of object contour, a method for grouping visual features is proposed. A very important aspect of this method is the wa
Hypoglycemia-Sensing Neurons of the Ventromedial Hypothalamus Require AMPK-Induced Txn2 Expression but Are Dispensable for Physiological Counterregulation.
The ventromedial nucleus of the hypothalamus (VMN) is involved in the counterregulatory response to hypoglycemia. VMN neurons activated by hypoglycemia (glucose-inhibited [GI] neurons) have been assumed to play a critical although untested role in this response. Here, we show that expression of a dominant negative form of AMPK or inactivation of AMPK α1 and α2 subunit genes in Sf1 neurons of the VMN selectively suppressed GI neuron activity. We found that Txn2, encoding a mitochondrial redox enzyme, was strongly downregulated in the absence of AMPK activity and that reexpression of Txn2 in Sf1 neurons restored GI neuron activity. In cell lines, Txn2 was required to limit glucopenia-induced reactive oxygen species production. In physiological studies, absence of GI neuron activity after AMPK suppression in the VMN had no impact on the counterregulatory hormone response to hypoglycemia or on feeding. Thus, AMPK is required for GI neuron activity by controlling the expression of the antioxidant enzyme Txn2. However, the glucose-sensing capacity of VMN GI neurons is not required for the normal counterregulatory response to hypoglycemia. Instead, it may represent a fail-safe system in case of impaired hypoglycemia sensing by peripherally located glucose detection systems that are connected to the VMN
Oxytocin neurone activity and release following administration of Melanotan-II in anaesthetised rats
Oxytocin release within the brain modulates several social behaviours
in animals and humans. Moreover, low central oxytocin content has been
linked to neuropsychiatric disorders, such as anxiety and autism. The
exogenous administration of oxytocin has been proposed for therapeutic
treatment, but oxytocin does not cross the blood-brain barrier (BBB) in
physiologically significant amounts. An alternative approach to oxytocin
administration is to stimulate central oxytocin release using melanocortins.
Central administration of the naturally occurring melanocortin,
α-MSH, has been shown to trigger somatodendritic oxytocin release in vitro.
Unfortunately, endogenous melanocortins also do not penetrate the BBB in
neuroactive amounts. In this study, I investigated whether systemic
administration of synthetic melanocortin receptor 3/4 (MC3/4) agonist,
Melanotan-II (MT-II), affects oxytocin neuronal activity and secretion in
anaesthetised rats. I hypothesised that systemic administration of MT-II
directly (centrally) acts on magnocellular oxytocin neurones to trigger
somatodendritic oxytocin release from neurones of the supraoptic nucleus
(SON) of the hypothalamus in vivo.
Firstly, using double immunohistochemistry against Fos protein, a
widely used marker for neural activity, and oxytocin, I showed that
intravenous (i.v.; 1 mg/kg), but not intranasal (1 and 30 ÎŒg rat),
administration of MT-II markedly induced Fos expression in magnocellular
oxytocin neurones of the SON and paraventricular nuclei (PVN) of the
hypothalamus, and this response was prevented by prior
intracerebroventricular (i.c.v.) administration of the melanocortin antagonist,
SHU-9119 (1 ÎŒg rat). In addition, brain areas receiving peripheral inputs
which are involved in the regulation of oxytocin and vasopressin release
were also analysed, showing that i.v. MT-II significantly increased Fos
expression in the nucleus tractus solitarii (NTS), but not in circumventricular
organs of the anteroventral third ventricle (AV3V) region. MT-II-induced Fos
in the NTS was not prevented by the i.c.v. melanocortin antagonist.
Then, using in vivo electrophysiology, I investigated whether i.v.
administration of MT-II affects the electrical activity of SON neurones.
Extracellular single-unit recordings from identified magnocellular neurones
of the SON showed that MT-II significantly increased the firing rate in
oxytocin neurones, however, no significant changes in firing rate were
detected in vasopressin neurones.
Finally, in vivo oxytocin release experiments showed that i.v.
administration of MT-II did not trigger somatodendritic oxytocin release
within the SON as measured by microdialysis and subsequent
radioimmunoassay. Interestingly, the i.c.v. administration of MT-II (1 ÎŒg rat)
also failed to trigger oxytocin release within the SON. The analysis of
oxytocin content in plasma revealed that the change in oxytocin
concentration was significantly greater in i.v. MT-II injected rats compared to
vehicle-injected rats.
Taken together, these results show that after i.v., but not intranasal,
administration of MT-II, the activity of magnocellular neurones of the SON is
increased. As previous studies showed that SON oxytocin neurones are
inhibited in response to direct application of melanocortin agonists, the
actions of i.v. MT-II are likely to be mediated, at least in part, indirectly by
activation of inputs from the caudal brainstem
Mapping and signaling of neural pathways involved in the regulation of hydromineral homeostasis
Regulation of hepatic lipid metabolism by AMPK : implications in the development and the treatment of fatty liver
La stĂ©atose hĂ©patique affecte 20 Ă 40% de la population et progresse de façon constante. Il sâagit dâune pathologie chronique fortement associĂ©e au syndrome mĂ©tabolique. Sa pathogenĂšse est mal comprise. Une altĂ©ration du mĂ©tabolisme des lipides dans le foie entraĂźnant une accumulation intra-hĂ©patique de lipides est probablement la cause majeure de la stĂ©atose hĂ©patique. A ce jour, il nâexiste pas de traitement spĂ©cifique de la stĂ©atose hĂ©patique. La protĂ©ine kinase activĂ©e par lâAMP (AMPK) est un rĂ©gulateur clĂ© du mĂ©tabolisme Ă©nergĂ©tique. Notamment, lâAMPK contrĂŽle le mĂ©tabolisme des lipides en inhibant la synthĂšse des acides gras et du cholestĂ©rol, et en stimulant l'oxydation des acides gras. Plusieurs Ă©tudes ont montrĂ© lâexistence dâune association entre lâaccumulation intracellulaire de lipides et une perte dâactivitĂ© de lâAMPK dans le foie. Ces observations suggĂšrent que lâAMPK pourrait ĂȘtre un facteur impliquĂ© dans la physiopathologie de la stĂ©atose hĂ©patique. Pour Ă©tudier cette hypothĂšse, nous avons gĂ©nĂ©rĂ© un nouveau modĂšle de souris knockout dĂ©pourvu des sous-unitĂ©s catalytiques α1 et α2 de lâAMPK spĂ©cifiquement dans le foie. Nous avons analysĂ© les consĂ©quences de cette dĂ©lĂ©tion sur le mĂ©tabolisme lipidique dans diffĂ©rentes situations nutritionnelles. La dĂ©lĂ©tion de lâAMPK dans le foie ne modifie pas le contenu hĂ©patique en triglycĂ©rides et en cholestĂ©rol au cours dâun jeĂ»ne ou aprĂšs une rĂ©alimentation riche en glucides. Egalement, lâexpression des gĂšnes de la lipogenĂšse nâest pas modifiĂ©e dans le foie de ces animaux. De plus, lâoxydation des acides gras nâest pas altĂ©rĂ©e mĂȘme aprĂšs un jeĂ»ne de 24h. Etonnamment, lâabsence de lâAMPK dans le foie nâamplifie pas la stĂ©atose hĂ©patique, ni lâhyperglycĂ©mie ou lâintolĂ©rance au glucose lorsque les souris sont nourries avec un rĂ©gime riche en lipides. Cependant, lâactivation de lâAMPK in vivo avec l'activateur direct, A-769662, normalise la stĂ©atose hĂ©patique chez des souris lipodystrophiques aP2-SREBP-1c et chez des souris obĂšses nourries avec un rĂ©gime riche en lipides. Cet effet est dĂ©pendant de lâAMPK car il est totalement perdu chez des souris dĂ©pourvues dâAMPK dans le foie. Dans des hĂ©patocytes de souris en culture primaire, lâactivation de l'AMPK par un activateur direct (A-769662) ou par des activateurs indirects (metformine et AICAR) rĂ©duit le flux lipogĂ©nique et augmente lâoxydation des acides gras. Ces effets sont totalement abolis dans des hĂ©patocytes AMPK KO, dĂ©montrant lâaction spĂ©cifique de l'AMPK sur le mĂ©tabolisme lipidique en rĂ©ponse Ă ces composĂ©s. Ces rĂ©sultats obtenus chez la souris sont extrapolables Ă l'homme puisque nous avons montrĂ© que l'activation de l'AMPK dans des hĂ©patocytes humains en culture primaire inhibe de maniĂšre efficace la synthĂšse des acides gras et du cholestĂ©rol. En conclusion, nos rĂ©sultats dĂ©montrent que lâinactivation de lâAMPK dans le foie nâest pas un facteur dĂ©clenchant ou aggravant dans la physiopathologie de la stĂ©atose hĂ©patique. En revanche, lâactivation pharmacologique de lâAMPK amĂ©liore efficacement la stĂ©atose hĂ©patique. Ainsi, lâAMPK est une cible potentielle pour le dĂ©veloppement d'activateurs dans le but de traiter la stĂ©atose hĂ©patique chez lâhomme.Fatty liver disease affects between 20-40% of the population. This pathology is usually associated with metabolic disease. Its pathogenesis is poorly understood. Altered lipids metabolism in the liver resulting on hepatic fat accumulation is probably due to fatty liver. There is no specific treatment for fatty liver disease. AMP-activated protein kinase (AMPK) is a key regulator of energy metabolism. In particular, AMPK regulates lipid metabolism by inhibiting fatty acids and cholesterol synthesis, and stimulating fatty acids oxidation. Several studies have shown an association between intracellular lipid accumulation and loss of AMPK activity in the liver. These observations suggest that AMPK may be a factor involved in the pathogenesis of hepatic steatosis. To investigate this hypothesis, we generated a new model of knockout mice lacking the catalytic subunits of AMPK α1 and α2 specifically in the liver. We analyzed the consequences of this deletion on lipid metabolism in different nutritional conditions. Deletion of AMPK in the liver does not affect hepatic triglyceride and cholesterol content in fasted or in refed conditions with a high carbohydrate diet. Also, lipogenic genes expression is not altered in the liver of these animals. Moreover, the oxidation of fatty acids is not impaired after 24 hour of fasting. Surprisingly, lacking AMPK specifically in the liver does not aggraving fatty liver, hyperglycemia, or impaired glucose tolerance when the mice are on high fat diet condition. However, the activation of AMPK in vivo with a direct activator, A-769662, normalizes hepatic steatosis in lipodystrophyc aP2-SREBP-1c mice and in obese mice placed on high-fat diet. This effect is AMPK dependent because it is completely abolished in mice lacking AMPK specifically in liver. In primary mice hepatocytes, AMPK activation by a direct activator (A-769662) or by indirect activators (metformin and AICAR) reduces lipogenesis rates and increases fatty acids oxidation rates. These effects were completely abolished in hepatocytes lacking AMPK, showing the specific action of AMPK on lipid metabolism in response to these compounds. These results obtained in mice can be extrapolated to humans. Indeed, we have shown that AMPK activation in primary humain hepatocytes inhibits effectively fatty acid and cholesterol synthesis rates. In conclusion, our results showed that inactivation of AMPK in the liver is not a triggering or an aggraving factor in the pathogenesis of hepatic steatosis. Nevertheless, AMPK re-activation has a therapeutic benefit for the treatment of fatty liver disease. Thus, AMPK is a potential target to treat fatty liver disease in human
The impact on trade of North African migration to Europe
Treball Final de Grau en Economia. Codi: EC1049. Curs acadĂšmic: 2021/2022In this project, we analyze the impact of the recent exodus of Africans to the European Union (EU) countries on trade flows. In concrete, we focus on North African countries and their main EU partners receiving African migrant for the period 2009-2019. The empirical method used to identify the influence of migrants from North Africa to EU on European-African bilateral trade rests on gravity econometric models. The results confirm that migration increases trade relations, specially export flows from EU to North African countries
Internuclear coupling of hypothalamic magnocellular nuclei by glutamate synaptic circuits
Glucose availability but not changes in pancreatic hormones sensitizes hepatic AMPK activity during nutritional transition in rodents
International audienceThe cellular energy sensor AMP-activated protein kinase (AMPK) is a metabolic regulator that mediates adaptation to nutritional variations in order to maintain a proper energy balance in cells. We show here that suckling-weaning and fasting-refeeding transitions in rodents are associated with changes in AMPK activation and the cellular energy state in the liver. These nutritional transitions were characterized by a metabolic switch from lipid to glucose utilization, orchestrated by modifications in glucose levels and the glucagon:insulin ratio in the bloodstream. We therefore investigated the respective roles of glucose and pancreatic hormones on AMPK activation in mouse primary hepatocytes. We found that glucose starvation transiently activates AMPK, whereas changes in glucagon and insulin levels had no impact on AMPK. Challenge of hepatocytes with metformin-induced metabolic stress strengthened both AMPK activation and cellular energy depletion limited-glucose conditions, whereas neither glucagon nor insulin altered AMPK activation. Although both insulin and glucagon induced AMPKα phosphorylation at its Ser-485/491 residue, they did not affect its activity. Finally, the decrease in cellular ATP levels in response to an energy stress was additionally exacerbated under fasting conditions and by AMPK deficiency in hepatocytes, revealing metabolic inflexibility and emphasizing the importance of AMPK for maintaining hepatic energy charge. Our results suggest that nutritional changes (i.e. glucose availability), rather than the related hormonal changes (i.e. the glucagon:insulin ratio), sensitize AMPK activation to the energetic stress induced by the dietary transition during fasting. This effect is critical for preserving the cellular energy state in the liver
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