Homocysteine metabolism pathway is involved in the control of glucose homeostasis: a cystathionine beta synthase deficiency study in mouse

Cystathionine beta synthase (CBS) catalyzes the first step of the transsulfuration pathway from homocysteine to cystathionine, and its deficiency leads to hyperhomocysteinemia (HHcy) in humans and rodents. To date, scarce information is available about the HHcy effect on insulin secretion, and the link between CBS activity and the setting of type 2 diabetes is still unknown. We aimed to decipher the consequences of an inborn defect in CBS on glucose homeostasis in mice. We used a mouse model heterozygous for CBS (CBS+/-) that presented a mild HHcy. Other groups were supplemented with methionine in drinking water to increase the mild to intermediate HHcy, and were submitted to a high-fat diet (HFD). We measured the food intake, body weight gain, body composition, glucose homeostasis, plasma homocysteine level, and CBS activity. We evidenced a defect in the stimulated insulin secretion in CBS+/- mice with mild and intermediate HHcy, while mice with intermediate HHcy under HFD presented an improvement in insulin sensitivity that compensated for the decreased insulin secretion and permitted them to maintain a glucose tolerance similar to the CBS+/+ mice. Islets isolated from CBS+/- mice maintained their ability to respond to the elevated glucose levels, and we showed that a lower parasympathetic tone could, at least in part, be responsible for the insulin secretion defect. Our results emphasize the important role of Hcy metabolic enzymes in insulin secretion and overall glucose homeostasis

Nonstrict hierarchical reinforcement learning for interactive systems and robots

Conversational systems and robots that use reinforcement learning for policy optimization in large domains often face the problem of limited scalability. This problem has been addressed either by using function approximation techniques that estimate the approximate true value function of a policy or by using a hierarchical decomposition of a learning task into subtasks. We present a novel approach for dialogue policy optimization that combines the benefits of both hierarchical control and function approximation and that allows flexible transitions between dialogue subtasks to give human users more control over the dialogue. To this end, each reinforcement learning agent in the hierarchy is extended with a subtask transition function and a dynamic state space to allow flexible switching between subdialogues. In addition, the subtask policies are represented with linear function approximation in order to generalize the decision making to situations unseen in training. Our proposed approach is evaluated in an interactive conversational robot that learns to play quiz games. Experimental results, using simulation and real users, provide evidence that our proposed approach can lead to more flexible (natural) interactions than strict hierarchical control and that it is preferred by human users

Front Behav Neurosci

Cognitive impairment in Down syndrome (DS) has been linked to increased synaptic inhibition. The underlying mechanisms remain unknown, but memory deficits are rescued in DS mouse models by drugs targeting GABA receptors. Similarly, administration of epigallocatechin gallate (EGCG)-containing extracts rescues cognitive phenotypes in Ts65Dn mice, potentially through GABA pathway. Some developmental and cognitive alterations have been traced to increased expression of the serine-threonine kinase DYRK1A on Hsa21. To better understand excitation/inhibition balance in DS, we investigated the consequences of long-term (1-month) treatment with EGCG-containing extracts in adult mBACtgDyrk1a mice that overexpress Dyrk1a. Administration of POL60 rescued components of GABAergic and glutamatergic pathways in cortex and hippocampus but not cerebellum. An intermediate dose (60 mg/kg) of decaffeinated green tea extract (MGTE) acted on components of both GABAergic and glutamatergic pathways and rescued behavioral deficits as demonstrated on the alternating paradigm, but did not rescue protein level of GABA-synthesizing GAD67. These results indicate that excessive synaptic inhibition in people with DS may be attributable, in large part, to increased DYRK1A dosage. Thus, controlling the level of active DYRK1A is a clear issue for DS therapy. This study also defines a panel of synaptic markers for further characterization of DS treatments in murine models

L’entrave de Glanon (Côte-d’Or) les Éduens et l’esclavage

Au cours de 1981, une drague travaillant sur la Saône, à hauteur de Glanon (en amont de Seurre, Côte-d’Or) a relevé de nombreux vestiges de la fin de l’Age du Fer et du début de l’Empire romain, sur une zone où les témoins du Néolithique au Mérovingien sont particulièrement denses (prospection L. Bonnamour). Parmi ceux-ci figure un objet, très oxydé au moment de sa découverte, traité et restauré par l’atelier du musée Denon (Chalon-sur-Saône) qui l’a acquis. Cet objet, que l’on peut définir c..

Caractérisation des changements environnementaux dans la basse vallée du Doubs (Neublans, Jura) durant le 1er millénaire après J.-C. Le rôle de l'Homme et de la rivière

International audienc

Basonuclin 2 has a function in the multiplication of embryonic craniofacial mesenchymal cells and is orthologous to disco proteins

Basonuclin 2 is a recently discovered zinc finger protein of unknown function. Its paralog, basonuclin 1, is associated with the ability of keratinocytes to multiply. The basonuclin zinc fingers are closely related to those of the Drosophila proteins disco and discorelated, but the relation between disco proteins and basonuclins has remained elusive because the function of the disco proteins in larval head development seems to have no relation to that of basonuclin 1 and because the amino acid sequence of disco, apart from the zinc fingers, also has no similarity to that of the basonuclins. We have generated mice lacking basonuclin 2. These mice die within 24 h of birth with a cleft palate and abnormalities of craniofacial bones and tongue. In the embryonic head, expression of the basonuclin 2 gene is restricted to mesenchymal cells in the palate, at the periphery of the tongue, and in the mesenchymal sheaths that surround the brain and the osteocartilagineous structures. In late embryos, the rate of multiplication of these mesenchymal cells is greatly diminished. Therefore, basonuclin 2 is essential for the multiplication of craniofacial mesenchymal cells during embryogenesis. Non-Drosophila insect databases available since 2008 reveal that the basonuclins and the disco proteins share much more extensive sequence and gene structure similarity than noted when only Drosophila sequences were examined. We conclude that basonuclin 2 is both structurally and functionally the vertebrate ortholog of the disco proteins. We also note the possibility that some human craniofacial abnormalities are due to a lack of basonuclin 2

Les âges du fer dans la vallée de la Saône (VIIe - Ier siècles avant notre ère)

La vallée de la Saône et ses environs se distinguent par leur richesse archéologique pour les deux Ages du fer et pour les vestiges relevant de la métallurgie ancienne. La comparaison des vestiges textiles, tombes à épées et tous les aspects de la paléométallurgie du bronze : mines, minerais, techniques de fabrication apporte des précisions sur cette période