What is the Machine Learning?

Applications of machine learning tools to problems of physical interest are often criticized for producing sensitivity at the expense of transparency. To address this concern, we explore a data planing procedure for identifying combinations of variables -- aided by physical intuition -- that can discriminate signal from background. Weights are introduced to smooth away the features in a given variable(s). New networks are then trained on this modified data. Observed decreases in sensitivity diagnose the variable's discriminating power. Planing also allows the investigation of the linear versus non-linear nature of the boundaries between signal and background. We demonstrate the efficacy of this approach using a toy example, followed by an application to an idealized heavy resonance scenario at the Large Hadron Collider. By unpacking the information being utilized by these algorithms, this method puts in context what it means for a machine to learn.Comment: 6 pages, 3 figures. Version published in PRD, discussion adde

Hypoxie hypobare et metabolisme des catecholamines cerebrales: effets d'un traitement par l'apomorphine ou par la cytidine-5'-diphosphocholine administree par voie orale

SIGLEINIST TD 19855 / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Étude fonctionnelle du récepteur alpha des œstrogènes (ERa) et mécanismes d'action dans un modèle de différenciation neuronale

L'œstradiol est une hormone stéroïde impliquée dans un grand nombre de processus physiologiques. Ses fonctions passent, pour la plupart, par l'adaptation de la transcription de gènes cibles. Ces actions génomiques sont assurées par la forme alpha du récepteur des œstrogènes (ERa). Les fonctions transcriptionnelles d'ERa s'exercent par l'intermédiaire de deux domaines de transactivation(AF-1 et AF-2) dont l'activité varie en fonction de la cellule cible. Notre étude indique l'existence d'une corrélation étroite entre la sensibilité d'une cellule aux fonctions AF-1 et AF-2 et l'état de différenciation de cette cellule. Ainsi, plus une cellule est différenciée, plus l'activité transcriptionnelle d'ERa est dépendante de la fonction AF-1. La fonction AF-1 d'ERa serait ainsi cruciale dans les effets trophiques et protecteurs des œstrogènes dans les neurones. Nos travaux basés sur l'utilisation d'un modèle cellulaire de différenciation et de mort neuronales, la lignée cellulaire PC12, corroborent cette hypothèse.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Effects of estrogens and endocrine-disrupting chemicals on cell differentiation-survival-proliferation in brain: contributions of neuronal cell lines.

International audienceEstrogens and estrogen receptors (ER) are key actors in the control of differentiation and survival and act on extrareproductive tissues such as brain. Thus, estrogens may display neuritogenic effects during development and neuroprotective effects in the pathophysiological context of brain ischemia and neurodegenerative pathologies like Alzheimer's disease or Parkinson's disease. Some of these effects require classical transcriptional "genomic" mechanisms through ER, whereas other effects appear to rely clearly on "membrane-initiated mechanisms" through cytoplasmic signal transduction pathways. Disturbances of these mechanisms by endocrine-disrupting chemicals (EDC) may exert adverse effects on brain. Some EDC may act via ER-independent mechanisms but might cross-react with endogenous estrogen. Other EDC may act through ER-dependent mechanisms and display agonistic/antagonistic estrogenic properties. Because of these potential effects of EDC, it is necessary to establish sensitive cell-based assays to determine EDC effects on brain. In the present review, some effects of estrogens and EDC are described with focus on ER-mediated effects in neuronal cells. Particular attention is given to PC12 cells, an interesting model to study the mechanisms underlying ER-mediated differentiating and neuroprotective effects of estrogens

Modulation of pituitary dopamine D1 or D2 receptors and secretion of follicle stimulating hormone and luteinizing hormone during the annual reproductive cycle of female rainbow trout

International audienceThe two gonadotrophins follicle stimulating hormone (FSH) and luteinizing hormone (LH) have distinct temporal expression and release profiles in fish, but little is known regarding their neuroendocrine control, especially for FSH. The present experiments were performed on previtellogenic, mature and preovulatory female trout. The catecholamine synthesis inhibitor, alpha -methyl-p-tyrosine, increased plasma LH and FSH concentrations of mature fish. The dopamine agonist apomorphine decreased and the dopamine antagonist domperidone increased plasma LH concentration of preovulatory fish and delayed ovulation, but did not modify plasma FSH concentration. The dopamine D-2 agonist bromocryptine inhibited LH release in cultured gonadotrophs from mature and preovulatory fish, but not from previtellogenic fish. Bromocryptine also Significantly inhibited basal and salmon gonadotrophin releasing-hormone (sGnRH)-induced FSH release from cultured gonadotrophs of mature fish, but not of preovulatory fish, and increased FSH release from gonadotrophs of previtellogenic fish. The dopamine D-1 agonist SKF 38393 had no observed effect on the release of FSH and LH, at any reproductive stage studied. The D-1 agonist SKF 38393, the D-2 agonist bromocriptine and sGnRH had no observed effects on cell contents of FSH and LH. Taken together, these data suggest that, at the level of the pituitary, dopamine inhibits LH release as vitellogenesis proceeds, via activation of dopamine D-2 receptors. We demonstrate for the first time in fish a control of FSH release (a dopamine control), especially in mature fish which have low circulating concentrations of FSH

Differential regulation of tyrosine hydroxylase and estradiol receptor expression in the rainbow trout brain.

International audienceIn numerous fish species, dopamine has been found to strongly inhibit gonadotropin release. Among the enzymes that regulate dopamine turnover, tyrosine hydroxylase (TH), the rate-limiting anabolic enzyme, could be a target for endocrine feedback regulation. Since dopamine turnover is stimulated by estradiol in rainbow trout, we have investigated the effect of estradiol on TH and estradiol receptor expression. In situ hybridization was used to quantify mRNA levels in the brain of ovariectomized female rainbow trout implanted or not with estradiol pellets. We demonstrated that preoptic TH and estradiol receptor mRNA levels are greatly decreased by gonadectomy during vitellogenesis. For TH expression, this effect was reversed in part by estradiol supplementation. We have also confirmed the existence of an inhibitory gonadal feedback on FSH secretion, mediated by estradiol. The stimulating effect of estradiol on TH expression found in this study could be a pathway involved in gonadal feedback on gonadotropin release

Unliganded Estrogen Receptor Alpha Promotes PC12 Survival during Serum Starvation

Many studies have reported proliferative, differentiating or protective effects of estradiol, notably through estrogen receptor alpha (ERα). On the contrary, the ligand-independent action of ERα is currently poorly documented notably in cell protection. The stable transfection of wild type, substituted or truncated form of ERα in PC12 cells (ERα negative cell line) lead the specific study of its ligand-independent action. Hence, we demonstrate here that, in the absence of E 2, the expression of ERα prevents cells from apoptosis induced by serum deprivation. This protection is not due to an ERE-mediated transcription and does not require either AF-1 or AF-2 transactivation functions. It is afforded to the Y537 residue of ERα and activation of c-Src/Stat3 signaling pathway

Dynamic characteristics of serotonin and dopamine metabolism in the rainbow trout brain : a regional study using liquid chromatography with electrochemical detection

International audienceAminergic metabolism was studied in discrete brain regions of the postovulated female rainbow trout using a liquid chromatography electrochemical detection method. 3 Methoxytyramine (3MT) was the major dopaminergic catabolite, suggesting that catechol-o-methyl transferase is the main dopamine (DA) catabolic enzyme. Two populations of brain regions were found: one with a high DA content and low 3MT/DA ratio (hypothalamus and telencephalon), suggesting that these regions could present a high density of DA perikarya; the other with a high 3MT/DA ratio (pituitary, preoptic area, myelencephalon and optic tectum) suggesting that these regions could present a high density of DA axonal endings. 5 Hydroxytryptamine (5HT) content differed, but an homogeneous distribution of monoamine oxidase was found in different brain regions. High 5HT content was found in the hypothalamus and telencephalon; 5HT was however not detectable in the pituitary

Estrogen receptor alpha mediates neuronal differentiation and neuroprotection in PC12 cells: critical role of the A/B domain of the receptor.

International audienceNumerous studies, both in vivo and in vitro, have reported neuronal differentiating and neuroprotective actions of estrogens. Most of these estrogenic effects are mediated through specific receptors termed estrogen receptors. The aim of this study was to assess the importance of the N-terminal A/B domain of the estrogen receptor-alpha (ER alpha) in its neuronal aspects. Consequently, estrogen effects on (i) the transcriptional activity of target genes, (ii) neuronal differentiation and (iii) neuroprotection in PC12 cells transfected with either a full length form of ER alpha or an A/B domain truncated form (ER alphaCF), have been studied. We demonstrate that the maximal estrogen-induced transcriptional activity of reporter genes requires a full length ER alpha, especially when cells are differentiated. Precisely, the transcriptional activity of ER alpha in differentiated cells relies, predominantly, on the activation function AF-1, located in the A/B domain. Furthermore, in PC12 cells stably expressing ER alpha, 17beta-estradiol markedly enhances the neurite outgrowth triggered by treatment with nerve growth factor and protects cells from oxidative shocks induced by depletion of glutathione. These estrogenic effects are not observed in non-transfected cells and in cells transfected with the truncated ER, devoid of the A/B domain. Altogether, these results underline the importance of the A/B domain of ER alpha in both the differentiating and the neuroprotective effects of estrogens

Distribution of dopamine D2 receptor mRNAs in the brain and the pituitary of female rainbow trout: an in situ hybridization study.

International audienceThe distribution of D(2)R (dopamine D(2) receptor) mRNAs was studied in the forebrain of maturing female rainbow trout by means of in situ hybridization using a (35)S-labeled riboprobe (810 bp) spanning the third intracytoplasmic loop. A hybridization signal was consistently obtained in the olfactory epithelium, the internal cell layer of the olfactory bulbs, the ventral and dorsal subdivisions of the ventral telencephalon, and most preoptic subdivisions, with the notable exception of the magnocellular preoptic nucleus, and the periventricular regions of the mediobasal hypothalamus, including the posterior tuberculum. In the pituitary, the signal was higher in the pars intermedia than in the proximal and the rostral pars distalis, but no obvious correspondence with a given cell type could be assigned. Labeled cells were also located in the thalamic region, some pretectal nuclei, the optic tectum, and the torus semicircularis. These results provide a morphologic basis for a better understanding on the functions and evolution of the dopaminergic systems in lower vertebrates