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1.
Neuropsychopharmacology ; 46(3): 579-602, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-32781459

RESUMEN

Maternal immune activation (MIA) and poor maternal nutritional habits are risk factors for the occurrence of neurodevelopmental disorders (NDD). Human studies show the deleterious impact of prenatal inflammation and low n-3 polyunsaturated fatty acid (PUFA) intake on neurodevelopment with long-lasting consequences on behavior. However, the mechanisms linking maternal nutritional status to MIA are still unclear, despite their relevance to the etiology of NDD. We demonstrate here that low maternal n-3 PUFA intake worsens MIA-induced early gut dysfunction, including modification of gut microbiota composition and higher local inflammatory reactivity. These deficits correlate with alterations of microglia-neuron crosstalk pathways and have long-lasting effects, both at transcriptional and behavioral levels. This work highlights the perinatal period as a critical time window, especially regarding the role of the gut-brain axis in neurodevelopment, elucidating the link between MIA, poor nutritional habits, and NDD.


Asunto(s)
Ácidos Grasos Omega-3 , Efectos Tardíos de la Exposición Prenatal , Animales , Conducta Animal , Encéfalo , Femenino , Humanos , Inflamación , Microglía , Embarazo
2.
Brain Behav Immun ; 85: 162-169, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31100369

RESUMEN

Essential polyunsaturated fatty acids (PUFA) from the n-3 and n-6 series constitute the building blocks of brain cell membranes where they regulate most aspects of cell physiology. They are either biosynthesized from their dietary precursors or can be directly sourced from the diet. An overall increase in the dietary n-6/n-3 PUFA ratio, as observed in the Western diet, leads to reduced n-3 PUFAs in tissues that include the brain. Some clinical studies have shown a positive correlation between dietary n-3 PUFA intake and sleep quantity, yet evidence is still sparse. We here used a preclinical model of dietary n-3 PUFA deficiency to assess the precise relationship between dietary PUFA intake and sleep/wake activity. Using electroencephalography (EEG)/electromyography (EMG) recordings on n-3 PUFA deficient or sufficient mice, we showed that dietary PUFA deficiency affects the architecture of sleep-wake activity and the oscillatory activity of cortical neurons during sleep. In a second part of the study, and since PUFAs are a potent modulator of inflammation, we assessed the effect of dietary n-3 PUFA deficiency on the sleep response to an inflammatory stimulus known to modulate sleep/wake activity. We injected mice with the endotoxin lipopolysaccharide (LPS) and quantified the sleep response across the following 12 h. Our results revealed that n-3 PUFA deficiency affects the sleep response in basal condition and after a peripheral immune challenge. More studies are now required aimed at deciphering the molecular mechanisms underlying the intimate relationship between n-3 PUFAs and sleep/wake activity.


Asunto(s)
Ácidos Grasos Omega-3 , Ácidos Grasos Omega-6 , Animales , Ácidos Grasos , Ácidos Grasos Insaturados , Ratones , Sueño
3.
Transl Psychiatry ; 7(6): e1154, 2017 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-28632203

RESUMEN

Early identification of Alzheimer's disease (AD) risk factors would aid development of interventions to delay the onset of dementia, but current biomarkers are invasive and/or costly to assess. Validated plasma biomarkers would circumvent these challenges. We previously identified the kinase DYRK1A in plasma. To validate DYRK1A as a biomarker for AD diagnosis, we assessed the levels of DYRK1A and the related markers brain-derived neurotrophic factor (BDNF) and homocysteine in two unrelated AD patient cohorts with age-matched controls. Receiver-operating characteristic curves and logistic regression analyses showed that combined assessment of DYRK1A, BDNF and homocysteine has a sensitivity of 0.952, a specificity of 0.889 and an accuracy of 0.933 in testing for AD. The blood levels of these markers provide a diagnosis assessment profile. Combined assessment of these three markers outperforms most of the previous markers and could become a useful substitute to the current panel of AD biomarkers. These results associate a decreased level of DYRK1A with AD and challenge the use of DYRK1A inhibitors in peripheral tissues as treatment. These measures will be useful for diagnosis purposes.


Asunto(s)
Enfermedad de Alzheimer/sangre , Factor Neurotrófico Derivado del Encéfalo/sangre , Homocisteína/sangre , Proteínas Serina-Treonina Quinasas/sangre , Proteínas Tirosina Quinasas/sangre , Anciano , Enfermedad de Alzheimer/diagnóstico , Enfermedad de Alzheimer/inmunología , Animales , Anticuerpos Monoclonales/metabolismo , Anticuerpos Monoclonales/farmacología , Biomarcadores/sangre , Femenino , Humanos , Masculino , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Proteínas Serina-Treonina Quinasas/inmunología , Proteínas Tirosina Quinasas/inmunología , Curva ROC , Quinasas DyrK
4.
Artículo en Inglés | MEDLINE | ID: mdl-18519217

RESUMEN

Piezoelectric actuators (PEAs) are commonly used as micropositioning devices due to their high resolution, high stiffness, and fast frequency response. Because piezoceramic materials are ferroelectric, they fundamentally exhibit hysteresis behavior in their response to an applied electric field. The positioning precision can be significantly reduced due to nonlinear hysteresis effects when PEAs are used in relatively long range applications. This paper describes a new, precise, and simple asymmetric hysteresis operator dedicated to PEAs. The complex hysteretic transfer characteristic has been considered in a purely phenomenological way, without taking into account the underlying physics. This operator is based on two curves. The first curve corresponds to the main ascending branch and is modeled by the function f1. The second curve corresponds to the main reversal branch and is modeled by the function g2. The functions f(1) and g(2) are two very simple hyperbola functions with only three parameters. Particular ascending and reversal branches are deduced from appropriate translations of f(1) and g(2). The efficiency and precision of the proposed approach is demonstrated, in practice, by a real-time inverse feed-forward controller for piezoelectric actuators. Advantages and drawbacks of the proposed approach compared with classical hysteresis operators are discussed.


Asunto(s)
Algoritmos , Fenómenos Electromagnéticos/instrumentación , Modelos Teóricos , Transductores , Simulación por Computador , Fenómenos Electromagnéticos/métodos , Retroalimentación , Dinámicas no Lineales
5.
J Mol Graph ; 10(4): 205-11, 1992 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-1476992

RESUMEN

The study presented herein is a bidimensional approach to the complementarity of two molecular surfaces. From two chosen sections we have established a methodology of generating the optimal matching of two shapes. Our approach consists in describing two molecular surface sections by a shape vector (the angular profile), in finding their matching patterns by comparison of the two profiles, and in optimizing the relative locations of the two sections in two-dimensional space, using rotations and translations defined by geometric characteristics. The set of optimal configurations are successively displayed on a screen. Satisfying results have been obtained for the matching of the complex kallikreine A-trypsin pancreatic bovin 2. This efficient method could be used as a preprocessing for a tridimensional shape complementarity approach between two molecular surfaces.


Asunto(s)
Conformación Molecular , Animales , Gráficos por Computador , Modelos Químicos , Estructura Molecular , Inhibidores de Proteasas/química , Programas Informáticos , Propiedades de Superficie
6.
Carbohydr Res ; 205: 323-31, 1990 Sep 19.
Artículo en Francés | MEDLINE | ID: mdl-2177378

RESUMEN

The periodate oxidation of some derivatives of sucrose at primary positions is generally selective for the D-glucopyranoside group. A cleavage at C-2-C3 or C-3-C-4 positions was observed for the 6,1',6'-tri-O-trityl and 6,1',6'-tri-O-(tert-butyldemethylsilyl) derivatives, respectively. The periodate oxidation was more complete for all other derivatives with a cleavage at C-2-C-3 and C-3-C-4.


Asunto(s)
Sacarosa/análogos & derivados , Secuencia de Carbohidratos , Espectroscopía de Resonancia Magnética , Datos de Secuencia Molecular , Estructura Molecular , Oxidación-Reducción , Ácido Peryódico , Sacarosa/síntesis química , Sacarosa/química
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