Un des facteurs de risque systématiquement lié à la survenue précoce et importante de problèmes sociaux, affectifs et cognitifs durant la petite enfance est la psychopathologie parentale et ...particulièrement maternelle. En effet, les enfants dont la mère souffre de dépression ont environ deux à trois fois plus souvent des difficultés précoces, et qui peuvent prédire la survenue de problèmes psychiatriques avérés ultérieurement. À partir des données longitudinales de la cohorte EDEN, des groupes de trajectoires latentes de dépression maternelle seront identifiées au sein de la population d’étude. Ensuite, ces trajectoires seront mises en relation avec les difficultés émotionnelles et de comportement et le développement cognitif chez l’enfant en utilisant des analyses de régression linéaire multivariée, en tenant compte de covariables pertinentes. Nous avons identifié cinq trajectoires de dépression maternelle au sein de la cohorte EDEN : 60,2 % des mères n’avaient pas de symptômes dépressifs ; 4,7 % avaient des symptômes dépressifs élevés seulement pendant la grossesse ; 4,9 % avaient des symptômes dépressifs élevés 3–5 ans après la naissance de l’enfant ; 25,2 % avaient des symptômes dépressifs de niveau intermédiaire persistants et 5,0 % avaient des symptômes dépressifs de niveau élevé persistants. La dépression maternelle est liée à des problèmes émotionnels et comportementaux des enfants, en particulier si elle est persistante. De même, on a trouvé que le développement cognitif des enfants, tel que mesuré par le QI, suit la même tendance. À l’âge de 5,5 ans, les enfants de mères ayant des symptômes dépressifs élevés et persistants montrent des scores de QI verbal, QI de performance et QI total réduits par rapport aux enfants de mères jamais déprimés. Les résultats de ces recherches montrent que la dépression maternelle chronique a un impact sur le développement cognitif et émotionnel de l’enfant, même quand les symptômes dépressifs sont d’un niveau intermédiaire.
MicroRNAs (miRs) are a class of small noncoding RNAs that suppress the expression of protein-coding genes by repressing protein translation. Although the roles that miRs and the miR processing ...machinery have in regulating epithelial stem cell biology are not fully understood, their fundamental contributions to these processes have been demonstrated over the last few years. The p53-family member p63 is an essential transcription factor for epidermal morphogenesis and homeostasis. p63 functions as a determinant for keratinocyte cell fate and helps to regulate the balance between stemness, differentiation and senescence. An important factor that regulates p63 function is the reciprocal interaction between p63 and miRs. Some miRs control p63 expression, and p63 regulates the miR expression profile in the epidermis. p63 controls miR expression at different levels. It directly regulates the transcription of several miRs and indirectly regulates their processing by regulating the expression of the miR processing components Dicer and DGCR8. In this review, we will discuss the recent findings on the miR-p63 interaction in epidermal biology, particularly focusing on the ΔNp63-dependent regulation of DGCR8 recently described in the ΔNp63(-/-) mouse. We provide a unified view of the current knowledge and discuss the apparent discrepancies and perspective therapeutic opportunities.
About 99 per cent of solar energy is produced through sequences of nuclear reactions that convert hydrogen into helium, starting from the fusion of two protons (the pp chain). The neutrinos emitted ...by five of these reactions represent a unique probe of the Sun's internal working and, at the same time, offer an intense natural neutrino beam for fundamental physics. Here we report a complete study of the pp chain. We measure the neutrino-electron elastic-scattering rates for neutrinos produced by four reactions of the chain: the initial proton-proton fusion, the electron-capture decay of beryllium-7, the three-body proton-electron-proton (pep) fusion, here measured with the highest precision so far achieved, and the boron-8 beta decay, measured with the lowest energy threshold. We also set a limit on the neutrino flux produced by the
He-proton fusion (hep). These measurements provide a direct determination of the relative intensity of the two primary terminations of the pp chain (pp-I and pp-II) and an indication that the temperature profile in the Sun is more compatible with solar models that assume high surface metallicity. We also determine the survival probability of solar electron neutrinos at different energies, thus probing simultaneously and with high precision the neutrino flavour-conversion paradigm, both in vacuum and in matter-dominated regimes.
Newly generated neurons pass through a series of well-defined developmental stages, which allow them to integrate into existing neuronal circuits. After exit from the cell cycle, postmitotic neurons ...undergo neuronal migration, axonal elongation, axon pruning, dendrite morphogenesis and synaptic maturation and plasticity. Lack of a global metabolic analysis during early cortical neuronal development led us to explore the role of cellular metabolism and mitochondrial biology during ex vivo differentiation of primary cortical neurons. Unexpectedly, we observed a huge increase in mitochondrial biogenesis. Changes in mitochondrial mass, morphology and function were correlated with the upregulation of the master regulators of mitochondrial biogenesis, TFAM and PGC-1α. Concomitant with mitochondrial biogenesis, we observed an increase in glucose metabolism during neuronal differentiation, which was linked to an increase in glucose uptake and enhanced GLUT3 mRNA expression and platelet isoform of phosphofructokinase 1 (PFKp) protein expression. In addition, glutamate-glutamine metabolism was also increased during the differentiation of cortical neurons. We identified PI3K-Akt-mTOR signalling as a critical regulator role of energy metabolism in neurons. Selective pharmacological inhibition of these metabolic pathways indicate existence of metabolic checkpoint that need to be satisfied in order to allow neuronal differentiation.
Today it is widely accepted that molecular mechanisms triggering cancer initiate with a genetic modification. However, a genetic alteration providing the aberrant clone with a growing advantage over ...neighboring cells is not sufficient to develop cancer. Currently, tumors are considered a heterogeneous population of cells and an extracellular matrix (ECM) that make up a characteristic microenvironment. Interactions between tumor cells and cancer microenvironment define cancer progression and therapeutic response. To investigate and clarify the role of ECM in the regulation of cancer cell behavior and response to therapy, the decellularization of ECM, a widely used technique in tissue engineering, has been recently employed to develop 3D culture model of disease. In this review, we briefly explore the different components of healthy and pathological ECM and the methods to obtain and characterize the ECM from native bioptic tissue. Finally, we highlight the most relevant applications of ECM in translational cancer research strategies: decellularized ECM, ECM-hydrogel and 3D bioprinting.
Electrochemical energy storage devices based on Li-ion cells currently power almost all electronic devices and power tools. The development of new Li-ion cell configurations by incorporating ...innovative functional components (electrode materials and electrolyte formulations) will allow to bring this technology beyond mobile electronics and to boost performance largely beyond the state-of-the-art. Here we demonstrate a new full Li-ion cell constituted by a high-potential cathode material, i.e. LiNi
Mn
O
, a safe nanostructured anode material, i.e. TiO
, and a composite electrolyte made by a mixture of an ionic liquid suitable for high potential applications, i.e. Pyr
PF
, a lithium salt, i.e. LiPF
, and standard organic carbonates. The final cell configuration is able to reversibly cycle lithium for thousands of cycles at 1000 mAg
and a capacity retention of 65% at cycle 2000.
A search for the solar neutrino effective magnetic moment has been performed using data from 1291.5 days exposure during the second phase of the Borexino experiment. No significant deviations from ...the expected shape of the electron recoil spectrum from solar neutrinos have been found, and a new upper limit on the effective neutrino magnetic moment of μνeff<2.8×10−11 μB at 90% C.L. has been set using constraints on the sum of the solar neutrino fluxes implied by the radiochemical gallium experiments. Using the limit for the effective neutrino moment, new limits for the magnetic moments of the neutrino flavor states, and for the elements of the neutrino magnetic moments matrix for Dirac and Majorana neutrinos, are derived.
The boundary region of the RFX-mod reversed field pinch experiment is strongly influenced by the value of the electron density. With increasing density the magnetic topology in the plasma core and in ...the plasma edge changes, together with the statistical properties of the edge turbulent fluctuations. Using the density normalized to the Greenwald density (n/nG), two density regimes are identified: the low density regime at n/nG < 0.3-0.4, and the high density regime for n/nG > 0.4-0.5, without a clear threshold between them. At low density the plasma is dominated by the (m, n) = (1, −7) magnetic mode, which gives the same shape to the magnetic boundary; at higher density a strong (0, 1) mode rises. When increasing n/nG, edge fluctuations develop strong non-Gaussian tails, turbulent structures become larger and their radial velocity become measurable with the gas puff imaging diagnostic when n/nG > 0.3-0.4. This phenomenology is described in detail for the two density regimes of RFX-mod.
Fatty acid synthase (FASN) is overexpressed and associated with poor prognosis in several human cancers. Here, we investigate the effect of FASN inhibitors on the metastatic spread and angiogenesis ...in experimental melanomas and cultured melanoma cells.
The lung colonisation assay and cutaneous melanomas were performed by the inoculation of mouse melanoma B16-F10 cells in C57BL6 mice. Blood vessel endothelial cells (RAEC and HUVEC) were applied to determine cell proliferation, apoptosis, and the formation of capillary-like structures. Vascular endothelial growth factor A (VEGFA) expression was evaluated by quantitative RT-PCR and ELISA in B16-F10, human melanoma (SK-MEL-25), and human oral squamous carcinoma (SCC-9) cells. Conditioned media from these cancer cell lines were used to study the effects of FASN inhibitors on endothelial cells.
B16-F10 melanoma-induced metastases and angiogenesis were significantly reduced in orlistat-treated mice. Fatty acid synthase inhibitors reduced the viability, proliferation, and the formation of capillary-like structures by RAEC cells, as well as the tumour cell-mediated formation of HUVEC capillary-like structures. Cerulenin and orlistat stimulated the production of total VEGFA in B16-F10, SK-MEL-25, and SCC-9 cells. Both drugs also enhanced VEGFA(121), (165), (189,) and (165b) in SK-MEL-25 and SCC-9 cells.
FASN inhibitors reduce metastasis and tumour-induced angiogenesis in experimental melanomas, and differentially modulate VEGFA expression in B16-F10 cells.
The long-term health risks of nanoparticles remain poorly understood, which is a serious concern given their prevalence in the environment from increased industrial and domestic use. The extent to ...which such compounds contribute to cellular toxicity is unclear, and although it is known that induction of oxidative stress pathways is associated with this process, the proteins and the metabolic pathways involved with nanoparticle-mediated oxidative stress and toxicity are largely unknown. To investigate this problem further, the effect of TiO2 on the HaCaT human keratinocyte cell line was examined. The data show that although TiO2 does not affect cell cycle phase distribution, nor cell death, these nanoparticles have a considerable and rapid effect on mitochondrial function. Metabolic analysis was performed to identify 268 metabolites of the specific pathways involved and 85 biochemical metabolites were found to be significantly altered, many of which are known to be associated with the cellular stress response. Importantly, the uptake of nanoparticles into the cultured cells was restricted to phagosomes, TiO2 nanoparticles did not enter into the nucleus or any other cytoplasmic organelle. No other morphological changes were detected after 24-h exposure consistent with a specific role of mitochondria in this response.
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