Explore the vast range of titles available.

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-1 α . 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.

One of the requirements of Heating and current drive Neutral Beam injectors for ITER is a beam homogeneity greater than 90%, to achieve an optimal beam transmission while keeping the heat load consistently low on the acceleration electrodes. The large size and complexity of ITER negative ion source play a key role in determining the homogeneity of the negative ion current of each of the 1280 beamlets and their divergence, and it is studied in the full-scale prototype source SPIDER. In this work the plasma properties are studied by spectroscopic and electrostatic measurements in the drivers, where the plasma is generated, and in the expansion region, where the plasma drifts and negative ions are produced, and they are correlated with the properties of the beam. The non-homogeneous plasma density profile is related to the non-homogeneous availability of negative ions along the beam vertical profile, with and without cesium evaporation. Visible tomography, a technique capable of characterizing isolated beamlet properties, is used to study the beam’s dependence on plasma uniformity along the entire beam profile. Using these tools, it has been demonstrated how an increase in plasma density is linked to an improvement in beam homogeneity. The latter has been directly correlated with plasma homogeneity. The magnetic filter field and biases of the plasma grid and bias plate are responsible for the variation in plasma density and its homogeneity. Non-uniformities in the plasma’s top/bottom and left/right distributions have been studied and partially addressed experimentally. The first issue was resolved by adjusting the radio-frequency power supplied to the plasma in different vertical regions, while the second issue was addressed by reversing the direction of the magnetic filter field and increasing the plasma density.

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.

The impact of plasma shaping on the properties of high density H-mode scrape-off layer (SOL) profiles and transport at the outer midplane has been investigated on Tokamakà configuration variable. The experimental dataset has been acquired by evolving the upper triangularity while keeping the other parameters constant. The scan comprises δup values between 0.0 and 0.6, excluding negative triangularity scenarios. Within this study, a transition from type-I edge localised modes to the quasi-continuous exhaust regime takes place from low to high δup . The modification of the upstream SOL profiles has been assessed, in terms of separatrix quantities, within the αt turbulence control parameter theoretical framework (Eich et al 2020 Nucl. Fusion 60 056016). The target parallel heat load and the upstream near-SOL density profiles have been shown to broaden significantly for increasing αt . Correspondingly, in the far SOL a density shoulder formation is observed when moving from low to high δup . These behaviours have been correlated with an enhancement of the SOL fluctuation level, as registered by wall-mounted Langmuir probes as well as the thermal helium beam diagnostic. Specifically, both the background and the filamentary-induced fluctuating parts of the first wall ion saturation current signal are larger at higher δup , with filaments being ejected more frequently into the SOL. Comparison of two pulses at the extremes of the δup scan range, but with otherwise same input parameters, shows that the midplane neutral pressure does not change much during the H-mode phase of the discharge. This indicates that indirect effects of the change in geometry, linked to first wall recycling sources, should not play a significant role. The total core radiation increases at high δup , on account of a stronger plasma–wall interaction and resulting larger carbon impurity intake from the first wall. This is likely associated to the enhanced first wall fluctuations, as well as a smaller outer gap and the close-to-double-null magnetic topology at high shaping.

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 0.5 Mn 1.5 O 4 , a safe nanostructured anode material, i.e. TiO 2 , and a composite electrolyte made by a mixture of an ionic liquid suitable for high potential applications, i.e. Pyr 1,4 PF 6 , a lithium salt, i.e. LiPF 6 , and standard organic carbonates. The final cell configuration is able to reversibly cycle lithium for thousands of cycles at 1000 mAg −1 and a capacity retention of 65% at cycle 2000.

The RFX-mod2 installation is planned to be completed by 2024 and the start of operations is expected in 2025. The high flexibility of the machine (already tested in the previous RFX-mod experiment) allows operation in Reversed Field Pinch and tokamak configuration as well as ultra-low q pulses. In this work we present predictive analysis on transport, performances and plasma control in RFX-mod2 in view of the first experimental campaigns.

Background: 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. Methods: 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. Results: 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. Conclusion: FASN inhibitors reduce metastasis and tumour-induced angiogenesis in experimental melanomas, and differentially modulate VEGFA expression in B16-F10 cells.

The RFX-mod2 device, the upgraded version of the previous RFX-mod with a modified magnetic boundary, is presently under realization and will start to be operated in 2025. Significant upgrades of the diagnostic capabilities have been proposed and are under development. These include a largely increased number of in-vessel magnetic and electrostatic sensors, a new fast reciprocating manipulator for the exploration of the edge plasma in a wide range of experimental conditions, the improved Thomson scattering and soft x-ray diagnostics system for a detailed determination of the behavior of the electron temperature profile, new dedicated systems for the space and time resolved analysis of x-ray spectra and neutron rate, a reflectometric diagnostic for real-time determination of plasma position, two diagnostics devoted to the imaging of light impurities and influxes behavior along with arrays of halo current sensors. These diagnostic upgrades will be accompanied by a significant effort to improve the control of the electron density and of the impurity influxes by means of proper treatment of plasma facing components with in-vessel fixed electrodes distributed over the first wall. The described advancements will allow a deeper understanding of physics phenomena in the wide variety of magnetic configurations, including the tokamak, the reversed-field pinch and the Ultra-low q, which can be produced in RFX-mod2 thanks to its flexibility and unique MHD control capabilities.

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 TiO 2 on the HaCaT human keratinocyte cell line was examined. The data show that although TiO 2 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, TiO 2 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.