Lack of Temporal Impairment in Patients With Mild Cognitive Impairment

In the present study, we investigate possible temporal impairment in patients with mild cognitive impairment (MCI) and the amount of temporal distortions caused by the presentation of emotional facial expressions (anger, shame, and neutral) in MCI patients and controls. Twelve older adults with MCI and 14 healthy older adults were enrolled in the present study. All participants underwent a complete neuropsychological evaluation. We used three timing tasks to tap temporal abilities, namely time bisection (standard intervals lasting 400 and 1600 ms), finger-tapping (free and 1 s), and simple reaction-time tasks. The stimuli used in the time bisection task were facial emotional stimuli expressing anger or shame to investigate a possible contribution of emotional information as previously observed in healthy adults. MCI patients showed temporal abilities comparable to controls. We observed an effect of facial emotional stimuli on time perception when data were analyzed in terms of proportion of long responses, and this result was mainly driven by the temporal overestimation when a facial expression of anger was presented in controls. Results seem to suggest that the severity of the cognitive dysfunction accounts more for subjective temporal impairment than a compromised internal clock

Many-nodes/many-links spinfoam: the homogeneous and isotropic case

I compute the Lorentzian EPRL/FK/KKL spinfoam vertex amplitude for regular graphs, with an arbitrary number of links and nodes, and coherent states peaked on a homogeneous and isotropic geometry. This form of the amplitude can be applied for example to a dipole with an arbitrary number of links or to the 4-simplex given by the compete graph on 5 nodes. All the resulting amplitudes have the same support, independently of the graph used, in the large j (large volume) limit. This implies that they all yield the Friedmann equation: I show this in the presence of the cosmological constant. This result indicates that in the semiclassical limit quantum corrections in spinfoam cosmology do not come from just refining the graph, but rather from relaxing the large j limit.Comment: 8 pages, 4 figure

Met-activating genetically improved chimeric factor-1 promotes angiogenesis and hypertrophy in adult myogenesis

BACKGROUND: Myogenic progenitor cells (activated satellite cells) are able to express both HGF and its receptor cMet. After muscle injury, HGF-Met stimulation promotes activation and primary division of satellite cells. MAGIC-F1 (Met-Activating Genetically Improved Chimeric Factor-1) is an engineered protein that contains two human Met-binding domains that promotes muscle hypertrophy. MAGIC-F1 protects myogenic precursors against apoptosis and increases their fusion ability enhancing muscle differentiation. Hemizygous and homozygous Magic-F1 transgenic mice displayed constitutive muscle hypertrophy. METHODS: Here we describe microarray analysis on Magic-F1 myogenic progenitor cells showing an altered gene signatures on muscular hypertrophy and angiogenesis compared to wild-type cells. In addition, we performed a functional analysis on Magic-F1+/+ transgenic mice versus controls using treadmill test. RESULTS: We demonstrated that Magic-F1+/+ mice display an increase in muscle mass and cross-sectional area leading to an improvement in running performance. Moreover, the presence of MAGIC-F1 affected positively the vascular network, increasing the vessel number in fast twitch fibers. Finally, the gene expression profile analysis of Magic-F1+/+ satellite cells evidenced transcriptomic changes in genes involved in the control of muscle growth, development and vascularisation. CONCLUSION: We showed that MAGIC -F1-induced muscle hypertrophy affects positively vascular network, increasing vessel number in fast twitch fibers. This was due to unique features of mammalian skeletal muscle and its remarkable ability to adapt promptly to different physiological demands by modulating the gene expression profile in myogenic progenitors

MYCN Amplification, along with Wild-Type RB1 Expression, Enhances CDK4/6 Inhibitors’ Efficacy in Neuroblastoma Cells

Neuroblastoma (NB) is one of the primary causes of death for pediatric malignancies. Given the high heterogeneity in NB's mutation landscape, optimizing individualized therapies is still challenging. In the context of genomic alterations, MYCN amplification is the most correlated event with poor outcomes. MYCN is involved in the regulation of several cellular mechanisms, including cell cycle. Thus, studying the influence of MYCN overexpression in the G1/S transition checkpoint of the cell cycle may unveil novel druggable targets for the development of personalized therapeutical approaches. Here, we show that high expression of E2F3 and MYCN correlate with poor prognosis in NB despite the RB1 mRNA levels. Moreover, we demonstrate through luciferase reporter assays that MYCN bypasses RB function by incrementing E2F3-responsive promoter activity. We showed that MYCN overexpression leads to RB inactivation by inducing RB hyperphosphorylation during the G1 phase through cell cycle synchronization experiments. Moreover, we generated two MYCN-amplified NB cell lines conditionally knockdown (cKD) for the RB1 gene through a CRISPRi approach. Indeed, RB KD did not affect cell proliferation, whereas cell proliferation was strongly influenced when a non-phosphorylatable RB mutant was expressed. This finding revealed the dispensable role of RB in regulating MYCN-amplified NB's cell cycle. The described genetic interaction between MYCN and RB1 provides the rationale for using cyclin/CDK complexes inhibitors in NBs carrying MYCN amplification and relatively high levels of RB1 expression

Reference genes for transcriptional analysis of flowering and fruit ripening stages in apple (Malus 3 domestica Borkh.).

Apple (Malus 9 domestica Borkh.) is the most important deciduous tree fruit crop grown around the world. Comparisons of gene expression profiles from different tissues, conditions or cultivars are valuable scientific tools to better understand the gene expression changes behind important silvicultural and nutritional traits. However, the accuracy of techniques employed to access gene expression is dependent on the evaluation of stable reference genes for data normalization to avoid statistical significance undue or incorrect conclusions. The objective of this work was to select the best genes to be used as references for gene expression studies in apple trees by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Vegetative and reproductive tissues of the apple ??Gala?? cultivar were evaluated during their seasonal cycle of growth and dormancy. The expression of 23 traditional housekeeping genes or genes suggested as constitutive by microarray data was investigated. Tested combinations of primers allowed the specific amplification and the generation of suitable efficiency curves for gene expression studies by RT-qPCR. Gene stability was determined by two different statistical descriptors, geNorm and Norm-Finder. The known variable PAL gene expression was used to validate selected normalizers. Results obtained allowed us to conclude that MDH, SAND, THFS, TMp1 and WD40 are the best reference genes to accurately normalize the relative transcript abundances using RT-qPCR in various tissues of apple.DOI 10.1007/s11032-014-0078-

Reference gene selection for gene expression studies in apple.

Apple (Malus x domestica Borkh.) is the most important deciduous tree fruit crop grown around the world, and also in the Southern of Brazil. Researches on apple genetic breeding include disease resistance mechanisms, grafting, chilling requirement, fruit ripening and production of nutraceutical compounds.Resumo

Optimal Dithering Configuration Mitigating Rayleigh-Backscattering-Induced Distortion in Radioastronomic Optical Fiber Systems

In the context of Radioastronomic applications where the Analog Radio-over-Fiber technology is used for the antenna downlink, detrimental nonlinearity effects arise because of the interference between the forward signal generated by the laser and the Rayleigh backscattered one which is re-forwarded by the laser itself toward the photodetector. The adoption of the so called dithering technique, which involves the direct modulation of the laser with a sinusoidal tone and takes advantage of the laser chirping phenomenon, has been proved to reduce such Rayleigh Back Scattering - induced nonlinearities. The frequency and the amplitude of the dithering tone should both be as low as possible, in order to avoid undesired collateral effects on the received spectrum as well as keep at low levels the global energy consumption. Through a comprehensive analysis of dithered Radio over Fiber systems, it is demonstrated that a progressive reduction of the dithering tone frequency affects in a peculiar fashion both the chirping characteristics of the field emitted by the laser and the spectrum pattern of the received signal at the fiber end. Accounting for the concurrent effects caused by such phenomena, optimal operating conditions are identified for the implementation of the dithering tone technique in radioastronomic systems

Single-cell gene network analysis and transcriptional landscape of MYCN-amplified neuroblastoma cell lines

Neuroblastoma (NBL) is a pediatric cancer responsible for more than 15% of cancer deaths in children, with 800 new cases each year in the United States alone. Genomic amplification of the MYC oncogene family member MYCN characterizes a subset of high-risk pediatric neuroblastomas. Several cellular models have been implemented to study this disease over the years. Two of these, SK-N-BE-2-C (BE2C) and Kelly, are amongst the most used worldwide as models of MYCN-Amplified human NBL. Here, we provide a transcriptome-wide quantitative measurement of gene expression and transcriptional network activity in BE2C and Kelly cell lines at an unprecedented single-cell resolution. We obtained 1105 Kelly and 962 BE2C unsynchronized cells, with an average number of mapped reads/cell of roughly 38,000. The single-cell data recapitulate gene expression signatures previously generated from bulk RNA-Seq. We highlight low variance for commonly used housekeeping genes between different cells (ACTB, B2M and GAPDH), while showing higher than expected variance for metallothionein transcripts in Kelly cells. The high number of samples, despite the relatively low read coverage of single cells, allowed for robust pathway enrichment analysis and master regulator analysis (MRA), both of which highlight the more mesenchymal nature of BE2C cells as compared to Kelly cells, and the upregulation of TWIST1 and DNAJC1 transcriptional networks. We further defined master regulators at the single cell level and showed that MYCN is not constantly active or expressed within Kelly and BE2C cells, independently of cell cycle phase. The dataset, alongside a detailed and commented programming protocol to analyze it, is fully shared and reusable

Design, Manufacturing Aspects and Performance of Recent 10 m Long Model Dipole Superconducting Magnets for the LHC Project

A number of twin aperture, 10 m long, model dipole magnets for the LHC Project have been built and tested. With regard to the models of the first generation, the inner coil diameter and the intra-beam distance were increased from 50 to 56 mm and from 180 to about 194 mm, respectively. Also with regard to the previous models, a 5-block (instead of a 6-block) coil cross-section was chosen and the wid th of the Rutherford cable was reduced from 17 mm to 15 mm. The coils were manufactured and collared in Industry, the assembly of their magnetic circuit and cold mass were carried out at CERN. The ind ividual design and manufacturing features of each of these magnets are described and the results of their warm and cold magnetic measurement are presented and discussed