Narcolepsy and emotional experience: a review of the literature

Narcolepsy is a chronic sleep disorder characterized by excessive daytime sleepiness, cataplexy, hypnagogic hallucinations, and sleep paralysis. This disease affects significantly the overall patient functioning, interfering with social, work, and affective life. Some symptoms of narcolepsy depend on emotional stimuli; for instance, cataplectic attacks can be triggered by emotional inputs such as laughing, joking, a pleasant surprise, and also anger. Neurophysiological and neurochemical findings suggest the involvement of emotional brain circuits in the physiopathology of cataplexy, which seems to depending on the dysfunctional interplay between the hypothalamus and the amygdala associated with an alteration of hypocretin levels. Furthermore, behavioral studies suggest an impairment of emotions processing in narcolepsy-cataplexy (NC), like a probable coping strategy to avoid or reduce the frequency of cataplexy attacks. Consistently, NC patients seem to use coping strategies even during their sleep, avoiding unpleasant mental sleep activity through lucid dreaming. Interestingly, NC patients, even during sleep, have a different emotional experience than healthy subjects, with more vivid, bizarre, and frightening dreams. Notwithstanding this evidence, the relationship between emotion and narcolepsy is poorly investigated. This review aims to provide a synthesis of behavioral, neurophysiological, and neurochemical evidence to discuss the complex relationship between NC and emotional experience and to direct future research

MUSE-inspired view of the quasar Q2059-360, its Lyman alpha blob, and its neighborhood

The radio-quiet quasar Q2059-360 at redshift $z=3.08$ is known to be close to a small Lyman $\alpha$ blob (LAB) and to be absorbed by a proximate damped Ly$\alpha$ (PDLA) system. Here, we present the Multi Unit Spectroscopic Explorer (MUSE) integral field spectroscopy follow-up of this quasi-stellar object (QSO). Our primary goal is to characterize this LAB in detail by mapping it both spatially and spectrally using the Ly$\alpha$ line, and by looking for high-ionization lines to constrain the emission mechanism. Combining the high sensitivity of the MUSE integral field spectrograph mounted on the Yepun telescope at ESO-VLT with the natural coronagraph provided by the PDLA, we map the LAB down to the QSO position, after robust subtraction of QSO light in the spectral domain. In addition to confirming earlier results for the small bright component of the LAB, we unveil a faint filamentary emission protruding to the south over about 80 pkpc (physical kpc); this results in a total size of about 120 pkpc. We derive the velocity field of the LAB (assuming no transfer effects) and map the Ly$\alpha$ line width. Upper limits are set to the flux of the N V $\lambda 1238-1242$, C IV $\lambda 1548-1551$, He II $\lambda 1640$, and C III] $\lambda 1548-1551$ lines. We have discovered two probable Ly$\alpha$ emitters at the same redshift as the LAB and at projected distances of 265 kpc and 207 kpc from the QSO; their Ly$\alpha$ luminosities might well be enhanced by the QSO radiation. We also find an emission line galaxy at $z=0.33$ near the line of sight to the QSO. This LAB shares the same general characteristics as the 17 others surrounding radio-quiet QSOs presented previously. However, there are indications that it may be centered on the PDLA galaxy rather than on the QSO.Comment: Accepted for publication in Astronomy & Astrophysics; 16 pages, 19 figure

Fingerprinting white marbles of archaeometric interest by means of combined SANS and USANS

We have performed a series of USANS and SANS measurements on a selected group of marble samples characterized by similar chemical composition but wide range of known metamorphic conditions. With these samples we start the building up of a data base in an attempt to correlate metamorphism and mesoscopic structure of white marbles. Experimental data have been analysed in terms of a hierarchical model. The present data highlight the importance of the structure at meso scale in identifying the provenance of the marble samples. A remarkable simple relation between the model parameters and the metamorphic degree has been found. This curve might represent a master curve to allow fingerprinting of white marbles. Also, two coloured marbles from Villa Adriana (Tivoli, Italy) have been investigated by means of the same techniques. Results obtained follow the general trend found for the white marbles

Viral and cellular mRNA-specific activators harness PABP and eIF4G to promote translation initiation downstream of cap binding

Regulation of mRNA translation is a major control point for gene expression and is critical for life. Of central importance is the complex between cap-bound eukaryotic initiation factor 4E (eIF4E), eIF4G, and poly(A) tail-binding protein (PABP) that circularizes mRNAs, promoting translation and stability. This complex is often targeted to regulate overall translation rates, and also by mRNA-specific translational repressors. However, the mechanisms of mRNA-specific translational activation by RNA-binding proteins remain poorly understood. Here, we address this deficit, focusing on a herpes simplex virus-1 protein, ICP27. We reveal a direct interaction with PABP that is sufficient to promote PABP recruitment and necessary for ICP27-mediated activation. PABP binds several translation factors but is primarily considered to activate translation initiation as part of the PABP-eIF4G-eIF4E complex that stimulates the initial cap-binding step. Importantly, we find that ICP27-PABP forms a complex with, and requires the activity of, eIF4G. Surprisingly, ICP27-PABP-eIF4G complexes act independently of the effects of PABP-eIF4G on cap binding to promote small ribosomal subunit recruitment. Moreover, we find that a cellular mRNA-specific regulator, Deleted in Azoospermia-like (Dazl), also employs the PABP-eIF4G interaction in a similar manner. We propose a mechanism whereby diverse RNA-binding proteins directly recruit PABP, in a non-poly(A) tail-dependent manner, to stimulate the small subunit recruitment step. This strategy may be particularly relevant to biological conditions associated with hypoadenylated mRNAs (e.g., germ cells/neurons) and/or limiting cytoplasmic PABP (e.g., viral infection, cell stress). This mechanism adds significant insight into our knowledge of mRNA-specific translational activation and the function of the PABP-eIF4G complex in translation initiation

PET/MR in recurrent glioblastoma patients treated with regorafenib: [18F]FET and DWI-ADC for response assessment and survival prediction

Objective: The use of regorafenib in recurrent glioblastoma patients has been recently approved by the Italian Medicines Agency (AIFA) and added to the National Comprehensive Cancer Network (NCCN) 2020 guidelines as a preferred regimen. Given its complex effects at the molecular level, the most appropriate imaging tools to assess early response to treatment is still a matter of debate. Diffusion-weighted imaging and O-(2-18F-fluoroethyl)-L-tyrosine positron emission tomography ([18F]FET PET) are promising methodologies providing additional information to the currently used RANO criteria. The aim of this study was to evaluate the variations in diffusion-weighted imaging/apparent diffusion coefficient (ADC) and [18F]FET PET-derived parameters in patients who underwent PET/MR at both baseline and after starting regorafenib. Methods: We retrospectively reviewed 16 consecutive GBM patients who underwent [18F]FET PET/MR before and after two cycles of regorafenib. Patients were sorted into stable (SD) or progressive disease (PD) categories in accordance with RANO criteria. We were also able to analyze four SD patients who underwent a third PET/MR after another four cycles of regorafenib. [18F]FET uptake greater than 1.6 times the mean background activity was used to define an area to be superimposed on an ADC map at baseline and after treatment. Several metrics were then derived and compared. Log-rank test was applied for overall survival analysis. Results: Percentage difference in FET volumes correlates with the corresponding percentage difference in ADC (R = 0.54). Patients with a twofold increase in FET after regorafenib showed a significantly higher increase in ADC pathological volume than the remaining subjects (p = 0.0023). Kaplan-Meier analysis, performed to compare the performance in overall survival prediction, revealed that the percentage variations of FET- and ADC-derived metrics performed at least as well as RANO criteria (p = 0.02, p = 0.024 and p = 0.04 respectively) and in some cases even better. TBR Max and TBR mean are not able to accurately predict overall survival. Conclusion In recurrent glioblastoma patients treated with regorafenib, [18F]FET and ADC metrics, are able to predict overall survival and being obtained from completely different measures as compared to RANO, could serve as semi-quantitative independent biomarkers of response to treatment. Advances in knowledge Simultaneous evaluation of [18F]FET and ADC metrics using PET/MR allows an early and reliable identification of response to treatment and predict overall survival

The completed SDSS-IV extended Baryon Oscillation Spectroscopic Survey: Measurement of the BAO and growth rate of structure of the emission line galaxy sample from the anisotropic power spectrum between redshift 0.6 and 1.1

We analyse the large-scale clustering in Fourier space of emission line galaxies (ELG) from the Data Release 16 of the Sloan Digital Sky Survey IV extended Baryon Oscillation Spectroscopic Survey. The ELG sample contains 173 736 galaxies covering 1170 deg^{2} in the redshift range 0.6 < z < 1.1. We perform a BAO measurement from the post-reconstruction power spectrum monopole, and study redshift space distortions (RSD) in the first three even multipoles. Photometric variations yield fluctuations of both the angular and radial survey selection functions. Those are directly inferred from data, imposing integral constraints which we model consistently. The full data set has only a weak preference for a BAO feature (1.4σ). At the effective redshift z_{eff} = 0.845 we measure D_{V}(z_{eff})/r_{drag}=18.33\tfrac{+0.57}{−0.62⁠},with DV the volume-averaged distance and r_{drag} the comoving sound horizon at the drag epoch. In combination with the RSD measurement, at z_{eff} = 0.85 we find fσ_{8}(z_{eff})=0.289\tfrac{+0.085}{−0.096⁠}, with f the growth rate of structure and σ_{8} the normalization of the linear power spectrum, D_{H}(z_{eff})/r_{drag} = 20.0\tfrac{2.4}{-2.2} and D_{M}(z_[eff})/r_{drag} = 19.17 ± 0.99 with D_{H} and D_{M} the Hubble and comoving angular distances, respectively. These results are in agreement with those obtained in configuration space, thus allowing a consensus measurement of fσ_{8}(z_{eff}) = 0.315 ± 0.095, D_{H}(z_{eff})/r_{drag} = 19.6\tfrac{+2.2}{−2.1} and D_{M}(z_{eff})/r_{drag} = 19.5 ± 1.0. This measurement is consistent with a flat ΛCDM model with Planck parameters

Nucleolar Accumulation of RNA Binding Proteins Induced by ActinomycinD Is Functional in Trypanosoma cruzi and Leishmania mexicana but Not in T. brucei

We have recently shown in T. cruzi that a group of RNA Binding Proteins (RBPs), involved in mRNA metabolism, are accumulated into the nucleolus in response to Actinomycin D (ActD) treatment. In this work, we have extended our analysis to other members of the trypanosomatid lineage. In agreement with our previous study, the mechanism seems to be conserved in L. mexicana, since both endogenous RBPs and a transgenic RBP were relocalized to the nucleolus in parasites exposed to ActD. In contrast, in T. brucei, neither endogenous RBPs (TbRRM1 and TbPABP2) nor a transgenic RBP from T. cruzi were accumulated into the nucleolus under such treatment. Interestingly, when a transgenic TbRRM1was expressed in T. cruzi and the parasites exposed to ActD, TbRRM1 relocated to the nucleolus, suggesting that it contains the necessary sequence elements to be targeted to the nucleolus. Together, both experiments demonstrate that the mechanism behind nucleolar localization of RBPs, which is present in T. cruzi and L. mexicana, is not functional in T. brucei, suggesting that it has been lost or retained differentially during the evolution of the trypanosomatid lineage

In Vivo Deficiency of Both C/EBPβ and C/EBPε Results in Highly Defective Myeloid Differentiation and Lack of Cytokine Response

The CCAAT/enhancer binding proteins (C/EBPs) are transcription factors involved in hematopoietic cell development and induction of several inflammatory mediators. Here, we generated C/EBPβ and C/EBPε double-knockout (bbee) mice and compared their phenotypes to those of single deficient (bbEE and BBee) and wild-type (BBEE) mice. The bbee mice were highly susceptible to fatal infections and died within 2–3 months. Morphologically, their neutrophils were blocked at the myelocytes/metamyelocytes stage, and clonogenic assays of bone marrow cells indicated a significant decrease in the number of myeloid colonies of the bbee mice. In addition, the proportion of hematopoietic progenitor cells [Lin(−)Sca1(+)c-Kit(+)] in the bone marrow of the bbee mice was significantly increased, reflecting the defective differentiation of the myeloid compartment. Furthermore, microarray expression analysis of LPS- and IFNγ-activated bone marrow-derived macrophages from bbee compared to single knockout mice revealed decreased expression of essential immune response-related genes and networks, including some direct C/EBP-targets such as Marco and Clec4e. Overall, the phenotype of the bbee mice is distinct from either the bbEE or BBee mice, demonstrating that both transcription factors are crucial for the maturation of neutrophils and macrophages, as well as the innate immune system, and can at least in part compensate for each other in the single knockout mice

The sleep EEG spectrum is a sexually dimorphic marker of general intelligence

The shape of the EEG spectrum in sleep relies on genetic and anatomical factors and forms an individual “EEG fingerprint”. Spectral components of EEG were shown to be connected to mental ability both in sleep and wakefulness. EEG sleep spindle correlates of intelligence, however, exhibit a sexual dimorphism, with a more pronounced association to intelligence in females than males. In a sample of 151 healthy individuals, we investigated how intelligence is related to spectral components of full-night sleep EEG, while controlling for the effects of age. A positive linear association between intelligence and REM anterior beta power was found in females but not males. Transient, spindle-like “REM beta tufts” are described in the EEG of healthy subjects, which may reflect the functioning of a recently described cingular-prefrontal emotion and motor regulation network. REM sleep frontal high delta power was a negative correlate of intelligence. NREM alpha and sigma spectral power correlations with intelligence did not unequivocally remain significant after multiple comparisons correction, but exhibited a similar sexual dimorphism. These results suggest that the neural oscillatory correlates of intelligence in sleep are sexually dimorphic, and they are not restricted to either sleep spindles or NREM sleep

Gene and genon concept: coding versus regulation: A conceptual and information-theoretic analysis of genetic storage and expression in the light of modern molecular biology

We analyse here the definition of the gene in order to distinguish, on the basis of modern insight in molecular biology, what the gene is coding for, namely a specific polypeptide, and how its expression is realized and controlled. Before the coding role of the DNA was discovered, a gene was identified with a specific phenotypic trait, from Mendel through Morgan up to Benzer. Subsequently, however, molecular biologists ventured to define a gene at the level of the DNA sequence in terms of coding. As is becoming ever more evident, the relations between information stored at DNA level and functional products are very intricate, and the regulatory aspects are as important and essential as the information coding for products. This approach led, thus, to a conceptual hybrid that confused coding, regulation and functional aspects. In this essay, we develop a definition of the gene that once again starts from the functional aspect. A cellular function can be represented by a polypeptide or an RNA. In the case of the polypeptide, its biochemical identity is determined by the mRNA prior to translation, and that is where we locate the gene. The steps from specific, but possibly separated sequence fragments at DNA level to that final mRNA then can be analysed in terms of regulation. For that purpose, we coin the new term “genon”. In that manner, we can clearly separate product and regulative information while keeping the fundamental relation between coding and function without the need to introduce a conceptual hybrid. In mRNA, the program regulating the expression of a gene is superimposed onto and added to the coding sequence in cis - we call it the genon. The complementary external control of a given mRNA by trans-acting factors is incorporated in its transgenon. A consequence of this definition is that, in eukaryotes, the gene is, in most cases, not yet present at DNA level. Rather, it is assembled by RNA processing, including differential splicing, from various pieces, as steered by the genon. It emerges finally as an uninterrupted nucleic acid sequence at mRNA level just prior to translation, in faithful correspondence with the amino acid sequence to be produced as a polypeptide. After translation, the genon has fulfilled its role and expires. The distinction between the protein coding information as materialised in the final polypeptide and the processing information represented by the genon allows us to set up a new information theoretic scheme. The standard sequence information determined by the genetic code expresses the relation between coding sequence and product. Backward analysis asks from which coding region in the DNA a given polypeptide originates. The (more interesting) forward analysis asks in how many polypeptides of how many different types a given DNA segment is expressed. This concerns the control of the expression process for which we have introduced the genon concept. Thus, the information theoretic analysis can capture the complementary aspects of coding and regulation, of gene and genon