A Spanish version of the athens insomnia scale

Objectives To develop and validate a Spanish version of the Athens Insomnia Scale (AIS). Methods The AIS is designed to assess sleep difficulty and comprises eight items: the first five refer to the sleep disturbance and the last three to the daytime consequences. Either the full eight-item scale (AIS-8) or the brief form (AIS-5) can be administered. The adaptation used a backtranslation design. The validation process was based on a sample of 323 participants (undergraduates, community sample and psychiatric outpatients), which completed the AIS and other questionnaires: anxiety (BAI), depression (BDI) and psychological well-being (GHQ-12) scales. Results The internal consistency coefficients for both versions were above 0.80. The study of dimensionality revealed a single factor with high loadings and a percentage of explained variance above 50% in both versions. Test-retest reliability was above 0.70 (AIS-5) and over 0.80 (AIS-8) at a one-month interval. The correlation between the AIS and the previously mentioned scales was for both the AIS-5 and the AIS-8 above 0.40 and 0.50, respectively

Diffusion capacity of single and interconnected networks

Understanding diffusive processes in networks is a significant challenge in complexity science. Networks possess a diffusive potential that depends on their topological configuration, but diffusion also relies on the process and initial conditions. This article presents Diffusion Capacity, a concept that measures a node’s potential to diffuse information based on a distance distribution that considers both geodesic and weighted shortest paths and dynamical features of the diffusion process. Diffusion Capacity thoroughly describes the role of individual nodes during a diffusion process and can identify structural modifications that may improve diffusion mechanisms. The article defines Diffusion Capacity for interconnected networks and introduces Relative Gain, which compares the performance of a node in a single structure versus an interconnected one. The method applies to a global climate network constructed from surface air temperature data, revealing a significant change in diffusion capacity around the year 2000, suggesting a loss of the planet’s diffusion capacity that could contribute to the emergence of more frequent climatic events.Research partially supported by Brazilian agencies FAPEMIG, CAPES, and CNPq. P.M.P. acknowledges support from the “Paul and Heidi Brown Preeminent Professorship in ISE, University of Florida”, and RSF 14-41- 00039, Humboldt Research Award (Germany) and LATNA, Higher School of Economics, RF. C.M. acknowledges partial support from Spanish MINECO (PID2021-123994NB-C21) and ICREA ACADEMIA. A.D.- G. knowledges support from the Spanish grants PGC2018-094754-BC22 and PID2021-128005NB-C22, funded by MCIN/AEI/ 10.13039/ 501100011033 and “ERDF A way of making Europe”; and from Generalitat de Catalunya (2021SGR00856). M.G.R acknowledges partial support from FUNDEP.Peer ReviewedPostprint (published version

A new metal exchanged zeolite for a present environmental problem. An in-situ XAS study

The medium pore zeolite, TNU-9, is prepared and studied for the selective catalytic reduction (SCR) of NO using C3H8 as the reducing agent. The catalytic activity of TNU-9 zeolites for the SCR is comparable to other known highly active zeolites but with the advantage of TNU-9 of having almost the same catalytic performance in the presence of H2O during reaction. The nature and behaviour of Cu and Co active sites contained in the TNU-9 catalysts have been studied under operation conditions using X-ray Absorption Spectroscopy (XAS) to understand the key parameters controlling the performance of this reaction.1 It was found that the well dispersed Cu and Co centres need to be in a mixed valence state to obtain good catalytic results for the SCR and that the catalytic performance is related to the topology of the TNU-9 itself.Alonso Escobar, C.; Franch Martí, C.; Palomares Gimeno, AE.; Rey Garcia, F.; Guilera, G. (2013). A new metal exchanged zeolite for a present environmental problem. An in-situ XAS study. Journal of Physics: Conference Series. 430:12055-12059. doi:10.1088/1742-6596/430/1/012055S1205512059430Burch, R., Breen, J. P., & Meunier, F. C. (2002). A review of the selective reduction of NOx with hydrocarbons under lean-burn conditions with non-zeolitic oxide and platinum group metal catalysts. Applied Catalysis B: Environmental, 39(4), 283-303. doi:10.1016/s0926-3373(02)00118-2Corma, A., Palomares, A. E., & Fornés, V. (1998). A comparative study on the activity of metal exchanged MCM22 zeolite in the selective catalytic reduction of NOx. Research on Chemical Intermediates, 24(5), 613-623. doi:10.1163/156856798x00131Shibata, J., Takada, Y., Shichi, A., Satokawa, S., Satsuma, A., & Hattori, T. (2004). Influence of zeolite support on activity enhancement by addition of hydrogen for SCR of NO by propane over Ag-zeolites. Applied Catalysis B: Environmental, 54(3), 137-144. doi:10.1016/j.apcatb.2004.03.005Gómez, S. A., Campero, A., Martı́nez-Hernández, A., & Fuentes, G. A. (2000). Changes in Cu2+ environment upon wet deactivation of Cu-ZSM-5 deNOx catalysts. Applied Catalysis A: General, 197(1), 157-164. doi:10.1016/s0926-860x(99)00546-3Palomares, A. ., Márquez, F., Valencia, S., & Corma, A. (2000). On the researching of a new zeolite structure for the selective catalytic reduction of NO. Journal of Molecular Catalysis A: Chemical, 162(1-2), 175-189. doi:10.1016/s1381-1169(00)00288-0Klementev, K. V. (2000). Extraction of the fine structure from x-ray absorption spectra. Journal of Physics D: Applied Physics, 34(2), 209-217. doi:10.1088/0022-3727/34/2/30

Quantification of network structural dissimilarities

Identifying and quantifying dissimilarities among graphs is a fundamental and challenging problem of practical importance in many fields of science. Current methods of network comparison are limited to extract only partial information or are computationally very demanding. Here we propose an efficient and precise measure for network comparison, which is based on quantifying differences among distance probability distributions extracted from the networks. Extensive experiments on synthetic and real-world networks show that this measure returns non-zero values only when the graphs are non-isomorphic. Most importantly, the measure proposed here can identify and quantify structural topological differences that have a practical impact on the information flow through the network, such as the presence or absence of critical links that connect or disconnect connected components

Activating cannabinoid receptor 2 preserves axonal health through GSK-3β/NRF2 axis in adrenoleukodystrophy

Aberrant endocannabinoid signaling accompanies several neurodegenerative disorders, including multiple sclerosis. Here, we report altered endocannabinoid signaling in X-linked adrenoleukodystrophy (X-ALD), a rare neurometabolic demyelinating syndrome caused by malfunction of the peroxisomal ABCD1 transporter, resulting in the accumulation of very long-chain fatty acids (VLCFAs). We found abnormal levels of cannabinoid receptor 2 (CB2r) and related endocannabinoid enzymes in the brain and peripheral blood mononuclear cells (PBMCs) of X-ALD patients and in the spinal cord of a murine model of X-ALD. Preclinical treatment with a selective agonist of CB2r (JWH133) halted axonal degeneration and associated locomotor deficits, along with normalization of microgliosis. Moreover, the drug improved the main metabolic disturbances underlying this model, particularly in redox and lipid homeostatic pathways, including increased lipid droplets in motor neurons, through the modulation of the GSK-3β/NRF2 axis. JWH133 inhibited Reactive Oxygen Species elicited by excess VLCFAs in primary microglial cultures of Abcd1-null mice. Furthermore, we uncovered intertwined redox and CB2r signaling in the murine spinal cords and in patient PBMC samples obtained from a phase II clinical trial with antioxidants (NCT01495260). These findings highlight CB2r signaling as a potential therapeutic target for X-ALD and perhaps other neurodegenerative disorders that present with dysregulated redox and lipid homeostasis.This study was funded by the Institute of Health Carlos III through projects [PI19/01008] to SF and [PI20/00759] to AP (co-funded by the European Regional Development Fund, ERDF, a way to build Europe), Miguel Servet program [CPII16/00016] to SF and [PFIS, FI18/00141] to LPS (co-funded by the European Social Fund, ESF investing in your future). This study was also funded by grants from the Spanish Ministry of Health, Social Services and Equality (EC10-137), the Autonomous Government of Catalonia [2017SGR1206], the Hesperia Foundation, CERTIS Obres i Serveis, and the Crowd funding Campaign Arnau’97 to AP. JP was a predoctoral fellow of IDIBELL. The Center for Biomedical Research on Rare Diseases (CIBERER), an initiative of the Institute of Health Carlos III, funded the position of MR. Locomotor experiments were performed by the SEFALer unit F5 led by AP, which belongs to the CIBERER structure. We thank the CERCA Program/Generalitat de Catalunya for institutional support

Oxidative damage compromises energy metabolism in the axonal degeneration mouse model of X-adrenoleukodystrophy

Aims: Chronic metabolic impairment and oxidative stress are associated with the pathogenesis of axonal dysfunction in a growing number of neurodegenerative conditions. To investigate the intertwining of both noxious factors, we have chosen the mouse model of adrenoleukodystrophy (X-ALD), which exhibits axonal degeneration in spinal cords and motor disability. The disease is caused by loss of function of the ABCD1 transporter, involved in the import and degradation of very long-chain fatty acids (VLCFA) in peroxisomes. Oxidative stress due to VLCFA excess appears early in the neurodegenerative cascade. Results: In this study, we demonstrate by redox proteomics that oxidative damage to proteins specifically affects five key enzymes of glycolysis and TCA (Tricarboxylic acid) cycle in spinal cords of Abcd1(-) mice and pyruvate kinase in human X-ALD fibroblasts. We also show that NADH and ATP levels are significantly diminished in these samples, together with decrease of pyruvate kinase activities and GSH levels, and increase of NADPH. Innovation: Treating Abcd1(-) mice with the antioxidants N-acetylcysteine and alpha-lipoic acid (LA) prevents protein oxidation; preserves NADH, NADPH, ATP, and GSH levels; and normalizes pyruvate kinase activity, which implies that oxidative stress provoked by VLCFA results in bioenergetic dysfunction, at a presymptomatic stage. Conclusion: Our results provide mechanistic insight into the beneficial effects of antioxidants and enhance the rationale for translation into clinical trials for X-adrenoleukodystrophy. Antioxid. Redox Signal. 15, 2095-2107

Oxidative stress and mitochondrial dynamics malfunction are linked in Pelizaeus-Merzbacher disease

Pelizaeus-Merzbacher disease (PMD) is a fatal hypomyelinating disorder characterized by early impairment of motor development, nystagmus, choreoathetotic movements, ataxia and progressive spasticity. PMD is caused by variations in the proteolipid protein gene PLP1, which encodes the two major myelin proteins of the central nervous system, PLP and its spliced isoform DM20, in oligodendrocytes. Large duplications including the entire PLP1 gene are the most frequent causative mutation leading to the classical form of PMD. The Plp1 overexpressing mouse model (PLP-tg66/66 ) develops a phenotype very similar to human PMD, with early and severe motor dysfunction and a dramatic decrease in lifespan. The sequence of cellular events that cause neurodegeneration and ultimately death is poorly understood. In this work, we analyzed patient-derived fibroblasts and spinal cords of the PLP-tg66/66 mouse model, and identified redox imbalance, with altered antioxidant defense and oxidative damage to several enzymes involved in ATP production, such as glycolytic enzymes, creatine kinase and mitochondrial proteins from the Krebs cycle and oxidative phosphorylation. We also evidenced malfunction of the mitochondria compartment with increased ROS production and depolarization in PMD patient's fibroblasts, which was prevented by the antioxidant N-acetyl-cysteine. Finally, we uncovered an impairment of mitochondrial dynamics in patient's fibroblasts which may help explain the ultrastructural abnormalities of mitochondria morphology detected in spinal cords from PLP-tg66/66 mice. Altogether, these results underscore the link between redox and metabolic homeostasis in myelin diseases, provide insight into the pathophysiology of PMD, and may bear implications for tailored pharmacological intervention

RINT1 deficiency disrupts lipid metabolism and underlies a complex hereditary spastic paraplegia

The Rad50 interacting protein 1 (Rint1) is a key player in vesicular trafficking between the ER and Golgi apparatus. Biallelic variants in RINT1 cause infantile-onset episodic acute liver failure (ALF). Here, we describe 3 individuals from 2 unrelated families with novel biallelic RINT1loss-of-function variants who presented with early onset spastic paraplegia, ataxia, optic nerve hypoplasia, and dysmorphic features, broadening the previously described phenotype. Our functional and lipidomic analyses provided evidence that pathogenic RINT1 variants induce defective lipid-droplet biogenesis and profound lipid abnormalities in fibroblasts and plasma that impact both neutral lipid and phospholipid metabolism, including decreased triglycerides and diglycerides, phosphatidylcholine/phosphatidylserine ratios, and inhibited Lands cycle. Further, RINT1 mutations induced intracellular ROS production and reduced ATP synthesis, affecting mitochondria with membrane depolarization, aberrant cristae ultrastructure, and increased fission. Altogether, our results highlighted the pivotal role of RINT1 in lipid metabolism and mitochondria function, with a profound effect in central nervous system development

Autophagy induction halts axonal degeneration in a mouse model of x-adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a rare neurometabolic disease characterized by the accumulation of very long chain fatty acids (VLCFAs) due to a loss of function of the peroxisomal transporter ABCD1. Here, using in vivo and in vitro models, we demonstrate that autophagic flux was impaired due to elevated mammalian target of rapamycin (mTOR) signaling, which contributed to X-ALD pathogenesis. We also show that excess VLCFAs downregulated autophagy in human fibroblasts. Furthermore, mTOR inhibition by a rapamycin derivative (temsirolimus) restored autophagic flux and inhibited the axonal degenerative process as well as the associated locomotor impairment in the Abcd1 (-) /Abcd2 (-/-) mouse model. This process was mediated through the restoration of proteasome function and redox as well as metabolic homeostasis. These findings provide the first evidence that links impaired autophagy to X-ALD, which may yield a therapy based on autophagy activators for adrenomyeloneuropathy patients