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BACKGROUND: We analysed the relationship between cerebrospinal fluid (CSF)/serum albumin quotient (Q-Alb) and phenotype in a large cohort of patients with amyotrophic lateral sclerosis (ALS). METHODS: Three hundred twenty-eight single-centre consecutive patients with ALS were evaluated for Q-Alb, basic epidemiological and clinical data, motor phenotype, cognitive/behavioural impairment, clinical staging, clinical and neurophysiological indexes of upper (UMN) and lower motor neuron (LMN) dysfunction, and presence of ALS gene mutations. RESULTS: Q-Alb did not correlate with age but was independently associated with sex, with male patients having higher levels than female ones; the site of onset was not independently associated with Q-Alb. Q-Alb was not associated with motor phenotype, cognitive/behavioural impairment, disease stage, progression rate, survival, or genetic mutations. Among measures of UMN and LMN dysfunction, Q-Alb only had a weak positive correlation with an electromyography-based index of active limb denervation. CONCLUSION: Previous work has documented increased Q-Alb in ALS compared to unaffected individuals. This, together with the absence of associations with nearly all ALS phenotypic features in our cohort, suggests dysfunction of the blood-CSF barrier as a shared, phenotype-independent element in ALS pathophysiology. However, correlation with the active denervation index could point to barrier dysfunction as a local driver of LMN degeneration.
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Esclerosis Amiotrófica Lateral , Masculino , Femenino , Humanos , Esclerosis Amiotrófica Lateral/genética , Estudios Retrospectivos , Neuronas Motoras , Albúmina Sérica , FenotipoRESUMEN
The church of Santa Maria della Lizza is one of the most important examples of medieval architecture in the Salento Peninsula in south Italy. In order to understand the extension and layout of the crypts, integrated ground-penetrating radar (GPR) prospections and laser scanner surveys were undertaken in the church and in the surrounding areas. The analysis of the GPR measurements revealed many anomalies that could be ascribed to unknown structures (crypts), as well as other anomalies related to the old church. The GPR data were supported by the laser scanner data establishing the spatial relationship between the surface and the level below the church.
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The Messapian necropolis of Monte D'Elia is related to one of the most important ancient settlements in the Salento Peninsula (in south Italy). In order to understand the extension and layout of this necropolis in the various periods of its use, a ground-penetrating radar (GPR) prospection was undertaken in some important sample areas by a team of the Institute for Archaeological and Monumental Heritage of the National Research Council of Italy. The analysis of the GPR measurements revealed many anomalies that could be ascribed to archaeological structures (tombs), as well as other anomalies of presumable natural origin or referable to modern features. The data collected were georeferenced in the digital archaeological map of the site and integrated with a virtual reconstruction of the surveyed area.
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Face masks can filter droplets containing viruses and bacteria minimizing the transmission and spread of respiratory pathogens but are also an indirect source of microbes transmission. A novel antibacterial and antiviral Ag-coated polypropylene surgical mask obtained through the in situ and one-step deposition of metallic silver nanoparticles, synthesized by silver mirror reaction combined with sonication or agitation methods, is proposed in this study. SEM analysis shows Ag nanoparticles fused together in a continuous and dense layer for the coating obtained by sonication, whereas individual Ag nanoparticles around 150 nm were obtained combining the silver mirror reaction with agitation. EDX, XRD and XPS confirm the presence of metallic Ag in both coatings and also oxidized Ag in samples by agitation. A higher amount of Ag nanoparticles is deposited on samples by sonication, as calculated by TGA. Further, both coatings are biocompatible and show antibacterial properties: coating by sonication caused 24 % and 40 % of bacterial reduction while coating by agitation 48 % and 96 % against S. aureus and E. coli, respectively. At 1 min of contact with SARS-CoV-2, the coating by agitation has an antiviral capacity of 75 % against 24 % of the one by sonication. At 1 h, both coatings achieve 100 % of viral inhibition. Nonetheless, larger samples could be produced only through the silver mirror reaction combined with agitation, preserving the integrity of the mask. In conclusion, the silver-coated mask produced by silver mirror reaction combined with agitation is scalable, has excellent physico-chemical characteristics as well as significant biological properties, with higher antimicrobial activities, providing additional protection and preventing the indirect transmission of pathogens.
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FAM46C is a multiple myeloma (MM) tumor suppressor whose function is only starting to be elucidated. We recently showed that in MM cells FAM46C triggers apoptosis by inhibiting autophagy and altering intracellular trafficking and protein secretion. To date, both a physiological characterization of FAM46C role and an assessment of FAM46C-induced phenotypes outside of MM are lacking. Preliminary reports suggested an involvement of FAM46C with regulation of viral replication, but this was never confirmed. Here, we show that FAM46C is an interferon-stimulated gene and that the expression of wild-type FAM46C in HEK-293T cells, but not of its most frequently found mutant variants, inhibits the production of both HIV-1-derived and HIV-1 lentiviruses. We demonstrate that this effect does not require transcriptional regulation and does not depend on inhibition of either global or virus-specific translation but rather mostly relies on FAM46C-induced deregulation of autophagy, a pathway that we show to be required for efficient lentiviral particle production. These studies not only provide new insights on the physiological role of the FAM46C protein but also could help in implementing more efficient antiviral strategies on one side and lentiviral particle production approaches on the other. IMPORTANCE FAM46C role has been thoroughly investigated in MM, but studies characterizing its role outside of the tumoral environment are still lacking. Despite the success of antiretroviral therapy in suppressing HIV load to undetectable levels, there is currently no HIV cure, and treatment is lifelong. Indeed, HIV continues to be a major global public health issue. Here, we show that FAM46C expression in HEK-293T cells inhibits the production of both HIV and HIV-derived lentiviruses. We also demonstrate that such inhibitory effect relies, at least in part, on the well-established regulatory role that FAM46C exerts on autophagy. Deciphering the molecular mechanism underlying this regulation will not only facilitate the understanding of FAM46C physiological role but also give new insights on the interplay between HIV and the cellular environment.
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Interferones , Proteínas , Interferones/genética , Proteínas/genética , Regulación de la Expresión Génica , Apoptosis , AutofagiaRESUMEN
This short review summarizes the improvements on biological fuel cells (BioFCs) with or without ionomer separation membrane. After a general introduction about the main challenges of modern energy management, BioFCs are presented including microbial fuel cells (MFCs) and enzymatic fuel cells (EFCs). The benefits of BioFCs include the capability to derive energy from waste-water and organic matter, the possibility to use bacteria or enzymes to replace expensive catalysts such as platinum, the high selectivity of the electrode reactions that allow working with less complicated systems, without the need for high purification, and the lower environmental impact. In comparison with classical FCs and given their lower electrochemical performances, BioFCs have, up to now, only found niche applications with low power needs, but they could become a green solution in the perspective of sustainable development and the circular economy. Ion exchange membranes for utilization in BioFCs are discussed in the final section of the review: they include perfluorinated proton exchange membranes but also aromatic polymers grafted with proton or anion exchange groups.
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Stem cell engineering of striatal medium spiny neurons (MSNs) is a promising strategy to understand diseases affecting the striatum and for cell-replacement therapies in different neurological diseases. Protocols to generate cells from human pluripotent stem cells (PSCs) are scarce and how well they recapitulate the endogenous fetal cells remains poorly understood. We have developed a protocol that modulates cell seeding density and exposure to specific morphogens that generates authentic and functional D1- and D2-MSNs with a high degree of reproducibility in 25 days of differentiation. Single-cell RNA sequencing (scRNA-seq) shows that our cells can mimic the cell-fate acquisition steps observed in vivo in terms of cell type composition, gene expression, and signaling pathways. Finally, by modulating the midkine pathway we show that we can increase the yield of MSNs. We expect that this protocol will help decode pathogenesis factors in striatal diseases and eventually facilitate cell-replacement therapies for Huntington's disease (HD).
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Neuronas Espinosas Medianas , Células Madre Pluripotentes , Humanos , Reproducibilidad de los Resultados , Neurogénesis , Cuerpo Estriado , Células Madre Pluripotentes/metabolismoRESUMEN
Miniaturized low-cost sensors for volatile organic compounds (VOCs) have the potentiality to become a fundamental tool for indoor and outdoor air quality monitoring, to significantly improve everyday life. Layered double hydroxides (LDHs) belong to the class of anionic clays and are largely employed for NO x detection, while few results are reported on VOCs. In this work, a novel LDH coprecipitation method is proposed. For the first time, a study comparing four LDHs (ZnAl-Cl, ZnFe-Cl, ZnAl-NO3, and MgAl-NO3) is carried out to investigate the sensing performances. As explored through several microscopy and spectroscopy analyses, LDHs show a morphology characterized by a large surface area and a three-dimensional hierarchical flowerlike architecture with micro- and nanopores that induce a fast diffusion and highly effective surface interaction of the target gases. The fabricated sensors, operating at room temperature, are able to reversibly and selectively detect acetone, ethanol, ammonia, and chlorine vapors, reaching significant sensing response values up to 6% at 21 °C. The results demonstrate that by changing the LDHs' composition, it is possible to modulate the sensitivity and selectivity of the sensor, helping the discrimination of different analytes, and the consequent integration on a sensor array paves the way for electronic nose development.
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Cancer is characterized by pervasive epigenetic alterations with enhancer dysfunction orchestrating the aberrant cancer transcriptional programs and transcriptional dependencies. Here, we epigenetically characterize human colorectal cancer (CRC) using de novo chromatin state discovery on a library of different patient-derived organoids. By exploring this resource, we unveil a tumor-specific deregulated enhancerome that is cancer cell-intrinsic and independent of interpatient heterogeneity. We show that the transcriptional coactivators YAP/TAZ act as key regulators of the conserved CRC gained enhancers. The same YAP/TAZ-bound enhancers display active chromatin profiles across diverse human tumors, highlighting a pan-cancer epigenetic rewiring which at single-cell level distinguishes malignant from normal cell populations. YAP/TAZ inhibition in established tumor organoids causes extensive cell death unveiling their essential role in tumor maintenance. This work indicates a common layer of YAP/TAZ-fueled enhancer reprogramming that is key for the cancer cell state and can be exploited for the development of improved therapeutic avenues.
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Proteínas Adaptadoras Transductoras de Señales/genética , Neoplasias Colorrectales/genética , Elementos de Facilitación Genéticos , Epigénesis Genética , Transactivadores/genética , Factores de Transcripción/genética , Regulación Neoplásica de la Expresión Génica , Código de Histonas , Humanos , Modelos Genéticos , Organoides/metabolismo , RNA-Seq , Análisis de la Célula Individual , Proteínas Coactivadoras Transcripcionales con Motivo de Unión a PDZ , Células Tumorales Cultivadas , Proteínas Señalizadoras YAPRESUMEN
The cathodic deposition of poly(styrene sulfonate) on nanoarchitectured TiO2 electrodes is explored by cyclic voltammetry and potentiostatic and galvanostatic experiments, showing a diffusion-controlled deposition described by Cottrell's law. The structure and composition of the polymer is evidenced by various spectroscopic techniques, including nuclear magnetic resonance, Fourier transform infrared, and X-ray photoelectron spectroscopy, and its morphology is studied by scanning electron microscopy. The average chain length can be estimated from the NMR spectra. The electropolymerization mechanism initiates by radical anion formation. The cycling behavior in half-cell batteries against Li metal is excellent, especially at high rates explored up to 10 C. The areal insertion capacity is above recent literature results, up to 80 µA h cm-2. The combination of normalized areal power density and areal energy density is one of the best reported in the literature.