Nusinersen ameliorates motor function and prevents motoneuron Cajal body disassembly and abnormal poly(A) RNA distribution in a SMA mouse model

Spinal muscular atrophy (SMA) is a devastating autosomal recessive neuromuscular disease characterized by degeneration of spinal cord alpha motor neurons (αMNs). SMA is caused by the homozygous deletion or mutation of the survival motor neuron 1 (SMN1) gene, resulting in reduced expression of SMN protein, which leads to αMN degeneration and muscle atrophy. The majority of transcripts of a second gene (SMN2) generate an alternative spliced isoform that lacks exon 7 and produces a truncated nonfunctional form of SMN. A major function of SMN is the biogenesis of spliceosomal snRNPs, which are essential components of the pre-mRNA splicing machinery, the spliceosome. In recent years, new potential therapies have been developed to increase SMN levels, including treatment with antisense oligonucleotides (ASOs). The ASO-nusinersen (Spinraza) promotes the inclusion of exon 7 in SMN2 transcripts and notably enhances the production of full-length SMN in mouse models of SMA. In this work, we used the intracerebroventricular injection of nusinersen in the SMN∆7 mouse model of SMA to evaluate the effects of this ASO on the behavior of Cajal bodies (CBs), nuclear structures involved in spliceosomal snRNP biogenesis, and the cellular distribution of polyadenylated mRNAs in αMNs. The administration of nusinersen at postnatal day (P) 1 normalized SMN expression in the spinal cord but not in skeletal muscle, rescued the growth curve and improved motor behavior at P12 (late symptomatic stage). Importantly, this ASO recovered the number of canonical CBs in MNs, significantly reduced the abnormal accumulation of polyadenylated RNAs in nuclear granules, and normalized the expression of the pre-mRNAs encoding chondrolectin and choline acetyltransferase, two key factors for αMN homeostasis. We propose that the splicing modulatory function of nusinersen in SMA αMN is mediated by the rescue of CB biogenesis, resulting in enhanced polyadenylated pre-mRNA transcription and splicing and nuclear export of mature mRNAs for translation. Our results support that the selective restoration of SMN expression in the spinal cord has a beneficial impact not only on αMNs but also on skeletal myofibers. However, the rescue of SMN expression in muscle appears to be necessary for the complete recovery of motor function.The authors wish to thank Raquel García-Ceballos for technical assistance and Alfonso Nieva for video editing. We are also grateful to Prof. A. I. Lamond (University of Dundee, UK) for anti-coilin antibody (204.10) and Prof. Larry Gerace (The Scripps Research Institute, La Jolla, USA) for anti-LaminA/C antibody. The authors are also indebted to Prof. Josep E. Esquerda for critical reading of the manuscript and helpful suggestions. This work was supported by the following grants: Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED, CB06/05/0037) Spain; Instituto de Investigación Sanitaria Valdecilla (IDIVAL, Next-Val 17/22), Santander, Spain; and Spanish Ministerio de Ciencia, Innovación y Universidades cofinanced by Fondo Europeo de Desarrollo Regional (FEDER) (RTI2018-099278-B-I00)

Xerostomia, the perception of general and oral health and health risk behaviours in people over 65 years of age

Background: This study investigated the association between xerostomia and health risk behaviours, general and oral health and quality of life. Methods: A cross-sectional study involving 800 adults over 65 years of age residing in Spain using a computerassisted telephone questionnaire. The severity of xerostomia was assessed through the Xerostomia Inventory (XI). Both univariate and adjusted multinomial logistic regression were used to determine the risk (OR) of xerostomia. Results: The sample comprised of 492 females (61.5%) and 308 males, with a mean age of 73.7 ± 5.8 years. Some, 30.7% had xerostomia: 25.6% mild, 4.8% moderate and 0.3% severe, the majority being female (34.8% vs 24%; p = 0.003). The mean XI was 24.6 ± 6.3 (95% CI 19.2–24.8) for those with poor health, whereas it was 17.4 ± 6.3 (95%CI 16.1–18.6) in those reporting very good health (p < 0.001). This difference was also observed in terms of oral health, with the XI mean recorded as 14.7 ± 10.7 for very poor oral health and 6.4 ± 5.4 for those with very good health (p = 0.002). Logistic regression showed that the highest OR for xerostomia was observed among adults with poor general health (2.81; 95%CI 1.8–4.3; p < 0.001) and for adjusted model the OR was still significant (2.18; 95%CI 1.4–3.4; p = 0.001). Those who needed help with household chores had 2.16 higher OR (95%CI 1.4–3.4; p = 0.001) and 1.69 (95%CI 1.1–2.7; p = 0.03) in the adjusted model. Females had a higher risk of suffering from xerostomia than males. Conclusion: The strong association between xerostomia and the general and oral health status of older adults justifies the need for early assessment and regular follow-up

Xerostomia, the perception of general and oral health and health risk behaviours in people over 65 years of age

Background: This study investigated the association between xerostomia and health risk behaviours, general and oral health and quality of life. Methods: A cross-sectional study involving 800 adults over 65 years of age residing in Spain using a computer-assisted telephone questionnaire. The severity of xerostomia was assessed through the Xerostomia Inventory (XI). Both univariate and adjusted multinomial logistic regression were used to determine the risk (OR) of xerostomia. Results: The sample comprised of 492 females (61.5%) and 308 males, with a mean age of 73.7 +/- 5.8 years. Some, 30.7% had xerostomia: 25.6% mild, 4.8% moderate and 0.3% severe, the majority being female (34.8% vs 24%; p = 0.003). The mean XI was 24.6 +/- 6.3 (95% CI 19.2-24.8) for those with poor health, whereas it was 17.4 +/- 6.3 (95%CI 16.1-18.6) in those reporting very good health (p < 0.001). This difference was also observed in terms of oral health, with the XI mean recorded as 14.7 +/- 10.7 for very poor oral health and 6.4 +/- 5.4 for those with very good health (p = 0.002). Logistic regression showed that the highest OR for xerostomia was observed among adults with poor general health (2.81; 95%CI 1.8-4.3; p < 0.001) and for adjusted model the OR was still significant (2.18; 95%CI 1.4-3.4; p = 0.001). Those who needed help with household chores had 2.16 higher OR (95%CI 1.4-3.4; p = 0.001) and 1.69 (95%CI 1.1-2.7; p = 0.03) in the adjusted model. Females had a higher risk of suffering from xerostomia than males. Conclusion: The strong association between xerostomia and the general and oral health status of older adults justifies the need for early assessment and regular follow-up

Assessing the environmental impacts of three different types of accommodations in Portugal and Spain by using an LCA approach

The tourism industry, affected by COVID-19, must reduce greenhouse gas emissions. This study evaluated the environmental impact of three hotels in coastal and mountainous regions of Spain and Portugal using Life Cycle Assessment (LCA). Data was gathered via surveys in the Greentour tool. Results indicate that the 2-star hotel (focused on cultural-urban tourism) has the highest impacts in most categories, except for CC, FRD, and POF indicators. The 3-star hotel (beach tourism) contributes the most to CC and FRD indicators, while the hostel (nature-religious tourism) has the highest value in the POF indicator. LCA findings reveal that diesel consumption in the hostel and electricity usage in both the 2-star and 3-star hotels are major contributors to environmental impacts across various categories. Overall, evidence suggests that fossil fuel and electricity usage significantly affect tourism activities environmentally. Interestingly, this study highlights that a 2-star hotel can have a higher carbon footprint (CC indicator) compared to a 3-star hotel, challenging the notion that higher star ratings imply lower environmental impact.This research was funded by the INTERREG SUDOE Programme, grant number GREENTOUR: Circular Economy and Sustainable Tourism in Destinations of the SUDOE space (SOE4/P5/E1089)

Higher COVID-19 pneumonia risk associated with anti-IFN-α than with anti-IFN-ω auto-Abs in children

We found that 19 (10.4%) of 183 unvaccinated children hospitalized for COVID-19 pneumonia had autoantibodies (auto-Abs) neutralizing type I IFNs (IFN-alpha 2 in 10 patients: IFN-alpha 2 only in three, IFN-alpha 2 plus IFN-omega in five, and IFN-alpha 2, IFN-omega plus IFN-beta in two; IFN-omega only in nine patients). Seven children (3.8%) had Abs neutralizing at least 10 ng/ml of one IFN, whereas the other 12 (6.6%) had Abs neutralizing only 100 pg/ml. The auto-Abs neutralized both unglycosylated and glycosylated IFNs. We also detected auto-Abs neutralizing 100 pg/ml IFN-alpha 2 in 4 of 2,267 uninfected children (0.2%) and auto-Abs neutralizing IFN-omega in 45 children (2%). The odds ratios (ORs) for life-threatening COVID-19 pneumonia were, therefore, higher for auto-Abs neutralizing IFN-alpha 2 only (OR [95% CI] = 67.6 [5.7-9,196.6]) than for auto-Abs neutralizing IFN-. only (OR [95% CI] = 2.6 [1.2-5.3]). ORs were also higher for auto-Abs neutralizing high concentrations (OR [95% CI] = 12.9 [4.6-35.9]) than for those neutralizing low concentrations (OR [95% CI] = 5.5 [3.1-9.6]) of IFN-omega and/or IFN-alpha 2

Hepatic levels of S-adenosylmethionine regulate the adaptive response to fasting

26 p.-6 fig.-1 tab.-1 graph. abst.There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)—the principal methyl donor—acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, β-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive β-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.M.V.-R. is supported by Proyecto PID2020-119486RB-100 (funded by MCIN/AEI/10.13039/501100011033), Gilead Sciences International Research Scholars Program in Liver Disease, Acción Estratégica Ciberehd Emergentes 2018 (ISCIII), Fundación BBVA, HORIZON-TMA-MSCA-Doctoral Networks 2021 (101073094), and Redes de Investigación 2022 (RED2022-134485-T). M.L.M.-C. is supported by La CAIXA Foundation (LCF/PR/HP17/52190004), Proyecto PID2020-117116RB-I00 (funded by MCIN/AEI/10.13039/501100011033), Ayudas Fundación BBVA a equipos de investigación científica (Umbrella 2018), and AECC Scientific Foundation (Rare Cancers 2017). A.W. is supported by RTI2018-097503-B-I00 and PID2021-127169OB-I00, (funded by MCIN/AEI/10.13039/501100011033) and by “ERDF A way of making Europe,” Xunta de Galicia (Ayudas PRO-ERC), Fundación Mutua Madrileña, and European Community’s H2020 Framework Programme (ERC Consolidator grant no. 865157 and MSCA Doctoral Networks 2021 no. 101073094). C.M. is supported by CIBERNED. P.A. is supported by Ayudas para apoyar grupos de investigación del sistema Universitario Vasco (IT1476-22), PID2021-124425OB-I00 (funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe,” MCI/UE/ISCiii [PMP21/00080], and UPV/EHU [COLAB20/01]). M.F. and M.G.B. are supported by PID2019-105739GB-I00 and PID2020-115472GB-I00, respectively (funded by MCIN/AEI/10.13039/501100011033). M.G.B. is supported by Xunta de Galicia (ED431C 2019/013). C.A., T.L.-D., and J.B.-V. are recipients of pre-doctoral fellowships from Xunta de Galicia (ED481A-2020/046, ED481A-2018/042, and ED481A 2021/244, respectively). T.C.D. is supported by Fundación Científica AECC. A.T.-R. is a recipient of a pre-doctoral fellowship from Fundación Científica AECC. S.V.A. and C.R. are recipients of Margarita Salas postdoc grants under the “Plan de Recuperación Transformación” program funded by the Spanish Ministry of Universities with European Union’s NextGeneration EU funds (2021/PER/00020 and MU-21-UP2021-03071902373A, respectively). T.C.D., A.S.-R., and M.T.-C. are recipients of Ayuda RYC2020-029316-I, PRE2019/088960, and BES-2016/078493, respectively, supported by MCIN/AEI/10.13039/501100011033 and by El FSE invierte en tu futuro. S.L.-O. is a recipient of a pre-doctoral fellowship from the Departamento de Educación del Gobierno Vasco (PRE_2018_1_0372). P.A.-G. is recipient of a FPU pre-doctoral fellowship from the Ministry of Education (FPU19/02704). CIC bioGUNE is supported by Ayuda CEX2021-001136-S financiada por MCIN/AEI/10.13039/501100011033. A.B.-C. was funded by predoctoral contract PFIS (FI19/00240) from Instituto de Salud Carlos III (ISCIII) co-funded by Fondo Social Europeo (FSE), and A.D.-L. was funded by contract Juan Rodés (JR17/00016) from ISCIII. A.B.-C. is a Miguel Servet researcher (CPII22/00008) from ISCIII.Peer reviewe

Food waste management during the COVID-19 outbreak: a holistic climate, economic and nutritional approach

Improving the food supply chain efficiency has been identified as an essential means to enhance food security, while reducing pressure on natural resources. Adequate food loss and waste (FLW) management has been proposed as an approach to meet these objectives. The main hypothesis of this study is to consider that the "strong fluctuations and short-term changes" on eating habits may have major consequences on potential FLW generation and management, as well as on GHG emissions, all taking into account the nutritional and the economic cost. Due to the exceptional lockdown measures imposed by the Spanish government, as a consequence of the emerging coronavirus disease, COVID-19, food production and consumption systems have undergone significant changes, which must be properly studied in order to propose strategies from the lessons learned. Taking Spain as a case study, the methodological approach included a deep analysis of the inputs and outputs of the Spanish food basket, the supply chain by means of a Material Flow Analysis, as well as an economic and comprehensive nutritional assessment, all under a life cycle thinking approach. The results reveal that during the first weeks of the COVID-19 lockdown, there was no significant adjustment in overall FLW generation, but a partial reallocation from extra-domestic consumption to households occurred (12% increase in household FLW). Moreover, the economic impact (+11%), GHG emissions (+10%), and the nutritional content (-8%) complete the multivariable impact profile that the COVID-19 outbreak had on FLW generation and management. Accordingly, this study once again highlights that measures aimed at reducing FLW, particularly in the household sector, are critical to make better use of food surpluses and FLW prevention and control, allowing us to confront future unforeseen scenarios.The authors are grateful for the funding of the Spanish Ministry of Economy and Competitiveness through the CERES-PROCON Project CTM2016-76176 (AEI/FEDER, UE) and the KAIROS-BIOCIR Project PID2019-104925RB (AEO/FEDER, UE)

Foro de Alumnos de Derecho

Las actividades del Foro de Alumnos de Derecho (FAD) se han desarrollado en la Facultad de Derecho de la Universidad de Valladolid. Aunque promovidas en un principio por catorce profesores de distintas áreas de conocimiento, progresivamente se han implicado un mayor número de docentes de la Facultad citada así como eminentes juristas de la provincia. Se han celebrado diversos seminarios y un cine-club jurídico, en los que los alumnos inscritos -veintiocho de distintos cursos de la licenciatura- y otros muchos que han asistido a los mismos, han podido acercarse a la utilización de la lógica argumentativa, básica para el futuro jurista. Se ha logrado así que se produzca un acercamiento dentro de los cuerpos docente y discente de la Facultad de Derecho, y entre ellos. La experiencia ha servido para que los estudiantes comprendan la dimensión axiológica que rodea la ciencia del derecho, con el asesoramiento de reconocidos especialistas en relación con cada una de las materias tratadas: nacionalismo, deontología jurídica, etcétera. Aunque este trabajo no se proyecta en un material tangible, muestra su utilidad como una relevante técnica pedagógica.Junta de Castilla y León. Consejería de Educación y CulturaCastilla y LeónES

‘Small-scale’ tourism versus traditional tourism: Which will be the new key to achieve the desired sustainable tourism?

The tourism sector after COVID-19 has raised different concerns that have lead to a development towards a more sustainable model of tourism. After the health crisis, the increase in environmental awareness of tourists has become evident. In this context, the great paradigm of "small-scale" tourism has been developed as opposed to traditional tourism. The present work seeks to contribute to sustainable development in the Spanish tourism sector, comparing a hostel in Cantabria (considered as "small scale" /religious tourism) and a hotel in Lloret de Mar (considered as a traditional tourism) one using the Life Cycle Assessment (LCA) methodology to verify advantages and disadvantages of both types of tourism. The functional unit (FU) used was "per guest night with breakfast included". The results have revealed similar results for both establishments in all impact categories, as can be seen in its contribution to Climate Change (4.41 kg CO2 eq./FU caused by the hotel and 4.78 kg CO2 eq./FU by the hostel). The electricity consumption and the impact of the breakfast in the hostel were identified as main contributors to environmental burdens (with 76.72 % of the hotel's impact to climate change and 77.36 % for the hostel); hence, improvement opportunities envisaged were focused on these critical points. On the one hand, a biomass boiler, a solar water-heating system and a hybrid solar/biomass heating are considered a more sustainable alternatives related to electricity. Natural gas and diesel Consumption, respectively. On the other hand, oatmeal, Greek yoghurt and berries are good options for a breakfast with a reduced environmental impact. It is also important to implement responsible and green practices in order to achieve more environmentally sustainable alternative and traditional accommodations. Therefore, it can be concluded by stating that LCA is a tool capable of identifying and studying the processes with the highest environmental impact in order to find out the most sustainable form of tourism.This research was funded by the INTERREG SUDOE Programme, grant number GREENTOUR: Circular Economy and Sustainable Tourism in Destinations of the SUDOE space (SOE4/P5/E1089). The authors of CESAM acknowledge Portuguese Foundation for Science and Technology (FCT)/MCTES for the contracts CEECIND/02174/2017 and CEECIND/00143/2017, and for the financial support to CESAM (UIDB/50017/2020+UIDP/50017/2020+LA/P/0094/2020), through national funds. The author of Galician Water Research Foundation (Cetaqua Galicia) belong to the Galician Competitive Research Group GRC (IN845A-2), programme co-funded by FEDER. The authors at the UNESCO Chair want to hereby state that the authors are responsible for the choice and presentation of information contained in this paper, as well as for the opinions expressed therein, which are not necessarily those of UNESCO and do not commit this Organization

Arte y medio ambiente. Comunicación y arte contemporáneo al servicio del desarrollo sostenible

Depto. de Teorías y Análisis de la ComunicaciónFac. de Ciencias de la InformaciónFALSEsubmitte