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Resumen: Introducción: La atrofia muscular espinal 5q (AME) es una enfermedad genética neurodegenerativa que afecta a las motoneuronas alfa produciendo debilidad progresiva. Actualmente se precisan nuevas herramientas que permitan medir y caracterizar con precisión la progresión de la enfermedad y la eficacia de los nuevos tratamientos. El objetivo del presente trabajo es realizar la validación preliminar de un nuevo teclado inteligente (Neuromyotype) capaz de medir la fuerza y la velocidad de tecleo en pacientes con AME. Material y métodos: Se incluyeron 22 pacientes mayores de 15 años con AME y 26 controles sanos. En ellos se realizaron tres mediciones con el teclado (fuerza máxima, tiempo de ejecución de una tarea aleatoria de tecleo, tiempo de ejecución de una tarea secuencial de tecleo) y el tiempo para completar el Nine-Hole Peg Test (9HPT). A los pacientes se les administraron además unas escalas motoras (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb Module [RULM]) y funcionales (Egen Klassification [EK2] y la versión revisada de Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]). Se analizaron la viabilidad y la validez de constructo de Neuromyotype, midiendo el poder discriminativo entre pacientes y controles (mediante curvas ROC y el estadístico de Bangdiwala) y entre los distintos tipos funcionales de AME (walker, sitter y non-sitter) y su correlación con el resto de escalas motoras. Resultados: Las mediciones del teclado se pudieron realizar en todos los pacientes, al contrario que el resto de las escalas. Su administración fue rápida y sencilla. Las tres variables del teclado discriminaron muy bien entre pacientes y controles, siendo la fuerza (ROC = 0,963) la que mejor diferencia de las tres, igualando al 9HPT (ROC = 0,966). También mostraron una buena capacidad para diferenciar por tipo funcional (especialmente a los non-sitter de los sitter y walker), siendo el tiempo secuencial (B = 0,83) la herramienta que mejor discriminaba entre los tres grupos por encima del resto de escalas motoras. Todas las escalas motoras y funcionales mostraron correlaciones fuertes o muy fuertes entre sí (rs = 0,71-0,99), con la fuerza correlacionando mejor con escalas motoras y las variables de tiempo con las escalas funcionales. Conclusión: Este estudio demuestra la viabilidad y la validez de Neuromyotype para la valoración de pacientes adolescentes y adultos con AME. Los datos obtenidos con esta herramienta podrían ser de gran relevancia clínica, ahorrando tiempo y recursos en comparación con el resto de las escalas. Abstract: Introduction: Spinal muscular atrophy 5q (SMA) is a genetic neurodegenerative disease that affects alpha motor neurons producing progressive weakness. New outcome measures are currently required to accurately characterize the disease progression and the efficacy of new available treatments. The objective of this work is to preliminarily validate a new intelligent keyboard (Neuromyotype) measuring typing strength and speed in patients with SMA. Material and methods: Twenty two SMA patients older than 15 years, and 26 healthy controls were included. Three measurements were obtained with the keyboard (maximum strength, execution time of a random typing task, execution time of a sequential typing task) together with the time to complete the Nine-Hole Peg Test (9HPT). Patients were also administered motor (Hammersmith Functional Motor Scale Expanded [HFMSE], Revised Upper Limb Module [RULM]), and functional scales (Egen Klassification [EK2] and the revised version of Amyotrophic Lateral Sclerosis Functional Rating Scale [ALSFRS-R]). The viability and construct validity of the Neuromyotype were analyzed, measuring the discriminative power between patients and controls (using ROC curves and the Bangdiwala statistic), between the different functional types of SMA (walker, sitter and non-sitter) and their correlation with the rest of motor scales. Results: Neuromyotype measurements could be performed in all patients, unlike the rest of the scales. Its administration was quick and easy. The 3 variables on the keyboard discriminated very well between patients and controls, with strength (ROC = 0.963) being the one that best differentiates from the 3, equaling 9HPT (ROC = 0.966). They also showed a good ability to differentiate by functional type (especially non-sitters from sitters and walkers), with sequential time (B = 0.83) being the tool that best discriminates between the three groups above the rest of motor scales. All motor and functional scales showed strong or very strong correlations with each other (rs = 0.71-0.99), with strength correlating better with motor scales and timed variables with functional scales. Conclusion: This study shows the feasibility and validity of Neuromyotype for the evaluation of adolescent and adult patients with SMA. Data obtained with this tool could be of great clinical relevance, saving time and resources compared to the rest of the scales.

Introduction: This study investigates the impact of smart refrigerators on the logistics and management of biological samples, emphasizing the critical phases of transport and storage to enhance the pre-analytical quality of blood samples. Efficient sample management is crucial for ensuring diagnostic accuracy. Objective: The primary objective is to evaluate the efficiency of smart refrigerators equipped with cloud technology in optimizing the transport and storage of biological samples. The secondary objective is to assess healthcare personnel's perceptions and satisfaction with these technologies. Method: A longitudinal prospective analysis was conducted to assess both the quantitative incidence of pre-analytical errors and the qualitative perceptions of healthcare personnel regarding these technologies. Samples were collected from six primary care centers within the Elche General Health Department, with one center using smart refrigerators and five using conventional methods. The refrigerators featured GPS, real-time temperature sensors, alert systems for cold chain interruptions, and RFID technology. Training on refrigerator use, systematic data collection on pre-analytical errors, and surveys and semi-structured interviews with healthcare personnel were conducted. Descriptive methods and hypothesis testing, including Z-statistics and logistic regression models, were used for statistical analysis. Results: The analysis revealed a significant decrease in the incidence of coagulated and hemolyzed samples at the center using smart refrigerators. Specifically, the rate of coagulated samples was reduced by 69.39%, while hemolyzed samples decreased by 78.12%. This improvement contrasts with trends observed in centers using conventional practices. A significant 94.62% of the staff reported a positive experience with the smart refrigerators, highlighting high satisfaction and the importance of stricter control in handling and transporting samples to prevent errors. Conclusions: The use of smart refrigerators in the transport and storage of biological samples effectively improves the pre-analytical quality of blood samples, reduces pre-analytical errors, and enhances staff satisfaction. These findings underscore the importance of incorporating advanced technologies in the management of biological samples in primary care settings.

Abstract Background The eukaryotic translation initiation protein eIF5A is a highly conserved and essential factor that plays a critical role in different physiological and pathological processes including stress response and cancer. Different proteomic studies suggest that eIF5A may be a small ubiquitin-like modifier (SUMO) substrate, but whether eIF5A is indeed SUMOylated and how relevant is this modification for eIF5A activities are still unknown. Methods SUMOylation was evaluated using in vitro SUMOylation assays, Histidine-tagged proteins purification from His6–SUMO2 transfected cells, and isolation of endogenously SUMOylated proteins using SUMO-binding entities (SUBES). Mutants were engineered by site-directed mutagenesis. Protein stability was measured by a cycloheximide chase assay. Protein localization was determined using immunofluorescence and cellular fractionation assays. The ability of eIF5A1 constructs to complement the growth of Saccharomyces cerevisiae strains harboring thermosensitive mutants of a yeast EIF5A homolog gene (HYP2) was analyzed. The polysome profile and the formation of stress granules in cells expressing Pab1–GFP (a stress granule marker) by immunofluorescence were determined in yeast cells subjected to heat shock. Cell growth and migration of pancreatic ductal adenocarcinoma PANC-1 cells overexpressing different eIF5A1 constructs were evaluated using crystal violet staining and transwell inserts, respectively. Statistical analysis was performed with GraphPad Software, using unpaired Student’s t-test, or one-way or two-way analysis of variance (ANOVA). Results We found that eIF5A is modified by SUMO2 in vitro, in transfected cells and under endogenous conditions, revealing its physiological relevance. We identified several SUMO sites in eIF5A and found that SUMOylation modulates both the stability and the localization of eIF5A in mammalian cells. Interestingly, the SUMOylation of eIF5A responds to specific stresses, indicating that it is a regulated process. SUMOylation of eIF5A is conserved in yeast, the eIF5A SUMOylation mutants are unable to completely suppress the defects of HYP2 mutants, and SUMOylation of eIF5A is important for both stress granules formation and disassembly of polysomes induced by heat-shock. Moreover, mutation of the SUMOylation sites in eIF5A abolishes its promigratory and proproliferative activities in PANC-1 cells. Conclusions SUMO2 conjugation to eIF5A is a stress-induced response implicated in the adaptation of yeast cells to heat-shock stress and required to promote the growth and migration of pancreatic ductal adenocarcinoma cells. Graphical Abstract

Abstract Background Eukaryotic Initiation Factor 5A (eIF-5A), an essential translation factor, is post-translationally activated by the polyamine spermidine. Two human genes encode eIF-5A, being eIF5-A1 constitutively expressed whereas eIF5-A2 is frequently found overexpressed in human tumours. The contribution of both isoforms with regard to cellular proliferation and invasion in non-small cell lung cancer remains to be characterized. Methods We have evaluated the use of eIF-5A2 gene as prognosis marker in lung adenocarcinoma (LUAD) patients and validated in immunocompromised mice. We have used cell migration and cell proliferation assays in LUAD lines after silencing each eIF-5A isoform to monitor their contribution to both phenotypes. Cytoskeleton alterations were analysed in the same cells by rhodamine-phalloidin staining and fluorescence microscopy. Polysome profiles were used to monitor the effect of eIF-5A2 overexpression on translation. Western blotting was used to study the levels of eIF-5A2 client proteins involved in migration upon TGFB1 stimulation. Finally, we have co-localized eIF-5A2 with puromycin to visualize the subcellular pattern of actively translating ribosomes. Results We describe the differential functions of both eIF-5A isoforms, to show that eIF5-A2 properties on cell proliferation and migration are coincident with its features as a poor prognosis marker. Silencing of eIF-5A2 leads to more dramatic consequences of cellular proliferation and migration compared to eIF-5A1. Overexpression of eIF-5A2 leads to enhanced global translation. We also show that TGFβ signalling enhances the expression and activity of eIF-5A2 which promotes the translation of polyproline rich proteins involved in cytoskeleton and motility features as it is the case of Fibronectin, SNAI1, Ezrin and FHOD1. With the use of puromycin labelling we have co-localized active ribosomes with eIF-5A2 not only in cytosol but also in areas of cellular protrusion. We have shown the bulk invasive capacity of cells overexpressing eIF-5A2 in mice. Conclusions We propose the existence of a coordinated temporal and positional interaction between TFGB and eIF-5A2 pathways to promote cell migration in NSCLC. We suggest that the co-localization of actively translating ribosomes with hypusinated eIF-5A2 facilitates the translation of key proteins not only in the cytosol but also in areas of cellular protrusion. Video Abstract

Abstract Background JUNB transcription factor contributes to the formation of the ubiquitous transcriptional complex AP-1 involved in the control of many physiological and disease-associated functions. The roles of JUNB in the control of cell division and tumorigenic processes are acknowledged but still unclear. Results Here, we report the results of combined transcriptomic, genomic, and functional studies showing that JUNB promotes cell cycle progression via induction of cyclin E1 and repression of transforming growth factor (TGF)-β2 genes. We also show that high levels of JUNB switch the response of TGF-β2 stimulation from an antiproliferative to a pro-invasive one, induce endogenous TGF-β2 production by promoting TGF-β2 mRNA translation, and enhance tumor growth and metastasis in mice. Moreover, tumor genomic data indicate that JUNB amplification associates with poor prognosis in breast and ovarian cancer patients. Conclusions Our results reveal novel functions for JUNB in cell proliferation and tumor aggressiveness through regulation of cyclin E1 and TGF-β2 expression, which might be exploited for cancer prognosis and therapy.

RESUMO A partir dos Estudos Sociais da Infância e da Psicologia do Desenvolvimento, o presente estudo teve como objetivo investigar a experiência das crianças de Salvador e região metropolitana no que diz respeito à organização do cotidiano durante a pandemia da Covid-19, considerando como percebem a passagem do tempo e como têm administrado o tempo livre e institucionalizado dentro do espaço doméstico. Os resultados apontam para um aumento significativo no tempo gasto em telas e/ou dispositivos eletrônicos, a diminuição de atividades físicas e a sensação de tédio por parte de algumas crianças. Essa sensação precedeu a reorganização de suas rotinas com as principais atividades que exerciam antes da pandemia – atividades escolares, extracurriculares e de lazer –, majoritariamente em formato remoto.

Las cosas empiezan a cambiar, la nueva conciencia ecológica nos permite ver con claridad y evidencia la interdependenciay la unidad entre todas las cosas, y conduce nuestra búsqueda hacia una nueva tradición, tras las diferentes vanguardias que expresa el postmodernismo. Y esta nueva conciencia nos permite dar un paso más en la ampliación de nuestra dimensión ética, para abarcar ahora el mundo natural y humano. Y desde la ética ecológica, llegar a la Justicia, a la exigencia y la construcción de una Justicia ecológica, porque una teoría de la justicia debe afrontar los problemas prácticos de su tiempo, porque a la Justicia corresponde dar a cada cual lo suyo, y precisamente en la Naturaleza están los fundamentos de las necesidades humanas y ecológicas, ahí está también lo que a cada cual nos corresponde.

O presente artigo debate a noção de sustentabilidade à luz da discussão conduzida por Amartya Sen sobre desenvolvimento humano e qualidade de vida, buscando redimensionar o papel e o valor do humano em meio aos desafios do desenvolvimento. O texto tenta refletir sobre a contribuição para uma socioecologia nas obras de Sen, e do sentido intelectual presumido de ser um antídoto às abordagens economicistas que codificaram a natureza como “reino das mercadorias” ao mesmo tempo em que cercaram o componente humano de profunda aridez de significado e valor explicativo.

Tal como afirma Michel Chion en el prólogo de su obra Cómo se escribe un guión, los buenos guionistas no surgen por generación espontánea, nacen de la intuición de las normas, de la profesionalidad adquirida por la experiencia y del estudio".

Sustentabilidade; Desenvolvimento; Socioecologia; Ética; Qualidade de vida;

Species of the genus Crocus are found over a wide range of climatic areas. In natural habitats, these geophytes diverge in the flowering strategies. This variability was assessed by analyzing the flowering traits of the Spanish collection of wild crocuses, preserved in the Bank of Plant Germplasm of Cuenca. Plants of the seven Spanish species were analyzed both in their natural environments (58 native populations) and in common garden experiments (112 accessions). Differences among species observed in the native habitats were maintained under uniform environmental conditions, suggesting a genetic basis for flowering mechanisms. Two eco-morphological types, autumn- and spring-flowering species, share similar patterns of floral induction and differentiation period in summer. The optimal temperature for this process was 23 °C for both types. Unlike Irano-Turanian crocuses, spring-flowering Spanish species do not require low winter temperatures for flower elongation. Hysteranthous crocuses flower in autumn prior to leaf elongation. We conclude that the variability in flowering traits in crocuses is related to the genetic and environmental regulation of flower primordia differentiation and elongation prior to emergence above the soil surface. The elucidation of the physiological differences between eco-morphological types of crocuses: synanthous with cold requirements and synanthous and hysteranthous without cold requirements, unlocks a new approach to the flowering evolution of geophytes in Mediterranean regions. Crocus species can serve both as a new model in the study of the molecular basis of hysteranthy and for the purposes of developing the molecular markers for desirable flowering traits.

ABSTRACT Cover crops may improve vineyard soil properties, grapevine nutrient status and berry composition, however, factors such as cover crop type, annual rainfall, climate and irrigation may change their effects on vineyards. From 2008 to 2011, the effects of a non-permanent cover crop and two pruning techniques on soil as well as vine nutrients and grapevine performance of two vineyards (cv. Tempranillo and cv. Bobal) were evaluated. For that purpose, two legumes were sown in inter-rows of hand-pruned vines in February and were tilled at flowering. Soil tillage, or cover cropping, was combined with either light pruning or severe pruning to study foliar nutrient variations. Soil N, P, K and total organic carbon (TOC) were determined in samples taken from the Ap1 horizon in January prior to vine pruning. Foliar N, P, K contents were measured in leaves sampled upon grape veraison. The differences between vineyards with cover cropping and bare soils suggest that legumes positively affected soil N (1.55 vs. 1.68 g kg−1 and 1.49 vs. 1.76 g kg−1 in Bobal and Tempranillo vineyards, respectively) and soil organic matter (SOM) (12.5 vs. 15.5 g kg−1 and 12.9 vs. 17.2 g kg−1 in Bobal and Tempranillo vineyards, respectively). The use of cover crops did not affect grapevine yields nor quality of Bobal and Tempranillo berry . Cover crops, or light pruning, did not alter the foliar N, P, K contents of both cultivars since their concentrations were similar to those found in the leaves from vineyards with soil tillage or severe pruning.

• Water stress is likely the main driver of pine mortality in the studied ecotone in Central Spain. • Higher tree sensitivity to spring precipitation and microsites with more water availability increase tree survival. • Drought tolerance may determine shifts in species dominance in the studied ecotone. Drought-induced tree decline and accelerated mortality under global change threaten forests worldwide. Identifying environmental and structural factors driving tree mortality of species with different ecology is essential to understand forest dynamics. We compared three coniferous species and trees with different health status (i.e. healthy, declining and dead) on a xeric Mediterranean ecotone where Pinus pinaster shows widespread decline (defoliation, mistletoe, high mortality) while more drought-tolerant Pinus pinea and Juniperus oxycedrus do not. We analysed individual tree and stand characteristics and regeneration of all species to understand how different abiotic factors at different time scales affected stand species dynamics in relation to tree decline and mortality. Only dead and declining pine trees showed recent multiannual negative radial growth trends. The growth decline started after two extreme droughts, being 10 years longer in the declining species, P. pinaster, than in non-declining P. pinea. We observed no signs of decline or mortality in the most drought-tolerant species, J. oxycedrus. Variables related to moisture availability, like stand dominant height and the tree response to precipitation, increased survival probability in P. pinaster but not in P. pinea. Despite P. pinaster dominating the canopy, its regeneration was very scarce and less abundant than that of co-occurring more drought-tolerant species. Our results suggest that drought-induced mortality was related to species-specific sensitivity to water stress and may be inducing compositional changes towards dominance of more drought-tolerant species. Consequently, at its lower elevation limit P. pinaster might be able to persist only in microsites with higher moisture availability. [ABSTRACT FROM AUTHOR]