USP49 deubiquitinase regulates the mitotic spindle checkpoint and prevents aneuploidy.

The spindle assembly checkpoint (SAC) is an essential mechanism that ensures the accurate chromosome segregation during mitosis, thus preventing genomic instability. Deubiquitinases have emerged as key regulators of the SAC, mainly by determining the fate of proteins during cell cycle progression. Here, we identify USP49 deubiquitinase as a novel regulator of the spindle checkpoint. We show that loss of USP49 in different cancer cell lines impairs proliferation and increases aneuploidy. In addition, USP49-depleted cells overcome the arrest induced by the SAC in the presence of nocodazole. Finally, we report new binding partners of USP49, including ribophorin 1, USP44, and different centrins.We thank A.P. Ugalde, D. Rodríguez, J.G. Pérez-Silva, Y. Español and F. Rodríguez for helpful comments and advice. We also thank S.A. Miranda, D. Álvarez-Puente and C. Garabaya for excellent technical assistance, as well as the staff of the scientific core facilities from the University of Oviedo (Unidad de Ensayos Biotecnológicos y Biomédicos, Servicios Científico-Técnicos). This work was supported by the Ministerio de Ciencia e Innovación (SAF2017-87655-R, PDI2020-118394RB-100 and PGC2018- 097019-B-I00), “la Caixa” Banking Foundation (project code HR17-00247), and the European Research Council (742067, DeAge). The IUOPA is funded by the Asturian Government and Fundación Cajastur-Liberbank.S

Frecuencia y severidad de los síntomas en pacientes con Fibromialgia y Migraña

Objetivos: estimar la frecuencia de migraña en pacientes con fibromialgia (FM). Describir y comparar características clínicas, socio demográficas y severidad de los síntomas de FM, según presencia o ausencia de migraña. Materiales y métodos: estudio analítico, observacional, transversal. Incluyó pacientes mayores de 18 años, de ambos sexos con diagnóstico de FM según criterios ACR 2010 de un centro reumatológico público de Argentina entre enero de 2019 y marzo de 2020. Pacientes con otras enfermedades reumatológicas concomitantes fueron excluidos. Se utilizó criterios IHS (International Headache Society) para diagnóstico de migraña, FIQ (fibromyalgia Impact Questionnaire) para evaluar severidad de los síntomas. Resultados: se incluyeron 59 pacientes, 99% eran mujeres. El 40.68% de los pacientes presentaba migraña. En los pacientes con migraña, la mediana de puntaje del FIQ fue 70.35 (RIC: 63.16-78.76) vs 53.91 (RIC: 37.93-66.05) en el grupo sin migraña, siendo esta diferencia estadísticamente significativa (p<0.01). El análisis mutivariado mostró al mayor puntaje del FIQ y de ansiedad, asociados de forma significativa e independiente con migraña (OR 1.048, IC 95%1.005-1.093); OR 1.189, IC 95%1.033-1.368, respectivamente. Conclusiones: la migraña es frecuente en pacientes con FM, y la severidad de los síntomas y la ansiedad serían más pronunciados en este grupo de pacientes

Implications on Mineral Elements, Sugars and Fatty Acids Accumulation in Tissues

Funding Information: This work received funding from PDR2020-101-030734 and Fundação para a Ciência e a Tecnologia, I.P. (FCT), Portugal, through the research units UIDB/04035/2020 (GeoBioTec), UIDB/00239/2020 (CEF) and UID/FIS/04559/2020 (LIBPhys) from the FCT/MCTES/PIDDAC. This work was further supported by the grant of Fundação para a Ciência e Tecnologia (FCT) UI/BD/150718/2020. Publisher Copyright: © 2022 by the authors.Following an agronomic approach for the Ca enrichment of Rocha pears, this study aimed to assess the interactions between mineral nutrients in fruit tissues at harvest and after storage for 5 months and to characterize the implications on the profile of sugars and fatty acids (FA). A total of seven foliar sprays (with concentrations of 0.1–0.6 kg·ha−1 Ca(NO3)2 and 0.8–8 kg·ha−1 CaCl2) were applied to pear trees. After harvest, the fruits were stored for 5 months, in environmentally controlled chambers, and the mineral contents in five regions (on the equatorial section) of the fruits were assessed, while the sugar and FA content were quantified. For both dates, all foliar sprayed treatments, at different extends, increased Ca content in the center and near the epidermis of Rocha pear fruits and the levels of K, Mn, Fe, Zn and Cu also varied. At harvest, the Ca treatments did not affect the levels of sucrose, glucose, fructose and sorbitol and, after storage, their concentrations remained higher in Ca-treated fruits. Additionally, the tendency of the relative proportions of FA was C18:2 > C18:1 > C16:0 > C18:3 > C18:0 > chains inferior to 16 C ( C16:0 > C18:3 > C18:0 > C18:1 > chains inferior to 16 C (<16:0). It is concluded that the heterogeneous distribution of Ca in the tissues of Rocha pear fruits results from its absorption in the peel after Ca(NO3)2 and CaCl2 sprays and from the xylemic flux in the core prior to maturity. Additionally, the hydrolysis of complex polysaccharides affects the contents of simpler sugars during maturation, ripening and senescence, while storage decreases the amount of total fatty acids (TFA), but the double bond index (DBI) indicate that cell membrane fluidity remains unaffected.publishersversionpublishe

Mineral Monitorization in Different Tissues of Solanum tuberosum L. during Calcium Biofortification Process

Funding Information: This work received funding from PDR2020-101-030719 and the Fundação para a Ciência e a Tecnologia, I.P. (FCT), Portugal, through the research units UIDP/04035/2020 (GeoBioTec), UIDB/00239/2020 (CEF), and UID/FIS/04559/2013 (LIBPhys). This work was further supported by the grant of the Fundação para a Ciência e Tecnologia (FCT) UI/BD/150806/2020. Publisher Copyright: © 2022 by the authors.Calcium is one of the 16 essential elements for plants, being required as Ca2+ and being involved in several fundamental processes (namely, in the stability and integrity of the cell wall, the development of plant tissue, cell division, and in stress responses). Moreover, Ca plays an important role in potato production. In this context, this study aimed to monitor the culture development (in situ and using an unmanned aerial vehicle (UAV)) and the mineral content of four essential elements (Ca, P, K, and S) in different organs of Solanum tuberosum L. (roots, stems, leaves, and tubers) during a calcium biofortification process, carried out with two types of solutions (CaCl2 and Ca-EDTA) with two concentrations (12 and 24 kg∙ha−1). The calcium content generally increased in the S. tuberosum L. organs of both varieties and showed, after the last foliar application, an increase in Ca content that varied between 5.7–95.6% and 20.7–33%, for the Picasso and Agria varieties, respectively. The patterns of accumulation in both varieties during the biofortification process were different between the variety and mineral element. Regarding the quality analysis carried out during the development of the tubers, only the Agria variety was suitable for industrial processing after the last foliar application.publishersversionpublishe

Mineral Interaction in Biofortified Tomatoes (Lycopersicum esculentum L.) with Magnesium

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Foliar Spraying of Solanum tuberosum L. with CaCl2 and Ca(NO3)2: Interactions with Nutrients Accumulation in Tubers

Calcium is essential for plants, yet as its mobility is limited, the understanding of the rate of Ca2+ accumulation and deposition in tissues of tubers, as well as the interactions with other critical nutrients prompted this study. To assess the interactions and differential accumulation of micro and macronutrients in the tissues of tubers, Solanum tuberosum L. varieties Agria and Rossi were cultivated and, after the beginning of tuberization, four foliar sprayings (at 8–10 day intervals) with CaCl2 (3 and 6 kg ha1) or Ca(NO3)2 (2 and 4 kg ha1) solutions were performed. It was found that both fertilizers increased Ca accumulation in tubers (mostly in the parenchyma tissues located in the center of the equatorial region). The functioning of the photosynthetic apparatus was not affected until the 3rd application but was somewhat affected when approaching the end of the crop cycle (after the 4th application), although the lower dose of CaCl2 seemed to improve the photochemical use of energy, particularly when compared with the greater dose of Ca(NO3)2. Still, none of these impacts modified tuber height and diameter. Following the increased accumulation of Ca, in the tubers of both varieties, the mean contents of P, K, Na, Fe, and Zn revealed different accumulation patterns. Moreover, accumulation of K, Fe, Mn, and Zn prevailed in the epidermis, displaying a contrasting pattern relative to Ca. Therefore, Ca accumulation revealed a heterogeneous trend in the different regions analyzed, and Ca enrichment of tubers altered the accumulation of other nutrientsinfo:eu-repo/semantics/publishedVersio

Enrichment of Grapes with Zinc-Efficiency of Foliar Fertilization with ZnSO4 and ZnO and Implications on Winemaking

PDR2020-101-030727Grapes and wine are widely consumed in the world, yet their mineral content can be influenced by many factors such as the mineral composition of soils, viticulture practices and environmental conditions. In this context, considering the importance of Zn in the human physiology, the enrichment of Moscatel and Castelão grapes (white and red variety, respectively) with this nutrient prompted this study; further assessment of tissue deposition and some implications for wine production. Using two foliar fertilizers (ZnO or ZnSO4, at 150, 450 and 900 g ha−1), decreases in net photosynthesis and stomatal conductance occurred in both varieties, suggesting that the physiological threshold of Zn toxicity was reached without visible symptoms. Following foliar spraying with both fertilizers, the content of Zn in leaves of the Castelão and Moscatel varieties showed higher values in all treatments relative to the control. Moreover, in grapes this tendency occurred only in Castelão. Concerning Cu, Fe, Ca, K, S and P, some significant differences also happened in leaves and grapes among treatments. At harvest, the indexes of Zn enrichment in grapes increased between 2.14-and 8.38-fold and between 1.02-and 1.44-fold in Castelão and Moscatel varieties, respectively. Zinc in the dried skin of Castelão only increased with ZnO and ZnSO4 sprayed at 900 g ha−1 (ca. 2.71-and 1.5-fold relative to the control, respectively), but in Moscatel a clear accumulation trend could not be found. The dry weight of grapes ranged (in %) between 16 and 23 (but did not vary significantly among treatments of each variety or in each treatment between varieties), and total soluble solids (e.g., mainly soluble sugars and proteins) and color parameters showed some significant variations. Through winemaking, the contents of Zn increased in both varieties (1.34-and 3.57-fold, in Castelão and Moscatel, respectively) and in all treatments, although non-significantly in Castelão. It is concluded that, to increase the contents of Zn in grapes without reaching the threshold of toxicity, ZnO or ZnSO4 can be used for foliar spraying of Castelão and Moscatel varieties until 900 g ha −1 And that winemaking augments the level of this nutrient.publishersversionpublishe

Interaction with Calcium at Tissue Level and Implications on Quality

This work received funding from PDR2020-101-030701 UID/FIS/04559/2020 (LIBPhys) from the FCT/MCTES/PIDDAC. Publisher Copyright: © 2022 by the authors.As the productivity and quality of tomato fruits are responsive to Mg applications, without surpassing the threshold of toxicity, the assessment of potential levels of Mg accumulation in tissues, as well as the interactions with Ca and physicochemical properties, prompt this study. An agronomic workflow for Mg enrichment, consisting of six foliar applications of MgSO4 with four concentrations (0%, 0.25%, 1% and 4%), equivalent to 0, 43.9, 175.5 and 702 g ha−1, was applied on two tomato (Lycopersicum esculentum L.) genotypes (Heinz1534 and Heinz9205). During fruit development, leaf gas exchange was screened, with only minor physiological deviations being found. At harvest, Mg contents among tissues and the interactions with Ca were analyzed, and it was found that in both varieties a higher Mg/Ca ratio prevailed in the most external part of the fruit sprayed with 4% MgSO4. However, Mg distribution prevailed relatively near the epidermis in H1534, while in H9205 the higher contents of this nutrient occurred in the core of the fruit, which indicated a decrease of the relative proportion of Ca. The morphologic (height and diameter), physical (dry weight and density) and colorimetric parameters, and the total soluble solids of fruits, did not reveal significant changes in both tomato varieties. It was further concluded that foliar application until 4% MgSO4 does not have physiological impacts in the fruit’s quality of both varieties, but in spite of the different patterns of Mg accumulation in tissues, if the mean value in the whole fruit is considered, this nutrient prevails in H1534. This study thus suggests that variety H1534 can be used to attain tomato fruits with added value, providing an option of further processing to achieve food products with functional properties, ultimately proving a beneficial option to producers, the food processing industry and consumers. Moreover, the study reinforces the importance of variety choice when designing enrichment workflows.publishersversionpublishe

Nanoinformatics: developing new computing applications for nanomedicine

Nanoinformatics has recently emerged to address the need of computing applications at the nano level. In this regard, the authors have participated in various initiatives to identify its concepts, foundations and challenges. While nanomaterials open up the possibility for developing new devices in many industrial and scientific areas, they also offer breakthrough perspectives for the prevention, diagnosis and treatment of diseases. In this paper, we analyze the different aspects of nanoinformatics and suggest five research topics to help catalyze new research and development in the area, particularly focused on nanomedicine. We also encompass the use of informatics to further the biological and clinical applications of basic research in nanoscience and nanotechnology, and the related concept of an extended ?nanotype? to coalesce information related to nanoparticles. We suggest how nanoinformatics could accelerate developments in nanomedicine, similarly to what happened with the Human Genome and other -omics projects, on issues like exchanging modeling and simulation methods and tools, linking toxicity information to clinical and personal databases or developing new approaches for scientific ontologies, among many others

Implications for Quality and Wine Production

UID/FIS/04559/2020Nowadays, there is a growing concern about micronutrient deficits in food products, with agronomic biofortification being considered a mitigation strategy. In this context, as Zn is essential for growth and maintenance of human health, a workflow for the biofortification of grapes from the Vitis vinifera variety Fernão Pires, which contains this nutrient, was carried out considering the soil properties of the vineyard. Additionally, Zn accumulation in the tissues of the grapes and the implications for some quality parameters and on winemaking were assessed. Vines were sprayed three times with ZnO and ZnSO4 at concentrations of 150, 450, and 900 g ha−1 during the production cycle. Physiological data were obtained through chlorophyll a fluorescence data, to access the potential symptoms of toxicity. At harvest, treated grapes revealed significant increases of Zn concentration relative to the control, being more pronounced for ZnO and ZnSO4 in the skin and seeds, respectively. After winemaking, an increase was also found regarding the control (i.e., 1.59-fold with ZnSO4-450 g ha−1). The contents of the sugars and fatty acids, as well as the colorimetric analyses, were also assessed, but significant variations were not found among treatments. In general, Zn biofortification increased with ZnO and ZnSO4, without significantly affecting the physicochemical characteristics of grapes.publishersversionpublishe