Aging disrupts MANF-mediated immune modulation during skeletal muscle regeneration

Copyright © 2023, The Author(s), under exclusive licence to Springer Nature America, Inc. Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.Age-related decline in skeletal muscle regenerative capacity is multifactorial, yet the contribution of immune dysfunction to regenerative failure is unknown. Macrophages are essential for effective debris clearance and muscle stem cell activity during muscle regeneration, but the regulatory mechanisms governing macrophage function during muscle repair are largely unexplored. Here, we uncover a new mechanism of immune modulation operating during skeletal muscle regeneration that is disrupted in aged animals and relies on the regulation of macrophage function. The immune modulator mesencephalic astrocyte-derived neurotrophic factor (MANF) is induced following muscle injury in young mice but not in aged animals, and its expression is essential for regenerative success. Regenerative impairments in aged muscle are associated with defects in the repair-associated myeloid response similar to those found in MANF-deficient models and could be improved through MANF delivery. We propose that restoring MANF levels is a viable strategy to improve myeloid response and regenerative capacity in aged muscle.This work was supported by EMBO (IG4448 to P.S.V.) and FCT (PTDC/MED-OUT/8010/2020 and EXPL/MED-OUT/1601/2021 to P.S.V. and J.N.). P.S.V. was supported by ‘la caixa’ Foundation Junior Leader Fellowship (LCF/BQ/PI19/11690006). J.N. was supported by an assistant research contract from FCT (2021.03843.CEECIND). P.L. was supported by the Academy of Finland (grant 343299) and by the Jane and Aatos Erkko Foundation.info:eu-repo/semantics/publishedVersio

Avaliação de citotoxicidade de nanotransportadores sem substância ativa em função da sua densidade populacional

A par da evolução da nanotecnologia, assiste-se a uma crescente preocupação sobre eventuais riscos/toxicidade que os nanotransportadores possam representar [1]. A maioria dos trabalhos publicados relativos à avaliação da citotoxicidade in vitro de nanotransportadores (NT) incide na comparação quando a substância ativa (SA) é administrada em solução ou nanoencapsulada, sendo escassos os estudos que visam avaliar a possível toxicidade do NT por si só (sem SA). O objetivo deste trabalho consistiu na avaliação da citotoxicidade de NT sem SA em função da sua densidade populacional, tendo sido testados quatro NT distintos: nanocápsulas (NC), nanoesferas (NE), transportadores lipídicos nanoestruturados (NLC) e lipossomas, com oito densidades populacionais (diluições décimais de 2,10×1012 part/mL a 2,10×105 part/mL). A avaliação da citotoxicidade realizou-se numa cultura primária (linfócitos) pelo teste do MTT e numa linha celular (fibroblastos 3T3) pelo teste do vermelho neutro (NR)

Influence of dual-task on sit-to-stand-to-sit postural control in Parkinson's disease

Postural control deficits are the most disabling aspects of Parkinson's disease (PD), resulting in decreased mobility and functional independence. The aim of this study was to assess the postural control stability, revealed by variables based on the centre of pressure (CoP), in individuals with PD while performing a sit-to-stand-to-sit sequence under single- and dual-task conditions. An observational, analytical and cross-sectional study was performed. The sample consisted of 9 individuals with PD and 9 healthy controls. A force platform was used to measure the CoP displacement and velocity during the sit-to-stand-to-sit sequence. The results were statistically analysed. Individuals with PD required greater durations for the sit-to-stand-to-sit sequence than the controls (p < 0.05). The anteroposterior and mediolateral CoP displacement were higher in the individuals with PD (p < 0.05). However, only the anteroposterior CoP velocity in the stand-to-sit phase (p = 0.006) was lower in the same individuals. Comparing the single- and dual-task conditions in both groups, the duration, the anteroposterior CoP displacement and velocity were higher in the dual-task condition (p < 0.05). The individuals with PD presented reduced postural control stability during the sit-to-stand-to-sit sequence, especially when under the dual-task condition. These individuals have deficits not only in motor performance, but also in cognitive performance when performing the sit-to-stand-to-sit sequence in their daily life tasks. Moreover, both deficits tend to be intensified when two tasks are performed simultaneously

Development of molecular biology techniques for the detection of genetically modified organisms in maize food products

In the last years, the increase in the cultivated area of genetically modified (GM) maize has become a reality. GA21, MON810 and MON 863 maize crops are some of the authorized maize events for food and feed under the European Union (EU) regulations. These crops of transgenic maize bring profit towards the conventional ones, as they confer resistence to some plagues and/or herbices. Concerning the raise of production and consumption of foodstuffs derived from genetically modified organisms (GMO), the EU has established new demand levels, including the labeling requirements when the product has GMO in proportion higher than 0.9% (Regulation (EC) Nº. 1829/2003)

Structural basis of proton-coupled potassium transport in the KUP family

Potassium homeostasis is vital for all organisms, but is challenging in single-celled organisms like bacteria and yeast and immobile organisms like plants that constantly need to adapt to changing external conditions. KUP transporters facilitate potassium uptake by the co-transport of protons. Here, we uncover the molecular basis for transport in this widely distributed family. We identify the potassium importer KimA from Bacillus subtilis as a member of the KUP family, demonstrate that it functions as a K+/H+ symporter and report a 3.7 Å cryo-EM structure of the KimA homodimer in an inward-occluded, trans-inhibited conformation. By introducing point mutations, we identify key residues for potassium and proton binding, which are conserved among other KUP proteins

Análise da sequência do movimento de levantar/sentar, em indivíduos pós AVE: Estudo da relação da activação dos músculos vasto medial oblíquo e vasto lateral

O objectivo deste estudo foi comparar o rácio dos músculos Vasto Medial Oblíquo (VMO) e Vasto Lateral (VL), na sequência de movimento de levantar e sentar, em indivíduos sem patologia e em indivíduos com Acidente Vascular Encefálico (AVE). Pretendeu-se também verificar a sequência de activação de alguns músculos do membro inferior na sequência de movimento de levantar. Verificou-se existir diferenças significativas para afirmar que, no movimento de levantar, indivíduos com sequelas de AVE apresentam menor rácio VMO/VL no membro predominantemente atingido em relação aos indivíduos sem patologia. Diferentes sequências de activação muscular durante o movimento de levantar foram observadas.The purpose of this study was to compare the ratio of the Vastus medialis oblique (VMO) and vastus lateralis (VL), in sit-to-stand movement in subjects without pathology and in individuals with stroke. The article tries to verify the sequence of activation of some muscles of the lower limb during standing up. There are significant differences to argue that, in standing up movement, subjects with sequelae of stroke have a lower ratio VMO / VL in predominantly affected limb compared to subjects without pathology. Different sequences of muscle activation during standing up movement were observed

Right ventricular lead in cardiac resynchronization therapy : what is the most electrically favorable stimulation site?

© The European Society of Cardiology 2018. All rights reserved.Introduction: The most recent studies in cardiac resynchronization therapy (CRT) have been focused on attempts to improve response rate, such as the determination of the optimal placement of the left ventricular (LV) lead. The position of the LV lead guided by the site of latest electrical delay (ED), seems to be a promising strategy. The same strategy may be useful in assessing the ideal positioning of right ventricular (RV) lead in CRT. Purpose: To determine the most favorable position of the RV lead (septal versus apical) in CRT, by measuring the ED of the LV poles during septal or apical RV pacing in patients with triple-site CRT (TRIV). Methods: A single-center prospective study of consecutive patients (Oct. 2014 to Oct. 2017) submited to CRT device implantation (Quadra Allure MPTM, which allows post-implantation ED measurement) in TRIV mode - with a quadripolar lead in the LV, a RV lead positioned at the septum and a RV lead at the apex. In the follow-up, the lead position was confirmed and determined by fluoroscopic evaluation (anterior, lateral and postero-lateral in the short axis and basal, mid and apical on the long axis). The ED was measured at the 4-pole LV lead, during apical and septal RV pacing and the relation between the ED and lead position was evaluated. Results: Twenty two patients were included: 82% male, median age 78 years; 50% implanted CRT with defibrillator; 27% had ischemic heart disease and 73% non-ischemic etiology; all patients had permanent atrial fibrillation and the QRS duration was of 176±29ms. The position of the LE lead poles was classified as lateral in 44% and postero-lateral in 56%, basal in 28%, medial in 39% and apical in 34%. We evaluated 160 ED. The mean ED between the apical RV lead and the LV poles was significantly higher than the delay between septal RV lead and the LV poles [161±33ms vs 75±45ms (p<0.001)]. This difference remained significant in LV poles located in a lateral position (76±62 vs. 166±36ms; p<0.001) or in a postero-lateral position (74±30 vs. 157±31ms; p<0.001); the same ocurred for LV poles in a basal (99±62 vs. 179±24ms, p<0.001), mid (72±38 vs. 167±31ms, p<0.001) and apical location (57±24 vs. 140±32ms, p<0.001). Conclusion: The LV lead position is an important determinant of the success of CRT, but is conditioned by anatomical and technical characteristics. The optimization of CRT may then depend on the positioning of RV lead. This study demonstrated that the apical (vs. septal) RV lead positioning presents higher ED in relation to LV lead, regardless of the latter position.info:eu-repo/semantics/publishedVersio

Motor and cognitive deficits in the heterozygous leaner mouse, a Cav2.1 voltage-gated Ca2+ channel mutant

Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.neurobiolaging.The leaner mutation in mice affects the Ca(v)2.1 voltage-gated calcium channel alpha(1A)-subunit gene (Cacna1a), causing a reduction in calcium currents predominantly in Purkinje cells. This reduction in calcium currents causes severe progressive cerebellar ataxia, beginning around postnatal day 10, in homozygous leaner mice (tg(la)/tg(la)), while their heterozygous littermates (tg(la)/+) present no obvious behavioral deficits. In humans, heterozygous mutations in the Cacna1a orthologous gene produce a broad range of neurological manifestations. To evaluate the phenotypic status of the tg(la)/+ animals, we assessed motor performance and cognition, at different ages, in these mutant mice. We were able to observe age-dependent impairment in motor and cognitive tasks; balance and motor learning deficits were found in demanding tasks on the rotarod and on the hanging wire test, while spatial learning and memory impairment was observed in the Morris water maze. Progressive dysfunction in escape reflexes, indicative of neurological impairment, was also present in tg(la)/+ animals. Although not presenting major motor alterations, tg(la)/+ mice show age-dependent motor and cognitive deficits.We would like to thank Carolina Lemos for her help with statistical analysis and Victor Mendes for image technical assistance. This work was supported by research grants POCTI/MGI/34517/00, POCTI/NSE/45352/2002 and POCI/SAU-MMO/56387/2004, FCT (Fundação para a Ciência e Tecnologia) and co-funded by FEDER. I.A. is recipient of a scholarship from FCT, Portugal

Potential of Coccolithophore microalgae as fillers in starch-based films for active and sustainable food packaging

Coccolithophore microalgae, such as Emiliania huxleyi (EHUX) and Chrysotila pseudoroscoffensis (CP), are composed of calcium carbonate (CaCO3) and contain bioactive compounds that can be explored to produce sustainable food packaging. In this study, for the first time, these microalgae were incorporated as fillers in starch-based films, envisioning the development of biodegradable and bioactive materials for food packaging applications. The films were obtained by solvent casting using different proportions of the filler (2.5, 5, 10, and 20%, w/w). For comparison, commercial CaCO3, used as filler in the plastic industry, was also tested. The incorporation of CaCO3 and microalgae (EHUX or CP) made the films significantly less rigid, decreasing Young’s modulus up to 4.7-fold. Moreover, the incorporation of microalgae hydrophobic compounds as lipids turned the surface hydrophobic (water contact angles > 90°). Contrary to what was observed with commercial CaCO3, the films prepared with microalgae exhibited antioxidant activity, increasing from 0.9% (control) up to 60.4% (EHUX 20%) of ABTS radical inhibition. Overall, the introduction of microalgae biomass improved hydrophobicity and antioxidant capacity of starch-based films. These findings should be considered for further research using coccolithophores to produce active and sustainable food packaging material.info:eu-repo/semantics/publishedVersio

A mixed-methods approach

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