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

Influences of Intermediation of Support Institutions on Innovativeness and Organizational Performance

Purpose: Identify the influence of relationships with support institutions on innovativeness and organizational performance. Theoretical framework: The innovation intermediaries are organizations that act as a link between those involved in the innovation process and whose purpose is to develop the innovative aspects of organizations. Although studies have pointed out the importance of relationships with support institutions for the development of innovation, the present study investigated the role of these institutions as intermediary actors in the innovation process.Design/methodology/approach: A systematic literature review was conducted. The Methodi Ordinatio Index was used as a protocol. In order to identify the most central theoretical approaches in the studies, as well to map the interactions between these approaches, the Social Network Analysis - SNA technique was used.Findings: The relationship with support institutions increases access to non-redundant contacts; these, in its turn, influence innovativeness. The performance of these actors as intermediaries will only influence innovativeness in the circumstances in which the idiosyncrasy of these institutions does not prevent or makes impossible access to non-redundant contacts.Originality/value: The study contributed with literature from the fields of interorganizational relations, innovation and strategy by identifying the theoretical approaches in which the role of innovation support organizations is inserted, as well as by identifying the influence for access to non-redundant contacts, relevant to the innovation process; in addition, theoretical propositions and a research agenda are presented

Assessment of male reproductive traits in endangered leuciscids from the Iberian Peninsula: first attempts to store gametes both at short- and long-term

During the spring of 2022, several endangered leuciscid species (Anaecypris hispanica, Squalius aradensis, Anachondrostoma Occidentale, and Iberochondrostoma lusitanicum) were sampled both at the Vasco da Gama aquarium facilities and in some rivers of the Algarve region, Portugal. Sperm samples were extracted by gentle abdominal pressure and sperm motion parameters were assessed for the first time in four species, using a computerized analysis system. The results obtained showed that spermatozoa kinetic patterns were similar for all 4 species, with high motility and velocity values after the sperm activation time and with a marked decrease after 20. On the other hand, sperm longevity was highly variable between species, with short longevities (around 40 s) for A. hispanica and S. aradensis, and longer longevities (100-120 s) for A. occidentale and I. lusitanicum, which could indicate a latitudinal pattern in terms of sperm longevity. At the same time, morphometric analysis was carried out for the four target species, revealing that spermatozoa showed similar sizes and shapes to other external fertilizers belonging to Leuscididae, with small spherical heads, uniflagellate, and without acrosomes. In addition, a short-term gamete storage trail was performed by diluting sperm in 1:9 (sperm:extender) and storing them at 4oC. Although the results obtained were uneven among the species studied, the dilution and extender used generated motilities above 40% up to day 4 of storage in S. aradensis and I. lusitanicum, and up to days 1-2 in A. hispanica and A. occidentale, respectively. Finally, gamete cryopreservation trials were also carried out on these threatened species. Although cryopreserved samples showed significantly lower motility than fresh samples, some protocols generate acceptable percentages of viability, DNA integrity, and sperm motility in some species such as I. lusitanicum and A. occidentale. The data revealed that the protocol based on 10% DMSO plus 7.5% egg yolk generated the best results.This study is the first to assess the reproductive traits of wild and captive populations of endangered leuciscids endemic from the Iberian Peninsula, describing the spermatozoa kinetics and developing protocols for managing male gametes both in short- and long-term storage. Outcomes will provide new and useful tools to complement the management and conservation of ex situ breeding programs that are being developed for these four endangered species.LA/P/0069/2020info:eu-repo/semantics/publishedVersio

Padronização da avaliação laboratorial do perfil lipídico: um apelo à ação com foco especial nas recomendações europeias de dislipidemia da ESC/EAS de 2016 – sumário executivo: Um consenso endossado pelo Grupo de Prevenção e Risco Cardiovascular da Sociedade Portuguesa de Medicina Interna, Sociedade Portuguesa de Cardiologia, Sociedade Portuguesa de Medicina Laboratorial e Associação Portuguesa de Analistas Clínicos

Even with improvements in lifestyle interventions, better control of cardiovascular (CV) risk factors, and improvements in CV outcomes, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in Portugal and Europe. Atherogenic dyslipidemias, particularly hypercholesterolemia, have a crucial causal role in the development of atherosclerotic CVD. The clinical approach to a patient with dyslipidemia requires an accurate diagnosis, based on harmonized and standardized lipid and lipoprotein laboratory assessments. Results and reports of these tests, together with assessment of total CV risk and the respective therapeutic targets, will help ensure that clinical guidelines and good clinical practices are followed, increasing the reliability of screening for lipid disorders, producing more accurate diagnoses and CV risk stratification, and improving CV prevention. To this end, this consensus aims to provide clinicians with practical guidance for the harmonization and standardization of laboratory lipid tests, focusing on the most recent dyslipidemia management guidelines.info:eu-repo/semantics/publishedVersio

Trophic Factors in Inflammation and Regeneration: The Role of MANF and CDNF

Regeneration is an important process in multicellular organisms, responsible for homeostatic renewal and repair of different organs after injury. Immune cell activation is observed at early stages of the regenerative response and its regulation is essential for regenerative success. Thus, immune regulators play central roles in optimizing regenerative responses. Neurotrophic factors (NTFs) are secreted molecules, defined by their ability to support neuronal cell types. However, emerging evidence suggests that they can also play important functions in the regulation of immune cell activation and tissue repair. Here we discuss the literature supporting a role of NTFs in the regulation of inflammation and regeneration. We will focus, in particular, in the emerging roles of mesencephalic astrocyte-derived neurotrophic factor (MANF) and cerebral dopamine neurotrophic factor (CDNF) in the regulation of immune cell function and in the central role that immune modulation plays in their biological activity in vivo. Finally, we will discuss the potential use of these factors to optimize regenerative success in vivo, both within and beyond the nervous system

High-resolution imagery data to assess the spatial variability of sugarcane fields/ Dados de imagens de alta resolução para avaliação da variabilidade espacial de talhões de cana-de-açúcar

The vegetation index (VI) generated from orbital images are essential tools to identify the spatial variability of the crops. The objective of this study was to evaluate the spatial variability of sugarcane fields using imagery data. Also, to explore the ideal period to correlate the Normalized Difference Vegetation Index (NDVI), Normalized Difference Red-Edge Index (NDRE) and Wide Dynamic Range Vegetation Index (WDRVI) with sugarcane yield. Four fields were selected in the state of São Paulo (56.37 ha) during the 2017/2018 and 2018/2019 growing seasons, as well as five fields in the state of Goiás (86.86 ha) during the 2019/2020 growing season. The VIs were calculated using orbital images from Sentinel-2 (spatial resolution of 10 m). The yield data were generated by a commercial sensor-system installed on the harvesters with a resolution of 0.20 Hz. Yield data were filtered and interpolated using the same resolution of the orbital images. Pearson's correlation was calculated between the yield and the VIs for each orbital image. The considered VIs were able to identify the spatial variability of sugarcane fields with coefficients of correlation of 0.95 and 0.96. The sugarcane stalks growth was the best period to correlate the VIs and the yield maps among the analyzed fields

Piwi Is Required to Limit Exhaustion of Aging Somatic Stem Cells

Please see the graphical abstract in the supplemental files

Biophysical characterization of the first ultra-cyclist in the world to break the 1,000 km barrier in 24-h non-stop road cycling: A case report

A plethora of factors determine elite cycling performance. Those include training characteristics, pacing strategy, aerodynamics, nutritional habits, psychological traits, physical fitness level, body mass composition, and contextual features; even the slightest changes in any of these factors can be associated with performance improvement or deterioration. The aim of the present case report is to compare the performances of the same ultra-cyclist in achieving two world records (WR) in 24 h cycling. We have analyzed and compared the distance covered and speed for each WR. The 24 h period was split into four-time intervals (0–6 h; > 6–12 h; > 12–18 h; > 18–24 h), and we compared the differences in the distance covered and speed between the two WRs. For both WRs, a strong negative correlation between distance and speed was confirmed (r = –0.85; r = –0.89, for old and new WR, respectively). Differences in speed (km/h) were shown between the two WRs, with the most significant differences in 12–18 h (Δ = 6.50 km/h). For the covered distance in each block, the most significant differences were observed in the last part of the cycling (Δ = 38.54 km). The cyclist effective surface area (ACd) was 0.25 m$^{2}$ less and 20% more drag in the new WR. Additionally, the mechanical power was 8%, the power to overcome drag was 31%, and the power-weight ratio was 8% higher in the new WR. The mechanical efficiency of the cyclist was 1% higher in the new WR. Finally, the heart rate (HR) presented significant differences for the first 6 h (Old WR: 145.80 ± 5.88 bpm; New WR: 139.45 ± 5.82 bpm) and between the 12 and 18 h time interval (Old WR: 133.19 ± 3.53 bpm; New WR: 137.63 ± 2.80 bpm). The marginal gains concept can explain the performance improvement in the new WR, given that the athlete made some improvements in technical specifications after the old WR

VENOUS RECONSTRUCTION AFTER IATROGENIC FEMOROILIAC INJURY: CASE REPORT

Deep venous sector injuries during lower limb varicose vein surgery are rare. They can have serious repercussions in terms of the patient’s quality of life, so reconstructive interventions are strongly recommended. We report a case of a patient referred to our Institution after an extensive lesion of the femoral venous sector. We performed a reconstructive surgery, through mechanical thrombectomy, as he presented an extensive deep vein thrombosis, and by performing an interposition graft bypass. After two years of follow no complications were reported. The patient is asymptomatic, with no significant signs or symptoms of post thrombotic syndrome. The interposition graft is still patent

A Machine Learning Approach to Finding the Fastest Race Course for Professional Athletes Competing in Ironman® 70.3 Races between 2004 and 2020

Our purpose was to find the fastest race courses for elite Ironman® 70.3 athletes, using machine learning (ML) algorithms. We collected the data of all professional triathletes competing between 2004 and 2020 in Ironman 70.3 races held worldwide. A sample of 16,611 professional athletes originating from 97 different countries and competing in 163 different races was thus obtained. Four different ML regression models were built, with gender, country of origin, and event location considered as independent variables to predict the final race time. For all the models, gender was the most important variable in predicting finish times. Attending to the single decision tree model, the fastest race times in the Ironman® 70.3 World Championship of around ~4 h 03 min would be achieved by men from Austria, Australia, Belgium, Brazil, Switzerland, Germany, France, the United Kingdom, South Africa, Canada, and New Zealand. Considering the World Championship is the target event for most professional athletes, it is expected that training is planned so that they attain their best performance in this event