Effect of temperature on crossbridge force changes during fatigue and recovery in intact mouse muscle fibers.

Repetitive or prolonged muscle contractions induce muscular fatigue, defined as the inability of the muscle to maintain the initial tension or power output. In the present experiments, made on intact fiber bundles from FDB mouse, fatigue and recovery from fatigue were investigated at 24°C and 35°C. Force and stiffness were measured during tetani elicited every 90 s during the pre-fatigue control phase and recovery and every 1.5 s during the fatiguing phase made of 105 consecutive tetani. The results showed that force decline could be split in an initial phase followed by a later one. Loss of force during the first phase was smaller and slower at 35°C than at 24°C, whereas force decline during the later phase was greater at 35°C so that total force depression at the end of fatigue was the same at both temperatures. The initial force decline occurred without great reduction of fiber stiffness and was attributed to a decrease of the average force per attached crossbridge. Force decline during the later phase was accompanied by a proportional stiffness decrease and was attributed to a decrease of the number of attached crossbridge. Similarly to fatigue, at both 24 and 35°C, force recovery occurred in two phases: the first associated with the recovery of the average force per attached crossbridge and the second due to the recovery of the pre-fatigue attached crossbridge number. These changes, symmetrical to those occurring during fatigue, are consistent with the idea that, i) initial phase is due to the direct fast inhibitory effect of [Pi]i increase during fatigue on crossbridge force; ii) the second phase is due to the delayed reduction of Ca(2+) release and /or reduction of the Ca(2+) sensitivity of the myofibrils due to high [Pi]i

Dexamethasone Induces the Expression and Function of Tryptophan-2-3-dioxygenase in SK-MEL-28 Melanoma Cells

Tryptophan-2,3-dioxygenase (TDO) is one of the key tryptophan-catabolizing enzymes with immunoregulatory properties in cancer. Contrary to expectation, clinical trials showed that inhibitors of the ubiquitously expressed enzyme, indoleamine-2,3-dioxygenase-1 (IDO1), do not provide benefits in melanoma patients. This prompted the hypothesis that TDO may be a more attractive target. Because the promoter of TDO harbors glucocorticoid response elements (GREs), we aimed to assess whether dexamethasone (dex), a commonly used glucocorticoid, modulates TDO expression by means of RT-PCR and immunofluorescence and function by assessing cell proliferation and migration as well as metalloproteinase activity. Our results show that, in SK-Mel-28 melanoma cells, dex up-regulated TDO and its downstream effector aryl hydrocarbon receptor (AHR) but not IDO1. Furthermore, dex stimulated cellular proliferation and migration and poten-tiated MMP2 activity. These effects were inhibited by the selective TDO inhibitor 680C91 and enhanced by IDO1 inhibitors. Taken together, our results demonstrate that the metastatic melanoma cell line SK-Mel-28 possesses a functional TDO which can also modulate cancer cell phenotype di-rectly rather than through immune suppression. Thus, TDO appears to be a promising, tractable target in the management or the treatment of melanoma progression

Subjective wellbeing of Italian healthcare professionals during the SARS-CoV-2 outbreak: A quasi-experiment

Italy was one of the strongest hit countries from the SARS-CoV-2 and the healthcare system was put under exceptional stress during the outbreak. The lockdown imposed on the population put the economy on hold and opened the way for a crisis that would have an impact on the healthcare system and the economy of the country. This study compares levels of subjective wellbeing among healthcare professionals before the outbreak and during the most critical moment of the lockdown, when Italy was the first country in the world by number of infections. Subjective wellbeing was measured with emotional wellbeing, job satisfaction, global happiness and satisfaction with life. Each measure was compared before and during the outbreak as well as among different subgroups of respondents. A special attention was put on inequalities in professional level, gender and educational level as well as their effect on subjective wellbeing. The study finds that while emotional wellbeing had a slight decrease, other measures were untouched and job satisfaction even increased during the lockdown period. Present wellbeing differences based in inequalities in professional and educational level were lifted once professionals were fighting the SARS-CoV-2 outbreak. This decrease in inequalities and increase in job satisfaction might be strongly related to a newfound trust in healthcare professionals, a high gratitude from the population and a feeling of accomplishment and meaning as described in the PERMA model. The findings of this study should help healthcare organizations to keep inequalities low as well as other organizations to apply those learnings in their structure

Towards an\u2028 EU research and innovation policy agenda for nature-based solutions & re-naturing cities. Final report of the Horizon 2020 expert group on nature-based solutions and re-naturing cities.

1. Nature-based solutions harness the power and sophistication of nature to turn environmental, social and economic challenges into innovation opportunities. They can address a variety of societal challenges in sustainable ways, with the potential to contribute to green growth, 'future-proofing' society, fostering citizen well-being, providing business opportunities and positioning Europe as a leader in world markets. \u2028 2. Nature-based solutions are actions which are inspired by, supported by or copied from nature. They have tremendous potential to be energy and resource-efficient and resilient to change, but to be successful they must be adapted to local conditions. \u2028 3. Many nature-based solutions result in multiple co-benefits for health, the economy, society and the environment, and thus they can represent more efficient and cost-effective solutions than more traditional approaches. \u2028 4. An EU Research & Innovation (R&I) agenda on nature-based solutions will enable Europe to become a world leader both in R&I and in the growing market for nature-based solutions. For this, the evidence base for the effectiveness of nature-based solutions needs to be developed and then used to implement solutions. Both need to be done in conjunction with stakeholders. The potential for transferability and upscaling of solutions also requires further investigation. There is also a need to develop a systemic approach that combines technical, business, finance, governance, regulatory and social innovation. \u2028 5. Four principal goals have been identified that can be addressed by nature-based solutions: �� Enhancing sustainable urbanisation through nature-based solutions can stimulate economic growth as well as improving the environment, making cities more attractive, and enhancing human well-being. \u2028 �� Restoring degraded ecosystems using nature-based solutions can improve the resilience of ecosystems, enabling them to deliver vital ecosystem services and also to meet other societal challenges. \u2028 �� Developing climate change adaptation and mitigation using nature-based solutions can provide more resilient responses and enhance the storage of carbon. \u2028 �� Improving risk management and resilience using nature-based solutions can lead to greater benefits than conventional methods and offer synergies in reducing multiple risks. \u2028 6. Based on the four goals, seven nature-based solutions for R&I actions are recommended to be taken forward by the European Commission and Member States: �� Urban regeneration through nature-based solutions \u2028 �� Nature-based solutions for improving well-being in urban areas \u2028 �� Establishing nature-based solutions for coastal resilience \u2028 �� Multi-functional nature-based watershed management and ecosystem restoration \u2028 �� Nature-based solutions for increasing the sustainability of the use of matter and energy \u2028 �� Nature-based solutions for enhancing the insurance value of ecosystems \u2028 �� Increasing carbon sequestration through nature-based solutions \u2028This report was produced by the Horizon 2020 Expert Group on 'Nature-Based Solutions and Re- Naturing Cities', informed by the findings of an e-consultation and a stakeholder workshop. \u202

Altered feeding behavior and immune competence in paper wasps : A case of parasite manipulation?

Acknowledgments The authors are grateful to Rita Cervo, Stefano Turillazzi and the members of the Florence Group for the Study of Social Wasps, first of all to Irene Pepiciello, for their assistance during this study, both in the field and in the laboratory. The authors also thank two anonymous Reviewers for their helpful comments and suggestions. Financial support to LB was provided by the University of Florence.Peer reviewedPublisher PD