Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the ne...Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.展开更多
In this study,we analyze the lead-lag relationships between the US industry index and those of six other major countries from January 1973 to May 2021.We identify the leading role played by the US internationally by s...In this study,we analyze the lead-lag relationships between the US industry index and those of six other major countries from January 1973 to May 2021.We identify the leading role played by the US internationally by showing that the weekly returns of US industries,especially the US basic materials and energy industries,significantly Granger cause the returns of most other countries’industries,suggesting that non-US industries react with some delay to new information.This delayed reaction is even more notice-able during periods of recession in the US when cross-country correlations are higher.This implies that the ability of the lagged returns of US industries to predict industries’returns from other countries is even more pronounced when the US experienced an economic recession.A similar asymmetric relationship is found between the volatil-ity of US industries and that of industries in other markets.The analysis of causality in the distribution of returns and volatility shows that causality runs mainly from the US to other countries,particularly in the presence of extreme negative shocks.Finally,we demonstrate that our predictions are valuable to real-world investors.Long-short strategies generate sizable and statistically significant alphas,and a constant relative risk-averse investor obtains certainty equivalent returns well above the risk-free rate.展开更多
The negative cardiorespiratory health outcomes due to extreme temperatures and air pollution are widely stud-ied,but knowledge about the effectiveness of the implementation of adaptive mechanisms remains unclear.The o...The negative cardiorespiratory health outcomes due to extreme temperatures and air pollution are widely stud-ied,but knowledge about the effectiveness of the implementation of adaptive mechanisms remains unclear.The objective of this paper is to explore the evidence of adaptive mechanisms for cardiorespiratory diseases regard-ing extreme temperatures and air pollution by comparing the results of two systematic literature review(SLR)processes sharing the same initial research question but led by two research groups with different academic back-grounds working in the same multidisciplinary team.We start by presenting the methodological procedures and the results of the SLR triggered by the research group mainly composed by researchers with a background in ge-ography(named geographical strategy).We then compare these results with those achieved in the SLR led by the research group with a background in epidemiology(named epidemiological strategy).Both SLR were developed under the EU Horizon 2020 Project“EXHAUSTION”.The results showed:1)the lack of evidence regarding the effectiveness of adaptation measures,namely due to the limited number of studies about the topic,the prepon-derance of studies dedicated to heat extremes or the unbalance between different adaptation measures;2)that the choice of search terms in the geographical strategy,despite being more comprehensive at first sight,ended up retrieving less results,but it brought new studies that can complement the results of the epidemiological strategy.Therefore,it is suggested that to strengthen the empirical evidence of the effectiveness of adaptation measures,powerful multidisciplinary teams should work together in the preparation of SLR in topics of great complexity,such as the one presented in this paper.展开更多
基金Claudia Machado(Instituto de Investigacao e Inovacao em Saude)for her help in preparing the bone slides for the immunohistochemistryThis work was financed by FEDER—Fundo Europeu de Desenvolvimento Regional funds through the COMPETE 2020—Operacional Programme for Competitiveness and Internationalisation(POCI),Portugal 2020,and by Portuguese funds through FCT/MCTES in the framework of the project SproutcORE—Inervagao patologica em metastases osseas:OSTEOCLASTOS,o que estao a fazer?(PTDC/MED-PAT/30158/2017,POCI-01-0145-FEDER-030158)+1 种基金D.M.S.is a recipient of a Post-Doc fellowship(SFRH/BPD/115341/2016)L.L.and F.C.are recipients of Ph.D.fellowships(SFRH/BD/109686/2015 and SFRH/BD/128771/2017,respectively).
文摘Tissue innervation is a complex process controlled by the expression profile of signaling molecules secreted by tissue-resident cells that dictate the growth and guidance of axons.Sensory innervation is part of the neuronal network of the bone tissue with a defined spatiotemporal occurrence during bone development.Yet,the current understanding of the mechanisms regulating the map of sensory innervation in the bone tissue is still limited.Here,we demonstrated that differentiation of human mesenchymal stem cells to osteoblasts leads to a marked impairment of their ability to promote axonal growth,evidenced under sensory neurons and osteoblastic-lineage cells crosstalk.The mechanisms by which osteoblast lineage cells provide this nonpermissive environment for axons include paracrine-induced repulsion and loss of neurotrophic factors expression.We identified a drastic reduction of NGF and BDNF production and stimulation of Sema3A,Wnt4;and Shh expression culminating at late stage of OB differentiation.We noted a correlation between Shh expression profile,OB differentiation stages,and OB-mediated axonal repulsion.Blockade of Shh activity and signaling reversed the repulsive action of osteoblasts on sensory axons.Finally,to strengthen our model,we localized the expression of Shh by osteoblasts in bone tissue.Overall,our findings provide evidence that the signaling profile associated with osteoblast phenotype differentiating program can regulate the patterning of sensory innervation,and highlight osteoblast-derived Shh as an essential player in this cue-induced regulation.
基金been funded by national funds through FCT–Fundacao para a Ciência e a Tecnologia,I.P.,Project UIDB/05037/2020.
文摘In this study,we analyze the lead-lag relationships between the US industry index and those of six other major countries from January 1973 to May 2021.We identify the leading role played by the US internationally by showing that the weekly returns of US industries,especially the US basic materials and energy industries,significantly Granger cause the returns of most other countries’industries,suggesting that non-US industries react with some delay to new information.This delayed reaction is even more notice-able during periods of recession in the US when cross-country correlations are higher.This implies that the ability of the lagged returns of US industries to predict industries’returns from other countries is even more pronounced when the US experienced an economic recession.A similar asymmetric relationship is found between the volatil-ity of US industries and that of industries in other markets.The analysis of causality in the distribution of returns and volatility shows that causality runs mainly from the US to other countries,particularly in the presence of extreme negative shocks.Finally,we demonstrate that our predictions are valuable to real-world investors.Long-short strategies generate sizable and statistically significant alphas,and a constant relative risk-averse investor obtains certainty equivalent returns well above the risk-free rate.
基金This research was conducted in the framework of the EXHAUSTION project.The project has received funding from the European Union’s Horizon 2020 Research and Innovation Program(Grant No.820655).
文摘The negative cardiorespiratory health outcomes due to extreme temperatures and air pollution are widely stud-ied,but knowledge about the effectiveness of the implementation of adaptive mechanisms remains unclear.The objective of this paper is to explore the evidence of adaptive mechanisms for cardiorespiratory diseases regard-ing extreme temperatures and air pollution by comparing the results of two systematic literature review(SLR)processes sharing the same initial research question but led by two research groups with different academic back-grounds working in the same multidisciplinary team.We start by presenting the methodological procedures and the results of the SLR triggered by the research group mainly composed by researchers with a background in ge-ography(named geographical strategy).We then compare these results with those achieved in the SLR led by the research group with a background in epidemiology(named epidemiological strategy).Both SLR were developed under the EU Horizon 2020 Project“EXHAUSTION”.The results showed:1)the lack of evidence regarding the effectiveness of adaptation measures,namely due to the limited number of studies about the topic,the prepon-derance of studies dedicated to heat extremes or the unbalance between different adaptation measures;2)that the choice of search terms in the geographical strategy,despite being more comprehensive at first sight,ended up retrieving less results,but it brought new studies that can complement the results of the epidemiological strategy.Therefore,it is suggested that to strengthen the empirical evidence of the effectiveness of adaptation measures,powerful multidisciplinary teams should work together in the preparation of SLR in topics of great complexity,such as the one presented in this paper.
