Browsing by Author "Neves, Joana"
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- Aging eyes and the immune systemPublication . Neves, JoanaA central promise of regenerative medicine is the ability to repair aged or diseased organs using stem cells (SCs). This approach will likely become an effective strategy for organ rejuvenation, holding the potential to increase human health by delaying age-related diseases. The successful translation of this scientific knowledge into clinical practice will require a better understanding of the basic mechanisms of aging, along with an integrated view of the process of tissue repair. The advent of SC therapies, now progressing into clinical trials, has made clear the many challenges limiting the application of SCs to treat disease. Our duty, as scientists, is to anticipate such limitations and propose solutions to effectively deliver on the promise of regenerative medicine.
- Dilemmas of proximity : motives influencing Portuguese firms’ internationalization to MoroccoPublication . Silva, Joaquim Ramos; Neves, Joana; Magrinho, André; Franco, Mário; Rodrigues, MargaridaThis study aims to identify Portuguese firms’ motives for internationalizing to Morocco. To achieve this objective, we used a mixed-method (quantitative and qualitative) approach, obtaining data from a questionnaire survey and interviewees from Portuguese enterprises involved in this internationalization process. From exploratory factor analysis (EFA), firms’ reasons for entering the Moroccan market were categorized into five dimensions: (a) Price and Business Infrastructure, (b) Regional Hub and Business Environment, (c) Financial Incentives and Raw Material, (d) Skilled Labour Force and (e) Weak Competition and International Business Partners. The study shows that the factors/dimensions identified are associated both with firms’ resources and capacities and with the characteristics that sometimes define the entrepreneur–manager’s perceptions. In addition, our study provides inside knowledge of this topic through small and medium-sized enterprise (SME) managers’ views on key aspects of their presence in Morocco, which leads to a more robust portrayal of this type of process.
- Dpp/TGFβ-superfamily play a dual conserved role in mediating the damage response in the retinaPublication . Kramer, Joshua; Neves, Joana; Koniikusic, Mia; Jasper, Heinrich; Lamba, Deepak A.Retinal homeostasis relies on intricate coordination of cell death and survival in response to stress and damage. Signaling mechanisms that coordinate this process in the adult retina remain poorly understood. Here we identify Decapentaplegic (Dpp) signaling in Drosophila and its mammalian homologue Transforming Growth Factor-beta (TGFβ) superfamily, that includes TGFβ and Bone Morphogenetic Protein (BMP) signaling arms, as central mediators of retinal neuronal death and tissue survival following acute damage. Using a Drosophila model for UV-induced retinal damage, we show that Dpp released from immune cells promotes tissue loss after UV-induced retinal damage. Interestingly, we find a dynamic response of retinal cells to this signal: in an early phase, Dpp-mediated stimulation of Saxophone/Smox signaling promotes apoptosis, while at a later stage, stimulation of the Thickveins/Mad axis promotes tissue repair and survival. This dual role is conserved in the mammalian retina through the TGFβ/BMP signaling, as supplementation of BMP4 or inhibition of TGFβ using small molecules promotes retinal cell survival, while inhibition of BMP negatively affects cell survival after light-induced photoreceptor damage and NMDA induced inner retinal neuronal damage. Our data identify key evolutionarily conserved mechanisms by which retinal homeostasis is maintained.
- MANF delivery improves retinal homeostasis and cell replacement therapies in ageing micePublication . Neves, Joana; Chirco, Kathleen R.; Cedron-Craft, Wendy; Chew, Shereen; Zhu, Jie; Jasper, Heinrich; Lamba, Deepak A.Ageing is a major risk factor for vision loss, and inflammation is an important contributor to retinal disease in the elderly. Regenerative medicine based on cell replacement strategies has emerged in recent years as a promising approach to restore vision. However, how the ageing process affects retinal homeostasis and inflammation in the retina and how this may impose a limitation to the success of such interventions remains unknown. Here we report that, in mice and humans, retinal ageing is associated with a reduction in MANF protein levels, specifically in the choroid, where increased densities of activated macrophages can be detected. We further show that the retina of old wild type mice, in the absence of any other genetic alteration, has limited homeostatic capacity after damage imposed by light exposure and reduced engraftment efficiency of exogenously supplied photoreceptors. Finally, we show that supplementation of MANF recombinant protein can improve retinal homeostasis and repair capacity in both settings, correlating with reduced numbers of activated macrophages in the old retina. Our work identifies age-related alterations in retinal homeostasis, independent of genetic alterations, leading to age-related retinal inflammation and damage susceptibility. We suggest that MANF therapy is a potential intervention to maintain retinal homeostasis in the elderly and improve the success of retinal regenerative therapies applied to aged individuals.
- Regulation of inflammation as an anti‐aging interventionPublication . Neves, Joana; Sousa-Victor, PedroAging is accompanied by a decline in physiological integrity and a loss of regenerative capacity in many tissues. The development of interventions that prevent or reverse age-related disease requires a better understanding of the interplay of cell intrinsic, inter-cellular communication and systemic deregulations that underlie the aging process. Immune dysfunction and changes in inflammatory pathways are transversal contributors to the aging process and are essential propagators of tissue deterioration. Here, we propose and discuss the rejuvenation potential of interventions that target chronic inflammation and how modulation of tissue repair capacity could be an important mediator of such anti-aging strategies. We highlight how current knowledge on the systemic nature of inflammatory dysregulation in old organisms, together with the development of new animal models that allow for the isolation of the inflammatory component of aging, could provide new targets for interventions in aging based on the modulation of inflammatory pathways.
- The triple helix model: evidence in the internationalization of the health industryPublication . Magrinho, André; Neves, Joana; Silva, Joaquim RamosThe chapter focuses on the role of the Triple Helix model that binds companies/business associations with the universities/research centers and the government at different levels, which has been widely used for policy purposes. This work examines the internationalization process of firms within the context of global value chains, and the study case is the Health Cluster of Portugal. The authors show that the recourse to the model is relevant to understand this industry, most notably in the regional context. However, on the basis of the case study, not all aspects of the relationships within the model attain the same level of satisfaction. It is concluded that the model enables the associated firms to more easily absorb the impact of the 4th Industrial Revolution but important challenges remain in the advance of this process.