CRISPR/Cas9‐mediated genome editing: from basic research to translational medicine

The recent development of the CRISPR/Cas9 system as an efficient and accessible programmable genome-editing tool has revolutionized basic science research. CRISPR/Cas9 system-based technologies have armed researchers with new powerful tools to unveil the impact of genetics on disease development by enabling the creation of precise cellular and animal models of human diseases. The therapeutic potential of these technologies is tremendous, particularly in gene therapy, in which a patient-specific mutation is genetically corrected in order to treat human diseases that are untreatable with conventional therapies. However, the translation of CRISPR/Cas9 into the clinics will be challenging, since we still need to improve the efficiency, specificity and delivery of this technology. In this review, we focus on several in vitro, in vivo and ex vivo applications of the CRISPR/Cas9 system in human disease-focused research, explore the potential of this technology in translational medicine and discuss some of the major challenges for its future use in patients.Portuguese Foundation for Science and Technology: UID/BIM/04773/2013 1334 Spanish Ministry of Science, Innovation and Universities RTI2018-094629-B-I00 Portuguese Foundation for Science and Technology SFRH/BPD/100434/2014 European Union (EU) 748585 LPCC-NRS/Terry Fox grantsinfo:eu-repo/semantics/publishedVersio

Targeted therapies for lung cancer: how did the game begin?

Landmark studies on genetic alterations underlying NSCLC have led to tailored therapies http://ow.ly/4nq0Ps.info:eu-repo/semantics/publishedVersio

Additive manufacturing: exploring the social changes and impacts

Despite the myriad of possibilities and applications of additive manufacturing (AM) technology, knowledge about the social impacts of this technology is very scarce and very limited in some areas. This paper explores how factors generated by the development of AM technology may create social impacts, affecting the health and social well-being of people, quality of life, working conditions, and the creation of wealth. This paper presents the results of an exploratory multiple case study conducted among four Portuguese organizations that use AM technology, aiming to determine their perceptions regarding the social impacts of AM, its effects, and causes. The results confirm that AM technology is mainly seen to create positive impacts on health and safety (regarding physical hazards), on expectations for the future, on leisure and recreation, on low disruption with the local economy, on economic prosperity, on the professional status, and on innovative employment types. Nevertheless, a negative impact was also found on health and safety (concerning hazardous substances), as well as several mixed and null impacts. The main limitations of the research arise from the use of a case study methodology, since the results can be influenced by contextual factors, such as the size of the organizations in the sample, and/or social, cultural, technological, political, economic, and ecological factors. This study gives an up-to-date contribution to the topic of AM social impacts and social changes, an area which is still little-explored in the literature.info:eu-repo/semantics/publishedVersio

Herbivory drives kelp recruits into ‘hiding’ in a warm ocean climate

Assessing effects of herbivory across broad gradients of varying ocean climate conditions and over small spatial scales is crucial for understand- ing its influence on primary producers. Effects of her- bivory on the distribution and abundance of kelp re- cruits were examined experimentally at two regions under contrasting ocean climate. Specifically, the abundance and survivorship of kelp recruits and the abundance of macro-herbivores were compared be- tween a ‘cool’ and a ‘warm’ region in northern and central Portugal, respectively. In each region, the abundance of kelp recruits and the intensity of grazing were compared between habitats of different topography within reefs (open reef vs. crevices). Com- pared to the ‘warm’ region, the abundance of kelp re- cruits was 3.9 times greater in the ‘cool’ region, where 85% of recruits were found in open reef habitats. In contrast, 87% of recruits in the ‘warm’ region were re- stricted to crevices. The ‘warm’ region had 140 times greater abundances of sea urchins, 45 times more herbivorous fish and 4.1 times more grazing marks on kelp recruits than the ‘cool’ region. Grazing assays showed ca. 50 times higher rates of kelp biomass con- sumption, mainly by fishes, and zero survivorship of kelp recruits in the ‘warm’ relative to the ‘cool’ region. This study suggests both temperature and herbivores affect abundances of kelp recruits across latitudes, and demonstrates how herbivores affect their distri- bution at local scales, driving kelp recruits into ‘hiding’ in crevices under intense herbivory. Conse- quently, where net recruitment success is compro- mised by herbivory, the persistence of kelps will be contingent on availability of topographical refuges

Framework for life cycle sustainability assessment of additive manufacturing

Additive manufacturing (AM) is a group of technologies that create objects by adding material layer upon layer, in precise geometric shapes. They are amongst the most disruptive technologies nowadays, potentially changing value chains from the design process to the end-of-life, providing significant advantages over traditional manufacturing processes in terms of flexibility in design and production and waste minimization. Nevertheless, sustainability assessment should also be included in the research agenda as these technologies affect the People, the Planet and the Profit: the three-bottom line (3BL) assessment framework. Moreover, AM sustainability depends on each product and context that strengthens the need for its assessment through the 3BL framework. This paper explores the literature on AM sustainability, and the results are mapped in a framework aiming to support comprehensive assessments of the AM impacts in the 3BL dimensions by companies and researchers. To sustain the coherence of boundaries, three life cycle methods are proposed, each one for a specific dimension of the 3BL analysis, and two illustrative case studies are shown to exemplify the model.info:eu-repo/semantics/publishedVersio

The influence of social support on the wellbeing of immigrants residing in Italy: Sources and functions as predictive factors for life satisfaction levels, sense of community and resilience

Moving from one country to another involves not only separation from the country of origin, but also the tiring process of integration into a new physical, institutional, and sociocultural context, which may expose migrants to acculturation stress. The loss of former support networks, or at the very least their transformation, presents immigrants with the need to rebuild their social support systems in the host country, involving an active search for support. Therefore, the aim of study is to analyze the structure of informal social support and its capacity to predict immigrants’ sense of community, resilience, and satisfaction with life. The results confirm that social support predicts satisfaction with life, sense of community, and resilience. Our findings highlight the way sources and frequency of support, and the satisfaction with which they are associated, have different degrees of predictive value on the dependent variables under investigation. In this study, it can be concluded that social support is an important factor in the well-being of migrants and their integration into the host community. The results have an important practical value in promoting interventions that improve immigrants’ support networks and, consequently, increase their satisfaction with life, sense of community, and resilience

Congruence between fine-scale genetic breaks and dispersal potential in an estuarine seaweed across multiple transition zones

Genetic structure in biogeographical transition zones can be shaped by several factors including limited dispersal across barriers, admixture following secondary contact, differential selection, and mating incompatibility. A striking example is found in Northwest France and Northwest Spain, where the estuarine seaweed Fucus ceranoides L. exhibits sharp, regional genetic clustering. This pattern has been related to historical population fragmentation and divergence into distinct glacial refugia, followed by post-glacial expansion and secondary contact. The contemporary persistence of sharp ancient genetic breaks between nearby estuaries has been attributed to prior colonization effects (density barriers) but the effect of oceanographic barriers has not been tested. Here, through a combination of mesoscale sampling (15 consecutive populations) and population genetic data (mtIGS) in NW France, we define regional genetic disjunctions similar to those described in NW Iberia. Most importantly, using high resolution dispersal simulations for Brittany and Iberian populations, we provide evidence for a central role of contemporary hydrodynamics in maintaining genetic breaks across these two major biogeographic transition zones. Our findings further show the importance of a comprehensive understanding of oceanographic regimes in hydrodynamically complex coastal regions to explain the maintenance of sharp genetic breaks along continuously populated coastlines.Foundation for Science and Technology (FCT-MEC, Portugal) [DL57/2016/CP1361/CT0035]National Research Foundation of South AfricaNational Research Foundation - South Africa [64801]FCTPortuguese Foundation for Science and TechnologyEuropean Commission [SFRH/BPD/88935/2012, SFRH/BPD/111003/2015]Pew Marine Fellowship (USA) [SFRH/BPD/111003/2015][BIODIVERSA/004/2015][IF/01413/2014/CP1217/CT0004][UID/Multi/04326/2019]info:eu-repo/semantics/publishedVersio