| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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| 2. |
- Basso, Marcos Fernando, et al.
(författare)
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Overexpression of a soybean Globin (GmGlb1-1) gene reduces plant susceptibility to Meloidogyne incognita
- 2022
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Ingår i: Planta. - : SPRINGER. - 0032-0935 .- 1432-2048. ; 256:4
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Tidskriftsartikel (refereegranskat)abstract
- Non-symbiotic globin class #1 (Glb1) genes are expressed in different plant organs, have a high affinity for oxygen, and are related to nitric oxide (NO) turnover. Previous studies showed that soybean Glb1 genes are upregulated in soybean plants under flooding conditions. Herein, the GmGlb1-1 gene was identified in soybean as being upregulated in the nematode-resistant genotype PI595099 compared to the nematode-susceptible cultivar BRS133 during plant parasitism by Meloidogyne incognita. The Arabidopsis thaliana and Nicotiana tabacum transgenic lines overexpressing the GmGlb1-1 gene showed reduced susceptibility to M. incognita. Consistently, gall morphology data indicated that pJ2 nematodes that infected the transgenic lines showed developmental alterations and delayed parasitism progress. Although no significant changes in biomass and seed yield were detected, the transgenic lines showed an elongated, etiolation-like growth under well-irrigation, and also developed more axillary roots under flooding conditions. In addition, transgenic lines showed upregulation of some important genes involved in plant defense response to oxidative stress. In agreement, higher hydrogen peroxide accumulation and reduced activity of reactive oxygen species (ROS) detoxification enzymes were also observed in these transgenic lines. Thus, based on our data and previous studies, it was hypothesized that constitutive overexpression of the GmGlb1-1 gene can interfere in the dynamics of ROS production and NO scavenging, enhancing the acquired systemic acclimation to biotic and abiotic stresses, and improving the cellular homeostasis. Therefore, these collective data suggest that ectopic or nematode-induced overexpression, or enhanced expression of the GmGlb1-1 gene using CRISPR/dCas9 offers great potential for application in commercial soybean cultivars aiming to reduce plant susceptibility to M. incognita.
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| 3. |
- Couch, Fergus J., et al.
(författare)
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Identification of four novel susceptibility loci for oestrogen receptor negative breast cancer
- 2016
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 7:11375, s. 1-13
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Tidskriftsartikel (refereegranskat)abstract
- Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P<5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P<0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and PPIL3 at 2q33 in ER-negative breast cancer aetiology. All ER-negative loci combined account for similar to 11% of familial relative risk for ER-negative disease and may contribute to improved ER-negative and BRCA1 breast cancer risk prediction.
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| 4. |
- Graca, Marisa, et al.
(författare)
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Designing urban green spaces for climate adaptation : A critical review of research outputs
- 2022
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Ingår i: Urban Climate. - : Elsevier. - 2212-0955. ; 42
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Forskningsöversikt (refereegranskat)abstract
- Urban green spaces provide important contributions to enhance climate adaptation, and therefore research in this area has increased exponentially in the last decades. While several studies showed that the morphology and type of living and built elements of urban green spaces greatly affect their performance, a persistent gap between theory and practice continues to pervade the design of green spaces. This study conducts a semi-systematic review of research published in the last decade to investigate to what extent recent research has produced evidence-based outputs relevant to practitioners concerning the design of outdoor urban green spaces in the context of climate adaptation. An innovative design-oriented approach is subsequently applied to critically review evidence-based research outputs considering a comprehensive spectrum of climate impacts and adaptation measures. Our specific objectives are to: i) identify evidence-based research outputs of relevance to practitioners according to type of climatic impact; ii) assess the level of relevance and geographical transferability of such outputs to support the design of urban green spaces; and iii) identify key challenges that might hinder the implementation of evidence-based guidelines. Our results support a call to align research to confront the wicked gap between scientific research and implementation in design practice.
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| 5. |
- Lawrenson, Kate, et al.
(författare)
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Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus
- 2016
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk.
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| 6. |
- Monteiro, Ana, et al.
(författare)
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Contributo para uma maior e melhor perceção e consciência dos Riscos Climáticos. Citizen Sensing - O caso do Porto
- 2019
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Konferensbidrag (refereegranskat)abstract
- O projeto Citizen Sensing (projecto europeu no âmbito do programa ERA4CS) pretende desenvolver um sistema participativo de gestão de risco climático capaz de incorporar informação local, no quadro das diretrizes sobre adaptação face aos riscos climáticos e analisar até que ponto um sistema deste tipo pode contribuir para melhorar o nível de preparação e de resposta por parte dos cidadãos e das autoridades de modo aumentar a resiliência urbana em diferentes contextos europeus.O projeto irá desenvolver e testar um sistema piloto de gestão de risco participativo em quatro cidades europeias - Porto (Portugal), Roterdão (Holanda), Norrköping (Suécia) e Trondheim (Noruega), estudando se e como o sistema poderá aumentar o envolvimento dos cidadãos e a contribuição para a resiliência urbana.A plataforma conjuga informação recolhida pelas formas clássicas com informação fornecida pelas pessoas e, simultaneamente, fornece-lhes informação para responderem de forma adequada às situações de risco a que estão expostas, tal como serão utilizados sensores de monitorização de elementos climáticos na cidade.
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| 7. |
- Neset, Tina-Simone, 1973-, et al.
(författare)
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Navigating urban heat – Assessing the potential of a pedestrian routing tool
- 2022
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Ingår i: Urban Climate. - : Elsevier. - 2212-0955. ; 46
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Tidskriftsartikel (refereegranskat)abstract
- Cities are experiencing unprecedented climate impacts related to increasing temperatures, which vary within a city due to the heterogenous nature of urban environments. Adapting urban areas to heat requires efforts on multiple levels from urban governance, spatial planning and design to adapting everyday activities. This paper presents the prototype of a pedestrian routing tool to support citizens in navigating urban heat, and the results of tests and interviews with 24 practitioners and experts in Portugal and Sweden. The study aims to assess how and to what extent a navigation tool on urban heat could support urban climate risk management, and to evaluate the potential of the tool to support everyday adaptation and increase citizen engagement. We explore what functionality and additional information would be required to make the tool useful and relevant for different user groups. Results indicate that (i) climate services that fit in your pocket increase access to climate information and have potential to guide everyday adaptation practices; and (ii) applications need to be contextualized and tailored to match the needs and decision contexts of the user through integration of relevant information or tools.
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| 8. |
- Wilk, Julie, 1962-, et al.
(författare)
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Citizen Sensing Stakeholder Interaction Manual
- 2021
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Rapport (populärvet., debatt m.m.)abstract
- This stakeholder interaction manual was prepared in the ERA4CS project: Citizen Sensing - Urban climate resilience through a Participatory Risk Management System(PRMS). The Participatory Risk Management System includes an app by which end-users upload reports (weather observations, eventual impacts, level of personal comfort accompanied by comments and/or images) and a spatial-temporal visualization platform (the CitizenSensing web-portal) that allows users to view, explore and analyze the reports (see Navarra et al. 2020). The aim of the manual is to guide stakeholder interactions within the project to assess and gain deeper insight into the perceptions, priorities and reflections of stakeholders2 that were involved in the co-design process and organize the end-user3 campaigns.The “Getting Started” section contains general information about participants, workshops, aims, outcomes, preparations, equipment, opening and closing workshops and communication. The following sections contain participatory exercises that could be performed with stakeholders and/or end-users to inform and guide the co-design process of CitizenSensing researchers and municipal through the set-up, testing and assessment of the PRMS. The exercises are organized under a number of workshops4. These would be performed with several participants, but the same exercises could be performed at or smaller meetings with a few people or individuals.The workshop sections contain a number of interactive exercises that cover a number of themes: Climate-related issues and project pre-conditions (Workshop 1A)Risks, sensitive groups and locations and climate-related variables (Workshop 1B)Sensor networks, databases and municipal tasks (Workshop 2A)App requirements, critical levels and recommendations (Workshop 2B)Assessing possibilities for measurement/observation campaigns (Workshop 3)Designing the end-user campaigns (Workshop 4)Preparing the end-user campaigns (Workshop 5)Initiating the end-user campaigns (Workshop 6)Concluding the end-user campaigns (Workshop 7).Assessing stakeholder perspectives: Workshop (Workshop 8)Assessing stakeholder perspectives: InterviewsAppendices I and II contain pre-campaign and post-campaign surveys to be conducted at Workshops 4 and 5. Appendix III contains an interview guide that could be used in Workshops 8 or 9. Appendix IV contains a guide to exploring the web-portal that could be used in Workshops 8 or 9.
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