Visions and Recommendations for By the IUCN Commission on Education and Communication (CEC)

Since its birth in 1949 the IUCN CEC has embraced an active advocacy for promoting education as a means to adopt attitudes and practices leading to nature conservation and human well-being. Against this target the UNESCO Futures of Education initiative resonates with the CEC in the quest for a knowledge-based education that forges a better future for humankind and Earth. The CEC and its partners in #NatureForAll movement have embarked on reconnection with nature as an evidenced approach to ensure a prosperous and sustainable coexistence of humanity and nature and found that education in both its formal and creative techniques should work on reestablishing these connections. In response to the UNESCO Futures of Education initiative the CEC conducted a two phase consultation process (guided by the minimally modified UNESCO survey on the top challenges and purposes of education) to explore its members’ views on which challenges are expected to most affect humankind in 2050 and are thus worth addressing in education directed at sustainable development. The process also included drawing members’ recommendations on how education in the fields of nature, biodiversity and sustainability can contribute in meeting these challenges. It may not be considered a surprise that among the top five challenges selected by the respondents the first four places were occupied by nature-related challenges namely climate change, biodiversity loss, environmental crises and human-nature disconnect, with this latter being added to the survey list in light of respondents’ relevant backgrounds and experiences. Several respondents who chose these challenges also selected other challenges that are not so distinctly related to nature issues thus pinpointing associations between the two types such as cause-effect relations. Hence we see economic inequalities, global health crises, poverty and injustice also significantly chosen as top five challenges. In voting for issues education should focus on to meet the top five challenges (the above four and population growth) the overwhelming majority of respondents cited systemic change and sustainability through knowledge transfer, problem solving, attitude change and promotion of active and conscious citizenship. Education, many respondents argued, should focus on behavioural change of students, adults and decision makers. It should also mainstream locality considerations such as the revival of traditional knowledge, be based on firsthand learning in natural settings and follow innovative approaches. Combating climate change, which was considered the top challenge, 2 exemplifies this emphasis on local knowledge transfer, place-based engagement, innovative education methods, systemic and critical thinking as to create awareness, change attitudes and develop skills to act effectively against its impact and best serve the education purposes necessary to minimize this impact on humankind and Earth in 2050.Fil: Czippan, Katalin. Education Committee of Hungarian National Commission for UNESCO; HungríaFil: Charles, Cheryl. Children & Nature Network; Estados UnidosFil: Abd-Alhadi, Firas. Education Task force IUCN; JordaniaFil: Abdallah, Aishah. Wilderness Leadership and Environmental Education; Arabia SauditaFil: Zavarzin, Aleksey. Steering Committee IUCN CEC; RusiaFil: Pisupati, Balakrishna. Steering Committee IUCN CEC; IndiaFil: Sziva, Daniel. IUCN CEC; HungríaFil: Li, Hanying. Steering Committee IUCN CEC; ChinaFil: Camargo, Luis. OpEPA; ColombiaFil: Ratiani, Manana. ESD Steering Committee. Expert Group on ESD Competences UNECE; GeorgiaFil: Otieno, Margaret. Steering Committee IUCN CEC; KeniaFil: Garnett, Tommy. Steering Committee IUCN CEC; Sierra LeonaFil: Horváth, Zsuzsanna. IUCN CEC; HungríaFil: Kray, Zsuzsanna. IUCN CEC; HungríaFil: Medero, Laura Silvina. Instituto Nacional de Tecnología Agropecuaria (INTA). Instituto de Recursos Biológicos; Argentin

VAV3 mediates resistance to breast cancer endocrine therapy

Introduction: Endocrine therapies targeting cell proliferation and survival mediated by estrogen receptor α (ERα) are among the most effective systemic treatments for ERα-positive breast cancer. However, most tumors initially responsive to these therapies acquire resistance through mechanisms that involve ERα transcriptional regulatory plasticity. Herein we identify VAV3 as a critical component in this process. Methods: A cell-based chemical compound screen was carried out to identify therapeutic strategies against resistance to endocrine therapy. Binding to ERα was evaluated by molecular docking analyses, an agonist fluoligand assay and short hairpin (sh)RNA–mediated protein depletion. Microarray analyses were performed to identify altered gene expression. Western blot analysis of signaling and proliferation markers, and shRNA-mediated protein depletion in viability and clonogenic assays, were performed to delineate the role of VAV3. Genetic variation in VAV3 was assessed for association with the response to tamoxifen. Immunohistochemical analyses of VAV3 were carried out to determine its association with therapeutic response and different tumor markers. An analysis of gene expression association with drug sensitivity was carried out to identify a potential therapeutic approach based on differential VAV3 expression. Results: The compound YC-1 was found to comparatively reduce the viability of cell models of acquired resistance. This effect was probably not due to activation of its canonical target (soluble guanylyl cyclase), but instead was likely a result of binding to ERα. VAV3 was selectively reduced upon exposure to YC-1 or ERα depletion, and, accordingly, VAV3 depletion comparatively reduced the viability of cell models of acquired resistance. In the clinical scenario, germline variation in VAV3 was associated with the response to tamoxifen in Japanese breast cancer patients (rs10494071 combined P value = 8.4 × 10−4). The allele association combined with gene expression analyses indicated that low VAV3 expression predicts better clinical outcome. Conversely, high nuclear VAV3 expression in tumor cells was associated with poorer endocrine therapy response. Based on VAV3 expression levels and the response to erlotinib in cancer cell lines, targeting EGFR signaling may be a promising therapeutic strategy. Conclusions: This study proposes VAV3 as a biomarker and a rationale for its use as a signaling target to prevent and/or overcome resistance to endocrine therapy in breast cancer.This work was supported by grants from the Eugenio Rodríguez Pascual Foundation (2012, to MAP), the Government of Catalonia (2009-SGR283, to AV and MAP), the National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health (R01 DK015556, to JAK), the Red Cooperative Research Thematic Network on Cancer (RTICC) (12/0036/0002 to XRB and 12/0036/0008 to XRB and MAP) and the Spanish Ministry of Health, Fund for Health Research–Institute of Health Carlos III (11/00951 to AU and 12/01528 to MAP