Proneural and mesenchymal glioma stem cells display major differences in splicing and lncRNA profiles

Therapy resistance and recurrence in high-grade gliomas are driven by their populations of glioma stem cells (GSCs). Thus, detailed molecular characterization of GSCs is needed to develop more effective therapies. We conducted a study to identify differences in the splicing profile and expression of long non-coding RNAs in proneural and mesenchymal GSC cell lines. Genes related to cell cycle, DNA repair, cilium assembly, and splicing showed the most differences between GSC subgroups. We also identified genes distinctly associated with survival among patients of mesenchymal or proneural subgroups. We determined that multiple long non-coding RNAs with increased expression in mesenchymal GSCs are associated with poor survival of glioblastoma patients. In summary, our study established critical differences between proneural and mesenchymal GSCs in splicing profiles and expression of long non-coding RNA. These splicing isoforms and lncRNA signatures may contribute to the uniqueness of GSC subgroups, thus contributing to cancer phenotypes and explaining differences in therapeutic responses.This study was supported by a grant from Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil to PAFG and LOFP and by NIH 7R21CA175875-03. This study was partially supported by grants from Serrapilheira foundation and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP; 2018/15579-8) to PAFG. GDAG and BRC were supported by fellowships from FAPESP (2017/19541-2) and (2013/25483-4 and 2013/07159-5), respectively. PRA was supported by CPRIT Training Grant - RP14010

A review of vulnerability indicators for deltaic social–ecological systems

The sustainability of deltas worldwide is under threat due to the consequences of global environmental change (including climate change) and human interventions in deltaic landscapes. Understanding these systems is becoming increasingly important to assess threats to and opportunities for long-term sustainable development. Here, we propose a simplified, yet inclusive social–ecological system (SES)-centered risk and vulnerability framework and a list of indicators proven to be useful in past delta assessments. In total, 236 indicators were identified through a structured review of peer-reviewed literature performed for three globally relevant deltas—the Mekong, the Ganges–Brahmaputra–Meghna and the Amazon. These are meant to serve as a preliminary “library” of potential indicators to be used for future vulnerability assessments. Based on the reviewed studies, we identified disparities in the availability of indicators to populate some of the vulnerability domains of the proposed framework, as comprehensive social–ecological assessments were seldom implemented in the past. Even in assessments explicitly aiming to capture both the social and the ecological system, there were many more indicators for social susceptibility and coping/adaptive capacities as compared to those relevant for characterizing ecosystem susceptibility or robustness. Moreover, there is a lack of multi-hazard approaches accounting for the specific vulnerability profile of sub-delta areas. We advocate for more comprehensive, truly social–ecological assessments which respond to multi-hazard settings and recognize within-delta differences in vulnerability and risk. Such assessments could make use of the proposed framework and list of indicators as a starting point and amend it with new indicators that would allow capturing the complexity as well as the multi-hazard exposure in a typical delta SES