The First Nation communities in northern Ontario have unique energy-related challenges within an interdisciplinary context, including historical, geographic, cultural, technological, and regulatory. ...Presently, undergoing an energy systems transition from off-grid to grid-connection and scoping renewable energy options, these remote communities are exhibiting characteristics of complex adaptive system principles. This is exhibited through non-linear interactions and connectedness among agents and components in the emerging energy system. This paper explores these interfaces through a case study of Poplar Hill First Nation, an Independent Power Authority community. The potentials of the complexity science through a community engagement process is used to encode and enhance understanding of the "contextual" complexities in the development of local economies, adapting to technology advancement, and social changes. The findings will help better appreciate the efforts made by Poplar Hill in their transition to self-sufficient systems with deliberations that may provide practical outcomes. This paper reflects on the deeper trajectories of the human elements embedded within the energy transition process. In conclusion, the paper adds to the academic dialogue on energy system transition adaptations in marginalised Indigenous communities in rural and remote locations.
Benzo(ghi)perylene (BghiP) and 1,2,3,4,6,7,8-Heptachlorodibenzo-p-dioxin (HpCDD) were elevated in serum from personnel deployed to sites with open burn pits. Here, we investigated the ability of ...BghiP and HpCDD to regulate microRNA (miRNA) expression through the aryl hydrocarbon receptor (AHR).
Human lung fibroblasts (HLFs) were exposed to BghiP and HpCDD. AHR activity was measured by reporter assay and gene expression. Deployment related miRNA were measured by quantitative polymerase chain reaction. AHR expression was depleted using siRNA.
BghiP displayed weak AHR agonist activity. HpCDD induced AHR activity in a dose-dependent manner. Let-7d-5p, miR-103-3p, miR-107, and miR-144-3p levels were significantly altered by HpCDD. AHR knockdown attenuated these effects.
These studies reveal that miRNAs previously identified in sera from personnel deployed to sites with open burn pits are altered by HpCDD exposure in HLFs.
Huntington’s disease (HD) is characterized by hypomyelination as well as neuronal loss. To assess the basis for myelin loss in HD, we generated bipotential glial progenitor cells (GPCs) from human ...embryonic stem cells (hESCs), derived from huntingtin (mHTT)-mutant embryos or normal controls, and performed RNAseq to assess mHTT-dependent changes in gene expression. In hGPCs derived from 3 mHTT hESC lines, transcription factors associated with glial differentiation and myelin synthesis were sharply down-regulated relative to normal hESC GPCs; NKX2.2, OLIG2, SOX10, MYRF and their downstream targets were all suppressed. Accordingly, when mHTT hGPCs were transplanted into hypomyelinated
shiverer
mice, the resultant glial chimeras were hypomyelinated; this defect could be rescued by forced expression of SOX10 and MYRF by mHTT hGPCs. The mHTT hGPCs also manifested impaired astrocytic differentiation, and developed abnormal fiber architecture. White matter involution in HD is thus a product of the cell autonomous, mHTT-dependent suppression of glial differentiation.
The authors show that glial progenitor cells derived from human ES cells expressing mutant Huntingtin (mHTT) are delayed and defective in their maturation; their suppressed transcription of differentiation-associated genes leads to both astrocytic dysfunction and myelin deficiency in vivo. Glial pathology may thus contribute to disease phenotype in Huntington’s disease.
In a comparison of gene expression by A2B5-defined glial tumor progenitor cells (TPCs) to glial progenitor cells derived from normal adult human brain (Cell Reports 3:2127-41, 2013), we found that ...the F2R gene encoding PAR1 was differentially over-expressed by TPCs isolated from primary gliomas at every stage of glioma progression. In this study, we therefore asked if PAR1 activation was causally associated with glioma progression. Lentiviral shRNAi knock-down of PAR1 inhibited the expansion and proliferation of glioma TPCs in vitro. We further found that the PAR-1 receptor antagonists SCH79797 and SCH530348 (vorapaxar) inhibited A2B5
+
TPC expansion and migration in vitro. PAR1 knockdown also suppressed the tumorigenic potential of A2B5
+
TPCs after transplantation into the brains of immunodeficient mice. In addition, mice given subcutaneous grafts of A2B5
+
human glioma TPCs exhibited delayed tumor growth if treated with Vorapaxar, relative to xenografted control mice treated with only vehicle. Together, these data suggest that PAR1 may contribute to glioma progenitor expansion and tumor growth; as such, the abrogation of PAR1 signaling may contribute to the treatment of malignant glioma.
Changes in the availability of soil moisture will be an important impact of climatic change in the future. Our ability to forecast these changes is somewhat suspect; modelled predictions frequently ...disagree not only in the magnitude, but even the direction of change. This study investigated the nature of these disagreements through the use of an off-line land surface scheme combined with forcing data from several AGCMs. A review of previous work identified three crucial factors in land surface schemes: (1) the plant-available moisture capacity of the soil, (2) the dependence of evapotranspiration and runoff on soil moisture, and (3) the inclusion of a canopy layer with a suitable stomatal conductance. These factors were incorporated into a simple land surface scheme, the Potential Evapotranspiration Leaky Bucket (PELB) model, to create a tool for off-line intercomparisons. PELB was successfully tested against AGCM results, with the conclusion that under steady climatic conditions, land surface scheme choices accounted for roughly half of the difference among AGCM simulations. PELB met with only moderate success in experiments with climatic change; in general, there was somewhat excessive drying in PELB compared to the AGCM results. Nevertheless, there was strong evidence that land surface scheme choices have a much less significant influence on soil moisture forecasts under expected global warming conditions. Temperature and precipitation changes have a dominant impact on the soil moisture regimes of AGCMs. The results of this study affirm the ability of off-line models to make practical contributions to our understanding of soil moisture change. The strengths and limitations of off-line modelling are discussed, along with prospects for further research.
In a comparison of gene expression by A2B5-defined glial tumor progenitor cells (TPCs) to glial progenitor cells derived from normal adult human brain (Cell Reports 3:2127-41, 2013), we found that ...the F2R gene encoding PAR1 was differentially over-expressed by TPCs isolated from primary gliomas at every stage of glioma progression. In this study, we therefore asked if PAR1 activation was causally associated with glioma progression. Lentiviral shRNAi knock-down of PAR1 inhibited the expansion and proliferation of glioma TPCs in vitro. We further found that the PAR-1 receptor antagonists SCH79797 and SCH530348 (vorapaxar) inhibited A2B5+ TPC expansion and migration in vitro. PAR1 knockdown also suppressed the tumorigenic potential of A2B5+ TPCs after transplantation into the brains of immunodeficient mice. In addition, mice given subcutaneous grafts of A2B5+ human glioma TPCs exhibited delayed tumor growth if treated with Vorapaxar, relative to xenografted control mice treated with only vehicle. Together, these data suggest that PAR1 may contribute to glioma progenitor expansion and tumor growth; as such, the abrogation of PAR1 signaling may contribute to the treatment of malignant glioma.
With computers now capable of easily handling all kinds of multimedia files in vast quantity, and with the Internet now well-suited to exchange these files, we are faced with the challenge of ...organizing this data in such a way so as to make the information most useful and accessible. This holds true as well for media pertaining to the field of biology, where multimedia is particularly useful in education, as well as in research. To help address this, a software system with a Web-based interface has been developed for improving the accuracy and specificity of multimedia searching and browsing by integrating semantic data pertaining to the field of biology from the Unified Medical Language System (UMLS). Using the Biology Media Repository with Semantic Augmentation (BioMeRSA) system, users who are considered to be ‘experts’ can associate concepts from UMLS with multimedia files submitted by other users to provide semantic context for the files. These annotations are used to retrieve relevant files in the searching and browsing interfaces. A wide variety of image files are currently supported, with some limited support for video and audio files.