RESUMO
Evaluating the uncertainty of climatic impacts on watershed systems is critical in planning for water supplies, water allocation, and demand at multiple scales. With the increasing frequency of water crises worldwide, understanding the nature of climatic impacts along spatial and temporal dimensions is vital to the development of timely, and spatially relevant mitigation options. This study aims to quantify the nature of hydrologic uncertainties at a spatial and temporal dimension in a regional watershed system under scenarios of varying climatic uncertainties. Watershed-wide impacts of climate change under uncertain future scenarios are modeled with the Soil and Water Assessment Tool (SWAT) for the Connecticut River Watershed of northeastern USA. Changes in watershed flows are quantified for at subbasin scale. The results show that uncertainty in climate change, primarily through variability in precipitation and temperature can lead to spatial and temporal uncertainty in hydrologic processes in the watershed system. In general, the results show that uncertainty in climate can significantly impact the spatial and temporal characteristics in runoff, infiltration, evapotranspiration, and water yield of watershed systems. Strategies to enhance watershed resilience to climatic uncertainty need dynamic information on the vulnerability. Spatial and temporal strategies for adaptation to climatic change conditions could include forest cover and management practices in sensitive locations at local and regional scales.
RESUMO
Human herpesvirus 6 (HHV-6) and cytomegalovirus (CMV) are population-prevalent betaherpesviruses with intermittent lytic replication that can be pathogenic in immunocompromised hosts. Elucidation of the adaptive immune response is valuable for understanding pathogenesis and designing novel treatments. Knowledge of T-cell antigens has reached the genome-wide level for CMV and other human herpesviruses, but study of HHV-6 is at an earlier stage. Using rare-cell enrichment combined with an HLA-agnostic, proteome-wide approach, we queried HHV-6B-specific CD4 T cells from 18 healthy donors with each known HHV-6B protein. We detected a low abundance of HHV-6-specific CD4 T cells in blood; however, the within-person CD4 T-cell response is quite broad: the median number of open reading frame (ORF) products recognized was nine per person. Overall, the data expand the number of documented HHV-6B CD4 T-cell antigens from approximately 11 to 60. Epitopes in the proteins encoded by U14, U90, and U95 were mapped with synthetic peptides, and HLA restriction was defined for some responses. Intriguingly, CD4 T-cell antigens newly described in this report are among the most population prevalent, including U73, U72, U95, and U30. Our results indicate that selection of HHV-6B ORFs for immunotherapy should consider this expanded panel of HHV-6B antigens.IMPORTANCE Human herpesvirus 6 is highly prevalent and maintains chronic infection in immunocompetent individuals, with the potential to replicate widely in settings of immunosuppression, leading to clinical disease. Antiviral compounds may be ineffective and/or pose dose-limiting toxicity, and therefore, immune-based therapies have garnered increased interest in recent years. Attempts at addressing this unmet medical need begin with understanding the cellular response to HHV-6 at the individual and population levels. The present study provides a comprehensive assessment of HHV-6-specific T-cell responses that may inform the development of cell-based therapies directed at this virus.
