ALBERT

Description: Climate change would significantly affect the temporal pattern and amount of annual precipitation at the regional level, which in turn would affect the regional water resources and future water availability. The Peace Region is a critical region for northern British Columbia’s social, environmental, and economic development, due to its potential in various land use activities. This study investigated the impacts of future climate change induced precipitation on water resources under the A2 and B1 greenhouse gas emission scenarios for 2020–2040 in a study area along the main river of the Kiskatinaw River watershed in the Peace Region as a case study using the Gridded Surface Subsurface Hydrologic Analysis (GSSHA) modeling system. The simulation results showed that climate change induced precipitation changes significantly affect monthly, seasonal and annual stream flows. With respect to the mean annual stream flow of the reference period (2000–2011), the mean annual stream flow from 2020 to 2040 under the A2 and B1 scenarios is expected to increase by 15.5% and 12.1%, respectively, due to the increased precipitation (on average 5.5% in the A2 and 3.5% in the B1 scenarios) and temperature (on average 0.76 °C in the A2 and 0.57 °C in the B1 scenarios) predicted, with respect to that under the reference period. From the seasonal point of view, the mean seasonal stream flow during winter, spring, summer and fall from 2020 to 2040 under the A2 scenario is expected to increase by 10%, 16%, 11%, and 11%, respectively. On the other hand, under the B1 scenario these numbers are 6%, 15%, 6%, and 8%, respectively. Increased precipitation also resulted in increased groundwater discharge and surface runoff. The obtained results from this study will provide valuable information for the study area in the long-term period for seasonal and annual water extractions from the river and allocation to the stakeholders for future water supply, and help develop a regional water resources management plan for climate change induced precipitation changes.

Description: This study presents the understanding of temporal dynamics of groundwater-surface water (GW-SW) interaction due to parameter uncertainty by using a physically-based and distributed gridded surface subsurface hydrologic analysis (GSSHA) model combined with a Monte Carlo simulation. A study area along the main stem of the Kiskatinaw River of the Kiskatinaw River watershed, Northeast British Columbia, Canada, was used as a case study. Two different greenhouse gas (GHG) emission scenarios (i.e., A2: heterogeneous world with self-reliance and preservation of local identities, and B1: a more integrated and environmental-friendly world) of the Special Report on Emissions Scenarios (SRES) from the Fourth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) for 2013 were used as case scenarios. Before conducting uncertainty analysis, a sensitivity analysis was performed to find the most sensitive parameters to the model output (i.e., mean monthly groundwater contribution to stream flow). Then, a Monte Carlo simulation was used to conduct the uncertainty analysis. The uncertainty analysis results under both case scenarios revealed that the pattern of the cumulative relative frequency distribution of the mean monthly and annual groundwater contributions to stream flow varied monthly and annually, respectively, due to the uncertainties of the sensitive model parameters. In addition, the pattern of the cumulative relative frequency distribution of a particular month’s groundwater contribution to the stream flow differed significantly between both scenarios. These results indicated the complexities and uncertainties in the GW-SW interaction system. Therefore, it is of necessity to use such uncertainty analysis results rather than the point estimates for better water resources management decision-making.

Description: This study presents the understanding of temporal dynamics of groundwater-surface water (GW-SW) interaction due to parameter uncertainty by using a physically-based and distributed gridded surface subsurface hydrologic analysis (GSSHA) model combined with a Monte Carlo simulation. A study area along the main stem of the Kiskatinaw River of the Kiskatinaw River watershed, Northeast British Columbia, Canada, was used as a case study. Two different greenhouse gas (GHG) emission scenarios (i.e., A2: heterogeneous world with self-reliance and preservation of local identities, and B1: a more integrated and environmental-friendly world) of the Special Report on Emissions Scenarios (SRES) from the Fourth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC) for 2013 were used as case scenarios. Before conducting uncertainty analysis, a sensitivity analysis was performed to find the most sensitive parameters to the model output (i.e., mean monthly groundwater contribution to stream flow). Then, a Monte Carlo simulation was used to conduct the uncertainty analysis. The uncertainty analysis results under both case scenarios revealed that the pattern of the cumulative relative frequency distribution of the mean monthly and annual groundwater contributions to stream flow varied monthly and annually, respectively, due to the uncertainties of the sensitive model parameters. In addition, the pattern of the cumulative relative frequency distribution of a particular month’s groundwater contribution to the stream flow differed significantly between both scenarios. These results indicated the complexities and uncertainties in the GW-SW interaction system. Therefore, it is of necessity to use such uncertainty analysis results rather than the point estimates for better water resources management decision-making.

Description: Background: MADS-box transcription factors (TFs) are important in floral organ specification as well as several other aspects of plant growth and development. Studies on stress resistance-related functions of MADS-box genes are very limited and no such functional studies in Brassica rapa have been reported. To gain insight into this gene family and to elucidate their roles in organ development and stress resistance, we performed genome-wide identification, characterization and expression analysis of MADS-box genes in B. rapa. Results: Whole-genome survey of B. rapa revealed 167 MADS-box genes, which were categorized into type I (Mα, Mβ and Mγ) and type II (MIKCc and MIKC*) based on phylogeny, protein motif structure and exon-intron organization. Expression analysis of 89 MIKCc and 11 MIKC* genes was then carried out. In addition to those with floral and vegetative tissue expression, we identified MADS-box genes with constitutive expression patterns at different stages of flower development. More importantly, from a low temperature-treated whole-genome microarray data set, 19 BrMADS genes were found to show variable transcript abundance in two contrasting inbred lines of B. rapa. Among these, 13 BrMADS genes were further validated and their differential expression was monitored in response to cold stress in the same two lines via qPCR expression analysis. Additionally, the set of 19 BrMADS genes was analyzed under drought and salt stress, and 8 and 6 genes were found to be induced by drought and salt, respectively. Conclusion: The extensive annotation and transcriptome profiling reported in this study will be useful for understanding the involvement of MADS-box genes in stress resistance in addition to their growth and developmental functions, which ultimately provides the basis for functional characterization and exploitation of the candidate genes for genetic engineering of B. rapa.

Description: This study assessed how hydraulic fracturing (HF) (water withdrawals from nearby river water source) and its associated activities (construction of well pads) would affect surface water and groundwater in 2021–2036 under changing climate (RCP4.5 and RCP8.5 scenarios of the CanESM2) in a shale gas and oil play area (23,984.9 km2) of northwestern Alberta, Canada. An integrated hydrologic model (MIKE-SHE and MIKE-11 models), and a cumulative effects landscape simulator (ALCES) were used for this assessment. The simulation results show an increase in stream flow and groundwater discharge in 2021–2036 under both RCP4.5 and RCP8.5 scenarios with respect to those under the base modeling period (2000–2012). This occurs because of the increased precipitation and temperature predicted in the study area under both RCP4.5 and RCP8.5 scenarios. The results found that HF has very small (less than 1%) subtractive impacts on stream flow in 2021–2036 because of the large size of the study area, although groundwater discharge would increase minimally (less than 1%) due to the increase in the gradient between groundwater and surface water systems. The simulation results also found that the construction of well pads related to HF have very small (less than 1%) additive impacts on stream flow and groundwater discharge due to the non-significant changes in land use. The obtained results from this study provide valuable information for effective long-term water resources decision making in terms of seasonal and annual water extractions from the river, and allocation of water to the oil and gas industries for HF in the study area to meet future energy demand considering future climate change.

Description: Background: Roxadustat (FG-4592) is an oral hypoxia-inducible factor (HIF) prolyl hydroxylase inhibitor that promotes coordinated erythropoiesis through HIF-mediated transcription. Transient, intermittent HIF activation by roxadustat mimics a physiological response that increases endogenous erythropoietin (EPO) production to near physiologic range and stimulates EPO receptor synthesis. In addition, roxadustat promotes iron metabolism by reducing serum hepcidin to allow absorption of iron from the gut and mobilize iron from cellular storage making more iron available for erythropoiesis. Roxadustat corrected and maintained hemoglobin (Hb) in chronic kidney disease patients in multiple Phase 3 trials irrespective of underlying inflammation. In these studies, roxadustat-treated patients required less IV iron to correct and maintain Hb compared to erythropoiesis-stimulating agent (ESA)-treated patients. MDS is characterized by symptomatic anemia and many patients require RBC transfusion and/or ESA treatment. As response to ESAs varies across sub-populations with limited durability, there is an unmet need for treatment of anemia in LR-MDS. This is the first study to evaluate the effect of roxadustat in treating anemia in primary MDS patients. Methods: This is a two-part study; an open-label (OL), dose-finding segment (N=24) followed by a randomized double-blind (DB) placebo-controlled segment (N=156, 3:2 ratio of roxadustat to placebo). The primary goal of the OL segment is to identify the starting roxadustat dose-level for the DB segment. A total 24 patients in the OL segment have been enrolled in three sequential cohorts with 8 patients in each starting dose cohort (1.5, 2.0, or 2.5 mg/kg). RBC transfusion has been allowed per institutional criteria. Eligible patients were very low, low or intermediate risk primary MDS patients based on the International Prognostic Scoring System Revised classification with 18 years old; and had LTB defined as receiving 1-4 RBC units per 8 week period. Patients were ineligible if they used an ESA within 8 weeks of the study start; had endogenous EPO levels 〉400 mIU/mL, or had a del(5q) cytogenetic abnormality. Roxadustat was administered TIW with doses titrated every 8 weeks per a dosing algorithm based on Hb response and transfusion need. Data from the OL segment were evaluated to identify the starting dose for the DB segment (currently enrolling). The primary endpoint is transfusion independence (TI) for ≥56 consecutive days during the first 28 weeks of treatment. The proportion of patients who achieve ≥50% reduction in RBC transfusion over any 8 weeks compared to baseline (8 weeks prior to Day 1) and proportion of patients who achieve TI for ≥20 consecutive weeks are evaluated. Safety and tolerability are assessed by adverse event reporting, percentage of patients progressing to acute myeloid leukemia (AML), and clinical laboratory values. Results: Twenty-four transfusion dependent, LR-MDS patients were enrolled in the OL segment of this global Phase 3 trial. Nine patients (38%) achieved TI for at least 56 consecutive days within the first 28 weeks.Three of 9 patients started at 1.5 mg/kg dose, 1 patient started at 2.0 mg/kg dose and 5 patients started at 2.5 mg/kg dose. At the time of achieving TI, 7 of 9 patients (78%) were on 2.5 mg/kg dose, 1 patient (11%) was on 2.0 mg/kg dose (started with 1.5 mg/kg dose) and one patient (11%) was on 1.5 mg/kg dose. Four patients remained TI for 〉20 weeks (one at 1.5 mg/kg dose level and three at 2.5 mg/Kg dose-level). One additional patient achieved TI after the initial 28-week dosing period at a dose-level of 3.5 mg/kg (starting dose 2.0 mg/kg). A total of 14 patients (58%) achieved a ≥50% reduction in RBC units in any 8-week period compared to baseline (range of 2-4 RBC units in 8 weeks before dosing); 12 of these patients were at ≥ 2.5 mg/kg dose level when achieving a 50% reduction in transfusion without need for IV iron. The overall safety profile observed is consistent with the patient population under study. Six patients reported 8 treatment-emergent SAEs with none being fatal. No patient has progressed to AML. Full results from the OL segment of the study will be presented. Conclusion: Based on the observed response (TI and transfusion reduction) and safety profile in LR-MDS patients, 2.5 mg/kg was selected as the starting dose for the ongoing 156-patient DB portion of the trial. Disclosures Harrup: Cooperative Trial Group for NeuroOncolog: Other: Collaborative Clinical Trials Group; Cancer Council of Tasmania: Membership on an entity's Board of Directors or advisory committees. Mittelman:Novartis: Honoraria, Research Funding, Speakers Bureau. Bradley:FibroGen Inc.: Employment, Equity Ownership. Saha:FibroGen Inc.: Employment, Equity Ownership. Bartels:FibroGen Inc.: Employment, Equity Ownership. Robert:FibroGen Inc.: Employment, Equity Ownership. Yu:FibroGen Inc.: Employment, Equity Ownership.

Description: The obligate biotroph Plasmodiophora brassicae causes clubroot disease in oilseeds and vegetables of the Brassicaceae family, and cytokinins play a vital role in clubroot formation. In this study, we examined the expression patterns of 17 cytokinin-related genes involved in the biosynthesis, signaling, and degradation in Chinese cabbage inoculated with the Korean pathotype group 4 isolate of P. brassicae, Seosan. This isolate produced the most severe clubroot symptoms in Chinese cabbage cultivar “Bullam-3-ho” compared to three other Korean geographical isolates investigated. BrIPT1, a cytokinin biosynthesis gene, was induced on Day 1 and Day 28 in infected root tissues and the upregulation of this biosynthetic gene coincided with the higher expression of the response regulators BrRR1, on both Days and BrRR6 on Day 1 and 3. BrRR3 and 4 genes were also induced during gall enlargement on Day 35 in leaf tissues. The BrRR4 gene, which positively interact with phytochrome B, was consistently induced in leaf tissues on Day 1, 3, and 14 in the inoculated plants. The cytokinin degrading gene BrCKX3-6 were induced on Day 14, before gall initiation. BrCKX2,3,6 were induced until Day 28 and their expression was downregulated on Day 35. This insight improves our current understanding of the role of cytokinin signaling genes in clubroot disease development.