Active Layer Groundwater Flow: The Interrelated Effects of Stratigraphy, Thaw, and Topography

The external drivers and internal controls of groundwater flow in the thawed “active layer” above permafrost are poorly constrained because they are dynamic and spatially variable. Understanding these controls is critical because groundwater can supply solutes such as dissolved organic matter to surface water bodies. We calculated steady‐state three‐dimensional suprapermafrost groundwater flow through the active layer using measurements of aquifer geometry, saturated thickness, and hydraulic properties collected from two major landscape types over time within a first‐order Arctic watershed. The depth position and thickness of the saturated zone is the dominant control of groundwater flow variability between sites and during different times of year. The effect of water table depth on groundwater flow dwarfs the effect of thaw depth. In landscapes with low land‐surface slopes (2–4%), a combination of higher water tables and thicker, permeable peat deposits cause relatively constant groundwater flows between the early and late thawed seasons. Landscapes with larger land‐surface slopes (4–10%) have both deeper water tables and thinner peat deposits; here the commonly observed permeability decrease with depth is more pronounced than in flatter areas, and groundwater flows decrease significantly between early and late summer as the water table drops. Groundwater flows are also affected by microtopographic features that retain groundwater that could otherwise be released as the active layer deepens. The dominant sources of groundwater, and thus dissolved organic matter, are likely wet, flatter regions with thick organic layers. This finding informs fluid flow and solute transport dynamics for the present and future Arctic.Plain Language SummaryGroundwater flow in permafrost watersheds is potentially a key component of global carbon budgets because permafrost soil stores vast amounts of carbon that could be mobilized due to a warming climate and the corresponding increase in soil thaw. In addition to carrying carbon, groundwater can supply important nutrients and solutes to surface waters. However, we do not yet understand the factors that control groundwater flow in soils above permafrost because saturation changes rapidly and continuously, and soil hydraulic properties are largely unknown. We created measurement‐informed calculations of groundwater flow from areas of permafrost with different characteristics and found that soil types, which vary based on the slope of the land surface, are the most important control. Near‐surface soils were identical in hillslopes and valleys, whereas deeper soils in hillslopes allowed for less groundwater flow than in valleys. In early summer, when only the near‐surface soils were thawed, groundwater flows in the hillslopes and valley were similar. In late summer, when the deeper soil was thawed, groundwater flow in the valley remained high, but flow in the hillslope was negligible. Our observations also showed that small mounds on the land surface caused groundwater to be trapped behind underground ice dams.Key PointsDetailed measurements of hydraulic head, hydraulic conductivity, and saturated thicknesses in active layers were made over time and spaceThree main soil layers consistently comprise the stratigraphy of the active layer across the studied Arctic watershedGroundwater flow depends most on the depth of the water table and the subsurface stratigraphy, which varies based on landscape typePeer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151862/1/wrcr24085_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151862/2/wrcr24085.pd

Active Layer Groundwater Flow: The Interrelated Effects of Stratigraphy, Thaw, and Topography

The external drivers and internal controls of groundwater flow in the thawed “active layer” above permafrost are poorly constrained because they are dynamic and spatially variable. Understanding these controls is critical because groundwater can supply solutes such as dissolved organic matter to surface water bodies. We calculated steady‐state three‐dimensional suprapermafrost groundwater flow through the active layer using measurements of aquifer geometry, saturated thickness, and hydraulic properties collected from two major landscape types over time within a first‐order Arctic watershed. The depth position and thickness of the saturated zone is the dominant control of groundwater flow variability between sites and during different times of year. The effect of water table depth on groundwater flow dwarfs the effect of thaw depth. In landscapes with low land‐surface slopes (2–4%), a combination of higher water tables and thicker, permeable peat deposits cause relatively constant groundwater flows between the early and late thawed seasons. Landscapes with larger land‐surface slopes (4–10%) have both deeper water tables and thinner peat deposits; here the commonly observed permeability decrease with depth is more pronounced than in flatter areas, and groundwater flows decrease significantly between early and late summer as the water table drops. Groundwater flows are also affected by microtopographic features that retain groundwater that could otherwise be released as the active layer deepens. The dominant sources of groundwater, and thus dissolved organic matter, are likely wet, flatter regions with thick organic layers. This finding informs fluid flow and solute transport dynamics for the present and future Arctic

Dynamics of Hyporheic Flow and Heat Transport Across a Bed-to-Bank Continuum in a Large Regulated River

The lower Colorado River (LCR) near Austin, Texas is heavily regulated for hydropower generation. Daily water releases from a dam located 23 km upstream of our study site in the LCR caused the stage to fluctuate by more than 1.5 m about a mean depth of 1.3 m. As a result, the river switches from gaining to losing over a dam storage-release cycle, driving exchange between river water and groundwater. We assessed the hydrologic impacts of this by simultaneous temperature and head monitoring across a bed-to-bank transect. River-groundwater exchange flux is largest close to the bank and decreases away from the bank. Correspondingly, both the depth of the hyporheic zone and the exchange time are largest close to the bank. Adjacent to the bank, the streambed head response is hysteretic, with the hysteresis disappearing with distance from the bank, indicating that transient bank storage affects the magnitude and direction of vertical exchange close to the bank. Pronounced changes in streambed temperature are observed down to a meter. When the river stage is high, which coincides with when the river is coldest, downward advection of heat from a previous cycles\u27 warm-water pulse warms the streambed. When the river is at its lowest stage but warmest temperature, upwelling groundwater cools the streambed. Future research should consider and focus on a more thorough understanding of the impacts of dam regulation on the hydrologic, thermal, biogeochemical, and ecologic dynamics of rivers and their hyporheic and riparian zones

Kinome rewiring reveals AURKA limits PI3K-pathway inhibitor efficacy in breast cancer.

Dysregulation of the PI3K-AKT-mTOR signaling network is a prominent feature of breast cancers. However, clinical responses to drugs targeting this pathway have been modest, possibly because of dynamic changes in cellular signaling that drive resistance and limit drug efficacy. Using a quantitative chemoproteomics approach, we mapped kinome dynamics in response to inhibitors of this pathway and identified signaling changes that correlate with drug sensitivity. Maintenance of AURKA after drug treatment was associated with resistance in breast cancer models. Incomplete inhibition of AURKA was a common source of therapy failure, and combinations of PI3K, AKT or mTOR inhibitors with the AURKA inhibitor MLN8237 were highly synergistic and durably suppressed mTOR signaling, resulting in apoptosis and tumor regression in vivo. This signaling map identifies survival factors whose presence limits the efficacy of targeted therapies and reveals new drug combinations that may unlock the full potential of PI3K-AKT-mTOR pathway inhibitors in breast cancer

In Vitro Analysis of Integrated Global High-Resolution DNA Methylation Profiling with Genomic Imbalance and Gene Expression in Osteosarcoma

Genetic and epigenetic changes contribute to deregulation of gene expression and development of human cancer. Changes in DNA methylation are key epigenetic factors regulating gene expression and genomic stability. Recent progress in microarray technologies resulted in developments of high resolution platforms for profiling of genetic, epigenetic and gene expression changes. OS is a pediatric bone tumor with characteristically high level of numerical and structural chromosomal changes. Furthermore, little is known about DNA methylation changes in OS. Our objective was to develop an integrative approach for analysis of high-resolution epigenomic, genomic, and gene expression profiles in order to identify functional epi/genomic differences between OS cell lines and normal human osteoblasts. A combination of Affymetrix Promoter Tilling Arrays for DNA methylation, Agilent array-CGH platform for genomic imbalance and Affymetrix Gene 1.0 platform for gene expression analysis was used. As a result, an integrative high-resolution approach for interrogation of genome-wide tumour-specific changes in DNA methylation was developed. This approach was used to provide the first genomic DNA methylation maps, and to identify and validate genes with aberrant DNA methylation in OS cell lines. This first integrative analysis of global cancer-related changes in DNA methylation, genomic imbalance, and gene expression has provided comprehensive evidence of the cumulative roles of epigenetic and genetic mechanisms in deregulation of gene expression networks

Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization

The cytogenetic characteristics of osteosarcoma (OS) remain controversial. The establishment of a new human OS cell line may improve the characterization. We report the establishment of a new human osteosarcoma cell line, UTOS-1, from a typical osteoblastic OS of an 18-year-old man. Cultured UTOS-1 cells are spindle-shaped, and have been maintained in vitro for over 50 passages in more than 2 years. Xenografted UTOS-1 cells exhibit features typical of OS, such as production of osteoid or immature bone matrix, and proliferation potency in vivo. UTOS-1 also exhibit morphological and immunohistochemical characteristics typical of osteoblastic OS. Chromosomal analysis by G-band show 73~85 chromosomes with complicated translocations. Array CGH show frequent gains at locus DAB2 at chromosome 5q13, CCND2 at 12p13, MDM2 at 12q14.3-q15, FLI and TOP3A at 17p11.2-p12 and OCRL1 at Xq25, and show frequent losses at HTR1B at 6q13, D6S268 at 6q16.3-q21, SHGC17327 at 18ptel, and STK6 at 20q13.2-q13.3. The UTOS-1 cell line may prove useful for biologic and molecular pathogenetic investigations of human OS

Copy Number Analysis Identifies Novel Interactions Between Genomic Loci in Ovarian Cancer

Ovarian cancer is a heterogeneous disease displaying complex genomic alterations, and consequently, it has been difficult to determine the most relevant copy number alterations with the scale of studies to date. We obtained genome-wide copy number alteration (CNA) data from four different SNP array platforms, with a final data set of 398 ovarian tumours, mostly of the serous histological subtype. Frequent CNA aberrations targeted many thousands of genes. However, high-level amplicons and homozygous deletions enabled filtering of this list to the most relevant. The large data set enabled refinement of minimal regions and identification of rare amplicons such as at 1p34 and 20q11. We performed a novel co-occurrence analysis to assess cooperation and exclusivity of CNAs and analysed their relationship to patient outcome. Positive associations were identified between gains on 19 and 20q, gain of 20q and loss of X, and between several regions of loss, particularly 17q. We found weak correlations of CNA at genomic loci such as 19q12 with clinical outcome. We also assessed genomic instability measures and found a correlation of the number of higher amplitude gains with poorer overall survival. By assembling the largest collection of ovarian copy number data to date, we have been able to identify the most frequent aberrations and their interactions

NuMA Overexpression in Epithelial Ovarian Cancer

Highly aneuploid tumours are common in epithelial ovarian cancers (EOC). We investigated whether NuMA expression was associated with this phenomenon

Expression profiling identifies genes involved in neoplastic transformation of serous ovarian cancer

Background: The malignant potential of serous ovarian tumors, the most common ovarian tumor subtype, varies from benign to low malignant potential (LMP) tumors to frankly invasive cancers. Given the uncertainty about the relationship between these different forms, we compared their patterns of gene expression. Methods: Expression profiling was carried out on samples of 7 benign, 7 LMP and 28 invasive (moderate and poorly differentiated) serous tumors and four whole normal ovaries using oligonucleotide microarrays representing over 21,000 genes. Results: We identified 311 transcripts that distinguished invasive from benign tumors, and 20 transcripts that were significantly differentially expressed between invasive and LMP tumors at p < 0.01 (with multiple testing correction). Five genes that were differentially expressed between invasive and either benign or normal tissues were validated by real time PCR in an independent panel of 46 serous tumors (4 benign, 7 LMP, 35 invasive). Overexpression of SLPI and WNT7A and down-regulation of C6orf31, PDGFRA and GLTSCR2 were measured in invasive and LMP compared with benign and normal tissues. Over-expression of WNT7A in an ovarian cancer cell line led to increased migration and invasive capacity. Conclusion: These results highlight several genes that may play an important role across the spectrum of serous ovarian tumorigenesis

A systems analysis of the chemosensitivity of breast cancer cells to the polyamine analogue PG-11047

<p>Abstract</p> <p>Background</p> <p>Polyamines regulate important cellular functions and polyamine dysregulation frequently occurs in cancer. The objective of this study was to use a systems approach to study the relative effects of PG-11047, a polyamine analogue, across breast cancer cells derived from different patients and to identify genetic markers associated with differential cytotoxicity.</p> <p>Methods</p> <p>A panel of 48 breast cell lines that mirror many transcriptional and genomic features present in primary human breast tumours were used to study the antiproliferative activity of PG-11047. Sensitive cell lines were further examined for cell cycle distribution and apoptotic response. Cell line responses, quantified by the GI₅₀(dose required for 50% relative growth inhibition) were correlated with the omic profiles of the cell lines to identify markers that predict response and cellular functions associated with drug sensitivity.</p> <p>Results</p> <p>The concentrations of PG-11047 needed to inhibit growth of members of the panel of breast cell lines varied over a wide range, with basal-like cell lines being inhibited at lower concentrations than the luminal cell lines. Sensitive cell lines showed a significant decrease in S phase fraction at doses that produced little apoptosis. Correlation of the GI₅₀values with the omic profiles of the cell lines identified genomic, transcriptional and proteomic variables associated with response.</p> <p>Conclusions</p> <p>A 13-gene transcriptional marker set was developed as a predictor of response to PG-11047 that warrants clinical evaluation. Analyses of the pathways, networks and genes associated with response to PG-11047 suggest that response may be influenced by interferon signalling and differential inhibition of aspects of motility and epithelial to mesenchymal transition.</p> <p>See the related commentary by Benes and Settleman: <url>http://www.biomedcentral.com/1741-7015/7/78</url></p