Seasonal Flow Rates along the Lower Bear River, UT

The goal of this research is to identify how flow on the Bear River in Cache Valley has changed over the last three years and how flow changes seasonally. Identifying flows is important to manage water resources along the Bear River. We collected and processed water pressure data every 30 minutes using HOBO transducers at two sites in Cache Valley (Morton, just downstream of highway 142, and Confluence which is located at the confluence of the Bear and Cub Rivers) south of the Idaho‐Utah border in 2015. We also measured flow and water stage up to three times per year at each site using an Acoustic Doppler Current profiler and transom survey equipment. We pooled these observations with measurements and data collected by prior undergraduate Bear River Fellow researchers in 2012 and 2013 and used the observations to generate linear regression models to relate water stage to flow at each site. By applying the linear regression model to our pressure measurements, we calculated flow at each time a pressure reading was recorded for its respective location on the lower Bear River. We used the flow rates to determine that very little water is lost or gained between the USGS gage and the Morton site but that during summer months nearly 300cfs is lost between the Morton and Confluence sites. This information can help Bear River pumpers better manage their use

Elevated polyamines induce c-MYC overexpression by perturbing quadruplex–WC duplex equilibrium

The biological role of quadruplexes and polyamines has been independently associated with cancer. However, quadruplex-polyamine mediated transcriptional regulation remain unaddressed. Herein, using c-MYC quadruplex model, we have attempted to understand quadruplex–polyamine interaction and its role in transcriptional regulation. We initially employed biophysical approach involving CD, UV and FRET to understand the role of polyamines (spermidine and spermine) on conformation, stability, molecular recognition of quadruplex and to investigate the effect of polyamines on quadruplex–Watson Crick duplex transition. Our study demonstrates that polyamines affect the c-MYC quadruplex conformation, perturb its recognition properties and delays duplex formation. The relative free energy difference (ΔΔG°) between the duplex and quadruplex structure indicate that polyamines stabilize and favor c-MYC quadruplex over duplex. Further, we investigated the influence of polyamine mediated perturbation of this equilibrium on c-MYC expression. Our results suggest that polyamines induce structural transition of c-MYC quadruplex to a transcriptionally active motif with distinctive molecular recognition property, which drives c-MYC expression. These findings may allow exploiting quadruplex–polyamines interaction for developing antiproliferative strategies to combat aberrant gene expression

Formation of a G-quadruplex at the BCL2 major breakpoint region of the t(14;18) translocation in follicular lymphoma

The t(14;18) translocation in follicular lymphoma is one of the most common chromosomal translocations. Most breaks on chromosome 18 are located at the 3′-UTR of the BCL2 gene and are mainly clustered in the major breakpoint region (MBR). Recently, we found that the BCL2 MBR has a non-B DNA character in genomic DNA. Here, we show that single-stranded DNA modeled from the template strand of the BCL2 MBR, forms secondary structures that migrate faster on native PAGE in the presence of potassium, due to the formation of intramolecular G-quadruplexes. Circular dichroism shows evidence for a parallel orientation for G-quadruplex structures in the template strand of the BCL2 MBR. Mutagenesis and the DMS modification assay confirm the presence of three guanine tetrads in the structure. 1H nuclear magnetic resonance studies further confirm the formation of an intramolecular G-quadruplex and a representative model has been built based on all of the experimental evidence. We also provide data consistent with the possible formation of a G-quadruplex structure at the BCL2 MBR within mammalian cells. In summary, these important features could contribute to the single-stranded character at the BCL2 MBR, thereby contributing to chromosomal fragility

Localization of type 1 diabetes susceptibility to the MHC class I genes HLA-B and HLA-A

The major histocompatibility complex (MHC) on chromosome 6 is associated with susceptibility to more common diseases than any other region of the human genome, including almost all disorders classified as autoimmune. In type 1 diabetes the major genetic susceptibility determinants have been mapped to the MHC class II genes HLA-DQB1 and HLA-DRB1 (refs 1-3), but these genes cannot completely explain the association between type 1 diabetes and the MHC region. Owing to the region's extreme gene density, the multiplicity of disease-associated alleles, strong associations between alleles, limited genotyping capability, and inadequate statistical approaches and sample sizes, which, and how many, loci within the MHC determine susceptibility remains unclear. Here, in several large type 1 diabetes data sets, we analyse a combined total of 1,729 polymorphisms, and apply statistical methods - recursive partitioning and regression - to pinpoint disease susceptibility to the MHC class I genes HLA-B and HLA-A (risk ratios >1.5; Pcombined = 2.01 × 10-19 and 2.35 × 10-13, respectively) in addition to the established associations of the MHC class II genes. Other loci with smaller and/or rarer effects might also be involved, but to find these, future searches must take into account both the HLA class II and class I genes and use even larger samples. Taken together with previous studies, we conclude that MHC-class-I-mediated events, principally involving HLA-B*39, contribute to the aetiology of type 1 diabetes. ©2007 Nature Publishing Group

INVESTIGATING THE UTILITY OF REMOTE SENSING TO EVALUATE DEEP GROUNDWATER STORAGE CHANGES

The common assumption that deep groundwater storage variations and interbasin lateral groundwater flow are a negligibly small component of the total water budget was tested using modelled, remotely sensed, and in-situ data. A total water budget using Gravity Recovery And Climate Experiment (GRACE) data was compared to a surface water budget derived from remotely sensed precipitation, evapotranspiration, and gauged streamflow to examine whether interbasin groundwater flow can be isolated using remote sensing tools. Additionally, GRACE observed changes in total water storage was disaggregated using data from the Global Land Data Assimilation System (GLDAS) to isolate groundwater storage anomalies and were compared to estimates of pumping in the Guarani Aquifer. Sen’s slope estimator and Mann-Kendall significance tests were used to evaluate groundwater storage trends. Head variations are calculated based on assumed partitioning of groundwater storage anomalies and used to demonstrate that nearly all monthly variations in groundwater storage are associated with storage changes in unconfined aquifers.Results of this study suggest that each of the six watersheds evaluated was experiencing net lateral groundwater flow out of the basin and that nearly all groundwater storage variations on the monthly timescale are associated with storage changes in shallow unconfined aquifers. It is further suggested that lateral groundwater flow in the Guarani Aquifer underlying the state of Sao Paulo is sufficiently large to partially offset pumping withdrawals

Flow on the Bear River over the Past Four Years

Managing the Bear River’s flow has allowed water users to get the most out of the available water. The goal of this research is to gain an understanding of how flow on the Bear River has changed over time and how flow changes throughout the course of the year on the Bear River. We collected and processed water pressure data at three Cache Valley sites south of the Idaho-Utah border in 2012, 2013, 2014 and 2015. Through the use of HOBO transducers (collecting data every thirty minutes), we have been able to measure water pressure data of the Bear River year round and calculate flow based on those levels and baseline measurements taken by an Acoustic Doppler Current Profiler. By using data and flow calculations from four years of monitoring we have generated a model to relate water pressure to flow for each site individually. Through this process, we have created a time series of flow rates at those sites along the Bear River. We used the flow rates to determine the relative locations of where water is being added to, or taken from, the Bear River, and how those amounts vary through time. Understanding how much water is available from the Bear River is important for users to know so they can better manage their use. Information generated by this research can help to paint a clearer picture of when and where water is available on the Bear River

Sequence effects of single base loops in intramolecular quadruplex DNA

We have examined the properties of intramolecular G-quadruplexes in which the G3 tracts are separated by single base loops. The most stable complex contained 1?,2?-dideoxyribose in all three loops, while loops containing T and C were slightly less stable (by about 2°C). Quadruplexes containing loops with single A residues were less stable by 8°C for each T to A substitution. These folded sequences display similar CD spectra, which are consistent with the formation of parallel stranded complexes with double-chain reversal loops. These results demonstrate that loop sequence, and not just length, affects quadruplex stability