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Description

Serum Amyloid A (SAA) is an acute phase protein complex consisting of several abundant isoforms. The N- terminus of SAA is critical to its function in amyloid formation. SAA is frequently truncated, either missing an arginine or an arginine-serine dipeptide, resulting in isoforms that may influence the capacity to form

Serum Amyloid A (SAA) is an acute phase protein complex consisting of several abundant isoforms. The N- terminus of SAA is critical to its function in amyloid formation. SAA is frequently truncated, either missing an arginine or an arginine-serine dipeptide, resulting in isoforms that may influence the capacity to form amyloid. However, the relative abundance of truncated SAA in diabetes and chronic kidney disease is not known.

Methods: Using mass spectrometric immunoassay, the abundance of SAA truncations relative to the native variants was examined in plasma of 91 participants with type 2 diabetes and chronic kidney disease and 69 participants without diabetes.

Results: The ratio of SAA 1.1 (missing N-terminal arginine) to native SAA 1.1 was lower in diabetics compared to non-diabetics (p = 0.004), and in males compared to females (p<0.001). This ratio was negatively correlated with glycated hemoglobin (r = −0.32, p<0.001) and triglyceride concentrations (r = −0.37, p<0.001), and positively correlated with HDL cholesterol concentrations (r = 0.32, p<0.001).

Conclusion: The relative abundance of the N-terminal arginine truncation of SAA1.1 is significantly decreased in diabetes and negatively correlates with measures of glycemic and lipid control.

ContributorsYassine, Hussein N. (Author) / Trenchevska, Olgica (Author) / He, Huijuan (Author) / Borges, Chad (Author) / Nedelkov, Dobrin (Author) / Mack, Wendy (Author) / Kono, Naoko (Author) / Koska, Juraj (Author) / Reaven, Peter D. (Author) / Nelson, Randall (Author) / Biodesign Institute (Contributor)
Created2015-01-21
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Description

The exploration of environmentally friendly energy resources is one of the major challenges facing society today. The last decade has witnessed rapid developments in renewable energy engineering. Wind and solar power plants with increasing sizes and technological sophistication have been built. Amid this development, meteorological modeling plays an increasingly important

The exploration of environmentally friendly energy resources is one of the major challenges facing society today. The last decade has witnessed rapid developments in renewable energy engineering. Wind and solar power plants with increasing sizes and technological sophistication have been built. Amid this development, meteorological modeling plays an increasingly important role, not only in selecting the sites of wind and solar power plants but also in assessing the environmental impacts of those plants. The permanent land-use changes as a result of the construction of wind farms can potentially alter local climate (Keith et al. [1], Roy and Traiteur [2]). The reduction of wind speed by the presence of wind turbines could affect the preconstruction estimate of wind power potential (e.g., Adams and Keith [3]). Future anthropogenic greenhouse gas emissions are expected to induce changes in the surface wind and cloudiness, which would affect the power production of wind and solar power plants. To quantify these two-way relations between renewable energy production and regional climate change, mesoscale meteorological modeling remains one of the most efficient approaches for research and applications.

ContributorsHuang, Huei-Ping (Author) / Hedquist, Brent C. (Author) / Lee, T.-W. (Author) / Myint, Soe (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2014-12-22
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Description

The oxidative modification of apolipoprotein A-I’s methionine148 (M148) is associated with defective HDL function in vitro. Multiple reaction monitoring (MRM) is a mass spectrometric technique that can be used to quantitate post-translational modifications. In this study, we developed an MRM assay to monitor the abundance ratio of the peptide containing

The oxidative modification of apolipoprotein A-I’s methionine148 (M148) is associated with defective HDL function in vitro. Multiple reaction monitoring (MRM) is a mass spectrometric technique that can be used to quantitate post-translational modifications. In this study, we developed an MRM assay to monitor the abundance ratio of the peptide containing oxidized M148 to the native peptide in ApoA-I. Measurement of the oxidized-to-unoxidized-M148 ratio was reproducible (CV < 5%). The extent of methionine M148 oxidation in the HDL of healthy controls, and type 2 diabetic participants with and without prior cardiovascular events (CVD) were then examined. The results suggest a significant increase in the relative ratio of the peptide containing oxidized M148 to the unmodified peptide in the HDL of participants with diabetes and CVD (p < 0.001), compared to participants without CVD. Monitoring the abundance ratio of the peptides containing oxidized and unoxidized M148 by MRM provides a means of examining the relationship between M148 oxidation and vascular complications in CVD.

ContributorsYassine, Hussein N. (Author) / Jackson, Angela M. (Author) / Reaven, Peter D. (Author) / Nedelkov, Dobrin (Author) / Nelson, Randall (Author) / Lau, Serrine S. (Author) / Borchers, Christoph H. (Author) / Biodesign Institute (Contributor)
Created2014-10-11
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Description

We quantified the spatio-temporal patterns of land cover/land use (LCLU) change to document and evaluate the daytime surface urban heat island (SUHI) for five hot subtropical desert cities (Beer Sheva, Israel; Hotan, China; Jodhpur, India; Kharga, Egypt; and Las Vegas, NV, USA). Sequential Landsat images were acquired and classified into

We quantified the spatio-temporal patterns of land cover/land use (LCLU) change to document and evaluate the daytime surface urban heat island (SUHI) for five hot subtropical desert cities (Beer Sheva, Israel; Hotan, China; Jodhpur, India; Kharga, Egypt; and Las Vegas, NV, USA). Sequential Landsat images were acquired and classified into the USGS 24-category Land Use Categories using object-based image analysis with an overall accuracy of 80% to 95.5%. We estimated the land surface temperature (LST) of all available Landsat data from June to August for years 1990, 2000, and 2010 and computed the urban-rural difference in the average LST and Normalized Difference Vegetation Index (NDVI) for each city. Leveraging non-parametric statistical analysis, we also investigated the impacts of city size and population on the urban-rural difference in the summer daytime LST and NDVI. Urban expansion is observed for all five cities, but the urbanization pattern varies widely from city to city. A negative SUHI effect or an oasis effect exists for all the cities across all three years, and the amplitude of the oasis effect tends to increase as the urban-rural NDVI difference increases. A strong oasis effect is observed for Hotan and Kharga with evidently larger NDVI difference than the other cities. Larger cities tend to have a weaker cooling effect while a negative association is identified between NDVI difference and population. Understanding the daytime oasis effect of desert cities is vital for sustainable urban planning and the design of adaptive management, providing valuable guidelines to foster smart desert cities in an era of climate variability, uncertainty, and change.

ContributorsFan, Chao (Author) / Myint, Soe (Author) / Kaplan, Shai (Author) / Middel, Ariane (Author) / Zheng, Baojuan (Author) / Rahman, Atiqur (Author) / Huang, Huei-Ping (Author) / Brazel, Anthony J. (Author) / Blumberg, Dan G. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2017-06-30
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Description

Asteroids provide fundamental clues to the formation and evolution of planetesimals. Collisional models based on the depletion of the primordial main belt of asteroids predict 10–15 craters >400 km should have formed on Ceres, the largest object between Mars and Jupiter, over the last 4.55 Gyr. Likewise, an extrapolation from the asteroid

Asteroids provide fundamental clues to the formation and evolution of planetesimals. Collisional models based on the depletion of the primordial main belt of asteroids predict 10–15 craters >400 km should have formed on Ceres, the largest object between Mars and Jupiter, over the last 4.55 Gyr. Likewise, an extrapolation from the asteroid Vesta would require at least 6–7 such basins. However, Ceres’ surface appears devoid of impact craters >∼280 km. Here, we show a significant depletion of cerean craters down to 100–150 km in diameter. The overall scarcity of recognizable large craters is incompatible with collisional models, even in the case of a late implantation of Ceres in the main belt, a possibility raised by the presence of ammoniated phyllosilicates. Our results indicate that a significant population of large craters has been obliterated, implying that long-wavelength topography viscously relaxed or that Ceres experienced protracted widespread resurfacing.

ContributorsMarchi, S. (Author) / Ermakov, A. I. (Author) / Raymond, C. A. (Author) / Fu, R. R. (Author) / O'Brien, D. P. (Author) / Bland, M. T. (Author) / Ammannito, E. (Author) / De Sanctis, M. C. (Author) / Bowling, T. (Author) / Schenk, P. (Author) / Scully, J. E. C. (Author) / Buczkowski, D. L. (Author) / Williams, David (Author) / Hiesinger, H. (Author) / Russell, C. T. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-07-26
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Description

Background: The cytokine MIF (Macrophage Migration Inhibitory Factor) has diverse physiological roles and is present at elevated concentrations in numerous disease states. However, its molecular heterogeneity has not been previously investigated in biological samples. Mass Spectrometric Immunoassay (MSIA) may help elucidate MIF post-translational modifications existing in vivo and provide additional clarity

Background: The cytokine MIF (Macrophage Migration Inhibitory Factor) has diverse physiological roles and is present at elevated concentrations in numerous disease states. However, its molecular heterogeneity has not been previously investigated in biological samples. Mass Spectrometric Immunoassay (MSIA) may help elucidate MIF post-translational modifications existing in vivo and provide additional clarity regarding its relationship to diverse pathologies.

Results: In this work, we have developed and validated a fully quantitative MSIA assay for MIF, and used it in the discovery and quantification of different proteoforms of MIF in serum samples, including cysteinylated and glycated MIF. The MSIA assay had a linear range of 1.56-50 ng/mL, and exhibited good precision, linearity, and recovery characteristics. The new assay was applied to a small cohort of human serum samples, and benchmarked against an MIF ELISA assay.

Conclusions: The quantitative MIF MSIA assay provides a sensitive, precise and high throughput method to delineate and quantify MIF proteoforms in biological samples.

ContributorsSherma, Nisha (Author) / Borges, Chad (Author) / Trenchevska, Olgica (Author) / Jarvis, Jason W. (Author) / Rehder, Douglas (Author) / Oran, Paul (Author) / Nelson, Randall (Author) / Nedelkov, Dobrin (Author) / Biodesign Institute (Contributor)
Created2014-10-14
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Description

Background: Cystatin C (CysC) is an endogenous cysteine protease inhibitor that can be used to assess the progression of kidney function. Recent studies demonstrate that CysC is a more specific indicator of glomerular filtration rate (GFR) than creatinine. CysC in plasma exists in multiple proteoforms. The goal of this study was

Background: Cystatin C (CysC) is an endogenous cysteine protease inhibitor that can be used to assess the progression of kidney function. Recent studies demonstrate that CysC is a more specific indicator of glomerular filtration rate (GFR) than creatinine. CysC in plasma exists in multiple proteoforms. The goal of this study was to clarify the association of native CysC, CysC missing N-terminal Serine (CysC des-S), and CysC without three N-terminal residues (CysC des-SSP) with diabetic chronic kidney disease (CKD).

Results: Using mass spectrometric immunoassay, the plasma concentrations of native CysC and the two CysC truncation proteoforms were examined in 111 individuals from three groups: 33 non-diabetic controls, 34 participants with type 2 diabetes (DM) and without CKD and 44 participants with diabetic CKD. Native CysC concentrations were 1.4 fold greater in CKD compared to DM group (p = 0.02) and 1.5 fold greater in CKD compared to the control group (p = 0.001). CysC des-S concentrations were 1.55 fold greater in CKD compared to the DM group (p = 0.002) and 1.9 fold greater in CKD compared to the control group (p = 0.0002). CysC des-SSP concentrations were 1.8 fold greater in CKD compared to the DM group (p = 0.008) and 1.52 fold greater in CKD compared to the control group (p = 0.002). In addition, the concentrations of CysC proteoforms were greater in the setting of albuminuria. The truncated CysC proteoform concentrations were associated with estimated GFR independent of native CysC concentrations.

Conclusion: Our findings demonstrate a greater amount of CysC proteoforms in diabetic CKD. We therefore suggest assessing the role of cystatin C proteoforms in the progression of CKD.

ContributorsYassine, Hussein N. (Author) / Trenchevska, Olgica (Author) / Dong, Zhiwei (Author) / Bashawri, Yara (Author) / Koska, Juraj (Author) / Reaven, Peter D. (Author) / Nelson, Randall (Author) / Nedelkov, Dobrin (Author) / Biodesign Institute (Contributor)
Created2016-03-25
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Description

Insulin-like growth factor 1 (IGF1) is an important biomarker for the management of growth hormone disorders. Recently there has been rising interest in deploying mass spectrometric (MS) methods of detection for measuring IGF1. However, widespread clinical adoption of any MS-based IGF1 assay will require increased throughput and speed to justify

Insulin-like growth factor 1 (IGF1) is an important biomarker for the management of growth hormone disorders. Recently there has been rising interest in deploying mass spectrometric (MS) methods of detection for measuring IGF1. However, widespread clinical adoption of any MS-based IGF1 assay will require increased throughput and speed to justify the costs of analyses, and robust industrial platforms that are reproducible across laboratories. Presented here is an MS-based quantitative IGF1 assay with performance rating of >1,000 samples/day, and a capability of quantifying IGF1 point mutations and posttranslational modifications. The throughput of the IGF1 mass spectrometric immunoassay (MSIA) benefited from a simplified sample preparation step, IGF1 immunocapture in a tip format, and high-throughput MALDI-TOF MS analysis. The Limit of Detection and Limit of Quantification of the resulting assay were 1.5 μg/L and 5 μg/L, respectively, with intra- and inter-assay precision CVs of less than 10%, and good linearity and recovery characteristics. The IGF1 MSIA was benchmarked against commercially available IGF1 ELISA via Bland-Altman method comparison test, resulting in a slight positive bias of 16%. The IGF1 MSIA was employed in an optimized parallel workflow utilizing two pipetting robots and MALDI-TOF-MS instruments synced into one-hour phases of sample preparation, extraction and MSIA pipette tip elution, MS data collection, and data processing. Using this workflow, high-throughput IGF1 quantification of 1,054 human samples was achieved in approximately 9 hours. This rate of assaying is a significant improvement over existing MS-based IGF1 assays, and is on par with that of the enzyme-based immunoassays. Furthermore, a mutation was detected in ∼1% of the samples (SNP: rs17884626, creating an A→T substitution at position 67 of the IGF1), demonstrating the capability of IGF1 MSIA to detect point mutations and posttranslational modifications.

ContributorsOran, Paul (Author) / Trenchevska, Olgica (Author) / Nedelkov, Dobrin (Author) / Borges, Chad (Author) / Schaab, Matthew (Author) / Rehder, Douglas (Author) / Jarvis, Jason (Author) / Sherma, Nisha (Author) / Shen, Luhui (Author) / Krastins, Bryan (Author) / Lopez, Mary F. (Author) / Schwenke, Dawn (Author) / Reaven, Peter D. (Author) / Nelson, Randall (Author) / Biodesign Institute (Contributor)
Created2014-03-24
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Description

Deforestation in Myanmar has recently attracted much attention worldwide. This study examined spatio-temporal patterns of deforestation and forest carbon flux in Myanmar from 2001 to 2010 and environmental impacts at the regional scale using land products of the Moderate Resolution Imaging Spectroradiometer (MODIS). The results suggest that the total deforestation

Deforestation in Myanmar has recently attracted much attention worldwide. This study examined spatio-temporal patterns of deforestation and forest carbon flux in Myanmar from 2001 to 2010 and environmental impacts at the regional scale using land products of the Moderate Resolution Imaging Spectroradiometer (MODIS). The results suggest that the total deforestation area in Myanmar was 21,178.8 km2, with an annual deforestation rate of 0.81%, and that the total forest carbon release was 20.06 million tons, with an annual rate of 0.37%. Mangrove forests had the highest deforestation and carbon release rates, and deciduous forests had both the largest deforestation area and largest amount of carbon release. During the study period, the south and southwestern regions of Myanmar, especially Ayeyarwady and Rakhine, were deforestation hotspots (i.e., the highest deforestation and carbon release rates occurred in these regions). Deforestation caused significant carbon release, reduced evapotranspiration (ET), and increased land surface temperatures (LSTs) in deforested areas in Myanmar during the study period. Constructive policy recommendations are put forward based on these research results.

ContributorsWang, Chuyuan (Author) / Myint, Soe (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-09-02
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Description

This paper reviews how remotely sensed data have been used to understand the impact of urbanization on global environmental change. We describe how these studies can support the policy and science communities’ increasing need for detailed and up-to-date information on the multiple dimensions of cities, including their social, biological, physical,

This paper reviews how remotely sensed data have been used to understand the impact of urbanization on global environmental change. We describe how these studies can support the policy and science communities’ increasing need for detailed and up-to-date information on the multiple dimensions of cities, including their social, biological, physical, and infrastructural characteristics. Because the interactions between urban and surrounding areas are complex, a synoptic and spatial view offered from remote sensing is integral to measuring, modeling, and understanding these relationships. Here we focus on three themes in urban remote sensing science: mapping, indices, and modeling. For mapping we describe the data sources, methods, and limitations of mapping urban boundaries, land use and land cover, population, temperature, and air quality. Second, we described how spectral information is manipulated to create comparative biophysical, social, and spatial indices of the urban environment. Finally, we focus how the mapped information and indices are used as inputs or parameters in models that measure changes in climate, hydrology, land use, and economics.

ContributorsWentz, Elizabeth (Author) / Anderson, Sharolyn (Author) / Fragkias, Michail (Author) / Netzband, Maik (Author) / Mesev, Victor (Author) / Myint, Soe (Author) / Quattrochi, Dale (Author) / Rahman, Atiqur (Author) / Seto, Karen C. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-04-30