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Description

S-cysteinylated albumin and methionine-oxidized apolipoprotein A-I (apoA-I) have been posed as candidate markers of diseases associated with oxidative stress. Here, a dilute-and-shoot form of LC–electrospray ionization–MS requiring half a microliter of blood plasma was employed to simultaneously quantify the relative abundance of these oxidized proteoforms in samples stored at −80

S-cysteinylated albumin and methionine-oxidized apolipoprotein A-I (apoA-I) have been posed as candidate markers of diseases associated with oxidative stress. Here, a dilute-and-shoot form of LC–electrospray ionization–MS requiring half a microliter of blood plasma was employed to simultaneously quantify the relative abundance of these oxidized proteoforms in samples stored at −80 °C, −20 °C, and room temperature and exposed to multiple freeze-thaw cycles and other adverse conditions in order to assess the possibility that protein oxidation may occur as a result of poor sample storage or handling. Samples from a healthy donor and a participant with poorly controlled type 2 diabetes started at the same low level of protein oxidation and behaved similarly; significant increases in albumin oxidation via S-cysteinylation were found to occur within hours at room temperature and days at −20 °C. Methionine oxidation of apoA-I took place on a longer time scale, setting in after albumin oxidation reached a plateau. Freeze–thaw cycles had a minimal effect on protein oxidation. In matched collections, protein oxidation in serum was the same as that in plasma. Albumin and apoA-I oxidation were not affected by sample headspace or the degree to which vials were sealed. ApoA-I, however, was unexpectedly found to oxidize faster in samples with lower surface-area-to-volume ratios. An initial survey of samples from patients with inflammatory conditions normally associated with elevated oxidative stress-including acute myocardial infarction and prostate cancer—demonstrated a lack of detectable apoA-I oxidation. Albumin S-cysteinylation in these samples was consistent with known but relatively brief exposures to temperatures above −30 °C (the freezing point of blood plasma). Given their properties and ease of analysis, these oxidized proteoforms, once fully validated, may represent the first markers of blood plasma specimen integrity based on direct measurement of oxidative molecular damage that can occur under suboptimal storage conditions.

ContributorsBorges, Chad (Author) / Rehder, Douglas (Author) / Jensen, Sally (Author) / Schaab, Matthew (Author) / Sherma, Nisha (Author) / Yassine, Hussein (Author) / Nikolova, Boriana (Author) / Breburda, Christian (Author) / Department of Chemistry and Biochemistry (Contributor)
Created2014-07-01
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Description

Vision and Change in Undergraduate Biology Education outlined five core concepts intended to guide undergraduate biology education: 1) evolution; 2) structure and function; 3) information flow, exchange, and storage; 4) pathways and transformations of energy and matter; and 5) systems. We have taken these general recommendations and created a Vision

Vision and Change in Undergraduate Biology Education outlined five core concepts intended to guide undergraduate biology education: 1) evolution; 2) structure and function; 3) information flow, exchange, and storage; 4) pathways and transformations of energy and matter; and 5) systems. We have taken these general recommendations and created a Vision and Change BioCore Guide—a set of general principles and specific statements that expand upon the core concepts, creating a framework that biology departments can use to align with the goals of Vision and Change. We used a grassroots approach to generate the BioCore Guide, beginning with faculty ideas as the basis for an iterative process that incorporated feedback from more than 240 biologists and biology educators at a diverse range of academic institutions throughout the United States. The final validation step in this process demonstrated strong national consensus, with more than 90% of respondents agreeing with the importance and scientific accuracy of the statements. It is our hope that the BioCore Guide will serve as an agent of change for biology departments as we move toward transforming undergraduate biology education.

ContributorsBrownell, Sara (Author) / Freeman, Scott (Author) / Wenderoth, Mary Pat (Author) / Crowe, Alison J. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-06-01
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Description

The U.S. scientific research community does not reflect America's diversity. Hispanics, African Americans, and Native Americans made up 31% of the general population in 2010, but they represented only 18 and 7% of science, technology, engineering, and mathematics (STEM) bachelor's and doctoral degrees, respectively, and 6% of STEM faculty members

The U.S. scientific research community does not reflect America's diversity. Hispanics, African Americans, and Native Americans made up 31% of the general population in 2010, but they represented only 18 and 7% of science, technology, engineering, and mathematics (STEM) bachelor's and doctoral degrees, respectively, and 6% of STEM faculty members (National Science Foundation [NSF], 2013). Equity in the scientific research community is important for a variety of reasons; a diverse community of researchers can minimize the negative influence of bias in scientific reasoning, because people from different backgrounds approach a problem from different perspectives and can raise awareness regarding biases (Intemann, 2009). Additionally, by failing to be attentive to equity, we may exclude some of the best and brightest scientific minds and limit the pool of possible scientists (Intemann, 2009). Given this need for equity, how can our scientific research community become more inclusive?

ContributorsBangera, Gita (Author) / Brownell, Sara (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-12-01
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Description

Women who start college in one of the natural or physical sciences leave in greater proportions than their male peers. The reasons for this difference are complex, and one possible contributing factor is the social environment women experience in the classroom. Using social network analysis, we explore how gender influences

Women who start college in one of the natural or physical sciences leave in greater proportions than their male peers. The reasons for this difference are complex, and one possible contributing factor is the social environment women experience in the classroom. Using social network analysis, we explore how gender influences the confidence that college-level biology students have in each other’s mastery of biology. Results reveal that males are more likely than females to be named by peers as being knowledgeable about the course content. This effect increases as the term progresses, and persists even after controlling for class performance and outspokenness. The bias in nominations is specifically due to males over-nominating their male peers relative to their performance. The over-nomination of male peers is commensurate with an overestimation of male grades by 0.57 points on a 4 point grade scale, indicating a strong male bias among males when assessing their classmates. Females, in contrast, nominated equitably based on student performance rather than gender, suggesting they lacked gender biases in filling out these surveys. These trends persist across eleven surveys taken in three different iterations of the same Biology course. In every class, the most renowned students are always male. This favoring of males by peers could influence student self-confidence, and thus persistence in this STEM discipline.

ContributorsGrunspan, Daniel Z. (Author) / Eddy, Sarah L. (Author) / Brownell, Sara (Author) / Wiggins, Benjamin L. (Author) / Crowe, Alison J. (Author) / Goodreau, Steven M. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-02-10
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Description

Background: Cysteine sulfenic acid (Cys-SOH) plays important roles in the redox regulation of numerous proteins. As a relatively unstable posttranslational protein modification it is difficult to quantify the degree to which any particular protein is modified by Cys-SOH within a complex biological environment. The goal of these studies was to move

Background: Cysteine sulfenic acid (Cys-SOH) plays important roles in the redox regulation of numerous proteins. As a relatively unstable posttranslational protein modification it is difficult to quantify the degree to which any particular protein is modified by Cys-SOH within a complex biological environment. The goal of these studies was to move a step beyond detection and into the relative quantification of Cys-SOH within specific proteins found in a complex biological setting--namely, human plasma.

Results: This report describes the possibilities and limitations of performing such analyses based on the use of thionitrobenzoic acid and dimedone-based probes which are commonly employed to trap Cys-SOH. Results obtained by electrospray ionization-based mass spectrometric immunoassay reveal the optimal type of probe for such analyses as well as the reproducible relative quantification of Cys-SOH within albumin and transthyretin extracted from human plasma--the latter as a protein previously unknown to be modified by Cys-SOH.

Conclusions: The relative quantification of Cys-SOH within specific proteins in a complex biological setting can be accomplished, but several analytical precautions related to trapping, detecting, and quantifying Cys-SOH must be taken into account prior to pursuing its study in such matrices.

ContributorsRehder, Douglas (Author) / Borges, Chad (Author) / Biodesign Institute (Contributor)
Created2010-07-01
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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 sensitivity of Earth’s wetlands to observed shifts in global precipitation and temperature patterns and their ability to produce large quantities of methane gas are key global change questions. We present a microwave satellite-based approach for mapping fractional surface water (FW) globally at 25-km resolution. The approach employs a land

The sensitivity of Earth’s wetlands to observed shifts in global precipitation and temperature patterns and their ability to produce large quantities of methane gas are key global change questions. We present a microwave satellite-based approach for mapping fractional surface water (FW) globally at 25-km resolution. The approach employs a land cover-supported, atmospherically-corrected dynamic mixture model applied to 20+ years (1992–2013) of combined, daily, passive/active microwave remote sensing data. The resulting product, known as Surface Water Microwave Product Series (SWAMPS), shows strong microwave sensitivity to sub-grid scale open water and inundated wetlands comprising open plant canopies. SWAMPS’ FW compares favorably (R2 = 91%–94%) with higher-resolution, global-scale maps of open water from MODIS and SRTM-MOD44W. Correspondence of SWAMPS with open water and wetland products from satellite SAR in Alaska and the Amazon deteriorates when exposed wetlands or inundated forests captured by the SAR products were added to the open water fraction reflecting SWAMPS’ inability to detect water underneath the soil surface or beneath closed forest canopies. Except for a brief period of drying during the first 4 years of observation, the inundation extent for the global domain excluding the coast was largely stable. Regionally, inundation in North America is advancing while inundation is on the retreat in Tropical Africa and North Eurasia. SWAMPS provides a consistent and long-term global record of daily FW dynamics, with documented accuracies suitable for hydrologic assessment and global change-related investigations.

ContributorsSchroeder, Ronny (Author) / McDonald, Kyle C. (Author) / Chapman, Bruce D. (Author) / Jensen, Katherine (Author) / Podest, Erika (Author) / Tessler, Zachary D. (Author) / Bohn, Theodore (Author) / Zimmermann, Reiner (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-12-09
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Description

The shift from cookbook to authentic research-based lab courses in undergraduate biology necessitates the need for evaluation and assessment of these novel courses. Although the biology education community has made progress in this area, it is important that we interpret the effectiveness of these courses with caution and remain mindful

The shift from cookbook to authentic research-based lab courses in undergraduate biology necessitates the need for evaluation and assessment of these novel courses. Although the biology education community has made progress in this area, it is important that we interpret the effectiveness of these courses with caution and remain mindful of inherent limitations to our study designs that may impact internal and external validity. The specific context of a research study can have a dramatic impact on the conclusions. We present a case study of our own three-year investigation of the impact of a research-based introductory lab course, highlighting how volunteer students, a lack of a comparison group, and small sample sizes can be limitations of a study design that can affect the interpretation of the effectiveness of a course.

ContributorsBrownell, Sara (Author) / Kloser, Matthew J. (Author) / Fukami, Tadashi (Author) / Shavelson, Richard J. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2013-12-02
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Description

A warming climate is altering land-atmosphere exchanges of carbon, with a potential for increased vegetation productivity as well as the mobilization of permafrost soil carbon stores. Here we investigate land-atmosphere carbon dioxide (CO2) cycling through analysis of net ecosystem productivity (NEP) and its component fluxes of gross primary productivity (GPP)

A warming climate is altering land-atmosphere exchanges of carbon, with a potential for increased vegetation productivity as well as the mobilization of permafrost soil carbon stores. Here we investigate land-atmosphere carbon dioxide (CO2) cycling through analysis of net ecosystem productivity (NEP) and its component fluxes of gross primary productivity (GPP) and ecosystem respiration (ER) and soil carbon residence time, simulated by a set of land surface models (LSMs) over a region spanning the drainage basin of Northern Eurasia. The retrospective simulations cover the period 1960–2009 at 0.5° resolution, which is a scale common among many global carbon and climate model simulations. Model performance benchmarks were drawn from comparisons against both observed CO2 fluxes derived from site-based eddy covariance measurements as well as regional-scale GPP estimates based on satellite remote-sensing data.

The site-based comparisons depict a tendency for overestimates in GPP and ER for several of the models, particularly at the two sites to the south. For several models the spatial pattern in GPP explains less than half the variance in the MODIS MOD17 GPP product. Across the models NEP increases by as little as 0.01 to as much as 0.79 g C m-2 yr-2, equivalent to 3 to 340 % of the respective model means, over the analysis period. For the multimodel average the increase is 135 % of the mean from the first to last 10 years of record (1960–1969 vs. 2000–2009), with a weakening CO2 sink over the latter decades. Vegetation net primary productivity increased by 8 to 30 % from the first to last 10 years, contributing to soil carbon storage gains. The range in regional mean NEP among the group is twice the multimodel mean, indicative of the uncertainty in CO2 sink strength.

The models simulate that inputs to the soil carbon pool exceeded losses, resulting in a net soil carbon gain amid a decrease in residence time. Our analysis points to improvements in model elements controlling vegetation productivity and soil respiration as being needed for reducing uncertainty in land-atmosphere CO2 exchange. These advances will require collection of new field data on vegetation and soil dynamics, the development of benchmarking data sets from measurements and remote-sensing observations, and investments in future model development and intercomparison studies.

ContributorsRawlins, M. A. (Author) / McGuire, A. D. (Author) / Kimball, J. S. (Author) / Dass, P. (Author) / Lawrence, D. (Author) / Burke, E. (Author) / Chen, X. (Author) / Delire, C. (Author) / Koven, C. (Author) / MacDougall, A. (Author) / Peng, S. (Author) / Rinke, A. (Author) / Saito, K. (Author) / Zhang, W. (Author) / Alkama, R. (Author) / Bohn, Theodore (Author) / Ciais, P. (Author) / Decharme, B. (Author) / Gouttevin, I. (Author) / Hajima, T. (Author) / Ji, D. (Author) / Krinner, G. (Author) / Lettenmaier, D. P. (Author) / Miller, P. (Author) / Moore, J. C. (Author) / Smith, B. (Author) / Sueyoshi, T. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-07-28
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Description

Soil temperature (Ts) change is a key indicator of the dynamics of permafrost. On seasonal and interannual timescales, the variability of Ts determines the active-layer depth, which regulates hydrological soil properties and biogeochemical processes. On the multi-decadal scale, increasing Ts not only drives permafrost thaw/retreat but can also trigger and

Soil temperature (Ts) change is a key indicator of the dynamics of permafrost. On seasonal and interannual timescales, the variability of Ts determines the active-layer depth, which regulates hydrological soil properties and biogeochemical processes. On the multi-decadal scale, increasing Ts not only drives permafrost thaw/retreat but can also trigger and accelerate the decomposition of soil organic carbon. The magnitude of permafrost carbon feedbacks is thus closely linked to the rate of change of soil thermal regimes. In this study, we used nine process-based ecosystem models with permafrost processes, all forced by different observation-based climate forcing during the period 1960–2000, to characterize the warming rate of Ts in permafrost regions. There is a large spread of Ts trends at 20 cm depth across the models, with trend values ranging from 0.010 ± 0.003 to 0.031 ± 0.005 °C yr-1. Most models show smaller increase in Ts with increasing depth. Air temperature (Tsub>a) and longwave downward radiation (LWDR) are the main drivers of Ts trends, but their relative contributions differ amongst the models. Different trends of LWDR used in the forcing of models can explain 61 % of their differences in Ts trends, while trends of Ta only explain 5 % of the differences in Ts trends. Uncertain climate forcing contributes a larger uncertainty in Ts trends (0.021 ± 0.008 °C yr-1, mean ± standard deviation) than the uncertainty of model structure (0.012 ± 0.001 °C yr-1), diagnosed from the range of response between different models, normalized to the same forcing. In addition, the loss rate of near-surface permafrost area, defined as total area where the maximum seasonal active-layer thickness (ALT) is less than 3 m loss rate, is found to be significantly correlated with the magnitude of the trends of Ts at 1 m depth across the models (R = −0.85, P = 0.003), but not with the initial total near-surface permafrost area (R = −0.30, P = 0.438). The sensitivity of the total boreal near-surface permafrost area to Ts at 1 m is estimated to be of −2.80 ± 0.67 million km2°C-1. Finally, by using two long-term LWDR data sets and relationships between trends of LWDR and Ts across models, we infer an observation-constrained total boreal near-surface permafrost area decrease comprising between 39 ± 14  ×  103 and 75 ± 14  ×  103km2yr-1 from 1960 to 2000. This corresponds to 9–18 % degradation of the current permafrost area.

ContributorsPeng, S. (Author) / Ciais, P. (Author) / Krinner, G. (Author) / Wang, T. (Author) / Gouttevin, I. (Author) / McGuire, A. D. (Author) / Lawrence, D. (Author) / Burke, E. (Author) / Chen, X. (Author) / Decharme, B. (Author) / Koven, C. (Author) / MacDougall, A. (Author) / Rinke, A. (Author) / Saito, K. (Author) / Zhang, W. (Author) / Alkama, R. (Author) / Bohn, Theodore (Author) / Delire, C. (Author) / Hajima, T. (Author) / Ji, D. (Author) / Lettenmaier, D. P. (Author) / Miller, P. A. (Author) / Moore, J. C. (Author) / Smith, B. (Author) / Sueyoshi, T. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-01-20