ASU Scholarship Showcase

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.

Background: Most excess deaths that occur during extreme hot weather events do not have natural heat recorded as an underlying or contributing cause. This study aims to identify the specific individuals who died because of hot weather using only secondary data. A novel approach was developed in which the expected number of deaths was repeatedly sampled from all deaths that occurred during a hot weather event, and compared with deaths during a control period. The deaths were compared with respect to five factors known to be associated with hot weather mortality. Individuals were ranked by their presence in significant models over 100 trials of 10,000 repetitions. Those with the highest rankings were identified as probable excess deaths. Sensitivity analyses were performed on a range of model combinations. These methods were applied to a 2009 hot weather event in greater Vancouver, Canada.

Results: The excess deaths identified were sensitive to differences in model combinations, particularly between univariate and multivariate approaches. One multivariate and one univariate combination were chosen as the best models for further analyses. The individuals identified by multiple combinations suggest that marginalized populations in greater Vancouver are at higher risk of death during hot weather.

Conclusions: This study proposes novel methods for classifying specific deaths as expected or excess during a hot weather event. Further work is needed to evaluate performance of the methods in simulation studies and against clinically identified cases. If confirmed, these methods could be applied to a wide range of populations and events of interest.

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.

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.

The Arctic, even more so than other parts of the world, has warmed substantially over the past few decades. Temperature and humidity influence the rate of development, survival and reproduction of pathogens and thus the incidence and prevalence of many infectious diseases. Higher temperatures may also allow infected host species to survive winters in larger numbers, increase the population size and expand their habitat range. The impact of these changes on human disease in the Arctic has not been fully evaluated. There is concern that climate change may shift the geographic and temporal distribution of a range of infectious diseases. Many infectious diseases are climate sensitive, where their emergence in a region is dependent on climate-related ecological changes. Most are zoonotic diseases, and can be spread between humans and animals by arthropod vectors, water, soil, wild or domestic animals. Potentially climate-sensitive zoonotic pathogens of circumpolar concern include Brucella spp., Toxoplasma gondii, Trichinella spp., Clostridium botulinum, Francisella tularensis, Borrelia burgdorferi, Bacillus anthracis, Echinococcus spp., Leptospira spp., Giardia spp., Cryptosporida spp., Coxiella burnetti, rabies virus, West Nile virus, Hantaviruses, and tick-borne encephalitis viruses.

The modified Thomas test was developed to assess the presence of hip flexion contracture and to measure hip extensibility. Despite its widespread use, to the authors’ knowledge, its criterion reference validity has not yet been investigated. The purpose of this study was to assess the criterion reference validity of the modified Thomas test for measuring peak hip extension angle and hip extension deficits, as defined by the hip not being able to extend to 0º, or neutral. Twenty-nine healthy college students (age = 22.00 ± 3.80 years; height = 1.71 ± 0.09 m; body mass = 70.00 ± 15.60 kg) were recruited for this study. Bland–Altman plots revealed poor validity for the modified Thomas test’s ability to measure hip extension, which could not be explained by differences in hip flexion ability alone. The modified Thomas test displayed a sensitivity of 31.82% (95% CI [13.86–54.87]) and a specificity of 57.14% (95% CI [18.41–90.10]) for testing hip extension deficits. It appears, however, that by controlling pelvic tilt, much of this variance can be accounted for (r = 0.98). When pelvic tilt is not controlled, the modified Thomas test displays poor criterion reference validity and, as per previous studies, poor reliability. However, when pelvic tilt is controlled, the modified Thomas test appears to be a valid test for evaluating peak hip extension angle.

Many strength and conditioning coaches utilize the good morning (GM) to strengthen the hamstrings and spinal erectors. However, little research exists on its electromyography (EMG) activity and kinematics, and how these variables change as a function of load. The purpose of this investigation was to examine how estimated hamstring length, integrated EMG (IEMG) activity of the hamstrings and spinal erectors, and kinematics of the lumbar spine, hip, knee, and ankle are affected by changes in load. Fifteen trained male participants (age = 24.6 ± 5.3 years; body mass = 84.7 ± 11.3 kg; height = 180.9 ± 6.8 cm) were recruited for this study. Participants performed five sets of the GM, utilizing 50, 60, 70, 80, and 90% of one-repetition maximum (1RM) in a randomized fashion. IEMG activity of hamstrings and spinal erectors tended to increase with load. Knee flexion increased with load on all trials. Estimated hamstring length decreased with load. However, lumbar flexion, hip flexion, and plantar flexion experienced no remarkable changes between trials. These data provide insight as to how changing the load of the GM affects EMG activity, kinematic variables, and estimated hamstring length. Implications for hamstring injury prevention are discussed. More research is needed for further insight as to how load affects EMG activity and kinematics of other exercises.

Training the bench press exercise on a traditional flat bench does not induce a level of instability as seen in sport movements and activities of daily living. Twenty participants were recruited to test two forms of instability: using one dumbbell rather than two and lifting on the COR bench compared to a flat bench. Electromyography (EMG) amplitudes of the pectoralis major, middle trapezius, external oblique, and internal oblique were recorded and compared. Differences in range of motion (ROM) were evaluated by measuring an angular representation of the shoulder complex. Four separate conditions of unilateral bench press were tested while lifting on a: flat bench with one dumbbell, flat bench with two dumbbells, COR Bench with one dumbbell, and COR Bench with two dumbbells. The results imply that there are no differences in EMG amplitude or ROM between the COR bench and traditional bench. However, greater ROM was found to be utilized in the single dumbbell condition, both in the COR bench and the flat bench.

Background: The purpose of this study was to compare the peak electromyography (EMG) of the most commonly-used position in the literature, the prone bent-leg (90°) hip extension against manual resistance applied to the distal thigh (PRONE), to a novel position, the standing glute squeeze (SQUEEZE).

Methods: Surface EMG electrodes were placed on the upper and lower gluteus maximus of thirteen recreationally active females (age = 28.9 years; height = 164 cm; body mass = 58.2 kg), before three maximum voluntary isometric contraction (MVIC) trials for each position were obtained in a randomized, counterbalanced fashion.

Results: No statistically significant (p < 0.05) differences were observed between PRONE (upper: 91.94%; lower: 94.52%) and SQUEEZE (upper: 92.04%; lower: 85.12%) for both the upper and lower gluteus maximus. Neither the PRONE nor SQUEEZE was more effective between all subjects.

Conclusions: In agreement with other studies, no single testing position is ideal for every participant. Therefore, it is recommended that investigators employ multiple MVIC positions, when possible, to ensure accuracy. Future research should investigate a variety of gluteus maximus MVIC positions in heterogeneous samples.

Muscle hypertrophy and atrophy occur frequently as a result of mechanical loading or unloading, with implications for clinical, general, and athletic populations. The effects of muscle hypertrophy and atrophy on force production and joint moments have been previously described. However, there is a paucity of research showing how hypertrophy and atrophy may affect moment arm (MA) lengths. The purpose of this model was to describe the mathematical relationship between the anatomical cross-sectional area (ACSA) of a muscle and its MA length. In the model, the ACSAs of the biceps brachii and brachialis were altered to hypertrophy up to twice their original size and to atrophy to one-half of their original size. The change in MA length was found to be proportional to the arcsine of the square root of the change in ACSA. This change in MA length may be a small but important contributor to strength, especially in sports that require large joint moments at slow joint angular velocities, such as powerlifting. The paradoxical implications of the increase in MA are discussed, as physiological factors influencing muscle contraction velocity appear to favor a smaller MA length for high velocity movements but a larger muscle MA length for low velocity, high force movements.