Publications by authors named "Michael Tilley"

40 Publications

microRNAs and Gene-Environment Interactions in Autism: Effects of Prenatal Maternal Stress and the Gene on Maternal microRNA Expression.

Front Psychiatry 2021 5;12:668577. Epub 2021 Jul 5.

Children's Mercy Hospital and University of Missouri-Kansas City School of Medicine, Kansas City, MO, United States.

Genetics and environment both are critical in autism spectrum disorder (ASD), but their interaction (G × E) is less understood. Numerous studies have shown higher incidence of stress exposures during pregnancies with children later diagnosed with ASD. However, many stress-exposed mothers have unaffected children. The serotonin transporter () gene affects stress reactivity. Two independent samples have shown that the association between maternal stress exposure and ASD is greatest with maternal presence of the short (S)-allele (deletion in the promoter region). MicroRNAs play a regulatory role in the serotonergic pathway and in prenatal stress and are therefore potential mechanistic targets in this setting. We profiled microRNA expression in blood from mothers of children with ASD, with known stress exposure during pregnancy. Samples were divided into groups based on genotypes (LL/LS/SS) and prenatal stress level (high/low). Two thousand five hundred mature microRNAs were examined. The ANOVA analysis showed differential expression (DE) of 119 microRNAs; 90 were DE in high- vs. low-stress groups (stress-dependent). Two (miR-1224-5p, miR-331-3p) were recently reported by our group to exhibit stress-dependent expression in rodent brain samples from embryos exposed to prenatal stress. Another, miR-145-5p, is associated with maternal stress. Across genotypes, with high stress exposure, 20 significantly DE microRNAs were detected, five were stress-dependent. These microRNAs may be candidates for stress × genotype interactions. This is remarkable as these changes were from mothers several years after stress-exposed pregnancies. Our study provides evidence for epigenetic alterations in relation to a G × E model (prenatal maternal stress × gene) in ASD.
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http://dx.doi.org/10.3389/fpsyt.2021.668577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8288023PMC
July 2021

High-resolution spectral information enables phenotyping of leaf epicuticular wax in wheat.

Plant Methods 2021 Jun 7;17(1):58. Epub 2021 Jun 7.

Department of Soil and Crop Sciences, Texas A&M University, College Station, Texas, 77840, USA.

Background: Epicuticular wax (EW) is the first line of defense in plants for protection against biotic and abiotic factors in the environment. In wheat, EW is associated with resilience to heat and drought stress, however, the current limitations on phenotyping EW restrict the integration of this secondary trait into wheat breeding pipelines. In this study we evaluated the use of light reflectance as a proxy for EW load and developed an efficient indirect method for the selection of genotypes with high EW density.

Results: Cuticular waxes affect the light that is reflected, absorbed and transmitted by plants. The narrow spectral regions statistically associated with EW overlap with bands linked to photosynthetic radiation (500 nm), carotenoid absorbance (400 nm) and water content (~ 900 nm) in plants. The narrow spectral indices developed predicted 65% (EWI-13) and 44% (EWI-1) of the variation in this trait utilizing single-leaf reflectance. However, the normalized difference indices EWI-4 and EWI-9 improved the phenotyping efficiency with canopy reflectance across all field experimental trials. Indirect selection for EW with EWI-4 and EWI-9 led to a selection efficiency of 70% compared to phenotyping with the chemical method. The regression model EWM-7 integrated eight narrow wavelengths and accurately predicted 71% of the variation in the EW load (mg·dm) with leaf reflectance, but under field conditions, a single-wavelength model consistently estimated EW with an average RMSE of 1.24 mg·dm utilizing ground and aerial canopy reflectance.

Conclusions: Overall, the indices EWI-1, EWI-13 and the model EWM-7 are reliable tools for indirect selection for EW based on leaf reflectance, and the indices EWI-4, EWI-9 and the model EWM-1 are reliable for selection based on canopy reflectance. However, further research is needed to define how the background effects and geometry of the canopy impact the accuracy of these phenotyping methods.
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http://dx.doi.org/10.1186/s13007-021-00759-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185930PMC
June 2021

Identification of gluten-like proteins in selected pod bearing leguminous tree seeds.

PLoS One 2021 5;16(4):e0249427. Epub 2021 Apr 5.

United States Department of Agriculture, Agricultural Research Service, Center for Grain and Animal Health Research, Manhattan, Kansas, United States of America.

The protein composition, molecular weight distribution, and rheological properties of honey locust, mesquite, Kentucky coffee tree, and carob seed germs were compared against wheat gluten. Polymeric and Osborne fractionation protocols were used to assess biochemical properties. Dynamic oscillatory shear tests were performed to evaluate protein functionality. All samples had similar ratios of protein fractions as well as high molecular weight disulfide linked proteins except for the Kentucky coffee tree germ proteins, which were found to have lower molecular weight proteins with little disulfide polymerization. Samples were rich in acidic and polar amino acids (glutamic acid and arginine,). Rheological analyses showed that vital wheat gluten had the most stable network, while Kentucky coffee seed proteins had the weakest. High molecular weight disulfide linked glutenous proteins are a common, but not universal feature of pod bearing leguminous trees.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0249427PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021184PMC
September 2021

Changes in phenolic profiles and antioxidant activities during the whole wheat bread-making process.

Food Chem 2021 May 10;345:128851. Epub 2020 Dec 10.

Department of Grain Science and Industry, Kansas State University, Manhattan, KS 66606, USA. Electronic address:

Health benefits of whole wheat products are partially attributed to their unique phenolic profiles. This study investigated the effect of bread-making processes on the phenolic profiles and antioxidant activities of four different varieties of hard red winter wheat. The fermentation process generally increased soluble phenolic content, flavonoid content, antioxidant activities, and soluble ferulic acid of whole wheat products. The baking process increased the soluble phenolic content and antioxidant activities. Some phenolic acids were incorporated into Maillard reaction products during baking. For the insoluble fraction, fermentation and baking slightly increased phenolic content, flavonoid content, and antioxidant activities of certain wheat varieties. Ferulic acid and isomers of di-ferulic acid (DFA) were not significantly affected by the baking process. Overall, the bread-making process demonstrated positive effects on the potential health benefits of whole wheat products.
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http://dx.doi.org/10.1016/j.foodchem.2020.128851DOI Listing
May 2021

Rapid determination of total phenolic content of whole wheat flour using near-infrared spectroscopy and chemometrics.

Food Chem 2021 May 13;344:128633. Epub 2020 Nov 13.

Department of Grain Science and Industry, Kansas State University, Manhattan, KS 66506, USA. Electronic address:

Phenolics in whole wheat products provide many health benefits. Wheat breeders, producers, and end-users are becoming increasingly interested in wheats with higher total phenolic content (TPC). Whole wheat flour with higher phenolics may have greater marketing value in the future. However, conventional methods determining TPC are costly and labor-intensive, which are not practical for wheat breeders to analyze several thousands of lines within a limited timeframe. We presented a novel application of near-infrared spectroscopy for TPC prediction in whole wheat flour. The optimal regression model demonstrated R values of 0.92 and 0.90 for the calibration and validation sets, and a residual prediction deviation value of 3.4. The NIR method avoids the tedious extraction and TPC assay procedures, making it more convenient and cost-effective. Our result also demonstrated that NIR can accurately quantify phenolics even at low concentration (less than 0.2%) in the food matrix such as whole wheat flour.
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http://dx.doi.org/10.1016/j.foodchem.2020.128633DOI Listing
May 2021

Individual effects of enzymes and vital wheat gluten on whole wheat dough and bread properties.

J Food Sci 2020 Dec 10;85(12):4201-4208. Epub 2020 Nov 10.

Department of Grain Science and Industry, Kansas State University, 1301 Mid Campus Drive, Manhattan, Kansas, 66506, USA.

The objective of this research was to determine effects of five enzymes on whole wheat bread properties, particularly loaf volume, bread texture, and staling. Enzymes containing conventional α-amylase (α-amyl), cellulase (cel), glucose oxidase, maltogenic α-amylase (m amyl), and xylanase (xyl) were added at three levels. Vital wheat gluten (VWG) was added as an additional, separate treatment at 2.5% (flour weight basis). Enzymes had minimal effect on water absorption and mixing time. Each enzyme increased specific loaf volume for at least one of the usage levels tested (P < 0.01). Among the enzyme treatments, the greatest loaf volume was seen for xyl at the medium and high levels. No enzyme was as effective as VWG at increasing loaf volume. Overall, enzymes did not significantly change cell structure. The greatest reduction in fresh bread hardness was obtained for the high level of xyl. VWG, m amyl, and xyl reduced the rate of bread firming over 7 days. α-Amyl, cel, and m amyl decreased starch retrogradation at day 7 as measured by differential scanning calorimetry (P < 0.01). M amyl nearly eliminated the endothermic peak for recrystallized amylopectin. This study demonstrated the specific application of enzymes in whole wheat bread to increase loaf volume and decrease initial crumb hardness and bread staling. PRACTICAL APPLICATION: This study will provide guidance for practical uses of enzymes in improving whole wheat dough and bread quality.
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http://dx.doi.org/10.1111/1750-3841.15517DOI Listing
December 2020

Analysis of corn and sorghum flour mixtures using laser-induced breakdown spectroscopy.

J Sci Food Agric 2021 Feb 2;101(3):1076-1084. Epub 2020 Sep 2.

Department of Food Engineering, Hacettepe University, Ankara, Turkey.

Background: In a world constantly challenged by climate change, corn and sorghum are two important grains because of their high productivity and adaptability, and their multifunctional use for different purposes such as human food, animal feed, and feedstock for many industrial products and biofuels. Corn and sorghum can be utilized interchangeably in certain applications; one grain may be preferred over the other for several reasons. The determination of the composition corn and sorghum flour mixtures may be necessary for economic, regulatory, environmental, functional, or nutritional reasons.

Results: Laser-induced breakdown spectroscopy (LIBS) in combination with chemometrics, was used for the classification of flour samples based on the LIBS spectra of flour types and mixtures using partial least squares discriminant analysis (PLS-DA) and the determination of the sorghum ratio in sorghum / corn flour mixture based on their elemental composition using partial least squares (PLS) regression. Laser-induced breakdown spectroscopy with PLS-DA successfully identified the samples as either pure corn, pure sorghum, or corn-sorghum mixtures. Moreover, the addition of various levels of sorghum flour to mixtures of corn-sorghum flour were used for PLS analysis. The coefficient of determination values of calibration and validation PLS models are 0.979 and 0.965, respectively. The limit of detection of the PLS models is 4.36%.

Conclusion: This study offers a rapid method for the determination of the sorghum level in corn-sorghum flour mixtures and the classification of flour samples with high accuracy, a short analysis time, and no requirement for time-consuming sample preparation procedures. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10717DOI Listing
February 2021

Traumatic Arthrotomy.

J Am Acad Orthop Surg 2020 Feb;28(3):102-111

From the Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas.

Evaluation of periarticular traumatic wounds for joint penetration is a common clinical concern for orthopaedic surgeons. Wounds that violate the joint capsule can result in deep infection and sepsis. Understanding the anatomic landmarks and capsular extensions of the major joints is key to proper evaluation. Initial evaluation of periarticular wounds includes thorough examination of the wound and plain radiographs. Historically, the saline load test has been the diagnostic test of choice for assessing traumatic arthrotomy; however, CT has recently been shown to have excellent sensitivity and specificity for detecting open knee joint injuries. Current treatment of traumatic arthrotomy includes intravenous antibiotics and surgical irrigation and débridement. Future areas of research must focus on further validation of CT evaluation and its use in other major joints, standardizing antibiotic treatment, and further delineating the role of nonsurgical management in minor injuries.
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http://dx.doi.org/10.5435/JAAOS-D-19-00153DOI Listing
February 2020

Effects of stress on functional connectivity during verbal processing.

Brain Imaging Behav 2020 Dec;14(6):2708-2723

Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO, USA.

Effects of stress on functional connectivity (FC) in specific language processing regions of the brain during verbal fluency tasks were explored. Roles of gender and serotonin transporter gene polymorphisms (5-HTTLPR), associated with stress susceptibility, were also examined to understand their effect. Forty-five healthy volunteers (Mean age: 19.6 ± 1.6 years; 28 females) participated. Functional magnetic resonance imaging was carried out while participants performed letter and category fluency tasks. These tasks were interposed with the Montreal Imaging Stress Test to induce stress or a no-stress control task. Buccal swabs collected were used to genotype for the presence of polymorphisms on the SLC6A4 gene known to contribute to atypical stress responses. Significant variations in strength of FC were noted between several ROIs, including left inferior frontal gyrus and left middle temporal gyrus. Overall, males showed regional increases in FC strength over long and short distances during task under stress. Additionally, variability in effects of stress on task performance was associated with effects of stress on FC. Results suggest that long distance FC may be strengthened to compensate for additional cognitive load of the stressor but that specific short distance functional connections may be strengthened in a gender specific manner. Additionally, FC may serve as a marker for effects of stress on performance. This is the first study exploring stress effects on language tasks with imaging markers. Future studies will need to explore stress susceptible populations and establish the role of FC as a marker, with implications for targeted therapeutic interventions.
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http://dx.doi.org/10.1007/s11682-019-00221-5DOI Listing
December 2020

Effects of stress on functional connectivity during problem solving.

Neuroimage 2020 03 4;208:116407. Epub 2019 Dec 4.

Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO, USA; Department of Psychological Sciences, University of Missouri, Columbia, MO, USA; Department of Radiology, University of Missouri, Columbia, MO, USA; Department of Neurology, University of Missouri, Columbia, MO, USA; Thompson Center for Autism and Neurodevelopmental Disorders, University of Missouri, Columbia, MO, USA; William and Nancy Thompson Endowed Chair in Radiology, University of Missouri, Columbia, MO, USA; School of Medicine, University of Missouri, Columbia, MO, USA. Electronic address:

Aim: Our purpose was to examine how stress affects functional connectivity (FC) in language processing regions of the brain during a verbal problem solving task associated with creativity. We additionally explored how gender and the presence of the stress-susceptible short allele of the serotonin transporter gene polymorphism influenced this effect.

Methods: Forty-five healthy participants (Mean age: 19.6 ​± ​1.6 years; 28 females) were recruited to be a part of this study and genotyped to determine the presence or absence of at least one copy of the short (S) allele of the serotonin transporter gene, which is associated with greater susceptibility to stress. The participants underwent functional magnetic resonance imaging in two separate sessions (stress and no stress control). One session utilized a modified version of the Montreal Imaging Stress Test (MIST) to induce stress while the other session consisted of a no stress control task. The MIST and control tasks were interleaved with task blocks during which the participants performed the compound remote associates task, a convergent task that engages divergent thinking, which is a critical component of creativity. We examined the relationship between stress effects on performance and effects on connectivity of language processing regions activated during this task.

Results: There was no main effect of stress on functional connectivity for individual ROI pairs. However, in the examination of whether stress effects on performance related to effects on connectivity, changes in middle temporal gyrus connectivity with stress correlated positively with changes in solution latency for individuals with the S allele, but anti-correlated for those with only the L allele. A trend towards a gene ​× ​stress interaction on solution latency was also observed.

Discussion: Results from the study suggest that genetic susceptibility to stress, such as the presence of the S allele, affects neural correlates of performance on tasks related to verbal problem solving, as indicated by connectivity of the middle temporal gyrus. Future work will need to determine whether connectivity of the middle temporal gyrus serves as a marker for the effect of stress susceptibility on cognition, extending into stress susceptible patient populations.
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http://dx.doi.org/10.1016/j.neuroimage.2019.116407DOI Listing
March 2020

Factors Influencing Zein-Whole Sorghum Flour Dough Formation and Bread Quality.

J Food Sci 2019 Dec 13;84(12):3522-3534. Epub 2019 Nov 13.

Center for Grain and Animal Health Research, USDA-ARS, 1515 College Ave, Manhattan, KS, 66502, U.S.A.

Zein is known to able to form viscoelastic dough with wheat-like properties under certain conditions. Several studies have been conducted to explain the mechanism behind this ability and to improve the functionality and end-use quality of zein-based dough systems. However, most of this research has been conducted using zein in combination with isolated starches or high-starch flours. To investigate the production of additional zein-whole sorghum flour breads, experiments were conducted to determine factors impacting zein-whole sorghum flour dough and bread quality. Optimizing water levels, using defatted zein and/or sorghum flour, and increasing zein content in dough formulas were investigated as initial formulation steps. Of these factors, increasing zein content from 20% to 30% (flour weight basis) had the greatest impact, resulting in stronger zein-based dough and improved bread quality. Additives and zein treatments shown to impact zein functionality were then investigated for their effect of zein-whole sorghum flour breads. Mixing zein and whole sorghum flour with 0.5% hydrogen peroxide, 5% ethanol, or 3% hydroxypropyl methylcellulose resulted in improved dough strength and bread quality. Breads made from whole white sorghum flour had improved quality compared to zein-based breads made with black or high-tannin whole sorghum flour. PRACTICAL APPLICATION: Zein is known to be able to form wheat-like dough when mixed under the right conditions. Most of the research on zein-based dough and food products has used high-starch flours. This project investigated optimizing the production of zein-whole sorghum flour dough and bread as an alternative. Increasing the zein content in the formula and using additives including ethanol and HPMC produced breads from zein-whole sorghum flour that were like those made with zein and pure starch.
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http://dx.doi.org/10.1111/1750-3841.14832DOI Listing
December 2019

Ipsilateral rotational double-barrel fibula autograft for limb salvage in a pediatric patient with lower extremity intramedullary osteosarcoma: A case report.

Microsurgery 2020 Feb 8;40(2):247-251. Epub 2019 Jul 8.

Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, Kansas.

Osteosarcoma is a relatively uncommon diagnosis that often requires limb salvage techniques in young patients. Due to the potential long-life expectancy of these patients, techniques which avoid prostheses are preferred to limit the need for future revision surgeries. This case report presents a 9-year-old male diagnosed with intramedullary well-differentiated osteosarcoma of the tibial diaphysis. This limb salvage procedure utilized a rotational ipsilateral vascularized double barrel fibula autograft measuring a total of 24.5 cm when harvested but osteotomized to lengths of 11 and 12.5 cm limbs to reconstruct an 11 cm tibial shaft defect. Anterior chamfer cuts were performed on one limb allowing it to be inserted intramedullary while the second limb was then placed with an inlay technique posterolaterally and then compressed with a carbon fiber plate. The patient recovered well initially postoperatively but was taken back for revision of the carbon fiber plate 10 weeks postoperatively secondary to asymptomatic loosening of the proximal screws. The patient subsequently healed and experienced full graft incorporation with expected hypertrophy of the graft. At most recent follow-up at 19 months, the patient reported no pain and was utilizing the extremity in a normal fashion with no activity limitations. In this report, we present a case of the use of an ipsilateral rotational double-barrel fibula autograft for limb salvage in a pediatric patient with lower extremity intramedullary osteosarcoma.
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http://dx.doi.org/10.1002/micr.30487DOI Listing
February 2020

Influence of Serotonin Transporter SLC6A4 Genotype on the Effect of Psychosocial Stress on Cognitive Performance: An Exploratory Pilot Study.

Cogn Behav Neurol 2018 06;31(2):79-85

Department of Pharmacology.

Background And Objective: Previous research has shown an effect of various psychosocial stressors on unconstrained cognitive flexibility, such as searching through a large set of potential solutions in the lexical-semantic network during verbal problem-solving. Functional magnetic resonance imaging has shown that the presence of the short (S) allele (lacking a 43-base pair repeat) of the promoter region of the gene (SLC6A4) encoding the serotonin transporter (5-HTT) protein is associated with a greater amygdalar response to emotional stimuli and a greater response to stressors. Therefore, we hypothesized that the presence of the S-allele is associated with greater stress-associated impairment in performance on an unconstrained cognitive flexibility task, anagrams.

Methods: In this exploratory pilot study, 28 healthy young adults were genotyped for long (L)-allele versus S-allele promoter region polymorphism of the 5-HTT gene, SLC6A4. Participants solved anagrams during the Trier Social Stress Test, which included public speaking and mental arithmetic stressors. We compared the participants' cognitive response to stress across genotypes.

Results: A Gene×Stress interaction effect was observed in this small sample. Comparisons revealed that participants with at least one S-allele performed worse during the Stress condition.

Conclusions: Genetic susceptibility to stress conferred by SLC6A4 appeared to modulate unconstrained cognitive flexibility during psychosocial stress in this exploratory sample. If confirmed, this finding may have implications for conditions associated with increased stress response, including performance anxiety and cocaine withdrawal. Future work is needed both to confirm our findings with a larger sample and to explore the mechanisms of this proposed effect.
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http://dx.doi.org/10.1097/WNN.0000000000000153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021134PMC
June 2018

Interaction mechanisms of condensed tannins (proanthocyanidins) with wheat gluten proteins.

Food Chem 2018 Apr 14;245:1154-1162. Epub 2017 Nov 14.

Texas A&M University, Soil & Crop Sciences Department, 2474 TAMU, College Station, TX 77843, USA; Texas A&M University, Nutrition & Food Science Department, College Station, TX 77843, USA. Electronic address:

Proanthocyanidins (PA) crosslink wheat gluten, increasing its polymer size and strength. However, mechanisms behind these interactions are unknown. This study used PA of different MW profiles (mean degree of polymerization 8.3 and 19.5) to investigate how PA polymerize gluten. The higher MW PA had greater binding affinity for both glutenins and gliadins than lower MW PA, whereas both PA precipitated glutenins more efficiently than gliadins. The PA preferentially bound the largest of the protein fractions available: high MW glutenin subunits (HMW-GS) over low MW-GS, and ω-gliadins over α- and γ-gliadins. Furthermore, within the HMW-GS, PA bound more of the larger x-type than the smaller y-type. Proanthocyanidins reduced gluten solubility in urea and decreased surface hydrophobicity of glutenins, but not gliadins. The PA appear to preferentially crosslink HMW-GS via hydrophobic interactions and hydrogen bonding, whereas their interaction with gliadins is dominated by hydrogen bonding and is relatively weaker.
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http://dx.doi.org/10.1016/j.foodchem.2017.11.054DOI Listing
April 2018

Using Anilines as Masked Cross-Coupling Partners: Design of a Telescoped Three-Step Flow Diazotization, Iododediazotization, Cross-Coupling Process.

Chemistry 2016 Nov 21;22(48):17407-17415. Epub 2016 Oct 21.

Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario, M3J 1P3, Canada.

The conversion of commercially available anilines into biaryl and biarylacetylene products was realized by using a telescoped, three-reactor flow diazotization/iododediazotization/cross-coupling process. The segmented flow stream created by off-gassing during the Sandmeyer sequence was restored to a continuous column of reaction solution by using a specially designed continuous-flow unit controlled by custom software created in-house. The resultant aryl iodide was then combined with a stream of cross-coupling solution that fed into the final reactor. The system proved versatile as modifications to the diazotization/iododediazotization sequence could be made rapidly to account for any substrate specificity (e.g., solubility problems), leading to a wide substrate scope of Suzuki-Miyaura and Sonogashira cross-coupled products.
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http://dx.doi.org/10.1002/chem.201603626DOI Listing
November 2016

Maternal serotonin transporter genotype affects risk for ASD with exposure to prenatal stress.

Autism Res 2016 11 19;9(11):1151-1160. Epub 2016 Apr 19.

Interdisciplinary Neuroscience Program, University of Missouri, Columbia, Missouri.

Stress exposure during gestation is implicated in several neuropsychiatric conditions, including autism spectrum disorder (ASD). Previous research showed that prenatal stress increases risk for ASD with peak exposure during the end of the second and the beginning of the third trimester. However, exposures to prenatal stress do not always result in ASD, suggesting that other factors may interact with environmental stressors to increase ASD risk. The present study examined a maternal genetic variation in the promoter region of the serotonin transporter gene (5-HTTLPR) affecting stress tolerance and its interaction with the effect of environmental stressors on risk for ASD. Two independent cohorts of mothers of ASD children recruited by the University of Missouri and Queen's University were surveyed regarding the prenatal environment and genotyping on 5-HTTLPR was performed to explore this relationship. In both samples, mothers of children with ASD carrying the stress susceptible short allele variant of 5-HTTLPR experienced a greater number of stressors and greater stress severity when compared to mothers carrying the long allele variant. The temporal peak of stressors during gestation in these mothers was consistent with previous findings. Additionally, increased exposure to prenatal stress was not reported in the pregnancies of typically developing siblings from the same mothers, regardless of maternal genotype, suggesting against the possibility that the short allele might increase the recall of stress during pregnancy. The present study provides further evidence of a specific maternal polymorphism that may affect the risk for ASD with exposure to prenatal stress. Autism Res 2016, 9: 1151-1160. © 2016 International Society for Autism Research, Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/aur.1629DOI Listing
November 2016

Joint instability and osteoarthritis.

Clin Med Insights Arthritis Musculoskelet Disord 2015 19;8:15-23. Epub 2015 Feb 19.

Department of Orthopedic Surgery, University of Kansas Medical Center, Kansas City, KS, USA.

Joint instability creates a clinical and economic burden in the health care system. Injuries and disorders that directly damage the joint structure or lead to joint instability are highly associated with osteoarthritis (OA). Thus, understanding the physiology of joint stability and the mechanisms of joint instability-induced OA is of clinical significance. The first section of this review discusses the structure and function of major joint tissues, including periarticular muscles, which play a significant role in joint stability. Because the knee, ankle, and shoulder joints demonstrate a high incidence of ligament injury and joint instability, the second section summarizes the mechanisms of ligament injury-associated joint instability of these joints. The final section highlights the recent advances in the understanding of the mechanical and biological mechanisms of joint instability-induced OA. These advances may lead to new opportunities for clinical intervention in the prevention and early treatment of OA.
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http://dx.doi.org/10.4137/CMAMD.S22147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4337591PMC
March 2015

Grain sorghum proteomics: integrated approach toward characterization of endosperm storage proteins in kafirin allelic variants.

J Agric Food Chem 2014 Oct 24;62(40):9819-31. Epub 2014 Sep 24.

School of Agriculture and Food Sciences and ⊥Institute for Molecular Bioscience, The University of Queensland , St Lucia, Brisbane, QLD 4072, Australia.

Grain protein composition determines quality traits, such as value for food, feedstock, and biomaterials uses. The major storage proteins in sorghum are the prolamins, known as kafirins. Located primarily on the periphery of the protein bodies surrounding starch, cysteine-rich β- and γ-kafirins may limit enzymatic access to internally positioned α-kafirins and starch. An integrated approach was used to characterize sorghum with allelic variation at the kafirin loci to determine the effects of this genetic diversity on protein expression. Reversed-phase high performance liquid chromatography and lab-on-a-chip analysis showed reductions in alcohol-soluble protein in β-kafirin null lines. Gel-based separation and liquid chromatography-tandem mass spectrometry identified a range of redox active proteins affecting storage protein biochemistry. Thioredoxin, involved in the processing of proteins at germination, has reported impacts on grain digestibility and was differentially expressed across genotypes. Thus, redox states of endosperm proteins, of which kafirins are a subset, could affect quality traits in addition to the expression of proteins.
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http://dx.doi.org/10.1021/jf5022847DOI Listing
October 2014

Multicomponent, flow diazotization/Mizoroki-Heck coupling protocol: dispelling myths about working with diazonium salts.

Chemistry 2014 May 17;20(22):6603-7. Epub 2014 Apr 17.

Department of Chemistry, York University, 4700 Keele Street, Toronto, Ontario, M3J1P3 (Canada).

A single pass flow diazotization/Mizoroki-Heck protocol has been developed for the production of cinnimoyl and styryl products. The factors that govern aryl diazonium salt stability have been examined in detail leading to the development of a MeOH/DMF co-solvent system in which the diazonium salts can be generated in the presence of all other reaction components and then coupled selectively to give the desired products. Finally the key role of the reaction quench for flow reactions has been demonstrated.
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http://dx.doi.org/10.1002/chem.201402092DOI Listing
May 2014

Effect of high molecular weight glutenin subunit composition in common wheat on dough properties and steamed bread quality.

J Sci Food Agric 2014 Oct 31;94(13):2801-6. Epub 2014 Mar 31.

Cereal Quality Lab, Department of Soil and Crop Sciences, Texas A&M University, College Station, TX, USA; Provincial Key Lab for Agrobiology, Jiangsu Academy of Agricultural Sciences, Nanjing, Jiangsu, China.

Background: Steamed bread is a popular staple food in Asia with different flour quality requirements from pan bread. Little is known about how glutenin characteristics affect steamed bread quality. This work investigated how deletions of high-molecular-weight glutenin subunits (HMW-GS) influence gluten properties and Chinese steamed bread quality using 16 wheat lines grown in Texas.

Results: Although similar in protein content (134-140 mg g⁻¹), gluten composition and dough properties differed widely among the lines. Compared with non-deletion lines, deletion lines had lower (P < 0.05) unextractable polymeric protein (294 vs 470 mg g⁻¹), HMW-GS/low-molecular-weight glutenin subunit ratio (0.25 vs 0.41), dough force to extend (0.16 vs 0.44 N) and mixing peak time (2.03 vs 4.52 min). Deletion lines with HMW-GS composition of 2*/17+_/5+_ and 2*/17+_/2+12 showed moderate gluten strength (mixing peak time, 1.96-2.94 min; force to extend, 0.18-0.23 N) and high dough extensibility (106-129 mm). These lines also produced good steamed bread quality (score, 60.8-65.0) with good elasticity and crumb structure.

Conclusion: Deletion at Glu-B1y and/or Glu-D1y loci in high-strength hard wheat produced good dough properties for steamed bread. This suggests that wheat functionality for steamed bread can be improved by manipulating HMW-GS composition.
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http://dx.doi.org/10.1002/jsfa.6635DOI Listing
October 2014

Behavior of knock-in mice with a cocaine-insensitive dopamine transporter after virogenetic restoration of cocaine sensitivity in the striatum.

Neuropharmacology 2014 Apr 9;79:626-33. Epub 2014 Jan 9.

Department of Pharmacology, The Ohio State University, 333 West 10th Avenue, 5184B Graves Hall, Columbus, OH 43210, USA. Electronic address:

Cocaine's main pharmacological actions are the inhibition of the dopamine, serotonin, and norepinephrine transporters. Its main behavioral effects are reward and locomotor stimulation, potentially leading to addiction. Using knock-in mice with a cocaine-insensitive dopamine transporter (DAT-CI mice) we have shown previously that inhibition of the dopamine transporter (DAT) is necessary for both of these behaviors. In this study, we sought to determine brain regions in which DAT inhibition by cocaine stimulates locomotor activity and/or produces reward. We used adeno-associated viral vectors to re-introduce the cocaine-sensitive wild-type DAT in specific brain regions of DAT-CI mice, which otherwise only express a cocaine-insensitive DAT globally. Viral-mediated expression of wild-type DAT in the rostrolateral striatum restored cocaine-induced locomotor stimulation and sensitization in DAT-CI mice. In contrast, the expression of wild-type DAT in the dorsal striatum, or in the medial nucleus accumbens, did not restore cocaine-induced locomotor stimulation. These data help to determine cocaine's molecular actions and anatomical loci that cause hyperlocomotion. Interestingly, cocaine did not produce significant reward - as measured by conditioned place-preference - in any of the three cohorts of DAT-CI mice with the virus injections. Therefore, the locus or loci underlying cocaine-induced reward remain underdetermined. It is possible that multiple dopamine-related brain regions are involved in producing the robust rewarding effect of cocaine.
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http://dx.doi.org/10.1016/j.neuropharm.2013.12.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4011184PMC
April 2014

High-throughput micro plate assays for screening flavonoid content and DPPH-scavenging activity in sorghum bran and flour.

J Sci Food Agric 2012 Aug 14;92(11):2326-31. Epub 2012 Mar 14.

USDA-ARS, Center for Grain and Animal Health Research, Manhattan, KS 66502, USA.

Background: Sorghum possesses phenolic compounds that are health-promoting constituents of the grain. There are approximately 40 000 sorghum accessions, many of which have not been evaluated for the grain's health-promoting potential. Conventional methods for measuring total phenolic content, flavonoid content and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging capacity are time-consuming and labour-intensive, resulting in low overall throughput. The objective of this study was to develop a high-throughput screening assay for large sorghum sample sets to determine flavonoid and phenolic content and to modify existing DPPH and total phenolic assays.

Results: The 96-well assays exhibited a correlation of > 0.9 with the conventional assays. The 96-well assays allowed for up to 64 samples to be run per day compared with 20-24 samples (depending on the test) for the conventional methods. The 96-well assays had excellent accuracy (97.65-106.16% recovery), precision (1.06-8.28% coefficient of variation (CV)) and reproducibility (1.32-2.13% CV inter-day and 1.36-2.09% CV intra-day).

Conclusion: The high-throughput 96-well plate method proved to be as robust and reproducible as the conventional method for determining total phenolic content, flavonoid content and DPPH-scavenging capacity in either sorghum bran or flour.
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http://dx.doi.org/10.1002/jsfa.5633DOI Listing
August 2012

Composition and molecular weight distribution of carob germ protein fractions.

J Agric Food Chem 2010 Jul;58(13):7794-800

Center for Grain and Animal Health Research, Agricultural Research Service, U.S. Department of Agriculture, Manhattan, Kansas 66502, USA.

Biochemical properties of carob germ proteins were analyzed using a combination of selective extraction, reversed-phase high-performance liquid chromatography (RP-HPLC), size exclusion chromatography (SEC) coupled with multiangle laser light scattering (SEC-MALS), and electrophoretic analysis. Using a modified Osborne extraction procedure, carob germ flour proteins were found to contain approximately 32% albumin and globulin and approximately 68% glutelin with no prolamins detected. The albumin and globulin fraction was found to contain low amounts of disulfide-bonded polymers with relatively low M(w) ranging up to 5 x 10(6) Da. The glutelin fraction, however, was found to contain large amounts of high molecular weight disulfide-bonded polymers with M(w) up to 8 x 10(7) Da. When extracted under nonreducing conditions and divided into soluble and insoluble proteins as typically done for wheat gluten, carob germ proteins were found to be almost entirely ( approximately 95%) in the soluble fraction with only ( approximately 5%) in the insoluble fraction. As in wheat, SEC-MALS analysis showed that the insoluble proteins had a greater M(w) than the soluble proteins and ranged up to 8 x 10(7) Da. The lower M(w) distribution of the polymeric proteins of carob germ flour may account for differences in functionality between wheat and carob germ flour.
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http://dx.doi.org/10.1021/jf101523pDOI Listing
July 2010

Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction in mice.

Int J Dev Neurosci 2010 Oct 12;28(6):529-36. Epub 2010 May 12.

Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO 65211, USA.

Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild-type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a three-chamber social approach task, ultrasonic vocalization detection, elevated-plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic-like behaviors in offspring.
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http://dx.doi.org/10.1016/j.ijdevneu.2010.05.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2918686PMC
October 2010

Potencies of cocaine methiodide on major cocaine targets in mice.

PLoS One 2009 Oct 26;4(10):e7578. Epub 2009 Oct 26.

Ohio State Biochemistry Program, The Ohio State University, Columbus, Ohio, United States of America.

Cocaine methiodide (CM), a charged cocaine analog, cannot pass the blood brain barrier. It has been assumed the effects of systemic CM represent cocaine actions in peripheral tissues. However, the IC(50) values of CM have not been clearly determined for the major cocaine targets: dopamine, norepinephrine, and serotonin transporters, and sodium channels. Using cells transfected with individual transporters from mice and synaptosomes from mouse striatum tissues, we observed that the inhibition IC(50) values for monoamine uptake by CM were 31-fold to 184-fold higher compared to cocaine at each of the transporters. In dorsal root ganglion neurons, cocaine inhibited sodium channels with an apparent IC(50) of 75 microM, while CM showed no observable effect at concentrations up to 3 mM. These results indicate that an equal dose of CM will not produce an equivalent peripheral effect of cocaine.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007578PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2762027PMC
October 2009

Comparison of methods for extracting kafirin proteins from sorghum distillers dried grains with solubles.

J Agric Food Chem 2009 Sep;57(18):8366-72

Department of Biological and Agricultural Engineering, Kansas State University, Manhattan, Kansas 66506, USA.

Use of coproducts generated during fermentation is important to the overall economics of biofuel production. The main coproduct from grain-based ethanol production is distillers dried grains with solubles (DDGS). High in protein, DDGS is a potential source of protein for many bioindustrial applications such as adhesives and resins. The objective of this research was to characterize the composition as well as chemical and physical properties of kafirin proteins from sorghum DDGS with various extraction methods including use of acetic acid, HCl-ethanol and NaOH-ethanol under reducing conditions. Extraction conditions affected purity and thermal properties of the extracted kafirin proteins. Extraction yields of 44.2, 24.2, and 56.8% were achieved by using acetic acid, HCl-ethanol and NaOH-ethanol, respectively. Acetic acid and NaOH-ethanol produced protein with higher purity than kafirins extracted with the HCl-ethanol protocol. The acetic acid extraction protocol produced protein with the highest purity, 98.9%. Several techniques were used to evaluate structural, molecular and thermal properties of kairin extracts. FTIR showed alpha-helix dominated in all three samples, with only a small portion of beta-sheet present. Electrophoresis results showed alpha(1), alpha(2) band and beta kafirins were present in all three extracts. Glass transition peaks of the extracts were shown by DSC to be approximately 230 degrees C. Kafirin degraded at 270-290 degrees C. Size exclusion chromatography revealed that the acetic acid and HCl-ethanol based extraction methods tended to extract more high molecular weight protein than the NaOH-ethanol based method. Reversed phase high-performance liquid chromatography showed that the gamma kafirins were found only in extracts from the NaOH-ethanol extraction method.
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http://dx.doi.org/10.1021/jf901713wDOI Listing
September 2009

Financial and psychological risk attitudes associated with two single nucleotide polymorphisms in the nicotine receptor (CHRNA4) gene.

PLoS One 2009 Aug 20;4(8):e6704. Epub 2009 Aug 20.

Department of Agricultural, Environmental and Development Economics, Ohio State University, Columbus, Ohio, USA.

With recent advances in understanding of the neuroscience of risk taking, attention is now turning to genetic factors that may contribute to individual heterogeneity in risk attitudes. In this paper we test for genetic associations with risk attitude measures derived from both the psychology and economics literature. To develop a long-term prospective study, we first evaluate both types of risk attitudes and find that the economic and psychological measures are poorly correlated, suggesting that different genetic factors may underlie human response to risk faced in different behavioral domains. We then examine polymorphisms in a spectrum of candidate genes that affect neurotransmitter systems influencing dopamine regulation or are thought to be associated with risk attitudes or impulsive disorders. Analysis of the genotyping data identified two single nucleotide polymorphisms (SNPs) in the gene encoding the alpha 4 nicotine receptor (CHRNA4, rs4603829 and rs4522666) that are significantly associated with harm avoidance, a risk attitude measurement drawn from the psychology literature. Novelty seeking, another risk attitude measure from the psychology literature, is associated with several COMT (catechol-O-methyl transferase) SNPs while economic risk attitude measures are associated with several VMAT2 (vesicular monoamine transporter) SNPs, but the significance of these associations did not withstand statistical adjustment for multiple testing and requires larger cohorts. These exploratory results provide a starting point for understanding the genetic basis of risk attitudes by considering the range of methods available for measuring risk attitudes and by searching beyond the traditional direct focus on dopamine and serotonin receptor and transporter genes.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0006704PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2724734PMC
August 2009

Effects of overexpression of high molecular weight glutenin subunit 1Dy10 on wheat tortilla properties.

J Agric Food Chem 2009 Jul;57(14):6318-26

Department of Grain Science and Industry, Kansas State University Manhattan, Kansas 66506, USA.

Wheat (Triticum aestivum L.) flour properties necessary for optimal tortilla production have not been identified. Transgenic wheats (Triticum aestivum L.) overexpressing high molecular weight glutenin subunit (HMW-GS) 1Dy10 were used to make tortilla and their quality was evaluated. The level of HMW-GS 1Dy10 in flours derived from transgenic wheats was 2.5-5.8-fold greater than in controls. Polymeric proteins in the transgenic samples had a molecular weight distribution shifted toward larger polymers as indicated by increased levels of polymeric proteins present and greater M(w) averages of the largest fractions in the insoluble polymeric proteins. Dough derived from transgenic wheats had greater resistance to extension and lower extensibility than controls. Tortilla quality evaluation revealed that tortillas originated from transgenic wheats had decreased diameter, greater thickness and rupture force, and lower rollability scores and stretchability than controls. The presence of 1RS chromosomal translocations from rye (Secale cereale L.) in transgenic wheat decreased the negative effects of overexpression of HMW-GS 1Dy10, as tortillas made with this flour mostly exhibited quality properties similar to those made from control flour. Results suggested that the negative effects of overexpression of HMW-GS 1Dy10 on tortilla properties were derived from a nonideal gluten matrix formation.
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http://dx.doi.org/10.1021/jf900629sDOI Listing
July 2009

Functionality of gliadin proteins in wheat flour tortillas.

J Agric Food Chem 2009 Feb;57(4):1600-5

Department of Soil and Crop Sciences, Texas A&M University, College Station, Texas 77843, USA.

Gliadins are monomeric proteins that are encoded by the genes at the loci Gli 1 and Gli 2 present on the short arm of homologous wheat chromosomes 1 and 6, respectively. Studies have suggested that gliadins may play an important role in determining the functional properties of wheat flour. The main objective of this study was to understand the functionality of gliadins with respect to tortilla quality. The important tortilla quality attributes are diameter, opacity, and shelf stability, designated here as rollability or the ability to roll or fold the tortilla without cracking. In this study gliadin functionality in tortilla quality was studied using near-isogenic wheat lines that have deletions in either Gli A1, Gli D1, Gli A2, or Gli D2 gliadin loci. The deletion lines are designated by the same abbreviations. Dough and tortillas were prepared from the parent line used to derive these deletion lines, each individual deletion line, and a control commercial tortilla flour. Quantitative and qualitative evaluations were performed on the dough and tortillas derived from the flour from each of these lines. None of the deletions in the gliadin loci altered the shelf stability versus that found for the parent to the deletion lines or control tortilla flour. However, deletions in the Gli 2 loci, in particular Gli A2 reduced the relative proportion of alpha- and beta-gliadins with a greater cysteine amino acid content and gluten cross-link function versus the chain-terminating omega-gliadins in Gli 1, which were still present. As such, the dough and gluten matrix appeared to have greater extensibility, which improved the diameter and overall quality of the tortillas while not altering the rollability. Deletions in the Gli 1 loci had the opposite result with increased cross-linking of alpha- and beta-gliadins, polymeric protein content, and a stronger dough that decreased the diameter and overall quality of the tortillas. The data suggest that altering certain Gli 2 loci through null alleles could be a viable strategy to develop cultivars improved for the specific functionality requirements needed for the rapidly growing tortilla market.
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http://dx.doi.org/10.1021/jf802105eDOI Listing
February 2009

Cocaine does not produce reward in absence of dopamine transporter inhibition.

Neuroreport 2009 Jan;20(1):9-12

Department of aPharmacology, Ohio State University College of Medicine, Columbus, Ohio 43210, USA.

We have previously reported that knockin mice with a cocaine-insensitive dopamine transporter (DAT-CI mice) do not experience cocaine reward, as measured by conditioned place preference. This conclusion has come under scrutiny because some genetically modified mice show cocaine-induced conditioned place preference in a narrow dose range, that is, responding at doses around 10 mg/kg, but not at 5 and 20 mg/kg, the doses we tested in DAT-CI mice. These results raise the possibility that we have missed the optimal dose for cocaine response. Here we report that cocaine does not produce reward in DAT-CI mice at low, moderate, and high doses, including 10 mg/kg. This study strengthens our conclusion that DAT inhibition is required for cocaine reward in mice with a functional dopaminergic system.
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http://dx.doi.org/10.1097/WNR.0b013e32831b9ce4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4277863PMC
January 2009
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