Matching Items (149)
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Description

Measuring small molecule interactions with membrane proteins in single cells is critical for understanding many cellular processes and for screening drugs. However, developing such a capability has been a difficult challenge. We show that molecular interactions with membrane proteins induce a mechanical deformation in the cellular membrane, and real-time monitoring

Measuring small molecule interactions with membrane proteins in single cells is critical for understanding many cellular processes and for screening drugs. However, developing such a capability has been a difficult challenge. We show that molecular interactions with membrane proteins induce a mechanical deformation in the cellular membrane, and real-time monitoring of the deformation with subnanometer resolution allows quantitative analysis of small molecule–membrane protein interaction kinetics in single cells. This new strategy provides mechanical amplification of small binding signals, making it possible to detect small molecule interactions with membrane proteins. This capability, together with spatial resolution, also allows the study of the heterogeneous nature of cells by analyzing the interaction kinetics variability between different cells and between different regions of a single cell.

ContributorsGuan, Yan (Author) / Shan, Xiaonan (Author) / Zhang, Fenni (Author) / Wang, Shaopeng (Author) / Chen, Hong-Yuan (Author) / Tao, Nongjian (Author) / Biodesign Institute (Contributor)
Created2015-10-23
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Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect

Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10-4) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10-60) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10[superscript -9]), BMI (5.4 x 10-6), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits.

ContributorsWinnier, Deidre A. (Author) / Fourcaudot, Marcel (Author) / Norton, Luke (Author) / Abdul-Ghani, Muhammad A. (Author) / Hu, Shirley L. (Author) / Farook, Vidya S. (Author) / Coletta, Dawn (Author) / Kumar, Satish (Author) / Puppala, Sobha (Author) / Chittoor, Geetha (Author) / Dyer, Thomas D. (Author) / Arya, Rector (Author) / Carless, Melanie (Author) / Lehman, Donna M. (Author) / Curran, Joanne E. (Author) / Cromack, Douglas T. (Author) / Tripathy, Devjit (Author) / Blangero, John (Author) / Duggirala, Ravindranath (Author) / Goring, Harald H. H. (Author) / DeFronzo, Ralph A. (Author) / Jenkinson, Christopher P. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-04-01
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Description
Obesity impairs skeletal muscle maintenance and regeneration, a condition that can progressively lead to muscle loss, but the mechanisms behind it are unknown. Muscle is primarily composed of multinucleated cells called myotubes which are derived by the fusion of mononucleated myocytes. A key mediator in this process is the cellular

Obesity impairs skeletal muscle maintenance and regeneration, a condition that can progressively lead to muscle loss, but the mechanisms behind it are unknown. Muscle is primarily composed of multinucleated cells called myotubes which are derived by the fusion of mononucleated myocytes. A key mediator in this process is the cellular fusion protein syncytin-1. This led to the hypothesis that syncytin-1 could be decreased in the muscle of obese/insulin resistant individuals. In contrast, it was found that obese/insulin resistant subjects had higher syncytin-1 expression in the muscle compared to that of the lean subjects. Across the subjects, syncytin-1 correlated significantly with body mass index, percent body fat, blood glucose and HbA1c levels, insulin sensitivity and muscle protein fractional synthesis rate. The concentrations of specific plasma fatty acids, such as the saturated fatty acid (palmitate) and monounsaturated fatty acid (oleate) are known to be altered in obese/insulin resistant humans, and also to influence the protein synthesis in muscle. Therefore, it was evaluated that the effects of palmitate and oleate on syncytin-1 expression, as well as 4E-BP1 phosphorylation, a key mechanism regulating muscle protein synthesis in insulin stimulated C2C12 myotubes. The results showed that treatment with 20 nM insulin, 300 µM oleate, 300 µM oleate +20 nM insulin and 300 µM palmitate + 300 µM oleate elevated 4E-BP1 phosphorylation. At the same time, 20 nM insulin, 300 µM palmitate, 300 µM oleate + 20 nM insulin and 300 µM palmitate + 300 µM oleate elevated syncytin-1 expression. Insulin stimulated muscle syncytin-1 expression and 4E-BP1 phosphorylation, and this effect was comparable to that observed in the presence of oleate alone. However, the presence of palmitate + oleate diminished the stimulatory effect of insulin on muscle syncytin-1 expression and 4E-BP1 phosphorylation. These findings indicate oleate but not palmitate increased total 4E-BP1 phosphorylation regardless of insulin and the presence of palmitate in insulin mediated C2C12 cells. The presence of palmitate inhibited the upregulation of total 4EB-P1 phosphorylation. Palmitate but not oleate increased syncytin-1 expression in insulin mediated C2C12 myotubes. It is possible that chronic hyperinsulinemia in obesity and/or elevated levels of fatty acids such as palmitate in plasma could have contributed to syncytin-1 overexpression and decreased muscle protein fractional synthesis rate in obese/insulin resistant human muscle.
ContributorsRavichandran, Jayachandran (Author) / Katsanos, Christos (Thesis advisor) / Coletta, Dawn (Committee member) / Dickinson, Jared (Committee member) / Arizona State University (Publisher)
Created2017
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Description

Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with

Although eusociality evolved independently within several orders of insects, research into the molecular underpinnings of the transition towards social complexity has been confined primarily to Hymenoptera (for example, ants and bees). Here we sequence the genome and stage-specific transcriptomes of the dampwood termite Zootermopsis nevadensis (Blattodea) and compare them with similar data for eusocial Hymenoptera, to better identify commonalities and differences in achieving this significant transition. We show an expansion of genes related to male fertility, with upregulated gene expression in male reproductive individuals reflecting the profound differences in mating biology relative to the Hymenoptera. For several chemoreceptor families, we show divergent numbers of genes, which may correspond to the more claustral lifestyle of these termites. We also show similarities in the number and expression of genes related to caste determination mechanisms. Finally, patterns of DNA methylation and alternative splicing support a hypothesized epigenetic regulation of caste differentiation.

ContributorsTerrapon, Nicolas (Author) / Li, Cai (Author) / Robertson, Hugh M. (Author) / Ji, Lu (Author) / Meng, Xuehong (Author) / Booth, Warren (Author) / Chen, Zhensheng (Author) / Childers, Christopher P. (Author) / Glastad, Karl M. (Author) / Gokhale, Kaustubh (Author) / Gowin, Johannes (Author) / Gronenberg, Wulfila (Author) / Hermansen, Russell A. (Author) / Hu, Haofu (Author) / Hunt, Brendan G. (Author) / Huylmans, Ann Kathrin (Author) / Khalil, Sayed M. S. (Author) / Mitchell, Robert D. (Author) / Munoz-Torres, Monica C. (Author) / Mustard, Julie (Author) / Pan, Hailin (Author) / Reese, Justin T. (Author) / Scharf, Michael E. (Author) / Sun, Fengming (Author) / Vogel, Heiko (Author) / Xiao, Jin (Author) / Yang, Wei (Author) / Yang, Zhikai (Author) / Yang, Zuoquan (Author) / Zhou, Jiajian (Author) / Zhu, Jiwei (Author) / Brent, Colin S. (Author) / Elsik, Christine G. (Author) / Goodisman, Michael A. D. (Author) / Liberles, David A. (Author) / Roe, R. Michael (Author) / Vargo, Edward L. (Author) / Vilcinskas, Andreas (Author) / Wang, Jun (Author) / Bornberg-Bauer, Erich (Author) / Korb, Judith (Author) / Zhang, Guojie (Author) / Liebig, Juergen (Author) / College of Liberal Arts and Sciences (Contributor)
Created2014-05-20
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Description

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m2) and lean (BMI, 22±1 kg/m2) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = – 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish impaired β-F1-ATPase translation as an important consequence of obesity.

ContributorsTran, Lee (Author) / Hanavan, Paul (Author) / Campbell, Latoya (Author) / De Filippis, Elena (Author) / Lake, Douglas (Author) / Coletta, Dawn (Author) / Roust, Lori R. (Author) / Mandarino, Lawrence (Author) / Carroll, Chad C. (Author) / Katsanos, Christos (Author) / College of Health Solutions (Contributor)
Created2016-08-17
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Description

Exposure to fine particles can cause various diseases, and an easily accessible method to monitor the particles can help raise public awareness and reduce harmful exposures. Here we report a method to estimate PM air pollution based on analysis of a large number of outdoor images available for Beijing, Shanghai

Exposure to fine particles can cause various diseases, and an easily accessible method to monitor the particles can help raise public awareness and reduce harmful exposures. Here we report a method to estimate PM air pollution based on analysis of a large number of outdoor images available for Beijing, Shanghai (China) and Phoenix (US). Six image features were extracted from the images, which were used, together with other relevant data, such as the position of the sun, date, time, geographic information and weather conditions, to predict PM2.5 index. The results demonstrate that the image analysis method provides good prediction of PM2.5 indexes, and different features have different significance levels in the prediction.

ContributorsLiu, Chenbin (Author) / Tsow, Francis (Author) / Zou, Yi (Author) / Tao, Nongjian (Author) / Biodesign Institute (Contributor)
Created2016-02-01
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Description

The production, characterization, and antioxidant capacity of the carotenoid fucoxanthin from the marine diatom Odontella aurita were investigated. The results showed that low light and nitrogen-replete culture medium enhanced the biosynthesis of fucoxanthin. The maximum biomass concentration of 6.36 g L-1 and maximum fucoxanthin concentration of 18.47 mg g-1 were

The production, characterization, and antioxidant capacity of the carotenoid fucoxanthin from the marine diatom Odontella aurita were investigated. The results showed that low light and nitrogen-replete culture medium enhanced the biosynthesis of fucoxanthin. The maximum biomass concentration of 6.36 g L-1 and maximum fucoxanthin concentration of 18.47 mg g-1 were obtained in cultures grown in a bubble column photobioreactor (Ø 3.0 cm inner diameter), resulting in a fucoxanthin volumetric productivity of 7.96 mg L-1 day-1. A slight reduction in biomass production was observed in the scaling up of O. aurita culture in a flat plate photobioreactor, yet yielded a comparable fucoxanthin volumetric productivity. A rapid method was developed for extraction and purification of fucoxanthin. The purified fucoxanthin was identified as all-trans-fucoxanthin, which exhibited strong antioxidant properties, with the effective concentration for 50% scavenging (EC50) of 1,1-dihpenyl-2-picrylhydrazyl (DPPH) radical and 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical being 0.14 and 0.03 mg mL-1, respectively. Our results suggested that O. aurita can be a natural source of fucoxanthin for human health and nutrition.

ContributorsXia, Song (Author) / Wang, Ke (Author) / Wan, Linglin (Author) / Li, Aifen (Author) / Hu, Qiang (Author) / Zhang, Chengwu (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2013-07-23
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Description

A novel portable wireless volatile organic compound (VOC) monitoring device with disposable sensors is presented. The device is miniaturized, light, easy-to-use, and cost-effective. Different field tests have been carried out to identify the operational, analytical, and functional performance of the device and its sensors. The device was compared to a

A novel portable wireless volatile organic compound (VOC) monitoring device with disposable sensors is presented. The device is miniaturized, light, easy-to-use, and cost-effective. Different field tests have been carried out to identify the operational, analytical, and functional performance of the device and its sensors. The device was compared to a commercial photo-ionization detector, gas chromatography-mass spectrometry, and carbon monoxide detector. In addition, environmental operational conditions, such as barometric change, temperature change and wind conditions were also tested to evaluate the device performance. The multiple comparisons and tests indicate that the proposed VOC device is adequate to characterize personal exposure in many real-world scenarios and is applicable for personal daily use.

ContributorsDeng, Yue (Author) / Chen, Cheng (Author) / Xian, Xiaojun (Author) / Tsow, Francis (Author) / Verma, Gaurav (Author) / McConnell, Rob (Author) / Fruin, Scott (Author) / Tao, Nongjian (Author) / Forzani, Erica (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-12-03
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Description
Capnography is the monitoring of concentrations of carbon dioxide in exhaled breath. It allows reliable insight into patients' metabolism, ventilation, and blood circulation. Capnography has become an integral part of anesthesiology monitoring in operating rooms. However, its used is limited in other contexts due to deeply engrained protocols, size of

Capnography is the monitoring of concentrations of carbon dioxide in exhaled breath. It allows reliable insight into patients' metabolism, ventilation, and blood circulation. Capnography has become an integral part of anesthesiology monitoring in operating rooms. However, its used is limited in other contexts due to deeply engrained protocols, size of capnographs, and the complexity of its interpretation. Intensive care units and in-home use could greatly benefit by a widespread usage of capnographs. Measuring methods include infrared spectroscopy, mass spectroscopy, and chemical colorimetric analysis. Infrared technology is currently the most widely used and cost-effective method for measuring carbon dioxide. However, this device can be bulky and costly. A novel portable breath CO2 analyzer was developed for this purpose. The analyzer features an accurate colorimetric CO2 sensor that can analyze ETCO2 in real time. Many advancements have been in made in the sensor fabrication process. Nevertheless, research on optimal packaging conditions and accelerated aging times have been limited. In this experiment, carbon dioxide sensors were packaged at four different environmental conditions to test their long-term stability. This was done to determine if these conditions had an effect on sensor degradation. In the second part of the experiment, a separate batch of sensors was placed inside an oven at 48 oC to investigate the effect of stabilization temperature dependence and accelerated aging. In conclusion, the data obtained from the sensors packaged at different conditions could not be concluded to be statistically different. Sensors packaged at ambient conditions had the highest average value at 0.45030 V and the ones at controlled 33% humidity had the lowest at 0.39348 V. The sensors packaged at 8.25% CO2 had the smallest variance in their voltage measurements. From these data, it can be concluded that environmental testing conditions had the greatest effect on the measured signal. The oven experiment showed that sensors rapidly stabilize at high temperature and these stay constant after reaching this stabilization. For future work, the signal difference at different environmental conditions should be done. Control of environmental conditions can be achieved by building a glove box to control temperature and humidity.
ContributorsCorral Clayton, Javier Alfonso (Author) / Forzani, Erica (Thesis director) / Tsow, Tsing (Committee member) / Barrett, The Honors College (Contributor) / Chemical Engineering Program (Contributor) / School of Sustainability (Contributor)
Created2015-05