bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nitric Oxide‐mediated Proteins' S‐nitrosation in Endothelial Cells under Shear Flow or Rosuvastatin Treatment
Authors: Wang Ling D. , Huang Bin 
Published: June 2021

Atheroprotection of shear flow to endothelial cells (ECs) is partly contributed by the increased nitric oxide (NO) production. Cholesterol lowing drug, statin, is known to increase NO levels via the induction of eNOS expression and activity. NO‐mediated S‐nitrosation of Cys residue has emerged as a fundamental post‐translational modification of proteins in ECs. S‐nitrosation can alter protein's function and affects vascular physiology. In the present study, proteins' S‐nitrosation was examined in HUVECs after shear flow or statin treament. Increased eNOS activation was observed in ECs after rosuvastatin (10 μM) or shear flow (25 dynes/cm2) treatment. The enhanced S‐nitrosoproteins in rosuvastatin‐treated ECs were detected by biotin switch method coupled with Western blot‐based 2‐DE, while the shear flow‐enhanced S‐nitrosated proteins were detected by CyDye DIGE. There were 12 and 18 proteins showing increased S‐nitrosation in ECs under flow and statin treatments, respectively. S‐nitrosation in protein disulfide isomerase (PDI), mitochondrial heat shock protein 70 (mt‐HSP70), heat shock transcription factor, tropomyosin and vimentin were shown to be increased in both treatments. Further analysis by nLC‐MS/MS and MASCOT in‐house algorithm, the S‐nitrosated Cys residues on the mt‐HSP70, tropomyosin and vimentin were also determined. Our results indicating that statin or shear flow exerts similar atheroprotection to ECs is at least partly due to the NO‐mediated S‐nitrosation in proteins. Proteins' S‐nitrosation may be essential for maintaining endothelial integrity.(This work ws supported by National Science Council and Academia Sinica, Taiwan)
The role of Nuclear Respiratory Factor‐1 in regulating GLUT4 expression
Authors: Mukwevho Emmanuel , Ojuka Edward 
Published: June 2021

Overexpression of NRF‐1 in transgenic mice has a dramatic increase in GLUT4 and myocyte enhancing factor (MEF)‐2 (Baar et al., 2003). The increase in GLUT4 was surprising since NRF‐1 has no binding sites on the Glut4 gene; hence the question is how does NRF‐1 regulate GLUT4? Our hypothesis is that GLUT4 expression is a secondary effect of NRF‐1 on the Mef2a gene, which has NRF‐1 binding sites. The aim of this study was to investigate the molecular mechanism leading to GLUT4 upregulation by NRF‐1.C2C12 cells were used to develop a tetracycline based gene expression system (Tet‐On) to form a double stable cell line which overexpresses NRF‐1 upon activation by Doxycycline.Our results show that NRF‐1 overexpression increases the binding of NRF‐1 to the Mef2a and δAlas promoters and MEF2A to Glut4 promoter. Furthermore NRF‐1 overexpression resulted in increase expressions for MEF2A, GLUT4 and δALAS proteins. Using small interference RNA directed against MEF2A, overexpression of NRF‐1 resulted in downregulation of GLUT4 protein expression.From these results we could conclude that NRF‐1 overexpression increases GLUT4 via Mef2a binding resulting in increased MEF2A which in turn increases its binding to the Glut4 gene resulting in GLUT4 expression. The parallel increases in mitochondrial and GLUT4 expression are essential in alleviating metabolic disease such as type II diabetes.
Effect of palmitoyl CoA on ADP‐evoked vasorelaxations in porcine isolated coronary and mesenteric arteries
Authors: Alefishat Eman , Alexander Stephen , Ralevic Vera 
Published: June 2021

Palmitoyl CoA (PaCoA) is an antagonist at human recombinant P2Y1 purine receptors (Coddou et al., 2003), HEK cells, human platelets (Manolopoulos et al., 2008), and rat thoracic aorta. The present study investigated the effect of PaCoA on vasorelaxation evoked by ADP in porcine isolated mesenteric and coronary arteries.In isometric tension recordings, ADP evoked concentration‐dependent relaxations of the pre‐contracted porcine mesenteric and coronary arteries with maximal responses of 40 ± 12 and 95 ± 7% and pEC50 values of 4.26 ± 0.33 and 3.27 ± 0.85 (n = 7–12), respectively. PaCoA (10 μM) had no significant effect on relaxations in the coronary artery but abolished relaxations in the mesenteric artery. Endothelium removal abolished ADP‐induced relaxations in the mesenteric but not coronary artery.The preferential inhibition by PaCoA of ADP‐evoked relaxations in the mesenteric, but not coronary, artery indicates the involvement of distinct mechanisms: endothelial P2Y1 receptors mediate vasorelaxation to ADP in the mesenteric artery while in the coronary artery ADP‐induced relaxation occurs via receptors on the smooth muscle that may involve adenosine release and activation of A2A receptors (Rayment et al., 2006).Coddou et al. (2003). FEBS Lett 536: 145–150Manolopoulos et al. (2008). Platelets 19: 134–145Rayment et al. (2007) FASEB J 21: 577–585Sponsored by the Jordanian government.
Involvement of Phosphoinositide 3‐kinase‐Akt signaling pathway in sodium channel activator‐induced neurite outgrowth
Authors: Jabba Sairam V , Gerwick William H , Murray Thomas F 
Published: June 2021

Calcium influx through N‐methyl D‐aspartate receptors (NMDAR) regulates signaling cascades that underlie neuronal development and synaptic plasticity. Earlier we demonstrated that the voltage‐gated sodium channel (VGSC) activators, brevetoxin and antillatoxin, increased [Na+]i, stimulated Ca2+ influx through NMDARs and enhanced NMDAR‐mediated neurite outgrowth (Joju et al., 2009, Jabba et al., 2010). Here we tested whether VGSC activator‐induced neurite outgrowth may involve NMDAR‐dependent activation of the PI3K‐Akt pathway. Veratridine (VRT), a VGSC activator, was used in this study. VRT enhanced neurite outgrowth and dendritic arborization in immature cerebrocortical neurons and displayed a biphasic concentration‐response curve. VRT produced an elevation of [Na+]i and [Ca2+]i in a tetrodotoxin‐sensitive manner. Exposure to VRT increased Akt phosphorylation in immature cerebrocortical neurons. Either the NMDAR antagonist MK‐801, PI3K inhibitor LY294002 or calmodulin‐dependent protein kinase kinase (CaMKK) inhibitor STO‐609 abolished VRT‐induced Akt phosphorylation. VRT‐induced neurite outgrowth and dendritic arborization was abrogated by LY294002. These data suggest that VGSC activator‐enhanced neuritogenisis and dendritic arborization involves elevation of [Na+]i, and [Ca2+]i, and activation of the NMDAR‐PI3K‐Akt pathway.(NIH RO1 NS053398‐06)
Mitochondria‐specific overexpression of phospholipid hydroperoxide glutathione peroxidase (GPx4) attenuates ischemia/reperfusion (I/R) associated apoptosis
Authors: Baseler Walter Allen , Williamson Courtney L. , Dabkowski Erinne R. , Croston Tara L. , Hollander John M 
Published: June 2021

A primary determinant of the extent of I/R injury in the mitochondrion is antioxidant defense capacity. Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a unique antioxidant enzyme capable of reducing peroxidized acyl groups in phospholipids, providing protection to biological membranes. The goal of this study was to evaluate the impact of mitochondria‐specific overexpression of PHGPx on apoptotic susceptibility following cardiac I/R. Transgenic mice were created in which PHGPx was overexpressed in the mitochondrion (mPHGPx). MPHGPx and control hearts were subjected to global no‐flow ischemia (20 min) followed by reperfusion (90 min). MPHGPx subsarcolemmal mitochondria (SSM) displayeda decreased propensity for undergoing apoptosis as compared to I/R controls, with no differences in interfibrillar mitochondria (IFM). Caspase‐3 and −9 activities were decreased in mPHGPx SSM relative to I/R control (P<0.05), with no differences in IFM. Mitochondrial permeability transition poreopening was decreased in mPHGPx SSM as compared to control(P<0.05), with no difference in IFM. Cyclophilin D was significantly decreased in mPHGPx SSM relative to I/R control (P<0.05), with no differences in IFM. These results indicate that mitochondria‐specific PHGPx overexpression protects SSM against I/R‐associated apoptosis.(Supported by NIH DP2 DK083095, AHA 0815406D, AHA 0855484D, NIH T32 HL090610)
Mass spectrometry quantitation and analysis of urinary metabolites of grape seed extract polyphenols in a rat model of menopause (1025.11)
Authors: Kim Helen , Cutts John , Moore Doyle , Barnes Stephen 
Published: June 2021

Differences in urinary biomolecules following ovariectomy, and the impact of dietary polyphenols (grapeseed extract [GSE]) in rodents were examined by nanoLC‐tandem mass spectrometry, and the impact of dietary polyphenols (grapeseed extract [GSE]). Urines from sham‐ovariectomy (OVX) and ovariectomized ((OVX) rats were analyzed, where both groups were given GSE, thus, any differences were due to the OVX. In positive mode LC‐MS/MS, 5,589 peaks were resolved with unique retention times. Of these, 12% were significantly different in abundance (p<0.05), with 2% of this subgroup (p<0.001). Conclusive identification of significant peaks required both the METLIN software on the Scripps XCMS server (Tautenhahn et al., Anal. Chem, 2012) and the Human Metabolome Database (Wishart et al., Nucleic Acids Res, 2007). Experiments are ongoing to continue identification of peaks using MS/MS, as well as to populate the appropriate databases with conjugated forms of polyphenols to enable deeper analysis. In TARGETED metabolomics analysis, we determined that glucuronidated grapeseed polyphenols were increased in the urines of OVX rats, indicating that OVX increased the amount or activity of the relevant glucuronosyltransferases. This is the first metabolomics analysis of urinary biomolecules in a model of menopause, and of effects and fate of dietary polyphenols.Grant Funding Source: NIH/NCCAM R21‐AT00480531
Image cytometry for 2D and 3D quantification in microscopic images (1050.5)
Authors: Van Noorden Cornelis 
Published: June 2021

Image cytometry is a powerful quantitative tool based on microscopy and digital imaging to obtain measurements in cells and tissues, either as stereological data (volumes, areas, lengths, profiles, etc.) or photometric data (absorbance, fluorescence and luminescence). Cytometry relies on careful calibration and control of acquisition of digital images that are evaluated with image analysis programs. The software used for cytometry may either take the form of general image analysis software or may be designed for a specific purpose. In either case, it has to be capable of assisting in the fundamental requirements of cytometry: calibration, interactivity, speed and sampling to obtain correct measurements. Stringent data acquisition and calculations are essential to obtain meaningful data. The major aim of the presentation is to provide simple but reliable procedures for valid image cytometry to obtain meaningful quantitative data from images of microscopic objects. Image cytometry instrumentation, software, validation and calibration and operation routines are discussed and protocols, hints and tips are presented.Grant Funding Source: None
Iron chelating agents lead to the formation of neutrophil extracellular traps and subsequent entrapment of Staphylocccus aureus (1056.8)
Authors: Völlger Lena , Akong Kathryn , Dewitz Carola , Wang Yanming , Naim Hassan , Nizet Victor , von Köckritz‐Blickwede Maren 
Published: June 2021

Neutrophil extracellular traps (NETs), decondensed chromatin structures that contain antimicrobial components and mediate the entrapment of microbes, have been described as a fundamental innate immune defense mechanism, in addition to phagocytosis and degranulation of neutrophils. In this study, we investigated the effect of iron‐chelating agents on NET‐formation. Primary neutrophils were isolated from human blood samples and treated with deferoxamine (DFO), AKB‐4924, or L‐mimosine. NET‐formation was subsequently visualized and quantified by immunofluorescence microscopy.All tested iron chelators significantly induced NET‐formation and Staphylococcus aureus entrapment. Addition of iron completely abolished the induction of NET‐formation. To gain insight into the underlying mechanism, cells were treated with DPI to block NADPH‐dependent reactive oxygen species generation, which significantly abrogated the DFO‐induced NET‐formation. Furthermore, pharmacological inhibition of peptidyl‐arginine‐deiminase 4 (PAD4) resulted in significantly reduced DFO‐mediated NET‐induction. In conclusion, we demonstrate that iron‐chelation contributes to the formation of NETs. This is of particular interest because iron‐chelators used for the treatment of iron overload have become promising therapeutic candidates for fighting microbial infections.Grant Funding Source: Supported by Deutsche Forschungsgemeinschaft
Short‐term Toll‐like receptor 9 stimulation increases blood pressure and vascular dysfunction via attenuated NO and exacerbated ROS generation (1140.9)
Authors: McCarthy Cameron , Goulopoulou Styliani , Wenceslau Camilla , Matsumoto Takayuki , Webb R. Clinton 
Published: June 2021

Toll‐like receptor (TLR) 9 is a pattern recognition receptor of the innate immune system. We have previously shown that TLR 9 activation attenuates nitric oxide (NO) production in the aorta; however, the mechanism for this decrease was not determined. We hypothesized that in vivo treatment with a TLR 9 agonist (ODN 2395; three i.p. injections‐0.1 μg/i.p.) would augment aortic contractile responses via increased reactive oxygen species (ROS) generation. In adult Sprague Dawley rats, blood pressure was measured pre‐ and post‐treatment via tail cuff and concentration response curves to norepinephrine (NE; 10‐11‐10‐5 M) were performed using the myograph, in the presence or absence of inhibitors for NO synthase (L‐NNA, 10‐4 M) and ROS (tempol, 10‐3 M and apocynin, 10‐4 M). ODN 2395 treatment increased systolic blood pressure (Δ SBP Veh: ‐3±1 vs. ODN 2395: 9±3 mmHg; *p<0.05). ODN 2395 amplified the contractile response to NE [Emax (% max KCl); Veh: 108±2 vs. ODN 2395: 124±3; *p<0.05] and this difference was abolished in the presence of L‐NNA (Veh: 131±5 vs. ODN 2395: 134±2). Tempol (Veh: 116±2 vs. ODN 2395: 115±3) and apocynin (Veh: 116±2 vs. ODN 2395: 110±4) also abolished the heightened contractile response to NE. These data indicate that ODN 2395 treated animals have exacerbated ROS generation that possibly quenches NO leading to vascular dysfunction and increased blood pressure responses.Grant Funding Source: Supported by AHA, CNPq, & NIH
Medical educators response to a web‐based nutrition implementation toolkit (WNCIT) for entry level medical courses (118.2)
Authors: Nowson Caryl , Perlstein Robyn , Beck Eleanor , Lindley Jennifer , Schafer Jennifer , Rooney Kim 
Published: June 2021

Medical educators response to a web‐based nutrition implementation toolkit (WNCIT) for entry level medical courses
Caryl A Nowson1, Robyn Perlstein1, Eleanor Beck2, Jennifer Lindley3, Jennifer Schafer4, Kim Rooney5
1 School of Exercise and Nutritional Sciences, Deakin University, Australia 2 DAA, Australia & University of Wollongong, Australia.3 Faculty of Medicine, Nursing & Health Sciences, Monash University, Australia4 School of Medicine, University of Queensland, Australia 5 School of Medicine, University of Tasmania, Australia In Australian medical courses there is no clear integration of nutrition knowledge and skills as a core component of curriculum. Four universities and the Dietitians Association of Australia (DAA) have partnered to develop a Web‐based Nutrition Competency Implementation Toolkit (WNCIT) for entry‐level medical courses. This is a systematic approach that facilitates mapping of curriculum to integrate nutrition competencies. To assess the expert views of medical educators on the development of a WNCIT, an online survey and paper‐based survey was developed. To date 37 educators have completed the survey and initial results indicate that although most respondents thought the WNCIT would be useful, they were less certain that their institution would actually use WNCIT. Barriers to implementation cited were: the already full nature of the curriculum (75%); inability to train educators and use the technology (17%); associated costs(19%). Factors that support the development and implementation of the toolkit cited were: highly relevant content (19%), ease of use(8%), clear exemplars(5%), distribution of content over whole curriculum(10%0, low cost(5%), support of higher management(10%). The results indicate that it will be important to address these issues to facilitate the widespread adoption of WNCIT in Australian medical courses.
Analysis of state of early year children nutrition status in children's home of Kazakhstan (1185.3)
Authors: Turgambayeva A. , Syzdykova A. , Tulemisova A. , Omarkulov B. , Alihanova K. 
Published: June 2021

Today social orphanage is one of acute problems for our society.There are about 35 thousand social orphans at living parentsin Kazakhstan. Study results of children‐orphans as study group (n=226) and children, brought up in families (n=100) composing control group were used in study.18,9% of children‐orphans in the age of 6‐12 months suffer from chronic malnutrition (‐2СО); 6,8% of them have growth inhibition(‐3СО); and 9,3% of them exceed measurement data of their age category,from 74 children‐orphans.In control group 10% have growth inhibition, and 2,04% are accelerates.From 92 studied children,in children of 12‐24 monthly ages46, 7% of study group are short ones and have growth inhibition that characterizes chronic malnutritionavailability. In 25% of them growth inhibition was revealed.In control group 35% of children of indicated age category have chronic malnutrition.On study results of 52 children in the age of 24‐36 months,in 38,2% of them chronic malnutrition was revealed, in 32,7% of them had growth inhibition. In control group only 18,7% of them hadchronic malnutrition, 12,7% of them had growth inhibition.Thus, it is necessary to draw conclusion from all above‐stated, that 35,3% of children arefoster childrenof children's home of health care system considered to be short and chronic malnutritionof one or another degree, that in 2,3 times exceeds these indexes in children growing with their parents.
The relation of human milk lutein, choline, and docosahexaenoic acid content to recognition memory abilities of 6‐month‐old breastfed infants (247.4)
Authors: Cheatham Carol , Stegall Julie , Sheppard Kelly , Armer Andrea , Millsap Grace , Wernimont Susan , Zeisel Steven 
Published: June 2021

OBJECTIVE: The aim of this study was to explore the relation of human milk lutein, choline, and DHA with recognition memory abilities of 6‐month‐olds.METHODS: Two hundred breastfeeding dyads were enrolled when the infants were 3‐4 months of age. Milk samples were obtained and analyzed for fatty acids, lutein, and choline. One hundred two of the 200 were invited at age 6 months to participate in an electrophysiology session. Recognition memory was tested with a 70‐30 oddball paradigm during which high‐density 128‐lead event‐related potential (ERP) data were collected. Sixty‐seven infants provided usable ERP data; of those, 59 had complete nutrient data. The differences between latency to minimum, minimum amplitude, and mean amplitude when viewing familiar and novel stimuli were analyzed by averaging activity at 6 different collections of leads (Frontal Right, Frontal Central, Frontal Left, Central, Midline, and Parietal) and subjecting the data to stepwise regression modeling.RESULTS: Final regression models revealed significant interactions. The lutein by free choline interaction was significant for the difference in latency scores at Frontal Left and Central areas (p<0.05 and p<0.001, respectively). Higher choline levels with higher lutein levels were related to better recognition memory. The DHA by lutein interaction was significant for the parietal area in mean amplitude and minimum amplitude (p<0.05). Recognition memory was higher when DHA was high and lutein was low.CONCLUSION: Interactions between human milk nutrients appear important in predicting infant cognition, and there may be benefit associated with specific nutrient combinations.Grant Funding Source: Nutrition Obesity Research Center (NIH grant), University of North Carolina at Chapel Hill, The Bill
Cognitive development among preschoolers improves in relation to endline ferritin and vitamin D levels only among recipients randomized to a fortified poultry‐based spread (Spammy™) intervention group (250.6)
Authors: Bracken Bruce , Bonorden Melissa , de Salazar Maria , Salazar Paola , Hernandez Liza , Salguero Sylvana , Armas Laura , Solomons Noel 
Published: June 2021

Background: Dietary improvements during early childhood have potential to both reduce nutritional deficiencies and improve cognitive outcomes.Objective: To assess the efficacy to improve cognitive function of a poultry‐based spread that provides between 20% to 333% of the RDA of 12 selected micronutrients, including vitamin D and iron.Methods: Sixty preschoolers, aged 4‐7 years, were randomized in a triple‐blinded format to receive 43 g of fortified (FS) or unfortified (US) SpammyTM during weekdays over a 20 week period as part of the institutional breakfast on the outskirts of Guatemala City. The Spanish language Bracken Basic Concept Scale‐ Receptive (BBCS‐R) was administered and circulating nutrient status indicators (25(OH)vit D and ferritin) were measured at both ends of the trial.Results: Reliability analyses for both the BBCS‐R School Readiness Component (SRC) and total test (TT) were high (.96 and .95, respectively). Both FS and US groups had larger than expected gains on the age‐standardized SRC scores (p=.068 and 0.03, respectively) with no difference between groups (p=.84). In the FS only, a significant, positive relationship was found between TT cognitive gain score and both endline vitamin D (Pearson r = .37) and ferritin (Pearson r = .42).Conclusion: Regular consumption of a fortified poultry spread to breakfasts, combined with educational programming, set the stage for improved cognitive functioning.Grant Funding Source: Supported by McGovern‐Dole Food for Education and Child Nutrition Program and Hormel Foods
Dietary glycemic index does not influence adaptation of resting energy expenditure during weight loss (371.7)
Authors: Karl J. , Schaefer Ernst , Fuss Paul , Das Sai Krupa , Saltzman Edward , Roberts Susan 
Published: June 2021

It has been suggested that low glycemic index (GI) diets may help prevent weight regain following weight loss by attenuating the decline in energy expenditure that is associated with lower body weight. To determine the independent impact of dietary GI on resting energy expenditure (REE) during and after weight loss, 79 overweight and obese adults (mean ± SD; 56 ± 6 y, BMI 33 ± 2 kg/m2) were randomized to 1 of 4 provided diets differing in fat proportion (15% or 30% of energy) and GI (low, 55 or high, 88), but matched for protein and fiber contents. Food was first provided at 67% of measured weight maintenance requirements for 12 wk, then at 100% of requirements for 5 wk. Body composition and measured REE (mREE) were determined at baseline, 12 wk and 17 wk. Predicted REE (pREE) at 12 wk and 17 wk was calculated from age, sex, fat mass (FM) and fat free mass (FFM) based on a regression model developed from baseline data (R2 = 0.91, p < 0.001). Measured decreases in body weight, FM, FFM and REE over 17 wk did not differ significantly by dietary fat or GI. In the combined‐cohort, mREE was 56 ± 89 kcal/d and 44 ± 108 kcal/d lower than pREE at 12 wk (p < 0.001) and 17 wk (p < 0.01), respectively, but did not differ by dietary fat or GI‐level (12 wk: p = 0.51, 17 wk: p = 0.83). Dietary GI does not appear to attenuate the reduction in REE associated with weight loss when potentially confounding factors such as dietary protein level are controlled.Grant Funding Source: Supported by NIH grant RO1HL 57981