bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aortic depressor nerve differences between Wistar and Wistar‐Kyoto rats
Authors: de Aguiar Mendes Vânia Alice , de Amorim Milena Menezes , da Silva Letícia Oliveira Neri , Salgado Helio Cesar , Fazan Valéria Paula Sassoli 
Published: June 2021

Previous reports from our laboratory [1, 2, 3] showed differences on the morphology of the aortic depressor nerve (ADN) between normotensive Wistar‐Kyoto (WKY) and spontaneously hypertensive rats (SHR). The aim of the present study was to investigate if there are morphological and morphometric differences on the AND of two different normotensive rats strains. Twelve Wistar rats (WR) and 13 WKY had their left ADN fixed in 2,5% glutaraldehyde. Semithin cross sections of proximal and distal segments of the ADN were analyzed by light microscopy and a morphometric study of the nerve fascicles and myelinated fibers was performed. Comparison between proximal and distal segments of the two strains revealed a longitudinal symmetry. Comparison between strains revealed that, despite the fact that WR are heavier (body weight = 339 ± 17g for WR and 277 ± 54 for WKY) than WKY, ADN fascicles and myelinated fibers are larger in WKY. Myelinated fiber distributions were unimodal in both segments for both strains, with peak in 2,5 μm but, there is a higher percentage of large fibers (> 4 μm) in WKY nerves. Average values of myelinated fibers morphometric parameters are higher in WKY due to a larger number of fibers bigger than 4 μm.Grant Funding Source : FAPESP, CNPq, CAPES and FAEPA
Role of LEK1 in Cardiac Disease and Function
Authors: Miller Paul Myron , Dees Ellen , Bader David 
Published: June 2021

In our lab, we have developed global as well as heart‐specific CENPF−/−(LEK1) mouse models. Utilizing our heart‐specific model, we have found that LEK1 mutation leads to a myriad of problems including: an overall decrease in intercalated disc number, significant fibrosis, erratic ECG patterns, progressive dilated cardiomyopathy, and a 20% chance of sudden death. To date, the molecular mechanism underlying LEK1 involvement in these processes remains unknown. Although LEK1 is a very large and multi‐functional protein, one common functional theme has emerged in the literature: the interaction of LEK1 with the microtubule cytoskeleton. Previous studies have identified an important role for LEK1 in microtubule nucleation at the centrosome as well regulation of vesicular transport and cell coupling. Here, using CENPF−/−mouse embryonic fibroblasts, we show that directionally persistent migration as well as overall microtubule network organization is disrupted. Our overall hypothesis is that cytoskeletal defects mediated by LEK1 mutation result in developmental, morphogenic, and functional abnormalities in the heart.Funding: 5 T32HL007751‐17, Training Grant in Mechanisms of Vascular DiseaseGrant Funding Source : NIH
Interleukin‐8 Regulation by Histone Deacetylase Inhibitors and Bortezomib in Human Macrophages
Authors: Sanacora Shannon Marie , Ramaswami Sitharam , Chang Tzu-Pei , Manna Subrata , Singha Bipradeb , Vancurova Ivana 
Published: June 2021

Interleukin‐8 (IL‐8) is a proinflammatory chemokine that plays a major role in inflammatory responses, as well as in tumor‐associated angiogenesis and tumor progression. Macrophages at the sites of tissue injury and cancer development are the major source of IL‐8. The transcriptional regulation of IL‐8 is mediated by the transcription factor NFκB. However, our previous results suggested that different mechanisms regulate the NFκB‐dependent transcription of IL‐8 and other cytokines, such as TNF, IL‐1 and IL‐6, in human macrophages. The goal of this study was to investigate the transcriptional regulation of IL‐8 in stimulated U‐937 human macrophages. Using chromatin immunoprecipitation, we show that while the NFκB promoter sites of TNF, IL‐1 and IL‐6 are occupied by p65 NFκB acetylated on K310, IL‐8 promoter is occupied by non‐acetylated p65. The histone deacetylase (HDAC) inhibitor, trichostatin A, enhances IL‐8, but not TNF transcription in stimulated macrophages, indicating that p65 K310 acetylation increases IL‐8 transcription. The proteasome inhibitor bortezomib, which down‐regulates HDACs expression, also increased IL‐8 expression in macrophages. Since HDAC inhibitors and bortezomib have emerged as promising new anti‐cancer therapies, understanding the mechanisms how they increase IL‐8 expression in macrophages may contribute to the development of more effective therapies.Funded by: NIH grants GM079581 and AI085497 to I.V.
Exercise translocates RIP140 to the cytoplasm in human skeletal muscle
Authors: Sällstedt Eva-karin Sara , Ydfors Mia , Norrbom Jessica , Sundberg Carl Johan 
Published: June 2021

In response to exercise, muscles adapt with a multitude of gene expression changes and protein modifications. One of the most profound changes is an increased mitochondrial biogenesis. The co‐repressor RIP140 interacts with several nuclear receptors and is recruited by transcription factors and co‐activators such as PGC‐1α and NRF‐1. Therefore, RIP140 may take part in the regulation of mitochondrial biogenesis.PurposeTo investigate 1. if an acute bout of exercise reduces the inhibitory action of RIP140 through translocation from the nucleus to the cytoplasm and 2. the temporal resolution of RIP140 mRNA expression before and up to 24h after exercise.MethodsHealthy men (n=4) and women (n=3) performed 1h of cycling exercise at 70 % of VO2max. Skeletal muscle biopsies were obtained before and after exercise (pre, 30′, 2h, 6h and 24h).ResultsRIP140 protein abundance increased in the cytoplasmic fraction 24h after exercise (n=3). RIP140 mRNA expression (n=7) was significantly increased 6h after exercise and returned to baseline values at 24h.ConclusionAn acute bout of exercise appears to translocate RIP140 protein from the nucleus to the cytoplasm. This would decrease the inhibitory action of RIP140 on nuclear genes encoding mitochondrial proteins and might therefore be part of the adaptive mitochondrial response seen with training.
Substrate tolerance of acyl‐CoA ligases
Authors: Go Maybelle Darlene Kho , Tai Ai Tee , Yew Wen Shan 
Published: June 2021

Acyl‐CoA ligases catalyze the activation of a carboxylic acid to an acyl‐CoA ester in a two‐step reaction via an adenylate intermediate. CoA esters are precursors in various biochemical processes such as fatty acid synthesis and polyketide synthesis. These enzymes are also known to have a remarkably broad substrate tolerance.Five acyl‐CoA ligases were studied – cinnamate:CoA ligase and phenylacetate:CoA ligase from Streptomyces coelicolor, benzoate:CoA ligase from Rhodopseudomonas palustris, malonate:CoA ligase from Rhizobium trifolii, and 4‐coumarate:CoA ligase from Nicotina tabacum. All enzymes were expressed in Escherichia coli and purified to homogeneity in a single step using Ni2+‐chelating chromatography. Using the purified enzyme, various derivatives of cinnamic acid, 3‐phenylpropanoic acid, and benzoic acid were used to screen for a possible conversion of the various aromatic carboxylic acids to their corresponding acyl‐CoA esters. Aliphatic carboxylic acids were also screened as possible substrates. This study found that these enzymes were able to catalyze the CoA esterification of various aliphatic and aromatic carboxylic acids, highlighting the potential use of acyl‐CoA ligases as biosynthetic enzymes; the generated carboxyl‐CoA esters can be used as precursors in the biosynthesis of various secondary metabolites.This project was supported by grants from the Ministry of Education, Singapore.
An Automated Reinvention of the Western Blot ‐ A Simple Western Analysis of the AKT Pathway Signaling Cascade
Authors: Boge Annegret , Ramirez Francisco , Nguyen Uyen , Kazakova Irina , Dermody Jessica , Yang Tom , Gavin Robert 
Published: June 2021

Protein kinase AKT is a central player for a variety of cell stimuli affecting downstream events such as the inhibition of apoptosis, regulation of glycogen synthesis, and cell cycle regulation. Many of these events are routinely assessed by Western blot analysis which exploits high sensitivity of enzyme amplification as well as specificity of antibody binding. The process itself, however, is very labor intensive and has not significantly changed since it was first introduced. Simple Western assays utilize capillary electrophoresis, a powerful separation technique with high resolution and reproducibility, and incorporate sample separation performed in capillaries followed by immobilization of the proteins directly onto the capillary walls, followed by immunodetection. Data comparing analysis of key targets of the AKT signaling cascade via Western blot and Simple Western highlighting workflow, biological response, sensitivity, and resolution is presented.ConclusionsSimple Western assays are a reinvention of the Western blot, automating all the manual steps associated with the process. Highly reproducible, quantitative, reliable and sensitive assessments of key targets in the AKT signaling cascade were observed. Additionally, total time to results was dramatically pared down to 3–5 hours in a walk‐away mode with a total hands‐on time of less than an hour.
A Mitochondrial Lipid Phosphatase in Cell Metabolism and Membrane Organization
Authors: Zhang Ji , Guan Ziqiang , Murphy Anne , Wiley Sandra , Perkins Guy , Worby Carolyn , Engel James , Raetz Christian R.H. , Dowhan William , Dixon Jack 
Published: June 2021

Cardiolipin, the signature phospholipid of mitochondria, plays pleiotropic roles in regulating the membrane integrity and activities of the organelle. The cardiolipin biosynthetic pathway is well characterized, but the mammalian enzyme that catalyzes the dephosphorylation of phosphatidylglycerophosphate (PGP) to phosphatidylglycerol (PG) has been long sought. Herein we demonstrated that PTPMT1, the first protein tyrosine phosphatase localized to the mitochondrion, is the elusive PGP phosphatase. Whole body deletion of Ptpmt1 in mice led to embryonic lethality, suggesting an indispensable role for PTPMT1 during mammalian development. Surprisingly, lipid analysis of Ptpmt1‐deficient fibroblasts revealed an accumulation of PGP along with a concomitant decrease in PG content. We further demonstrated that PTPMT1 specifically dephosphorylated PGP in vitro. Moreover, loss of PTPMT1 led to dramatic diminution of cardiolipin, inhibition of mitochondrial respiration and mitochondrial fragmentation. Together, our study identifies PTPMT1 as a major mammalian PGP phosphatase and points to its role as a novel player in cardiolipin biosynthesis.This work was supported by grants from the National Institutes of Health. (DK18024 and NIDDK DK18849 to J.E.D.), and the Larry L. Hillblom Foundation (2007‐D‐016‐FEL) to J.Z.
Leptin Reduces hypoxia‐reoxygenation‐induced Fas/FasL gene overexpression and apoptosis in human L02 cells
Authors: Zhou Shaoli , Chen Guihua , Li Xiaoyun , Li Shangrong , Guo Na , Irwin Michael G , Xia Zhengyuan , Hei Ziqing 
Published: June 2021

Fas/FasL activation induces caspase‐3 activation that may exacerbate hepatic ischemia‐reperfusion injury (IRI) by increasing apoptotic cell death. Leptin, an endogenous cytokine, facilitates cell growth and attenuates hypoxic brain injury (Stroke, 2007;8:2329–2336). We postulated that leptin may attenuate hypoxia/reoxygenation‐induced hepatocyte injury by reducing apoptosis and suppressing Fas/FasL gene expression. Human hepatic L02 cell IRI was induced by exposing the cell to hypoxia for 12 hours followed by 12 hours reoxygenation in the absence or presence of different concentrations of leptin (100 μg/L, 200 μg/L, 400 μg/L, 800 μg/L and 1600 μg/L). Cell survival rates were significantly reduced in cells subjected to IRI compared to control cells receiving normoxia accompanied with increased apoptotic index as measured by flow cytometry and terminal dUTP nick‐end labeling, which was coincident with increased gene expressions of Fas and FasL (all P<0.01, group IRI vs. control). All the above changes were significantly attenuated by treatments with various concentrations of leptin (all P<0.05, vs. group IRI), while the optimal effects were seen at leptin concentration of 400 μg/L. It is concluded that leptin may have reduced hypoxia/reoxygenation‐induced hepatic L02 cell apoptosis by down‐regulating Fas/FasL gene expression.Supported by a Doctoral Start‐up Foundation grant in (NO. 10451008901004797)
Solution Structures and Models Describing the Thioredoxin System from Mycobacterium tuberculosis
Authors: Neumann Terrence S , Olson Andrew , Cai Sheng , Sem Daniel 
Published: June 2021

Mycobacterium tuberculosis (M. tb) resists oxidative killing in part by using the thioredoxin (Trx) system. Trx's catalyzes thioldisulfide exchange reactions using redox active cysteine thiols to reduce disulfides of other essential proteins, including metabolically essential enzymes. Oxidized Trx is reduced by thioredoxin reductase (TrxR) in an NADPH dependant reaction. The M. tb Trx system consists of three Trx's (TrxA, TrxB, and TrxC) and one Trx reductase (TrxR). TrxB and TrxC are known substrates of TrxR, while TrxA has been reported to not bind to TrxR, and to possibly be “cryptic.” The M. tb Trx system is dissimilar to the human Trx system (25–35% identity) indicating inhibitor specificity for the M. tb Trx system is achievable. The M. tb Trx system appears to be a viable anti‐tuberculosis drug target.This study's objective was to calculate NMR solution structures of oxidized and reduced Trx's from M. tb. Structures were calculated using standard NMR methods and indicate that TrxA is wellfolded in oxidized and reduced states. Structures of the Trx's and binding models of the TrxN(N=A,B, or C)‐TrxR, constructed from NMR titrations of each 15N enriched TrxN and TrxR, will be presented. These binding models show a pocket between the Trx and the TrxR which are being used to identify uncompetitive inhibitors that would be effective as drugs even at saturating substrate (Trx) levels. Supported by NIH GM085739.
Postoperative vitamin deficiencies in patients undergoing laparoscopic roux‐en‐y gastric bypass
Authors: Lodhia Nayna A , Almario Leanne V , Eltorai Adam , Kattan Jaffer , Nkansah Margaret M , Kerolus Matthew , Kiely Kate , Morton John 
Published: June 2021

BACKGROUNDNutritional abnormalities are common in severely obese patients and can be worsened following laparoscopic Roux‐en‐Y Gastric Bypass (LRYGB). This study aimed to determine the relationship between postoperative vitamin B12, folate and iron deficiency to LRYGB outcomes.METHODS630 patients underwent LRYGB by three surgeons at a single academic institution. Patient records were reviewed for vitamin levels, weight loss, and cardiac risk factors postoperatively.RESULTSOverall patient demographics were: mean age 44.4 years, mean BMI 46.3, and 89% female. At 3, 6 and 12 months postoperative, 0.2, 1.2 and 1.6% had Vitamin B12 deficiency; 0.3, 0.7 and 0% had folate deficiency; and 11.3, 4.5, and 7.3% had iron deficiency, respectively. Men had higher rates than women of vitamin deficiencies at all time points (p<0.001). Patients who had a known deficiency at 3 months had significantly higher weights preoperative (278lbs vs 311lbs, p<0.001), at 3 months (227lbs vs 254lbs, p=0.01) and at 12 months (185lbs vs 208lbs, p=0.01).CONCLUSIONSMale patients and patients with higher preoperative weight should be monitored closely for nutritional deficiencies following LRYGB.Grant Funding Source: NIH Clinical and Translational Science Award
Formative Evaluation of a Community‐Based Nutrition Education Curriculum for Hispanics in South Carolina
Authors: Aragon M. Catalina , Cason Katherine L. , Hernandez-Garbanzo Yenory , Ugalde-Gonzalez Maciel , Rossi Maria Mercedes , Senior-Angulo Joyce 
Published: June 2021

ObjectiveTo assess through formative evaluation an Expanded Food and Nutrition Program (EFNEP) curriculum designed for South Carolina Hispanics.MethodsThe formative evaluation process consisted of a 4‐step approach: 1) curriculum initial pilot testing (n=31), 2) curriculum review/refinement, 3) pilot testing of the refined curriculum (n=16) and 4) focus groups with Hispanic participants (n=14).ResultsCultural Appropriateness. Recipes and vocabulary were appropriate for Mexican participants; however, some terminology used was unfamiliar to other Latin American audiences. Educational Strategies. The first curriculum delivered lessons through storytelling with visual aids. In the second version, storytelling was eliminated and more individual and group activities were included. Accuracy. The curriculum was updated with the 2010 Dietary Guidelines and MyPlate. The subjects of physical activity, food security and food shopping practices were incorporated to meet EFNEP's goals. Theory adherence. Goal setting, environmental strategies and selfmonitoring were included after the review.ConclusionsThe 4‐step‐formative‐evaluation approach used in this study revealed important strengths, limitations and opportunities for curriculum improvement. Overall, activities, language and recipes used were improved to meet the specific needs of the audience.
Skipping Breakfast and Having Snacks of Middle School Students in Incheon and Factors Affecting Their Dietary Habits
Authors: Chung Hyun-Jung , Park Ju-Il 
Published: June 2021

This study was to investigate habits of skipping breakfast and having snacks of middle school students in Incheon, Korea and to identify factors that affect their dietary habits, to help them take the right nutrients and form the right dietary habits, and to provide basic data for dietary life education to improve their health. The subjects were 392 boys and girls attending a middle school in Incheon. Of the middle school students in Incheon, 46.7% had breakfast every day. Having breakfast had not much influence on having snacks. They preferred taste(66.6%) and price(13%) to nutrition(8.4%) and hygiene(10.2%) when choosing snacks. There were small differences in the kinds of snacks preferred between boys and girls; while the girls often had “flour‐based foods and street foods”(26%), “confectionery”(41%) and “candy and chocolate”(42.7%), the boys had “ices”(32.5%) and “soft drinks”(30%) more often. As for dietary habits and attitudes, there were significant differences between the boys and the girls in that the former drinks milk more often (34.5%) and finish foods faster(81.5%) than the girls. BMI, sleeping hours, stress, and mother's educational background affected having breakfast and snacks, dietary habits and attitudes. Those who did not experience stress(56.3%) had more snacks than those who suffered a lot of stress(39.4%). The subjects with normal weight (34.1%) had meals regularly than the underweight(21.3%) and overweight(28.6%) subjects. The less stress they had, the more likely they were to have all three meals, have meals on scheduled time, and have meals slowly with more leisure. Most of the middle school students in Incheon were aware of the importance of breakfast but failed to have breakfast every morning due to various reasons. These results indicate that there are needs for education and research about the criteria of choosing snacks so that the students can have desirable and nutritious snacks on their own.Grant Funding Source : Inha University
POSTPRANDIAL RESPONSE OF BEAN CONSUMPTION ON INFLAMMATION, OXIDATIVE STRESS, GLUCOSE, AND INSULIN IN ADULTS WITH METABOLIC SYNDROME
Authors: Reverri Elizabeth J. , Randolph Jody M. , Steinberg Francene M. , Kappagoda C. Tissa , Edirisinghe Indika , Burton-Freeman Britt 
Published: June 2021

Metabolic Syndrome (MS) is a condition associated with inflammatory and oxidative stress. Consumption of a high carbohydrate/fat meal induces postprandial increases in markers of oxidative stress and insulin resistance. The present investigation aimed to determine whether inclusion of beans with a high fat meal would modify these postprandial responses. After an overnight fast, 12 adults with MS consumed a nutrient‐matched standard breakfast with either black beans (BB), fiber matched (FM), or antioxidant matched (AM) in a randomized crossover design. Postprandial responses (triglycerides (TG), cholesterol, glucose, insulin, and markers of oxidative stress and inflammation) were measured for 5 hours. Baseline characteristics include BMI 32.2±5.7 kg/m2, HOMA‐IR 2.4±1.0, and HOMA‐β cell function 92.6±32.0%. Preliminary results show that postprandial TG (mg/dL) was significantly lower after BB (162.5±17.3), compared to AM (176.8±17.3 P=0.0208) and FM (179.4±17.3 P=0.0091). Postprandial insulin (μIU/mL) was significantly lower after BB (33.5±4.3), compared to FM (38.4±4.3 P=0.0310) and AM (50.3±4.3 P=<0.0001). Postprandial oxLDL was significantly higher 5 hours after FM, compared to BB (50.7±3.2 vs 43.7±3.2 P=0.0438). Current results suggest that black beans may transiently attenuate exaggerated postprandial TG and insulin responses in adults with MS.Grant Funding Source : UC Davis Departmental Funds and Dry Bean Council
Dietary obesity impairs regulation of hepatic AMP‐activated kinase in rats
Authors: Harper Marianna A. , Kuo Yu-Fu , Clarke Steven D. , Axen Kenneth , Axen Kathleen 
Published: June 2021

Hepatic AMP‐activated kinase (AMPK), activated under conditions of energy depletion such as fasting, increases fatty acid oxidation and inhibits fatty acid synthesis and lipogenic gene expression. Our hypothesis is that regulation of AMPK activity by fasting and feeding may be impaired in obesity and hepatic steatosis.MethodMale Sprague‐Dawley rats were fed either a low‐fat (LF, n=12) – 15% fat, 55% carbohydrate – or a high‐fat (HF, n=8) – 55% fat, 19% carbohydrate diet for 8 wk. After a 20 h fast rats were either dissected in the fasted state (D) or 3 h after an oral glucose gavage (G); liver samples were flash‐frozen and homogenized. AMPK activity was measured by degree of density.ResultsHF‐fed rats developed obesity and hepatic steatosis. AMPK activity was greater in the deprived state in LF vs. HF rats. The ability of glucose to reduce AMPK phosphorylation was also greater in LF vs. HF rats.ConclusionsHF induced obesity decreased the ability of hepatic AMPK to act as an energy sensor, suggesting impaired regulation of fat mobilization and synthesis in response to nutritional state. Grant number: 1 SC3 GM086298‐01A1Grant Funding Source: 1 SC3 GM086298
Broccoli seedlings prevent glucose‐induced inflammation of peripheral blood mononuclear cells in humans
Authors: Meijer Kees , de Jong Ingrid , Koehorst Martijn , Priebe Marion , Roelofsen Han , Vonk Roel 
Published: June 2021

We studied the effect of anti‐inflammatory components in vegetables on postprandial inflammation using broccoli seedlings (Broccocress®, Koppert Cress BV, Monster, The Netherlands), which are rich in the isothiocyanate sulforaphane (SFN). In an NF‐κB reporter cell line, increasing concentrations of 2–15 μM SFN lead to inhibition of TNFα‐stimulated NF‐κB activation up to 98% (p<0.05). Five healthy subjects ingested a load of 75 gram glucose with or without a smoothie of broccoli seedlings (45 min. prior to glucose). NF‐κB activation in the nuclear fraction of peripheral blood mononuclear cells was determined by ELISA. 75 gram glucose leads to a 36.5% ± 20.3% increase in NF‐κB activation. In combination with the smoothie, NF‐κB was decreased by 64.8% (p<0.005) and 29.3% ± 9.3% (p<0.005) compared to high‐glucose‐induced and basal NF‐κB levels, respectively. The level of NF‐κB activation correlated to blood glucose levels after the oral glucose load, but not when the smoothie was ingested as well. SFN could be detected in plasma after 1.5 hrs. Total SFN (free SFN plus conjugated SFN) correlated to inhibition of NF‐κB. This suggests that broccoli seedlings are effective in reducing metabolic inflammation in humans.Grant Funding Source: Food Nutrition Delta project # FND09002