bluuebunny/crossref_metadata_2025_split huggingface dataset:
Starch chemistry affects the kinetics of glucose and SCFA absorption, and insulin and incretin release in pigs
Authors: Regmi Prajwal R. , Matte J. Jacques , van Kempen Theo A. T. G. , Zijlstra Ruurd T. 
Published: June 2021

The objective was to understand the role of starch chemistry on kinetics of glucose and SCFA absorption, and on insulin and incretin release. Four purified starches (crystallinity, 24 to 40%; granule size, 12 to 229 sq. μm; amylose, 0 to 80%; resistant starch, 1.9 to 70.2%; reflected by max. rate of in vitro digestion: from slow, 0.22; 0.38; 1.02; to rapid digestible, 1.92%/min) were included at 70% in diets fed to 4 porto‐arterial catheterized pigs (38.7 ± 1.7 kg BW). Slow vs. rapid digestible starch lowered (P<0.05) postprandial (PP) net portal appearance (NPA) of glucose 53%, insulin and C‐peptide (peak and 0.5 to 1 h) 55%, NPA glucose to insulin ratio (2 to 10 h) 71%, portal GIP (2 to 2.5 h) 81%, and GLP‐1 (1.5 to 2 h) 36%, and it increased (P<0.01) NPA of SCFA 196%. Incremental area under the curve (iAUC) of insulin NPA was linearly positively related (P<0.01) with iAUC of glucose (R2=0.49) and incretins NPA (R2=0.27) and iAUC of incretin NPA was similarly related with iAUC of glucose (R2=0.78) and SCFA NPA (R2=0.35) in a regression model. Addition of predicted gastric emptying in the model improved the relation of iAUC of insulin NPA with iAUC of incretins and glucose NPA (R2=0.86). Conclusion: slow digestible starch reduces glucose and insulin responses and increases SCFA absorption. Glucose absorption, incretin release, and gastric emptying appear important factors for insulin release.Funding Source: ALMA, Provimi, Alberta Pulse Growers
Bone morphogenetic protein signaling is essential for correct vascularization of lungs and kidneys
Authors: Yao Yucheng , Jumabay Medet , Wang Anthony , Bostrom Kristina I 
Published: June 2021

Vascularization of growing organs is a highly coordinated process. Matrix Gla Protein (MGP) is expressed in lungs and kidneys during organ growth and inhibits bone morphogenetic protein (BMP)‐4 and ‐7, essential for both lung and kidney formation and angiogenesis. We hypothesized that BMP signaling is essential for correct organ vascularization. MGP deficient and MGP transgenic mice were used to study BMP signaling and vascularization in lungs and kidneys. Micro CT imaging showed a dramatic increase in vascular formation with evidence of abnormal arteriovenous connection in MGP deficient mice, whereas vascular growth was inhibited in MGP transgenic mice. Expression of activin‐like kinase receptor (ALK)1, ALK2, ALK5 and VEGF, known to be induced by BMP in endothelial cells, was significantly increased in MGP deficiency, but decreased when MGP was overexpressed. Unexpectedly, similar changes occurred in the type II epithelial lung cells and the mesenchymal kidney cells, suggesting that this system may coordinate vessel growth with the growth of organ‐specific elements. The levels of BMP‐4 and BMP‐7 did not significantly change, although BMP‐7 appeared to play a more important role in kidney vascularization. We conclude that timely inhibition of BMP‐4 and ‐7 by MGP in lungs and kidneys is essential for appropriate organ vascularization.Research support: NIH/NHLBI, AHA.
An alternative step‐wise mechanism for arterial and venous differentiation in mammals
Authors: Wang Rong A. , Kim Yung Hae , Lindskog Henrik , Gallardo Salvador Guevara , Jelin Eric 
Published: June 2021

Arterial and venous (AV) differentiation is critical for vascular homeostasis. To understand the mechanism of AV differentiation, we studied the developing dorsal aorta (DA) and cardinal vein (CV) pair. Using transgenic mice, we found that the primordial DA and CV assembled without Notch signaling. Furthermore, the primordial DA was composed of endothelial cells (ECs) lacking arterial markers, suggesting it forms before arterial specification. Later, the primordial DA and CV expressed both arterial and venous markers. We thus propose a model of mammalian AV differentiation, distinct from the current model, where primordial vessels emerge before AV specification, transiently harbor both arterial and venous ECs, and then mature into the ultimate arteries and veins with uniform AV identities.This work was supported by NIH R01 HL075033 to R.A.W., and by a generous grant from the Foundation for Accelerated Vascular Research. This work was also supported in part by a Swedish Research Council Postdoctoral Fellowship to H.L, T32 HL007544 to S.G.G. and NIH F32 HL097400 to E.J.
MEF2 activity is required for maintenance of endothelial barrier function and vessel integrity
Authors: Schwarz John J , Adam Alejandro P , Herron Crystal R , Vincent Peter A 
Published: June 2021

Transcription factors of the MEF2 family are critical regulators of the development and physiology of several organ systems. We are investigating their role in the endothelium by the combined endothelial‐specific deletion of Mef2c and global deletion of Mef2a. This results in hemorrhage and death during embryonic development, indicating that the MEF2s are required for vessel integrity. We explored the possibility that the MEF2s are critical for endothelial barrier function by blocking MEF2 activity in a mature monolayer of human dermal microvascular endothelial cells (HDMEC) with an adenovirus expressing a dominant negative MEF2 (DN‐MEF2). Expression of DN‐MEF2 decreased the barrier function of EC monolayers as assessed by changes in transendothelial resistance (TEER) beginning 30 hrs post infection and produced gaps in the endothelial junctions as assessed by immunofluorescence to ZO‐1 and VE‐cadherin. We also found that the thrombin‐induced increase in permeability was enhanced by DN‐MEF2 prior to the onset of increased basal permeability. These results demonstrate that the MEF2s play a role in the regulation of endothelial monolayer integrity.RO1‐HL77870
Aging‐induced collateral impairment: role of arterial rarefaction, decreased eNOS expression/signaling, and increased susceptibility of endothelial cells to apoptosis
Authors: Epstein Stephen Edward , Wang Jinsong , Peng XinZhi , Zhuang Zhenwu , Simons Michael , Xue Zhenyi , Burnett Mary Susan 
Published: June 2021

Despite positive animal studies, clinical angiogenesis trial outcomes have been disappointing. Because 1) aging impairs ischemia‐induced collaterogenesis in animals, and 2) patients targeted for angiogenesis therapy are older, we determined whether aging‐induced changes in collateral phenotype could contribute to the disappointing clinical results.ObjectiveTo determine a) whether aging alters collateral phenotype such that they are more resistant to therapeutic interventions and, if so, b) what are the contributing molecular mechanisms.Methods and ResultsMicro‐computed tomography (MicroCT) was used to assess vessel phenotype in young (4 month) and old (20 month) wildtype C57 mice under baseline conditions. Old mice had approximately 60% fewer pre‐existing arterioles ≤25μm in the calf and thigh, approximately 50% fewer arterioles >25μm in the calf, and decreased baseline endothelial nitric oxide synthase (eNOS) protein and phosphorylation at serine‐1177 (indicating both decreased eNOS expression and signaling) than young mice. To determine if this association reflected causality, we examined vessel phenotype in eNOS knockout (KO) mice; young eNOS KO mice exhibited significantly fewer arterioles than young wild‐type mice, similar to the findings in old wild‐type mice. Interestingly, endothelial cells obtained from older mice a) exhibited decreased eNOS protein and serine‐117 phosphorylation, and b) were more sensitive to an apoptotic stimulus, findings that may contribute mechanistically to vessel dropout.ConclusionsAging leads to arteriolar rarefaction, an effect contributed to by decreased eNOS expression and signaling, which predisposes endothelial cells to undergo apoptosis. This microvasculature rarefaction may importantly contribute to the thus‐far disappointing results of clinical angiogenesis trials.This work was supported by NIH RO1 HL085003‐01A2.
Contribution of enhancer sequences and spliceosomal core components to substrate positioning for splicing catalysis
Authors: Konarska Magda , Templeton Richard , Lisanti Antonella , Pani Bibhusita , Kostyukovskiy Ilya 
Published: June 2021

One of the main questions in the splicing field concerns the nature of the catalytic center of the spliceosome. To investigate the mechanism of splice site (SS) selection, and in particular the role of 5′ exon interactions in positioning the 5′SS for catalysis, we carried out a genetic screen in yeast to identify exon sequences capable of compensating for 1st step splicing defects. We identified several classes of yeast exon and intron enhancers that are strikingly similar to known metazoan motifs: AC‐rich and purine‐rich enhancers, hnRNP A1‐binding sites, and poly‐pyrimidine tracts. These results reveal a fundamental similarity of splicing regulation between yeast and metazoan systems and suggest that splicing enhancers represent sequences that are recognized multiple times during spliceosome assembly and catalysis, affecting multiple highly conserved interactions that modulate spliceosome formation and catalytic function.In a complementary approach, we monitor the contribution of spliceosomal components to positioning of the substrate. Using reporters with an unconventional, suboptimal 5′SS, we have screened for and identified spliceosomal mutants that favor an altered 5′SS positioning. These experiments form part of a broader direction of developing orthogonal spliceosome systems, in which selected spliceosome mutants function only in the context of a specialized, orthogonal substrate.
Oral Tolerance Reduces Pulmonary Inflammation in a Cockroach Antigen Murine Model of Allergic Asthma
Authors: Vaickus Louis Joseph , Natarajan Sudha , Bouchard Jacqueline , Kim Jiyoun , Remick Daniel G. 
Published: June 2021

Our lab previously demonstrated that German cockroach allergens (CRA) induce allergic‐type airways inflammation in outbred (ICR:CD‐1) mice which closely resembles human allergic asthma. We determined the efficacy of oral tolerization in alleviating asthmatic symptoms. Mice were given 8ug/day CRA by oral gavage for 4 days beginning with day ‐7, followed by intratracheal challenges with 4.75ug on day 0 and 2.4ug on days 14 and 21. Cytokines and cells were measured in the bronchoalveolar lavage (BAL) fluid and cytokines and myeloperoxidase activity were measured in lung homogenate. Samples were collected 4 hours post final challenge and the results compared to PBS fed, CRA challenged mice. BAL eosinophils were significantly reduced in the CRA fed mice and eosinophil specific peroxidase activity was reduced in the lung homogenate as compared to PBS fed mice. In addition, multiple respiratory factors were significantly improved in the orally tolerized mice. These results indicate that oral tolerance abrogates eosinophil infiltration into the lung space. These beneficial effects are reflected by an improvement in pulmonary health as evaluated by respiratory parameters.
BAL eosinophils and eosinophil specific peroxidase activity in the lung homogenate. Respiratory parameters, respiratory rate (RR), minute ventilation (MV), peak inspiratory flow (PIF), time of expiration (Te), time of inspiration (Ti), enhanced pause (Penh).

BAL Eos
EPO
RR
MV
PIF
Te
Ti
Penh

CRA Fed
43,300
0.6
273.9
84.9
5.9
0.15
0.09
2.3

PBS Fed
158,800
1.2
223.2
67.8
4.8
0.2
0.11
3.9

p value
0.007
0.02
0.01
0.01
0.002
0.04
0.002
0.03
Human antioxidant status is not altered by quercetin supplementation
Authors: Shanely R. Andrew , Knab Amy M. , Nieman David C. , Jin Fuxia , McAnulty Steven R. , Landram Michael J. 
Published: June 2021

The purpose of this study was to measure the influence of ingesting quercetin for 12 weeks at two doses relative to placebo on plasma measures for oxidative stress and antioxidant capacity in a large community group of male (40%) and female (60% female) subjects (N=1,002) varying widely in age (18 to 85 years) and body mass index (BMI) (16.7 to 52.7 kg/m2). Subjects were randomized to one of three groups, with supplements administered using double blinded procedures: Q‐500 (500 mg quercetin/day), Q‐1000 (1000 mg quercetin/day), or placebo (PL). Fasting blood samples were obtained pre‐ and post‐study. Plasma quercetin in Q‐500 and Q‐1000 increased significantly above PL, and monthly measures on a subset of subjects found that the increase peaked during the first month and was maintained for 12‐weeks. Plasma F2‐isoprostanes, oxidized low density lipoprotein (oxLDL), reduced glutathione (GSH), ferric reducing ability of plasma (FRAP), and oxygen radical absorbance capacity (ORAC) did not differ between supplementation groups, even after adjustment for gender, age, BMI, and disease status. In summary, quercetin supplementation, 500 mg or 1000 mg/day, for 12 weeks significantly increased plasma quercetin levels in a dose‐responsive manner, but did not influence several measures of oxidative stress and antioxidant capacity.Supported by grants from Coca‐Cola and Quercegen Pharma.
Smarter Lunchrooms: Payment Systems that Nudge Healthier School Lunch Choices
Authors: Wansink Brian , Just David R. , Payne Collin R. 
Published: June 2021

How can increasingly scrutinized school lunch programs encourage children to make better food choices? Placing restrictions on the use of prepaid lunch accounts use may influence nutritious food selection without eliminating free choice or reducing profitability.A controlled field experiment in a school lunch cafeteria involved 166 students with a modal age of 19‐years. These students were allowed to purchase their lunch in one of three ways: 1) cash only, 2) cash and an unrestricted debit card, or 3) cash and a restricted debit card that could be used to purchase items marked as healthy. Their selection of items and intake was measured, and follow‐up questions were asked.Those given restricted debit cards ate significantly fewer calories than those given the unrestricted card 517.3 p=0.045), and a much higher percentage of what they selected and consumed were healthy foods compared to both those given an unrestricted debit card and those given cash (78.6%, p=0.000).This cross‐sectional study of older teenagers shows that restricting prepaid lunch cards to foods marked as reasonably healthy dramatically improved nutritious food choice and consumption. Because this payment procedure still allowed students to use their own cash to purchase less healthy options, it did not unduly restrict dining options or reduce cafeteria revenue.
Macrophage Endothelial Lipase Expression is Regulated by Fatty Acids and PPAR gamma Expression
Authors: Jung Un Ju , Torrejon Claudia , Hamai Hiroko , Deckelbaum Richard J. 
Published: June 2021

Macrophages within atherosclerotic lesions highly express endothelial lipase (EL) and PPARγ. We previously demonstrated that a saturated fatty acid (FA), palmitic acid (PA), increased macrophage EL mRNA and protein expression, whereas a n‐3 FA, EPA, inhibited the higher expression induced by LPS and PA. We now explored mechanisms by which EPA, in contrast to PA, lowers EL expression in macrophages. Murine J774 and elicited peritoneal macrophages (PM, from C57BL/6 mice) were cultured with 50–300 μM of EPA or PA for 7–24h in the presence or absence of a PPARγ agonist or antagonist. PPARγ mRNA levels were significantly increased by PA (4 fold, p<0.01), whereas EPA abrogated effects of LPS on increasing PPARγ mRNA. PPARγ mRNA positively correlated with EL mRNA expression in J774 and PM (r=0.339, p<0.05; r=0.428, p<0.01, respectively). PPARγ activation by rosiglitazone (a PPARγ agonist) increased EL mRNA (8 fold, p<0.01) and protein expression (2 fold, p<0.01), whereas GW9662 (a PPARγ antagonist) abrogated the stimulation of both rosiglitazone and PA. EPA blocked the increase of EL expression caused by rosiglitazone. Thus, EL expression closely linked to PPARγ expression, and this macrophage‐derived lipase is regulated by fatty acids, in part, through modifying macrophage PPARγ expression.Grant Funding Source: HL40404
Acute Response of Equicaloric Test Meals Varying in Glycemic Index and Glycemic Load on Postprandial Glycemia, Arterial Stiffness and Blood Pressure in Healthy Adults
Authors: Jenkins Alexandra , Bateman Emma , Brissette Christy , Guendelman Yael , Fairgrieve Christopher , Vuksan Vladimir 
Published: June 2021

ObjectivesThe relative importance of the type of carbohydrate (Glycemic Index, GI) and/or the quantity (Glycemic Load, GL) in the context of a mixed meal on glycemia is still debated; whereas the effects on vascular health are unknown. This study therefore investigated the acute effect all 4 permutations of high and low GI and GL meals on postprandial glycemia and vascular function.MethodsA total of 15 healthy subjects were recruited; preliminary data on the first eight are presented (3M, 5F; age 33 ± 16 y; BMI 21.6 ± 2.7 kg/m2). On 4 separate occasions, subjects received 4 equicaloric meals where the GI and GL levels were manipulated in a block design. Capillary blood samples were collected at fasting and 15, 30, 45, 60, 90, 120, 180 and 240 minutes post‐consumption. Aortic augmentation index (AIx) and central BP were measured hourly using applanation tonometry by radial pulse wave analysis and peripheral BP was evaluated oscillometrically.ResultsThe iAUC blood glucose response after the HiGI‐HiGL and LoGI‐HiGL meals were significantly higher than the LoGI‐LoGL and HiGI‐LoGL meals (p<0.0001), while AIx was significantly reduced at 60min after the HiGI‐LoGL and LowGI‐HiGL meals compared to HiGI‐HiGL (p<0.05).ConclusionsPreliminary data analysis demonstrates that manipulating the GI and GL of a meal result in significantly different blood glucose responses and may acutely modulate vascular function.
Brain activation patterns in response to normal vs. protein‐rich breakfast meals in overweight and obese ‘breakfast skipping’ adolescent girls
Authors: Harris Corey T. , Leidy Heather J. 
Published: June 2021

PurposeTo examine the brain activation responses to visual food cues in ‘breakfast skipping’ adolescents before and after the daily incorporation of 500 kcal breakfast meals containing either normal protein (NP) (15% of energy as pro) or higher protein (HP) (40% of energy as pro).Methods12 overweight/obese adolescent girls (age 15 ± 1 y; BMI 93 ± 1.3%ile; skip breakfast 6 ± 1 times/week) completed a baseline (‘breakfast skipping’, BS) testing day then randomly consumed NP or HP breakfast meals at home for six consecutive days. On day seven of each breakfast pattern, the subjects came to the laboratory to consume their respective breakfast meal followed by an fMRI brain scan prior to lunch (i.e., 3‐h post‐breakfast).ResultsBoth breakfast meals led to reductions in brain activation in the prefrontal cortex, cingulated gyrus, and parahippocampal gyrus compared to BS (all regions, P <0.001). In addition to these responses, the PN meal also led to reductions in brain activation in the amygdala (P<0.001), whereas the PR meal led to reductions in the insula (P<0.001).ConclusionThe daily addition of breakfast led to reductions in brain activation in specific brain regions associated with food motivation and reward in overweight and obese ‘breakfast skipping’ adolescent girls with differential responses attributable to the dietary protein of the breakfast meal. Support: NIH‐5 K12 HD052027‐04Grant Funding Source: NIH‐5 K12 HD052027‐04
Refeeding an ad libitum Diet to Energy Restricted C57BL/6 Mice Restores Natural Killer Cell Numbers and Percentages during Primary Influenza Infection
Authors: Clinthorne Jonathan Frederick , Beli Eleni , Duriancik David M , Gardner Elizabeth M 
Published: June 2021

We have previously shown that C57BL/6 mice fed a 40% energy‐restricted (ER) diet impairs the Natural Killer (NK) cell response to primary influenza infection. We hypothesized that refeeding ER mice with an ad libitum (AL) diet would restore the innate immune response to influenza virus. In this study three dietary groups were compared: 1) 40% ER, 2) AL fed, and 3) ER mice fed an AL diet (RF). All groups were monitored for 3 days after infection with 100 HAU of influenza A virus. Body weight and body composition were monitored over the course of the feeding (10–14 days) and after infection (3 days). RF mice exhibited a hyperphagic response, increasing body weight and body fat percentage within 5–7 days to restore to levels comparable to AL mice. Importantly, refeeding partially restored cell numbers and percentages, but not phenotypes, of NK cells in lungs, blood and spleen. In ER and RF groups, the percentages of CD27hi/Mac‐1lo (immature) NK cells were decreased in blood, but increased in spleens, compared to the AL mice. NK cells in RF and ER mice also exhibited higher expression of the activation marker B220. Lung virus titers accumulated, and remained higher, in both ER and RF animals, despite increased survival of RF mice. These data suggest that this nutritional refeeding paradigm may be necessary to increase the NK cell response to influenza infection in susceptible populations. Supported by R15AG029637 (E.M.G.)Grant Funding Source: R15AG029637
Perspectives and Practices related to Nutrition and Physical Activity among Home‐Based Child Care Providers
Authors: Kim Juhee , Shim Jae Eun 
Published: June 2021

ObjectivesTo understand the obesity related practices and perceptions among home‐based childcare providers.MethodThe CRAYON (Caretaker Research Advance Youth Obesity Knowledge) group and Child Care Resource Services (CCRS) at University of Illinois at Urbana‐Champaign conducted a survey study in child care training workshops in Champaign County, IL. Total 40 home‐based care providers completed a self‐administered survey.ResultsAbout 78% child care providers received training on nutrition and 72% on physical activity during the past year. 95% providers taught children about nutrition and 61% provided nutrition information to parents. The important factors in deciding food menu are followed: 90% CACFP guideline or state regulation, 89% nutritional contents, 89% availability, 77% convenience, 73% children's preferences, 72% cost, and 70% parent requests. It is noted that providers consider they have about the same influence on food preferences, eating habits, and physical activity compared with those of parents. However, providers think that home environment has a stronger influence on weight status of children than child care environment.DiscussionNot enough child care providers offer parents information on nutrition, physical activity, and obesity prevention. Further studies are needed to understand the barriers and facilitators of health promotion opportunity in home‐based child care setting.