bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of milk fat on LDL cholesterol and other cardiovascular risk markers in healthy humans: the INNOVALAIT project (269.3)
Authors: Bard Jean‐Marie , Drouet Ludovic , Lairon Denis , Cazaubiel Murielle , Marmonier Corinne , Bal dit Sollier Claire 
Published: June 2021

The atherogenicity of milk fat is under debate. Milk fatty acid content may depend on the animal breed, its feeding and the season of collection. Dairy calcium may change the kinetics of fat absorption. This study aims to compare the effect on LDL Cholesterol (LDLC) and other risk markers of 4 isolipidic regimen (R) which differ by the fat sources: spring milk fat (R2), winter milk fat (R3), winter milk fat supplemented with calcium (R4) and vegetable fat (R1).This double blind clinical study included 174 hypercholesterolemic adults (130 mg/dL<LDLC<220 mg/dL, TG <300 mg/dL) randomized in the 4 regimen groups for 8 weeks. R1 and R2 have the same saturated fat (SF) content (12.7% Energy vs 15% for R3, R4). R1, R3 and R4 have similar palmitic acid content (7% vs 5.2% for R2). For 2250 Kcal, the experimental dairy food brings 1040 mg Ca daily (R4) vs 415 mg (R1, R2, R3). 154 subjects (64% women) constitute the per protocol population. LDLC (R1 : 158±29 mg/dL, R2: 154±25 mg/dL, R3: 158±19 mg/dL, R4: 166±37 mg/dL) and TG are comparable at inclusion. After 8 weeks, there is no diet effect on LDLC, HDLC and TG, after adjustment for BMI, sex and baseline values. A diet effect is observed for apo B, apo C3 and CRP but the inter‐group comparison (Dunett) was not significant.It is concluded that high levels of SF (12.7 to 15%) from milk does not alter conventional cardiovascular risk markers after 8 weeks. In our trial, the origin of milk fat had no influence.Grant Funding Source: Supported by French Government, BBA, CNIEL and local fundings (Pays de Loire and Bretagne)
Choline status modulates the development of atherosclerosis in LDL receptor knockout mice (272.7)
Authors: Al Rajabi Ala , Leonard Kelly‐Ann , Vine Donna , Proctor Spencer , Jacobs René 
Published: June 2021

Background: Phosphatidylethanolamine N‐methyltransferase (Pemt) is the only de novo pathway for phosphatidylcholine (PC) synthesis in mammals; as such, Pemt ‐/‐ mice are chronically choline‐deficient. PEMT deficiency dramatically reduces atherosclerosis development in LDL receptor (LDLR) knockout mice. This atheroprotective effect is believed to be mediated by reduction in circulating lipid levels.Purpose: to investigate the effect of altering choline status on plasma lipid profiles and atherosclerosis development in LDLR‐/‐ mice, and to test the hypothesis that choline supplementations reverse the atheroprotective effect of PEMT deletion via normalization plasma lipid profiles.Methods: LDLR‐/‐ and PEMT‐/‐/ LDLR‐/‐ male mice were given free access to high fat high cholesterol diet. Choline in diet (g/Kg) ranged from 0‐10. Atherosclerosis development was assessed by measuring plaque area in cross sectional aortic root.Results: In LDLR‐/‐ mice, choline‐deficient group gained less weight, presented higher liver TG, CE and PL compared to other groups. Excessive choline group presented significantly higher liver PC and plasma TG.Choline supplementation caused step‐wise increase in atherosclerosis development in LDLR‐/‐ mice. Significant correlations were observed between choline in diet and plasma PL (r=0.8075, P<0.0001), plasma total cholesterol (r=0.8369, P<0.0001), plasma TG (r=0.7551, P<0.0001), and aortic root atherosclerotic plaque area (r=0.6985, P<0.0001).As previously reported, PEMT‐/‐/ LDLR‐/‐ mice were protected from atherosclerosis. Increasing dietary choline from 3‐10 (g/Kg) decreased liver weight, TG, and PL. Surprisingly; it didn’t promote atherogenic plasma lipid profiles nor increased plaque formation.Conclusion: There is a positive correlation between dietary choline and the development of atherosclerosis in the LDLR‐/‐ mice. Choline deficiency cannot solely explain the atheroprotective effect of PEMT deletion in the LDLR‐/‐ mice.Grant Funding Source: Supported by Canadian Institutes of Health Research (CIHR) & Alberta Innovates Bio Solutions (AI B)
Pkr‐like endoplasmic reticulum kinase (PERK) and glycogen synthase kinase‐3α/β signaling regulate atherosclerosis development (278.5)
Authors: McAlpine Cameron , Werstuck Geoff 
Published: June 2021

Recently, a role for endoplasmic reticulum (ER) stress signaling through glycogen synthase kinase (GSK)‐3α/β has been proposed in atherogenesis; this study sought to delineate the underlying molecular mechanisms.Cultured THP1‐derived macrophages were treated with the ER stress‐inducing agents, glucosamine, thapsigargin or palmitate in the presence or absence of inhibitors of the unfolded protein response (UPR) pathways (PERK, IRE, ATF6) or GSK3α/β (CT99021). ER stress enhanced GSK3α/β activity while inhibition of the PERK pathway, but not the IRE or ATF6 pathways, attenuated GSK3α/β activity. GSK3α/β inhibition did not affect adaptive components of the UPR but did repress the expression of factors downstream of PERK (ATF4 and CHOP). ER stress enhanced the mRNA expression of genes controlling lipid biosynthesis and uptake; while GSK3α/β inhibition attenuated this effect. GSK3α/β inhibition blocked ER stress‐induced cholesterol accumulation in macrophages. To investigate the roles of macrophage GSK3α and GSK3β in a mouse model of atherosclerosis, LDLR‐/‐ myeloid cell GSK3α knockout (LDLR‐/‐GSK3αflox/floxLyzMCre+/‐) and GSK3β knockout (LDLR‐/‐GSK3βflox/floxLyzMCre+/‐) mice were placed on a high fat diet. Myeloid cell GSK3α deficiency, but not GSK3β deficiency, attenuated atherogenesis.Our findings support a role for macrophage PERK ‐ GSK3α signaling in atherosclerosis development.
Textpresso for oro‐pharyngeal anatomy: a system for searching the full text of anatomy literatures (338.3)
Authors: Van Auken Kimberly , Druzinsky Robert , Done James , Sternberg Paul , Mueller Hans‐Michael 
Published: June 2021

Biological databases are a useful resource for parlaying existing data into new experimental hypotheses. Populating such databases with information from the published literature, however, can be labor intensive and thus is aided greatly by text mining tools capable of retrieving key facts from full text.The Textpresso information retrieval system (http://www.textpresso.org) is used by several Model Organism Database (MOD) communities to assist in curation [Müller HM, Kenny EE, Sternberg PW. 2004. PLoS Biol. Nov;2(11):e309; Van Auken KM, Fey P, Berardini TZ, et al. 2012. Database (Oxford). Nov 17;2012:bas040.] Textpresso searches the full text of literature using keywords and/or categories, groups of semantically related words, to identify sentences within a paper that describe specific aspects of biology.Using the anatomy ontology of oro‐pharyngeal structures developed in the FEED project [Druzinsky R, et al., in prep ], we are constructing a Textpresso site to aid in curation of the oro‐pharyngeal muscle literature. At this time, we have amassed a database of over 2000 searchable references. We will present a demonstration of Textpresso for Oro‐Pharyngeal Anatomy and show how it can be used to construct meaningful queries on the full text of the literature.
TGFβR3 is required for normal vascularization and ossification of the palate (342.5)
Authors: Hill Cynthia , Barnett Joey , Goudy Steven 
Published: June 2021

Cleft palate occurs in up to 1:500 live births associated with mutations in multiple genes. Palatogenesis involves a complex choreography of palate shelf elongation, elevation, and fusion. Transforming Growth Factor β (TGFβ) and Bone Morphogenic Protein 2 (BMP2) are known regulators of palatal development, but the contributions of the specific receptors remain elusive. The Type III TGFβ Receptor (TGFβR3) binds all three TGFβ ligands, inhibin, and BMP2. To address the role of TGFβR3 during palatal development we examined Tgfbr3‐/‐ mice. These mice do not survive to E15.5 when palate fusion occurs, but at E14.5, palatal elongation and elevation had failed. Tgfbr3‐/‐ embryos display unorganized and reduced vascularization of the palate at E13.5 and E14.5 which was accompanied by aberrant expression of arterial, venous, and lymphatic markers. Analysis of osteoblast differentiation demonstrated reduced expression of osteoblast determinants at E13.5 and E14.5. In vitro bone mineralization assays revealed reduced capacity of Tgfbr3‐/‐ mouse embryonic palatal mesenchymal cells to undergo osteoblast differentiation and to form bone which was rescued by overexpression of TGFβR3. These data demonstrate that TGFβR3 contributes to palatal development by regulating vascularization and osteoblast differentiation.Grant Funding Source: 5K08DE17953‐5
β‐Catenin in the renal stroma regulates apoptosis via Bcl2l1 during kidney development (344.4)
Authors: Boivin Felix , Bridgewater Darren 
Published: June 2021

Kidney development is dependent upon reciprocal inductive interactions between epithelium, mesenchyme, and stroma cells. β‐catenin is essential for the formation of mesenchyme derived nephrons and epithelial derived collecting duct system. β‐catenin protein is expressed in medullary, cortical, and capsular stroma in embryonic and mature kidneys. However, its role in the renal stroma is not well understood. We generated mice with ß‐catenin deficiency exclusively in the renal stroma (termed ß‐catLOF‐S). Kidneys from ß‐catLOF‐S demonstrated a paucity of renal capsule and a significant reduction in the stromal cell population (4.55 +/‐ 0.19 stromal cells/mm2 WT vs 2.52 +/‐ 0.26 in ß‐catLOF‐S). Analysis of apoptosis in ß‐catLOF‐S revealed a significant increase in apoptotic stromal cells by E13.5 (0.54 +/‐ 0.03 WT apoptotic cells/mm2 vs 1.19 +/‐ 0.14 in ß‐catLOF‐S). We investigated β‐catenin targets that regulate apoptosis and observed significant reductions in Bcl2l1 mRNA and protein in ß‐catLOF‐S kidneys. We demonstrate β‐catenin forms a novel molecular complex with transcriptional co‐activators TBX5, YAP1, and YES1, and binds to the TBX5 consensus site within the Bcl2l1 promoter. These results suggest β‐catenin controls stromal cell survival via regulation of Bcl2l1 by forming a novel transcriptional complex during kidney development.Grant Funding Source: Supported by NSERC (Natural Sciences and Engineering Research Council of Canada) and KFOC (The Kidne
Design of a novel redox biocatalyst to specification (363.3)
Authors: Bommarius Andreas , Abrahamson Michael , Schuermann Martin , Au Samantha , Bommarius Bettina 
Published: June 2021

Recently, we obtained the first amine dehydrogenases, termed L‐AmDH and F‐AmDH, from leucine DH [1] and phenylalanine DH [2], respectively, allowing direct reductive amination of ketones to chiral amines.Starting from a scaffold devoid of such activity, a robust AmDH has been evolved with a single two‐site library allowing for the direct production of (R)‐1‐(4‐fluorophenyl)‐propyl‐2‐amine from para‐fluoro phenyl acetone with a kcat value of 6.85 s‐1 at 25oC. Only (R)‐amine was formed (> 99.8% e.e.), showing that perfect enantioselectivity of the template was conserved.Successful domain shuffling created a chimeric amine DH with enhanced substrate specificity that allows to accommodate sterically very demanding side chains, such as adamantly groups. We will elucidate the impact of restricted libraries in the evolution towards higher activity and broader specificity.Many interesting substrates feature low solubility in aqueous solution. We describe how utilizing a two‐phase system can also lead to pinpointing broadened substrate specificity, as substrate candidates that were previously missed, can register as hits in the search.
Seafood consumption and blood mercury concentrations in youth ages 1‐19 years, 2007‐2010 (369.4)
Authors: Nielsen Samara Joy , Kit Brian , Aoki Yutaka , Ogden Cynthia 
Published: June 2021

Background: Consuming seafood has health benefits, but seafood can also contain methyl mercury, a neurotoxin.Objective: To examine seafood consumption and blood mercury concentrations in US youth.Design: In the 2007‐2010 National Health and Nutrition Examination Survey, blood mercury and seafood consumption in the past thirty days were collected from 5,744 youth, ages 1‐19 years. Seafood consumption was categorized as fish or shellfish and by frequency of consumption: none, 1‐2, 3 or more times per month. Association between seafood consumption and blood mercury was examined using multiple linear regression adjusted for sex, age and race/Hispanic origin.Results: In 2007‐2010, 60.5% (SE,1.0), of youth reported consuming seafood, 35.9%, (SE,1.2), shellfish, and 47.6% (SE,1.0) fish in the preceding month. Less than 1% of youth had blood mercury concentrations at or above 5.8 µg/L. The geometric mean blood mercury concentrations were 0.31 (SE, 0.01) for non‐seafood consumers and 0.54 (SE, 0.02) for seafood consumers. Higher frequency of seafood consumption was associated with higher log10(blood mercury concentrations) in the adjusted model (fish: (β=0.70 (95% CI, 0.62,0.78), shellfish:(β=0.43 (95% CI, 0.31,0.54)).Conclusions: Very few youth have blood mercury concentrations at or above 5.8 µg/L but among US youth, blood mercury concentration is associated with both fish and shellfish consumption.
Central adiposity influences the relationship between 25(OH)D and indices of plasma insulin (37.7)
Authors: Wright Christian , Weinheimer‐Haus Eileen , Fleet James , Peacock Munro , Campbell Wayne 
Published: June 2021

Low serum 25‐hydroxyvitamin D3 (25(OH)D) is inversely associated and central adiposity is positively associated with plasma insulin (INS) concentrations. We assessed whether the relationship between 25(OH)D and INS is confounded by central adiposity. 336 overweight and obese adults (age: 48 ± 8 y, BMI: 30 ± 3 kg/m2) from West Lafayette, IN (40.4°N) were studied. Among all subjects, vitamin D status was as follows: 2% deficient (8‐10 ng/ml); 26% insufficient (10‐20 ng/ml); 53% adequate (20‐30 ng/ml); and 19% proposed optimal (>30 ng/ml). After controlling for age, race, and sex, 25(OH)D was inversely correlated with indices of INS (fasting INS, r= ‐0.12; oral glucose challenge INS area under the curve (AUC), r= ‐0.12; HOMA‐IR, r= ‐0.12; all p<0.05). Android fat mass index was also correlated with indices of INS (fasting INS, r= 0.32; INS AUC, r= 0.32; HOMA IR, r= 0.31; p<0.001) and 25(OH)D (r= ‐0.11, p<0.05). Similar correlations were observed for trunk fat mass and trunk body fat percent. These correlations (p<0.001) between central adiposity and INS persisted after controlling for 25(OH)D. However, after adjusting for individual markers of central adiposity, the significant correlations between 25(OH)D and indices of plasma INS did not persist. Our data do not support an independent effect of 25(OH)D on INS, but suggest that 25(OH)D is a marker for the relationship between central adiposity and insulin sensitivity.Grant Funding Source: U.S. Whey Protein Research Consortium; NIH T32AG025671 and UL1 TR000006
Metabolites of polyphenols preserve indices of endothelial cell nitric oxide bioavailability under glucotoxic conditions (372.6)
Authors: Qian Ying , Panneerseelan Leenalitha , Babu P.V.A. , Symons J. , Jalili Thunder 
Published: June 2021

We hypothesized that biological metabolites of quercetin, resveratrol, and grape seed extract previously identified in human plasma can prevent impairment of nitric oxide (NO) bioavailability due to glucotoxic conditions (e.g. Type 1 or 2 diabetes).Human aortic endothelial cells were treated for 24 h with 2μΜ Quercetin‐3‐O‐glucoronide, 5μΜ Piceatannol, or 1μΜ 3‐Hydroproponoic acid. Cells were next exposed to normal (5mM) or high (25mM) glucose for 48h, then treated with insulin (100nM, 10 min) to stimulate NO production.In the absence of polyphenols, insulin stimulation increased (P<0.05) indices of NO production, phosphorylated to total Akt (p‐AktSer473:Akt), and endothelial nitric oxide synthase (p‐eNOSser1177:eNOS) in cells grown in 5mM but not 25mM glucose. Pretreatment of cells with polyphenol metabolites prior to 25mM glucose exposure preserved insulin stimulated increases (P<0.05) in NO, p‐AktSer473:Akt and p‐eNOSser1177:eNOS. These effects may be secondary to oxidative stress as elevations (P<0.05) in reactive oxygen and nitrogen species in cells treated with 25mM glucose were completely prevented by all polyphenol metabolites.These data indicate that biological metabolites of quercetin, resveratrol, and grape seed extract protected against gluocotoxic impairment of insulin dependent NO bioavailability, and preserved the insulin ‐ Akt ‐ eNOS signaling axis.
DNA methylation in an enhancer region of the FADS cluster is associated with FADS activity in human liver (373.8)
Authors: Chilton Floyd , Mathias Rasika , Seeds Michael , Herrington David , Hixson James , Hawkins Greg , Sergeant Susan , Miller Leslie , Howard Timothy 
Published: June 2021

Omega‐6 (n‐6) and omega‐3 (n‐3), long chain polyunsaturated fatty acids (LcPUFAs) impact a wide range of biological activities ranging from immune signaling to brain function. Two desaturase steps (Δ6, encoded by FADS2 and Δ5, encoded by FADS1) are rate‐limiting in the conversion of dietary essential 18 carbon PUFAs such as linoleic acid (n‐6) to arachidonic acid and α‐linolenic acid (n‐3) to eicosapentaenoic and docosahexaenoic acids. Genetic variants in and around FADS1 and FADS2 are highly associated with levels of LcPUFAs as well as cardiovascular disease risk factors. Particularly, rs174537 is associated with both FADS activity and circulating AA levels (p = 5.95 x 10‐46). FADS1 and FADS2 sit adjacent (5’ to 5’) on chromosome 11 (11q12.2). We hypothesized that SNPs such as rs174537 were associated with DNA methylation variation that impacted LcPUFA levels and FADS activities. To test this hypothesis, we performed a genome‐wide allele‐specific methylation study with rs174537 in 144 human liver samples. This approach identified a strong association of rs174537 with CpG sites in an enhancer region between FADS1 and FADS2 (p=2.69x10‐29). These data suggested that rs174537 was serving as a genetic proxy for methylation variability in a critical enhancer region sitting between two proximal promoters for FADS1 and FADS2. Importantly, methylation levels of the significant probes were shown to be strongly associated with FADS1 and FADS2 activities within the liver.Grant Funding Source: NIH ‐ P50 AT002782
Overexpression of glutathione peroxidase‐1 induces steatosis in mouse (374.3)
Authors: Pan Zhixiong , Lei Xin Gen 
Published: June 2021

Our laboratory has previously found insulin resistance and obesity in mice overexpressing Se‐dependent glutathione peroxidase‐1 (GPX1‐OE). The present study was conducted to determine if and how hepatic lipid metabolism was related to these metabolic phenotypes in the GPX1‐OE mice. Liver samples were collected from male GPX1‐OE and the wild‐type mice at ages of 3 wk and 2, 6, 9, and 12 mo (n = 5‐10, fed an Se‐adequate Torula yeast‐sucrose diet) to determine lipid profiles and the mRNA and protein levels of factors involved in triglyceride synthesis, lipid deposition, β‐oxidation, and lipid hydrolysis. The time‐course indicated that obesity was observed at 6 mo of age and was preceded by the development of insulin resistance in the GPX1‐OE mice. Steatosis was developed between 6 and 12 mo of age in these mice. Compared with the wild‐type, the GPX1‐OE mice showed up‐regulation (P < 0.05) of fatty acid synthase (FASN), carbohydrate response element‐binding protein (ChREBP), and sterol regulatory element‐binding proteins‐1c (SREBP1c) protein or enzyme activity. In contrast, these mice, starting from 6 mo of age, showed down‐regulations (P < 0.05) of peroxisome proliferator‐activated receptor beta (PPARβ), carnitine palmitoyltransferase I (CPT1α), and adipose triglyceride lipase (ATGL) protein or activity. In conclusion, overexpression of GPX1 induced steatosis in mice from 6 mo of age by stimulating the triglyceride synthesis pathway and inhibiting the fatty acid oxidation and lipid pathway. These findings imply that the GPX1‐OE mouse may be a novel model for studying steatohepatitis associated with obesity and diabetes.Grant Funding Source: (NIH DK53018)
Acute effects of higher protein, sausage and egg‐based convenience breakfast meals on postprandial glucose homeostasis in healthy, premenopausal women (381.6)
Authors: Leidy Heather , Ortinau Laura , Rains Tia , Maki Kevin 
Published: June 2021

Purpose: To examine the acute effects of commercially‐prepared breakfast meals, varying in protein and carbohydrate content, on plasma glucose (PG) and plasma insulin (PI) responses. Methods: Using a randomized, crossover design, 34 healthy women (age 32 ± 2 y; BMI 24.8 ± 0.5 kg/m2) consumed, on separate days, ~290 kcal breakfasts which were higher protein sausage and egg‐based meals containing 30 g protein (HP‐30) or 39 g protein (HP‐39) or lower protein pancake‐based breakfast meal containing 3 g protein (LP). Pre and post‐breakfast PG and PI concentrations were assessed every 30 min for 240 min; 4h net incremental area under the curve (niAUC) was determined. Results: PG niAUC was not different between meals (HP‐30: ‐140 ± 268; HP‐39: ‐267 ± 219; LP: ‐413 ± 254 mg/dL*240 min; NS). However, post‐breakfast peak PG was 10 ± 1% lower following HP‐30 and 14 ± 1% lower following HP‐39 vs. LP (both, p<0.05). HP‐39 had a 4 ± 1% lower peak PG vs. HP‐30 (p<0.05). PI niAUC was lower following HP‐30 (1067 ± 120) and HP‐39 (952 ± 138) vs. LP (1585 ± 167 µU/mL *240 min; both, p<0.05) with no differences between HP meals. Peak PI was 45 ± 2% lower following HP‐30 and 56 ±2% lower following HP‐39 vs. LP (both, p<0.05). HP‐39 had a 20 ± 2% lower peak PI vs. HP‐30 (p<0.05). Conclusions: Higher protein, sausage and egg convenience meals providing 30 g or 39 g protein improve postprandial glucose homeostasis vs. a lower protein breakfast with greater benefits observed with the 39 g protein breakfast.Grant Funding Source: Supported by Hillshire Brands
Early infant feeding and childhood adiposity (391.3)
Authors: Anderson Alex , Whitworth Christina 
Published: June 2021

The purpose of this study was to examine the role of early childhood feeding practices on childhood obesity. The specific aims were to examine the relationship between infant feeding and age of introduction of complementary foods, and childhood adiposity. This was a cross‐sectional study of 4 to 6 years old children and their mothers. Infant feeding and timing of introduction of complementary foods were reported by the mother. Child adiposity was assessed via the BOD POD Pediatric Option. Participants were mostly Caucasians (88.9%), female (66.7%) and average age was 4.9±0.8 years. About 41% of the children were breastfeed exclusively (EBF) for at least 4 months, while complementary foods were introduced as early as 6 weeks of age. There was no statistically significant relationship between infant feeding practice and adiposity or age of introduction to complementary foods and adiposity, although children who were mixed fed weighed about 1 kg heavier and had about 3% less body fat than their (EBF) counterparts. Children introduced to early complementary feeding (<4 months) weighed more and had slightly higher percent body fat. There was, however, a significant, positive correlation between the mother’s pre‐pregnancy BMI and the birth weight of the child (P=.009) and the child’s current weight (P=.031). Our findings suggest in‐utero and other external factors besides the child’s diet may be contributing to childhood obesity.Grant Funding Source: Hatch ‐ GEO00701