bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adding prebiotic fiber to a maternal high fat, sucrose diet during pregnancy and lactation reduces offspring body fat in Sprague‐Dawley rats
Authors: Paul Heather Anne , Bomhof Marc R , Reimer Raylene A 
Published: June 2021

The prebiotic fiber oligofructose (OFS) may help reduce the negative effects associated with intake of a high‐fat/high sucrose (HFS) diet during pregnancy and lactation. Obesity was induced in female SD rats (n=90) with a HFS diet for 10 wk. Top weight gainers were randomized to 1 of 3 groups for pregnancy and lactation (n=14 per group): 1) HFS; 2) HFS + 10% OFS; 3) Weight matched (WM) to group 2. A 4th lean control (LC) group was kept on standard AIN‐93G diet. Primary outcomes included maternal and offspring body weight (BW) and composition (via DXA). Secondary outcomes included an oral glucose tolerance test, satiety hormone analysis and fecal microbiota profiles. At baseline, obesity induced dams had significantly higher BW (p<0.001) and fasting glucose (p<0.05) than LC. During gestation, BW was lower in LC than all other groups (p=0.001) up to 1 day before due date, then was only lower than the HFS dams; OFS and WM dams were not different than LC. At weaning, HFS dams had higher % body fat than all other groups (p<0.015). Gestational glycemic response was highest in HFS dams (p<0.05). Offspring of HFS dams had higher % body fat than all other groups (p<0.001); offspring of OFS dams were no different then LC or WM pups. Gut microbiota and satiety hormone analysis is ongoing. In conclusion, consumption of OFS during pregnancy and lactation normalizes the high body fat found in HFS‐fed dams and their offspring. Funded by CIHR, AIHS, NSERC.Grant Funding Source: CIHR, NSERC, AIHS
Effect of mental stress on skin sympathetic nerve activity: Are responses reproducible?
Authors: Ray Chester A , Sauder Charity L , Muller Matthew D 
Published: June 2021

The primary aim of this study was to quantify the effect of mental stress (MS) on skin sympathetic nerve activity (SSNA). There is limited quantitative data showing SSNA response to MS. Previous studies report divergent MSNA responses to MS. The second aim was to determine the reproducibility of SSNA to MS within a given day and 1 week later. Ten subjects (26±1 yr.) performed two bouts of mental arithmetic lasting 3 min. The bouts were separated by 45 min. One week later the subjects returned to repeat MS. All experiments were conducted in the supine posture during the morning hours. To maintain neutral skin temperature, each subject wore a custom suit (34–35°C). Skin blood flow and sweat rate were measured on the dorsal foot. MS elicited a marked increase in SSNA within the first 10 s (184±42%; P<0.01) in all subjects, which was less during the remaining period of MS but remained elevated (87±20; P<0.01). The pattern of responses to MS was unchanged during the second bout (10 s, 247±55%; 3 min avg., 133±29%) and during the retest 1 week later (10 s, 196±55%; 3 min avg., 117±36%). MS did not significantly affect cutaneous vascular conductance and sweat rate during any trial. In summary, MS elicits robust and reproducible increases in SSNA in humans. Thus unlike MS effect on MSNA, the pattern of SSNA is consistent during repeated trials on the same day and when performed 1 week later.Supported by NIH (HL109952)
Diminished baroreflex function following ovariectomy is a consequence of the reduced excitability of a sex specific population of low threshold myelinated baroreceptor afferents in the rat
Authors: Chavez Grace Corina Santa Cruz , Li Baiyan , Schild John H. 
Published: June 2021

Concomitant with menopause there is a significant reduction in the capacity of the baroreflex (BRx). Loss of so‐called sex hormones is but one factor. Our previous in situ BRx studies have validated and quantified the contribution of a sex specific subpopulation of low‐threshold myelinated aortic baroreceptor afferents (Ah‐type) in eliciting depressor dynamics not observed in male rats. Ovariectomy greatly reduces the excitability of these Ah‐type afferents while the excitability of low threshold myelinated A‐type and high threshold unmyelinated C‐type afferents is unchanged.OBJECTIVEDetermine if the ovariectomy‐mediated loss in excitability of Ah‐type afferents alters the depressor response evoked by this sex specific baroreceptor afferent pathway. Age‐matched, normal (NF) and ovariectomized (OVX) female rats were prepared for selective, bipolar electrical stimulation of the left aortic depressor nerve. The OVX (n = 9) presented with a significantly diminished parasympathetic mediated reduction in mean arterial pressure in comparison to the NF (n = 16). Interestingly, the most significant changes in depressor dynamics occurs at electrical thresholds and frequencies most closely aligned with Ah‐type baroreceptor fibers. We conclude that these sex specific afferents may provide a neuromodulatory pathway uniquely associated with the hormonal regulation of BRx function. HL072012, HL081819
Sympatho‐inhibition in an Ovine Model of Septic Shock: Cardiovascular and Renal Effects
Authors: May Clive , Bellomo Rinaldo , Calzavacca Paolo 
Published: June 2021

There is evidence that inhibition of the increased sympathetic outflow in sepsis is beneficial, but the mechanisms are unclear. In conscious sheep, at 24 hours of septic shock induced by intravenous infusion of live E. coli, the effect of intravenous infusion of clonidine for 8 hours on cardiovascular and renal function was examined. Administration of E. coli caused hyperdynamic septic shock: hypotension, tachycardia, increased cardiac output, increased renal blood flow, oliguria and decreased glomerular filtration rate. During sepsis, clonidine (1.0 μg/kg/h) reduced cardiac index (from 7.5±0.8 to 5.9±0.5 L/min), heart rate (from 146±9 to 124±8 b/min), but mean arterial pressure did not significantly fall (79±4 vs. 73±5 mmHg). Clonidine reduced renal blood flow (363±9 to 312±30 mL/min) and increased urine output (22±5 to 46±19 mL/h), but did not improve creatinine clearance (42±4 to 29±9 mL/min). In hyperdynamic sepsis, clonidine treatment did not increase the degree of hypotension despite a fall in cardiac output, it increased urine output but did not improve glomerular filtration rate.This research was supported by the NHMRC, Australia.
Circulating inflammatory mediators as potential biomarkers for Heart Failure: a study of the baseline levels in healthy volunteers
Authors: Altara Raffaele , Hessel Marleen H.M. , Manca Marco , La Rocca Hans Peter Brunner , Gorgels Anton P.M. , Hermans Rob J.J. , Janssen Ben J.A. , Boudier Harry A.J. Struijker , Blankesteijn Matthijs W. 
Published: June 2021

During Heart Failure (HF) inflammatory mediators are modulated. Our animal experiments showed an increase of four chemokines in the early stage of cardiac hypertrophy development which have never been investigated in this setting. Here we established the baseline values of these molecules in healthy people.30 volunteers were selected with no known inflammatory condition. A membrane‐based planar method, called Proteome Profiler™, has been improved with fluorescence into a semi quantitative assay. The screening of ~40 inflammatory analytes, including the four identified in animal experiments, was done in serum and plasma of different genders, sampling time and blood components.The physiological variability of the analytes was homogeneous within the cohort. There were no consistent differences among gender, serum or plasma and time of collection.In a pilot study of a heterogeneous cohort of CHF patients, two of the four analytes discovered as elevated in animal models for HF had higher concentrations when compared to healthy controls.The two up‐regulated chemokines in animal models of HF and in HF patients could be candidates for biomarkers for prognostics and diagnostics of HF.
miR204/RUNX2 axis regulates HIF‐1α activation in pulmonary arterial hypertension
Authors: Margaillan Guillaume , Barrier Marjorie , Potus François , Meloche Jolyane , Courboulin Audrey , Couture Christian , Bonnet Pierre , Provencher Steeve , Bonnet Sebastien 
Published: June 2021

Pulmonary arterial hypertension (PAH) is characterized by proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMC). This phenotype is sustained by an elusive HIF‐1α activation RUNX2 activates HIF‐1α in vascular diseases, and is controlled by miR‐204 that is decrease in PAH. We hypothesized that miR‐204 downregulation triggers RUNX2‐dependent activation of HIF‐1 contributing to PAH.HIF‐1α and RUNX2 activation are increased in humans and rats distal PA and PAH‐PASMC vs control. In PAH‐PASMC, RUNX2 downregulation resulted in HIF‐1α inhibition (immunoblot, IF; p<0.05) decreasing proliferation (p<0.05) and resistance to apoptosis (p<0.05); while RUNX2 upregulation in control PASMC has the opposite effects. As RUNX2 is one of the predicted targets of miR‐204 its upregulation in PAH‐PASMC could be explained by the miR‐204 downregulation seen in PAH. Thus miR‐204 supplementation (mimic) in PAH‐PASMC decreases RUNX2 and HIF‐1α activation (Western blot; p<0.05), while miR‐204 downregultion in control PASMC increases RUNX2 and HIF‐1. In vivo, siRUNX2 nebulization or miR‐204 nebulization in SUGEN‐induced PAH rats reverses PAH.We demonstrated the implication of miR‐204/RUNX2 axis in HIF‐1 activation in PAH.
Activation of gut calcium‐sensing receptor by peptide agonists promotes glucose tolerance in rats
Authors: Hira Tohru , Muramatsu Maya , Mitsunaga Arimi , Sato Eri , Nakajima Shingo , Kitahara Yoshiro , Eto Yuzuru , Hara Hiroshi 
Published: June 2021

PurposeCalcium‐sensing receptor (CaSR) is widely expressed in various tissues including gastrointestinal tract. However, the role of gut CaSR in digestion/absorption of macronutrients is yet not known. In the present study, we examined whether single oral administration of CaSR agonist peptides affects glycemic response in rats, and also investigated the mechanism by which CaSR agonists modulate the glycemic response.MethodsGlucose tolerance tests were performed under oral or duodenal administration of various CaSR agonist peptides {γGlu‐Cys (γEC), protamine, and poly‐lysine} in conscious rats. Gastric emptying rate was measure by using phenol red method.ResultsOral and duodenal administration of CaSR agonists (γEC, protamine, and poly‐lysine) attenuated the glycemic response under oral glucose tolerance test. Gastric emptying rate was decreased by oral administration of these CaSR agonists. Glucose‐lowering effect of the agonists was partially cancelled by luminal pretreatment with a CaSR inhibitor. In addition, intraperitoneal treatment with 5‐HT3 receptor antagonist partially reversed the glucose‐lowering effect of the agonists.These results demonstrate the activation of gut CaSR by peptide agonists attenuates glycemic response. Involvement of 5‐HT3 receptor and delayed gastric emptying are suggested in the glucose‐lowering effect of these CaSR agonists.
Preventable decrements of cerebral microvascular volume and vasodilatation in a rat model of diet‐induced Vascular Cognitive Impairment: non‐invasive detection by absolute Near Infrared Spectroscopy
Authors: Vayman Vered , Martsiano Shani , Weinstein Merav , Nachum‐Biala Yaarit , Troen Aron M 
Published: June 2021

The brain microvascular circulation has considerable structural plasticity and can expand or regress in response to metabolic and dietary challenges We hypothesized that such changes might underlie the association of folate deficiency and hyperhomocysteinemia with cerebrovascular and neurodegenerative disease. Previously, we found that dietary folate deficiency can impair cognition in Sprague Dawley rats and that this can be mitigated by adding methionine to the folate‐deficient diet. Separately, we used non‐invasive absolute Near Infrared Spectroscopy (NIRS) to obtain evidence of brain microvascular changes in folate‐deficient rats, finding diminished cerebral blood volume and vasoreactivity compared to controls. Here we extend these findings by showing that folate deficiency reproducibly diminishes cerebral blood volume and vascular reactivity, and that these changes can be reversed by methionine supplementation. Our findings are consistent with the hypothesis that reversible microvascular changes may contribute to cognitive impairment. The ability to non‐invasively manipulate, detect and measure such changes can help to understand the role of microvascular plasticity in dementia.Support: Israel Science Foundation and EU‐IRG
Improving the redox potential of gestational diabetic endothelial cells: protective actions of sulforaphane
Authors: Patel Bijal , Siow Richard CM , Mann Giovanni E. 
Published: June 2021

RationaleGestational diabetes mellitus (GDM) is characterized by hyperglycemia and/or impaired glucose tolerance and affects 2–7% of pregnancies. In utero exposure to enhanced oxidative stress increases the risk of type 2 diabetes and cardiovascular disease in offspring due to fetal programming. We have previously shown that GDM impairs nuclear factor erythroid 2‐related factor 2 (Nrf2) mediated upregulation of heme oxygenase‐1 (HO‐1) and NAD(P)H: quinone oxidoreductase 1 (NQO1) expression in fetal umbilical vein endothelial cells (HUVEC).Methods and ResultsIn the present study, we examined whether SFN, a known electrophilic inducer of Nrf2, modulates antioxidant stress protein expression differentially in HUVEC from normal and GDM pregnancies. Cells were treated with SFN (2.5μM) for 0–24h, immunoblotted for HO‐1, NQO1 and Nrf2 and mRNA levels determined by qRT‐PCR. NQO1 activity was determined using the Prochaska assay. Immunfluorescence was employed to study nuclear translocation of Nrf2. Basal levels of HO‐1 and NQO1 mRNA and protein expression were significantly lower in GDM (p<0.05), however SFN significantly (p<0.05) upregulated mRNA (HO‐1 by ~5‐fold, NQO1 by ~2‐fold) and protein (12h and 24h) levels and increased NQO1 activity.ConclusionsOur findings suggest that impaired antioxidant defences in cells derived from GDM pregnancies, may be restored by SFN. We hypothesize that SFN may potentially maintain antioxidant defences and thereby delay the onset and consequences of GDM.Supported by British Heart Foundation
Pre‐diagnostic Leukocyte Genomic DNA Methylation and the Risk of Colorectal Cancer in Women
Authors: Cho Eunyoung , Nan Hongmei , Giovannucci Edward L. , Wu Kana , Selhub Jacob , Paul Ligi , Rosner Bernard , Fuchs Charles 
Published: June 2021

ObjectiveWe evaluated the association between pre‐diagnostic leukocyte genomic DNA methylation levels and colorectal cancer risk.MethodsWe conducted a nested case‐control study of 358 colorectal cancer cases and 661 matched controls within the Nurses’ Health Study of women. Among the controls, we further examined major plasma components in one‐carbon metabolism pathway in relation to genomic DNA methylation levels. Liquid chromatography electrospray ionization mass spectrometry method was used to measure DNA methylation. We calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) using logistic regression.ResultsGenomic DNA methylation levels were not associated with colorectal cancer risk. Compared with women in the lowest quintile of methylation, the multivariate OR of colorectal cancer was 1.32 (95% CI, 0.82–2.13) for those in the highest quintile (p for trend, 0.45). We did not find associations of major plasma components of one‐carbon metabolism or several risk factors for colorectal cancer with genomic DNA methylation levels. The plasma components and risk factors for colorectal cancer did not modify the association between genomic DNA methylation and colorectal cancer risk.ConclusionsWe found no evidence that hypomethylation of leukocyte genomic DNA increases risk of colorectal cancer among women. Additional studies are needed in other populations including men.Funding source: This work was supported by research grants CA136950 and CA55075 from the National Institutes of Health
Marginal zinc deficiency impairs ductal growth and alveologenesis in mammary glands leading to compromised secretory function
Authors: Bostanci Zeynep , Dempsey Colleen , Soybel David I , Kelleher Shannon L 
Published: June 2021

Post‐pubertal mammary gland (MG) growth consists of ductal elongation and side‐branching. With pregnancy, mammary epithelial cells proliferate, invade the stroma and differentiate to form alveoli in preparation for lactation. Zinc (Zn) regulates cell proliferation, differentiation and invasion. Women are at risk for marginal Zn deficiency due to decreased intake of bioavailable Zn compounded by increased Zn needs during pregnancy and lactation. We hypothesized that marginal Zn intake impairs post‐pubertal MG expansion and compromises secretory capacity during lactation. We fed female mice (n=10/group) control (CON; 30 μg/g) or marginal (ZD, 15 μg/g) Zn diet for 22 wk. ZD mice had significantly greater MG Zn content, fewer terminal end buds (59 ± 26 vs. 29 ± 19, p<0.05) and thinner ducts (48 ± 12 vs. 36 ± 7 μm, p<0.05). MG from ZD mice had less myoepithelial lining and peri‐ductal collagen which was associated with decreased estrogen receptor α staining. We next fed mice (n=12/group) a CON or ZD diet for 30 d prior to pregnancy through lactation d10. MG from ZD mice had fewer alveoli, less myoepithelial lining and less peri‐ductal collagen. ZD mice had lower milk secretion (0.9 ± 0.2 vs. 0.2 ± 0.1 g, p<0.05) and milk Zn concentration (374 ± 35 vs. 320 ± 37 μmol/L, p<0.05). These studies show that Zn is critical for MG growth, differentiation and function and suggest that marginal Zn intake may compromise breast function in women.Grant Funding Source: Intramural support from Departments of Nutritional Sciences and Surgery, NIH RO1 HD058614 to SLK
Maternal indicators and reported causes of perceived insufficient milk supply among a sample of Chinese mothers
Authors: Lou Zixin , Zeng Guo , Huang Lujiao , Wang Yu , Zhou Lan , Kavanagh Katherine 
Published: June 2021

Though breastfeeding initiation is high in China, exclusivity is rare. The study objective was to explore perceived indicators and causes of perceived insufficient milk (PIM) supply among Chinese mothers. A convenience sample, consisting of 392 mothers of healthy infants (<12 months of age), completed a questionnaire in a Maternal and Child Hospital in Chengdu, China. Three hundred and forty one surveys were considered eligible for analysis. Breastfeeding initiation (defined as ever offering the breast) was high (95.3%). However, 54.2% of mothers reported experiencing PIM, with 43.9% of these mothers reporting PIM occurring within 2 days postpartum. Primary maternal indicators of PIM were not feeling the presence of milk in the breast (36.9%), perceived lack of infant satiation after feeding (33.5%), and perceived post‐nursing infant fussiness (27.8%). Over one third of mothers reported not knowing what caused PIM (34.4%), 21.1% believed PIM to be caused by poor maternal appetite, and 13.1% believed a lack of maternal liquid intake to be the cause. PIM appears to be common among Chinese mothers, especially in the early post‐partum period, and it appears that mothers are using subjective indicators to reach this conclusion. Prenatal and early post‐partum interventions, assisting mothers to correctly assess milk supply, may result in improved exclusive breastfeeding rates in China.Grant Funding Source: The University of Tennessee, Department of Nutrition, the Office of the Dean, and the Office of Research (SARIF Award)
Perinatal and post‐weaning diets high in omega‐3 fatty acids upregulate genes involved in neurotrophin signaling
Authors: Balogun Kayode Adeniyi , Cheema Sukhinder Kaur 
Published: June 2021

We investigated the effects of perinatal and post‐weaning diets high in omega (n)‐3 polyunsaturated fatty acids (PUFA) on cerebral cortical phospholipid fatty acid composition, and the impact on mRNA expression of neurotrophins. Female C57BL/6 mice were fed semi‐purified diets (20% w/w fat) containing n‐6 to n‐3 PUFA ratios of 5:1 (high n‐3 PUFA) or 30:1 (low n‐3 PUFA) before mating, during pregnancy, and until weaning. Male offspring (n=8) continued on their mothers’ diets for four months. Brain cortex phospholipid fatty acids were determined by thin layer and gas chromatography, and mRNA expressions of brain‐derived neurotrophic factor (BDNF), nerve growth factor (NGF), cAMP response element binding protein (CREB), and TrkB were measured at weaning and four months. Docosahexanoic acid and total n‐3 PUFA were significantly higher in cortical phospholipids of the high n‐3 PUFA group compared to the low n‐3 PUFA group at weaning (P<0.0001), and at four months (P<0.05). The high n‐3 PUFA group showed a trend towards an increase in mRNA expressions of BDNF, NGF, and TrKB at weaning, however a significant (P<0.0001) increase was observed at four months in the high n‐3 PUFA group compared to low n‐3 PUFA group. Our data shows that accretion of n‐3 PUFA in the brain upregulates gene expression of neurotrophins and their target receptors, thereby stimulating neuroprotection and enhanced cognitive function. Supported by NSERCGrant Funding Source: NSERC
Maternal n‐3 Fatty Acid Supplementation Before and During Pregnancy Provides Neuroprotection after Neonatal Hypoxic‐ischemic Brain Injury
Authors: Fan Chaonan , Mayurasakorn Korapat , Ten Vadim S. , Qi Kemin , Deckelbaum Richard J. 
Published: June 2021

Acute n‐3 fatty acid (n‐3 FA) injection has been shown to markedly attenuate hypoxic‐ischemic (H/I) injury in neonatal mice. We now investigated the effects of maternal n‐3 FA supplementation during pregnancy on neonatal brain survival in a model of H/I injury. C57BL/6J female mice (12 week) were fed with one of two experimental diets: an n‐3 FA deficient diet and an n‐3 FA‐rich containing diet. The feeding regimens began one month before mouse conception and continued throughout gestation. Brain fatty acid composition and expression of pro‐apoptotic Bax, and anti‐apoptotic Bcl‐x were determined in pups at 7 d of age. H/I injury was produced by right carotid artery ligation and exposure to 8% O2 for 15 minutes in pups at 10 d of age. Compared to maternal n‐3 FA deficient diets, pups from n‐3 fed mothers had 2 fold higher brain concentrations of DHA and total n‐3 FA (p < 0.05), decreased Bax by 20% and increased Bcl‐x by 50% (p < 0.05). Cerebral infarct volumes at 24 hours after H/I were decreased in pups from n‐3 fed mothers compared to n‐3 FA deficient diets, 16.4% vs. 40.3%, respectively (p = 0.03). Our findings indicate that maternal n‐3 FA diet affects brain fatty acid composition, modulates apoptosis related gene expression in the off‐spring, and that these changes improve neuronal brain survival after H/I injury.Supported in part by NIH grants HL 40404 (RJD) and the International Training Fellowship from the Nutricia Research Foundation (2011‐T2).Grant Funding Source: Nutrition (ASN)
Ramping Up for STEM Success: New Models for Transfer
Authors: Albertine Susan 
Published: June 2021

Successful transfer of students from 2‐year colleges to 4‐year institutions is critical to their ultimate success in higher education, particularly in STEM fields. In this project, the Association of American Colleges & Universities (AAC&U) and Project Kaleidoscope (PKAL) planned and held two national convenings, organized as Action Labs, of selected community college/four‐year institution partnerships from six states. The partners were focused on developing effective models for STEM student transfer success. They emphasized holistic program models that go beyond coursework articulation agreements and build partnerships, programmatic alignment, and community.The presentation will report on findings, including key features of replicable and scalable models for STEM student success, emphasizing general education and entry into STEM baccalaureate programs.