bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biochemical diversity of human skeletal muscle
Authors: Tirrell Timothy F , Cook Mark , Carr John A , Choi Anthony J , Lin Evie , Esparza Mary C , Ward Samuel R , Lieber Richard L 
Published: June 2021

INTRODUCTIONThe molecular components largely responsible for muscle attributes such as passive tension development (titin and collagen), active tension development (myosin heavy chain [MHC]), and mechanosensitive signaling (titin) are well studied in animals but less is known about their roles in humans.METHODS599 biopsies were obtained from 6 human cadaveric donors. Three assays were performed on each biopsy ‐ titin molecular weight determination, hydroxyproline content (a surrogate for collagen content), and MHC isoform distribution.RESULTSDiscriminant function analysis (DFA) showed that titin MW was the strongest predictive factor of anatomic region and muscle functional group. On average, human muscles had more slow myosin than lower mammals. Average %MHC‐1 of muscles in this study was 65% (compare to 6% for mouse, 8% for rat, and 19% for rabbit). Overall, larger titins were associated with faster muscles.DISCUSSIONThe finding that titin was the strongest discriminating factor for DFA with anatomic region and muscle functional group as grouping variables is unexpected; titin is currently primarily considered to be a signal transduction cascade activator or determinant of passive tension. The titin‐MHC‐1 relationship we observed is opposite to that previously observed in rabbits, where large titins were associated with slower muscles.
Maternal Continuous vs. Intermittent Exercise and the Fetal heart
Authors: May Linda Elizabeth , Suminski Richard R , Gustafson Kathleen M 
Published: June 2021

ObjectiveWe tested the hypothesis that regular intermittent exercise (i.e. yoga) during pregnancy is associated with changes in fetal cardiac development.MethodsWe used magnetocardiograms from 32 and 36 week fetuses (N=60). We marked normal R‐peaks to measure heart rate (HR) and heart rate variability (HRV). Activity questionnaires were used to calculate time (minutes) and intensity (kcal/min) for continuous and intermittent exercise per trimester. Correlation and regression analysis was performed. Maternal pre‐pregnancy BMI, weight gain, and fetal activity state were also assessed.ResultsMaternal body weight and BMI was not correlated with fetal measurements. Only 3rd trimester maternal activity was significantly related to fetal measures. Total continuous time is significantly associated with fetal HRV (VLF; p=0.04). Continuous intensity is significantly associated with lower fetal HR (p=0.03). Total time spent in intermittent activity is significantly associated with increased HRV (p≤0.04). There is no significant effect on fetal sympathovagal balance.ConclusionMaternal time spent exercising appears to be consistently important in influencing fetal heart outcomes. These data suggest a combination of continuous and intermittent exercise provide fetal heart benefits. Further studies need to be done to determine if noncontinuous exercise alone provides fetal cardiac changes.Grant Funding Source : none
Pre‐pregnancy BMI Impacts Bone Loss across Pregnancy in Adolescents
Authors: Young Bridget E , McNanley Thomas , Cooper Beth , Witter Frank , Harris Z. Leah , O'Brien Kimberly 
Published: June 2021

Pregnant teens may be at increased risk for pregnancy‐induced bone loss. To assess the impact of dietary Ca and vitamin D status on bone loss, 171 teens (13–18 yrs) were followed from 22.3±5.9 weeks of gestation through delivery. Bone quality was assessed up to three times across pregnancy using calcaneus heel ultrasound (US) measures. Vitamin D, calcitropic hormones, and osteoprotegerin (OPG) were assessed at mid‐gestation and delivery. Speed of sound (SOS) at the heel decreased as pregnancy progressed (p<0.001, after controlling for multiple measures). SOS decreased by 8.6±17.0 m/s (over an 11.7±5.6 week interval), which is equivalent to a 0.28±0.54 decrease in T‐score. The change in SOS/week was positively associated with pre‐pregnancy weight (p=0.012) and BMI (p=0.007), such that heavier teens experienced less bone loss. Bone loss did not differ by race, age, gynecological age, or diet (caloric, protein, or Ca intake). The decrease in SOS across pregnancy was not influenced by mid‐gestation or delivery 25(OH)D, calcitriol, or PTH concentrations. Teens who did not lose bone SOS exhibited a trend for higher OPG at delivery (p=0.089). Maternal bone loss was not associated with infant weight, ponderal index, or gestational age at birth. These findings suggest that teens are at risk for pregnancy‐induced bone loss and BMI pre‐conception plays a role in adolescents’ skeletal response to pregnancy.USDA: 2005‐35200
Choline dehydrogenase polymorphism rs12676 is a functional variation associated with changes in human sperm cell function
Authors: Johnson Amy Rose , Lao Sai , Wang Tongwen , Galanko Joseph , Zeisel Steven 
Published: June 2021

Approximately 15% of couples are affected by infertility and up to half of these cases arise from male factor infertility. Unidentified genetic aberrations such as chromosomal deletions, translocations and single nucleotide polymorphisms (SNPs) may be the underlying cause of many cases of idiopathic male infertility. Choline dehydrogenase (CHDH), a mitochondrial enzyme, catalyzes the conversion of choline to betaine, a methyl group donor and organic osmolyte. Deletion of the Chdh gene in mice results in decreased male fertility due to diminished sperm motility; sperm from Chdh−/− males have decreased ATP concentrations likely stemming from abnormal sperm mitochondrial morphology and function in these cells. SNPs have been identified in the human CHDH gene that may result in altered CHDH enzymatic activity. rs12676 (G233T), a non‐synonymous SNP located in the CHDH coding region, is associated with increased susceptibility to dietary choline deficiency and risk of breast cancer. We now report evidence that this SNP is also associated with altered sperm motility patterns and dysmorphic mitochondrial structure in sperm. Sperm produced by men who are GT or TT for rs12676 have 40% and 73% lower ATP concentrations, respectively, in their sperm. rs12676 is associated with decreased CHDH protein in human hepatocytes. We hypothesize that nutritional intervention involving dietary betaine supplementation may improve the function of sperm produced by men with the rs12676 SNP. This research was funded by NIH grants DK055865 and DK056350.Grant Funding Source: National Institutes of Health
Regulatory T cells: a mechanism for impaired immunity to influenza infection in obese mice?
Authors: Milner J Justin , Paich Heather A , Sheridan Patricia A , Beck Melinda A 
Published: June 2021

Obese individuals are at greater risk of morbidity and mortality when infected with pandemic influenza. The underlying mechanism for the increased risk is unknown, although our work in a vaccinated obese population suggests an impaired immune response. Using a mouse model to study the immune response to influenza infection under conditions of diet‐induced obesity, we previously found reduced NK cell activity, impaired dendritric cell function, and failure of CD8+ T cells to respond to virus. What could cause this seemingly global immune failure? One possibility is alterations in the highly suppressive T cell subset, regulatory T cells (Tregs). CD25+Foxp3+ Tregs regulate nearly all aspects of the immune response, making them a plausible candidate for the impaired immunity in obese mice and likely obese humans. Diet‐induced obese and lean mice were infected with a mild dose of influenza A/PR/8/34. Obese mice had a greater number of Tregs in the lungs during the peak of the adaptive immune response. At an increased dose, obese mice had a greater percentage and number of Tregs in mediastinal lymph nodes. Further, Tregs isolated from obese mice were found to be less suppressive and more proliferative than those of lean mice. This data suggests that alterations in Treg distribution and function may be a novel, modifiable mechanism contributing to the impaired immune response and worse outcome to infection in the obese.Grant Funding Source : NORC DK56350
Early life growth trajectories and future risk for overweight
Authors: Jones-Smith Jessica C , Laraia Barbara , Neufeld Lynnette M , Fernald Lia C.H. 
Published: June 2021

Using a newly developed statistical technique, our objective was to test whether key aspects of growth trajectories between 0–24 months of age, such as size, velocity, and timing of peak velocity, were independently associated with overweight in late childhood. We used data from a birth cohort in Mexico (n=586) and the SuperImposition by Translation and Rotation (SITAR) method to estimate infant/childhood (0–24 months) growth trajectories for BMI, height, and weight. The SITAR method uses a nonlinear random‐effects model to estimate the average growth curve and each individual's deviation from this average curve on three dimensions—size, velocity, and timing of peak velocity. In separate models for each of the anthropometric measures (BMI, height, and weight), logistic regression estimated the association between overweight in late childhood and size, velocity, and timing of the BMI/height/weight trajectory. In crude models, relative BMI/height/weight (size) and BMI/height/weight velocity during 0–24 months were each associated with increased odds of overweight. In the mutually‐adjusted models, only relative BMI/height/weight (size), but not velocity, remained statistically significant. We found no evidence that the association between velocity and overweight varied by size. These results are not consistent with the hypothesis that growth velocity in infancy programs future risk for overweight.Grant Funding Source : This work was supported by pilot funds from the Berkeley Population Center NICHD R21 (HD056581).
Conduction abnormalities in metabolically stressed CD36 deficient mouse
Authors: Sulkin Matthew S , Pietka Terri A , Abumrad Nada A , Efimov Igor R 
Published: June 2021

CD36 facilitates myocardial uptake of fatty acids (FA), and has recently been shown to be involved in the regulation of intracellular Ca2+ dynamics in both non‐electrically excitable cells and cardiomyocytes. The heart derives the majority of its energy from FA oxidation and during fasting as glucose utilization diminishes, the heart has an even greater reliance on FA. We investigated whether CD36 dysfunction would accelerate metabolic changes during fasting (18 hrs) that would lead to electrophysiological abnormalities. Conscious non‐anesthetized wild type (WT) (n=5) and CD36 knock out (CD36 KO) (n=5) mice were placed in a restraining device to obtain a baseline ECG before and after fasting. Following fasting, hearts were excised, Langendorff perfused, and subjected to several pacing protocols while being optically mapped. Before fasting, RR, PR, and QTc values were not significant (NS) (p>.05) between groups. After fasting, WT mice displayed a NS increase in RR (75.7 ± 1.0 to 85.4 ± 2.9 ms) and PR (32.8 ± 0.9 to 36.2 ±0.9); whereas, CD36 KO mice showed a significant increase in RR (78.2 ± 1.2 to 120 ± 7.5 ms) and PR (35.9 ±0.9 to 58.7 ± 3.8). CD36 KO mice exhibited a significant increase in the effective refractory period of the atrioventricular (AV) node, ventricular action potential duration, cycle length with which Wenchebach block was observed, and a NS increase in AV‐delay.This work was supported by NIH Grants P01‐HL057278, R01 DK33301.
Inhibitory effect of adiponectin on breast cancer cell growth: evidences of the crucial role of ERα expression
Authors: Mauro Loredana , Pellegrino Michele , De Amicis Francesca , Giordano Cinzia , Andò Sebastiano 
Published: June 2021

Adiponectin (adipo) has emerged as a possible link between obesity and breast cancer. Here, we demonstrated that adipo inhibited proliferation in ER‐negative cells, while stimulated growth in MCF‐7 cells. Adipo transactivated ERα in MCF‐7 cells and upregulated mRNA and protein content of the estrogen target gene cyclin D1 (CD1) involved in cell cycle progression. In contrast, in MDA‐MB‐231 cells adipo induced a downregulation of CD1 expression. The latter findings fitted with the opposite effects of adipo on CD1 promoter elicited in the two different cell lines. Mutagenesis studies and ChIP assays revealed that the Sp1 motif, present on CD1 promoter, was important for the modulatory role of adipo on CD1 promoter activity. In the presence of ERα, ChIP analysis revealed an increase in Sp1/ERα complex, concomitant with an enhanced Pol II and pCAF recruitment, addressing the involvement of an activator complex that mediated the adipo‐induced transcriptional activation of CD1. In contrast, in the absence of ERα, adipo exposure increased the recruitment of corepressors SMRT and NCoR and the association of HDAC‐1, that correlated with a significant decrease in Pol II on Sp1 site. Thus, we propose that the possible mechanism through which adipo may modulate CD1 expression affecting breast cancer growth is tightly related to the estrogen receptor dependency.The research has been supported by AIRC MFAG 6180.
Growth Factor Signaling Pathways in Lung Development and Cancer
Authors: Yin Yongjun , Hill Ashley , Ornitz David M 
Published: June 2021

Lung mesenchyme is a critical determinant of the shape and size of the lung, the extent and patterning of epithelial branching, the formation of the pulmonary vasculature, and the formation of mesenchymal components of the adult lung. Fibroblast Growth Factor 9 (FGF9) is expressed in developing lung epithelium and mesothelium and has an essential primary role in regulating mesenchymal growth and differentiation through signaling to mesenchymal FGF receptors (FGFRs) 1 and 2.Pleuropulmonary Blastoma (PPB) is a pediatric lung cancer syndrome with onset in late gestation and early childhood. PPB is a unique lung cancer in that its cellular origins are derived from lung mesenchyme. Germline loss‐of‐function mutations in Dicer1, an essential gene for the production of microRNAs, predisposes to PPB in humans. In this talk I will discus mechanisms by which FGF9 regulates mesenchymal growth and differentiation, evidence that Fgf9 may be regulated by microRNAs during lung development, and evidence that FGF9 may be an important factor for the initiation PPB.This work is funded by a grant from the March of Dimes foundation.
In vivo magnetic resonance spectroscopy of lipid handling in steatotic rat liver
Authors: Janssens Sharon , Jonkers Richard AM , van Riel Natal AW , Nicolay Klaas , Prompers Jeanine J 
Published: June 2021

ObjectiveExamine lipid handling in liver of rats fed with different high‐fat diets using 1H‐[13C] magnetic resonance spectroscopy (MRS) together with oral administration of 13C labeled lipids.Methods6 male Wistar rats (11 weeks old; 348 ± 8g) were divided into three diet groups: low‐fat (10% fat, CON), high‐fat lard (45% fat, HFL), and high‐fat palm oil (45%, HFP). After 10 weeks of diet, MRS experiments were performed at baseline, and 4 and 24 h after oral administration of 1.5 g [U‐13C] Algal lipid mixture per kg body weight.ResultsAt 4 h after administration of the 13C labeled lipids, 13C enrichment of intracellular liver lipids was similarly increased in all three groups compared to baseline (CON: 0.031 ± 0.017 %; HFL: 0.045 ± 0.022 %; HFP: 0.033 ± 0.013 %), demonstrating that lipid uptake was not affected by the diet regimen. At 24 h, on the other hand, 13C enrichment of liver lipids decreased in CON, whereas in both high‐fat diet groups the 13C enrichment did not change compared to 4 h, indicating a lower turnover of the stored liver lipids.ConclusionHigh‐fat diet feeding did not alter liver lipid uptake in rats, but resulted in a decreased turnover of the lipids stored in the liver. This research was funded by the Netherlands Consortium for Systems Biology (NCSB) which is part of the Netherlands Genomics Initiative/Netherlands Organisation for Scientific Research.
Identification of genetic loci controlling intestinal calcium (Ca) absorption using BXD recombinant inbred (RI) mice fed high or low dietary Ca
Authors: Replogle Rebecca , Wang Libo , Zhang Min , Fleet James 
Published: June 2021

Intestinal Ca absorption (Ca Abs) is affected by race and is similar between mothers and daughters suggesting genetic regulation of this trait. However, the impact of genetics on CaAbs and the adaptation of Ca Abs to inadequate dietary Ca intake is not known. We examined the role of genetics on Ca Abs efficiency in 51 lines of BXD RI mice. Mice were fed AIN93G diets with either 0.5% or 0.25% Ca from 4 to 12 wks of age (n=8/line/diet). Afterwards, Ca Abs was measured by Ca45 appearance in the blood 10 min after an oral gavage of 0.1 mM Ca. After correcting for covariates, considerable diversity was observed between the lines in Ca Abs on each diet. Narrow‐sense heritability for Ca Abs was 0.37 and 0.56 in the 0.5% and 0.25% Ca diets, respectively, demonstrating increased penetrance of genetic effects controlling Ca Abs with low Ca diets. Linkage mapping was conducted using both traditional and Bayesian methods. Quantitative trait loci (QTL) affecting Ca Abs were identified that were diet‐specific (0.25%: on Chr 5, 8 (distal), 9, 12, 17; 0.5% on Chr 8 (proximal), 10) and shared (Chr 4, 7). No known Ca regulatory genes were found around these QTL demonstrating the potential of this approach for discovery of new genes controlling Ca Abs. This study provides a foundation for determining genetic regulators that may underlie individual differences in Ca Abs and ultimately dietary Ca requirements. Supported by NIEHS award ES019103.Grant Funding Source : NIEHS
Bioactive compounds of dealcoholized fermented berry fruit beverages inhibit inflammation in vitro and are a good source of antioxidants
Authors: Johnson Michelle , de Mejia Elvira Gonzalez , Lila Mary Ann , Yousef Gad G 
Published: June 2021

Berries are one of the best dietary sources of polyphenolic compounds and are associated with decreased markers of chronic inflammation linked with metabolic diseases. The objective was to evaluate bioactive compounds from dealcoholized blueberry‐blackberry fermented beverages in order to optimize blends based on in vitro inhibition of markers of inflammation and antioxidant capacity. Polyphenolic‐enriched fractions obtained from fermented beverages were analyzed. Main anthocyanins (ANCY) in blueberry and blackberry blended beverages, as identified by HPLC, were malvidin‐3‐glucoside and delphinidin‐3‐arabinoside. Total anthocyanins in enriched fractions ranged from 642 to 1550 mg/ml, cyanidin‐3‐glucoside (C3G) equivalents. Antioxidant capacity ranged from 5.2 ± 0.3 to 16.4 ± 1.8 and 6.2 ± 0.8 to 8.1 ± 1.0 mmol trolox equivalents (TE)/L for the ANCY‐ and proanthocyanidin (PAC)‐enriched fractions, respectively. None of the fractions were cytotoxic to macrophages at concentrations up to 100 μM C3G equivalents, the concentration used to measure markers of inflammation iNOS, COX‐2, PGE‐2, IL‐6, TNF‐α, and NF‐κB. The in vitro anti‐inflammatory activities were correlated with total anthocyanins and antioxidant capacity. These results suggest that bioactive compounds in highbush blueberry and blackberry fermented beverages are beneficial sources of antioxidants and inhibitors of inflammation.Grant Funding Source: Office of Research, Dixon Springs Research Center
Ecklonia cava polyphenol prevents ethanol‐induced liver injury in rats
Authors: Kojima-Yuasa Akiko , Takahashi Mai , Tabuchi Masaki , Akahoshi Yasumitsu , Terada Masaki , Matsui-Yuasa Isao 
Published: June 2021

IntroductionThe development of alcoholic liver disease is a complex process involving both the parenchymal and non‐parenchymal cells in the liver. Here, we examined the effect of the extract of Ecklonia cava, a brown algae, on ethanol‐induced liver injury.Methods1) Isolated hepatocytes or hepatic stellate cells (HSCs) were cultured with or without 100 mM ethanol. The cells were cultured with Ecklonia cava polyphenol (ECP) (0~25 μg/ml) for 0~24 hrs. 2) Male Wistar rats were fed a diet with or without 0.02 or 0.2% ECP. Animals were given drinking 5% (v/v) ethanol with two doses of CCl4 (0.1 ml/kg BW, i.p.) weekly for 3 weeks.ResultsIn cultured hepatocytes, the treatment of ECP suppressed ethanol‐induced increase in cell death via the protecting the levels of intracellular glutathione (GSH). In HSCs, the treatment with ECP suppressed ethanol‐induced increase in expression of type I collagen and α‐SMA via the remaining the levels of intracellular ROS and GSH. It has been reported that hepatic histological changes in ethanol‐CCl4 induced fibrosis model were similar to those found in human alcoholic cirrhosis. Therefore, we examined the effect of ECP on serum AST and ALT activities and liver fibrosis in rats treated with ethanol plus CCl4. The treatment of ECP suppressed the leakage of AST and ALT in the ethanol plus CCl4 treated rats. The collagen accumulation in the liver and hepatic necrosis was observed in ethanol plus CCl4 treated rats, but ECP treatment totally protected against ethanol plus CCl4 induced liver fibrosis and necrosis.ConclusionThese results suggest that ECP may be a candidate for preventing ethanol‐induced liver injury.
IFNg influences epithelial proliferation by modulating Aktbeta catenin signaling downstream of cadherins.
Authors: Dominguez Porfirio Nava , Kolegraff Keli N. , Koch Stefan , Parkos Charles , Nusrat Asma 
Published: June 2021

Intestinal mucosal inflammation in inflammatory bowel disease (IBD) is associated with perturbed intestinal epithelial homeostasis (proliferation/differentiation) and barrier function that are mediated, in part, by pro‐inflammatory cytokines such as IFNγ. However, the mechanisms governing IFNγ‐mediated regulation of epithelial homeostasis (proliferation/differentiation) and barrier function are not understood. Since a master regulator of epithelial homeostasis is E‐cadherin we investigated if IFNγ modulates epithelial homeostasis by regulating signaling proteins downstream of intestinal epithelial cadherins that also regulate cell proliferation. Using complementary in vitro and in vivo approaches, we identified protein kinase B (PKB/Akt) as a key protein that regulates stability of b‐catenin down‐stream of Ecadherin. IFNγ but not TNFα was observed to initially promote phosphorylation and activation of Akt and β‐catenin resulting in a burst of cell proliferation. However, sustained exposure to IFNγ induced stabilization of E‐cadherin and β‐catenin that was dependent on the cytoplasmic scaffold protein, 14‐3‐3ζ and Akt resulted in inhibition of β‐catenin induced cell proliferation. These results provide a novel paradigm through which sustained exposure to IFNγ results in inhibition β‐catenin signaling, reduced cell proliferation and barrier function in IBD.This work was supported by CCFA Fellowship and AGA Research Scholar Awards (PN) and NIH grants DK61379 (CP), DK55679 and DK59888 (AN).