bluuebunny/crossref_metadata_2025_split huggingface dataset:
Contribution of Inflammatory Markers to Changes in Bone in Postmenopausal Women: A 1‐Year Investigation
Authors: Gertz Erik R , Silverman Natalie , Wise Kristine S , Stewart Jeanne W , Hanson Kathy B , Alekel D Lee , Van Loan Marta D 
Published: June 2021

Bone formation and resorption can be influenced by inflammation as reflected by inflammatory markers. The objectives of our study were to examine the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determine the contribution of inflammatory markers to 1‐year changes in BMC and BMD in healthy postmenopausal women. Data from the Soy Isoflavones to Reduce Bone Loss study (n=235) were examined. BMC and BMD from the lumbar spine & total proximal femur (hip) were measured by dual energy x‐ray absorptiometry and 4% tibia by peripheral quantitative computed tomography. Inflammatory markers (C‐reactive protein (CRP), interleukin (IL)‐1β, IL‐6, TNF‐α) were measured at baseline, 6 & 12 mos. Significant negative associations among inflammatory markers (Il‐6, TNFα) were observed at 6 & 12 mo. for % change in hip, spine, and whole body BMC and BMD. There were no significant associations with inflammatory markers for 4% tibia BMC or BMD. Multiple regression analysis was used to model the contribution of inflammatory markers to %change in BMC and BMD, accounting for ~ 2–7% of the variance. Inflammatory markers made a small but significant contribution to the observed changes in BMC and BMD in healthy postmenopausal women.Research was supported by NIH‐NIAMS (RO1 AR046922), USDA/ARS, WHNRC, NWRC, ISU; CTSC, CCRC, UCD (1M01RR19975‐01), National Center for Medical Research (UL1 RR024146).
Leucine Supplementation of a Low Protein Meal Increases Skeletal Muscle and Visceral Tissue Protein Synthesis in Neonatal Pigs by Stimulating mTOR‐Dependent Translation Initiation
Authors: Torrazza Roberto Murgas , Suryawan Agus , Gazzaneo Maria C. , Orellana Renan A. , Nguyen Hanh V. , Davis Teresa A. 
Published: June 2021

Leucine appears to be the most effective single amino acid to trigger the activation of translation initiation factors that regulate protein synthesis in muscle. The effects of Leu in visceral tissues are not well understood. We hypothesized that enteral Leu supplementation of a low protein diet (LP) in neonatal pigs will acutely increase skeletal muscle and visceral tissue protein synthesis to a rate similar to that achieved by feeding a high protein diet (HP). Fasted 5‐d‐old piglets (n=21) were gavage fed at 0 and 60 min either: 1) LP diet, 2) low protein diet supplemented with Leu (LP+L) to equal HP diet, or 3) HP diet. Diets were isocaloric and lactose was equal. Fractional protein synthesis rates and translational control mechanisms were examined 90 min after feeding. Protein synthesis increased in longissimus dorsi, gastrocnemius, masseter, heart, jejunum, kidney and pancreas, but not liver, of the LP+L group compared to LP group alone and did not differ from HP group. LP+L and HP increased translational efficiency and phosphorylation of S6K1 and 4E‐BP1 in all tissues except liver. Our results suggest that low protein diets supplemented with leucine stimulates protein synthesis in muscle and most visceral tissues to a rate similar to that achieved by high protein diets and this stimulation involves activation of mTOR downstream effectors. (Supported by Ajinomoto Amino Acid Research Program and USDA 58‐6250‐6‐001).Grant Funding Source: Ajinomoto Amino Acid Research Program and USDA 58‐6250‐6‐001
Pregnancy and choline intake alter the metabolic use of orally consumed choline in women consuming deuterium labeled choline
Authors: Yan Jian , West Allyson , Perry Cydne , Jiang Xinyin , Yousef Leyla , Malysheva Olga , Devapatla Srisatish , Pressman Eva , Caudill Marie A. 
Published: June 2021

A 12‐week choline intervention study was conducted to investigate the effects of pregnancy and choline intake on the fate of orally consumed choline. Healthy non‐pregnant (n = 21) and pregnant women (n=27, 27wk gestation) were randomized to controlled choline intakes of either 450 (choline AI) or 900 mg/day; 350 mg/day dietary choline and either 100 or 550 mg/d supplemental choline chloride. During the last six weeks of the study, ~20% of the total choline intake was provided as deuterium labeled choline (d9‐choline). The labeling of choline and its metabolites was examined at the end of the study (wk 12) in plasma and urine. Pregnancy affected the use of dietary choline with higher concentrations of plasma d9‐choline (P = 0.008), lower concentrations of plasma d6‐dimethylglycine (d6‐DMG) (P < 0.001), and higher urinary d9‐choline excretion (P = 0.001) in pregnant women. A higher choline intake (900 vs 450 mg/d) yielded higher plasma concentrations of d9‐choline (P = 0.003), d6‐DMG (P = 0.02), and d‐9 betaine (especially in pregnant women; P= 0.002 for choline x pregnancy) as well as greater urinary d6‐DMG excretion (P = 0.006). These data show that (i) pregnancy alters the use of orally consumed choline and (ii) a choline intake level exceeding the choline AI increases the availability of labile methyl groups for one‐carbon metabolic reactions especially in pregnant women.Supported by grants from the USDA, ENC, and NCBA.
The effect of dietary fat and omega‐3 fatty acids on whole body lipid oxidation
Authors: Ainslie-Waldman Cheryl , Young Lindsay R. , Kurzer Mindy S. , Raatz Susan K. , Csallany A. Saari 
Published: June 2021

Lipid peroxidation of polyunsaturated fatty acids yields several electrophilic, reactive carbonyl metabolites. We hypothesized that an increased intake of omega‐3 fatty acids (n‐3) would lead to increased lipid peroxidation metabolites compared to a diet low in n‐3. As part of a randomized crossover dietary intervention trial, urinary markers of whole body lipid peroxidation were analyzed. Study subjects (n=15) included healthy, postmenopausal women who were fed a low‐fat diet (20% of energy from fat, LF) or low‐fat diet supplemented with 3% of energy from n‐3 fatty acids (LFn3) for 8 weeks. Urine was collected during two consecutive 24‐hour collections in the last two days of each diet. Whole body lipid peroxidation within each subject was measured via complementary methods. Analysis via urinary TBARS was followed by a sensitive HPLC separation and quantification of 2,4‐ dinitrophenylhydrazine‐reactive lipophilic aldehydes, including 4‐ hydroxynonenal, 4‐hydroxyhexenal, and other nonpolar aldehydes. The HPLC technique demonstrated that LFn3 resulted in increased levels of lipid peroxidation products by two‐fold relative to LF. These results show that increased n‐3 intake leads to increased production of in vivo secondary lipid peroxidation products. The impact of these results requires further investigation. This work was supported by the US DOD, NCI, NCRR, and Salmon of the Americas, Inc.Grant Funding Source: National Cancer Institute
RGD‐peptide lunasin inhibits PI3‐kinase/Akt‐mediated NF‐κB activation in human and murine macrophages through interaction with αvβ3 integrins
Authors: Cam Anthony , de Mejia Elvira Gonzalez 
Published: June 2021

Regulation of aberrant macrophage activity under inflammatory conditions is critical in the prevention of cardiovascular disease (CVD). Integrin receptor αvβ3 is highly expressed on macrophages in atherosclerotic lesions and binds Arg‐Gly‐Asp (RGD) ligands. Lunasin is a food derived peptide that contains a RGD cell adhesion motif. The objective was to comparatively determine the effect of lunasin on pro‐inflammatory markers from LPS‐induced RAW 264.7 murine and THP‐1 human macrophages and its role on αvβ3 integrins, important mediators of PI3K/Akt activation of NF‐κB. Lunasin significantly inhibited NO (IC50 = 41 μM; <10 μM), iNOS (IC35 = 36 μM; IC50 <10 μM), COX‐2 (IC50 = 31 μM; <10 μM) and p‐Akt (IC35 = 29 μM; IC50 = 11 μM) in murine and human macrophages, respectively. In RAW 264.7, lunasin significantly inhibited PGE2 (IC50 = 48 μM) and reduced nuclear NF‐κB subunits p65 and p50 by 26% and 43% at 50 μM, respectively. Lunasin significantly reduced p‐p65 (IC50 <10 μM) and αvβ3 integrin expression (IC50 = 10 μM) in THP‐1. Vitronectin, a ligand of αvβ3 integrin, internalizes and increases expression of pro‐inflammatory markers, whereas a PI3K inhibitor attenuated these effects. After treatment of both cell lines with lunasin, co‐immunoprecipitation confirmed direct interaction between lunasin and αvβ3 integrin. Lunasin reduced integrin‐mediated inflammatory responses and has potential in the prevention of CVD.Grant Funding Source : USDA
Initial Adipose Tissue Responses to High Milk‐fat Diet
Authors: Camell Christina , Smith Wayne 
Published: June 2021

Obesigenic diets cause inflammation in adipose tissue (AT) including infiltration of lymphocytes and macrophages. Changes in macrophage polarization are observed, which apparently reflect the tissue microenvironment including available cytokines and fatty‐acids. The project goal is to analyze very early responses to a diet high in milk‐fat (MF) that is rich in palmitic (16:0) and oleic (18:1) acid. We have examined AT molecular and cellular changes after 3 days of MF feeding, and utilized genetically‐deficient mice to test if TLR4 is necessary for diet‐induced effects. The earliest responses in wildtype (WT) mice were limited to the mesenteric AT (MAT) and peritoneal leukocytes. There were increases in gene expression in MAT including monocyte chemotactic factor (MCP)‐1, chemokine (C‐X‐C motif) ligand (CXCL)‐1, secreted phosphoprotein (SPP)‐1 and the macrophage marker: F4/80. Additionally, we identified a decrease in the number of low and high expressing F4/80 positive peritoneal macrophages. TLR4−/− mice failed to exhibit diet‐induced increases in MCP‐1 in the MAT, and they failed to exhibit the decrease in peritoneal macrophages seen in WT mice. They also exhibited hyper‐expression of anti‐inflammatory macrophage markers in the MAT, suggesting a biased response to the MF diet. To test for fatty‐acid specific action in macrophages an in‐vitro model of fatty‐acid treatment was utilized. RAW 264.7 cells upregulated pro‐inflammatory macrophage markers (eg. TNF‐α) upon treatment with palmitic acid while oleic acid treatment upregulated anti‐inflammatory markers (eg. Arginase‐1). Treatment with a mixture of palmitic and oleic acid inhibited genes upregulated by treatment with a single fatty acid. These results suggest the early changes in response to a MF diet are localized in the mesentery and involve peritoneal cells, ATMs and their response to fatty‐acids.Grant Funding Source : F31DK084841; USDA 6250‐51000‐055
Magnesium Oxide Nanoparticles Induce Cytotoxic and Proinflammatory Effects in Schwann cells and DRG Neurons
Authors: Idikuda Vinaykumar , Jaiswal Ashvin , wong Yin Yin wendy , leung solomon , Daniels christopher , lai james 
Published: June 2021

Applications of metal oxide nanoparticles in diverse fields have been accelerating in the last decade. For example, magnesium oxide (MgO) nanoparticles have been employed in ceramics, and as adhesive and additive in chemical raw materials, leading to their increased human exposure, thereby posing potential health hazards. We have therefore investigated the hypothesis that MgO nanoparticles exert differential cytotoxic effects on neural cells in the peripheral nervous system employing cell models consisting of Schwann cells and dorsal root ganglion neurons (DRG) in vitro. Results of our ongoing studies revealed MgO nanoparticles exerted differential effects on lowering the survival of Schwann cells and DRG neurons. Along with their morphological changes, we also found the nanoparticles induced differential dose‐related increases in expression of markers of inflammatory responses such as Interleukin‐6 (IL‐6) and Peroxisome Proliferated Activated Receptor PPAR‐? in the two neural cell types. Thus, our results suggest that MgO nanoparticles can induce differential cytotoxic effects and elicit inflammatory responses in Schwann cells and DRG neurons and as such may have implications in health hazard of human exposure to the nanoparticles.Supported by: USAMRMC project grant (contract#W81xWH‐07‐2‐0078) and NIH grant #P20 RR016454 from Idaho INBRE program of the National Center for Research Resources.
Overexpression of mitochondrial GSH transporters in renal proximal tubular cells from control and diabetic rats
Authors: Lash Lawrence Harold , Benipal Bavneet , Putt David Alan 
Published: June 2021

We hypothesize that overexpression of mitochondrial glutathione (mtGSH) transporters in renal proximal tubular (PT) cells from diabetic rats will reverse the oxidative stress and diminish susceptibility to chemically induced cytotoxicity by producing sustained increases in mtGSH content. cDNAs encoding either the dicarboxylate (DIC; Slc25a10) or 2‐oxoglutarate (OGC; Slc25a11) carrier were expressed in renal PT cells from either control or streptozotocin‐induced diabetic Sprague‐Dawley rats using Lipofectamine. Transfection with either DIC or OGC cDNA produced 7,800‐ or 5,000‐fold increases in DIC or OGC mRNA, respectively, in cells from control rats and 600‐ and 1900‐fold increases in DIC or OGC mRNA, respectively, in cells from diabetic rats. Carrier overexpression provided significant protection, as judged by LDH release and MTT fluorescence, from injury due to the mitochondrial toxicant antimycin A. These results suggest that mtGSH carrier overexpression may be a viable approach to improving redox status of renal cells in chronic disease states.(Supported by DOD Grant PR64340)
Anti‐Phase Expression of the BK Channel (Kcnma1) Alters Circadian Locomotor Activity in Mice
Authors: Lai Michael , Wright Breanne , Whitt Joshua , Meredith Andrea 
Published: June 2021

Circadian rhythmicity, driven by the suprachiasmatic nucleus (SCN) of the hypothalamus, is essential to the survival or fitness of all organisms. The BK Ca2+ and voltage‐activated K+ channel is expressed in a circadian manner in the SCN, peaking at night, and genetic deletion of the BK channel (Kcnma1−/−) disrupts circadian behavioral rhythms. To determine whether the nighttime‐phased expression pattern was essential for normal circadian rhythmicity, we analyzed wheel running activity of transgenic mice that expressed the BK channel opposite to its normal phase in the SCN (Per1:BKR207Q ). We predicted this alteration of BK phase by expression of one or two copies (1C, 2C) of the Per1:BKR207Q transgene, or one copy of Per1:BKR207Q with one deleted endogenous copy of Kcnma1 (1C; BK het) would disrupt circadian wheel rhythms. In contrast, 1C, 2C, and 1C; BK het mice all had relatively normal baseline circadian rhythms. However, 2C mice had a longer active interval compared to WT, suggesting that nighttime‐phased expression of the BK channel is important for restricting locomotor activity. Additionally, 2C mice had a larger light‐pulse induced phase delays, suggesting these mice were more sensitive to phase‐shifting stimuli than WT. A better understanding of the neural encoding of circadian rhythms may impact the treatment of sleep and other disorders of circadian rhythmicity.This work was funded by an APS summer research fellowship to (B.N.W.) and NSF (IOS‐0956237) and NHLBI (R01HL102758) to A.L.M.
Anion transporter links to urolithiasis and hepatotoxicity
Authors: Markovich Daniel , McLeay Sarah , Lee Soohyun 
Published: June 2021

Urolithiasis and hepatotoxicity are linked to perturbations in oxalate and sulfate homeostasis. Urolithiasis is a common disorder leading to significant health care costs. Drug‐induced liver damage is a major cause of death in patients with acute liver failure. Sat1 (Slc26a1) is an anion transporter that mediates epithelial transport of oxalate and sulfate in the kidney, liver and intestine. Creation of Sat1 null (Sat1−/−) mice revealed the physiological roles of Slc26a1 in vivo. Sat1−/− mice exhibit hyperoxaluria with hyperoxalemia, nephrocalcinosis and calcium oxalate stones in their renal tubules and bladder. Sat1−/− mice also have hypersulfaturia, hyposulfatemia and enhanced liver toxicity when subjected to drugs such as acetaminophen. These data suggest Sat1 regulates both oxalate and sulfate homeostasis and is critical to the development of calcium oxalate urolithiasis and hepatotoxicity.Funding from NHMRC, ARC and CCQ grants.
FGF signaling is involved in physiological adaptation to pressure overload in developing heart
Authors: Krejci Eliska , Pesevski Zivorad , Nanka Ondrej , Sedmera David 
Published: June 2021

Fibroblast growth factors (FGFs) play an important role during embryonic induction, growth and patterning. Exogenous FGF2 as well as pressure loading were shown to induce embryonic myocyte proliferation. Here we tested whether FGF2 signaling is involved in transmission of pressure overload to increased myocyte proliferation in vivo.Pressure overload was induced by conotruncus constriction in Stage 21 chick embryos. Anti‐bromodeoxyuridine labeling was used to assess proliferation at 24, 48 and 72 h. Western blotting and RT‐PCR to measure FGF2 protein and mRNA levels was performed on ventricular extracts at 48 h interval. Blood was collected at 48 h to assess the amount of FGF2 in serum by ELISA. Proliferation of ventricular myocytes was increased significantly at 48 h. Neither western blotting, nor immunohistochemistry revealed any changes in the amount of myocardial FGF2. ELISA showed a 93% increase of FGF2 in the serum. Increased amount of FGF2 mRNA in ventricular myocardium was confirmed by real time PCR.We conclude that FGF2 synthesis is increased in embryonic ventricular cardiomyocytes in response to increased stretch due to pressure overload. Increased stretch causes its release into serum, causing it to act in endocrine, rather then paracrine manner.Supported by Ministry of Education VZ 0021620806, ASCR AV0Z50450515 and AV0Z50110509 and GACR P302/11/1308.Grant Funding Source : P302/11/1308
Notch signaling through the Jagged‐1 ligand regulates mesenchymal progenitor differentiation and tissue regeneration
Authors: Hankenson Kurt D 
Published: June 2021

Notch signaling regulates stem cell differentiation and expansion and influences formation and maintenance of bone. Loss‐of‐function mutations in the Notch ligand Jagged‐1, which are associated with Allagille's Syndrome, result in decreased bone mass. Notch signaling is also implicated in modulating the regeneration of a variety of non‐mineralized tissues. We hypothesize that Notch signaling through Jagged‐1 is crucial for bone regeneration through the regulation of mesenchymal progenitor cell (mesenchymal stem cell – MSC) expansion and differentiation. Canonical notch signaling through Jagged‐1 has pleiotropic, variable effects on MSC lineage progression and proliferation. Jagged‐1 activity is influenced by bone morphogenetic signaling and modulatory proteins of the thrombospondin family. Blocking canonical Notch signaling in mice results in age‐associated bone loss, while mice with conditional deletion of Jagged‐1 show related alterations in bone mass. Notch signaling is up‐regulated during both intramembranous and endochondral bone regeneration and corresponds to increases in expression of Jagged‐1. Jagged‐1 can be coupled to biodegradable biomaterials and induces increased osteoblast differentiation of MSC. Jagged‐1 coupled biomaterial can then be implanted at the site of bone defects and used to modulate bone regeneration.This work was supported by the DOD and NIH.
The expanded repertoire of a classical intranuclear domain
Authors: Pederson Thoru 
Published: June 2021

The first structure to be observed within the cell nucleus was the nucleolus, described in 1836–1839. A century would go by before it was found that this intranuclear domain is the site of ribosome biosynthesis. After another three decades, my laboratory discovered that the nucleolus also is the assembly site of the signal recognition particle, a ribonucleoprotein complex involved in the synthesis on membrane and secreted proteins. This unanticipated finding prompted us to consider yet additional functions, leading us and others to the finding that the nucleolus is involved in cell cycle control. Recently, and most surprising of all, we have found that the nucleoli of myogenic stem cells harbor a set of microRNAs, suggesting a role for this intranuclear domain beyond anything previously even remotely imagined. We are presently trying to understand the meaning of these nucleolar microRNAs and will report an initial clue. Keeping an open mind has proven essential in our work on the nucleolus.Supported by grants from NIH, NSF and the Human Frontier Science Program Organization.
What do College Students Want? A Qualitative Study Exploring Nutrition Language and Knowledge
Authors: Hirshberg Shira , Lipschitz Jessica , Lofgren Ingrid 
Published: June 2021

Overweight and obesity can cause dyslipidemia, which has been reported in college students. Dietary therapy is an ideal form of treatment for young adults because it is effective, economical, and safe. The Focus on Food Project conducted student focus groups (N= 38) at a mid‐sized northeastern university. The sample was 68.4% female, 19.0 ± 0.9 years old and mean body mass index was 23.1 ± 2.9 kg/m2. Qualitative analysis included data reduction, display, conclusion drawing and verification and coding and data display used NVivo 9. Analysis highlighted several themes; first, students use language different from that of common health messages (i.e “greasy” instead of “high in fat”). Second, students care about nutrition and want more information in the dining halls, including nutrition facts‐type labels and ideas for quick, healthful meals. Third, students were knowledgeable about the health benefits of fruits and vegetables, the importance of moderation and variety, and the health concerns related to consuming sugary beverages. Fourth, they are unsure of how to eat healthfully on‐campus and of the difference between healthful and unhealthful fats, and do not know where to obtain reliable nutrition information. Findings provide awareness of student language and knowledge that can direct nutrition educators in creating relevant, appropriate and attention‐grabbing education programs for college students.Research was supported by the USDAGrant Funding Source: USDA
Effect of ω3 PUFA on diet induced non‐alcoholic fatty liver disease (NAFLD) development and progression in C57BL/6J mice
Authors: Depner Christopher M , Jump Donald B 
Published: June 2021

The incidence of NAFLD and non‐alcoholic steatohepatitis (NASH) has increased in parallel with obesity. While both are characterized by excessive hepatic lipid accumulation, NASH is defined as hepatic inflammation with hepatocellular damage. Our goal was to examine the effect of C20–22 ω3 PUFA on diet induced NASH in LDLR−/− C57BL/6J mice. Mice consumed the Western Diet (WD) supplemented with olive oil, eicosapentaenoic acid (20:5ω3; EPA), docosahexaenoic acid (22:6 ω3; DHA) or both EPA and DHA for 16 weeks. The WD induced a severe phenotype similar to human NASH; including robust induction of hepatosteatosis, inflammation (MCP1) and fibrosis (ProCol1α1). While dietary C20–22 ω3 PUFA failed to suppress hepatic steatosis, ω3 PUFA attenuated markers of inflammation, fibrosis, and liver damage (plasma ALT, AST). The ω3 PUFA effect on inflammation & fibrosis correlated with the down regulation of multiple transcripts involved in toll‐like receptor signaling (TRL2, TRL4, CD14). Moreover, DHA was significantly more effective than EPA or the combination of EPA & DHA at suppressing markers of inflammation and fibrosis associated with NASH. Thus, dietary ω3 PUFA attenuates inflammation & fibrosis without suppressing hepatic lipid.Research Support: USDA Grant 2009‐65200‐05846