bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Regulation of Protein Synthesis and mTOR Signaling in Skeletal Muscle and Visceral Tissues of Neonatal Pigs after a Meal
Authors: Gazzaneo Maria C , Suryawan Agus , Orellana Renán A. , Torrazza Roberto Murgas , Nguyen Hanh V. , Wilson Fiona A. , Fiorotto Marta L. , Davis Teresa 
Published: June 2021

Neonates have a high rate of growth driven by elevated rates of skeletal muscle protein synthesis. Feeding stimulates protein synthesis but the time course of the changes in different tissues has not been determined. The aim of this study was to evaluate the time course of the changes in protein synthesis rates and translation initiation factor activation in skeletal muscle and visceral tissues after a meal. Neonatal pigs (n=36; 5–7 day old) received a meal providing one‐sixth of daily requirements and were sacrificed at 0, 30, 60, 90, 120, or 240 min after feeding. Protein synthesis increased 30 to 120 min in glycolytic muscles, 30 to 90 min in mixed fiber type muscle and did not increase in oxidative muscle post‐feeding. Protein synthesis increased in liver 30 to 120 min, jejunum 30 to 60 min and pancreas 30 min post‐feeding and did not increase in kidney and heart. Eukaryotic initiation factor (eIF) 4E binding protein (4EBP1) and rp S6 kinase 1 (S6K1) phosphorylation increased 30 to 90 min in all tissues. These results suggest that feeding stimulates mTOR signaling in skeletal muscle and visceral tissues. However, mTOR activation alone was not sufficient to stimulate protein synthesis in all tissues. (Supported by NIH grants AR‐44474 and AR‐51563 and USDA/ARS 6250510000‐33).Grant Funding Source: NIH grants AR‐44474 and AR‐51563 and USDA/ARS 6250510000‐33
Plasma folate's association with depressive symptoms among US adults: the role of dietary intake and diet quality
Authors: Beydoun May A , Fanelli‐Kuczmarski Marie T , Beydoun Hind A , Shroff Monal R , Mason Marc , Evans Michele K , Zonderman Alan B 
Published: June 2021

Folate deficiency has been implicated in the etiology of unipolar depression. Using a population‐based study of 1,681 subjects aged 30–64 years (Healthy Aging in Neighborhoods of Diversity across the Lifespan Study) the association of folate with depressive symptoms, measured with the Center for Epidemiologic Studies Depression scale (CES‐D), was examined. Folate was measured by plasma levels and dietary intakes based on two 24‐hr recalls. The 2005‐Healthy Eating Index (HEI) was computed. Multivariate logistic regression and structural equation modeling (SM) were conducted. Compared to the lowest tertile, the middle and uppermost tertiles of plasma folate were associated with a 39–40% reduced odds of elevated CES‐D (≥16) among women [adjusted OR (T3 vs. T1)=0.60(95% CI=0.42–0.86), P=0.006]. Confounding of this association by HEItotal was noted, though dietary folate did not confound this association appreciably. In SM, plasma folate completely mediated the inverse HEItotal‐CES‐D association among men only, particularly in six HEI components. Among women, HEItotal and four components had an inverse direct effect on CES‐D score suggesting an independent mechanism from plasma folate. Depressive symptoms may be alleviated by improving dietary quality with plasma folate playing a potential mediating role only among men.Plasma folate's association with depressive symptoms among US adults: the role of dietary intake and diet quality
A surprising level of unmetabolized folic acid in serum from the Tsimane Amerindians of Bolivia
Authors: Bailey Steven W. , Gurven Michael , Kaplan Hillard , Alverson Patricia B , Ayling June E. 
Published: June 2021

We have previously analyzed plasma from fasting subjects in the U.S., who were neither consumers of supplements nor breakfast cereals, and found persistent levels of unmetabolized folic acid (FA). We have also previously detected low levels of unmetabolized FA in samples from Europe, despite the lack of national FA fortification in these countries. We hypothesized that the presence of FA, even in European samples, could be due to any of the following:
Subjects in countries without FA fortification were, none the less, consuming some FA in their purchased foods, or
FA is generated by oxidation of natural food tetrahydrofolate during cooking or storage, or
FA is generated by oxidation of endogenous tetrahydrofolate within the body.
We have now determined the folate status of the Tsimane, a remote population of forager‐horticulturalists in the lowland Bolivian Amazon. The total serum folate averaged 13 nM, consistent with a relatively modest folate intake. Despite this and the lack of exposure to manufactured FA, unmetabolized FA was detected in all samples. Although lower on average than the above group in the U.S., this was significantly higher than those from Europe. Thus, it appears that humans may have been subject to persistent low FA throughout most of their recent evolution. Efforts are now underway to resolve whether this FA is due to cooking and/or oxidative stress.
Ganoderma lucidum suppresses colon carcinogenesis and inflammation
Authors: Sliva Daniel , Jedinak Andrej , Jiang Jiahua , Adamec Jiri , Sandusky George , Dudhgaonkar Shailesh 
Published: June 2021

Medicinal mushroom Ganoderma lucidum, well recognized natural product that have been used in the traditional Chinese medicine, is currently used as a popular dietary supplement. Here, we show that an oral application of G. lucidum triterpene extract (GLT) suppressed colon carcinogenesis induced by the food‐borne carcinogen (2‐Amino‐1‐methyl–6‐phenylimidazol[4,5‐b]pyridine [PhIP]) and inflammation (dextran sodium sulfate [DSS]) in mice. PhIP and DSS induced formation of colonic tumors, whereas GLT treatment significantly decreased the number of tumors. Furthermore, GLT suppressed focal hyperplasia and aberrant crypt foci (ACF) formation. These anti‐proliferative effects of GLT were confirmed by the decreased staining with Ki‐67 in colon tissues. PhIP/DSS‐induced colon inflammation was demonstrated by the significant shortening of the large intestine, whereas GLT treatment reversed the shortening of colon lengths to the levels comparable to the control group. Moreover, PhIP/DSS‐induced infiltration of macrophages was significantly reduced in colon tissue in animals treated with GLT. Our data suggest that GLT could be considered as an alternative dietary approach for the suppression of the food‐borne carcinogen‐ and inflammation‐induced colon carcinogenesis.Supported by P50 AT00477 from NCCAM and the NIH Office of Dietary Supplements.
Thymosin‐β4 (Tβ4) Inhibits Transdifferentiation of Human Hepatic Stellate Cells by an Akt‐dependent, PI3K‐independent Mechanism
Authors: Reyes‐Gordillo Karina , Shah Ruchi , Fu Sidney , Hindle Anna , Brody Frederick , Rojkind Marcos 
Published: June 2021

Hepatocyte growth factor (HGF) is used in the treatment of liver fibrosis. It is known to up‐regulate Thymosin‐β4 (Tβ4), a chemokine expressed by hepatic stellate cells (HSC), the main collagen producing cells of the liver. Thus, we investigated whether Tβ4 could prevent the expression of platelet‐derived growth factor receptor (PDGF‐βR), a hallmark of HSC activation, in cells treated with PDGF‐BB.METHODSHuman HSCs (passage 4–6) were either treated with PDGF‐BB (50 ng/ml), Tβ4 (10 ng/ml), or both. Cell proliferation was determined by the MTT assay and cell migration analyzed by wounding confluent cultures of HSCs. Expression of PDGF‐βR and several protein kinases was determined by Western analysis. PDGF‐βR, α1(I) collagen and α‐SMA mRNAs were determined by qPCR.RESULTSTβ4 downregulated the expression of PDGF‐βR and abolished PDGF‐BB‐induced HSC proliferation and migration, as well as expression of PDGFβR, α1(I) collagen and α‐SMA mRNAs. Tβ4 blunted PDGF‐BB‐dependent phosphorylation of AKT (Thr 308) and PRAS40 (Thr 246) but had no effect on PTEN, 85PI3K, and PDK1 phosphorylation.CONCLUSIONTβ4 prevents expression of key parameters of HSC activation by an AKT‐dependent, PI3K‐independent mechanism. Because Tβ4 is the major actin sequestering protein in mammalian cells we speculate that Tβ4 may prevent binding of AKT to actin and thus its phosphorylation by PDK1. Supported by NIAAA.
Anatomy ‐ Assuring a firm foundation in a fluid veterinary curriculum
Authors: Mizer Linda Allen 
Published: June 2021

Veterinary anatomy is the foundation of veterinary medicine and surgery, yet it is a foundation that must be laid on a very uncertain terrain, the veterinary curriculum. A graduating veterinarian must be capable of constructing a mental image of the animal body whether for physical examination, imaging, surgery or pathology. In no other profession is the individual expected to be competent in so many potential specialties, all of which require a firm foundation in anatomy from gross to microscopic to developmental.Gross anatomy is usually taught as one companion animal course and a second equine or production animal course. Histology and embryology are usually offered as separate courses. Horizontal integration of multiple disciplines within a single course is not generally achieved.Vertical integration over the four years may include required core components such as applied anatomy or surgical anatomy and elective components. Reinforcement in the clinical years of the curriculum is highly variable. The total hours of anatomy in a curriculum footprint vary greatly among veterinary colleges, as does the mode of delivery and the range of resources is used.My goal is to present some strategies that have been used in selected veterinary curricula and to open discussion of strategies for the vertical integration of veterinary anatomy training.
Astrocytes in the Amygdala
Authors: Johnson Ryan Taylor , Breedlove Marc , Jordan Cynthia L 
Published: June 2021

The amygdala is connected to numerous brain regions and is involved in complex behaviors such as survival and reproduction. This highly conserved brain region is sexually dimorphic in several species with the most dramatic differences found in the medial subregion. Neuroendocrine research has repeatedly demonstrated the plasticity of the medial amygdala across the lifespan. Astrocytes are a type of glial cell involved in synapse formation and functioning, and in several brain nuclei, astrocytes change morphology in response to gonadal hormones, leading to alterations in surrounding neurons. We have begun investigating astrocytes in the medial postero‐dorsal amygdala and our results reveal interesting sex and hemisphere differences in this dynamic brain region. Furthermore, our use of testicular feminized mutant rats demonstrates that functional androgen receptors may be necessary for formation of these differences.Grant Funding Source: NIH
Adenosine A2B Receptor Expression by Myeloid Cells Mediates Airway Inflammation in Asthma
Authors: Belikoff Bryan , Viackus Louis , Sitkovsky Michail , Remick Daniel G 
Published: June 2021

Allergic‐type airway inflammation characteristic of human asthma is modeled in mice by direct inhalation of German cockroach allergens (CRA). The role of adenosine A2B receptors (A2B) in asthma was studied in mice lacking A2B (A2B KO) and myeloid specific A2B KO (Lys‐M). CRA was given intratracheally on day 0 with two pulmonary challenges on day 14 and 21. 24 hours after final challenge lungs and brochoalveolar lavage fluid (BAL) were collected.Virtually all measures of pulmonary inflammation were reduced in the A2B KO and Lys‐M compared to wild type mice. Lung homogenate (LH) eosinophil peroxidase (WT, 1.0 ± 0.2; A2B KO, 0.2 ± 0.04*; Lys‐M, 0.3 ± 0.04*; *p < 0.01), but not myeloperoxidase (WT, 0.4 ± 0.1; A2B KO, 0.4 ± 0.1; Lys‐M 0.6 ± 0.1) levels were decreased. Our results demonstrate A2B expression by myeloid cells is an important contributor to the pulmonary inflammation in asthma.
*LH and ^BAL cytokines ng/mL. *^p < 0.05 compared to WT

Parameter
WT
KO
Lys‐M

Eotaxin 1
2.6 ± 0.2
0.9 ± 0.1*
1.0 ± 0.2*

Eotaxin 2
14.7 ± 1.6
2.3 ± 0.3*^
4.8 ± 0.1*^

IFN‐γ
8.6 ± 0.9
4.1 ± 0.2*
5.6 ± 0.6*

IL‐4
3.3 ± 0.3
1.8 ± 0.1*
1.8 ± 0.2*

IL‐5
3.2 ± 0.3
1.3 ± 0.1*
1.8 ± 0.3*

IL‐13
7.8 ± 0.9
4.1 ± 0.3*
4.3 ± 0.6*

TNF‐α
5.0 ± 0.6
1.9 ± 0.4*
2.7 ± 0.2*

BAL cells *p < 0.05 compared to WT

Parameter (x 104)
WT
KO
Lys‐M

Eosinophils
26.2 ± 5.8
1.7 ± 0.3*
1.5 ± 0.6*

Macrophages
14.9 ± 1.8
9.5 ± 0.4*
9.0 ± 0.9*

Lymphocytes
7.9 ± 1.3
2.0 ± 0.3*
3.4 ± 0.5*

Neutrophils
55.4 ± 5.4
43.8 ± 2.4
35.4 ± 3.8*

This work was supported by NIH Grant R01 ES0135283‐03
Middle schoolers want more than games for health education on the internet
Authors: Muzaffar Henna , Castelli Darla , Goss David , Scherer Jane , Chapman‐Novakofski Karen 
Published: June 2021

A diabetes awareness website (the HOT project: Healthy Outcomes for Teens) with content (diet and exercise) specific for 14–17 year olds with type 2 diabetes or at risk for type 2 diabetes was developed. The content focused on skills/knowledge assessment, overview of diabetes/food, food groups/diabetes, physical activity/weight management, and eating for target blood glucose levels in 5 modules. Our objective was to elicit information from those participants relative to the appeal of the website after the intervention to enhance its sustainability/usability. Subjects (n=42) were recruited from 3 school districts in central Illinois and had participated in the HOT project intervention (12 focus groups, n=2–5 each). The interview sessions took an average of 60–90 minutes, were audio taped and then transcribed verbatim. Content analysis was used to identify 3 themes: kid appeal, healthy living, and living with and without diabetes. Within kid appeal, three sub themes were found: social, entertainment and information. The most significant finding of this study was that while participants wanted more games, they also wanted more information and more social interaction. Sleeping, friendship, and studying along with website content were mentioned concerning healthy living. About half had relatives with diabetes and were more familiar with diabetes terminology and concepts. Funding: ADAF, NSRL, ISA.Grant Funding Source: Funded by ADAF, NSRL and ISA
Effects of α‐Linolenic Acid (ALA) Versus Eicosapentaenoic Acid (EPA) and Docosahexaenoic Acid (DHA) on Mood Status in Healthy Adults
Authors: Mazhar Wajeeha , Wien Michelle , Sabaté Joan 
Published: June 2021

Study ObjectiveThere is mounting evidence associating intake of n‐3 essential fatty acids ALA, EPA and DHA with mood states. This study aims to compare the effects of flaxseed oil, a terrestrial source of the n‐3 ALA versus algae oil, a marine source of EPA/DHA (V‐Pure) on mood status in healthy adults.MethodsWe performed a randomized cross‐over feeding study (three 8‐week dietary study periods) in 24 healthy adults. Subjects consumed three eucaloric diets Control, flaxseed oil (6–7g of ALA/2400 kcal/d) and algae (0.20/0.72g EPA/DHA per 2400 kcal/d). Mood state was assessed by two self‐rating questionnaires: Profile of Mood States (POMS) and Depression Anxiety and Stress Scale (DASS) administered at the end of each study period.ResultsCompared with control, the flaxseed diet exhibited a tendency to decrease POMS and DASS depression scores by 14% and 39% respectively. Algae diet tended to raise depression scores by 31% and 33% respectively (all p>0.05). Similar trends were observed for stress scores while scores for vigor were reversed for the diets.ConclusionsLonger studies are needed to test the effects of diet enriched with ALA and/or EPA/DHA on mood states which may clarify the tendencies observed during our short term study.
All‐trans retinoic acid increases matrix metalloproteinase‐9 expression in murine myeloid dendritic cells through retinoic acid receptor‐α interaction with and histone acetylation of the promoter
Authors: Lackey Denise E. , Hoag Kathleen A. 
Published: June 2021

Myeloid dendritic cells (DC) are antigen presenting cells that migrate to secondary lymphoid tissues following activation. We have previously shown that treatment of mouse DC with all‐trans retinoic acid (atRA) decreases adherence through production and activity of matrix metalloproteinase (MMP)‐9. The Mmp‐9 promoter does not, however, contain a traditional retinoic acid response element for atRA to transduce its signal for gene regulation. To identify the mechanism by which atRA increases MMP‐9 production in DC, we performed electrophoretic mobility shift assays for the consensus Sp1, AP‐1 and NFκB binding sites located in the Mmp‐9 promoter. We found no consistent change in nuclear protein binding to Sp1 or AP‐1 consensus sequences in response to atRA, while binding to NFκB decreased compared to retinoic acid receptor (RAR)‐alpha antagonist treatment. We next performed chromatin immunoprecipitation assays to assess the effect of atRA on Mmp‐9 promoter activity. We found that atRA increased recruitment of RARα (38%) and histone acetyltransferase p300 (24%) to the Mmp‐9 promoter and increased histone H3 acetylation in the promoter by 29%. We conclude that atRA increases transcription of Mmp‐9 directly by enhancing RARα promoter binding, recruitment of p300, and subsequent acetylation of histone H3. Supported by the Department of Food Science and Human Nutrition, Michigan State University.Grant Funding Source: Department of Food Science and Human Nutrition, Michigan State University
Vitamin A is Required for Maintenance of Plasmacytoid Dendritic Cells in Mouse Peyer's Patches
Authors: Duriancik David M , Hoag Kathleen A 
Published: June 2021

In the mouse, myeloid dendritic cells (DCs) and lymphoid DCs are responsible for stimulating T helper (Th) 2 and Th1 responses, respectively. Plasmacytoid (pDCs) secrete large amounts of type 1 interferons (IFN‐α/β) in response to virus infection. Vitamin A up‐regulates CCR9 on numerous cell populations for homing to the small intestine. In addition, pDCs express high amounts of CCR9. The objective of our study was to determine the effects of vitamin A deficiency on the DC populations of Peyer's patches. We hypothesized that pDCs would be decreased in the Peyer's patches of vitamin A‐deficient mice. In house bred, specific pathogen‐free, C57BL/6J mice were depleted of vitamin A through diet and sacrificed at 8, 10, and 12 weeks of age. Flow cytometry was used to identify the DC subpopulations of Peyer's patches and High Performance Liquid Chromatography was used to assess liver retinol activity equivalents. Precursor DCs and pDCs decreased as severity of vitamin A deficiency increased. Plasmacytoid DCs of the Peyer's patches are more tolerogenic than pDCs of the spleen. In addition, vitamin A plays a critical role in maintaining the balance of T regulatory and T helper 17 cell populations. Therefore, vitamin A deficiency decreases pDCs of the Peyer's patches, likely contributing to impaired tolerance and increased Th17 cells in the mucosa.Grant Funding Source: Intramural Funds
The “muscle‐full” effect after oral protein: time‐dependent concordance/discordance between muscle protein synthesis (MPS) and mammalian target of rapamycin (mTOR)‐associated signaling
Authors: Atherton Philip James , Etheridge Timothy , Watt Peter William , Wilkinson Daniel , Selby Anna Louise , Rankin Debbie , Smith Kenneth , Rennie Michael John 
Published: June 2021

How the brief rise‐and‐fall of MPS occurs after raising blood amino acids (AA) by IV infusion is unknown. We predicted that mTOR‐associated signaling responses would prefigure those of MPS after oral protein. 8 men (~21 y, BMI 22–24 kg.m−2) received [1,2‐13C2]leucine (1mg.kg.h−1) over 8.5 h, the first 2.5 of which preceded drinking 48 g whey suspension; muscle was intermittently biopsied throughout. MPS was measured as capture of [1,2‐13C2]leucine and signaling markers by immunoblotting. MPS rate trebled 45–90 min after whey (i.e. myofibrillar 0.03±0.01 vs. 0.1±0.01%.h−1; means±SE, P<0.001) thereafter falling to baseline, despite raised plasma (+105%; P<0.01) and muscle [leucine] (+54%; P<0.01) at 180 min. Increases in kinase activity of protein kinase B (PKB) and of eukaryotic initiation‐factor 4GSer1108 phosphorylation preceded the MPS rise, whereas increases in phosphorylation of p70S6 kinaseTh389 (+112%; P<0.01) and eIF4E‐binding protein‐1Thr37/46 (+155%; P<0.01) were superimposable with the MPS profile for 90 min. However, whereas MPS fell thereafter, all signals (except PKB, which mirrored insulin responses) remained elevated, echoing declining plasma [AA]. We confirm that MPS responses to [AA] are brief but large; however, as mTOR signaling outlasts them, the latter probably reflects [AA] only and unknown elements signal “muscle full”, thereby inhibiting MPS. Support: RCUK, BBSRC, EXGENESISGrant Funding Source: Physiology (APS)
Nutrient sensing anabolic pathway is increased in the elderly following chronic dietary leucine supplementation
Authors: Casperson Shanon , Sheffield‐Moore Melinda , Paddon‐Joones Douglas 
Published: June 2021

Leucine has been shown to act as a key regulator of the nutrient sensing anabolic pathway. Acute administration of leucine affects the phosphorylation status of several proteins involved in translation initiation that are regulated by the mTOR pathway. We conducted a 14 day pilot study in which we supplemented regular daily meals of community dwelling elders (n=8, 63–76 yrs) with a small amount of leucine (4 g per meal; 3 meals per day; days 2–13). On days 1 and 14, muscle biopsies were obtained in the post‐absorptive state to determine leucine‐induced modulation of the mTOR signaling pathway. After 14 days of leucine supplementation, there was a trend toward increased phosphorylation of mTOR (P=0.06). In addition, the phosphorylation of the downstream effectors 4E‐BP1 (P=0.03) and p70S6K (P=0.08) were increased. These data suggest that a provision of leucine supplementation facilitates an adaptive change in components of the mTOR signaling pathway in aging human muscle.Grant Funding Source: UTMB Claude D. Pepper Older Americans Independence Center # P30 AG024832 (to D. Paddon‐Jones) and NIH/NCI grant 5R01 CA127971 (to M. Sheffield‐Moore).
Phytosterols (PS) as immunomodulators of Multiple Sclerosis (MS)
Authors: Valerio Michael , Liu Hongbaio , Heffner Reid , Zivadinov Robert , Ramanathan Murali , Weinstock‐Guttman Bianca , Awad Atif B. 
Published: June 2021

MS is a neurological autoimmune disorder affecting millions globally. Experimental Autoimmune Encephalomyelitis (EAE) is a well accepted animal model which is widely used to study MS. MS is characterized by CNS infiltration with immune cells and demyelination. PS are plant sterols which have been shown to have anti‐inflammatory properties. The objective of this project was to examine the effect of PS on EAE clinical score and identify a possible underlying mechanism. Mice were divided into PS and control groups, treated with PS or vehicle by gavage one week before disease induction and continue thereafter while maintained on a low PS diet. Mean clinical disease score (0–5) of PS treated mice was 0.33 versus 2.4 in control mice. Brain histological studies indicated significantly (p=0.007) less lymphocyte infiltration in PS treated mice. Immunohistochemical staining for macrophages/microglia, using F4/80 antibodies, indicated significantly (p=0.029) less infiltration in brains of PS treated mice. Demyelination was significantly (p=0.029) less in PS treated mice compared to controls. Cytokine analysis on brain tissue and splenocyte homogenate showed significant increase in IL‐10 and decrease in MCP‐1 in PS treated animals. It was concluded that PS reduces the clinical signs of the disease and this could be mediated by immune modulation. Supported by grants from NMSS and JFJ.Grant Funding Source: National Multiple Sclerosis Society and JFJ Foundations