bluuebunny/crossref_metadata_2025_split huggingface dataset:
Make Physical Activity (PA) a STAPLE in Children's Lives: Development of a Mnemonic to Assist Parents of Preschoolers in Planning PA Opportunities for their Children
Authors: Golem Devon , Martin‐Biggers Jennifer , Byrd‐Bredbenner Carol 
Published: June 2021

Higher PA levels during early childhood are linked with healthy weight, motor skill proficiency, and healthy PA habits later in life. Many preschoolers do not meet PA recommendations, often because parents are not aware of or do not know how to operationalize them. A comprehensive literature review (n=58 articles) conducted using IOM's LEAD framework for obesity prevention documented PA levels, recommendations, and correlates for preschoolers. A mnemonic applying literature findings for PA benefits, guidelines and tips for parents was created. The mnemonic, based on Social Cognitive Theory, includes Space (for activity), Two‐hours (goal/day) with half this time for planned Activity and half for Play (unstructured activity), Leadership (let child choose activities), and Encourage (child to be active and modeling PA). Key informant interviews (n=10 parents, n=8 experts) validated the figure and documented its perceived utility to change parent PA behavioral intentions. Overall, informants felt the mnemonic was useful and enlightening. Mnemonics, like the one developed in this study that present a synthesis of research findings in a “matter‐of‐fact” manner, could help parents explore and resolve ambivalence or resistance toward behavior change, strengthen motivation for change, and reduce preschoolers’ obesity risk and associated health outcomes.Grant Funding Source: United States Department of Agriculture, National Institute of Food and Agriculture, Grant Number 2011–68001‐30170
Naturally Occurring Peptides in Human Milk: Identification and Evidence for Antibacterial Action
Authors: Dallas David Charles , Guerrero Andres , Khaldi Nora , Barile Daniela , German J. Bruce , Lebrilla Carlito 
Published: June 2021

For over 200 million years, milk has co‐evolved with mammalian infants to be nourishing and immunoprotective. Scientists are now realizing that milk is not simply a mixture of basic nutritional building blocks, but rather a dynamic, active and personal source of nourishment to the human infant. Fragments of milk proteins released during infant digestion have an array of biological functions within the gut and systemically including opioid‐like activity, immune system modulation and antimicrobial action. These peptides are typically inactive within the sequence of the parent protein and only become active when released by proteolysis.This study aimed to identify the extent of milk protein degradation within the breast and identify released peptides with potential bioactivity. Pooled, mature term breast milk was analyzed for presence of protein fragments by nano‐LC Chip Quadrupole Time‐of‐Flight Tandem Mass Spectrometry (Chip‐Q‐TOF). Of the 508 unique milk peptides identified, most (62%) were derived from ß‐casein. Sixty‐two peptides had significant sequence overlap with known bioactive peptides with antimicrobial or immunomodulatory functions. These 500 unique peptides represent a five‐fold increase in the number of naturally occurring peptides identified in the entire history of milk research.Grant Funding Source: USDA
Energy intake modulates intramuscular mTORC1 signaling and ubiquitin‐mediated proteolysis during energy deficit independent of dietary protein variations
Authors: Carbone John Walter , Margolis Lee M , McClung James P , Cao Jay J , Young Andrew J , Pasiakos Stefan M 
Published: June 2021

Effects of variations in habitual and acute dietary protein consumption on intracellular regulators of human skeletal muscle mass during energy deficit (ED) were investigated. Using a randomized‐block design, 32 men and 7 women consumed diets providing protein at 0.8, 1.6, or 2.4 g·kg−1·d−1 for 31 days. A 10‐day weight maintenance (WM) period preceded 21 days of ED, during which energy intake was reduced to 60% of daily requirements. Phosphorylation of mTORC1 associated signaling proteins, protein ubiquitylation (Ub), and NFκB expression were assessed in vastus lateralis muscle samples obtained after an overnight fast (FAST) and again 120 min after consuming a mixed meal (480 kcal, 20 g protein; FED) on days 10 and 31. Independent of dietary protein level and feeding state, Ub was 25% higher (P< 0.05) for ED versus WM. Energy state and feeding altered p70S6K1 phosphorylation, as FED‐ED levels were 26% lower than FED‐WM (energy‐by‐feeding, P< 0.05). Overall, Akt and rpS6 phosphorylation were higher (P< 0.05), and NFκB and Ub were lower (P< 0.05), for FED versus FAST. These data suggest that ED may upregulate intramuscular ubiquitin‐mediated proteolysis, and attenuate p70S6K1 sensitivity to feeding, although energy consumption, independent of habitual protein intake, may confer skeletal muscle protection through concomitant stimulation of mTORC1 signaling and inhibition of Ub during ED.Supported by USAMRMC, EMU CHHS SSSA, and USDA ARS
Astaxanthin supplementation lowers plasma triglyceride concentrations in diet‐induced obese C57BL/6J mice
Authors: Yang Yue , Pham Tho , Wegner Casey , Kim Bohkyung , Ku Chai Siah , Park Young‐Ki , Lee Ji‐Young 
Published: June 2021

Elevated plasma triglyceride (TG) and cholesterol concentrations are risk factors for cardiovascular diseases. We previously reported that astaxanthin (ASTX), a xanthophyll carotenoid, lowers plasma total cholesterol and TG concentrations in apolipoprotein E knockout mice. To investigate if ASTX exerts hypolipidemic effects in the diet‐induced obesity (DIO) mice and if so, to determine an effective supplementation level, male C57BL/6J mice were fed a high fat (HF) control diet (60% energy from fat) or a HF diet supplemented with 0.003%, 0.01% or 0.03% ASTX by weight for 12 wk. Only mice fed 0.03% ASTX showed a significant reduction in plasma TG levels, suggesting this level of supplementation is necessary for ASTX to have a TG‐lowering effect. Compared with control, plasma high density lipoprotein cholesterol (HDLc) levels were significantly higher in 0.03% ASTX‐fed mice without a difference in plasma non‐HDLc levels. The ASTX supplementation also decreased plasma aspartate aminotransferase levels, suggesting it protects against high fat‐induced tissue damages. In conclusion, 0.03% ASTX in diet decreased plasma TG and increased HDLc in DIO mice and therefore, it is potentially beneficial for lowering CVD risk.Grant Funding Source: USDA AFRI 2012–67018‐19290
Biotinylation of the c‐myc promoter binding protein MBP‐1 decreases c‐myc expression in mammary carcinoma MCF‐7 cells
Authors: Zhou Jie , Wijeratne Subhashinee S. K. , Zempleni Janos 
Published: June 2021

Biotin feeding studies in mice predisposed to developing breast cancer suggest that the tumor load increases by ~100% in biotin‐deficient mice compared with controls, and that the increase is associated with metastasis rather than new tumors. The oncogene c‐myc is implicated in cancer metastasis, and its expression is repressed by binding of MBP‐1 to the c‐myc promoter. Discovery‐based studies for identifying novel biotin‐containing proteins suggest that MBP‐1 contains covalently bound biotin, judged by mass spectrometry. We hypothesized that biotinylation of MBP‐1 increases the binding of MBP‐1 to the c‐myc promoter, thereby decreasing c‐myc expression and metastasis. MCF‐7 cells were cultured in biotin‐defined media (deficient, sufficient, supplemented) and transfected with a reporter gene construct for the c‐myc promoter. Reporter activity was ~100% greater in biotin‐deficient cells compared with sufficient and supplemented controls. Likewise, c‐myc mRNA levels were 10% higher in deficient compared with sufficient cells, and 10% high in sufficient compared with supplemented cells. Biotinylation of MBP‐1 is an enzymatic process, judged by streptavidin blots. These observations are consistent with our hypothesis and preliminary studies, suggesting that biotin depletion causes an increased expression of the oncogene c‐myc, thereby increasing cancer risk.Grant Funding Source: ARD Hatch, NIFA, and NIH
Polyunsaturated fatty acids (PUFA) modulate association between PIK3CA‐KCNMB3 variants and insulin resistance
Authors: Zheng Ju‐Sheng , Arnett Donna K , Parnell Laurence D , Lee Yu‐Chi , Ma Yiyi , Smith Caren E , Richardson Kris , Li Duo , Borecki Ingrid B , Tucker Katherine L , Ordovás José M , Lai Chao‐Qiang 
Published: June 2021

The objective was to examine associations of PIK3CA‐KCNMB3 variants with glucose‐related traits and interaction with dietary fat. We investigated genetic associations and modulation by dietary fat in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (n=820) and replicated the findings in the Boston Puerto Rican Health Study (BPRHS) (n=844). For KCNMB3 missense mutation rs7645550, homeostasis model assessment of insulin resistance (HOMA‐IR) was significantly lower in TT homozygotes compared with CT carriers in both GOLDN (P=0.005) and BPRHS (P=0.042); this SNP interacted with dietary n‐3: n‐6 PUFA ratio for HOMA‐IR (P=0.006) in GOLDN. For rs1183319, G allele carriers had higher fasting glucose compared with non‐carriers in GOLDN (P=0.008), and had marginally higher glycosylated hemoglobin (HbA1c) than non‐carriers in the BPRHS (P=0.053); this SNP showed significant interaction with n‐3:n‐6 ratio on HOMA‐IR in GOLDN and on HbA1c in the BPRHS. In summary, PIK3CA‐KCNMB3 variants are associated with glucose‐related traits in populations of different ancestries, and are modified by dietary PUFA.Grant Funding Source: USDA
Skeletal muscle vitamin D receptor associated with serum 25‐hydroxyvitamin D
Authors: Pojednic Rachele M. , Ceglia Lisa , Lichtenstein Alice , Dawson‐Hughes Bess , Fielding Roger 
Published: June 2021

BACKGROUNDThe effects of vitamin D on aging muscle may be mediated by its receptor (VDR). VDR is expressed in human skeletal muscle and when bound to the active metabolite, 1,25‐dihydroxyvitamin‐D3, regulates expression of genes that affect muscle cell differentiation and contractility. Evidence on the relationship between serum 25‐hydroxyvitamin‐D (25OHD) and VDR in human skeletal muscle is limited.PURPOSETo examine the association between VDR in skeletal muscle and 25OHD in older mobility‐limited adults.METHODSA cross‐sectional analysis of 18 mobility limited older adults (age 65–95) was conducted. Serum 25OHD and a muscle biopsy of the vastus lateralis were sampled. VDR protein expression was assessed via Western Blot.RESULTSMean (±SD) 25OHD was 28.9 (±11.6) ng/mL (range: 15.0 to 53.0 ng/mL). 25OHD was strongly associated with VDR concentration (R=0.67; p=0.001). VDR concentration differed significantly between vitamin D sufficient (>;20ng/mL) and insufficient groups (≤20ng/mL, p=.02).CONCLUSIONVDR in skeletal muscle is strongly associated with circulating 25‐Hydroxyvitamin‐D in older mobility limited adults. Individuals with sufficient 25OHD have significantly greater concentrations of VDR than those with insufficient 25OHD. This study provides support to the hypothesis that 25OHD may affect VDR protein expression in human skeletal muscle. NHLBI Training Grant T32HL69772.
Maternal iron status and depressive symptoms in rural Bangladesh
Authors: English Laural Kelly , Murray‐Kolb Laura E , Chang Stephanie , Hamadani Jena , El Arifeen Shams , Baqui Abdullah , Black Robert E 
Published: June 2021

Iron deficiency and maternal depression are prevalent in developing countries like Bangladesh. Our aim was two‐fold: 1) determine the relationship between iron status and maternal depressive symptoms; 2) assess the Center for Epidemiological Studies Depression Scale (CESD) in women of rural Bangladesh. Mother‐infant dyads taken from a larger RCT (Chang et al., 2010) to improve diarrhea and anemia in rural Bangladesh were analyzed. Depressive symptoms were collected at baseline (n=113), 3 mo (n=319), and 6 mo (n=328). Maternal ferritin and transferrin receptor were collected between baseline and 3 mo (n=307) and at 6 mo (n=108). Factor analysis of CESD structure resulted in a 3‐factor solution: interpersonal difficulty/somatic inhibition, depressed affect, and well‐being. We found a 70.3% prevalence of high depressive symptoms (CESD ≥ 16) but low prevalence (11.2%) of iron depletion (ferritin < 20 ng/mL). Nonetheless, iron depleted (ID) women had higher depressive symptoms than iron sufficient (IS) women at every time point (ANOVA, p<0.04). Multivariate regression adjusted for covariates (child age & sex, WAZ, assets), revealed that body iron at 6 mo (assessed with Cook's equation) was related to the “depressed affect” factor scores at 6 mo (p<0.048). This relationship between iron depletion and CESD symptomatology warrants validation of CESD factor structure and cutoff point in Bangladesh.Grant Funding Source: USAID to the Johns Hopkins Global Research Activity Cooperative Agreement
Maternal vitamin D status and inflammation across adolescent pregnancy
Authors: Akoh Christine , Pressman Eva , Cooper Elizabeth , Queenan Ruth Anne , O'Brien Kimberly 
Published: June 2021

Vitamin D is known to play a role in both innate and adaptive immunity, but the role of vitamin D in the inflammatory process during pregnancy is unclear. The purpose of this study was to examine associations between vitamin D status and inflammation across pregnancy using extant biospecimens obtained from a cohort of 168 pregnant adolescents (≤18 y). In this longitudinal study, serum was collected from adolescents at mid‐gestation (MG~26 weeks), delivery, and from cord blood; 66.1% of teens were African American, 33.9% Caucasian, and 24.1% Hispanic. Half of the teens and 60% of their newborns were 25(OH)D insufficient (≤20 ng/mL). Analyses are on‐going to measure inflammatory cytokines (IL‐6, IL‐10, TNF‐α, and CRP) in archived maternal and cord serum. To date maternal 25(OH)D at MG was positively correlated with TNF‐α in cord blood (p=0.0284, n=89). Maternal 1,25(OH)2D was positively associated with both TNF‐α (p=0.0364, n=96) and CRP at MG (p=0.0305, n=86) but was significantly negatively correlated with TNF‐α at delivery (p=0.0004, n=92). These results suggest that vitamin D may impact inflammatory activity in pregnant adolescents and their infants at birth.Grant Funding Source: USDA AFRI 2012–67017‐30216
Dietary patterns and weight change in older adults ≥ 75 years old: What's the relationship?
Authors: Hsiao Pao Ying , Coffman Donna L. , Wood G. Craig , Mitchell Diane C. , Still Christopher D. , Jensen Gordon L. , Hartman Terryl J. 
Published: June 2021

Weight change is a common health concern among the elderly, yet little is known about the relationship between weight change and dietary patterns (DP) in older adults, especially the very old (≥ 75 y). This investigation examined the association between DP and 5‐ year weight change in community‐dwelling older adults (n=270; mean ± SD age: 78.6±3.9 y) of the Geisinger Rural Aging Study, a longitudinal cohort study. Using baseline 24‐hour dietary recall data, cluster analysis was used to derive ‘Sweets and dairy’ (SD), ‘Western’ (W) and ‘Health‐conscious’ (HC) DP. Weight change data was extracted from electronic medical records and was characterized using three methods: 1) overall 5‐y weight change, 2) 10 pounds gained or lost (y/n) and 3) 10% gained or lost (y/n). Kaplan‐Meier plots and Cox proportional hazards regression were used to examine the association between DP and weight change. Mean overall weight change was not significantly different across DP: −5.56 (all), −7.2, −4.8 and −3.3 pounds for the SD, the W, and the HC DP, respectively (p=0.17). In gender‐stratified analyses, compared to the HC DP, females characterized by the SD and W DP, were three and two times more likely to lose 10 pounds (Hazard ratio (95% CI): SD=3.2 (1.5–6.7); W=2.4 (1.1–5.6)), respectively. Findings suggest that a HC DP may be associated with weight stability in females, which provides additional impetus for promoting healthy DP in older women.Grant Funding Source: USDA #1950–51530‐010–02G
Maternal metabolic changes with dietary intake of blueberry during pregnancy and lactation predispose adult progeny to lower mammary tumor growth rate
Authors: Montales Maria Theresa E , Melnyk Stepan , Prior Ronald L , Simmen Rosalia CM 
Published: June 2021

We have shown the lower growth rates of tumors that developed from Wnt1‐transgenic (Tg) offspring of dams consuming whole blueberry powder (3% BB) during pregnancy and lactation, compared to those of control (Casein) dams. Dietary exposure at post‐weaning through lifetime did not mimic the effects of early BB exposure. The basis for maternal BB effects on mammary tumor growth was examined in dams exposed to BB or control diet as young adults (beginning at age 8 weeks) and throughout pregnancy and lactation. Dams at weaning were evaluated for growth and metabolic parameters. BB‐fed dams had lower abdominal and retroperitoneal fat pad weights than control‐fed dams, although their body weights did not differ. BB dams also displayed increased insulin sensitivity (lower blood glucose, serum insulin, HOMA) and higher serum glutathione and methionine levels. Isolated epithelial cells from pre‐neoplastic mammary tissues of Tg offspring exposed to maternal control and BB diets were analyzed for percentage of basal (CD29highCD24+) and luminal progenitor (CD29lowCD24+) populations. Maternal BB exposure (relative to control) resulted in lower percentage of the luminal subpopulation (6.4% vs 21%), which comprise the tumor bulk in Tg tissues. Results implicate the influence of the favorable metabolic and anti‐oxidative maternal environment with BB diet on developing mammary glands for the improved mammary tumor outcome.Grant Funding Source: USDA‐CRIS 6251–51000‐005–004S, Arkansas Biosciences Institute
In vitro and in vivo anti‐inflammatory effect of 4′‐hydroxylnobiletin, a major colonic metabolite of nobiletin
Authors: Wu Xian , Song Mingyue , Zheng Jinkai , Guo Shanshan , Xiao Hang 
Published: June 2021

Nobiletin, a citrus flavonoid has been associated with various biological activities including anti‐inflammation. We have found that 4′‐hydroxylnobiletin (4HN) was a major colonic metabolite of nobiletin in mice after oral administration, and the colonic levels of 4HN were much higher than nobiletin. Herein, we studied anti‐inflammatory effects of 4HN in lipopolysaccharide (LPS)‐stimulated RAW 264.7 macrophages and 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA)‐induced skin inflammation in mice. Treatments of 4HN dose‐dependently inhibited LPS‐induced NO production in macrophages. These inhibitory effects were much stronger than those produced by nobiletin. Western blot analysis, ELISA and real‐time qRT‐PCR showed that 4HN significantly reduced the expression levels of iNOS, COX‐2, IL‐1 and IL‐6, and inhibited activation of NF‐κB, Akt and JNK in LPS‐stimulated macrophages. Furthermore, our results demonstrated that topical application of 4HN decreased TPA‐induced mouse ear edema by more than 80%. This inhibitory effect was associated with inhibition on TPA‐induced expression of iNOS, COX‐2, IL‐1, IL‐6, and TNF‐α in the mice. Overall, our results demonstrated that 4HN had strong anti‐inflammatory effects both in vitro and in vivo, which provided a solid scientific basis for using nobiletin to inhibit inflammation related diseases in the colon such as colitis and colon cancer.Grant Funding Source: AICR, NIH, NAS, USDA
Mode of administration affected the capability of soybean‐derived peptide lunasin to prevent metastasis of human colon cancer cells in a mouse model
Authors: Dia Vermont P. , de Mejia Elvira Gonzalez 
Published: June 2021

The objective was to evaluate soybean‐derived peptide lunasin to inhibit KM12L4 human colon cancer cell metastasis in mouse model of colorectal cancer. Mouse was injected with 1 × 106 KM12L4 colon cancer cells in the spleen and randomization was made after 4 days. Mice that received 4 mg lunasin/kg body weight per day (i.p.) had a reduced number of liver metastatic tumors compared to group that received PBS (P = 0.047). Liver‐tumor tissue showed lunasin (4 mg/kg bw, per day, i.p.) reduced the expression of histone H3K18 (P = 0.002) and H4K8 (P < 0.0001) with reduction in the expression of p300 enzyme (P = 0.039). Orally administered lunasin for 28 days reduced the number of liver metastatic nodules from 18 (PBS, n = 6) to 8 (8 mg/kg bw, n = 5, P = 0.293) to 1 (20 mg/kg bw, n = 3, P = 0.247); however, these values were not statistically significant. Gavage lunasin (8 mg/kg bw) did not significantly affect expression of proliferating cell nuclear antigen, pro‐apoptotic Bax, anti‐apoptotic Bcl‐2 and H3K18 and significantly increased the expression of H4K8 in liver‐tumor tissue. No liver‐tumor tissue was present for analysis after gavage lunasin (20 mg/kg bw). In conclusion, intraperitoneally‐administered lunasin (4 mg/kg bw) was effective in preventing colon cancer metastasis but not after oral administration of the bioactive peptide lunasin up to 20 mg/kg bw.Grant Funding Source: USDA
The Kelch‐Like 1 Actin Binding Protein Modulates Neuronal Voltage Gated Calcium Channels
Authors: Piedras‐Renteria Erika Sofia , Perissinotti Paula Patricia , Ethington Elizabeth Gibbs , He Yungui , Martin Jody , Cribbs Leanne , Koob Michael D 
Published: June 2021

Kelch‐like 1 (KLHL1) is a neuronal actin‐binding protein first identified in humans as part of the genetic locus of the neurological movement disorder Spinocerebellar Ataxia type 8. KLHL1 is expressed in the cytosol, axons and dendrites. KLHL1 KO causes loss of post‐synaptic structures, loss of motor coordination and gait abnormalities. KLHL1 is an ion channel modulator and upregulates HVA and LVA calcium currents in vitro by increased recycling endosome activity and by alteration of the kinetics of τdeactivation. We analyzed the endogenous HVA and LVA calcium currents in neurons from WT and KLHL1 KO mice, and compared these data with the acute down‐regulation of KLHL1 using a knock‐down shRNA (KD) strategy. KLHL1 KD caused decreased HVA and LVA calcium current expression. In contrast, the KO had no differences in total LVA current density, yet changes in current kinetics suggest there is a down‐regulation of α1H and compensatory expression of α1I. HVA current density was also decreased in KO (40%) at 4–6 DIV but not at 7–10 DIV, suggesting this deficit was also compensated for after 7 DIV. Our data confirm that KLHL1 modulates LVA and HVA channel function in vivo; the compensatory modulation of currents in the KO may contribute to the mild motor phenotype seen in these mice.This material is based upon work supported by the National Science Foundation under Grant No. 1022075
The structure, regulation and activity of non‐canonical inteins
Authors: Mills Kenneth V. , Reitter Julie N. , Connor Katherine R. , Nicastri Michael C. , Williams Jennie E. , Colelli Kathryn M. , Marieni Michelle D. 
Published: June 2021

Protein splicing is the post‐translational excision of an intervening polypeptide (intein) from its flanking domains (the exteins), concomitant with extein ligation. The third step of splicing is Asn cyclization coupled to cleavage of the peptide bond linking the intein and C‐extein. Both the Methanoculleus marisnigri (Mma) and the Pyrococcus abyssi (Pab) PolII inteins promote efficient splicing with C‐terminal Gln in place of Asn. The activity of both inteins is regulated by disulfide bond formation, which might suggest a regulatory role for splicing. The Pab PolII intein splices only at elevated temperatures, allowing for isolation of a stable precursor and for study of each step of splicing in vitro. An NMR solution structure of the Pab PolII intein reveals a particularly rigid structure, a disordered loop absent in a highly similar P. horikoshii intein, and a β‐hairpin specific to inteins from archaebacteria.This material is based upon work supported by the National Science Foundation under grant MCB‐0950245 and the Camille and Henry Dreyfus Foundation.