bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can variability in energy intake be attributed to one meal versus another?
Authors: Sieber Jessica Lynne , Raynor Hollie , Carriquiry Alicia , Jahns Lisa 
Published: June 2021

Objective: Stability of meal patterns has been suggested to be associated with lower body weight. To examine the stability of energy contribution by meal type, estimates of within‐ (WIV) and between‐(BIV) individual variation (WIV) in energy intake by meal was compared to determine which meal accounts for the largest variation in daily energy intake among young adults.Methods: Mean ± SD and estimated coefficients of variation (CVw, CVb) in energy intake for self‐defined breakfast (B), lunch (L), dinner (D), and snack (S) meals were calculated using a mixed effects regression model. Intake was measured using 7 day food records (FR) entered into NDSR for analysis. Subjects were 105 18–19 yo college students.Results: Mean daily energy intake was 2180 ± 847 kcal, of which S contributed 20% (438 ± 507 kcal). CVw and CVb for B, L, D, S were 93/57, 74/31, 68/31, and 101/55%, respectively. Ratios of WIV and BIV were 1.6, 2.4, 2.2, and 1.8 for B,L, D, S, respectively.Conclusion: S were associated with the greatest CVw and D with the least, however, the higher WIV/BIV ratios for L and D suggest that there may be much more variation in these meals. All ratios exceeded unity, suggesting there is greater variation within individuals than between individuals.
Ethnicity and differences in mammary myoepithelial cell layers and inflammatory cell infiltration: Implications for differences in tumor development and behavior
Authors: Man Yan‐gao , Sheng Joy , Firpo Adolfo , Zhang Xichen 
Published: June 2021

Objective:The incidence and clinical course of breast cancer vary significantly between Asian and Western females. Despite tremendous intervention efforts focused on tumor cells, the trend has remained unchanged during the past 30 years. This study attempted to examine the tumor surroundings that may contribute to the racial disparity. Methods: Tissue sections from 15 Western and 15 Asian females with similar breast tumors were compared for a panel of tumor suppressor‐ and inflammation‐related markers.Results:Compared to their Asian counterparts, Western females had the following unique features: [1] a significantly higher frequency of focal disruptions and lower tumor suppressor expression in myoepithelial (ME) cell layers, [2] significantly higher rate of leukocyte and mast cell infiltration.Conclusions:As the ME cell layer is the physical barrier to prevent tumor invasion, and chronic inflammation is a potential tumor promoter, these differences in tumor surroundings may contribute to the observed higher incidence and severity of breast cancer in Western women (Supported by grant 2006CB910505 from the Ministry of Chinese Science and Technology Department, and DAMD17‐01‐1‐0129, DAMD17‐01‐1‐0130, and PC051308 from US Congressionally Directed Medical Research Programs, and BCTR0706983 from The Susan G. Komen Breast Cancer Foundation).
The mammalian genome as an RNA machine
Authors: Mattick John S , Croft Larry J , Pheasant Michael , Mercer Tim R , Dinger Marcel E 
Published: June 2021

It appears that the genetic programming of the higher organisms has been fundamentally misunderstood for the past 50 years. It is now evident that the majority of the mammalian genome is transcribed, apparently in a developmentally regulated manner, and that most complex genetic phenomena in the higher organisms are RNA‐directed. Evidence will be presented (i) that regulation scales quadratically with function in integrated systems, including organisms, and that multicellular eukaryotes have solved this problem by the cooption of RNA as an analog‐digital regulatory system; (ii) that much, if not most, of the mammalian genome is not evolving neutrally, but is comprised of different types of sequences evolving at different rates under different structure‐function constraints; and (iii) that there are thousands of non‐protein‐coding transcripts in mammals that are dynamically expressed during differentiation, many of which show precise expression patterns and subcellular localization in different regions of the brain. These and other observations suggest that the majority of the mammalian genome is devoted to a hidden RNA regulatory system that directs developmental trajectories by controlling chromatin architecture and epigenetic memory, transcription, splicing, RNA modification and editing, mRNA translation and RNA stability.(This work was supported by the Australian Research Council).
Engineering small molecules that nucleate assembly of protein complexes
Authors: Ansari Aseem Z. 
Published: June 2021

Cooperative assembly permits weak interactions between components of the gene expression machinery to be harnessed together in the creation of a multicomponent complex of high affinity and exquisite specificity. In the context of transcription factors, weak molecular interactions between transcription factors facilitate the assembly of multiprotein complexes. These complexes present multiple activation modules thereby nucleating the assembly of the transcriptional machinery.The modular nature of transcription factors lends itself to creation of ligands that utilize multivalent cooperative interactions to enhance binding affinity and specificity. We will present our design of synthetic Hox mimics that cooperatively stabilize the assembly of cellular transcription factor to a targeted DNA sequence. Our modular design can be broadly applied to engineer molecules that nucleate the assembly of other transcription factors. These molecules can then be used to modulate gene networks and thereby regulate cell fate.
Effect of three supplements with identical micronutrient content on length and weight of Mexican children
Authors: Neufeld Lynnette M , Dominguez Clara P , Guerra Armando Garcia , Feregrino Raquel Garcia , Cabrera Amira Hernandez 
Published: June 2021

The objective of this analysis was to assess the impact of three nutritional supplements with identical micronutrient content on length and weight of children at 24 mo of age. Communities (18 per supplement) were randomly assigned to receive a fortified food (FF), syrup (SY) or Sprinkles (SK). Children 6 to 12 m of age, beneficiaries of the Oportunidades program were eligible to participate. Supplements were delivered daily (6 mo) then weekly. Measurements were taken at baseline and 24 m of age. Appropriate statistical analyses for cluster randomized trials were used. 927 children were assigned to treatment (FF n=265; SY n=323; SK n=339) and 80% completed the trial. There were no statistically significant differences between groups at baseline for mean height‐age Z (HAZ −1.0±1.0) weight‐height Z (WHZ 0.4±1.0) or prevalence of stunting (FF 14.7%; SY 18.5%; SK 19.3%, p>0.10). At 24 mo of age, there was no difference between groups in mean HAZ (FF −1.0±1.0; SY −1.2±1.0; SK −1.1±1.0, p>0.10), WHZ (FF 0.12±0.96; SY 0.08±1.10; SK 0.17±0.96, p>0.10) or the prevalence of stunting (FF 14.8%; SY 21.6%; SK 17.5%, p>0.10). There was no difference in the prevalence of stunting between baseline (17.7) and 24 mo (18.1) (p>0.10). This study had no true placebo and we do not know to what extent the supplements influenced growth. The lack of change in mean HAZ and the prevalence of stunting from baseline to follow‐up may suggest that the three supplements were equally efficacious to prevent further growth retardation.The Oportunidades program financed this study and holds the rites to the data presented.
Copper deficient rats exhibit no alterations in plasma or brain NO metabolites, 3‐nitrotyrosine peptide abundance, or NOS mRNA expression
Authors: Prohaska Joseph R , Walters Mark 
Published: June 2021

Others have reported that copper deficient (Cu−) rodents have alterations in nitric oxide (NO) biology including: higher nitric oxide synthase (NOS) activity and expression, and higher 3‐nitrotyrosine abundance (a marker of peroxynitrite production predicted to be higher because of higher NO and superoxide). Altered NO could impact brain development and metabolism. Holtzman rat dams were fed a Cu− diet and given either Cu supplemented (Cu+) or deionized water starting on gestation day 7. Cu− dams at weaning and their male pups at P26 had near zero plasma ceruloplasmin activity. Compared to Cu+ P26 male rats Cu− rats had heart/body weight values more than twice as high. However, plasma levels of NO metabolites (nitrite and nitrate) were not altered by Cu deficiency in dams or pups. Mean values in all groups were approximately 60 μM. Cerebellar extracts of P24 Cu− and Cu+ rats contained equivalent NO metabolite levels; furthermore, a 30kD 3‐nitrotyrosine containing peptide was detected in equal amounts in P24 Cu− and Cu+ cerebellar extracts. However, levels of CCS were markedly higher and CCO subunit IV nearly absent in Cu− lanes confirming severe Cu deficiency. Abundance of brain nNOS and eNOS mRNA, detected by real time qPCR, was not different between Cu− and Cu+ rat pups. We conclude perturbation in NO biology is unlikely to impact the altered development and metabolism of Cu− rat brain.Supported in part by NIH HD‐39708.
Relatives’ migration to the US and overweight among Mexican school‐age, rural children
Authors: Flores Mario , Macias Nayeli , Rivera Marta , Merlos Claide , Barquera Simon 
Published: June 2021

The objective was to evaluate the influence of relatives’ migration to the US on weight status among rural Mexican children. Anthropometric measurements, body composition and physical activity were assessed in a cross‐sectional study of 119 school‐age children (9–12y) with at least one household member living in the US and sending remittances, and 120 community‐matched children who did not have a relative living in the US. Data on physical activity was obtained (steps/d during 7d). BMI was calculated as W/H2(kg/m2). Mean age was 10.9 ± 1.03y. Mean BMI was 20.4 ± 4.1. Average steps/d was 12,359 ± 4487. Mean percent body fat was 35.4 ± 7.9. Forty‐seven percent were girls. According to Cole's BMI cutoffs, 52.2% of children had normal weight, 28.4% were overweight, and 13.4% were obese.After adjusting by age and community, logistic regression analysis showed a 35% reduction in the risk of obesity, per 1000 steps/d, among girls with a migrant relative (OR: 0.65, 95%CI: 0.44, 0.97). Among those without a migrant relative, a 19% reduction in the risk of obesity per 1000 steps/d was observed in boys, but not in girls (OR: 0.81, 95%CI: 0.68, 0.98), (p for interaction=0.067).A relative's migration to the US is related to sex‐differential effects of physical activity in weight status among these rural Mexican school‐age children.Funded by CONACyT, Mexico; No. 2005–01–14089.
Impact of dairy products and dietary calcium on bone mineral content in children: Results of a meta‐analysis
Authors: Huncharek MIchael , Muscat Joshua , Kupelnick Bruce 
Published: June 2021

Objective: Although calcium is essential for maintaining bone health in children, the optimum dietary intake of calcium in this age group, particularly in the form of dairy foods, is a matter of debate. A meta‐analysis was conducted to examine the impact of dietary calcium/dairy supplementation on bone mineral content in this age group.Methods: Data were pooled from randomized controlled intervention trials and observational studies using previously described methods. The outcome of interest was a summary mean difference bone mineral content.Results: Combining data from twenty‐one randomized controlled trials (RCTs) using total body bone mineral content (TB‐BMC) as the outcome of interest, yielded a non‐statistically significant increase in TB‐BMC of 2 grams. These data demonstrated substantial statistical heterogeneity with sensitivity analyses revealing that among study subjects with normal or near normal baseline dietary calcium/dairy intakes, supplemental dairy/calcium showed little impact on bone mineral content. Sensitivity analyses suggested that baseline calcium intake could potentially account for the statistical heterogeneity. Pooling the three reports utilizing low intake subjects yielded a statistically significant summary mean BMC of 49 grams (24.0–76‐6). Pooling two RCTs using calcium/dairy supplement plus vitamin D was also associated with an increase in lumbar spine BMC of, on average, 35g (−6.8–41.8).Conclusion: Increased dietary calcium/dairy products, with and without vitamin D, significantly increases total body and lumbar spine BMC in children. Among children with “high baseline intakes” supplemental calcium/dairy products had little effect on TB‐BMC.
Effects of food form and portion size on postprandial appetite, ghrelin, and energy expenditure in healthy, older adults
Authors: Leidy Heather J , Apolzan John W , Mattes Richard D , Campbell Wayne W 
Published: June 2021

Objective: To examine the independent and combined influences of food form and portion size on appetite and metabolic responses. Methods: 43 older men and women (age: 72 ± 1 y; BMI: 25.6 ± 0.3 kg/m2) consumed, on 2 separate days, preloads in solid (S) vs. beverage (B) form as either 12.5% (264 ± 8 kcal) or 25% (533 ± 14 kcal) of estimated daily energy need. Postprandial (PP) appetite (hunger, fullness, desire to eat), plasma ghrelin concentration, and energy expenditure (EE) were measured over 4 h. Results: Main effects of food form (p<0.05) and portion size (p<0.05) were observed for appetite; PP hunger and desire to eat area under the curve (AUC) values were higher and fullness AUC values were lower for B vs. S and between 12.5% vs. 25%. Post‐hoc analyses revealed no difference in appetite between the S‐12.5% vs. S‐25%. However, B‐12.5% led to higher hunger and desire to eat and lower fullness AUC values vs. the B‐25% (p<0.05). No difference in 4‐h ghrelin was observed between S vs. B and 12.5% vs. 25%. Concerning PPEE, the B treatment led to lower overall PPEE vs. S when consuming 25% (p<0.01) but not 12.5%. Conclusion: Several key parameters of appetite appear to be independently and additively influenced by food form and portion size with particular insensitivity to lower energy beverages in healthy, older adults.Support: NIH R01 AG021911; The Solae Company; IBRC, Purdue University
Identification of a new potential human epoxide hydrolase (ABHD7)
Authors: Decker Martina , Adamska Magdalena , Arand Michael 
Published: June 2021

Two human EHs are well‐investigated. The microsomal EH (mEH) hydrolyzes a large variety of structurally different xenobiotic‐derived genotoxic epoxides and therefore is implicated in detoxification. The soluble EH (sEH) converts signalling molecules such as epoxyeicosatrienoic acids (EETs) to the corresponding dihydroxyeicosatrienoic acids (DHETs) and thus is involved in the regulation of physiological processes. Using the signature sequence RVIAPDLRGYGDSDKP that is reasonably conserved among epoxide hydrolases and some other structurally related enzymes of the &#945;/&#946; hydrolase fold superfamily, we could recently identify two new genes ABHD9 and ABHD7. All features so far identified to be necessary for a functional EH, including a catalytic triad with an aspartic acid in the position of the catalytic nucleophile, as well as two catalytic tyrosines, are conserved in the primary structures of the proteins predicted from these genes. The amino acid sequences of ABHD9 and ABHD7 share 42% identity and therefore belong to the same family being different from mEH and sEH (sequence similarity below 25%). Our previous studies show an EET converting activity of ABHD9. To elucidate the function of ABHD7 we are presently working on the recombinant expression and biochemical characterization of this new enzyme.The present work is supported by the Swiss National Fonds.
Curcumin attenuates leukocyte and platelet adhesion in cerebral microcirculation in sepsis
Authors: Vachharajani Vidula Tushar 
Published: June 2021

Sepsis and septic shock are leading causes of death in non‐coronary intensive care units worldwide. Septic encephalopathy, a reversible CNS dysfunction independently increases mortality. We have demonstrated increased leukocyte (LA) and platelets (PA) adhesion in cerebral microcirculation (CM) of mice with experimental sepsis (cecal ligation and puncture: CLP) previously. Curcumin, a yellow pigment in turmeric known for its anti‐inflammatory properties in Ayurveda, has been used successfully in various experimental models of inflammation including sepsis. Although neuroprotective effect of curcumin has been studied in ischemic stroke, its effect in septic ephalopathy is unknown.This study shows the effects of curcumin on LA and PA in CM of mice with CLP.Hypothesis: Curcumin attenuates LA and PA in CM in mice with CLP.Materials and methods: Five to seven weeks old WT (C57Bl/6) mice underwent CLP or sham surgery. A separate group of animals were pre‐treated with 100 mg/kg/d curcumin for 48 hours prior to CLP. Cerebral post‐capillary venules were monitored for LA and PA 4 hours post‐surgery with intravital microscopy.Results: LA and PA were significantly increased in CLP vs sham groups with significant attenuation of both in curcumin pre‐treated CLP animals (Fig 1).Conclusion: Curcumin attenuates LA and PA in CM in experimental sepsis, suggesting a potential role for curcumin in sepsis.
Extracellular ATP is a pro‐angiogenic factor for systemic microvascular endothelial cells
Authors: Gerasimovskaya Evgenia V. , Woodward Heather N. , Roedersheimer Mark , Tucker Doug A. , Stenmark Kurt R. 
Published: June 2021

We recently reported that neovascularization of the vasa vasorum network occurs in the pulmonary artery (PA) adventitia of chronically hypoxic calves. Because extracellular adenine nucleotides are important regulators of vascular functions, we hypothesized that extracellular ATP may have a direct angiogenic effect on vasa vasorum endothelial cells (VVEC). We found that ATP dramatically increases DNA synthesis, migration, and tube formation on Matrigel in isolated VVEC. The PI3K/mTOR and ERK1/2 play a critical role in ATP‐induced mitogenic and migratory responses. However, only ERK1/2 contribute in part, to ATP‐induced tube formation on Matrigel. In contrast to VVEC, mitogenic responses to extracellular ATP were not observed in aortic and PA endothelial cells, indicating that VVEC, isolated from the sites of angiogenesis, exhibit a unique pro‐angiogenic phenotype with an augmented sensitivity to extracellular ATP. Further, using an in vivo Matrigel plug assay, we found subcutaneous injection of Matrigel containing MeSATP, ATPγ, MeSADP, and ADPβS resulted in plug neovessel formation (n=3). However, adenine nucleotides diminished the effect of total platelet lysates (n=11) on plug neovascularization (n=3). Together, our studies demonstrated that a fundamental molecule, ATP could be recognized as a potent regulator and/or modulator of angiogenesis in microvascular endothelial cells.(Supported by NIH grant: HL‐14985 and AHA grant: 0665464Z)
The Roles of p38α MAP Kinase in the Regulation of Embryonic Stem Cell Differentiation to Endothelial Cells and Cardiomyocytes
Authors: Guo Yan‐Lin , Ye Jianming , Huang Faqing 
Published: June 2021

p38 mitogen‐activated protein (MAP) kinase α (p38α) is a broadly expressedsignaling molecule that regulates various cellular processes in mammalian cells. Most studies of p38α have been focusing on adult somatic cells, but little is known about its function in embryonic stem cells (ESCs). We investigated the roles of p38α in mouse ESC differentiation to endothelial cells (ECs) and cardiomyocytes (CMs) using wild type and p38α deficient ESCs. ESC‐derived ECs formed monolayers similar to mature EC in culture. Furthermore, they could assemble into vascular structures that remarkably resembled the process of vasculogenesis. p38α−/−ESCs were able to differentiate into ECs as judged by the expression of EC specific markers PECAM‐1 and VE‐cadherin and expected morphology. Although it is not certain whether or not the vascular structures developed from p38α−/−ESCs are functionally normal, morphologically they do not significantly differ from the vessel structures derived from p38α+/+ ESCs. On the other hand, deletion of p38α may impair the differentiation of ESCs to CMs. CMs differentiated from ESCs were clearly identified in embryobodies (EBs) by their ability of spontaneous and rhythmical contracting (beating cells), which is a characteristic of mature CMs. The number of beating EBs derived from p38α−/−ESCs was significantly less than that obtained from wild type ESCs. Further analysis by real‐time PCR revealed that the mRNA expression of CM markers, MLC‐2v, α‐MHC and β‐MHC, in p38α−/−EBs was down regulated, indicating that p38α is important for CM differentiation. Taken together, our data suggest that p38α may play different roles in vasculogenesis and cardiomyogenesis.This work is supported by a grant from the National Institutes of Heath (HL082731, YLG).
Polymorphic Perversity in Protein Polymers
Authors: Egelman Edward Herschel 
Published: June 2021

We ask questions such as “What is the structure of F‐actin”. Since many proteins polymerize into helical filaments, answering these questions is essential to understanding the functional forms of these proteins. Unfortunately, high resolution structural information is available for very few polymers. One of the main reasons for this lack of structural information has to do with the variability of these polymers. Over the past 7 years, we have developed a new approach for reconstructing helical filaments from electron microscopic images. This method surmounts many of the problems present when using traditional approaches, and has now been applied to systems as diverse as the myosin thick filament, filamentous bacteriophage, pili, bacterial actin homologs and recombination filaments.I will show, using examples from a number of polymers, that these filaments can exist in a multiplicity of states. While we have described this phenomenon for F‐actin in the past, we can now show that it applies also to RecA‐DNA filaments or Rad51‐DNA filaments, or even bacterial Type III secretion system needles. Thus, for many of these polymers there is no single structure. Rather, explicating the function of these polymers requires understanding the multiplicity of states that can exist.
In vivo Uptake of BrdU, GFP and Iron Oxide Nanoparticles by Local Tissue Macrophages from Labeled Stem Cells. Implications for Cell Transplantation
Authors: Pawelczyk Edyta , Jordan Eleine Kay , Johnson‐Barelo Janna , Smith Melissa , Chaudhry Aneeka , Frank Joseph Alan 
Published: June 2021

There is increasing interest in using exogenous labels (bromodeoxyuridine (BrdU), green fluorescent protein (GFP) or dextran coated iron oxide nanoparticles (SPION) to label cells, to identify transplanted cells and monitor their migration by fluorescent microscopy or in vivo magnetic resonance imaging. Direct implantation of cells into target tissue can result in >70% cell death. Bystander uptake of labeled cells by tissue macrophages (TM) can confound the interpretation of imaging studies. This study investigates the frequency of BrdU, GFP and SPION uptake by TM from labeled cells using a model of angiogenesis and inflammation.Methods:BrdU, GFP, SPION labeled, unlabeled human mesenchymal stromal cells (MSC) were mixed with Matrigel? and implanted over shoulders of mice. Animals (n=72) were euthanized on days 7, 10, 14 post‐implantation and Matrigel? plaques (MPs) dissected and digested. Recovered cells were analyzed by fluorescence microscopy and flow cytometry (FACS) with anti‐CD11b, ‐dextran, ‐GFP or ‐BrdU antibodies.Results:FACS analysis of MPs with BrdU‐labeled MSC revealed 7% of BrdU positive TM, while MPs containing GFP or SPION –labeled MSC had 15% of GFP or dextran positive TM across time points.Conclusions:Direct implantation of labeled stem cells into target tissue can result in about 15 % of label being taken up by macrophages. Care should be taken to validate labeled cells by microscopy.