bluuebunny/crossref_metadata_2025_split huggingface dataset:
3D Atlas of the developing human
Authors: de Bakker Bernadette S. , de Jong Kees H. , Hagoort Jaco , Oostra Roelof-Jan , Moorman Antoon F.M. 
Published: June 2021

Knowledge of complex morphogenetic processes that occur during embryonic development is essential for understanding the anatomy of the (human) body and to get insight in the pathogenesis of various congenital malformations. Understanding these processes, which are difficult to comprehend for (bio)medical students, can be facilitated by using a three‐dimensional (3D) developmental series of the different organ systems of human embryos. In this project we aim to create such a 3D atlas of human development.Serial sections of 33 human embryos between Carnegie stages 7 (16 days) and 23 (56 days) are used to create 3D reconstructions of different organ systems. Digital images of the first series of sections were received from the Computer Imaging Laboratory of the Louisiana State University in New Orleans and additional images of a second series of sections were captured at the Carnegie Collection of the Walter Reed Army Medical Center in Washington D.C.. Amira version 5.3 is used to align the sections and to create the 3D reconstructions. The reconstructed organ systems are: Central Nervous system/Peripheral Nervous system/Eyes and Ears/Cardiovascular system/Intestines/Lungs, Liver, Spleen/Urogenital system/Somites and Skeleton/and the Coelom.Since January 2010, 25 (bio)medical students of the University of Amsterdam have been involved in this project via different educational projects. Each student focused on an individual organ system of interest (OOI). They studied the development of their OOI from textbooks and learned to understand embryology from serial sections, after which they produced 3D reconstructions of different stages of their OOI and presented their data to each other and to the department staff. In this way the students learned a great deal about human organogenesis and additionally produced a large amount of 3D reconstructions that will be included in the atlas and be used for both future education and for research purposes.Grant Funding Source: Academic Medical Center
Effects of calpain inhibition in excitation‐contraction coupling properties in dystrophic muscle exposed to fatiguing contractions
Authors: Mazala Davi Augusto Garcia , Chen Dapeng , English Sam A , Grange Robert W , Chin Eva R 
Published: June 2021

Duchenne muscular dystrophy (DMD) is the most severe type of muscular dystrophy affecting humans. Alterations in intracellular calcium (Ca2+) are thought to play an important role in skeletal muscle weakness in DMD due to the activation of Ca2+‐regulated proteases (calpains).Purposeto evaluate if impairments in Ca2+ regulation are exacerbated in muscle from three mouse models of DMD and if calpain inhibition could attenuate the muscle weakness induced by fatiguing contractions.Methodscontrol (C57BL10/ScSn; n=3), mdx (n=5), mdx/Utr+/− (n=6), and mdx/Utr−/− (n=4) mice were used in the present study. The flexor digitorum brevis single muscle fibres (SMF) were obtained by collagenase digestion and loaded with Fura‐2 AM to evaluate resting [Ca2+]i, peak [Ca2+]i, and time to fatigue with and without a calpain inhibitor (ALLN).Resultsresting [Ca2+]i was higher in two dystrophic mouse models (mdx and mdx/Utr+/−) compared to the control (CON) group (p<0.05). No differences were reported in peak [Ca2+]i or time to fatigue. However, dystrophic fibres (all groups) exposed to ALLN were able to maintain their pre‐fatigue [Ca2+]i levels compared to Vehicle‐treated fibres (p<0.05). These data suggest that calpain activation leads to the reduction in [Ca2+]i observed after fatiguing tetani and therefore likely contributes to muscle weakness following a bout of muscle contractions in DMD.
Molecular mechanisms of the crosstalk between mitochondrial and NADPH oxidase derived reactive oxygen species in white blood cells – implications for cardiovascular diseases
Authors: Steven Sebastian , Schuhmacher Swenja , Wenzel Philip , Oelze Matthias , Daub Steffen , Scholz Alexander , Xia Ning , Schulz Eberhard , Li Huige , Lackner Karl J. , Münzel Thomas , Daiber Andreas 
Published: June 2021

BackgroundOxidants and antioxidant enzymes are involved in the development of many disease such as atherosclerosis. There are reports on a crosstalk between different sources of oxidative stress. With the present study we sought to determine the underlying mechanism of this crosstalk.Methods and resultsComplex III inhibitors were used to induce the Nox‐dependent oxidative burst by mitochondrial ROS (mtROS) in human neutrophils. Nox2 derived ROS were measured by a chemiluminescence assay. Inhibitors for the involved signaling cascade such as cyclosporine A (effects mitochondrial permeability transition pore [mPTP]), chelerythine (effects protein kinase C) and apocynin (effects Nox) were used. This crosstalk between mtROS and Nox was absent in white blood cells from p47phox deficient mice (Nox2 subunit) or from cyclophilin D knockout mice (mPTP subunit), whereas this crosstalk was amplified in white blood cells from MnSOD+/− mice. We observed that increases in blood pressure, endothelial dysfunction or Nox activity were more pronounced in MnSOD+/− mice as compared to wild type‐mice.ConclusionsDikalov et al. have demonstrated that Nox derived ROS increases mtROS contributing to overall angiotensin‐II dependent cellular dysfunction. Our data show that mtROS trigger the activation of Nox, which may have severe effects on progression of cardiovascular diseases since it represents a feedback loop.
Simultaneous EGF receptor and thrombin receptor activation synergistically induces pro‐angiogenic immediate early genes in endothelial cells
Authors: Waitkus Matthew , Chandrasekharan Unni , DiCorleto Paul 
Published: June 2021

Signaling interactions between G‐protein coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs) function in a number of pathophysiological processes, including cellular proliferation, invasion, and acquired resistance to chemotherapeutic agents. Here, we examine the consequences of simultaneous EGF receptor (EGFR) and thrombin receptor (protease‐activated receptor‐1, PAR‐1) activation in human endothelial cells (EC). We observe that concurrent EGFR and PAR‐1 activation causes the synergistic induction of at least six pro‐angiogenic immediate early genes (IEGs), including the transcription factor early growth response‐1 (EGR‐1). In contrast to other cell types, matrix metalloprotease‐mediated transactivation of EGFR by PAR‐1 does not appear to be a major signaling mechanism in EC. Instead, an intracellular mechanism involving glycogen synthase kinase‐3 (GSK‐3α/β) mediates receptor crosstalk by integrating signals from EGFR and PAR‐1. These findings provide a mechanistic basis for how cells integrate information of concurrent receptor activation to enhance EGR‐1 expression in EC.This study was supported by grant HL29582 from the National Institutes of Health (Dr. DiCorleto).
Detection of antibodies to HPV vaccine types using a multiplexed immunoassay
Authors: Panicker Gitika , Rajbhandari Ira , Unger Elizabeth 
Published: June 2021

Measurement of HPV antibodies in unvaccinated individuals has been used as measure of lifetime exposure to HPV. With the implementation of HPV vaccines, reliable assays are needed to evaluate the impact of altered dosing schemes or of new vaccine formulations. An ideal assay platform would allow multiplex type‐specific detection with minimal sample requirement.We used the Meso Scale Discovery (MSD) electrochemiluminescence ECL based detection platform to develop a multiplex direct‐ virus‐like particles (VLP) assay. HPV 6, 11, 16, and 18 VLPs were produced in mammalian cell‐culture and purified using Optiprep™ gradient followed by agarose gel filtration. MSD prepared the plates in the 7‐spot/well format, using the purified VLPs (4 spots) and PBS pH 7.4 as blank (one spot). We used four different coating conditions, varying VLP concentrations with and without bovine serum albumin (BSA). Results were evaluated using a set of 17 sera, WHO International Standard for HPV 16, and an optimized ELISA protocol for MSD plates on the SI6000 imager. Three point titrations and the parallel line method was used to calculate antibody titers. Stability of the plates was evaluated by comparing results after varying times of storage.The use of BSA in spot‐coating allowed for increased stability of the VLPs on the plate as indicated by similar RLUs on plates tested 1 month apart. The intra and inter‐assay CVs between PLL values calculated for each type was less than 8% and 17% respectively. No cross‐reactivity was observed between HPV types. The MSD platform shows promise for simultaneous quantitation of the antibody responses to several HPV types in a high‐ throughput manner. Funding for this project was provided by the American Recovery and Reinvestment Act.The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the funding agency
Chemical Imaging of Cholesterol and Sphingolipid Distribution in the Plasma Membranes of Fibroblast Cells
Authors: Kraft Mary L , Frisz Jessica F. , Klitzing Haley A. , Lou Kaiyan , Lizunov Vladimir , Zimmerberg Joshua , Weber Peter K. 
Published: June 2021

Cholesterol‐ and sphingolipid‐enriched membrane microdomains, which are referred to as lipid rafts, appear to mediate important biological functions. Yet, the distributions of cholesterol and sphingolipids within the plasma membrane remain poorly defined. The goal of this work is to use high‐resolution secondary ion mass spectrometry (SIMS) to directly image the distributions of cholesterol and sphingolipids within the plasma membranes of fibroblast cells. In our approach, we metabolically labeled the cells so that the cellular sphingolipids contained nitrogen‐15, and the cellular cholesterol contained oxygen‐18. We then employed a SIMS instrument designed for high‐resolution isotopic imaging of surfaces (Cameca NanoSIMS 50) to visualize the distributions of 18O‐cholesterol and 15N‐sphingolipids in the plasma membrane by mapping the 18O‐enrichment and 15N‐enrichment, respectively, on the cell surface (top <5 nm) with a lateral resolution of approximately 90 nm. Whether the cholesterol and sphingolipids were heterogeneously distributed and co‐localized within the plasma membrane was quantitatively assessed. Our data demonstrates that lipids within the plasma membrane are spatially organized on length scales that range from two hundred nanometers to a few micrometers.This research was supported by the National Science Foundation under CHE – 1058809 and a Career Award at the Scientific Interface from the Burroughs Wellcome Fund.
Effects of a Low‐carbohydrate vs. High‐carbohydrate, Highfiber Diet on Soluble Cell Adhesion Molecules and Endothelial Function in Adults With Metabolic Syndrome
Authors: Angadi Siddhartha , Weltman Nathan , Patrie James , Barrett Eugene , Weltman Arthur , Brock David , Irving Brian , Davis Christopher , Rodriguez Jessica , Gaesser Glenn 
Published: June 2021

Twenty‐three adults (6 males) with the metabolic syndrome participated in a randomized cross‐over study to assess the effects of a low‐carbohydrate diet [LC: 15–20% carbohydrate (fiber ≤ 10 g/day), 55–60% fat, 25–30% protein] and a high‐carbohydrate, high‐fiber diet [HCHF: 55–60% carbohydrate (fiber ~45g/day), 20–25% fat,15–20% protein] on serum biomarkers of endothelial function and brachial artery flow‐mediated dilation (BAFMD). Each ad libitum diet lasted 4 weeks, with a 4‐week washout. sE‐selectin was reduced (P < 0.02) by 10–15% after both diets. Inter‐cellular adhesion molecule 1 was reduced only after LC (6.6%; P < 0.03); vascular cell adhesion molecule 1 was unchanged by either diet. After HCHF, adiponectin decreased by 8.3% (P < 0.01), with a trend for increased fibrinogen (5.3%, P = 0.075). For BAFMD a significant (P = 0.01) diet interaction was observed for pre vs. post diet changes (LC: 10.1 ± 1.4% vs. 7.2 ± 1.1%, P = 0.06; HCHF: 9.5 ± 1.3% vs. 10.4 ± 1.5%, P = 0.61). Despite greater improvements in circulating adhesion molecules following LC, BAFMD was impaired relative to a HCHF diet. This may be due in part to significant elevations in plasma free fatty acids after LC (±16.7%, P < 0.02). Biomarkers of endothelial function may not accurately reflect the vascular dysfunction that results after following a LC diet in adults with metabolic syndrome.Funded by NIH RR MO100847 and a grant from the Wheat Foods Council.
Calcium intake, restrained eating, physical activity and bone health in college‐aged Caucasian women
Authors: Joyeux Danielle , Durham Holiday , Zanovec Michael , Tuuri Georgianna 
Published: June 2021

Building peak bone mass through young adulthood is important in the prevention of osteoporosis. This study examined if bone quality was associated with calcium (Ca) intake, restrained eating and physical activity in a group of 99 young adult women. Caucasian volunteers, 20–29 years of age completed a Block Food Frequency Questionnaire, Dutch Eating Behavior Questionnaire (DEBQ) and the International Physical Activity Questionnaire. Heights and weights were measured using standard procedures, and calcaneus stiffness index (SI) scores were recorded using an Achilles Insight GE quantitative ultrasound. Participants had a mean ± SD age, height, weight, BMI, bone quality, restrained eating and physical activity of 21.5 ± 1.7 yrs, 164.0 ± 6.4 cm, 61.4 ± 9.2 kg, 22.8 ± 2.7 g/m2, 100.5 ± 15.7 SI, 26.6 ± 7.4 restrained eating DEBQ score and 1523.4 ±1346.8 MET‐min/wk, respectively. Mean ± SE Ca intake was higher among women who supplemented versus those who consumed only dietary Ca (980.11 ± 488.4 mg and 932.2 ± 487.2 mg, respectively (P=0.04)). Based on the EAR, neither group was at risk for inadequate Ca intake. Multiple linear regression controlled for body weight indicated that SI score was not associated with Ca intake, restrained eating or physical activity. Bone quality in this group of young adults was not related to behavioral factors commonly associated with bone health.Funded in part by Federal Hatch Act Funds # LAB 93846
Buffets and obesity: is there a connection?
Authors: Temple Norman Joseph , Nowrouzi Behdin 
Published: June 2021

ObjectiveTo determine whether buffets have become more common over the last 30 years in Greater Toronto.MethodsWe measured advertising for buffets (newspapers and Yellow Pages) as a proxy measure of buffet restaurants. Searches were done in two time periods: 1963–1988, and 2011 (up to September).ResultsBetween 1963 and 1988, we found 6 advertisements for buffet restaurants in Toronto (4 in the Yellow Pages and 2 in newspapers). In 2011 we found 16 advertisements (all in the Yellow Pages).CommentBuffets are restaurants that allow unlimited amounts of varied food to be eaten at a fixed price. They combine together several factors that encourage an excessive intake of food energy: they are a fast‐food restaurant, customers can take large portions, and (in most cases) they supply unlimited amounts of energy‐dense food at a relatively low price. Virtually no research has been conducted on the relationship between buffets, energy intake, and weight gain. Our findings indicate that there has been a large growth in the number of restaurants in Toronto offering buffets during the time period that obesity rates were climbing rapidly. These findings are consistent with the possibility that buffets are a factor involved in the epidemic of obesity. Future studies should measure actual food intake when customers eat at a buffet.
Intake, Knowledge, Beliefs and Perception Regarding the Benefits and Barriers of Nuts Intake Among Individuals with or at Risk of Cardiovascular Disease and/or Diabetes
Authors: Pawlak Roman , London Hilary , Colby Sarah , Wall-Bassett Elizabeth , Sira Natalia 
Published: June 2021

ObjectiveTo assess the knowledge regarding health effect and nutrient content of nuts and to assess intake of nuts. Also, assess perceptions regarding benefits and barriers of nuts intake among individuals with or at risk of cardiovascular disease (CVD) and/or diabetes.MethodsA cross‐sectional survey was administered to 85 participants (Caucasians ‐77.6% and African Americans ‐ 22.4%, mean (SD) age = 62.91 (9.40).ResultsAbout one‐third of the participants had been diagnosed with diabetes and two‐thirds with one or more forms of CVD; heart disease (61.4%), heart attack (56.4%), angina (51.8%), and stroke (50.0%). About 40% of individuals were not aware nuts could help lower the risk for heart attack or diabetes. Approximately 33% were unsure of the impact of nuts on cholesterol level and additional 21% disagreed that nuts can decrease cholesterol. Only 27.1% agreed or strongly agreed that their doctor advises them to eat nuts. However, 63.5% agreed or strongly agreed that they would consume nuts on most days of the week if the doctor made such a recommendation.ConclusionResults indicate low intake and knowledge regarding the health benefits of nuts.Research was not funded.
U.S. Trends in dietary variety and its association with BMI and micronutrient intakes
Authors: Ebner Rachel Eve , Burke Aoife P , Kranz Sibylle , Boushey Carol J , Roberts Susan B , McCrory Megan A 
Published: June 2021

One proposed contributor to excess energy intake is dietary variety, particularly energy‐dense variety (McCrory et al 1999). Using national survey data, we examined the potential role of dietary variety in the obesity epidemic and relationships among variety and micronutrient intake. Usual dietary intake data from the Continuing Survey of Food Intakes by Individuals (CSFII) 1989–91 and 1994–96 were coded and six dietary variety scores were calculated as described previously (Roberts et al 2005). We included adults aged 21–60 y, and excluded individuals with implausible energy intake reports (Huang et al 2005) and BMI<17 kg/m2. Results showed all types of dietary variety increased from 1989–91 to 1994–96 (p≤.025), except for food group variety which remained constant. In both surveys, energy‐dense variety was higher and energy‐weak variety was lower with higher BMI (p≤.05). Micronutrient dense variety was positively associated with mean micronutrient intake (%EAR) in both surveys (p≤0.001), whereas energy‐dense variety was only weakly associated with greater micronutrient intake in 1989–91 and not associated in 1994–96. Increasing energy‐dense variety over time may lead to weight gain with minimal contribution to micronutrient intake.Grant Funding Source : n/a
Complementary foods for appetite suppression
Authors: Sussman Elizabeth , Johnston Carol S 
Published: June 2021

New diet strategies are needed to aid with weight loss and adherence to energy‐restricted diets. This study examined the appetite suppression and antiglycemic effects of two novel foods: algae and gelatin. In a double‐blind, randomized, crossover study, 15 healthy individuals (7 M, 8 F; 28±7y, BMI 26.1±5.6kg/m2) consumed an isocaloric breakfast meal under three treatments separated by 1–2 wk: control (buttered bagel, juice); algae (algae [4g protein] enriched butter, bagel, juice); and gelatin (gelatin [4g protein] enriched butter, bagel, juice). Five blood samples (0, 30, 60, 90, 120 min postprandial) were collected and analyzed for glucose. Hunger was assessed using a 100mm visual analog scale. Food and beverage consumption for the remainder of the day was recorded. Neither algae nor gelatin altered postprandial glycemia or perceptions of hunger up to 2 h post‐ingestion. However, there was a marked decrease (300–400 kcal) in subsequent 24 h energy consumption in the gelatin group when compared to the algae (p=0.01) or control (p=0.07) groups. These data suggest that gelatin ingestion may be associated with appetite suppression over a 24 h period. Supported by ASU Graduate and Professional Student AssociationGrant Funding Source: Graduate and Professional Student Association, Arizona State University
Genotypic differences impact serum and hepatic lipids in mice lacking carotenoid cleavage enzymes
Authors: Elsen Amy Christine , Ford Nikki A. , Erdman John W. 
Published: June 2021

Adult mice lacking the β‐carotene central cleavage enzyme, carotene‐15,15′‐monoxygenase (CMO‐I), have been reported by Hessel and colleges to have altered lipid metabolism, but little is known about the lipid content in carotene‐9′10′‐monooxygenase II knock‐out (CMO‐II KO) mice or whether tomato powder or lycopene alters lipid deposition in either genotype. Serum and hepatic lipid content was measured in female CMO‐I KO, CMO‐II KO and wild type (C57BL/6Jx129x1/SvJ) mice fed AIN‐93G based diets: 10% tomato powder diet, 100 mg lycopene/kg beadlet diet or placebo beadlet diet for 4 days. Hepatic lipid content was significantly greater in CMO‐I KO mice and CMO‐II KO mice relative to wild‐type mice, independent of dietary intervention (p <0.005). H&E staining revealed that 25% of CMO‐I KO adult mice have minimal hepatic lipidosis. The diets in this study negligibly impacted lipid content. Specifically, hepatic cholesterol levels were elevated in CMO‐II KO mice when fed lycopene beadlet diet compared to placebo beadlet diet (p <0.05) and decreased in mice when fed tomato powder compared to AIN‐93 G diet (p<0.05). This data suggests that a lack of CMO‐I or CMO‐II alters serum and hepatic lipids but short term feeding of carotenoid diets has minimal impact on lipid deposition in these mice.Grant Funding Source : NIH grant PHS‐RO1 CA125384
Biomarker erythrocyte copper chaperone for superoxide dismutase (CCS) is higher following marginal copper deficiency
Authors: Prohaska Joseph R , Lassi Katie , Broderius Margaret 
Published: June 2021

There is a critical need to identify an accurate copper biomarker to diagnose and treat adult onset copper deficiency. Prevalence is rising due to secondary impacts of antagonists such as zinc and popularity of bariatric surgery. Marginal copper deficiency (CuM) and iron deficiency (FeD) were studied in Sprague Dawley rat and Swiss Webster mouse models using modified AIN‐93G diets. Red blood cell (RBC) superoxide dismutase (Sod1) and plasma ceruloplasmin (Cp) protein were found to be altered by both FeD and copper deficiency (CuD), while CCS and CCS/Sod1 ratio were found only to be altered in CuD rats; and importantly, after only 1 week of treatment in post weanling males. RBC CCS levels were highly negatively correlated, r = −0.91, with liver copper in CuD, CuM and copper adequate (CuA) rats. Post weanling CuD male mice reared in plastic cages for 5 weeks had no significant reduction in liver copper, plasma Cp protein, or RBC Sod1 compared to CuA mice but CuD mice displayed 2‐fold higher RBC CCS. CuD adult male mice with no significant changes in Cp activity and protein after 5 weeks of dietary treatment displayed augmented RBC CCS. Additional research is needed to establish that erythrocyte CCS is a suitable copper biomarker for humans but RBC CCS appears to be a robust marker for marginal copper deficiency in rodent models.Supported by the International Copper Association and USDA NIFA 2006‐35200‐17378.