bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inter‐relationship Between the In vivo Metabolism of Apolipoprotein B100‐Containing Lipoproteins and LDL Particle Size and LDL Particle Number
Authors: Leclerc Myriam , Ooi Esther , Couture Patrick , Richard Caroline , Desroches Sophie , Marin Johanne , Tremblay André , Lamarche Benoît 
Published: June 2021

Studies have shown that small dense LDL particles confer an increased risk of coronary heart disease (CHD) compared with large LDL. LDL particle number is also an important risk factor for CHD.The objective was to investigate the inter‐relationship between the in vivo kinetics of apolipoprotein (apo) B100‐containing lipoproteins and LDL particle size (LDLsi) and LDL particle number (LDL‐apoB).This analysis is based on data from 154 male and female subjects among whom in vivo lipoprotein kinetics were investigated using a bolus/infusion of D3‐leucine. LDLsi was assessed by non‐denaturing polyacrylamide gradient gel electrophoresis. Participants' mean age (±SD) was 44.7±12.6 yrs. Mean body mass index (BMI) and triglyceride levels were 28.6±4.7 kg/m2 and 1.97±1.4 mmol/l respectively.LDLsi correlated positively with plasma adiponectin levels (age and BMI‐adjusted Spearman r=0.41, P<0.001) and the fractional catabolic rate (FCR) of VLDL‐apoB (r=0.43, P<0.001) and negatively with plasma TG (r=‐0.42 P<0.001) and the pool size of VLDL‐apoB (r=‐0.38, P<0.001). Plasma LDL‐apoB levels correlated positively with the production rate of VLDL‐apoB (r=0.27, P=0.006) and negatively LDL‐apoB FCR (r=‐0.59, P<0.001). LDL‐apoB showed no correlation with plasma TG (r=0.07, P=0.47), LDLsi (r=0.18, P=0.08) and adiponectin (r=‐0.02, P=0.82).These data suggest that LDL size and LDL particle number are determined by distinct metabolic pathways.Funding provided by the Canadian Institutes of Health Research and the Chair of Nutrition, Université Laval
Vitamin D Inhibits ROS, ICAM‐1, and Monocyte Adhesion in High Glucose and Acetoacetate Treated Endothelial Cells by Upregulating GSH
Authors: Kanikarla Marie Preeti , Jain Sushil 
Published: June 2021

The incidence of developing microvascular dysfunction is significantly higher in type 1 diabetic (T1D) patients. Monocyte adhesion to the endothelium plays a central role in the progression of endothelial dysfunction. This study examines whether vitamin D (VD) supplementation is beneficial in preventing endothelial dysfunction in diabetes. Human umbilical vein endothelial cells (HUVEC) were treated with 1, 25‐(OH)2‐D3 (0‐25 nM, 24 h) and later exposed to the ketone body acetoacetate (AA, 4 mM) or high glucose (HG, 25 mM) for 24 h. Treatment with AA or HG causes an increase in ROS, ICAM‐1 expression, and monocyte adhesion, along with a decrease in GSH levels in HUVEC. VD supplementation (25 nM) significantly lowered ROS (41%, p<0.05), ICAM‐1 (73%, p=0.05) and monocyte adhesion (37.5%, p=0.05) in AA treated HUVEC. VD had a similar beneficial effect on HG treated cells. Interestingly, we also saw an upregulation in GSH levels following treatment with VD. We hypothesize that the beneficial effect of VD is mediated by the upregulation of GSH. Glutamyl cysteine ligase (GCLC) catalyzes GSH biosynthesis. Knocking down GCLC using siRNA reduced GSH levels as well as abolished the beneficial effect of VD on ketone‐ or HG‐induced ROS, ICAM‐1, and monocyte adhesion. This suggests that VD mediates its beneficial effects via the upregulation of GCLC. This study provides the biochemical mechanism through which VD can lower ROS, ICAM‐1 expression, monocyte–endothelial adhesion, and thereby lower the risk of endothelial dysfunction in diabetes.
Supported by the NIH, the Malcolm Feist chair in Diabetes, and a fellowship from the Malcolm Feist Cardiovascular Research Endowment, LSUHSC‐Shreveport.
Selection Gradients and Ecogeographic Variance in the Human Post‐Crania
Authors: Savell Kristen , Roseman Charles , Auerbach Benjamin 
Published: June 2021

Recent work by Roseman and Auerbach (in press) indicates that the ecogeographic distribution of human body proportions is driven by a combination of neutral evolutionary forces and natural selection. This contrasts with assumptions that natural selection produces morphological variance along ecogeographic clines (i.e., Bergmann's and Allen's “rules”). Roseman and Auerbach's approach, however, does not distinguish between direct and indirect responses to the natural selection acting on these morphologies. This study uses retrospectively estimated selection gradients for limb lengths, femoral head size, and body breadth to assess the nature of selective forces on ecogeographic variance in human morphology.We estimated the vectors of selection gradients required to evolve one group into another for pairs of populations across major climate regions, and used parametric bootstraps to determine 95% confidence intervals. Equatorial African populations are assumed to have been drifting atop a plateau on the adaptive landscape, reflecting a tropically‐adapted human state. Results indicate that strong selection on distal limb lengths, femoral head size, and body breadth effected an evolutionary transition to morphologies found in arctic populations. The patterns of selection necessary to effect a transition to proportions found in more temperate regions (i.e. North Africa and Europe) were qualitatively similar but much less strong. These results in part support the findings of Roseman and Auerbach, but suggest that the action of natural selection may be entangled with random genetic drift, gene flow, and neutral mutation.
A Novel Nutrient Profiling Score To Drive Food Reformulation
Authors: Masset Gabriel , Vlassopoulos Antonis , Potter Monika , Leroy Fabienne 
Published: June 2021

BackgroundNutrient profiling (NP) has been mainly used for regulation or food labeling purposes; few systems have been proposed to track food reformulation across a wide range of manufactured foodsObjectiveTo present a category‐specific NP model, the NF score, which aim is to facilitate the tracking of nutritional characteristics of foods; and to show examples of NF score implementationMethodsThe NF score is calculated as an unweighted average of common (energy, added sugars, fructose, sodium, and total, saturated, and trans fats) and category‐specific (e.g. calcium for dairy products, fiber for breads) nutrient ratios (R) calculated per serving: NF score=Average R. For nutrients to limit, R=content/criteria; for nutrients to encourage R=criteria/content. The criteria are category‐specific and linked to public health recommendations, target population (children or adults), and to the role of the food category in the diet. If the food content for one nutrient does not reach the criteria (i.e. R>1), then all Rs蠄1 are set to 1, to ensure that a nutritional weakness cannot be compensated for. Any score above 2 is capped at 2. The final NF score, ranging from 0 to 2, is reversed for a more intuitive reading; any score below 1 indicates that the food has at least one nutritional weakness.ResultsThe NF score was used to assess the evolution of nutritional characteristics of reformulated foods. For all the examples but one, there was an improvement of the NF score (Figure). Improvements for the Cereal bar, Sugar candies, and Pepperoni pizza were also linked to a reduced serving size.imageConclusionsThe NF score allows for a sensitive tracking of food reformulation. Testing the NF score in standard food composition databases should highlight how effective the NF score could be in improving the food environment.
Epigenetic Regulation of the FXR by High Fat Diet and APC in Colon Cells
Authors: Lyon Adam , Selmin Ornella , Fang Changming , Smith Jeffrey , Doetschman Tom , Thompson Patricia , Martinez Jesse , Lance Peter , Romagnolo Donato 
Published: June 2021

The farnesoid‐X‐receptor (FXR) controls hepatic and intestinal bile acid (BA) homeostasis. BAs not reabsorbed via the enterohepatic circulation are converted in the colon to deoxycholic acid (DCA) and other cancer‐promoting secondary BAs. Loss of FXR expression is observed in adenomatous polyposis coli (APC) gene‐deficient colonocytes from mice and the majority of colon cancers.OBJECTIVETo investigate whether Western high‐fat diet (HFD) and APC status influence colonic mucosal epigenetic regulation of the Fxr.METHODSWeaned C57BL/6J male mice were fed a HFD (22% safflower oil=SO) or low fat diet (LFD; 5% SO) for 6 wks. Effects on CpG methylation of Fxr, and expression of FXR, peroxisome‐proliferator activated receptor (PPAR)‐γ, and cyclooxygenase‐2 (COX‐2) were examined. The influence of APC status on CpG methylation of the Fxr gene, and expression of FXR, ileal bile acid‐binding protein (IBABP), small heterodimer partner (SHP), and COX‐2 in normal colonic mucosa and colon tumors from APCMin/+ mice was investigated.RESULTSA 60% reduction in Fxr promoter methylation and 2 to 3‐fold increases in FXR, COX‐2, and PPARγ levels were observed with the HFD. APC‐deficiency was associated with constitutive hypermethylation of the Fxr gene, elevated COX‐2 levels, and 60‐90% reductions in baseline FXR, IBABP, and SHP expression. In human HCT‐116 colon cells, siRNA knock‐down of APC caused a 50% reduction in basal FXR expression, which was lowered by an additional 30% on exposure to DCA.CONCLUSIONSAPC deficiency leads to constitutive epigenetic silencing of Fxr that combined with a HFD enhances BA‐induced inflammation and colon cancer.
Heterogeneity in the Proliferative Capacity of Smooth Muscle Cells (SMCs)
Authors: Sandison Mairi , McCarron John 
Published: June 2021

In cardiovascular disease, artery walls remodel through an increase in SMC numbers. The predominant hypothesis for this is that SMCs in the tunica media undergo phenotypic modulation into a proliferative cell type. However, direct evidence for SMC phenotypic modulation is scant. We therefore exploited time‐lapse microscopy methods to track the fate of freshly isolated, contractile SMCs. As SMCs isolated from different smooth muscle (SM) tissues are heterogeneous in nature, we have used time lapse microscopy in combination with immunocytochemistry to investigate the proliferative capacity of SMCs from portal vein (PV), carotid artery (CA) and distal colon.The adventia/endothelium and mucosa/serosa were mechanically removed before isolating cells by enzymatic digestion and trituration. Highly elongated, contractile SMCs that stained for both SM α‐actin (SMA) and SM myosin heavy chain (SM‐MHC) were obtained from all tissues. Significantly, both colon and PV tissues also contained large numbers of spherical cells that did not stain for SMA or SM‐MHC (nonSMCs). In standard culture conditions, the SMCs showed limited proliferative capacity: with the exception of one SMC that divided once (out of 15 tracked cells), colon SMCs did not proliferate. Of 11 PV SMCs tracked, 7 SMCs did divide, though none progressed beyond the 3rd generation (daughter of daughter) by confluency. Conversely, the nonSMCs proliferated rapidly (reaching the 5th generation in 5 days) and dominated the resulting cultures. In contrast, all CA cells stained for both SMA and SM‐MHC i.e. no nonSMCs were present. Whilst most CA SMCs underwent apoptosis early in culture (27 of 31 cells), those that survived went on to proliferate at varying rates (up to the 6th generation in 5 days). These results illustrate the complexities involved in creating models of SMC proliferation.
Coxsackieviral Infection Causes Cytoplasmic Aggregation and Cleavage of TAR DNA Binding Protein‐43
Authors: Fung Gabriel , Shi Junyan , Deng Eric , Zhang Jingchun , Hong Andy , Luo Honglin 
Published: June 2021

Coxsackievirus B3 (CVB3) is a positive single‐stranded enterovirus that infects the heart. CVB3 infection can cause myocarditis and lead to dilated cardiomyopathy (DCM). In North America, DCM accounts for approximately 20% of heart failure and sudden death in children and young adults. Recent findings have shown similar molecular pathologies between cardiomyopathies and neurodegenerative diseases. In neurodegenerative diseases such as frontotemporal dementia and amyotrophic lateral sclerosis, insoluble‐cytoplasmic TAR DNA binding protein‐43 (TDP‐43)‐aggregates are a common biomarker contributing directly to pathological disease progression. The importance of insoluble protein aggregates in viral pathogenesis has also been recognized, resembling that of neurodegenerative diseases. However, the significance of TDP‐43 in CVB3‐induced cardiomyopathy remains unstudied.In this study, we investigated the interplay between CVB3 and TDP‐43 using A/J mice, a strain susceptible to virus‐induced cardiomyopathy, and HeLa cell culture models. Our studies demonstrated that CVB3 infection leads to redistribution of nuclear TDP‐43 into cytoplasmic aggregates in a viral protease 2A dependent manner. We also found that viral protease 3C, actively cleaves TDP‐43 at amino acid 327 into two respective cleavage fragments. The respective N‐terminal cleavage fragment inhibited native TDP43 activity in the nucleus as a transcriptional regulator. We conclude that TDP‐43 pathologies in CVB3‐induced cardiomyopathy may be similar to those previously found in neurodegenerative diseases.This work was supported by the Canadian Institutes of Health Research (HL)
Measuring Brain Activity in Fourth Grade Students Through Biopac Science Lab
Authors: Hamilton Shannon , Brown Carson , Evans LeVisa , Majors Katharyn , Thomas Destini , Gurovich Alvaro 
Published: June 2021

Recently the American Physiology Society (APS) has been working to increase learning and making science fun for elementary school students. Physiology Understanding Week (PhUn) is the APS initiative to use interactive experiments to engage school‐age children with science and physiology. In this project we used a Biopac MP40 system to measure brain activity of fourth grade students at Dixie Bee Elementary School. The activity was divided in 5 different sessions, one per room, in two different days, reaching 116 elementary school students. Each room was divided in small 4‐student groups with the following general activity set‐up: 1) brief presentation about brain physiology using a brain model, 2) measuring brain activity during 3 different conditions, 3) analyzing collected data, and 4) discussing obtained results. Three electrodes were placed behind the student's ear, 2 students per group. Brain activity was collected during 4 different activities: 1) resting with eyes closed, 2) doing a math problem, 3) writing a sentence in cursive, and 4) playing catch with tennis ball. Our goal was to illustrate how brain activity changes while performing different tasks. The other 2 students controlled the computer and observe the changes in brain activity while they recorded the results. The students completed charts with the values of alpha, beta, and delta waves for each of the activities performed. This activity allowed the students to use applied technology while learning about the functions of the brain. This interactive method enables students to be more involved and interested in science; it also captures their attention and makes learning ‘PhUn’.Supported by IU AHEC 14/15 #PIU081 and APS PhUn week program
Variations in Branching of the Profunda Femoris Artery
Authors: Hurley Mary , Stevens Todd , Estaris Sharine , Duen Kelvin , Olivieri Marion 
Published: June 2021

The profunda femoris artery is a major branch of the femoral artery in the femoral triangle. The medial and lateral femoral circumflex arteries are typically branches of the profunda femoris artery within a few centimeters of its branching from the femoral. Netter's atlas shows the profunda femoris branching off the femoral artery closer to the inguinal ligament than is shown by Grant's atlasIn addition, Netter shows the medial and lateral circumflex femoral arteries branching opposite of each other close to the beginning of the profunda femoris, while Grant shows the lateral circumflex artery branching from the profundus femoris much more distal to the branching of the medial circumflex. After approval from D'Youville College IRB, thirteen cadavers were examined for variations in the branching of these arteries. Besides typical branching, in 6 of the cadavers the medial circumflex branched off the femoral artery, and in one, both medial and lateral circumflex were branches of the femoral artery.
The cardiac potassium channel HERG is blocked by calcium at a site near the outer mouth of the channel
Authors: Nguyen Andrew , Wong Alice , Oberoi Angad , Le Thuyvy , Miller Alan 
Published: June 2021

A reduction in the number of HERG channels has been implicated in Long QT Syndrome, which can degenerate into the lethal arrhythmia Torsades de Pointes. Patients can present with abnormal serum electrolyte levels due to a variety of conditions including gastrointestinal dysfunction, renal and endocrine disorders, diuretic use, alcoholism, and aging. The aim of this study is to determine if extracellular calcium blocks the pore of the HERG channel by acting at a site in the outer vestibule of the channel.Divalent block was measured using two‐electrode voltage clamping of Xenopus oocytes expressing either wild‐type HERG or the HERG mutants S631A, and G628CS631C. S631 is thought to be located in the outer pore of the HERG channel.Changing extracellular potassium from 0 mM to 20 mM resulted in a greater decrease in WT HERG current due to an increase in extracellular calcium, as well as a number of other divalent ions (Mg2+, Co2+ and Mn2+). In addition, block of WT HERG by calcium was voltage dependent, with increased block at negative voltages. Finally, there was little or no block of the HERG double mutant G628CS631C by calcium at all voltages tested, whereas there was increased block of the HERG mutant S631A by calcium at negative voltages.3 results suggest that calcium blocks HERG by physically occluding the pore of the channel: 1) the dependence of block on extracellular potassium. 2) the lack of block of G628CS631C 3) the altered voltage dependence of block of S631A. This study has implications for an increased risk of cardiac arrhythmias with hypokalemia as well as for patients with acute promyelocitic leukemia treated with arsenic, a trivalent ion that might block HERG at the same site as calcium.Funded by Touro University and NIHR 15‐1R15HL079971
PrdxI Encode Peroxiredoxin is Required for Vascular Development in Zebrafish
Authors: Wu Changyi , Syue Hai‐hong 
Published: June 2021

Genetic signaling and redox homeostasis are required for proper growth of blood vessels. Using zebrafish as a model organism have been intensively identified many molecules that control vasculature. Some antioxidant genes have been shown important for vascular growth. However, there is still limited information about oxidative stress and vascular development during embryogenesis. Here, we report a novel function of prdx1 that play critical roles in vascular growth during zebrafish developmentPrdx1 encodes a cytosolic peroxidase responsible for the remove of hydrogen peroxide and is highly conserved from yeast to mammal. Our in situ hybridization data showed the expression pattern of prdx1 is in developing vessels. Knockdown of prdx1 by morpholino injection impairs the vascular growth of ISV (intersegmental vessel) and CVP (cardinal vein plexus). We further showed the reduction of ISV is due to a decrease of cell proliferation and migration, but not cell death. Consistent with the vascular defects in prdx1MO, we found a decreased expression of vascular markers, flt4,mrc1, stabilin and ephrinb2. Loss of prdx1 results in vascular defects suggests the antioxidant function is important. Thus, we test if oxidative stress could cause vascular defects. Our data showed H2O2 treatment impaired CVP formation and synergetic effects are showed while H2O2‐treated in prdx1MO. We also found the expression of main antioxidant genes (SOD1, SOD2, catalase and prdx2) are decreased while loss of prdx1. Finally, prdx1 likely regulates hemangioblast fate decision because the increased expression of blood marker gata1 concurrent with the decreased expression of endothelial markers in prdx1 MO. Together, we showed a novel function of prdx1 that play critical roles in vascular growth during zebrafish development.
Selective Inhibition of Osteosarcoma Cell Functions Induced By Curcumin‐Loaded Self‐assembled Arginine‐Rich‐RGD Nanospheres
Authors: Chang Run , Sun Linlin , Webster Thomas 
Published: June 2021

ObjectivesTo develop a treatment against osteosarcoma with higher selectivity towards osteosarcoma cells and lower cytotoxicity towards normal osteoblast cells.Statement of methodsCurcumin was found to have significant selectivity against osteosarcoma cells in vitro, and the ampiphilic peptide C18GR7RGDS was used as a carrier in aqueous solution. This peptide contains an arginine‐rich and an arginine‐glycine‐aspartic acid (RGD) structure, which may lead to efficient cell penetration and targeting for cancerous cells since RGD sequence can target to the overexpressed ανβ3 integrin. Using a method of co‐dissolution with acetic acid and dialysis tubing, the solubility of curcumin was enhanced and formed a homogeneous solution with the help of amphiphilic nanoparticles (APNPs). The cytotoxicity and cellular uptake of these materials on both osteosarcoma and normal healthy osteoblast cell lines were evaluated by MTT assays and confocal fluorescent microscopyResultsIt was demonstrated for the first time that APNPs formed nanospheres with diameters of 10‐20 nm in water and phosphate buffer saline (PBS), and opened up when the pH value was reduced to 4. The successful encapsulation of curcumin in APNPs was confirmed by Fourier transform infrared (FT‐IR) and X‐ray diffraction (XRD) analysis. The curcumin‐loaded APNPs exhibited a significant selective internalization against the MG‐63 osteosarcoma cell lineimageConclusionsAPNPs can encapsulate hydrophobic curcumin in their hydrophobic cores, and the curcumin‐loaded APNPs could be an innovative candidate for the selective inhibition against osteosarcoma.
Saccharomyces cerevisiae as a Tool to Examine Rpa2 N‐Terminal Phosphorylation Across Common Eukarya
Authors: Wilson Timothy , Ghospurkar Padmaja , Senger Barbara , Haring Stuart 
Published: June 2021

BackgroundReplication Protein A (RPA) is a heterotrimeric complex that serves critical roles in eukaryotic genome duplication and maintenance. In human cells, the N‐terminus of the 32‐kDa subunit of RPA (Rpa2) is hyper‐phosphorylated by multiple kinases in response to DNA damage. We demonstrated previously in the budding yeast Saccharomyces cerevisiae that Rpa2 N‐terminal phosphorylation does not occur under genotoxic conditions, yet this domain is vital for the damage response.Study Objective: Determine why there is a difference between yeast and human Rpa2 phosphorylation in response to genomic insult and its importance for the DNA damage response.Methods: We utilized chimeric Rpa2 proteins, yeast Rpa2 antibodies, and human Rpa2 phospho‐specific antibodies to examine the potential for human and other eukaryotic Rpa2 N‐termini to be phosphorylated and their contribution to the DNA damage response in yeast.Results andConclusionsWe determined that the human Rpa2 N‐terminal domain is phosphorylated in yeast. Furthermore, hyper‐phosphorylation of chimeric Rpa2 in yeast occurs in a manner analogous to that of Rpa2 in human cells. We also determined the yeast kinases responsible for phosphorylating specific residues within the human N‐terminus of chimeric Rpa2. Finally, we identified other eukaryotic Rpa2 N‐termini that have the potential to be phosphorylated. Identification and characterization of phosphorylation of eukaryotic Rpa2 N‐termini in yeast allow for an understanding of why yeast Rpa2 phosphorylation does not occur as well as insight into the evolutionary significance of higher eukaryotic Rpa2 phosphorylation.Funding: This research was supported by NSF‐CAREER 1253723 to SJH.