bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of high‐ and low‐carbohydrate diets on glycogen branching enzyme activity in the liver of C57BL/6J mice
Authors: Fuller Scott , Nelson Arnold , Stewart Laura , Henagan Tara , Waldrop Grover 
Published: June 2021

INTRODUCTIONGlycogen has a highly branched structure with the branch points formed by glucose molecules being joined by α 1,6‐glycosidic linkages. These linkages are formed by the action of branching enzyme (BE). While glycogen BE has been studied in clinical medicine, modulation of the enzyme has received little attention. This study measured the degree of branching in glycogen from mouse liver in response to low versus high carbohydrate diets.METHODSSix week old, male C57BL/6J mice (n = 68) were randomly assigned to either a low‐carbohydrate (35% CHO) or a high‐carbohydrate (70% CHO) diet for 8 weeks. Food consumption, body weight and body composition were evaluated weekly (NMR). At the 8 week time point, mice were euthanized and liver samples were collected and assayed for the degree of glycogen branching. Degree of branching was determined by spectrophotometrically quantifying the ratio of branch points to total glucose residues.RESULTSFood consumption did not differ between the groups. However, body weight and body fat percentage were different between the two groups (p < 0.001) at the 8 week time point. Degree of glycogen branching did not differ between the groups.CONCLUSIONGlycogen BE activity in mouse liver does not appear to be affected by varying carbohydrate intake, despite the observation that both body fat percentage and body weight were higher in mice consuming the LC diet. Further investigation should aim to discover how BE activity is modulated in skeletal muscle.
Effects of Hypoxic Training on Serum Lipoprotein of Obese Rats
Authors: Lu yingli , Zhang li , Feng lianshi , Xu jianfang , He zihong 
Published: June 2021

ObjectiveTo study the effects of hypoxic training on serum lipoprotein of obese rats.Method130 obese rats were divided into 13 groups at random:control group, normoxic training 1,2,3,4 week group, hypoxia sedentary1,2,3,4 week group, and hypoxic training 1,2,3,4 week group. The rats in training groups ran on a treadmill for 60 min a day at 26 m/min in normoxia or 21 m/min in hypoxia(13.6%), 6 days a week for 1–4 weeks. After corresponding week, the serum level of cholesterol(TC), triglyceride(TG), high‐density lipoprotein(HDL), low‐density lipoprotein (LDL), apolipoprotein AI (ApoAI) and apolipoprotein B(ApoB) were measured.Results1) hypoxic training significantly reduced serum TC, TG and ApoB of obese rats respectively in 1–4week,3–4week and 1–2week, and serum TC, TG and ApoB were also lower in above hypoxic training groups compared with the corresponding week groups of normoxic training and hypoxia sedentary. 2) hypoxic training significantly increased serum HDL and ApoAI of obese rats respectively in 3–4week and 1–4week, and serum HDL and ApoAI were also higher in above hypoxic training groups compared with the corresponding week groups of normoxic training and hypoxia sedentary.ConclusionHypoxic training can ameliorate serum lipoprotein in obese rats especially in 3–4 week, the effect is also better than hypoxia sedentary and normoxic training.(Supported by NSFC: Grant No. 30971415)
Examination of luminal acetylcholine on CFTR activity in porcine airway epithelium
Authors: Dittrich Nikolaus P , Clauss Wolfgang G , Kummer Wolfgang , Fronius Martin 
Published: June 2021

The CFTR plays a crucial role in airway fluid homeostasis since mutations are associated with cystic fibrosis lung disease. Luminal acetylcholine (ACh) has been identified to activate Cl− secretion in airway epithelia although the underlying mechanisms and targets are not identified. The present study investigates whether or not the CFTR is a putative target of luminal ACh.Porcine tracheal preparations were mounted in Ussing‐chambers for short‐circuit‐current (ISC) recordings. ACh (100 μM) was applied from the luminal side. CFTR‐dependent Cl− secretion was assessed by application of IBMX/forskolin (100/10 μM, luminal) in the presence of amiloride (10 μM, luminal). GlyH‐101 (50 μM, luminal) was used to block CFTR currents.Application of luminal ACh significantly increased ISC. This ACh effect was not changed by amiloride. In the presence of amiloride the IBMX/forskolin‐activated current (ΔII/F) was 32.4±6.4 μA/cm2 (n=6). GlyH‐101 reduced ΔII/F to 13.1±3.7 μA/cm2 (n=6) demonstrating that a substantial portion of that current is CFTR dependent. However, GlyH‐101 did not altered the effect of luminal ACh (ΔIACh: 11.3±2.3 (control); 10.1±2.2 (GlyH‐101); n=5).From these results it can be concluded that luminal ACh activates ion transport processes in porcine airway epithelium. Nevertheless this neither includes CFTR‐dependent Cl− secretion nor ENaC‐dependent Na+ reabsorption.
Omeprazole inhibits biliary proliferation during extrahepatic cholestasis
Authors: Afroze Syeda , Jensen Kendal , Rahal Kinan , Guerrier Micheleine , Glaser Shannon 
Published: June 2021

Omeprazole (OME) has been shown to reduce liver regeneration and enhance gastrin serum levels. Since gastrin inhibits biliary growth, we tested the hypothesis that omeprazole inhibits cholangiocyte proliferation in BDL rats by increasing gastrin serum levels.MethodsIn vivo, male Fischer 344 rats (immediately BDL) were treated with vehicle or OME (40 mg/Kg BW daily) for 1 wk. We measured changes in: liver histology, and intrahepatic bile duct mass in liver sections; H3 histone and PCNA and secretin receptor (SR) gene expression; basal and secretin‐stimulated cAMP levels in cholangiocytes bile and bicarbonate secretion in bile fistula rats. Changes in SR and secretin‐stimulated secretion are key functional tools for evaluating the degree of biliary hyperplasia.ResultsChronic in vivo administration of OME to BDL rats increased gastrin serum levels and reduced biliary proliferation and hyperplasia and decreased SR expression and significantly inhibited the stimulatory effects of secretin on cAMP levels and ductal secretion compared to vehicle treated controls.ConclusionThe usage of OME may be important for the management of chronic cholestatic liver diseases.
The application of Chinese Visible Human dataset
Authors: Zhang Shaoxiang , Jie Bin , Tan Liwen 
Published: June 2021

The objective of the study was to establish the Chinese Visible Human (CVH) dataset and to explore its application on clinical field and basic research.We have achieved five CVH dataset up to 2003. The CVH project achieved greater integrity of images, easier blood vessel identification, and free of organic lesion. The establish of CVH dataset was done in a low temperature laboratory, which contributed to prevention of small structures from falling off of the milling surface and better integrity of images.We're taking our step toward application by acquiring new data sets, performing segmentation and setting up a platform of computer‐assisted medicine. We have established the three‐dimensional (3D) digital model for transjugular intrahepatic portosystemic shunt pathway and model for the craniocervical junction region by using the serial sectional images from CVH dataset. These models correctly reflected the complicated anatomic structural characteristics and spatial adjacency relationships for diagnostics and interventional therapy. We also use the dataset to display anatomic features of the superior mediastinal and the left extraperitoneal space for diagnostic imaging, which is better than CT image at visualizing the small soft tissue structures. In additionally, the CVH dataset was used to construct Chinese adult anatomical models for evaluation of radio frequency electromagnetic field exposures. Further more, we use the CVH sectional image and the Duel‐Sources CT image to establish the 3D visible model of heart to display the third‐level branch of the coronary artery, and combine with the echocardiogram to diagnose the coronary heart disease by Beta ultrasound. Our study on the clinical application of CVH dataset will go on.
N‐Terminal Propeptide of Type III Procollagen (P3NP) Responses to Resistance Exercise in Older Adults
Authors: Fragala Maren S. , Jajtner Adam R , Beyer Kyle S , Wells Adam J , Townsend Jeremy R , Emerson Nadia S , Scanlon Tyler C , Stout Jeffrey R , Oliveira Leonardo P , Hoffman Jay R 
Published: June 2021

Circulating P3NP, a peptide fragment cleaved from type 3 procollagen during collagen synthesis, is lower in older adults than younger adults and is predictive of changes in lean muscle mass. The purpose of this investigation was to determine whether circulating P3NP changes in response to resistance exercise training and if potential changes correspond to changes in muscle strength or quality (MQ). Twenty‐one older adults (69.4±5.2 y; BMI =28.1±5.4 kg·m−2) completed a 6‐week resistance training program in a randomized, controlled design. Resting circulating plasma P3NP, lean muscle mass, cross sectional area of the rectus femoris, muscle strength, and muscle quality were determined at baseline and after the intervention or control period by ELISA, DXA, ultrasound, leg extension 1‐RM prediction, and relative strength, respectively. P3NP changes were evaluated with repeated measures ANOVA and relationships between variables were evaluated with bivariate correlations. Short term resistance training did not result in uniform changes in circulating P3NP. Interestingly, baseline P3NP (mean ± SD = 4.91 ± 2.5 ng·mL−1) correlated to lean body mass (r=.471, p=.031) and muscle cross‐sectional changes (r=.527, p=.014), but not changes in strength or muscle quality. While further research is needed, P3NP appears to be reflective of muscle mass but not muscle quality.This research was supported from by grants from the Learning Institute for Elders (LIFE) and the Toni Jennings Exceptional Education Institute.
Baroreflex mechanism as a model for integration of genotype, phenotype, computational model, and pathway information within a user‐friendly graphical interface
Authors: Munzenmaier Diane H. , Zientek Amy , Carlson Brian , Tabesh‐Saleki Nazanin , Shimoyama Mary , Jacob Howard J. 
Published: June 2021

Translational research requires effective integration of physiological and genomic data with informative predictive modeling. Our goal was to develop a tool that would allow physiology, genetics, and computational biology researchers to explore existing data and models within an intuitive pathway framework that allows logical integration of multiple, diverse datasets with physiological processes and mathematical equations developed to describe them.A multi‐level diagram depicting the baroreflex mechanism was created using a program designed for the Rat Genome Database (www.rgd.mcw.edu) to model physiological pathways. The diagram was integrated with a well‐established baroreceptor model (Bugenhagen, et al, 2010). Images were imported, linked and labeled to identify various components of the process. Processes were linked to multiple datasets, genomic information, and computational model equations. Weekly meetings with physiologists, bioinformaticians, and computational physiologists elucidated the challenges in creating the model and established effective guidelines for enhancement of the tool. Additional communication with the graphical design artist and software developer allowed for refinement of the image quality and improvement in the ease of use and functionality of the tool.Funding was made possible by NIH HL64541 (RGD) and the APS Frontiers in Physiology program.
Hydrophobic residues as a key determinant in hexoses exchange urate mechanism mediated by human glucose transporter 9, hSLC2A9
Authors: Long Wentong , Cheeseman Chris I. , Witkowska Kate 
Published: June 2021

Human GLUT9 (hSLC2A9) is a urate/hexose transporter expressed predominantly in the liver and kidney where human urate homeostasis is achieved. hSLC2A9 has two splice variants: 9a and 9b differing in their N‐termini and targeted differentially within polarized epithelia. The transporter shows trans‐acceleration between urate and hexoses, however, the mechanism is unknown. Hydrophobic residues in TM7 of GLUTs have been shown to play a role in hexose selectivity.ObjectiveTo investigate urate/hexose exchange mediated by SLC2A9 isoforms and their mutants.MethodshSLC2A9 isoforms and I335V mutants were overexpressed in X. laevis oocytes. Urate induced currents and I‐V curves were obtained using Two Micro‐Electrode Voltage Clamp (TEVC) recordings. Urate transport and hexose trans‐stimulation activities were determined by radiolabelled urate uptake and efflux measurements.ResultsTEVC studies demonstrated that the membrane potential plays a major role in urate transport mediated by hSLC2A9. Fructose was found to trans‐stimulate urate uptake and efflux in wild type hSLC2A9a; whereas it stimulates only urate efflux in the I335V mutant. These finding advance our understanding of how fructose intake is linked with serum urate levels and implicates hSLC2A9 as an important transporter that may contribute to pathophysiological conditions involving urate or fructose. Supported by CIHR.
Carbon Monoxide Induces Dose‐Dependent Relaxation of Airway Smooth Muscle via cGMP Signaling Pathway
Authors: Jakupaj Muharrem , Lajçi Azem , Bexheti Sadi , Temaj Gazmend , Cenaj Asllan , Sopi Ramadan B 
Published: June 2021

In present study we investigated the effect of endogenous carbon monoxide (CO) on relaxation of rat airway smooth muscle (ASM). Airway segments were excised from 28 day‐old rats. In pre‐constricted tracheal smooth muscle (TSM), electrical field stimulation (EFS) was applied to induce relaxation in absence or presence of heme oxigenase (HO) substrate ‐ hematin (10 μM and 100 μM); HO inhibitor tin protoporphyrin‐IX (SnPP‐IX; 100 μM); nitric oxide (NO) synthase (NOS) inhibitor Nω‐nitro‐L‐arginine methyl ester (L‐NAME; 100 μM); soluble guanylyl cyclase inhibitor 1H‐[1,2,4]oxadiazolo[4,3‐a]quinoxalin‐1‐one (ODQ; 10 μM) and the SnPP‐IX + L‐NAME. All experiments were performed in presence of isoproterenol (100 μM) and indomethacin. Hematin increased relaxant responses of ASM in a dose‐dependent manner. SnPP‐IX and L‐NAME, alone or combined significantly reduced relaxant responses induced by EFS in control and hematin‐preincubated tissues. ODQ also reduced relaxant responses to the level obtained by combining SnPP‐IX and L‐NAME.According to the results we conclude that in rat TSM, CO induces dose‐dependent relaxation and nondrenergic noncholinergic (NANC) inhibitory responses use CO and NO as main molecules to induce relaxation via cGMP signaling pathway.
Diaphragm Activation via High Frequency Spinal Cord Stimulation (HF‐SCS) in a Rodent Model of Spinal Cord Injury
Authors: Kowalski Krzysztof E , Hsieh Yee‐Hsee , Dick Thomas E , DiMarco Anthony F 
Published: June 2021

ObjectiveHF‐SCS is a novel technique of inspiratory muscle activation involving activation of spinal cord pathways. All previous studies of this method were performed in a dog model of spinal cord injury. Since the rodent respiratory system is also a relevant model for study of neuronal circuitry function and this species is more accessible, we sought to a) evaluate the effects of HF‐SCS and b) determine the methodology of application of this technique in rats.MethodsIn 9 rats, diaphragm multiunit and single motor unit EMG activity was assessed during spontaneous breathing and HF‐SCS applied on the ventral epidural surface of the spinal cord at the T2 level following C1 spinal section.ResultsMean maximum firing frequencies of the diaphragm during spontaneous breathing and HF‐SCS were 23.3 ± 1.4 Hz (range: 9.8 – 51.6 Hz) and 26.6 ± 1.3 Hz; range: 12.0 – 72.9 Hz, respectively, at comparable inspired volumes. Moreover, HF‐SCS was successful in pacing these animals over a 60‐min period without evidence of system fatigue.ConclusionOur results suggest that, similar to the dog model, HF‐SCS in rodents results in activation of spinal cord tracts which synapse with the phrenic motoneuron pools, allowing processing of the stimulus and consequent physiologic activation of the inspiratory muscles. The rat may be a useful model for further studies evaluating phrenic motoneuron physiology.
A new pathway to STEM ‐ the marble game
Authors: Nelson Peter Hugo 
Published: June 2021

Recently there have been multiple calls for curricular reforms to develop new pathways to the science, technology, engineering and math (STEM) disciplines. The Marble Game answers these calls by providing a conceptual framework for quantitative scientific modeling skills useful across all the STEM disciplines. The approach actively engages students in a process of directed scientific discovery. In a “Student Assessment of their Learning Gains” (SALG) survey, students identified this approach as producing “great gains” in their understanding of real world problems and scientific research. Using the marble game, students build a conceptual framework that applies directly to random molecular‐level processes in biology such as diffusion and interfacial transport. It is also isomorphic with a reversible first‐order chemical reaction providing conceptual preparation for chemical kinetics. The computational and mathematical framework can also be applied to investigate the predictions of quantitative physics models ranging from Newtonian mechanics through RLC circuits. To test this approach, students were asked to derive a novel theory of osmosis. The test results confirm that they were able to successfully apply the conceptual framework to a new situation under final exam conditions. The marble game thus provides a pathway to the STEM disciplines that includes quantitative biology concepts in the undergraduate curriculum ‐ from the very first class.Student modules (and instructor guides) are available for testing and evaluation at http://circle4.com/biophysics. Support from the NSF (Grant DUE‐0836833) is gratefully acknowledged.
Cholesterol homeostasis in mouse bone marrow‐derived macrophages from RA‐ and SLE‐like murine models: a possible mechanism for atherogenesis (1001.1)
Authors: Voloshyna Iryna , Littlefield Michael , Teboul Isaac , Archer Amy , Palaia Thomas , Ragolia Louis , Perlman Harris , Reiss Allison 
Published: June 2021

Objective: Atherosclerosis contributes to 30% of deaths in systemic lupus erythematosus (SLE) and cardiovascular mortality is 50% higher in rheumatoid arthritis (RA) than in the general population. Little is known about mechanisms leading to progression of atherosclerosis at the cellular level. Here we analyze expression of key cholesterol transport proteins that impact atheroma development in BMDM from KRNAg7 (RA) and apoE‐/‐Fas‐/‐ (SLE) mice as disease evolves.Methods: Male homozygous C57BL/6J, apoE‐/‐ , apoE‐/‐Fas‐/‐ , KRN and KRNAg7 mice (n=5 per group) were studied. Femurs were dissected and cell suspensions obtained by flushing bones. BMDM were generated by culturing cells for 7 days with MCSF. Expression of efflux proteins ATP binding cassette transporters (ABC)A1 and ABCG1, and scavenger receptors CD36 and LOX1 were evaluated by QRT‐PCR.Results: 6 wk mice had no significant changes in cholesterol efflux proteins. 30 wk apoE‐/‐, apoE‐/‐Fas‐/‐ mice display 2‐fold reduction in ABCA1 and ABCG1 mRNA (n=3, P<0.01). 6 wk KRNAg7 mice show increased CD36 (225.5±54% vs. wt mice at 100%) (n=3, P<0.01). LOX‐1 did not differ significantly from C57BL/6J and KRN mice. ApoE‐/‐Fas‐/‐ mice had increase in CD36 mRNA (150±23% at 6 wk; 161.3±12.3% at 30 wk, n=3, P<0.05) LOX1 expression was unchanged. In contrast, apoE‐/‐ mice display a 2‐fold increase in both CD36 and LOX1 at 6 wk and up to a 5‐fold increase at 30 wk.Conclusions: This study provides insight into molecular alterations that contribute to atherogenesis in SLE and RA. We demonstrate that imbalance between cholesterol efflux and influx contributes to atherosclerosis progression. Further metabolic screening may identify optimal time‐points for intervention.
Apolipoproteins C‐I and C‐III inhibit lipoprotein lipase activity by displacement of the enzyme from lipid droplets (1002.4)
Authors: Larsson Mikael , Vorrsjo Evelina , Talmud Philippa , Lookene Aivar , Olivecrona Gunilla 
Published: June 2021

Apolipoproteins (apo) C‐I and C‐III are known to inhibit lipoprotein lipase (LPL) activity but the molecular mechanisms for this remain obscure. We present evidence that either apoC‐I or apoC‐III, when bound to triglyceride‐rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site‐directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC‐III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride‐rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin‐like protein 4 (angptl4). Addition of either apoC‐I or apoC‐III to triglyceride‐rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC‐II more of apoC‐I or apoC‐III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC‐I and apoC‐III inhibit lipolysis by displacing LPL from lipid emulsion particles. We propose a role for these apolipoproteins also in the irreversible inactivation of LPL by factors such as angptl4.Grant Funding Source: Supported by Swedish Science Council Grant 12203
Protein self‐association of N‐terminal domain of β‐1,3‐glucan recognition protein upon binding to β‐1,3‐glucan stimulates the prophenoloxidase activation in Manduca sexta (1007.4)
Authors: Takahashi Daisuke , Dai Huaien , Hiromasa Yasuaki , Krishnamoorthi Ramaswamy , Kanost Michael 
Published: June 2021

Insect β‐glucan recognition protein (βGRP), a pathogen recognition receptor for innate immune responses, detects β‐1,3‐glucan on fungal surfaces via its N‐terminal carbohydrate binding domain (N‐βGRP) and triggers serine protease cascades leading to the activation of prophenoloxidase (proPO) or Toll pathway. Here we use biochemical and biophysical techniques to probe the molecular interaction of N‐βGRP from Manduca sexta with laminarin, soluble β‐1,3‐glucan. Intriguingly, the carbohydrate binding induces the formation of two types of protein self‐association of N‐βGRPs depending on the molar ratio of carbohydrate to protein (C/P). Insoluble aggregation occurs at the lower molar ratio (C/P ~1), and a soluble oligomer, likely containing at least six N‐βGRP molecules, forms at the higher molar ratio (C/P >5). Further, the PO activation is significantly enhanced in the naïve plasma supplemented with the insoluble aggregate of N‐βGRP. The soluble complex formed in plasma with laminarin also stimulates the PO activation, but at a lower level. Our results indicate that the self‐association of βGRPs on binding to β‐1,3‐glucan is an essential step to stimulate the immune responses against fungal infection. We also discuss the possible involvement of other hemolymph proteins in the self‐association complex of βGRP for downstream signaling.Grant Funding Source: Supported by NIH grant GM‐41247