bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estrogen Attenuation of Post‐Exercise Muscle Leukocyte Infiltration is not Receptor Mediated
Authors: Iqbal Sobia , Enns Deborah L. , Tiidus Peter M. 
Published: June 2021

Previous work from our laboratory has demonstrated that estrogen will attenuate leukocyte infiltration into skeletal muscle following eccentric exercise. However the mechanisms by which estrogen exerts its effects are still uncertain. We investigated the role of estrogen receptors (ER) on muscle leukocyte infiltration following eccentric exercise through administration of the ER antagonist ICI 182,780 following downhill running to ovariectomized female rats with (E+) or without (E−) estrogen supplementation. At 24 and 48 h post‐exercise, soleus and white vastus muscles were removed and immunostained for HIS 48 (neutrophil) and ED1 (macrophage) positive cells. The increase in number of fibres positive for HIS 48 in soleus and positive for ED1 in the soleus and white vastus was significantly attenuated (p<0.05) in E+ relative to E− rats at 24 hours post‐exercise. E+ rats administered the ER agonist also had significantly (p<0.05) attenuated 24 h post‐exercise increases in HIS 48 and ED1 positive soleus and white vastus muscle fibres similar (p>0.05) to those without ER antagonist. This suggests that the ability of estrogen to attenuate post‐exercise leukocyte infiltration into skeletal muscle is not ER‐mediated.Supported by NSERC Canada
Gender dymorphism in muscle leptin receptors
Authors: Guerra Borja , Fuentes Teresa , Delgado‐Guerra Safira , Guadalupe‐Grau Amelia , Olmedillas Hugo , Santana Alfredo , Dorado Cecilia , Calbet José A.L. 
Published: June 2021

To determine if there is gender dymorphism in the expression of leptin receptors (OB‐R170, OB‐R128 and OB‐R98) and perilipin in skeletal muscle we obtained muscle biopsies from thirty‐six healthy men (age = 27.2 ± 1.1 yr, height = 176.5 ± 0.97 cm, body mass = 77.1 ± 1.9 kg, body fat = 18.1 ± 0.5%; mean ± s.e.m.) and thirty‐two females (age = 26.7 ± 1.2 yr, height = 165.3 ± 1.1 cm, body mass = 61.3 ± 1.5 kg, body fat = 28.1 ± 1.2%; mean ± s.e.m.). The expression of OB‐R protein, perilipin and tubulin were analysed by Western blot in muscle biopsies obtained from the m. vastus lateralis, and in subcutaneous adipose tissue of the thigh (n=10). While the OB‐R128 and OB‐R98 where found in the skeletal muscle and adipose tissue, the OB‐R170 isoform was only detected in skeletal muscle. Leptin receptor expression was 43% (OB‐R170, P<0.05), 153% (OB‐R128, P<0.05) and 28% (OB‐R98; P=0.07) higher in females than in males, as well as perilipin content (+99%, P<0.001) and was related to the plasma leptin concentration (r=0.57, P<0.001). Plasma leptin concentration was 85% higher in females than in the males (P<0.05). Perilipin content in the adipose tissue was similar in males (n=5) and females 5(n=5).In summary, females express a greater amount of the long isoform of the leptin receptor in skeletal muscle. These results can not be explained by differences in fat tissue inside the skeletal muscle.
Non‐uniform transmural remodeling in ovine chronic mitral regurgitation
Authors: Ennis Daniel B , Nguyen Tom C , Itoh Akinobu , Carlhäll Carl Johan , Oakes Robert A , Bothe Wolfgang , Liang David , Miller D Craig , Ingels Neil B 
Published: June 2021

Objective:Test the hypothesis that chronic “pure” mitral regurgitation (MR) induces non‐uniform transmural LV remodeling.Methods:Surgical creation of a ∼4.8mm hole in the posterior mitral leaflet created “pure” MR in 12 sheep (HOLE); 8 were sham operated (CNTL). Radiopaque transmural beads in the anterobasal wall were used to quantify epicardial (EPI) and endocardial (ENDO) remodeling strains in the circumferential (EC) and radial (ER) directions. Remodeling strains were calculated using end‐diastole (ED) 1 week (WK‐01) postoperatively as the reference and ED at 12 weeks (WK‐12) as the deformed configuration.Results:MR grade was greater in HOLE (∼3) than CNTL (<1) (P<0.001) at WK‐01 and WK‐12. LVED volume index increased in HOLE from WK‐01 to WK‐12 (P<0.05) and LV mass index was greater in HOLE at WK‐12 (P<0.01). HOLE EC was greater in ENDO than EPI (0.09±0.12 vs. 0.02±0.07, P<0.05) and HOLE EC in ENDO was greater than CNTL EC in ENDO (0.09±0.12 vs. −0.01±0.06, P<0.05). ER was less in EPI than ENDO for HOLE (−0.23±0.13 vs. −0.04±0.23, P<0.05) and CNTL (−0.15±0.07 vs. 0.15±0.44, P<0.05).Conclusion:EC and ER remodeling strains demonstrated significant transmural non‐uniformity. This non‐uniformity may arise from transmural differences in tissue stress. Such a transmural imbalance may underlie the decrease in LV torsion associated with chronic MR.Support:NIH HL29589/HL67025 (DCM) and HL087614 (DBE).
Roles of c‐Src and PKC in production of persistent calcium sparklet activity
Authors: Gulia Jyoti , Gui Peichun , Chao Jun‐Tzu , Navedo Manuel F , Santana Luis F , Davis Michael J 
Published: June 2021

The L‐type calcium channel (Cav1.2) is regulated by multiple kinases, including PKA and c‐Src, which phosphorylate the Cav1.2 C‐terminus at residues S1901 and Y2122 (Cav1.2c), respectively, to enhance Ca2+ entry. PKC also enhances Cav1.2 current under some conditions and promotes persistent Cav1.2 Ca2+ sparklet activity (quantal Ca2+ entry events); however, the PKC phosphorylation site is unclear. We addressed two questions using TIRF microscopy to measure Ca2+ sparklets in patch clamped HEK cells expressing Cav1.2c. 1) Does PKC produce persistent calcium sparklet activity through phosphorylation of S1901? 2) Is c‐Src involved in the production of persistent sparklet activity?Persistent sparklets (indicating a prolonged channel opening state) were defined as nPs > 0.2, where n= # of quantal levels and Ps= probability that a given sparklet site was active. Our results suggest that both PKC and c‐Src promote persistent calcium sparklet activity, possibly by phosphorylating residue Y2122 rather than S1901 on Cav1.2c.
Modeling approaches to the estimate of plasma variables from exhaled volatile organic compounds
Authors: Oliver Stacy R , Newcomb Robert L , Blake Donald R , Ngo Jerry , Lee Jane S , Meinardi Simone , Rosa Jaime S , Galassetti Pietro R 
Published: June 2021

Exhaled volatile organic compounds (VOC) are potential biomarkers of biological processes, such as glucose (GL), insulin (INS), and lipid (FFA) metabolism. The accuracy of VOC‐derived estimates of plasma variables, though, depends on analytical methods and mathematical modeling. Here we report evolving modeling approaches in consecutive studies with simultaneous collection of plasma and exhaled gases at multiple time points, during 2‐4 h fluctuations of plasma GL, INS and FFA.a) Plasma GL estimate from multi‐linear regression (MLR) of exhaled ethanol + acetone, after GL ingestion; avg R of measured vs estimated GL = .70b) Plasma GL estimate from MLR of ethanol, acetone, methyl nitrate + 3 aromatic gases after i.v. GL bolus (scaling back models from 6 to 4 gases, see figure); avg R = .91c) Plasma GL, INS, FFA estimates from MLR of 4‐gas clusters during continuous i.v. GL infusion; avg Rs = .86 (GL), .92 (INS), .89 (FFA)d) Plasma INS estimate from MLR of a 5‐gas cluster + time, using residual values for gases (instead of breath‐room air differences used in a, b, c); avg R = .91 (same regression equation for all subjects, unlike a, b, c, where individual equations were used).MLR models of 4‐6 residual gas values and time can therefore accurately estimate blood variables related to glucose metabolism, providing the developmental basis of a non‐invasive methodology for diabetes screening, diagnosing and monitoring.
Role of viscosity and fermentability of dietary fibers on satiety‐related hormones in rats
Authors: Schroeder Natalia , Gallaher Daniel D , Marquart Len 
Published: June 2021

The objective of this study was to determine the effect of two dietary fiber characteristics ‐small intestinal contents viscosity and large intestinal fermentability ‐on satiety‐related hormones in rats. Diets contained fiber sources that were either not viscous, somewhat viscous, or highly viscous, and either highly fermentable or non‐fermentable, in a 2 X 3 factorial design. The dietary fiber content was 8% (w/w). Blood was drawn in the fasting state after 35 days. At 42 days, rats were food‐deprived for 15 hours then fed 4 g of their respective diets. Two h later, plasma and small intestinal contents were collected. In the fed state, rats fed non‐fermentable fibers had significantly greater plasma GLP‐1 concentration than fermentable fibers. In the fasted state, among non‐fermentable fibers, viscosity had no effect on GLP‐1 concentration. However, among fermentable fibers, greater viscosity reduced GLP‐1 concentration. In the fed state, rats fed fermentable fibers had a significantly greater plasma ghrelin concentration than non‐fermentable fibers. In the fasted state, ghrelin concentration was influenced by a complex interaction between viscosity and fermentability. Plasma leptin was unaffected by either viscosity or fermentability. In conclusion, fiber fermentability alters short‐acting satiety‐related hormones such that non‐fermentable fibers may increase satiety. (Support by GTC Nutrition)Grant Funding SourceIndustry
Spinal nitric oxide synthase activity is necessary for phrenic long‐term facilitation following intermittent hypoxia
Authors: MacFarlane Peter M , Mitchell Gordon S 
Published: June 2021

Acute intermittent hypoxia (AIH) elicits a serotonin‐dependent form of respiratory plasticity known as phrenic long‐term facilitation (pLTF). Although reactive oxygen species (ROS) from spinal NADPH oxidase activity are necessary for AIH‐induced pLTF, little is known about the role of reactive nitrogen species (RNS). Since RNS, and specifically nitric oxide (NO), are necessary for other forms of neuroplasticity, including ventilatory LTF in unanesthetized mice (Kline et al., 2002), we hypothesized that spinal nitric oxide synthase (NOS) activity and NO are required for pLTF. To test this hypothesis, the NOS inhibitor, L‐NAME, was injected intrathecally over the cervical spinal cord (C4) prior to AIH (3, 5‐min episodes, 10% O2) in anesthetized, paralyzed and ventilated rats. In control, vehicle treated rats (aCSF, 12µl volume), AIH elicited a progressive increase in integrated phrenic nerve burst amplitude (ie. pLTF) lasting 60 min post‐AIH. However, pLTF was attenuated in rats pre‐treated with L‐NAME (10mM; 12µl volume; p<0.05), suggesting spinal NOS activity/NO is necessary for AIH‐induced pLTF. The specific role of NO is not yet known.Supported by NIH HL‐80209 and the Francis Family Foundation (PMM)
Aldosterone and Salt Induces Hypertension Associated with Increased Oxidative Stress in the Brain of Apolipoprotein E Knockout Mice
Authors: Araki Shuichiro , Hirooka Yoshitaka , Kishi Takuya , Ito Koji , Koga Yasuaki , Konno Satomi , Yasukawa Keiji , Utsumi Hideo , Sunagawa Kenji 
Published: June 2021

BackgroundOxidative stress in brain plays a crucial role in the neural mechanism of hypertension. Apolipoprotein E‐knockout mice (apoEKO) reveal increased oxidative stress in the vasculature, heart, and kidney. Aldosterone (ALDO)‐salt load promotes hypertension and organ damage. We hypothesized that apoEKO was susceptible to ALDO‐salt thereby causing hypertension associated with the increased oxidative stress in the brain using an in vivo electron spin resonance (ESR) method.Methods and ResultsEight‐week‐old apoEKO and their wild type (WT) were treated with either ALDO (6 microg/mouse/d, s.c. osmotic minipump) and 8% NaCl‐containing chow, or vehicle and standard chow (Veh). After 6‐week treatments, differences in SBP and the in vivo ESR/spin probe decay rates in brain, an index of oxidative stress in brain, between ALDO‐salt and Veh treatments were compared between apoEKO and WT. SBP was increased significantly in apoEKO (117.8±2.1 vs 105.2±1.8 mm Hg, n=6 each, P<0.05), but not in WT (111.8±2.1 vs 104.8±1.8 mm Hg, n=6 each, ns). In vivo ESR decay rate was increased significantly in apoEKO (0.297±0.009 vs 0.243±0.008 min−1, P<0.01), but not in WT (0.248±0.011 vs 0.232±0.012, min−1, ns). Oxidative stress evaluated by dihydroethidium staining in the rostral ventrolateral medulla was increased in ALDO‐salt‐treated apoEKO compared with Veh‐treated apoEKO.ConclusionThese results suggest that ALDO‐salt induces hypertension associated with the increased oxidative stress in the brain in ApoEKO.
T1α/Podoplanin through regulation of RhoA activation directs human lymphatic endothelial cell migration
Authors: Navarro Angels , Perez Ricardo E , Rezaiekhaligh MO , Mabry Sherry M , Ekekezie Ikechukwu I 
Published: June 2021

We have recently shown that early activation of RhoA in the lymphangiogenic process, which is required for the successful establishment of the capillary network, is dependent on podoplanin expression in human lung lymphatic microvascular endothelial cells HMVEC‐LLy (Am J Physiol Lung Cell Mol Physiol 295: L543‐L551, 2008). We have also reported that podoplanin is required for a full migratory response to VEGF in these cells and that complete reorientation of the microtubule‐organizing center (MTOC) in response to VEGF in scratch‐wound assays, necessary for directional migration, is achieved only if the cells express podoplanin (FASEB J 2008; 22:1178.20). In the present study our objective was to determine if podoplanin regulates the migratory response of HMVEC‐LLy to VEGF via modulation of RhoA activation.RESULTSHMVEC‐LLy treated with CT04, a Rho inhibitor, achieve 60% wound closure by 48 hr in the presence of VEGF vs 100% in controls. Also, MTOC polarization in treated vs control cells is only 40% vs 80% as assesed at 3 hr after wounding. Furthermore, in transfection experiments, cells expressing a dominant negative mutant RhoA achieve only 20% wound closure vs 60% in control cells by 48 hr in the presence of VEGF.CONCLUSIONTaken together our findings indicate that the migratory response of HMVEC‐LLy to VEGF stimulation is dependent on precise regulation of RhoA activity, a process dependent on podoplanin.
Resolution of experimental liver fibrosis in mice by targeted delivery of connective tissue growth factor siRNA
Authors: Brigstock David , Lawrencia Carmel 
Published: June 2021

Resolution of experimental liver fibrosis in mice by targeted delivery of connective tissue growth factor siRNAConnective tissue growth factor (CTGF) promotes liver fibrosis by stimulating collagen production in activated hepatic stellate cells (HSC). Here, we investigated the curative properties of CTGF siRNA delivered to activated HSC in acute or chronic models of CCl4‐induced liver fibrosis. Modified liposomes containing CTGF siRNA were coated with a collagen Type VI receptor‐binding peptide. Balb/c mice received daily injections of CCl4 or oil control for either 3 or 5 weeks. During the last 2 weeks of these regimens, some mice also received concurrent daily injections of CTGF siRNA in targeted liposomes ("CTGF siRNA‐TL") or scrambled CTGF siRNA in targeted liposomes ("CTGF SsiRNA‐TL"). Administration of CCl4 for 3 or 5 weeks resulted in high levels of α‐SMA‐positive cells and deposition of collagen. Whereas this response was unaffected by administration of CTGF SsiRNA‐TL, neither α‐SMA‐positive cells nor collagen deposits were present in CTGF siRNA‐TL‐treated livers. Real‐time PCR showed that the CCl4‐induced mRNA expression of α‐SMA, collagen Type I α1, TGF‐β, or CTGF was restored to baseline values by CTGF siRNA‐TL (p< 0.01) but not by CTGF SsiRNA‐TL. Thus, this targeted liposomal delivery system designed to deliver CTGF siRNA to activated HSC was effective in either preventing or reversing fibrosis even in the continued presence of the fibrotic insult.
Gestational weight gain is associated with adherence to a Western dietary pattern in low‐income women
Authors: Rahn Maike , Strawderman Myla M , Olson Christine M 
Published: June 2021

The association of dietary patterns with gestational weight gain (GWG) has not been investigated. Body size, diet and behavioral factors were assessed in a prospective observational cohort of pregnant women in rural New York. GWG was the difference between weight at first and last prenatal visit, excessive GWG was based on Institute of Medicine criteria (IOM 1990). Dietary patterns were determined with orthogonal factor analysis utilizing food groups created from the Willett FFQ. Computed factor scores of the identified dietary patterns were inserted into regression equations with GWG measures as outcome, adjusting for BMI, income, gestational age, timing of weight and diet assessments, parity, physical activity, smoking and energy intake. Factor analysis (n=503) resulted in a Prudent factor with high loadings for fruits and vegetables and other healthful foods, a Western factor (WF) composed of soda, meats and processed foods, and a Fat factor. The 481 women with complete data had a mean GWG of 30 lbs, with 40% experiencing excessive GWG and 43% low income. In low‐income women, GWG increased by 1.5 lbs with each unit rise in the WF, and the odds of excessive GWG were 2.34 times greater when WF scores ≥ median compared to reference (interaction p's ≤ 0.05).In low‐income women, a Western dietary pattern is associated with higher GWG and increased risk of excessive GWG.This research was supported by the NIH Grant No. DK69448.
Evidence that protein requirements in healthy school‐age children are significantly underestimated in current recommendations
Authors: Elango Rajavel , Humayun Mohammad A , Ball Ronald O , Pencharz Paul B 
Published: June 2021

Protein (PRO) requirements in healthy school‐age children were determined by the indicator amino acid oxidation (IAAO) method. Seven, healthy children (6 ‐ 11 y) each randomly received a minimum of 6 graded PRO intakes (range= 0.1 ‐ 2.56 g/kg/d) to a total of 47 studies. The diets provided energy at 1.7 X REE and were made isocaloric using carbohydrates. PRO was given as an amino acid mixture based on egg protein pattern, except phenylalanine and tyrosine intakes, which were maintained constant across intakes. Oxidation of L‐[1‐13C]‐phenylalanine to 13CO2 (F13CO2) was measured in breath samples at baseline and isotopic steady state. Linear regression crossover analysis identified a breakpoint (requirement) at minimal F13CO2 in response to different PRO intakes.Figure 1. Phenylalanine oxidation (F13CO2, µmol/kg/hr) in response to graded protein intakesThe mean and population‐safe PRO requirements were determined to be 1.35 and 1.6 g/kg/d, respectively (Figure 1). These results are significantly higher than the mean and population‐safe PRO requirements of 0.76 and 0.95 g/kg/d, respectively, currently recommended by the Dietary Reference Intakes (DRI 2005) for macronutrients. This study is the first to directly estimate protein requirements in children using stable isotopes and indicates that the current recommendations are severely underestimated. (CIHR supported)
Stereoscopic three‐dimensional reconstruction of the female pelvis and pelvic contents for education
Authors: Sergovich Aimee Lynn , Johnson Marjorie , Wilson Timothy D 
Published: June 2021

The anatomy of the pelvis is complex, and its three‐dimensional organization is conceptually difficult for students to grasp. The aim of this project is to create an explorable and projectable stereoscopic three‐dimensional (3‐D) model of the female pelvis and pelvic contents for anatomical education. The model is created using cyrosection images obtained from the Visible Human Project in conjunction with a general purpose three‐dimensional segmentation and surface rendering program. Anatomical areas of interest are identified and labeled on consecutive images. They are then reassembled into a three‐dimensional model. Currently the model includes the pelvic girdle, organs of the pelvic cavity, surrounding muscles, the perineum, and large blood vessels. Each structure can be individually controlled (ex. added, subtracted, made transparent) in order to reveal the organization of and relationships between structures. The model can also be manipulated and/or projected stereoscopically in order to visualize structures and relationships from different angles with excellent spatial perception. Due to its ease of use and versatility this model may provide powerful teaching tool for learning in the classroom or in the laboratory. Research support: Ontario Graduate Scholarship.Grant Funding SourceInternal
Reconstruction of the Cerebral Ventricular System System in Stereoscopy
Authors: Lew Christina , Wilson Timothy D 
Published: June 2021

The complexity of the human cerebral ventricular system, coupled with its deep position within the brain, may pose a problem for conceptualizing its anatomy. Cadaveric dissection may be inadequate for learning the anatomy of the cerebral ventricular system as ventricular structures represent spaces rather than physical structures. Three‐dimensional (3D) computer reconstruction of the ventricular system may offer a solution. This study aims to create an accurate 3D computer reconstruction of the ventricular system with surrounding structures from 4T magnetic resonance (MR) scans of a male cadaver. Using 3D segmentation and rendering software, structures of interest were reconstructed through manual segmentation. The finished model can be manipulated by adding or removing structures, altering opacity, or taking slices through the model to highlight inner structures. Complex physiologic concepts, such as cerebrospinal fluid flow, can be shown using the 3D model through a video animation. Stereoscopic projection can be used increase depth perception and emphasize spatial relationships between anatomical structures. This model is suited for both self‐directed learning and classroom teaching of 3D anatomical structure and spatial orientation of the ventricles, their connections, and their relation to adjacent neural and skeletal structures. Research support: Ontario Graduate Scholarship.Grant Funding SourceInternal
The actin cytoskeleton regulates matrix‐metalloproteinase‐2 expression in vascular smooth muscle cells in response to insulin‐like growth factor
Authors: Risinger George Mitchell , Updike Dawn L , Bullen Elizabth C , Tomasek James J , Howard Eric W 
Published: June 2021

Vascular smooth muscle cells (VSMCs) can display a variety of phenotypes from a differentiated contractile phenotype to a de‐differentiated migratory one. This plasticity facilitates VSMC participation in vessel remodeling events like atherogenesis. The cytoskeleton can regulate the expression of contractile genes through the actin‐mediated regulation of myocardin‐related transcription factor (MRTF)‐A. We asked if the cytoskeleton was capable of regulating factors associated with the de‐differentiated phenotype, namely, matrix‐metalloproteinase (MMP)‐2. We used insulin‐like growth factor‐1 (IGF‐1) to induce VSMC de‐differentiation, which was characterized by changes in the actin cytoskeleton and a decreased level of the contractile marker smooth muscle α‐actin, and found that IGF‐1 induced up‐regulation of MMP‐2. Alteration of the actin cytoskeleton affected this regulation. Co‐stimulation of VSMCs with IGF‐1 and the F‐actin stabilizing agent jasplakinolide blocked MMP‐2 up‐regulation, while the F‐actin de‐stabilizing agent latrunculin B enhanced up‐regulation. These data suggest that the F‐actin cytoskeleton plays an inhibitory role in the regulation of MMP‐2 in VSMCs. Since MRTF‐A is critical for regulation of the contractile genes in VSMCs, future work will determine the role of MRTF‐A in MMP‐2 regulation. (Funding: NIH R01 GM60651)Grant Funding SourceNIH