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Physiological Reports

Cover image for Vol. 2 Issue 7

July 2014

Volume 2, Issue 7

  1. Issue Information

    1. Top of page
    2. Issue Information
    3. Original Research
    4. Corrigendum
    5. Original Research
    1. You have full text access to this Open Access content
      Issue Information

      Version of Record online: 3 JUL 2014 | DOI: 10.14814/phy2.12074

  2. Original Research

    1. Top of page
    2. Issue Information
    3. Original Research
    4. Corrigendum
    5. Original Research
    1. You have full text access to this OnlineOpen article
      Ventriculo-arterial coupling in children with Still's murmur

      Juliane Engel, Sigrid Baumgartner, Silvia Novak, Christoph Male and Ulrike Salzer-Muhar

      Version of Record online: 3 JUL 2014 | DOI: 10.14814/phy2.12041

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      So far, the physiology of Still's murmur has not yet been defined. This study is the first to describe a significant difference in ventriculo-arterial coupling in healthy children with and without Still's murmur.

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      Galacto-oligosaccharides attenuate renal injury with microbiota modification

      Satoshi U. Furuse, Takamoto Ohse, Airi Jo-Watanabe, Akira Shigehisa, Koji Kawakami, Takahiro Matsuki, Osamu Chonan and Masaomi Nangaku

      Version of Record online: 3 JUL 2014 | DOI: 10.14814/phy2.12029

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      GOS ameliorated the renal injury with lower indoxyl sulfate. GOS could be a novel therapeutic agent to protect against kidney disease.

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      Efficient training protocol for rapid learning of the two-alternative forced-choice visual stimulus detection task

      Shogo Soma, Naofumi Suematsu and Satoshi Shimegi

      Version of Record online: 3 JUL 2014 | DOI: 10.14814/phy2.12060

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      We developed an effective and stable training system for the two-alternative forced-choice visual stimulus detection task, which introduced a spout-lever as the operandum and a three-step training program with four ingenuities: (1) a salient stimulus to draw passive attention, (2) a reward-guaranteed trial to keep motivation, (3) a behavior-corrective trial, and (4) switching from a reward-guaranteed trial to a nonguaranteed one to correct behavioral patterns. This system realized 1-week completion of the whole learning process.

    4. You have full text access to this OnlineOpen article
      Clathrin complexes with the inhibitor kappa B kinase signalosome: imaging the interactome

      Fabia Gamboni, Guillermo A. Escobar, Ernest E. Moore, Monika Dzieciatkowska, Kirk C. Hansen, Sanchayita Mitra, Trevor A. Nydam, Christopher C. Silliman and Anirban Banerjee

      Version of Record online: 3 JUL 2014 | DOI: 10.14814/phy2.12035

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      Clathrin forms complexes with IKKa, IKKb, and NEMO, but apparently not the canonical signalosome. These complexes are identified, for the first time, by affinity proteomics and triple FRET without altering molecular structure.

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      Blood viscosity during coagulation at different shear rates

      Marco Ranucci, Tommaso Laddomada, Matteo Ranucci and Ekaterina Baryshnikova

      Version of Record online: 3 JUL 2014 | DOI: 10.14814/phy2.12065

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      Measurement of blood viscosity with cone-on-plate technology allows to detect the transition point between liquid and gel phases of blood during coagulation (gel point). The time-to-gel point is dependent on the shear rate and demonstrated an association with the activated partial thromboplastin time.

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      Association of serum interleukin-27 with the exacerbation of chronic obstructive pulmonary disease

      Takashi Angata, Takeo Ishii, Congxiao Gao, Kazuaki Ohtsubo, Shinobu Kitazume, Akihiko Gemma, Kozui Kida and Naoyuki Taniguchi

      Version of Record online: 3 JUL 2014 | DOI: 10.14814/phy2.12069

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      Chronic obstructive pulmonary disease (COPD) patients who do not have Siglec-14 (a myeloid cell protein that triggers inflammatory responses) are less prone to exacerbation of the disease. We tested whether soluble mediators secreted by myeloid cells responding to Siglec-14 engagement could be utilized as biomarkers of exacerbation, and found serum concentration of interleukin-27 (IL-27) was elevated during exacerbation, particularly in exacerbations accompanied with sputum purulence. We concluded that IL-27 might be mechanistically involved in the exacerbation of COPD and could potentially serve as a systemic biomarker of exacerbation.

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      Interleukin-6 deficiency causes tissue-specific changes in signaling pathways in response to high-fat diet and physical activity

      Jessica L. Sarvas, Sarah Niccoli, Eric Walser, Neelam Khaper and Simon J. Lees

      Version of Record online: 4 JUL 2014 | DOI: 10.14814/phy2.12064

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      This study was designed to investigate the role of interleukin-6 (IL-6) on high-fat diet (HFD)-induced glucose intolerance, and the response to voluntary physical activity in the prevention of insulin resistance. This study provides new insight into the role of the IL-6 in metabolism and energy storage, and highlights tissue-specific changes in early signaling pathways in response to HFD for 4 weeks. The collective findings suggest that endogenous IL-6 is important for the prevention of insulin resistance leading to type 2 diabetes.

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      Efficient estimation of the total number of acini in adult rat lung

      Sébastien F. Barré, David Haberthür, Marco Stampanoni and Johannes C. Schittny

      Version of Record online: 4 JUL 2014 | DOI: 10.14814/phy2.12063

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      An efficient method to estimate the number of acini in young adult rats has been developed. All entrances of the acini were counted, labeled, and visualized in three-dimensional stacks of X-ray tomographic images. We observed that acinar airways start at various generations and that one transitional bronchiole may serve more than one acinus. A mean of 5612 (±547) acini per lung and a mean acinar airspace volume of 0.907 (±0.108) µL were estimated.

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      Amino acid-induced impairment of insulin sensitivity in healthy and obese rats is reversible

      Senthure Jeganathan, Abdikarim Abdullahi, Sana Zargar, Naomi Maeda, Michael C. Riddell and Olasunkanmi A. J. Adegoke

      Version of Record online: 4 JUL 2014 | DOI: 10.14814/phy2.12067

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      Using in vitro and in vivo systems, we show that amino acid-induced modulation of mTORC1/S6K1 signaling and serine phosphorylation of IRS-1 in muscle cells/skeletal muscle are temporal and reversible. In addition, in both lean and obese rats, leucine-induced impairment of whole body insulin sensitivity of glucose and amino acid is reversible within 24 h of treatment. Our data suggest that the use of leucine/amino acid in body weight management is unlikely to carry any lasting negative effect on insulin sensitivity.

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      Obesity-dependent dysregulation of glucose homeostasis in kinase suppressor of ras 2/ mice

      MaLinda D. Henry, Diane L. Costanzo-Garvey, Paula J. Klutho and Robert E. Lewis

      Version of Record online: 4 JUL 2014 | DOI: 10.14814/phy2.12053

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      A fraction of individuals with obesity-induced insulin resistance and diabetes respond to diet with improved glucose metabolism. The phenotype of C57BL/6 ksr2−/− mice, including obesity and obesity-related dysregulation of glucose homeostasis, recapitulates that of humans with KSR2 mutations. These data show that the glucose intolerance and AICAR insensitivity that accompanies KSR2 disruption in mice is preventable or reversible by diet, suggesting that dietary intervention in humans with KSR2 mutations should have similar effects.

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      Hyperpolarized 3He and 129Xe magnetic resonance imaging apparent diffusion coefficients: physiological relevance in older never- and ex-smokers

      Miranda Kirby, Alexei Ouriadov, Sarah Svenningsen, Amir Owrangi, Andrew Wheatley, Roya Etemad-Rezai, Giles E. Santyr, David G. McCormack and Grace Parraga

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12068

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      We aimed to better understand how 129Xe MRI measurements might explain well-established measurements of emphysema, and explored different 129Xe MRI apparent diffusion coefficients (ADCs) in a small group of older never-smokers and ex-smokers with chronic obstructive pulmonary disease (COPD). In the same visit, 3He ADC, the diffusing capacity of carbon monoxide and computed tomography (CT) emphysema measurements were acquired. In this small group of older never-smokers and ex-smokers with COPD, 129Xe ADCb12 provided a physiologically appropriate estimate of gas exchange abnormalities and alveolar microstructure.

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      Enhanced muscle pump during mild dynamic leg exercise inhibits sympathetic vasomotor outflow

      Keisho Katayama, Koji Ishida, Mitsuru Saito, Teruhiko Koike, Ai Hirasawa and Shigehiko Ogoh

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12070

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      Muscle sympathetic nerve activity during leg cycling was reduced when central blood volume was manipulated by increasing the pedaling frequency. This result suggest that sympathetic vasomotor outflow is strongly affected by loading of cardiopulmonary baroreceptors at light and mild dynamic leg exercise to maintain arterial blood pressure.

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      Moderate exercise training provides modest protection against adipose tissue inflammatory gene expression in response to high-fat feeding

      Melissa A. Linden, Yair Pincu, Stephen A. Martin, Jeffrey A. Woods and Tracy Baynard

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12071

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      We report that moderate exercise training provides modest protection from inflammation within white adipose tissue over time when mice are concomitantly placed on a high-fat diet. The exercise-induced protection of white adipose tissue was associated with reductions in both total and M1 macrophage polarization. Our findings highlight that moderate exercise training may delay the onset of white adipose tissue inflammation and impaired glycemic control when mice consume a high-fat diet; however, the benefits of exercise may be limited when poor lifestyle choices are maintained.

    14. You have full text access to this OnlineOpen article
      Three-dimensional myocardial scarring along myofibers after coronary ischemia–reperfusion revealed by computerized images of histological assays

      Monica Y. Katz, Yoichiro Kusakari, Hiroko Aoyagi, Jason K. Higa, Chun-Yang Xiao, Ahmed Z. Abdelkarim, Karra Marh, Toshinori Aoyagi, Anthony Rosenzweig, Scott Lozanoff and Takashi Matsui

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12072

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      In a mouse model of ischemia–reperfusion injury induced by left anterior descending coronary artery ligation, three-dimensional images of myocardial scarring obtained from tissue sections (solid yellow area) indicate that the scar sequentially extends from the base to the apex in the midcardium. At the apex, the scar formation tracks along the myofibers in an incomplete C-shaped ring that converges to a triangular shape toward the end. These findings suggest that myocyte injury after transient coronary ligation extends along myofibers, rather than following the path of coronary arteries penetrating the myocardium.

    15. You have full text access to this OnlineOpen article
      Functional diversity of voltage-sensing phosphatases in two urodele amphibians

      Joshua Mutua, Yuka Jinno, Souhei Sakata, Yoshifumi Okochi, Shuichi Ueno, Hidekazu Tsutsui, Takafumi Kawai, Yasuhiro Iwao and Yasushi Okamura

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12061

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      To gain insights into physiological roles of VSP, VSP orthologs were identified from two urodeles, newt and salamander. Cp-VSP has voltage-dependent phosphatase activity. Hn-VSP lacks phosphatase activity due to its truncation in the C2 domain of the cytoplasmic region.

    16. You have full text access to this OnlineOpen article
      Exploring the physiologic role of human gastroesophageal reflux by analyzing time-series data from 24-h gastric and esophageal pH recordings

      Luo Lu, John C. Mu, Sheldon Sloan, Philip B. Miner Jr and Jerry D. Gardner

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12051

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      e12051

      We found that in pH records from normal subjects, as well as from subjects with gastroesophageal reflux disease alone and after treatment with a proton pump inhibitor, gastric pH values provided important information regarding subsequent values of esophageal pH and values of esophageal pH provided important information regarding subsequent values of gastric pH. Our findings are consistent with the hypothesis that depending on the value of gastric acidity, the esophagus can signal the stomach to alter gastric acidity, and that this ability is impaired in subjects with gastroesophageal reflux disease.

    17. You have full text access to this OnlineOpen article
      Low oxygen tension enhances the generation of lung progenitor cells from mouse embryonic and induced pluripotent stem cells

      Elena Garreta, Esther Melo, Daniel Navajas and Ramon Farré

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12075

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      Differentiation of pluripotent stem cells into lung progenitors is improved at low oxygen tension (5% oxygen) as compared with the conventional culture conditions of room air (20% oxygen).

    18. You have full text access to this OnlineOpen article
      Mineralocorticoid effects in the late gestation ovine fetal lung

      Jarret McCartney, Elaine M. Richards, Charles E. Wood and Maureen Keller-Wood

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12066

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      Infusion of the mineralocorticoid receptor agonist, aldosterone, to the ovine fetus resulted in reduced airway pressures with initial lung inflation. However, aldosterone did not alter lung surfactant or epithelial sodium transport genes which are classical MR gene targets. Transcriptomic analysis revealed an aldosterone effect on genes related to cell cycle, suggesting that MR have a role distinct form that of GR in the maturing lung.

    19. You have full text access to this OnlineOpen article
      Reduced inhibitory gate in the barrel cortex of Neuroligin3R451C knock-in mice, an animal model of autism spectrum disorders

      Giada Cellot and Enrico Cherubini

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12077

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      Autism spectrum disorders (ASDs) comprise a heterogeneous group of neurodevelopmental abnormalities, characterized by impaired social interactions. Here, using mice carrying the R451C mutation of the Nlgn3 gene (found in few familial cases of ASDs), and exhibiting behavioral deficits reminiscent of those present in ASD patients, we found that, in layer IV barrel cortex microcircuit, parvalbumin-expressing basket cells display a reduced probability of GABA release into spiny neurons. Alterations of GABAergic signaling in layer IV somatosensory cortex of NL3R451C knock-in mice may alter sensory processing leading to misleading sensory representations with difficulties to combine pieces of information into a unified perceptual whole.

    20. You have full text access to this OnlineOpen article
      Acute cyclooxygenase inhibition does not alter muscle sympathetic nerve activity or forearm vasodilator responsiveness in lean and obese adults

      Jill N. Barnes, Nisha Charkoudian, Luke J. Matzek, Christopher P. Johnson, Michael J. Joyner and Timothy B. Curry

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12079

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      Obesity is often characterized by chronic inflammation that may contribute to increased cardiovascular risk via sympathoexcitation. However, an acute dose of the cyclooxygenase inhibitor ibuprofen did not alter blood pressure or muscle sympathetic nerve activity in lean and obese humans.

    21. You have full text access to this OnlineOpen article
      PYK2 selectively mediates signals for growth versus differentiation in response to stretch of spontaneously active vascular smooth muscle

      Anirban Bhattachariya, Karolina M. Turczyńska, Mario Grossi, Ina Nordström, Leonard Buckbinder, Sebastian Albinsson and Per Hellstrand

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12080

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      We studied the role of the calcium- and integrin-activated proline-rich tyrosine kinase 2 (PYK2) in stretch-induced responses of the rat portal ex vivo. PYK2 phosphorylation at Tyr-402 was increased both by a 10-min stretch and by organ culture under stretch for 3 days. Protein and DNA synthesis were reduced by the novel PYK2 inhibitor PF-4594755 (0.5–1 μmol/L), but contractile differentiation was not affected. Basal and stretch-induced PYK2 phosphorylation in culture were inhibited by PF-4594755, closely mimicking inhibition of non-voltage-dependent calcium influx by 2-APB (30 μmol/L). In contrast, the L-type calcium channel blocker, nifedipine (1 μmol/L) eliminated stretch-induced but not basal PYK2 phosphorylation. The results suggest that PYK2 signaling functionally distinguishes effects of voltage- and non-voltage-dependent calcium influx.

    22. You have full text access to this OnlineOpen article
      Eccentric contractions disrupt FKBP12 content in mouse skeletal muscle

      Cory W. Baumann, Russell G. Rogers, Nidhi Gahlot and Christopher P. Ingalls

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12081

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      Eccentric contraction-induced muscle injury is associated with immediate and prolonged strength deficits that stem in part from impaired sarcoplasmic reticulum (SR) calcium release. The content of FKBP12, a 12-kD immunophilin known to bind to the SR calcium release channel and influence SR calcium release, is reduced in mouse skeletal muscle immediately after injury induction and is significantly associated with strength deficits.

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      Delay of left ventricular longitudinal expansion with diastolic dysfunction: impact on load dependence of e′ and longitudinal strain rate

      Hiroyuki Iwano, Min Pu, Bharathi Upadhya, Brett Meyers, Pavlos Vlachos and William C. Little

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12082

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      In patients with diastolic dysfunction, longitudinal LV expansion is delayed occurring after mitral flow and the termination of the pressure difference from the left atrium to the LV apex. Thus, with diastolic dysfunction longitudinal expansion (e' and longitudinal early diastolic global strain rate) become nearly independent of load.

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      Age-related differences in postsynaptic increases in sweating and skin blood flow postexercise

      Jill M. Stapleton, Naoto Fujii, Ryan McGinn, Katherine McDonald and Glen P. Kenny

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12078

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      Centrally mediated factors of nonthermal origin modulate the control of heat loss following exercise in young adults. It remains unclear if peripheral factors also play a role and whether the mechanisms modulating the postexercise suppression of heat loss differ as a function of age. We show that peripheral factors do not modulate postexercise sweating and skin blood flow in both young and older adults.

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      Hypomethylation of the promoter of the catalytic subunit of protein phosphatase 2A in response to hyperglycemia

      Fabiola Tros, Aline Meirhaeghe, Samy Hadjadj, Philippe Amouyel, Pierre Bougnères and Delphine Fradin

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12076

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      In order to identify epigenetic mechanisms through which hyperglycemia can affect gene expression durably in β cells, we screened DNA methylation changes induced by high glucose concentration in the BTC3 murine cell line. We identified one interesting gene, PP2AC, and confirmed it in type 2 diabetic patients.

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      Nerve growth factor reduces amiloride-sensitive Na+ transport in human airway epithelial cells

      Michael J. Shimko, Eric J. Zaccone, Janet A. Thompson, Diane Schwegler-Berry, Michael L. Kashon and Jeffrey S. Fedan

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12073

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      Nerve growth factor (apical, 1 ng/mL) reduced amiloride-sensitive Na+ transport in human cultured bronchial epithelial cells. We determined that this reduction in Na+ transport occurred through NGF-mediated activation of the trkA receptor and Erk 1/2 signaling cascade to cause phosphorylation of ENaC.

    27. You have full text access to this OnlineOpen article
      Assessment of total retinal blood flow using Doppler Fourier Domain Optical Coherence Tomography during systemic hypercapnia and hypocapnia

      Ayda M. Shahidi, Sunni R. Patel, David Huang, Ou Tan, John G. Flanagan and Chris Hudson

      Version of Record online: 17 JUL 2014 | DOI: 10.14814/phy2.12046

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      Total retinal blood flow changes in response to the manipulation of systemic partial pressure of CO2 was measured in healthy individuals using Doppler Fourier Domain Optical Coherence Tomography. Increased total retinal blood flow and decreased blood flow were found in response to hypercapnia and hypocapnia, respectively.

    28. You have full text access to this OnlineOpen article
      Quantitative immunofluorescence microscopy of subcellular GLUT4 distribution in human skeletal muscle: effects of endurance and sprint interval training

      Helen Bradley, Christopher S. Shaw, Philip L. Worthington, Sam O. Shepherd, Matthew Cocks and Anton J. M. Wagenmakers

      Version of Record online: 22 JUL 2014 | DOI: 10.14814/phy2.12085

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      This paper first describes the development of a novel confocal immunofluorescence microscopy method that allows quantitation of GLUT4 content in the plasma membrane and 1 µm layers below it in a muscle fibre-type specific manner. Skeletal muscle biopsies obtained from sedentary young men before and after 6 weeks of traditional endurance training (ET) and sprint interval training (SIT) were then analysed to show for the first time increases in large and small GLUT4 clusters with greater increases in the layer within 1 µm of the plasma membrane, which is the layer from which most GLUT4 fusion events emanate. This training-induced redistribution is likely to contribute to the increase in insulin sensitivity seen following both ET and SIT.

    29. You have full text access to this OnlineOpen article
      Lack of megalin expression in adult human terminal ileum suggests megalin-independent cubilin/amnionless activity during vitamin B12 absorption

      Louise L. Jensen, Rikke K. Andersen, Henrik Hager and Mette Madsen

      Version of Record online: 22 JUL 2014 | DOI: 10.14814/phy2.12086

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      Studies of human terminal ileum samples demonstrate lack of LRP2/megalin expression in adult terminal ileum and point to a megalin-independent cubilin-amnionless-driven uptake mechanism for vitamin B12.

    30. You have full text access to this OnlineOpen article
      Automated quantification of renal fibrosis with Sirius Red and polarization contrast microscopy

      Jonathan M. Street, Ana Carolina P. Souza, Alejandro Alvarez-Prats, Taro Horino, Xuzhen Hu, Peter S. T. Yuen and Robert A. Star

      Version of Record online: 22 JUL 2014 | DOI: 10.14814/phy2.12088

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      Histological assessment of interstitial fibrosis is commonly achieved by subjective scoring of Masson trichrome-stained sections. We have developed an alternative approach that is rapid, reproducible, and precise by combining whole-section imaging and automated image analysis with Sirius Red and polarization contrast microscopy. This new tool shall enhance our search for novel therapeutics and noninvasive biomarkers for fibrosis.

      Join Physiological Reports editor Tom Kleyman and author Jonathan Street as they discuss a manuscript here

    31. You have full text access to this OnlineOpen article
      Ascorbic acid does not enhance hypoxia-induced vasodilation in healthy older men

      Jonathan P. Pollock, Hardikkumar M. Patel, Brittney J. Randolph, Matthew J. Heffernan, Urs A. Leuenberger and Matthew D. Muller

      Version of Record online: 22 JUL 2014 | DOI: 10.14814/phy2.12091

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      In Experiment 1, heart rate (HR), mean arterial pressure (MAP), forearm vascular conductance (FVC), and forearm cutaneous vascular conductance (CVC) were measured in response to 5 min of continuous hypoxia (10% oxygen) in young men (black diamonds) and older men (white squares). In Experiment 2, older men breathed continuous hypoxia after receiving normal saline solution (NSS, white squares) and ascorbic acid (Vit C, black squares). These findings advance our basic understanding of how aging influences vascular responses to hypoxia and suggest that, in healthy humans, hypoxia-induced vasodilation is not restrained by reactive oxygen species.

  3. Corrigendum

    1. Top of page
    2. Issue Information
    3. Original Research
    4. Corrigendum
    5. Original Research
    1. You have full text access to this OnlineOpen article
      Corrigendum

      Version of Record online: 22 JUL 2014 | DOI: 10.14814/phy2.12062

      This article corrects:
  4. Original Research

    1. Top of page
    2. Issue Information
    3. Original Research
    4. Corrigendum
    5. Original Research
    1. You have full text access to this OnlineOpen article
      Prolonged acute kidney injury exacerbates lung inflammation at 7 days post-acute kidney injury

      Ana Andres-Hernando, Christopher Altmann, Rhea Bhargava, Kayo Okamura, Jasna Bacalja, Brandi Hunter, Nilesh Ahuja, Danielle Soranno and Sarah Faubel

      Version of Record online: 22 JUL 2014 | DOI: 10.14814/phy2.12084

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      Our data demonstrate that prolonged AKI is associated with lung inflammation up to 7 days post-AKI consistent with the notion that duration of AKI is important in the adverse outcomes associated with AKI.

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      Dietary nitrate reduces skeletal muscle oxygenation response to physical exercise: a quantitative muscle functional MRI study

      Rachel Bentley, Stuart R. Gray, Christian Schwarzbauer, Dana Dawson, Michael Frenneaux and Jiabao He

      Version of Record online: 22 JUL 2014 | DOI: 10.14814/phy2.12089

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      It is known that nitrate supplement improves skeletal muscle metabolic efficiency, and postulated to be attributed to improved oxygen delivery to the tissue. We examines the effects of dietary nitrate on skeletal muscle oxygen regulation in healthy subjects under two levels of physical exercise intensities, and found that the tissue oxygenation change induced by physical exercise is reduced by nitrate supplement primarily at a lower exercise intensity in type 1 muscle fibers. Our results indicate that the hypoxic stress associated with a higher exercise intensity does not augment the oxygen delivery to skeletal muscle in healthy subjects.

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      Low-dose maternal alcohol consumption: effects in the hearts of offspring in early life and adulthood

      Vivian B. Nguyen, Megan E. Probyn, Fiona Campbell, Kom V. Yin, Chrishan S. Samuel, Monika A. Zimanyi, John F. Bertram, Mary Jane Black and Karen M. Moritz

      Version of Record online: 31 JUL 2014 | DOI: 10.14814/phy2.12087

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      Low dose alcohol consumption during gestation in rats illustrated no differences in cardiomyocyte and cardiac growth in the offspring in early life. However, in adulthood, induction of left ventricular hypertrophy was observed suggesting low doses of alcohol during pregnancy can be detrimental to long-term cardiac health in offspring.

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      The obesity-associated gene Negr1 regulates aspects of energy balance in rat hypothalamic areas

      Arjen J. Boender, Margriet A. van Gestel, Keith M. Garner, Mieneke C. M. Luijendijk and Roger A. H. Adan

      Version of Record online: 31 JUL 2014 | DOI: 10.14814/phy2.12083

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      Decreased expression of Negr1 in periventricular hypothalamic areas leads to increases in body weight, presumably via increased intake of carbohydrates. Moreover, we observed that both increased and decreased levels of Negr1 lead to reduced locomotor activity and body temperature. In sum, our results provide further support for a role of hypothalamic expressed Negr1 in the regulation of energy balance.

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