November 2016; volume 311, issue 5 - American Physiological Society [PDF]

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November 2016; volume 311, issue 5 The below Table of Contents is available online at: http://ajpcell.physiology.org/content/311/5

Themes Tuning the proteasome to brighten the end of the journey Thibault Mayor, Michal Sharon, Michael H. Glickman November 11, 2016 : C793-C804 DOI: 10.1152/ajpcell.00198.2016

Editorial Focus Making isotonic milk. Focus on “Ca2+-activated Cl -  channel currents in mammary secretory cells from lactating mouse” Bruce D. Schultz November 11, 2016 : C805-C807 DOI: 10.1152/ajpcell.00279.2016

CALL FOR PAPERS | Regulation of Cell Signaling Pathways cAMP-dependent recruitment of acidic organelles for Ca2+ signaling in the salivary gland John F. Imbery, Sumit Bhattacharya, Sura Khuder, Amanda Weiss, Priyodarshan Goswamee, Azwar K. Iqbal, David R. Giovannucci November 1, 2016 : C697-C709 DOI: 10.1152/ajpcell.00010.2016 sFRP2 activates Wnt/β-catenin signaling in cardiac fibroblasts: differential roles in cell growth, energy metabolism, and extracellular matrix remodeling Huey Lin, Mia Angeli, Kwang Jin Chung, Chukwuemeka Ejimadu, Angelica Rivera Rosa, Techung Lee November 1, 2016 : C710-C719 DOI: 10.1152/ajpcell.00137.2016 SM22α inhibits lamellipodium formation and migration via Ras-Arp2/3 signaling in synthetic VSMCs Pin Lv, Fan Zhang, Ya-Juan Yin, Yu-Can Wang, Min Gao, Xiao-Li Xie, Li-Li Zhao, Li-Hua Dong, Yan-Ling Lin, Ya-Nan Shu, Dan-Dan Zhang, Gui-Xia Liu, Mei Han November 1, 2016 : C758-C767 DOI: 10.1152/ajpcell.00033.2016

Articles Insulin and SGK1 reduce the function of Na+ /monocarboxylate transporter 1 (SMCT1/SLC5A8)

Adriana López-Barradas, Tania González-Cid, Norma Vázquez, Marisol Gavi-Maza, Adriana Reyes-Camacho, Laura A. VelázquezVillegas, Victoria Ramírez, Kambiz Zandi-Nejad, David B. Mount, Nimbe Torres, Armando R. Tovar, Michael F. Romero, Gerardo Gamba, Consuelo Plata November 1, 2016 : C720-C734 DOI: 10.1152/ajpcell.00104.2015 Functional assessment of SLC4A11, an integral membrane protein mutated in corneal dystrophies Sampath K. Loganathan, Hans-Peter Schneider, Patricio E. Morgan, Joachim W. Deitmer, Joseph R. Casey November 1, 2016 : C735-C748 DOI: 10.1152/ajpcell.00078.2016 Malignant hyperthermia-associated mutations in the S2-S3 cytoplasmic loop of type 1 ryanodine receptor calcium channel impair calcium-dependent inactivation Angela C. Gomez, Timothy W. Holford, Naohiro Yamaguchi November 1, 2016 : C749-C757 DOI: 10.1152/ajpcell.00134.2016 Angiotensin II counteracts the effects of cAMP/PKA on NHE3 activity and phosphorylation in proximal tubule cells Renato O. Crajoinas, Juliano Z. Polidoro, Carla P. A. Carneiro de Morais, Regiane C. Castelo-Branco, Adriana C. C. Girardi November 1, 2016 : C768-C776 DOI: 10.1152/ajpcell.00191.2016 Chenodeoxycholic acid requires activation of EGFR, EPAC, and Ca2+ to stimulate CFTR-dependent Cl -  secretion in human colonic T84 cells Jada C. Domingue, Mei Ao, Jayashree Sarathy, Mrinalini C. Rao November 1, 2016 : C777-C792 DOI: 10.1152/ajpcell.00168.2016 Ca2+-activated Cl -  channel currents in mammary secretory cells from lactating mouse Akihiro Kamikawa, Osamu Ichii, Junpei Sakazaki, Toru Ishikawa November 11, 2016 : C808-C819 DOI: 10.1152/ajpcell.00050.2016 Multifunctional ion transport properties of human SLC4A11: comparison of the SLC4A11-B and SLC4A11-C variants Liyo Kao, Rustam Azimov, Xuesi M. Shao, Ricardo F. Frausto, Natalia Abuladze, Debra Newman, Anthony J. Aldave, Ira Kurtz November 11, 2016 : C820-C830 DOI: 10.1152/ajpcell.00233.2016

Rapid Reports RACK1 is required for adipogenesis Qinghua Kong, Lan Gao, Yanfen Niu, Pianchou Gongpan, Yuhui Xu, Yan Li, Wenyong Xiong November 11, 2016 : C831-C836 DOI: 10.1152/ajpcell.00224.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 311, issue 5 The below Table of Contents is available online at: http://ajpendo.physiology.org/content/311/5

CALL FOR PAPERS | Endocrine and Metabolic Dysfunction during Aging and Senescence Does the muscle protein synthetic response to exercise and amino acid-based nutrition diminish with advancing age? A systematic review Brandon J. Shad, Janice L. Thompson, Leigh Breen November 1, 2016 : E803-E817 DOI: 10.1152/ajpendo.00213.2016

CALL FOR PAPERS | Metabolic Control by Inflammation and Immunity Inflammation mediates the association between visceral adiposity and obstructive sleep apnea in adolescents Jordan Gaines, Alexandros N. Vgontzas, Julio Fernandez-Mendoza, Susan L. Calhoun, Fan He, Duanping Liao, Marjorie D. Sawyer, Edward O. Bixler November 15, 2016 : E851-E858 DOI: 10.1152/ajpendo.00249.2016

Articles Novel single skeletal muscle fiber analysis reveals a fiber type-selective effect of acute exercise on glucose uptake Gregory D. Cartee, Edward B. Arias, Carmen S. Yu, Mark W. Pataky November 1, 2016 : E818-E824 DOI: 10.1152/ajpendo.00289.2016 Saturated fatty acids activate caspase-4/5 in human monocytes, triggering IL-1β and IL-18 release Nicolas J. Pillon, Kenny L. Chan, Shitian Zhang, Marios Mejdani, Maya R. Jacobson, Alexandre Ducos, Philip J. Bilan, Wenyan Niu, Amira Klip November 1, 2016 : E825-E835 DOI: 10.1152/ajpendo.00296.2016 Protein coingestion with alcohol following strenuous exercise attenuates alcohol-induced intramyocellular apoptosis and inhibition of autophagy William J. Smiles, Evelyn B. Parr, Vernon G. Coffey, Orly Lacham-Kaplan, John A. Hawley, Donny M. Camera November 1, 2016 : E836-E849 DOI: 10.1152/ajpendo.00303.2016 Development of a reliable automated screening system to identify small molecules and biologics that promote human β-cell regeneration Kristie I. Aamodt, Radhika Aramandla, Judy J. Brown, Nathalie Fiaschi-Taesch, Peng Wang, Andrew F. Stewart, Marcela Brissova, Alvin C. Powers November 15, 2016 : E859-E868 DOI: 10.1152/ajpendo.00515.2015 Zinc finger protein 407 overexpression upregulates PPAR target gene expression and improves glucose homeostasis in mice Alyssa Charrier, Li Wang, Erin J. Stephenson, Siddharth V. Ghanta, Chih-wei Ko, Colleen M. Croniger, Dave Bridges, David A. Buchner November 15, 2016 : E869-E880 DOI: 10.1152/ajpendo.00234.2016 Caspase-1 deficiency promotes high-fat diet-induced adipose tissue inflammation and the development of obesity Hiroaki Kimura, Tadayoshi Karasawa, Fumitake Usui, Akira Kawashima, Yuka Endo, Motoi Kobayashi, Ai Sadatomo, Jun Nakamura, Yusaku Iwasaki, Toshihiko Yada, Hiroko Tsutsui, Tadashi Kasahara, Masafumi Takahashi November 15, 2016 : E881-E890 DOI: 10.1152/ajpendo.00174.2016 Prolonged sitting negatively affects the postprandial plasma triglyceride-lowering effect of acute exercise Il-Young Kim, Sanghee Park, Ting-Heng Chou, Justin R. Trombold, Edward F. Coyle November 15, 2016 : E891-E898 DOI: 10.1152/ajpendo.00287.2016

Corrigendum Corrigendum November 15, 2016 : E899 DOI: 10.1152/ajpendo.zh1-7676-corr.2016

Retraction Retraction November 1, 2016 : E850 DOI: 10.1152/ajpendo.zh1-7671-retr.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 311, issue 5 The below Table of Contents is available online at: http://ajpgi.physiology.org/content/311/5

Themes Neuroimmune Cross Talk in the Gut. Neuroendocrine and neuroimmune pathways contribute to the pathophysiology of irritable bowel syndrome Dervla O'Malley November 1, 2016 : G934-G941 DOI: 10.1152/ajpgi.00272.2016

Minireview Chemical and molecular factors in irritable bowel syndrome: current knowledge, challenges, and unanswered questions Michael Camilleri, Ibironke Oduyebo, Houssam Halawi November 1, 2016 : G777-G784 DOI: 10.1152/ajpgi.00242.2016

Editorial Focus Arterial hypertension as an uninvited player in hepatic stiffness? Vlad Ratziu, Dominique Valla, Pierre-Emmanuel Rautou November 1, 2016 : G942-G944 DOI: 10.1152/ajpgi.00276.2016

Rapid Report TLR9 activation suppresses inflammation in response to Helicobacter pylori infection Matthew G. Varga, M. Blanca Piazuelo, Judith Romero-Gallo, Alberto G. Delgado, Giovanni Suarez, Morgan E. Whitaker, Uma S. Krishna, Rachna V. Patel, Eric P. Skaar, Keith T. Wilson, Holly M. S. Algood, Richard M. Peek Jr.

November 1, 2016 : G852-G858 DOI: 10.1152/ajpgi.00175.2016 Helicobacter pylori (H. pylori) activates Toll-like receptor 9 (TLR9) via translocation of DNA through its main virulence constituent, the cag pathogenicity island. In this study, we utilized Tlr9- and IL-17-deficient mice to demonstrate that H. pylori-induced activation of TLR9 in vivo induces an anti-inflammatory phenotype suppressing IL-17-mediated responses. These results suggest that H. pylori utilizes the cag island to manipulate the intensity of the host immune response.

Epithelial Biology and Secretion Segmental differences in upregulated apical potassium channels in mammalian colon during potassium adaptation Matthew D. Perry, Vazhaikkurichi M. Rajendran, Kenneth A. MacLennan, Geoffrey I. Sandle November 1, 2016 : G785-G793 DOI: 10.1152/ajpgi.00181.2015 Mammalian colon is an important K+ homeostatic organ. In rats, chronic dietary K+ loading stimulates apical BK channel-mediated pan-colonic K+ secretion, the overall K+ secretory response being greater distally than proximally. Here we show that K+ loading induced a 3.5-fold increase in BK channel abundance and increased BK protein expression in surface and upper crypt cells in distal colon, but not in proximal colon, highlighting the importance of the distal colon in maintaining K+ homeostasis. Somatostatin regulates NHE8 protein expression via the ERK1/2 MAPK pathway in DSS-induced colitis mice Xiao Li, Lin Cai, Hua Xu, Chong Geng, Jing Lu, Liping Tao, Dan Sun, Fayez K. Ghishan, Chunhui Wang November 1, 2016 : G954-G963 DOI: 10.1152/ajpgi.00239.2016

Neurogastroenterology and Motility Characterization and mechanisms of the pharyngeal swallow activated by stimulation of the esophagus Ivan M. Lang, Bidyut K. Medda, Sudarshan R. Jadcherla, Reza Shaker November 1, 2016 : G827-G837 DOI: 10.1152/ajpgi.00291.2016 We characterized the stimuli that best activate the pharyngeal swallow response to esophageal stimulation (EPSR) that occurs primarily in human infants and animals and identified the type and location of receptors that mediate this response. The EPSR is activated in a probabilistic manner and is best activated by acidic solutions in more proximal areas of the esophagus. Our findings suggest that this swallow response is very important in human infants to prevent supraesophageal reflux. Convergence of inhibitory neural inputs regulate motor activity in the murine and monkey stomach Lara A. Shaylor, Sung Jin Hwang, Kenton M. Sanders, Sean M. Ward November 1, 2016 : G838-G851 DOI: 10.1152/ajpgi.00062.2016 Inhibitory neurotransmitters regulate gastric motor activity. However, the exact role of how different neurotransmitters contribute to this activity remains to be fully investigated. In the present study we demonstrate a convergence of nitric oxide and purine components to inhibitory motor responses of the gastric antrum. We also show that these responses are highly conserved from rodents to primates demonstrating the importance of these inhibitory pathways in the modulation of gastric motor activity across diverse species. Measurement of strains experienced by viscerofugal nerve cell bodies during mechanosensitive firing using digital image correlation Gwen Palmer, Timothy J. Hibberd, Tiina Roose, Simon J. H. Brookes, Mark Taylor November 1, 2016 : G869-G879 DOI: 10.1152/ajpgi.00397.2015 High-resolution, noncontact optical measurement of gut strain (digital image correlation) was combined with neurophysiological recordings of viscerofugal neurons for the first time. Isotonic circumferential and longitudinal distensions activated viscerofugal neurons. Distensions evoked heterogeneous strain in gut preparations. Local strain measured at viscerofugal nerve cell bodies correlated closely with stretch-evoked firing. Accounting for strain in multiple axes increased the correlation with viscerofugal neuron firing. Digital image correlation can be usefully combined with gastrointestinal neurophysiology. Imaging activation of peptidergic spinal afferent varicosities within visceral organs using novel CGRPα-mCherry reporter mice Nick J. Spencer, Julian Sorensen, Lee Travis, Lukasz Wiklendt, Marcello Costa, Tim Hibberd November 1, 2016 : G880-G894

DOI: 10.1152/ajpgi.00250.2016 Until now, all recordings from spinal afferent neurons have been made outside their target peripheral organ, which is not where sensory transduction takes place. This study shows that transgenic CGRPα-mCherry reporter mice can be used to visualize and record directly, for the first time, from the major class of spinal afferent nerve axon within a peripheral organ. Circumferential stretch activates calcium transients along CGRPα-expressing spinal afferent varicosities. Functional physiology of the human terminal antrum defined by high-resolution electrical mapping and computational modeling Rachel Berry, Taimei Miyagawa, Niranchan Paskaranandavadivel, Peng Du, Timothy R. Angeli, Mark L. Trew, John A. Windsor, Yohsuke Imai, Gregory O'Grady, Leo K. Cheng November 1, 2016 : G895-G902 DOI: 10.1152/ajpgi.00255.2016 Aging-associated changes in microRNA expression profile of internal anal sphincter smooth muscle: Role of microRNA-133a Jagmohan Singh, Ettickan Boopathi, Sankar Addya, Benjamin Phillips, Isidore Rigoutsos, Raymond B. Penn, Satish Rattan November 1, 2016 : G964-G973 DOI: 10.1152/ajpgi.00290.2016

Hormones, Neurotransmitters, Growth Factors, Receptors, and Signaling Nerve growth factor is critical requirement for in vitro angiogenesis in gastric endothelial cells Amrita Ahluwalia, Michael K. Jones, Tomasz Brzozowski, Andrzej S. Tarnawski November 1, 2016 : G981-G987 DOI: 10.1152/ajpgi.00334.2016 Angiogenesis—new blood vessel formation—is critical for gastric mucosal injury healing. The endothelial cells lining blood vessels are the targets and effectors of angiogenesis, and vascular endothelial growth factor is recognized as the main regulator. The role of nerve growth factor (NGF) in gastric angiogenesis is unknown. Our study uncovered a critical role of NGF in gastric angiogenesis and identified some of the underlying mechanisms.

Liver and Biliary Tract Physiology/Pathophysiology Inhibition of miR-21 rescues liver regeneration after partial hepatectomy in ethanol-fed rats Egle Juskeviciute, Rachael P. Dippold, Anil N. Antony, Aditi Swarup, Rajanikanth Vadigepalli, Jan B. Hoek November 1, 2016 : G794-G806 DOI: 10.1152/ajpgi.00292.2016 MicroRNA-21 (miR-21) is thought to promote liver regeneration after partial hepatectomy (PHx), but it also facilitates fibrosis in liver and other tissues. In ethanol-fed rats, hepatocyte proliferation after PHx is suppressed, miR-21 expression is enhanced, and hepatic stellate cell (HSC) activation markers are upregulated. Inhibition of miR-21 restored cell cycle progression and prevented upregulation of HSC activation markers after PHx in ethanol-fed rats, suggesting that a miR-21-promoted profibrotic state of HSCs contributes to inhibition of hepatocyte proliferation. Hepatocyte ERBB3 and EGFR are required for maximal CCl4 -induced liver fibrosis Lawrence A. Scheving, Xiuqi Zhang, David W. Threadgill, William E. Russell November 1, 2016 : G807-G816 DOI: 10.1152/ajpgi.00423.2015 Epidermal growth factor receptor (EGFR) and its ligands have been implicated in liver fibrosis. We show that the genetic ablation of EGFR or ERBB3, particularly in combination, results in reduced liver fibrosis upon chronic CCl4 administration. Our results suggest that EGFR-ERBB3 heterodimeric signaling may play a more important role in liver fibrosis than the EGFR-EGFR signaling. We also show in this model increased tyrosine phosphorylation EGFR and ERBB3 in hepatocytes as well as nonparenchymal cells. A novel transgenic mouse model of lysosomal storage disorder Sonia Ortiz-Miranda, Rui Ji, Agata Jurczyk, Ken-Edwin Aryee, Shunyan Mo, Terry Fletcher, Scott A. Shaffer, Dale L. Greiner, Rita Bortell, Ronald G. Gregg, Alan Cheng, Leah J. Hennings, Ann R. Rittenhouse November 1, 2016 : G903-G919 DOI: 10.1152/ajpgi.00313.2015 We provide an explanation for striking pathology found in a subset of genetically engineered mice homozygous for a rat CaVβ2a transgene (Tg+/+). Multiple transgene (Tg) copies inserted into chromosome 19; at this same site a large deletion occurred, ablating cholesterol 25-hydroxylase and

partially deleting lysosomal acid lipase and CD95. Their loss of function can account for lipid build up and immune system hypertrophy, which defines this phenotype and serendipitously provides a novel model of lysosomal storage disorder. Arterial pressure suffices to increase liver stiffness Felix Piecha, Teresa Peccerella, Tom Bruckner, Helmut-Karl Seitz, Vanessa Rausch, Sebastian Mueller November 1, 2016 : G945-G953 DOI: 10.1152/ajpgi.00399.2015

Pancreatic Physiology/Pathophysiology Comprehensive analysis of microRNA signature of mouse pancreatic acini: overexpression of miR-21-3p in acute pancreatitis Ajay Kumar Dixit, Anne E. Sarver, Zuobiao Yuan, John George, Usman Barlass, Hassam Cheema, Archana Sareen, Sulagna Banerjee, Vikas Dudeja, Rajinder Dawra, Subbaya Subramanian, Ashok K. Saluja November 1, 2016 : G974-G980 DOI: 10.1152/ajpgi.00191.2016

Inflammation, Immunity, Fibrosis, and Infection Lactobacillus acidophilus counteracts inhibition of NHE3 and DRA expression and alleviates diarrheal phenotype in mice infected with Citrobacter rodentium Anoop Kumar, Arivarasu N. Anbazhagan, Hayley Coffing, Ishita Chatterjee, Shubha Priyamvada, Tarunmeet Gujral, Seema Saksena, Ravinder K. Gill, Waddah A. Alrefai, Alip Borthakur, Pradeep K. Dudeja November 1, 2016 : G817-G826 DOI: 10.1152/ajpgi.00173.2016 Dysregulated ion transport is a hallmark of diarrhea. Therefore, present studies examined the alleviation of downregulation of the expression of NHE3 and DRA by the probiotic Lactobacillus acidophilus in a murine model of infection by Citrobacter rodentium, a diarrheal pathogen. Our studies demonstrate for the first time that counteracting C. rodentium-induced inhibition of NHE3 and DRA expression could contribute to antidiarrheal effects of L. acidophilus. Acetylcholine-producing T cells in the intestine regulate antimicrobial peptide expression and microbial diversity Shobhit Dhawan, Giada De Palma, Rose A. Willemze, Francisca W. Hilbers, Caroline Verseijden, Misha D. Luyer, Sabine Nuding, Jan Wehkamp, Yuri Souwer, Esther C. de Jong, J. Seppen, René M. van den Wijngaard, Sven Wehner, Elena Verdu, Premek Bercik, Wouter J. de Jonge November 1, 2016 : G920-G933 DOI: 10.1152/ajpgi.00114.2016 T cells secreting the neurotransmitter acetylcholine were detected in the mouse and human intestine. We found that sympathetic, adrenergic, activity stimulates the generation of these cells. In genetically modified mice that lack the potential to secrete acetylcholine in their T cell compartment, we demonstrate impaired host defense mechanisms in the intestine and an elevated microbial diversity. As such, T cell-derived acetylcholine may act to fortify antimicrobial defense in the gut.

Nutrient Sensing, Nutrition, and Metabolism Hepatic aberrant glycosylation by N-acetylglucosaminyltransferase V accelerates HDL assembly Yoshihiro Kamada, Sachiho Kida, Ken-ichi Hirano, Satoshi Yamaguchi, Akira Suzuki, Chikako Hashimoto, Akihiro Kimura, Motoya Sato, Hironobu Fujii, Tomoaki Sobajima, Akiko Yamamoto, Yusuke Ebisutani, Shinji Takamatsu, Shinichiro Shinzaki, Yuichi Yoshida, Makoto Yamada, Hironori Nagasaka, Tetsuo Takehara, Eiji Miyoshi November 1, 2016 : G859-G868 DOI: 10.1152/ajpgi.00231.2016 In the present study, we have found that GnT-V accelerates HDL assembly in the liver of GnT-V transgenic mice and may be a novel regulator for plasma HDL levels in both mice and humans that provides a novel mechanism for HDL synthesis induced by GnT-V, possibly through aberrant glycosylation. We think that the glycan changes are new targets of metabolism biology. Copyright © 2016 by the American Physiological Society.

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November 2016; volume 311, issue 5 The below Table of Contents is available online at: http://ajpheart.physiology.org/content/311/5

Review Oh, the places you'll go! My many colored serotonin (apologies to Dr. Seuss) Stephanie W. Watts November 1, 2016 : H1225-H1233 DOI: 10.1152/ajpheart.00538.2016

CALL FOR PAPERS | Cardiovascular Epigenetics: Phenotypes and Mechanisms The chromatin-binding protein Smyd1 restricts adult mammalian heart growth Sarah Franklin, Todd Kimball, Tara L. Rasmussen, Manuel Rosa-Garrido, Haodong Chen, Tam Tran, Mickey R. Miller, Ricardo Gray, Shanxi Jiang, Shuxun Ren, Yibin Wang, Haley O. Tucker, Thomas M. Vondriska November 1, 2016 : H1234-H1247 DOI: 10.1152/ajpheart.00235.2016 This study is the first to demonstrate that loss of a muscle-specific chromatin-binding protein, Smyd1, is sufficient to induce cardiac hypertrophy and failure. Moreover, the findings demonstrate that augmentation of Smyd1 levels can block hypertrophy in cell models. These studies may support novel strategies for cardiac-targeted epigenetic therapy.

CALL FOR PAPERS | Cardiovascular Mitochondria and Redox Control in Health and Disease Reduced mitochondrial respiration in the ischemic as well as in the remote nonischemic region in postmyocardial infarction remodeling Diogo T. Galan, Virginie Bito, Piet Claus, Patricia Holemans, Joëlle Abi-Char, Chandan K. Nagaraju, Eef Dries, Kristel Vermeulen, Renée VenturaClapier, Karin R. Sipido, Ronald B. Driesen November 1, 2016 : H1075-H1090 DOI: 10.1152/ajpheart.00945.2015 After myocardial infarction, areas of chronic ischemia in the left ventricle (LV) persist. Yet, reduction of mitochondrial respiration, ultrastructural reorganization, and glycogen accumulation occur in all LV regions indicating that, not reduced perfusion, but increased hemodynamic load is the major driver for changes. Catalase-dependent H2 O2  consumption by cardiac mitochondria and redox-mediated loss in insulin signaling Paul M. Rindler, Angela Cacciola, Michael Kinter, Luke I. Szweda November 1, 2016 : H1091-H1096 DOI: 10.1152/ajpheart.00066.2016 Catalase contributes to H2 O2  consumption in cardiac mitochondria, particularly when mitochondria are compromised. Overexpression of catalase (50-fold) within mitochondria prevents diet-induced loss in insulin-stimulated Akt phosphorylation implicating mitochondrial-derived H 2 O2 . Endogenous increases in mitochondrial catalase ( 50%) do not, however, prevent this loss. Catalase likely limits H 2 O2  toxicity without perturbing redox-dependent signaling.

CALL FOR PAPERS | Plasma Membrane Integrity in Cardiovascular Physiology and Pathophysiology Dopamine induces lipid accumulation, NADPH oxidase-related oxidative stress, and a proinflammatory status of the plasma membrane in H9c2 cells Mark P. V. Begieneman, Ellis N. ter Horst, Liza Rijvers, Elisa Meinster, René Leen, Jeannette E. Pankras, Jan Fritz, Bela Kubat, René J. P.

Musters, André B. P. van Kuilenburg, Jan Stap, Hans W. M. Niessen, Paul A. J. Krijnen November 1, 2016 : H1097-H1107 DOI: 10.1152/ajpheart.00633.2015 Stress-induced heart failure is associated with excess catecholamines. Research into the cardiotoxic effects of catecholamines has focused almost exclusively on norepinephrine and epinephrine. Here, we show that dopamine also has cardiotoxic effects because it induces lipid accumulation, oxidative stress, and a proinflammatory status of the plasma membrane in H9c2 cells. Mitochondrial tRNA mutation with high-salt stimulation on cardiac damage: underlying mechanism associated with change of Bax and VDAC Zhu Chao, Tian Liuyang, Li Nan, Chen Qi, Cai Zhongqi, Li Yang, Liu Yuqi November 1, 2016 : H1248-H1257 DOI: 10.1152/ajpheart.00874.2015 We examined the effects of mitochondrial transfer RNA (tRNA) mutation and high-salt stimulation on cardiac damage in spontaneously hypertensive rats. tRNA mutation caused increased levels and coexpression of the voltage-dependent anion channel and the apoptosis regulator Bax, which may promote reactive oxygen species formation and initiate apoptosis.

CALL FOR PAPERS | Quantitative Analyses of Coronary Vascular and Cardiac Mechanics in Health and Disease Intraspecific scaling laws are preserved in ventricular hypertrophy but not in heart failure Yanjun Gong, Yundi Feng, Xudong Chen, Wenchang Tan, Yunlong Huo, Ghassan S. Kassab November 1, 2016 : H1108-H1117 DOI: 10.1152/ajpheart.00084.2016 A scaling law analysis was performed to enhance the understanding of fractal-regulated remodeling of coronary arterial trees in moderate left ventricular hypertrophy, severe right ventricular hypertrophy, and congestive heart failure (CHF) pig hearts. The findings show that the altered scaling exponents reflect the impaired structure-function hierarchy of coronary arterial trees in CHF.

CALL FOR PAPERS | Small Vessels-Big Problems: Novel Insights into Microvascular Mechanisms of Diseases Traumatic brain injury-induced autoregulatory dysfunction and spreading depression-related neurovascular uncoupling: Pathomechanisms, perspectives, and therapeutic implications Peter Toth, Nikolett Szarka, Eszter Farkas, Erzsebet Ezer, Endre Czeiter, Krisztina Amrein, Zoltan Ungvari, Jed A. Hartings, Andras Buki, Akos Koller November 1, 2016 : H1118-H1131 DOI: 10.1152/ajpheart.00267.2016 Pathways for insulin access to the brain: the role of the microvascular endothelial cell Rick I. Meijer, Sarah M. Gray, Kevin W. Aylor, Eugene J. Barrett November 1, 2016 : H1132-H1138 DOI: 10.1152/ajpheart.00081.2016 New understanding of the directional flow of subarachnoid cerebrospinal fluid (CSF) through the Virchow-Robin space (VRS) to brain parenchyma, coupled with the demonstration here of rapid, insulin receptor-dependent trapping of plasma insulin by the brain microvasculature, underscores the direct role of insulin's blood-brain barrier transit to insulin delivery to the brain.

Cardiac Excitation and Contraction Changes in cardiac Nav 1.5 expression, function, and acetylation by pan-histone deacetylase inhibitors Qin Xu, Dakshesh Patel, Xian Zhang, Richard D. Veenstra November 1, 2016 : H1139-H1149 DOI: 10.1152/ajpheart.00156.2016 Therapeutic histone deacetylase inhibition with vorinostat or romidepsin significantly reduces ventricular sodium current density and NaV1.5 protein expression. A slight positive shift in the voltage activation curve, presumably the result of lysine acetylation, decreases the inactivation rate at low activating potentials but does not increase the late sodium current amplitude.

Integrative Cardiovascular Physiology and Pathophysiology

Cardiac neural crest ablation results in early endocardial cushion and hemodynamic flow abnormalities Pei Ma, Shi Gu, Ganga H. Karunamuni, Michael W. Jenkins, Michiko Watanabe, Andrew M. Rollins November 1, 2016 : H1150-H1159 DOI: 10.1152/ajpheart.00188.2016 This study features quantitative phenotyping of cardiac neural crest ablation-induced great vessel defects and valvular defects at four-chambered stages, as well as structural and functional abnormalities in cardiac cushions and blood flow at cardiac looping stages. The imaging tool used to make these measurements was optical coherence tomography. Defective branched chain amino acid catabolism contributes to cardiac dysfunction and remodeling following myocardial infarction Wei Wang, Fuyang Zhang, Yunlong Xia, Shihao Zhao, Wenjun Yan, Helin Wang, Yan Lee, Congye Li, Ling Zhang, Kun Lian, Erhe Gao, Hexiang Cheng, Ling Tao November 1, 2016 : H1160-H1169 DOI: 10.1152/ajpheart.00114.2016 Cardiac BCAA catabolism is dysregulated after MI, which contributes to post-MI cardiac dysfunction and remodeling through activating mTOR. Importantly, our results show that pharmacological enhancement of BCAA catabolism alleviates post-MI cardiac pathologies. This study illustrates that targeting BCAA catabolism may be a novel therapeutic strategy for post-MI heart failure treatment. Arterial baroreflex control of sympathetic nerve activity and heart rate in patients with type 2 diabetes Seth W. Holwerda, Lauro C. Vianna, Robert M. Restaino, Kunal Chaudhary, Colin N. Young, Paul J. Fadel November 1, 2016 : H1170-H1179 DOI: 10.1152/ajpheart.00384.2016 We show for the first time preserved arterial baroreflex control of sympathetic nerve activity in type 2 diabetes patients with selective impairment in cardiac baroreflex control that appears related to obesity. These findings lend important insight into blood pressure regulation in a patient population prone to developing hypertension. Resistance-based interval exercise acutely improves endothelial function in type 2 diabetes Monique E. Francois, Cody Durrer, Kevin J. Pistawka, Frank A. Halperin, Jonathan P. Little November 1, 2016 : H1258-H1267 DOI: 10.1152/ajpheart.00398.2016 This is the first study to demonstrate improved endothelial function after an acute bout of resistance-based interval exercise. Our data indicate a potential therapeutic effect of resistance interval exercise on endothelial function in older adults with and without type 2 diabetes. The mechanisms underlying these effects warrant further investigation. Interaction between the muscle metaboreflex and the arterial baroreflex in control of arterial pressure and skeletal muscle blood flow Jasdeep Kaur, Alberto Alvarez, Hanna W. Hanna, Abhinav C. Krishnan, Danielle Senador, Tiago M. Machado, Yasir H. Altamimi, Abe T. Lovelace, Maryetta D. Dombrowski, Marty D. Spranger, Donal S. O'Leary November 1, 2016 : H1268-H1276 DOI: 10.1152/ajpheart.00501.2016 We found that carotid baroreceptor unloading during muscle metaboreflex activation results in an additive interaction and causes vasoconstriction of all vascular beds, including ischemic active skeletal muscle. However, there is a larger vasoconstriction in other vascular beds causing redistribution of blood flow toward ischemic active skeletal muscle. Vascular function assessed by passive leg movement and flow-mediated dilation: initial evidence of construct validity Matthew J. Rossman, H. Jonathan Groot, Ryan S. Garten, Melissa A. H. Witman, Russell S. Richardson November 1, 2016 : H1277-H1286 DOI: 10.1152/ajpheart.00421.2016 This study explores the relationship between a novel assessment of vascular health, passive leg movement (PLM), and an established measure, flowmediated dilation (FMD), to aid in the interpretation and implementation of the novel technique. Overall, positive relationships between PLM and FMD support PLM as a relevant gauge of vascular health. Cardiac-deleterious role of galectin-3 in chronic angiotensin II-induced hypertension Germán E. González, N.-E. Rhaleb, Martin A. D'Ambrosio, Pablo Nakagawa, Tang-Dong Liao, Edward L. Peterson, Pablo Leung, Xiangguo Dai, Branislava Janic, Yun-He Liu, Xiao-Ping Yang, Oscar A. Carretero November 1, 2016 : H1287-H1296 DOI: 10.1152/ajpheart.00096.2016

Our study suggests that galectin-3 should be considered not merely a marker for heart failure, but also a direct mediator of cardiac inflammation, fibrosis, and dysfunction. Thus, antagonistic strategies targeting galectin-3 may be a novel therapeutic approach in providing cardiac protection in hypertension and heart failure. Exercise intensity modulates the appearance of circulating microvesicles with proangiogenic potential upon endothelial cells Eurico N. Wilhelm, José González-Alonso, Christopher Parris, Mark Rakobowchuk November 1, 2016 : H1297-H1310 DOI: 10.1152/ajpheart.00516.2016 Increases in intravascular platelet microvesicle concentration occur during exercise, but this depends on exercise intensity, and correlates with elevations in vascular shear stress and plasma norepinephrine concentration. Circulating microvesicles isolated from exercising humans display proangiogenic potential on cultured endothelial cells. Thus, it is possible that microvesicles are involved in vascular responses to exercise. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation Siamak Salavatian, Eric Beaumont, Jean-Philippe Longpré, J. Andrew Armour, Alain Vinet, Vincent Jacquemet, Kalyanam Shivkumar, Jeffrey L. Ardell November 1, 2016 : H1311-H1320 DOI: 10.1152/ajpheart.00443.2016 Focal and excessive neural inputs to the intrinsic cardiac nervous system increase activity and coherence among intrinsic cardiac neurons in association with an increased potential for atrial fibrillation; preemptive vagus nerve stimulation prevents such neurocardiac effects. The antiarrhythmic effects imparted by vagus nerve stimulation have memory. Exposure to cigarette smoke abrogates the beneficial effect of ischemic postconditioning Sofia-Iris Bibli, Ioanna Andreadou, Constantinos Glynos, Athanasia Chatzianastasiou, Dimitris Toumpanakis, Spyros Zakynthinos, Theodoros Vasilakopoulos, Efstathios K. Iliodromitis, Andreas Papapetropoulos November 1, 2016 : H1321-H1332 DOI: 10.1152/ajpheart.00925.2015 Smoking and hypertension are two major risk factors in coronary heart disease. Patients who smoke often develop hypertension and left ventricular hypertrophy. The results of the present study suggest that patients with these comorbidities might not be protected by postconditioning application during reperfusion following myocardial infarction.

Muscle Mechanics and Ventricular Function Exercise training improves neurovascular control and calcium cycling gene expression in patients with heart failure with cardiac resynchronization therapy Thais S. Nobre, Ligia M. Antunes-Correa, Raphaela V. Groehs, Maria Janieire N. N. Alves, Adriana O. Sarmento, Aline V. Bacurau, Ursula Urias, Guilherme B. Alves, Maria Urbana P. B. Rondon, Patrícia C. Brum, Martino Martinelli, Holly R. Middlekauff, Carlos E. Negrao November 1, 2016 : H1180-H1188 DOI: 10.1152/ajpheart.00275.2016 Cardiac resynchronization therapy improves neurovascular control and exercise capacity in patients with heart failure (HF) with intraventricular conduction block. Our study shows that, in patients with HF on guideline-recommended pharmacological therapy in whom a biventricular pacemaker has recently been implanted, exercise training further improves exercise tolerance, neurovascular control, and Ca2+ -handling gene expression in skeletal muscle.

Signaling and Stress Response TNF receptor signaling inhibits cardiomyogenic differentiation of cardiac stem cells and promotes a neuroadrenergic-like fate Tariq Hamid, Yuanyuan Xu, Mohamed Ameen Ismahil, Qianhong Li, Steven P. Jones, Aruni Bhatnagar, Roberto Bolli, Sumanth D. Prabhu November 1, 2016 : H1189-H1201 DOI: 10.1152/ajpheart.00904.2015 Whether tumor necrosis factor-α (TNF) modulates cardiac stem cell (CSC) function is unknown. We show that TNF, primarily via TNF receptor-1, inhibits cardiomyogenic commitment of CSCs, and channels an alternate neuroadrenergic-like fate via both receptors. This suggests that TNF diminishes the efficacy of cardiac repair and enhances local adrenergic activation.

Vascular Biology and Microcirculation Selective head cooling during neonatal seizures prevents postictal cerebral vascular dysfunction without reducing epileptiform activity

Mimily Harsono, Massroor Pourcyrous, Elliott J. Jolly, Amy de Jongh Curry, Alexander L. Fedinec, Jianxiong Liu, Shyamali Basuroy, Daming Zhuang, Charles W. Leffler, Helena Parfenova November 1, 2016 : H1202-H1213 DOI: 10.1152/ajpheart.00227.2016 Neonatal epileptic seizures produce cerebrovascular disabilities that may contribute to neonatal encephalopathy. This study in newborn pigs provides evidence that selective head cooling during seizures can be used as an effective intervention that protects the neonatal brain by preventing cerebral vascular dysfunction. GLP-1 inhibits VEGFA-mediated signaling in isolated human endothelial cells and VEGFA-induced dilation of rat mesenteric arteries Cecilie Egholm, Makhala Michell Khammy, Thomas Dalsgaard, Aleksandra Mazur, Katerina Tritsaris, Anker J. Hansen, Christian Aalkjaer, Steen Dissing November 1, 2016 : H1214-H1224 DOI: 10.1152/ajpheart.00316.2016 Human endothelial cells from dermal and retinal origin and rat mesenteric resistance arteries express mRNA for GLP-1R. Upon activation with GLP-1, VEGFA-mediated vasodilation is inhibited because of reduction in PLCγ activity, attenuated Ca2+ signaling, and reduced eNOS activity. These findings reveal new aspects of artery functionality after food intake.

Letters to the Editor Letter to the editor: Why persist in the fallacy that mean systemic pressure drives venous return? George L. Brengelmann November 1, 2016 : H1333-H1335 DOI: 10.1152/ajpheart.00536.2016 Reply to “Letter to the editor: Why persist in the fallacy that mean systemic pressure drives venous return?” David Berger, Per W. Moller, Jukka Takala November 1, 2016 : H1336-H1337 DOI: 10.1152/ajpheart.00622.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 311, issue 5 The below Table of Contents is available online at: http://ajplung.physiology.org/content/311/5

Perspectives Update on novel targets and potential treatment avenues in pulmonary hypertension John C. Huetsch, Karthik Suresh, Meghan Bernier, Larissa A. Shimoda November 1, 2016 : L811-L831 DOI: 10.1152/ajplung.00302.2016 Searching for better animal models of BPD: a perspective Namasivayam Ambalavanan, Rory E. Morty November 2, 2016 : L924-L927 DOI: 10.1152/ajplung.00355.2016

Reviews Regulation of pulmonary endothelial barrier function by kinases Nektarios Barabutis, Alexander Verin, John D. Catravas November 1, 2016 : L832-L845 DOI: 10.1152/ajplung.00233.2016

Rapid Report Of mice and men: correlations between microRNA-17 92 cluster expression and promoter methylation in severe bronchopulmonary dysplasia Mary E. Robbins, Duaa Dakhlallah, Clay B. Marsh, Lynette K. Rogers, Trent E. Tipple November 9, 2016 : L981-L984 DOI: 10.1152/ajplung.00390.2016

CALL FOR PAPERS | Age-Related Dysfunction in Lung Barrier Function in Health and Disease Attenuated heme oxygenase-1 responses predispose the elderly to pulmonary nontuberculous mycobacterial infections Ranu Surolia, Suman Karki, Zheng Wang, Tejaswini Kulkarni, Fu Jun Li, Shikhar Vohra, Hitesh Batra, Jerry A. Nick, Steven R. Duncan, Victor J. Thannickal, Adrie J. C. Steyn, Anupam Agarwal, Veena B. Antony November 2, 2016 : L928-L940 DOI: 10.1152/ajplung.00397.2015

CALL FOR PAPERS | Biomarkers in Lung Diseases: from Pathogenesis to Prediction to New Therapies 14,15-Epoxyeicosatrienoic acid suppresses cigarette smoke condensate-induced inflammation in lung epithelial cells by inhibiting autophagy Yunxiao Li, Ganggang Yu, Shaopeng Yuan, Chunting Tan, Jianlin Xie, Yasi Ding, Puqiao Lian, Lixia Fu, Qi Hou, Bo Xu, Haoyan Wang November 2, 2016 : L970-L980 DOI: 10.1152/ajplung.00161.2016 Correction of lung inflammation in a F508del CFTR murine cystic fibrosis model by the sphingosine-1-phosphate lyase inhibitor LX2931 Mieke Veltman, Marta Stolarczyk, Danuta Radzioch, Gabriella Wojewodka, Juan B. De Sanctis, Willem A. Dik, Oleh Dzyubachyk, Tamas Oravecz, Ismé de Kleer, Bob J. Scholte November 9, 2016 : L1000-L1014 DOI: 10.1152/ajplung.00298.2016

CALL FOR PAPERS | Real-time Visualization of Lung Function: from Micro to Macro Real-time imaging of inflation-induced ATP release in the ex vivo rat lung Kishio Furuya, Ju Jing Tan, Francis Boudreault, Masahiro Sokabe, Yves Berthiaume, Ryszard Grygorczyk November 2, 2016 : L956-L969 DOI: 10.1152/ajplung.00425.2015

CALL FOR PAPERS | Translational Research in Acute Lung Injury and Pulmonary Fibrosis The unfolded protein response controls ER stress-induced apoptosis of lung epithelial cells through angiotensin generation Hang Nguyen, Bruce D. Uhal November 1, 2016 : L846-L854 DOI: 10.1152/ajplung.00449.2015 Human lung fibroblasts produce proresolving peroxisome proliferator-activated receptor-γ ligands in a cyclooxygenase-2-dependent manner Shannon H. Lacy, Collynn F. Woeller, Thomas H. Thatcher, Krishna Rao Maddipati, Kenneth V. Honn, Patricia J. Sime, Richard P. Phipps November 1, 2016 : L855-L867 DOI: 10.1152/ajplung.00272.2016 Protective effect of suppressing STAT3 activity in LPS-induced acute lung injury Jiping Zhao, Hao Yu, Yudong Liu, Sara A. Gibson, Zhaoqi Yan, Xin Xu, Amit Gaggar, Pui-Kai Li, Chenglong Li, Shi Wei, Etty N. Benveniste, Hongwei Qin

November 1, 2016 : L868-L880 DOI: 10.1152/ajplung.00281.2016 Activation of heat shock response augments fibroblast growth factor-1 expression in wounded lung epithelium Rachel G. Scheraga, Christopher Thompson, Mohan E. Tulapurkar, Ashish C. Nagarsekar, Mark Cowan, Ratnakar Potla, Junfeng Sun, Rongman Cai, Carolea Logun, James Shelhamer, Nevins W. Todd, Ishwar S. Singh, Irina G. Luzina, Sergei P. Atamas, Jeffrey D. Hasday November 2, 2016 : L941-L955 DOI: 10.1152/ajplung.00262.2016

Articles Susceptibility for cigarette smoke-induced DAMP release and DAMP-induced inflammation in COPD Simon D. Pouwels, Laura Hesse, Alen Faiz, Jaap Lubbers, Priya K. Bodha, Nick H. T. ten Hacken, Antoon J. M. van Oosterhout, Martijn C. Nawijn, Irene H. Heijink November 1, 2016 : L881-L892 DOI: 10.1152/ajplung.00135.2016 Focal adhesion kinase (FAK) and mechanical stimulation negatively regulate the transition of airway smooth muscle tissues to a synthetic phenotype Yidi Wu, Youliang Huang, Susan J. Gunst November 1, 2016 : L893-L902 DOI: 10.1152/ajplung.00299.2016 Protein phosphatase 2A activation attenuates inflammation in murine models of acute lung injury Walker M. McHugh, William W. Russell, Andrew J. Fleszar, Paul E. Rodenhouse, Skyler P. Rietberg, Lei Sun, Thomas P. Shanley, Timothy T. Cornell November 1, 2016 : L903-L912 DOI: 10.1152/ajplung.00007.2016 Acrolein and thiol-reactive electrophiles suppress allergen-induced innate airway epithelial responses by inhibition of DUOX1 and EGFR Karamatullah Danyal, Willem de Jong, Edmund O'Brien, Robert A. Bauer, David E. Heppner, Andrew C. Little, Milena Hristova, Aida Habibovic, Albert van der Vliet November 1, 2016 : L913-L923 DOI: 10.1152/ajplung.00276.2016 Simvastatin prevents and reverses chronic pulmonary hypertension in newborn rats via pleiotropic inhibition of RhoA signaling Mathew J. Wong, Crystal Kantores, Julijana Ivanovska, Amish Jain, Robert P. Jankov November 9, 2016 : L985-L999 DOI: 10.1152/ajplung.00345.2016 IL-17A-mediated expression of epithelial IL-17C promotes inflammation during acute Pseudomonas aeruginosa pneumonia Lisa Wolf, Sandra Sapich, Anja Honecker, Christopher Jungnickel, Frederik Seiler, Markus Bischoff, Bodo Wonnenberg, Christian Herr, Nicole Schneider-Daum, Claus-Michael Lehr, Robert Bals, Christoph Beisswenger November 9, 2016 : L1015-L1022 DOI: 10.1152/ajplung.00158.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 311, issue 5

The below Table of Contents is available online at: http://ajpregu.physiology.org/content/311/5

Editorial Oxygen signaling: Call for papers Roger G. Evans November 10, 2016 : R948 DOI: 10.1152/ajpregu.00416.2016

Reviews Diffusive shunting of gases and other molecules in the renal vasculature: physiological and evolutionary significance Jennifer P. Ngo, Connie P.C. Ow, Bruce S. Gardiner, Saptarshi Kar, James T. Pearson, David W. Smith, Roger G. Evans November 1, 2016 : R797-R810 DOI: 10.1152/ajpregu.00246.2016 Reassessing wanting and liking in the study of mesolimbic influence on food intake Saleem M. Nicola November 1, 2016 : R811-R840 DOI: 10.1152/ajpregu.00234.2016

Editorial Focus Advances in Technology: Blood-sampling at depth. Focus on “Development of an animal-borne blood sample collection device and its deployment for the determination of cardiovascular and stress hormones in submerged phocid seals” Paul J. Ponganis November 1, 2016 : R917-R918 DOI: 10.1152/ajpregu.00411.2016

CALL FOR PAPERS | Model Systems for the Study of Integrative Physiology: The Rebirth of Translational Biology Cholinergic and β-adrenergic control of cardiovascular reflex responses to brief repeated asphyxia in term-equivalent fetal sheep Robert Galinsky, Christopher A. Lear, Kyohei Yamaguchi, Guido Wassink, Jennifer A. Westgate, Laura Bennet, Alistair J. Gunn November 10, 2016 : R949-R956 DOI: 10.1152/ajpregu.00340.2016

CALL FOR PAPERS | Oxygen as a Regulator of Biological Systems Hypoxia-induced contraction of chicken embryo mesenteric arteries: mechanisms and developmental changes Leonie Brinks, Rob M. J. Moonen, Javier Moral-Sanz, Bianca Barreira, Lilian Kessels, Francisco Perez-Vizcaino, Angel Cogolludo, Eduardo Villamor November 1, 2016 : R858-R869 DOI: 10.1152/ajpregu.00461.2015

CALL FOR PAPERS | Sex and Gender Differences in Cardiovascular, Renal and Metabolic Diseases Endothelial and inflammatory responses to acute exercise in perimenopausal and late postmenopausal women Corinna Serviente, Lisa M. Troy, Maxine de Jonge, Daniel D. Shill, Nathan T. Jenkins, Sarah Witkowski November 1, 2016 : R841-R850 DOI: 10.1152/ajpregu.00189.2016 Nitric oxide synthase-mediated blood pressure regulation in obese melanocortin-4 receptor-deficient pregnant rats Frank T. Spradley, Jennifer M. Sasser, Jacqueline B. Musall, Jennifer C. Sullivan, Joey P. Granger November 1, 2016 : R851-R857

DOI: 10.1152/ajpregu.00285.2016 Hormone phase influences sympathetic responses to high levels of lower body negative pressure in young healthy women Charlotte W. Usselman, Chantelle A. Nielson, Torri A. Luchyshyn, Tamara I. Gimon, Nicole S. Coverdale, Stan H. M. Van Uum, J. Kevin Shoemaker November 21, 2016 : R957-R963 DOI: 10.1152/ajpregu.00190.2016

Neural Control Carotid baroreflex function at the onset of cycling in men Thales C. Barbosa, Lauro C. Vianna, Takeshi Hashimoto, Lonnie G. Petersen, Niels D. Olesen, Hayato Tsukamoto, Henrik Sørensen, Shigehiko Ogoh, Antonio C. L. Nóbrega, Niels H. Secher November 1, 2016 : R870-R878 DOI: 10.1152/ajpregu.00173.2016 Vagal afferent activation induces salivation and swallowing-like events in anesthetized rats Hirotaka Ueda, Mayu Suga, Takakazu Yagi, Ikue Kusumoto-Yoshida, Hideki Kashiwadani, Tomoyuki Kuwaki, Shouichi Miyawaki November 21, 2016 : R964-R970 DOI: 10.1152/ajpregu.00292.2016 α1D-Adrenoceptor blockade increases voiding efficiency by improving external urethral sphincter activity in rats with spinal cord injury Hirokazu Ishida, Hiroki Yamauchi, Hideaki Ito, Hironobu Akino, Osamu Yokoyama November 21, 2016 : R971-R978 DOI: 10.1152/ajpregu.00030.2016

Physical Activity and Inactivity Intramyocellular ceramides and skeletal muscle mitochondrial respiration are partially regulated by Toll-like receptor 4 during hindlimb unloading Oh Sung Kwon, Daniel S. Nelson, Katherine M. Barrows, Ryan M. O'Connell, Micah J. Drummond November 1, 2016 : R879-R887 DOI: 10.1152/ajpregu.00253.2016 Predominant cause of prolonged low-frequency force depression changes during recovery after in situ fatiguing stimulation of rat fast-twitch muscle Daiki Watanabe, Masanobu Wada November 1, 2016 : R919-R929 DOI: 10.1152/ajpregu.00046.2016

Obesity, Diabetes and Energy Homeostasis Chronic binge alcohol administration impairs glucose-insulin dynamics and decreases adiponectin in asymptomatic simian immunodeficiency virusinfected macaques Stephen M. Ford Jr, Liz Simon, Curtis Vande Stouwe, Tim Allerton, Donald E. Mercante, Lauri O. Byerley, Jason P. Dufour, Gregory J. Bagby, Steve Nelson, Patricia E. Molina November 1, 2016 : R888-R897 DOI: 10.1152/ajpregu.00142.2016 Dorsomedial hypothalamic NPY affects cholecystokinin-induced satiety via modulation of brain stem catecholamine neuronal signaling Claire B. de La Serre, Yonwook J. Kim, Timothy H. Moran, Sheng Bi November 1, 2016 : R930-R939 DOI: 10.1152/ajpregu.00184.2015 The role of proximal versus distal stomach resection in the weight loss seen after vertical sleeve gastrectomy Bhushan V. Kulkarni, Kathleen LaSance, Joyce E. Sorrell, Lisa Lemen, Stephen C. Woods, Randy J. Seeley, Darleen Sandoval November 21, 2016 : R979-R987 DOI: 10.1152/ajpregu.00125.2016

Cardiovascular and Renal Integration Effects of estrogen replacement on stress-induced cardiovascular responses via renin-angiotensin system in ovariectomized rats Shoko Tazumi, Naoko Yokota, Mizuho Kawakami, Sayo Omoto, Akira Takamata, Keiko Morimoto November 1, 2016 : R898-R905 DOI: 10.1152/ajpregu.00415.2015

Respiration Metabolic pathways of lung inflammation revealed by high-resolution metabolomics (HRM) of H1N1 influenza virus infection in mice Joshua D. Chandler, Xin Hu, Eun-Ju Ko, Soojin Park, Young-Tae Lee, Michael Orr, Jolyn Fernandes, Karan Uppal, Sang-Moo Kang, Dean P. Jones, Young-Mi Go November 1, 2016 : R906-R916 DOI: 10.1152/ajpregu.00298.2016 Hypercapnic ventilatory response is decreased in a mouse model of excessive erythrocytosis Sofien Laouafa, Elizabeth Elliot-Portal, Susana Revollo, Edith M. Schneider Gasser, Vincent Joseph, Nicolas Voituron, Max Gassmann, Jorge Soliz November 1, 2016 : R940-R947 DOI: 10.1152/ajpregu.00226.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 311, issue 5 The below Table of Contents is available online at: http://ajprenal.physiology.org/content/311/5

Reviews Rethinking glomerular basement membrane thickening in diabetic nephropathy: adaptive or pathogenic? Caroline B. Marshall November 1, 2016 : F831-F843 DOI: 10.1152/ajprenal.00313.2016 Extracellular vesicles in diagnosis and therapy of kidney diseases Wei Zhang, Xiangjun Zhou, Hao Zhang, Qisheng Yao, Yutao Liu, Zheng Dong November 1, 2016 : F844-F851 DOI: 10.1152/ajprenal.00429.2016 The Gomez equations and renal hemodynamic function in kidney disease research Petter Bjornstad, Marko Škrtić, Yuliya Lytvyn, David M. Maahs, Richard. J. Johnson, David Z. I. Cherney November 1, 2016 : F967-F975 DOI: 10.1152/ajprenal.00415.2016

Translational Physiology Human epithelial Na+  channel missense variants identified in the GenSalt study alter channel activity Evan C. Ray, Jingxin Chen, Tanika N. Kelly, Jiang He, L. Lee Hamm, Dongfeng Gu, Lawrence C. Shimmin, James E. Hixson, Dabeeru C. Rao, Shaohu Sheng, Thomas R. Kleyman

November 1, 2016 : F908-F914 DOI: 10.1152/ajprenal.00426.2016 Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species Julia Dolinina, Kristinn Sverrisson, Anna Rippe, Carl M. Öberg, Bengt Rippe November 11, 2016 : F984-F990 DOI: 10.1152/ajprenal.00152.2016

CALL FOR PAPERS | Endothelin in Renal Physiology and Disease Loss of endothelin B receptor function impairs sodium excretion in a time- and sex-dependent manner Jermaine G. Johnston, Joshua S. Speed, Chunhua Jin, David M. Pollock November 11, 2016 : F991-F998 DOI: 10.1152/ajprenal.00103.2016

CALL FOR PAPERS | Inflammation and Inflammatory Mediators in Kidney Disease HMGB1/TLR4 signaling induces an inflammatory response following high-pressure renal pelvic perfusion in a porcine model Yi Shao, Minglei Sha, Lei Chen, Deng Li, Jun Lu, Shujie Xia November 1, 2016 : F915-F925 DOI: 10.1152/ajprenal.00480.2015

CALL FOR PAPERS | Mechanism and Treatment of Renal Fibrosis An additive effect of anti-PAI-1 antibody to ACE inhibitor on slowing the progression of diabetic kidney disease Chunyan Gu, Jiandong Zhang, Nancy A. Noble, Xiao-Rong Peng, Yufeng Huang November 1, 2016 : F852-F863 DOI: 10.1152/ajprenal.00564.2015 Age-dependent shifts in renal response to injury relate to altered BMP6/CTGF expression and signaling Lucas L. Falke, Hiroshi Kinashi, Amelie Dendooven, Roel Broekhuizen, Reinout Stoop, Jaap A. Joles, Tri Q. Nguyen, Roel Goldschmeding November 1, 2016 : F926-F934 DOI: 10.1152/ajprenal.00324.2016

CALL FOR PAPERS | Purinergic Signaling Mechanisms in the Lower Urinary Tract Effect of orchiectomy and testosterone replacement on lower urinary tract function in anesthetized rats Chen-Li Cheng, William C. de Groat November 1, 2016 : F864-F870 DOI: 10.1152/ajprenal.00016.2016

Perspective Catalytic iron and acute kidney injury David E. Leaf, Dorine W. Swinkels November 1, 2016 : F871-F876 DOI: 10.1152/ajprenal.00388.2016 Peritoneal dialysis: from bench to bedside and bedside to bench Jeffrey Perl, Joanne M. Bargman November 11, 2016 : F999-F1004 DOI: 10.1152/ajprenal.00012.2016

Articles Lack of hepcidin ameliorates anemia and improves growth in an adenine-induced mouse model of chronic kidney disease Oleh Akchurin, Angara Sureshbabu, Steve B. Doty, Yuan-Shan Zhu, Edwin Patino, Susanna Cunningham-Rundles, Mary E. Choi, Adele

Boskey, Stefano Rivella November 1, 2016 : F877-F889 DOI: 10.1152/ajprenal.00089.2016 Activation of the metabolic sensor AMP-activated protein kinase inhibits aquaporin-2 function in kidney principal cells Mohammad M. Al-bataineh, Hui Li, Kazuhiro Ohmi, Fan Gong, Allison L. Marciszyn, Sajid Naveed, Xiaoqing Zhu, Dietbert Neumann, Qi Wu, Lei Cheng, Robert A. Fenton, Núria M. Pastor-Soler, Kenneth R. Hallows November 1, 2016 : F890-F900 DOI: 10.1152/ajprenal.00308.2016 A fate-mapping approach reveals the composite origin of the connecting tubule and alerts on “single-cell”-specific KO model of the distal nephron Francesco Trepiccione, Christelle Soukaseum, Anna Iervolino, Federica Petrillo, Miriam Zacchia, Gunther Schutz, Dominique Eladari, Giovambattista Capasso, Juliette Hadchouel November 1, 2016 : F901-F906 DOI: 10.1152/ajprenal.00286.2016 The vasopressin type 2 receptor and prostaglandin receptors EP2 and EP4 can increase aquaporin-2 plasma membrane targeting through a cAMPindependent pathway Emma T. B. Olesen, Hanne B. Moeller, Mette Assentoft, Nanna MacAulay, Robert A. Fenton November 1, 2016 : F935-F944 DOI: 10.1152/ajprenal.00559.2015 Both CLIC4 and CLIC5A activate ERM proteins in glomerular endothelium Mahtab Tavasoli, Abass Al-Momany, Xin Wang, Laiji Li, John C. Edwards, Barbara J. Ballermann November 1, 2016 : F945-F957 DOI: 10.1152/ajprenal.00353.2016 This study reveals a novel function for chloride intracellular channel (CLIC) 4, namely that it acts upstream of moesin and ezrin activation, similar to the function of CLIC5A. Thus the function of CLIC proteins is not restricted to Cl -  channel activity. Chronic insulin treatment phosphorylates the renal Na-K-ATPase α 1 -subunit at serine 16/23 and reduces its activity involving PI3-kinase-dependent PKC activation Anees Ahmad Banday November 1, 2016 : F958-F966 DOI: 10.1152/ajprenal.00355.2016 Lymphocyte-specific deletion of IKK2 or NEMO mediates an increase in intrarenal Th17 cells and accelerates renal damage in an ischemiareperfusion injury mouse model Linlin Guo, Hannah Heejung Lee, María de las Mercedes Noriega, Hans J. Paust, Gunther Zahner, Friedrich Thaiss November 11, 2016 : F1005-F1014 DOI: 10.1152/ajprenal.00242.2016 Characterization and phosphoproteomic analysis of a human immortalized podocyte model of Fabry disease generated using CRISPR/Cas9 technology Ester M. Pereira, Anatália Labilloy, Megan L. Eshbach, Ankita Roy, Arohan R. Subramanya, Semiramis Monte, Guillaume Labilloy, Ora A. Weisz November 11, 2016 : F1015-F1024 DOI: 10.1152/ajprenal.00283.2016 Nrf2-AKT interactions regulate heme oxygenase 1 expression in kidney epithelia during hypoxia and hypoxia-reoxygenation Haranatha R. Potteti, Chandramohan R. Tamatam, Rakesh Marreddy, Narsa M. Reddy, Sanjeev Noel, Hamid Rabb, Sekhar P. Reddy November 11, 2016 : F1025-F1034 DOI: 10.1152/ajprenal.00362.2016 Role of the deubiquitinating enzyme ubiquitin-specific protease-14 in proteostasis in renal cells Kapil Sareen-Khanna, Joan Papillon, Simon S. Wing, Andrey V. Cybulsky November 11, 2016 : F1035-F1046 DOI: 10.1152/ajprenal.00252.2016 A model of calcium homeostasis in the rat

David Granjon, Olivier Bonny, Aurélie Edwards November 11, 2016 : F1047-F1062 DOI: 10.1152/ajprenal.00230.2016 Sex-dependent expression of TRPV1 in bladder arterioles Thieu X. Phan, Hoai T. Ton, Yue Chen, Maureen E. Basha, Gerard P. Ahern November 11, 2016 : F1063-F1073 DOI: 10.1152/ajprenal.00234.2016 Collecting duct-specific knockout of nitric oxide synthase 3 impairs water excretion in a sex-dependent manner Yang Gao, Deborah Stuart, Jennifer S. Pollock, Takamune Takahishi, Donald E. Kohan November 11, 2016 : F1074-F1083 DOI: 10.1152/ajprenal.00494.2016

Innovative Methodology Lengths of nephron tubule segments and collecting ducts in the CD-1 mouse kidney: an ontogeny study Sarah L. Walton, Karen M. Moritz, John F. Bertram, Reetu R. Singh November 11, 2016 : F976-F983 DOI: 10.1152/ajprenal.00435.2016

Letter to the Editor Letter to the editor: “Urothelial barrier dysfunction: cause or outcome of ketamine-induced voiding dysfunction” Zhao Wang, Long Wang, Long-fei Liu, Yu-meng Huang, Zheng-yan Tang November 1, 2016 : F907 DOI: 10.1152/ajprenal.00374.2016 Reply to “Letter to the editor: ‘Urothelial barrier dysfunction: cause or outcome of ketamine-induced voiding dysfunction’” Weiqun Yu November 11, 2016 : F1084 DOI: 10.1152/ajprenal.00555.2016

Corrigendum Corrigendum November 11, 2016 : F1086 DOI: 10.1152/ajprenal.zh2-8091-corr.2016

Retraction Retraction November 11, 2016 : F1085 DOI: 10.1152/ajprenal.zh2-8076-retr.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 121, issue 5 The below Table of Contents is available online at: http://jap.physiology.org/content/121/5

Synthesis Review Deflation-activated receptors, not classical inflation-activated receptors, mediate the Hering-Breuer deflation reflex Jerry Yu November 1, 2016 : 1041-1046 DOI: 10.1152/japplphysiol.00903.2015

Articles Evidence for the infiltration of gas bubbles into the arterial circulation and neuronal injury following “yo-yo” dives in pigs Dror Ofir, Yoav Yanir, Michael Mullokandov, Ben Aviner, Yehuda Arieli November 1, 2016 : 1059-1064 DOI: 10.1152/japplphysiol.00392.2016 Four “peeps” and square dives increased the risk of decompression illness. Two-peep dives reduce the risk for DCI as was expressed in more “nonbubbling” pigs. We have detected a higher incidence of bubbles in the left ventricle after four-peep dives. Frequency of “red neurons” decreases with increasing number of “peeps.” Validity and reliability of measuring resting muscle sympathetic nerve activity using short sampling durations in healthy humans Karambir Notay, Jeremy D. Seed, Anthony V. Incognito, Connor J. Doherty, Massimo Nardone, Matthew J. Burns, Philip J. Millar November 1, 2016 : 1065-1073 DOI: 10.1152/japplphysiol.00736.2016 Short sampling durations are used commonly to assess baseline muscle sympathetic nerve activity (MSNA) before a stress to quantify sympathetic responsiveness. The validity and reliability of these measures have not been tested. Our analyses demonstrate that MSNA, sampled from 2 and 1 min and 30 and 15 s epochs, possesses high agreement and no fixed bias compared with a standard 5-min control but consistent evidence of a proportional bias that would confound interindividual comparisons. Dissociation between short-term unloading and resistance training effects on skeletal muscle Na+ ,K+ -ATPase, muscle function, and fatigue in humans Ben D. Perry, Victoria L. Wyckelsma, Robyn M. Murphy, Collene H. Steward, Mitchell Anderson, Itamar Levinger, Aaron C. Petersen, Michael J. McKenna November 1, 2016 : 1074-1086 DOI: 10.1152/japplphysiol.00558.2016 This is the first study to investigate the effects of controlled unloading on muscle sodium-potassium pumps (NKA) in human muscle, being measured in both whole homogenate and single fibers. Despite considerable functional deficits caused by disuse, which were recovered by resistance training, muscle NKA content and isoform abundances were resilient to change, despite some fiber type-specific changes in NKA isoforms. Hence muscle NKA regulation in response to disuse is more complex than previously thought. Effect of alterations in blood volume with bed rest on glucose tolerance S. Dandanell, L. Oberholzer, S. Keiser, A. B. Andersen, T. Haider, M. P. Hilty, A. K. Meinild-Lundby, C. Lundby November 1, 2016 : 1098-1105 DOI: 10.1152/japplphysiol.00624.2016 A concomitantly reduced plasma volume and glucose tolerance were observed after 3 days of bed rest. For the first time the relationship between changes in dilution space for glucose after bed rest and impaired glucose tolerance was investigated. No relationship between glucose tolerance and dilution space was observed. A novel finding was a transiently reduced plasma glucose concentration after restoration of plasma volume by albumin infusion; however, glucose tolerance was not restored. Postinjury biomechanics of Achilles tendon vary by sex and hormone status George W. Fryhofer, Benjamin R. Freedman, Cody D. Hillin, Nabeel S. Salka, Adam M. Pardes, Stephanie N. Weiss, Daniel C. Farber, Louis J. Soslowsky November 1, 2016 : 1106-1114 DOI: 10.1152/japplphysiol.00620.2016

This study identified sex- and hormone-related differences in Achilles tendon healing, which support the notion that patient sex and hormone status should be considered in future clinical investigations defining optimal treatments for Achilles tendon rupture. The prefrontal oxygenation and ventilatory responses at start of one-legged cycling exercise have relation to central command Ryota Asahara, Kanji Matsukawa, Kei Ishii, Nan Liang, Kana Endo November 7, 2016 : 1115-1126 DOI: 10.1152/japplphysiol.00401.2016 Preexercise increase in prefrontal oxygenation and exercise hyperpnea occurred with arbitrary one-legged cycling, whereas such responses were absent or blunted with cued cycling. Prefrontal oxygenation did not result from the changes in end-tidal CO 2 . Neither imagery nor passive performance of one-legged cycling increased prefrontal oxygenation. The in-advance activation of central command enhanced the minute ventilatory response and was reflected in preexercise increase in prefrontal oxygenation during exercise. Energy substrate utilization with and without exogenous carbohydrate intake in boys and men exercising in the heat Gabriela T. Leites, Giovani S. Cunha, Lisa Chu, Flavia Meyer, Brian W. Timmons November 7, 2016 : 1127-1134 DOI: 10.1152/japplphysiol.00535.2016 This study provides the new finding that during exercise in the heat, boys experience a lower exogenous carbohydrate oxidation rate and oxidation efficiency compared with men. In contrast, endogenous substrate metabolism and the relative contribution of substrate for the total energy during exercise were not different in boys and men. These age-related differences observed in the heat are noteworthy because they expand our knowledge of exercise metabolism in children. Generation of active expiration by serotoninergic mechanisms of the ventral medulla of rats Eduardo V. Lemes, Eduardo Colombari, Daniel B. Zoccal November 7, 2016 : 1135-1144 DOI: 10.1152/japplphysiol.00470.2016 The retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) houses a conditional expiratory oscillator that emerges during metabolic challenges and generates active expiration. Herein we identify a 5-HT2-dependent mechanism in the RTN/pFRG that triggers active expiration at resting conditions. This mechanism is recruited during intermittent hypoxia exposure and essential for the development of expiratory long-term facilitation. These findings help to understand the central mechanisms underpinning the development of cardiorespiratory adaptations associated with hypoxia exposure. Effects of body position on exercise capacity and pulmonary vascular pressure-flow relationships Kevin Forton, Yoshiki Motoji, Gael Deboeck, Vitalie Faoro, Robert Naeije November 7, 2016 : 1145-1150 DOI: 10.1152/japplphysiol.00372.2016 Body position does not affect exercise stress echocardiography of the pulmonary circulation or aerobic exercise capacity as measured by a maximum oxygen uptake. However, the semirecumbent position is associated with a decreased maximum workload, and the range of predicted cardiac output at any level of workload or oxygen uptake is wide. Therefore, pulmonary vascular function is better described by referring pulmonary vascular pressures to cardiac output rather than to workload or oxygen uptake. Pulmonary artery pressure and arterial oxygen saturation in people living at high or low altitude: systematic review and meta-analysis Rodrigo Soria, Matthias Egger, Urs Scherrer, Nicole Bender, Stefano F. Rimoldi November 7, 2016 : 1151-1159 DOI: 10.1152/japplphysiol.00394.2016 Many millions of people are living at high altitude. An increase of pulmonary artery pressure (PAP) is a hallmark of high-altitude exposure and may be associated with important morbidity, however there is little information on it. The findings of this systematic review and meta-analysis show that pulmonary hypertension in healthy high-altitude dwellers is rare. The provided reference values and distributions for PAP and SaO2 will be useful to future studies on high-altitude (mal)adaptation in humans. Adverse postresuscitation myocardial effects elicited by buffer-induced alkalemia ameliorated by NHE-1 inhibition in a rat model of ventricular fibrillation Lorissa Lamoureux, Jeejabai Radhakrishnan, Thomas G. Mason, Jeffrey A. Kraut, Raúl J. Gazmuri November 7, 2016 : 1160-1168 DOI: 10.1152/japplphysiol.00336.2016 The study showed a detrimental postresuscitation effect of the CO 2 -consuming buffer disodium carbonate/sodium bicarbonate compromising myocardial function and survival. The effect was attributed to intensification of the sarcolemmal Na+-H+ exchanger isoform-1 (NHE-1) activity and

was ameliorated by the NHE-1 inhibitor zoniporide. The study raises concerns about inducing alkalemia when tissues are recovering from ischemia after cardiac arrest and identifies NHE-1 as a mediator of this effect susceptible to therapeutic intervention. Interstitial glucose concentrations and hypoglycemia during 2 days of caloric deficit and sustained exercise: a double-blind, placebo-controlled trial Tracey J. Smith, Marques A. Wilson, J. Philip Karl, Krista Austin, Asma Bukhari, Stefan M. Pasiakos, Kristie L. O’Connor, Harris R. Lieberman November 16, 2016 : 1208-1216 DOI: 10.1152/japplphysiol.00432.2016 This paper provides novel data characterizing glucose homeostasis during acute, severe energy deficit, in conjunction with extensive aerobic exercise in normal, healthy volunteers using continuous interstitial glucose monitoring. This study demonstrated that glucose regulation is, generally, tightly-controlled in normal-weight, healthy young adults in response to severe, short-term energy restriction, accompanied by an ~1,500 kcal/day increase in exercise-induced energy expenditure. Findings have practical implications for military personnel, ultra-endurance athletes, and select groups of first responders. The effect of body mass and sex on the accuracy of respiratory magnetometers for measurement of end-expiratory lung volumes Joanne Avraam, Rosie Bourke, John Trinder, Christian L. Nicholas, Danny Brazzale, Fergal J. O’Donoghue, Peter D. Rochford, Amy S. Jordan November 16, 2016 : 1169-1177 DOI: 10.1152/japplphysiol.00571.2016 Respiratory magnetometers are increasingly being used in obese populations while in the supine position for measurement of end-expiratory lung volume changes despite the fact that they have only been validated in normal-weight individuals while seated/standing for tidal volume measurements. In this study, we determined that both sex and body mass influenced the accuracy of respiratory magnetometers for measurement of tidal volume and end-expiratory lung volumes. Whole body heat stress attenuates the pressure response to muscle metaboreceptor stimulation in humans Jian Cui, Cheryl Blaha, Lawrence I. Sinoway November 16, 2016 : 1178-1186 DOI: 10.1152/japplphysiol.00212.2016 This study examined the effects of whole body heat stress on the sympathetic and cardiovascular responses to stimulation of muscle metaboreceptors and mechanoreceptors in healthy humans. Whole body heat stress accentuated the heart rate response, did not alter the muscle sympathetic nerve activity response, and lowered the pressure response to stimulation of muscle metaboreceptors. Moreover, whole body heat stress attenuated the blood pressure and sympathetic nerve responses to mechanoreceptor stimulation. Bouncing on Mars and the Moon—the role of gravity on neuromuscular control: correlation of muscle activity and rate of force development Ramona Ritzmann, Kathrin Freyler, Anne Krause, Albert Gollhofer November 16, 2016 : 1187-1195 DOI: 10.1152/japplphysiol.00692.2016 For the first time, this article documents human locomotor behavior under Martian and lunar gravity. Experiments executed during parabolic flights provide unique data, which give insight into neuromuscular behavior when whole body movement is required in gravity conditions equivalent to our astronomical neighbors Mars and the Moon. Findings emphasize that gravitational variation is anticipated and that gravity-adjusted muscle activities compensate for reduced gravitational forces. Thus kinematic adaptations are accompanied by muscle- and phase-specific modulations in neural control. Modeling the detailed kinetics of mitochondrial cytochrome c oxidase: Catalytic mechanism and nitric oxide inhibition Venkat R. Pannala, Amadou K. S. Camara, Ranjan K. Dash November 16, 2016 : 1196-1207 DOI: 10.1152/japplphysiol.00524.2016 We developed a thermodynamically constrained mechanistic mathematical model for the kinetics of cytochrome c oxidase, incorporating several salient features, e.g., electron transfer, proton pumping, and nitric oxide inhibition. The model realistically and explicitly accounts for the thermodynamic dependence of the electron transport and proton translocation mechanisms through its rate constants. The model accurately describes the cytochrome c oxidase kinetics under both isolated mitochondria and purified enzyme conditions in the presence and absence of nitric oxide with a minimal number of kinetic parameters. Effects of repetitive transcranial magnetic stimulation of upper airway muscles during sleep in obstructive sleep apnea patients Eric Rousseau, César Augusto Melo-Silva, Simon Gakwaya, Frédéric Sériès November 23, 2016 : 1217-1225 DOI: 10.1152/japplphysiol.00487.2015 Altogether with previous data obtained in the wake/sleep state, the present results demonstrate that repetitive transcranial magnetic stimulation

(rTMS) over the submental muscles corticomotor somatotopic representation is associated with detrimental upper airway (UA) mechanical response, thus pointing to an effect of the stimulation paradigms per se. Additional monitoring of UA dilators and constrictor muscles during rTMS would be needed to further investigate the mechanisms leading to such results.

Innovative Methodology Novel methodology to perform sulfur hexafluoride (SF6)-based multiple-breath wash-in and washout in infants using current commercially available equipment P. M. Gustafsson, P. D. Robinson, A. Lindblad, D. Oberli November 1, 2016 : 1087-1097 DOI: 10.1152/japplphysiol.00115.2016 The paper describes novel methodology for indirect calculation of true SF6 concentration from molar mass, O2, and CO2 sensors contained within currently available commercial equipment. An improved dynamic method for synchronizing these signals to respiratory flow is also described. Finally, in vitro FRC validation data are presented from recordings using a series of dry lung models across realistic infant lung volumes and breathing patterns. Estimating oxygen uptake and energy expenditure during treadmill walking by neural network analysis of easy-to-obtain inputs Thomas Beltrame, Robert Amelard, Rodrigo Villar, Mohammad J. Shafiee, Alexander Wong, Richard L. Hughson November 23, 2016 : 1226-1233 DOI: 10.1152/japplphysiol.00600.2016 New technologies for the continuous assessment of aerobic fitness based on oxygen uptake data have the potential to be used for the early detection of deterioration of physical health. However, direct oxygen uptake is costly, cumbersome, and not applicable to the general population. An artificial neural network was trained to predict the oxygen uptake signal from easy-to-obtain inputs, possibly allowing future investigations of changes in aerobic fitness, with higher applicability for general population.

HIGHLIGHTED TOPIC | Aging and Exercise Age-induced oxidative stress: how does it influence skeletal muscle quantity and quality? Cory W. Baumann, Dongmin Kwak, Haiming M. Liu, LaDora V. Thompson November 1, 2016 : 1047-1052 DOI: 10.1152/japplphysiol.00321.2016 Influence of exercise and aging on extracellular matrix composition in the skeletal muscle stem cell niche Koyal Garg, Marni D. Boppart November 1, 2016 : 1053-1058 DOI: 10.1152/japplphysiol.00594.2016

Letters to the Editor Age-related changes in skeletal muscle function: the sum of the parts could be greater than the whole Massimo Venturelli, Russell S. Richardson, Carlo Reggiani, Federico Schena November 23, 2016 : 1234 DOI: 10.1152/japplphysiol.00770.2016 Reply to Venturelli and colleagues Greg J. Grosicki, Robert A. Standley, Kevin A. Murach, Ulrika Raue, Kiril Minchev, Paul M. Coen, Stephen Kritchevsky, Bret H. Goodpaster, Scott Trappe November 23, 2016 : 1235 DOI: 10.1152/japplphysiol.00832.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 116, issue 5 The below Table of Contents is available online at: http://jn.physiology.org/content/116/5

Neuro Forum Contrasting roles of I h  and the persistent sodium current at subthreshold voltages during naturalistic stimuli Michael G. Thor, Gareth Morris November 1, 2016 : 2001-2003 DOI: 10.1152/jn.00031.2016

Review Is realistic neuronal modeling realistic? Mara Almog, Alon Korngreen November 1, 2016 : 2180-2209 DOI: 10.1152/jn.00360.2016

CALL FOR PAPERS | Auditory System Plasticity Contextual processing in unpredictable auditory environments: the limited resource model of auditory refractoriness in the rhesus Tobias Teichert, Kate Gurnsey, Dean Salisbury, Robert A. Sweet November 1, 2016 : 2125-2139 DOI: 10.1152/jn.00419.2016 Refractoriness may reflect the gradual decay of an auditory perceptual short-term memory trace that mirrors expenditure and gradual recovery of a limited physiological resource. Our findings suggest that items are cleared from the trace not only by recovering expended resource but also by partially overwriting traces of previous tones when little resource remains. This nonlinearity and the ensuing shift toward a single-item memory trace provide new perspectives on refractoriness and performance on short-term memory tasks.

CALL FOR PAPERS | Glial Cells and Neuronal Signaling White matter and cognition: making the connection Christopher M. Filley, R. Douglas Fields November 1, 2016 : 2093-2104 DOI: 10.1152/jn.00221.2016

Cellular and Molecular Properties of Neurons Postsynaptic nicotinic acetylcholine receptors facilitate excitation of developing CA1 pyramidal neurons Beryl Y. T. Chung, Warren Bignell, Derek L. Jacklin, Boyer D. Winters, Craig D. C. Bailey November 1, 2016 : 2043-2055 DOI: 10.1152/jn.00370.2016 This study demonstrates that postsynaptic heteromeric nicotinic acetylcholine receptors facilitate the excitation of hippocampus CA1 pyramidal neurons. This receptor function is developmentally regulated with its strongest influence on neuron excitability occurring for mice during early postnatal life. Given the role of nicotinic signaling to mediate neuron physiological and morphological development, these findings show that postsynaptic heteromeric nicotinic acetylcholine receptors are positioned to influence the maturation of CA1 pyramidal neurons within hippocampal learning and memory networks. Nonreciprocal mechanisms in up- and downregulation of spinal motoneuron excitability by modulators of KCNQ/K v 7 channels Joseph Lombardo, Melissa A. Harrington November 1, 2016 : 2114-2124 DOI: 10.1152/jn.00446.2016

The voltage threshold of spinal motoneurons has been shown to be preferentially targeted by the nervous system to regulate output and set the recruitment order of motor units. Voltage threshold is also modulated transiently during fictive locomotion and persistently after physical training, operant conditioning, weight bearing, and spinalization. Although much work has been undertaken to understand the mechanisms that underlie the modulation of the voltage threshold, little insight has been obtained so far. Developmental restoration of LTP deficits in heterozygous CaMKIIα KO mice Dayton J. Goodell, Tim A. Benke, K. Ulrich Bayer November 1, 2016 : 2140-2151 DOI: 10.1152/jn.00518.2016 CaMKIIα+/− mice were described previously to have a schizophrenia-related phenotype. While the long-term potentiation (LTP) deficits seen here in young CaMKIIα+/− mice are restored during development, the initially normal basal synaptic transmission in the hippocampus becomes impaired. Dynamic compensation mechanism gives rise to period and duty-cycle level sets in oscillatory neuronal models Horacio G. Rotstein, Motolani Olarinre, Jorge Golowasch November 1, 2016 : 2431-2452 DOI: 10.1152/jn.00357.2016 Variability is a hallmark of neuronal activity. However, neurons of the same type have been shown to exhibit constant values of their oscillatory attributes (e.g., frequency, duty cycle), despite having different levels of the parameters (e.g., maximal conductances) defining their intrinsic ionic currents, thus generating the so-called level sets in parameter space. Here, we examine theoretically the biophysical and dynamic mechanisms that generate these level sets for a set of key, biophysically plausible models.

Control of Homeostasis Synaptic and intrinsic homeostasis cooperate to optimize single neuron response properties and tune integrator circuits Jonathan Cannon, Paul Miller November 1, 2016 : 2004-2022 DOI: 10.1152/jn.00253.2016 Individual neurons' firing rates are regulated by homeostatic synaptic scaling and homeostatic regulation of intrinsic excitability. In this work, we perform simulations that demonstrate that a synaptic and an intrinsic mechanism operating in parallel naturally regulate both firing rate and variance. Such a dual homeostatic system can tune a neuron's output to match the dynamic range of it input and offers a novel approach to tuning a recurrent excitatory network to act as an integrator. Hypoxia and hypercapnia inhibit hypothalamic orexin neurons in rats Olga Dergacheva, Akihiro Yamanaka, Alan R. Schwartz, Vsevolod Y. Polotsky, David Mendelowitz November 1, 2016 : 2250-2259 DOI: 10.1152/jn.00196.2016 Hypothalamic orexin neurons that regulate many physiological functions are, in turn, controlled by various internal and external factors. In diseases, such as sleep apnea, these hypothalamic neurons are challenged by and generate network responses to hypoxia and hypercapnia (H/H). This work tests the hypothesis that orexin neurons are inhibited by H/H and elucidates the mechanisms responsible for the reduced activity in these fluorescently identified orexin neurons upon acute exposure to H/H. A neuronal lactate uptake inhibitor slows recovery of extracellular ion concentration changes in the hippocampal CA3 region by affecting energy metabolism Eskedar Ayele Angamo, Joerg Rösner, Agustin Liotta, Richard Kovács, Uwe Heinemann November 1, 2016 : 2420-2430 DOI: 10.1152/jn.00327.2016 Reduced lactate uptake by α-cyano-4-hydroxycinnamic acid (4-CIN), a monocarboxylate-transporter 2 (MCT2) blocker, interferes with oxidative metabolism and leads to subsequent disturbances in ion homeostasis due to decreased ATP synthesis. This was indicated by an increase in extracellular oxygen tension, accumulation of flavin adenine dinucleotide (FAD), and baseline potassium concentration and effects on evoked potentials. 4-CIN led to extracellular acidosis, which could be mimicked by addition of lactate to artificial cerebrospinal fluid. These effects are not due to activation of lactate receptors.

Control of Movement The destination defines the journey: an examination of the kinematics of hand-to-mouth movements Jason W. Flindall, Claudia L. R. Gonzalez

November 1, 2016 : 2105-2113 DOI: 10.1152/jn.00222.2016 Two experiments were performed, aimed at exploring a previously identified right-hand kinematic advantage for grasping movements whose end goal is to bring an item to the mouth. We provide evidence that this advantage for hand-to-mouth grasping movements is 1) nonspecific with respect to a target's edibility and 2) dependent on the concurrent opening of the mouth to accept the transported target. Coordinating long-latency stretch responses across the shoulder, elbow, and wrist during goal-directed reaching Jeffrey Weiler, James Saravanamuttu, Paul L. Gribble, J. Andrew Pruszynski November 1, 2016 : 2236-2249 DOI: 10.1152/jn.00524.2016 Here we examined the flexibility and utility of coordinating the long-latency stretch response across multiple joints during reaching. After elbow perturbations, long-latency stretch responses evoked in shoulder and wrist muscles counteracted intersegmental dynamics but did not appear to exploit kinematic redundancy. Feedforward compensation for novel dynamics depends on force field orientation but is similar for the left and right arms Eva-Maria Reuter, Ross Cunnington, Jason B. Mattingley, Stephan Riek, Timothy J. Carroll November 1, 2016 : 2260-2271 DOI: 10.1152/jn.00425.2016 This is the first study to compare how the dominant and nondominant arms can learn to compensate novel force fields oriented in different directions predictively. Field direction strongly influenced the rate and amount of predictive compensation, the reduction of kinematic errors, and compensatory aiming angles, but the effects were similar for both arms. This implies that both limbs can learn compensatory feedforward control policies equally well despite well-documented interlimb differences in habitual control. Maximal intermittent contractions of the first dorsal interosseous inhibits voluntary activation of the contralateral homologous muscle Justin J. Kavanagh, Matthew R. Feldman, Michael J. Simmonds November 1, 2016 : 2272-2280 DOI: 10.1152/jn.00367.2016 Strong voluntary contractions of a single limb cause unintended excitatory activity in the opposite limb. However, when contractions are repeated to fatigue, activity in the opposite nonfatigued limb is substantially decreased. Given that repeated single-limb contractions reduced the maximal forcegenerating capacity in the opposite limb, it appears that inhibitory mechanisms are activated on the opposite side of the body, most likely at the level of the motor cortex. The duration of reaching movement is longer than predicted by minimum variance Chunji Wang, Yupeng Xiao, Etienne Burdet, James Gordon, Nicolas Schweighofer November 1, 2016 : 2342-2345 DOI: 10.1152/jn.00148.2016 Despite more than a century of research, it is unclear how we select the duration of arm movements. Here we show that the preferred duration is longer than the duration that minimizes end-point variability. These results show the need to modify the minimum variance theory of motor control. Instead, our data are consistent with the view that humans choose movement durations that achieve a compromise between minimum variance and minimum effort. Effects of reward on oculomotor control Brónagh McCoy, Jan Theeuwes November 1, 2016 : 2453-2466 DOI: 10.1152/jn.00498.2016 A novel eye movement task was used in which observers continuously followed a target around the screen. Distractors with different reward magnitude were presented along with the target. The eyes went more often to a high than low reward distractor. Reward magnitude also affected the global and remote distractor effect and saccade amplitude. Distractors in the opposite visual hemifield to the target resulted in more erroneous saccades than equidistant distractors in the same hemifield.

Higher Neural Functions and Behavior Cerebellar tDCS dissociates the timing of perceptual decisions from perceptual change in speech Daniel R. Lametti, Leonie Oostwoud Wijdenes, James Bonaiuto, Sven Bestmann, John C. Rothwell November 1, 2016 : 2023-2032

DOI: 10.1152/jn.00433.2016 The role of the cerebellum in behavior has classically been confined to the control of movement. However, the cerebellum projects to nonmotor areas, and neuroimaging studies show neural changes in the cerebellum during perception and language tasks. This paper provides initial evidence in healthy humans that alterations of the cerebellum impair the timing of perceptual decisions in speech without impacting the outcome of perceptual decisions. Robust modulation of arousal regulation, performance, and frontostriatal activity through central thalamic deep brain stimulation in healthy nonhuman primates Jonathan L. Baker, Jae-Wook Ryou, Xuefeng F. Wei, Christopher R. Butson, Nicholas D. Schiff, Keith P. Purpura November 1, 2016 : 2383-2404 DOI: 10.1152/jn.01129.2015 Severe brain injuries (SBI) annually encumber an estimated 125,000 individuals in the US with life-long cognitive disabilities, and no effective therapies exist. Central thalamic deep brain stimulation (CT-DBS) is proposed as an effective therapy to reestablish arousal regulation to support cognition, and here we demonstrate that CT-DBS robustly modulates cognition when stimulating a specific central thalamic target using a novel method. These results support ongoing clinical studies to provide effective therapies for SBI patients.

Nervous System Pathophysiology Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice Dong Wang, Shi-Ping Li, Jin-Sheng Fu, Sheng Zhang, Lin Bai, Li Guo November 1, 2016 : 2173-2179 DOI: 10.1152/jn.00510.2016 Our study demonstrates that resveratrol exhibits protective effects in experimental autoimmune encephalomyelitis therapy through its antiinflammation and antioxidant activities by protecting the basement membrane tight junction proteins to improve blood-brain barrier integrity. Progressive resistance exercise restores some properties of the triphasic EMG pattern and improves bradykinesia: the PRET-PD randomized clinical trial Fabian J. David, Julie A. Robichaud, David E. Vaillancourt, Cynthia Poon, Wendy M. Kohrt, Cynthia L. Comella, Daniel M. Corcos November 1, 2016 : 2298-2311 DOI: 10.1152/jn.01067.2015 Progressive resistance exercise training over 24 mo in patients with mild-to-moderate Parkinson's disease partially restores the triphasic electromyographic pattern and improves movement velocity. This finding is similar to the effect of medication and deep brain stimulation. Additionally, the improvement in the triphasic electromyographic pattern and muscle strength is significantly associated with improvement in peak velocity. Our findings indicate that resistance exercise can drive neurophysiological changes that underlie the improvement in movement velocity in Parkinson's disease.

Neural Circuits High-fidelity optical excitation of cortico-cortical projections at physiological frequencies Charles A. Hass, Lindsey L. Glickfeld November 1, 2016 : 2056-2066 DOI: 10.1152/jn.00456.2016 Optical stimulation of axons enables the selective interrogation of pathways connecting distant brain regions. However, despite the importance of driving inputs with known timing and reliability, the efficacy of optical axonal activation has only been inferred from somatic recordings. We have directly quantified the efficacy of axonal stimulation, demonstrating that oChIEF and Chronos, but not ChR2, are suited to high-frequency stimulation. Additionally, we suggest that fidelity of axon stimulation cannot be inferred from somatic recordings. Responses of cerebellar Purkinje cells during fictive optomotor behavior in larval zebrafish Karina Scalise, Takashi Shimizu, Masahiko Hibi, Nathaniel B. Sawtell November 1, 2016 : 2067-2080 DOI: 10.1152/jn.00042.2016 Although the cerebellum is one of the simplest and most highly ordered circuits in the vertebrate brain, links between its structure and function remain elusive. Zebrafish may be an ideal model system for making such links because of the accessibility of their brains to optical imaging and manipulations of neural activity. Our study provides one of the first detailed electrophysiological descriptions in zebrafish of the responses of identified cerebellar neurons during behavior. Sciatic nerve stimulation activates the retrotrapezoid nucleus in anesthetized rats

Roy Kanbar, Ruth L. Stornetta, Patrice G. Guyenet November 1, 2016 : 2081-2092 DOI: 10.1152/jn.00543.2016 Retrotrapezoid nucleus (RTN) neurons encode brain Pco2 and activate breathing. We show by unit recording that these central respiratory chemoreceptors are strongly activated by somatic afferent stimulation, like the neighboring presympathetic neurons. This finding, in anesthetized rats, underscores that RTN neurons integrate multiple types of information besides monitoring the surrounding Pco2. Inputs from somatic afferents to RTN may contribute to the hyperpnea of exercise or mediate respiratory stimulation elicited by activation of nociceptive or thermosensitive afferents. Experience-dependent plasticity of excitatory and inhibitory intertectal inputs in Xenopustadpoles Abigail C. Gambrill, Regina L. Faulkner, Hollis T. Cline November 1, 2016 : 2281-2297 DOI: 10.1152/jn.00611.2016 The optic tectum is required for multisensory integration underlying sensorimotor behaviors. Communication between tectal lobes is thought to play important roles in tectal function. We investigated the development and plasticity of intertectal connections and found that excitatory and inhibitory intertectal connections converge with retinotectal input and are plastic in response to visual experience. This suggests that intertectal inputs are key players in tectal development and may preserve excitatory-inhibitory balance in response to changing sensory input. Model of the songbird nucleus HVC as a network of central pattern generators Eve Armstrong, Henry D. I. Abarbanel November 1, 2016 : 2405-2419 DOI: 10.1152/jn.00438.2016 Building on the observations by Hahnloser et al. of a remarkable sparse command center for sculpting avian song production, and accounting for significant input from the New York University laboratory of M. Long, we have developed a model of nucleus HVC in the songbird system. It accounts for many observed properties of song production and provides a biophysical foundation for the sparse firing of projection neurons as well as the occasional “anomalous neuron” observed by Hahnloser et al.

Sensory Processing Sour taste increases swallowing and prolongs hemodynamic responses in the cortical swallowing network Rachel W. Mulheren, Erin Kamarunas, Christy L. Ludlow November 1, 2016 : 2033-2042 DOI: 10.1152/jn.00130.2016 A sour bolus increased the frequency of swallowing to a greater degree than water and sweet stimuli. Using functional near-infrared spectroscopy, there were no differences in early hemodynamic responses to swallowing between taste conditions; however, hemodynamic responses long after the initial bolus was swallowed were greater during the sour + infusion condition than the water condition. Correlations between swallowing frequency and hemodynamic response suggest an initial activation of swallowing followed by suppression. A systematic analysis of neurons with large somatosensory receptive fields covering multiple body regions in the secondary somatosensory area of macaque monkeys M. Taoka, T. Toda, S. Hihara, M. Tanaka, A. Iriki, Y. Iwamura November 1, 2016 : 2152-2162 DOI: 10.1152/jn.00241.2016 Receptive fields (RFs) of the secondary somatosensory cortex of Japanese monkeys were analyzed. We found large RFs, mostly bilateral ones, covering more than one body region when the entire body was divided into the four: forelimb, hindlimb, trunk, and head. Two tendencies of RF enlargement—interconnecting limb extremities and the mouth and expansion of the trunk RF toward limb extremities to cover the entire body—were found. Neurons with either tendency were distributed in a specific subregion. Comparison of the color selectivity of macaque V4 neurons in different color spaces Takahisa M. Sanada, Tomoyuki Namima, Hidehiko Komatsu November 1, 2016 : 2163-2172 DOI: 10.1152/jn.00108.2016 Color tuning of V4 neurons in the macaque monkey was compared in the CIE-xy chromaticity diagram and DKL color spaces. A good match was generally observed, except for some neurons tuned to high- and low-saturation colors. We show that regardless of the choice of color space, the sampling of colors across the entire gamut is important to characterize neural color selectivity and to compare color selectivities in different areas to

understand color representation in the visual system. Interactive effect of acute pain and motor learning acquisition on sensorimotor integration and motor learning outcomes Erin Dancey, Bernadette Murphy, Danielle Andrew, Paul Yielder November 1, 2016 : 2210-2220 DOI: 10.1152/jn.00337.2016 Enhanced learning was found when motor skill acquisition took place in the presence of acute capsaicin-induced experimental pain, indicating that pain does not always have negative effects on motor learning, a finding relevant for rehabilitation and skill training. Differential changes in somatosensory evoked potentials (SEPs) were seen between those whose performed the motor skill acquisition during pain vs. control, indicating that SEPs may serve as markers for the early neuroplastic changes accompanying motor learning. Masking reduces orientation selectivity in rat visual cortex Dasuni S. Alwis, Katrina L. Richards, Nicholas S. C. Price November 1, 2016 : 2331-2341 DOI: 10.1152/jn.00366.2016 We examined how masks that preceded or succeeded oriented target stimuli affected neuronal responses in rat primary visual cortex. Regardless of the spatial or temporal arrangement of stimuli, the greatest reductions in firing rate and orientation selectivity occurred when target and mask appeared closely in time. On the basis of our neuronal data, we suggest that monotonic patterns of perceptual visual masking are explained by a combination of long neural integration windows and lateral inhibition. Evidence of degraded representation of speech in noise, in the aging midbrain and cortex Alessandro Presacco, Jonathan Z. Simon, Samira Anderson November 1, 2016 : 2346-2355 DOI: 10.1152/jn.00372.2016 We investigate the underlying neurophysiology of age-related auditory temporal processing deficits in normal-hearing listeners using natural speech (in noise). Two neurophysiological techniques are used—magnetoencephalography and EEG—to investigate two different brain areas— cortex and midbrain—within each subject. Older adults have more exaggerated cortical speech representations than younger adults in both quiet and noise. Midbrain speech representations depend more critically on noise level and synchronize more weakly in older adults than younger. Effect of informational content of noise on speech representation in the aging midbrain and cortex Alessandro Presacco, Jonathan Z. Simon, Samira Anderson November 1, 2016 : 2356-2367 DOI: 10.1152/jn.00373.2016 We investigate the underlying neurophysiology of age-related auditory temporal processing deficits in normal-hearing listeners using two different types of noise: comprehensible and incomprehensible natural speech. Two neurophysiological techniques are used—magnetoencephalography and EEG—to investigate two different brain areas—cortex and midbrain—within each participant. Older adults' cortical and midbrain responses depend more critically on noise level and are more affected by the type of noise than younger adults' responses. Cortex dynamically modulates responses of thalamic relay neurons through prolonged circuit-level disinhibition in rat thalamus in vivo Lu Li, Ford F. Ebner November 1, 2016 : 2368-2382 DOI: 10.1152/jn.00424.2016 Dense corticothalamic projections modulate thalamic sensory responses in the rat vibrissa system as cortex selectively changes thalamic whisker responses depending upon the direction preference of thalamic and cortical neurons. We argue that this is best explained as a circuit-level “disinhibition” within the thalamo-cortico-thalamic loop. This study thus provides insight into how the rat somatic sensory system can filter incoming information to enhance selected inputs and suppress others when extracting information from the environment with its whiskers.

Innovative Methodology Rapid classification of hippocampal replay content for real-time applications Xinyi Deng, Daniel F. Liu, Mattias P. Karlsson, Loren M. Frank, Uri T. Eden November 1, 2016 : 2221-2235 DOI: 10.1152/jn.00151.2016 We develop a novel clusterless decoding algorithm that can categorize hippocampal sharp-wave ripple replay events in real time. This work provides an approach for experimental neurophysiologists to identify the content of replay events using multiunit spiking activity, and to interrupt individual events based on their content, in a real-time, closed-loop experimental setting.

Large-scale recording of thalamocortical circuits: in vivo electrophysiology with the two-dimensional electronic depth control silicon probe Richárd Fiáth, Patrícia Beregszászi, Domonkos Horváth, Lucia Wittner, Arno A. A. Aarts, Patrick Ruther, Hercules P. Neves, Hajnalka Bokor, László Acsády, István Ulbert November 1, 2016 : 2312-2330 DOI: 10.1152/jn.00318.2016 Recording the electrical activity of a large number of neurons located in the thalamocortical network is a prerequisite for the understanding of mechanism underlying higher order brain functions. We verified the in vivo performance of an innovative electrophysiological recording system that allows the electronic selection of recording sites on multi-shank, high-density, silicon-based probes. This approach is well-suited to record local field potentials and multiple- and single-unit activity from spatially distinct brain areas of anesthetized rodents.

Retraction Retraction November 1, 2016 : 2467 DOI: 10.1152/jn.z9k-3963-retr.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 48, issue 11 The below Table of Contents is available online at: http://physiolgenomics.physiology.org/content/48/11

CALL FOR PAPERS | Genetics of Metabolic Syndrome Effects of dietary forage and calf starter on ruminal pH and transcriptomic adaptation of the rumen epithelium in Holstein calves during the weaning transition Yo-Han Kim, Noriyuki Toji, Keiichiro Kizaki, Shiro Kushibiki, Toshihiro Ichijo, Shigeru Sato November 1, 2016 : 803-809 DOI: 10.1152/physiolgenomics.00086.2016

CALL FOR PAPERS | Gut Microbiota in Health and Disease Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41 Niranjana Natarajan, Daijiro Hori, Sheila Flavahan, Jochen Steppan, Nicholas A. Flavahan, Dan E. Berkowitz, Jennifer L. Pluznick November 1, 2016 : 826-834 DOI: 10.1152/physiolgenomics.00089.2016

CALL FOR PAPERS | Systems Biology and Polygenic Traits Association of ADAMTS7 gene polymorphism with cardiovascular survival in coronary artery disease A. Pereira, R. Palma dos Reis, R. Rodrigues, A. C. Sousa, S. Gomes, S. Borges, I. Ornelas, A. I. Freitas, G. Guerra, E. Henriques, M. Rodrigues, S. Freitas, C. Freitas, A. Brehm, D. Pereira, M. I. Mendonça November 1, 2016 : 810-815 DOI: 10.1152/physiolgenomics.00059.2016 Selection-, age-, and exercise-dependence of skeletal muscle gene expression patterns in a rat model of metabolic fitness Yu-yu Ren, Lauren G. Koch, Steven L. Britton, Nathan R. Qi, Mary K. Treutelaar, Charles F. Burant, Jun Z. Li

November 1, 2016 : 816-825 DOI: 10.1152/physiolgenomics.00118.2015 Peptide affinity analysis of proteins that bind to an unstructured region containing the transactivating domain of the osmoprotective transcription factor NFAT5 Jenna F. Dumond, Xue Zhang, Yuichiro Izumi, Kevin Ramkissoon, Guanghui Wang, Marjan Gucek, Xujing Wang, Maurice B. Burg, Joan D. Ferraris November 1, 2016 : 835-849 DOI: 10.1152/physiolgenomics.00100.2016

Comparative, Statistical, and Computational Genomics and Model Organism Databases Muscle dysfunction in a zebrafish model of Duchenne muscular dystrophy Jeffrey J. Widrick, Matthew S. Alexander, Benjamin Sanchez, Devin E. Gibbs, Genri Kawahara, Alan H. Beggs, Louis M. Kunkel November 1, 2016 : 850-860 DOI: 10.1152/physiolgenomics.00088.2016

General Interest Comparative transcriptomic analysis identifies genes differentially expressed in human epicardial progenitors and hiPSC-derived cardiac progenitors Jane Synnergren, Lauren Drowley, Alleyn T. Plowright, Gabriella Brolén, Marie-José Goumans, Adriana C. Gittenberger-de Groot, Peter Sartipy, Qing-Dong Wang November 1, 2016 : 771-784 DOI: 10.1152/physiolgenomics.00064.2016 Strain survey and genetic analysis of vasoreactivity in mouse aorta Seung Kyum Kim, Joshua J. Avila, Michael P. Massett November 1, 2016 : 861-873 DOI: 10.1152/physiolgenomics.00054.2016

Genome-wide Assocation Studies and Function Genome-wide association study of plasma resistin levels identified rs1423096 and rs10401670 as possible functional variants in the Japanese population Ryoichi Kawamura, Yasuharu Tabara, Akiko Tsukada, Michiya Igase, Jun Ohashi, Ryo Yamada, Yasunori Takata, Ryuichi Kawamoto, Isao Saito, Hiroshi Onuma, Takeshi Tanigawa, Kazuya Yamada, Norihiro Kato, Yasumasa Ohyagi, Tetsuro Miki, Katsuhiko Kohara, Haruhiko Osawa November 1, 2016 : 874-881 DOI: 10.1152/physiolgenomics.00040.2016

Physiological and Genetic Control of Neural Function Transcriptome assessment of the Pompe (Gaa-/- ) mouse spinal cord indicates widespread neuropathology S. M. F. Turner, D. J. Falk, B. J. Byrne, D. D. Fuller November 1, 2016 : 785-794 DOI: 10.1152/physiolgenomics.00075.2016

Systems Biology of Exercise Immune and inflammatory responses to freediving calculated from leukocyte gene expression profiles Ingrid Eftedal, Arnar Flatberg, Ivan Drvis, Zeljko Dujic November 1, 2016 : 795-802 DOI: 10.1152/physiolgenomics.00048.2016 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 31, issue 6 The below Table of Contents is available online at: http://physiologyonline.physiology.org/content/31/6

Editorial APS Takes a Look in the Mirror Jane F. Reckelhoff, Dennis Brown, Patricia E. Molina October 5, 2016 : 384-385 DOI: 10.1152/physiol.00023.2016 Challenges, Opportunities, and the Future of Physiological Publications in the Hype Cycle David J. Paterson October 5, 2016 : 386-387 DOI: 10.1152/physiol.00024.2016

Physiology Education: Student's Corner Integration and Inspiration: A Spartan's Take on Physiology Brian Whaley October 5, 2016 : 388-389 DOI: 10.1152/physiol.00028.2016

Physiology in Perspective Physiology in Perspective: We Learn From Evolutionary/Comparative Physiology Gary C. Sieck October 5, 2016 : 390-391 DOI: 10.1152/physiol.00027.2016

Reviews Evolutionary Medicine: The Ongoing Evolution of Human Physiology and Metabolism Frank Rühli, Katherine van Schaik, Maciej Henneberg October 5, 2016 : 392-397 DOI: 10.1152/physiol.00013.2016 Primate Torpor Expression: Ghost of the Climatic Past Kathrin H. Dausmann, Lisa Warnecke October 5, 2016 : 398-408 DOI: 10.1152/physiol.00050.2015 Physiological Challenges to Fishes in a Warmer and Acidified Future Göran E. Nilsson, Sjannie Lefevre October 5, 2016 : 409-417 DOI: 10.1152/physiol.00055.2015 Cephalopod Susceptibility to Asphyxiation via Ocean Incalescence, Deoxygenation, and Acidification Brad A. Seibel

October 5, 2016 : 418-429 DOI: 10.1152/physiol.00061.2015 Cardiovascular Physiology of Dinosaurs Roger S. Seymour October 5, 2016 : 430-441 DOI: 10.1152/physiol.00016.2016 Breathtaking Songs: Coordinating the Neural Circuits for Breathing and Singing Marc F. Schmidt, Franz Goller October 5, 2016 : 442-451 DOI: 10.1152/physiol.00004.2016 Copyright © 2016 by the American Physiological Society.

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December 2016; volume 40, issue 4 The below Table of Contents is available online at: http://advan.physiology.org/content/40/4 All articles for this journal are open access.

Editorial Humor promotes learning! Heidi L. Lujan, Stephen E. DiCarlo December 1, 2016 : 433-434 DOI: 10.1152/advan.00123.2016

A Personal View Systems biology: impressions from a newcomer graduate student in 2016 Melanie Rae Simpson December 1, 2016 : 443-445 DOI: 10.1152/advan.00172.2015 Attention span during lectures: 8 seconds, 10 minutes, or more? Neil A. Bradbury December 1, 2016 : 509-513 DOI: 10.1152/advan.00109.2016

Staying Current Physiology and pathophysiology of potassium homeostasis Biff F. Palmer, Deborah J. Clegg December 1, 2016 : 480-490 DOI: 10.1152/advan.00121.2016

Conference | Institute on Teaching and Learning Team-based learning in large enrollment classes Jonathan D. Kibble, Christine Bellew, Abdo Asmar, Lisa Barkley December 1, 2016 : 435-442 DOI: 10.1152/advan.00095.2016

How We Teach: Generalizable Education Research Faculty and second-year medical student perceptions of active learning in an integrated curriculum Alexander Tsang, David M. Harris December 1, 2016 : 446-453 DOI: 10.1152/advan.00079.2016 The pipeline of physiology courses in community colleges: to university, medical school, and beyond Jenny McFarland, Pamela Pape-Lindstrom December 1, 2016 : 473-476 DOI: 10.1152/advan.00141.2016 Status of physiology education in US Doctor of Pharmacy programs Mohammed A. Islam, Seher A. Khan, Rahmat M. Talukder December 1, 2016 : 501-508 DOI: 10.1152/advan.00073.2016 Medical students’ perceptions of the effectiveness of integrated clinical skills sessions using different simulation adjuncts Muhammad Zafar December 1, 2016 : 514-521 DOI: 10.1152/advan.00097.2016 The flipped classroom allows for more class time devoted to critical thinking Lara R. DeRuisseau December 1, 2016 : 522-528 DOI: 10.1152/advan.00033.2016 Assessment of first-year medical students’ perceptions of teaching and learning through team-based learning sessions Adam S. Obad, Ahmed A. Peeran, Mohammad Abrar Shareef, Wissal J. Alsheikh, Dana A. Kalagi, Abdulhadi A. AlAmodi, Tehreem A. Khan, Abdul Ahad Shaikh, Paul Ganguly, Ahmed Yaqinuddin December 1, 2016 : 536-542 DOI: 10.1152/advan.00001.2016

How We Teach: Classroom and Laboratory Research Projects Performance in physiology evaluation: possible improvement by active learning strategies Luís H. Montrezor December 1, 2016 : 454-457 DOI: 10.1152/advan.00022.2016 Winter course in physiology: a successful example of continuing education for secondary school teachers in Brazil Cecília C. Café-Mendes, Luana L. Righi, Jamile Calil-Silveira, Maria Tereza Nunes, Fernando Abdulkader December 1, 2016 : 491-498 DOI: 10.1152/advan.00031.2016

Illuminations Renal clearance: using an interactive activity to visualize a tricky concept Kerry Hull December 1, 2016 : 458-461 DOI: 10.1152/advan.00059.2016 Active learning in neuroscience: a manipulative to simulate visual field defects Andrew Yue-Lin Li, Helena Carvalho December 1, 2016 : 462-464 DOI: 10.1152/advan.00071.2016 Intrinsic motivation: an overlooked component for student success Robert A. Augustyniak, Adrienne Z. Ables, Philip Guilford, Heidi L. Lujan, Ronald N. Cortright, Stephen E. DiCarlo December 1, 2016 : 465-466 DOI: 10.1152/advan.00072.2016 Shock and awe pedagogy! Heidi L. Lujan, Stephen E. DiCarlo December 1, 2016 : 467-468 DOI: 10.1152/advan.00085.2016 An active learning exercise to facilitate understanding of nephron function: anatomy and physiology of renal transporters Amie J. Dirks-Naylor December 1, 2016 : 469-471 DOI: 10.1152/advan.00111.2016 Conceptualizing physiology of arterial blood pressure regulation through the logic model Lalitbhushan S. Waghmare, Tripti K. Srivastava December 1, 2016 : 477-479 DOI: 10.1152/advan.00074.2016 Isosmotic is not always isotonic: the five-minute version Dee U. Silverthorn December 1, 2016 : 499-500 DOI: 10.1152/advan.00080.2016 The inclusion of undergraduate students in physiology outreach activities improves their physiology learning and understanding skills Caroline Altermann, Ben-Hur S. Neves, Pâmela B. Mello-Carpes December 1, 2016 : 529-532 DOI: 10.1152/advan.00012.2016 Medical myth busting to engage physiology students in scientific literature Sarah McLean December 1, 2016 : 533-535 DOI: 10.1152/advan.00150.2015 An intuitive approach to understanding the resting membrane potential David Cardozo December 1, 2016 : 543-547

DOI: 10.1152/advan.00049.2016

Letter to the Editor Simulation for undergraduates: is there a worthy return on investment? David M. Harris December 1, 2016 : 472 DOI: 10.1152/advan.00125.2016 Copyright © 2016 by the American Physiological Society.

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January 2017; volume 97, issue 1 The below Table of Contents is available online at: http://physrev.physiology.org/content/97/1

Reviews Mechanistic Pathways of Sex Differences in Cardiovascular Disease Vera Regitz-Zagrosek, Georgios Kararigas November 2, 2016 : 1-37 DOI: 10.1152/physrev.00021.2015 Molecular Determinants of BK Channel Functional Diversity and Functioning Ramon Latorre, Karen Castillo, Willy Carrasquel-Ursulaez, Romina V. Sepulveda, Fernando Gonzalez-Nilo, Carlos Gonzalez, Osvaldo Alvarez November 2, 2016 : 39-87 DOI: 10.1152/physrev.00001.2016 Molecular Pathophysiology of Congenital Long QT Syndrome M. S. Bohnen, G. Peng, S. H. Robey, C. Terrenoire, V. Iyer, K. J. Sampson, R. S. Kass November 2, 2016 : 89-134 DOI: 10.1152/physrev.00008.2016 Estrogens and Androgens in Skeletal Physiology and Pathophysiology Maria Almeida, Michaël R. Laurent, Vanessa Dubois, Frank Claessens, Charles A. O'Brien, Roger Bouillon, Dirk Vanderschueren, Stavros C. Manolagas November 2, 2016 : 135-187 DOI: 10.1152/physrev.00033.2015 Leveraging Physiology for Precision Drug Delivery Wujin Sun, Quanyin Hu, Wenyan Ji, Grace Wright, Zhen Gu November 9, 2016 : 189-225 DOI: 10.1152/physrev.00015.2016 Cardiac T-Tubule Microanatomy and Function TingTing Hong, Robin M. Shaw November 23, 2016 : 227-252 DOI: 10.1152/physrev.00037.2015 Copyright © 2016 by the American Physiological Society.

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November 2016; volume 4, issue 22 The below Table of Contents is available online at: http://physreports.physiology.org/content/4/22

Original Research The roles of the Na+ /K+ -ATPase, NKCC, and K+  channels in regulating local sweating and cutaneous blood flow during exercise in humans in vivo Jeffrey C. Louie, Naoto Fujii, Robert D. Meade, Glen P. Kenny November 23, 2016 : e13024 DOI: 10.14814/phy2.13024 We demonstrated the roles of the Na+ /K+ -ATPase and, for the first time, the NKCC and K + channels in regulating the sweating and cutaneous vascular response during exercise. Furthermore, their contributions to these responses differ as a function of exercise intensity (i.e., 30, 50, and 70% VO 2peak ) and therefore rates of metabolic heat production. Local sweat rate (Panel A) and cutaneous vascular conductance (CVC, Panel B) at the end of each time period during intermittent 30-min graded intensity exercise bouts separated by 20-min recovery periods (n = 11). Four forearm skin sites were continuously perfused with: (1) lactated Ringer solution (Control, white), (2) 6 mmol·L −1 10 mmol·L −1

 bumetanide (NKCC inhibitor, medium grey), or (4) 50 mmol·L −1

 ouabain (Na + /K+ -ATPase inhibitor, light grey), (3)

BaCl2  (non-specific K +  channel inhibitor, dark grey). Values are presented as mean ± 95% confidence interval. Baseline values represent the 5 min prior to the first exercise bout. All

other values represent the final 5 min of the corresponding period. BL, baseline; LOW/MODERATE/HIGH, Low/Moderate/High intensity exercise bout; Rec, recovery period; VO2peak , peak rate of oxygen consumption. * Significantly different from

Control;  P ≤ 0.05.

Intestinal Na+ , K+ , 2Cl -  cotransporter 2 plays a crucial role in hyperosmotic transitions of a euryhaline teleost Andrew J. Esbaugh, Brett Cutler November 23, 2016 : e13028 DOI: 10.14814/phy2.13028 Many fish species are capable of moving between freshwater and seawater habitats, which requires a shift in osmoregulatory strategy. Here, we describe the osmotic challenges and intestinal plasticity associated with transition into seawater for a marine teleost. Altered CO 2 sensitivity of connexin26 mutant hemichannels in vitro Elizabeth de Wolf, Joseph van de Wiel, Jonathan Cook, Nicholas Dale November 24, 2016 : e13038 DOI: 10.14814/phy2.13038 Connexin26 (Cx26) mutations underlie human pathologies ranging from hearing loss to keratitis ichthysosis deafness (KID) syndrome. We show that some of these mutations reduce or abolish the sensitivity of the hemichannel to CO 2 . Activity-dependent redistribution of Kv2.1 ion channels on rat spinal motoneurons Shannon H. Romer, Adam S. Deardorff, Robert E. W. Fyffe November 24, 2016 : e13039 DOI: 10.14814/phy2.13039

Delayed rectifier Kv2.1 ion channels are key homeostatic regulatory elements in several neuronal systems, but the functional implications of large Kv2.1 channel clusters in spinal motoneurons (MNs) are not well established. Here, for the first time, we demonstrate that both motor and sensory nerve activity rapidly influence Kv2.1 clustering in spinal MNs in vivo and suggest that Kv2.1 channels contribute to the homeostatic regulation of motoneuron firing properties. These data provide important mechanistic insight into the prominent and puzzling Kv2.1 cluster dynamics that have been observed in spinal MNs. Impact of external pneumatic compression target inflation pressure on transcriptome-wide RNA expression in skeletal muscle Jeffrey S. Martin, Wesley C. Kephart, Cody T. Haun, Anna E. McCloskey, Joshua J. Shake, Christopher B. Mobley, Michael D. Goodlett, Andreas Kavazis, David D. Pascoe, Lee Zhang, Michael D. Roberts November 24, 2016 : e13029 DOI: 10.14814/phy2.13029 Herein, we investigated the impact of target inflation pressure settings with peristaltic pulse external pneumatic compression on transcriptome-wide gene expression in human vastus lateralis skeletal muscle tissue. In general, a lower pressure setting (30–40 mmHg) was associated with upregulation of genes, whereas a higher pressure was associated with down-regulation or a minimal response. In addition, subsequent analyses (i.e., PGC-1αlocalization to the nucleus, phosphorylation of eNOS) also demonstrated marked heterogeneity in the cellular response to different target inflation pressures. Effect of exercise-induced muscle damage on vascular function and skeletal muscle microvascular deoxygenation Jacob T. Caldwell, Garrett C. Wardlow, Patrece A. Branch, Macarena Ramos, Christopher D. Black, Carl J. Ade November 24, 2016 : e13032 DOI: 10.14814/phy2.13032 We provide new insight that shows exercise induced muscle damage of the quadriceps does not influence fractional O 2 extraction or . Additionally, exercise induced muscle damage may play a role in decreased local, but not global flow-mediated dilation. Cardiac responses to exercise distinguish postural orthostatic tachycardia syndrome variants Paolo T. Pianosi, Darrell R. Schroeder, Philip R. Fischer November 24, 2016 : e13040 DOI: 10.14814/phy2.13040 Alterations in resting limb blood flow have been documented in patients with postural orthostatic tachycardia syndrome. We have not extended this model to exercise, showing there are three subgroups within this heterogeneous population. The unifying underlying pathophysiology is likely dysregulation of autonomic control of blood supply. Regional effects of streptozotocin-induced diabetes on shortening and calcium transport in epicardial and endocardial myocytes from rat left ventricle Manal M. A. Smail, Muhammad A. Qureshi, Anatoliy Shmygol, Murat Oz, Jaipaul Singh, Vadym Sydorenko, Alya Arabi, Frank C. Howarth, Lina Al Kury November 24, 2016 : e13034 DOI: 10.14814/phy2.13034 Results from this study suggest that transmural differences in calcium transport in the ventricular myocardium may underlie some of the disturbances in contractile properties of myocytes in diabetic heart. Can inorganic phosphate explain sag during unfused tetanic contractions of skeletal muscle? Ian C. Smith, Catherine Bellissimo, Walter Herzog, A. Russell Tupling November 24, 2016 : e13043 DOI: 10.14814/phy2.13043 Fast-twitch skeletal muscle commonly exhibits force declines (sag) when electrically stimulated at frequencies which produce unfused tetanic contractions, while slow-twitch muscle is sag-resistant. In this study we provide preliminary experimental and modeling evidence which suggests that accumulation of cytosolic inorganic phosphate concentration during contraction can abbreviate twitch duration to impair summation and facilitate sag. As this mechanism appears most effective in muscles with very low cytosolic phosphate concentrations at the onset of contraction (e.g., well rested fast-twitch skeletal muscle), this may account for the fiber-type dependent properties of sag. An arginase-1 SNP that protects against the development of pulmonary hypertension in bronchopulmonary dysplasia enhances NO-mediated apoptosis in lymphocytes

Jennifer K. Trittmann, Yi Jin, Louis G. Chicoine, Yusen Liu, Bernadette Chen, Leif D. Nelin November 27, 2016 : e13041 DOI: 10.14814/phy2.13041 Arginase 1 (ARG1) single nucleotide polymorphism (SNP) rs2781666 decreases the risk of pulmonary hypertension in patients with bronchopulmonary dysplasia. In this study, we compare neonatal cord blood lymphocytes differentiated by ARG1 SNP (TT) or wild type (GG) to determine a potential protective mechanism of the ARG1 SNP. We found that patients with ARG1 SNP (TT) had greater levels of NO production leading to greater apoptosis than patients with ARG1 wild type (GG). Validation of an integrative mathematical model of dehydration and rehydration in virtual humans W. Andrew Pruett, John S. Clemmer, Robert L. Hester November 29, 2016 : e13015 DOI: 10.14814/phy2.13015 We validate HumMod, an integrative physiological model, against multiple human experiments involving dehydration and rehydration. We especially focus on vasopressin secretion and its effects on body water compartmentalization. Influence of PECAM-1 ligand interactions on PECAM-1-dependent cell motility and filopodia extension Valsamma Abraham, Andrew Parambath, Debria S. Joe, Horace M. DeLisser November 27, 2016 : e13030 DOI: 10.14814/phy2.13030 The authors report that by cooperatively activating Cdc42 to stimulate the extension of filopodia, both homophilic and heparin/glycosaminoglycanmediated heterophilic ligand interactions of PECAM-1 are involved in the ability of PECAM-1 to promote cell motility and the extension of filopodia.

November 2016; volume 4, issue 21 The below Table of Contents is available online at: http://physreports.physiology.org/content/4/21

Original Research Inhibition of GSK-3β increases trabecular bone volume but not cortical bone volume in adenine-induced uremic mice with severe hyperparathyroidism Narihito Tatsumoto, Masaki Arioka, Shunsuke Yamada, Fumi Takahashi-Yanaga, Masanori Tokumoto, Kazuhiko Tsuruya, Takanari Kitazono, Toshiyuki Sasaguri November 1, 2016 : e13010 DOI: 10.14814/phy2.13010 The aim of this study is to determine whether inhibition of GSK-3β increases bone volume in chronic kidney disease (CKD) by using GSK-3β heterozygous knockout mice and lithium, a GSK-3 inhibitor. Inhibition of GSK-3β increased trabecular bone volume but did not rescue a decrease in cortical bone volume in uremic mice. These results suggest that an inhibitor of GSK-3β may be a potential candidate as a bone anabolic agent in the CKD. Promotion of adipogenesis by neuropeptide Y during the later stages of chicken preadipocyte differentiation Steven L. Shipp, Mark A. Cline, Elizabeth R. Gilbert November 1, 2016 : e13006 DOI: 10.14814/phy2.13006 The objective of this study was to evaluate effects of neuropeptide Y (NPY) on chick preadipocyte proliferation and differentiation. Preadipocytes were treated with NPY during proliferation and differentiation, and effects on proliferation, lipid accumulation, enzyme activity, and gene expression were evaluated. Increased expression of proliferation markers in preadipocytes, and during differentiation increased expression of transcription factors and a fatty acid transporter, increased lipid accumulation, and increased activity of G3PDH suggest that NPY may enhance preadipocyte activity, adipogenesis, and promotes lipid accumulation throughout chicken adipocyte differentiation. Optimizing human hepatocyte models for metabolic phenotype and function: effects of treatment with dimethyl sulfoxide (DMSO) Nikolaos Nikolaou, Charlotte J. Green, Pippa J. Gunn, Leanne Hodson, Jeremy W. Tomlinson November 1, 2016 : e12944

DOI: 10.14814/phy2.12944 Current in vitro cell models have significant limitations to their use. Cell lines are often of malignant origin and primary human hepatocytes, which are regarded as the current gold standard, are challenging to obtain and work with. In this article, we describe a novel innovative methodology to supplement cell culture media to enhance the metabolic phenotype of liver cell lines to make them more closely resemble primary human hepatocytes. Marginal dietary zinc deprivation augments sepsis-induced alterations in skeletal muscle TNF-α but not protein synthesis Kristen T. Crowell, Shannon L. Kelleher, David I. Soybel, Charles H. Lang November 3, 2016 : e13017 DOI: 10.14814/phy2.13017 Mild dietary zinc deprivation in male mice exaggerated the increase in skeletal muscle TNF-αacutely after sepsis. Despite the elevation of this local inflammatory cytokine, the sepsis-induced decrease in muscle protein synthesis was unchanged with mild zinc deprivation. In the chronic phase of sepsis, zinc deprivation did not affect the normalization of muscle TNF-αand protein synthesis rate. Postnatal regulation of MAMDC4 in the porcine intestinal epithelium is influenced by bacterial colonization Alex J. Pasternak, Glenn M. Hamonic, Andrew Van Kessel, Heather L. Wilson November 7, 2016 : e13018 DOI: 10.14814/phy2.13018 Porcine intestine expresses the transcript and protein of MAMDC4, however, this is strictly limited to the immediate postnatal period. Expression of the protein is found on the apical surface of fetal-type enterocytes, but loss of expression is not associated with cellular replacement. Furthermore, down-regulation of the protein was found to be associated with bacterial colonization in a species-specific manner. A novel diet-induced murine model of steatohepatitis with fibrosis for screening and evaluation of drug candidates for nonalcoholic steatohepatitis Chieko Ejima, Haruna Kuroda, Sonoko Ishizaki November 7, 2016 : e13016 DOI: 10.14814/phy2.13016 We successfully constructed an in vivo screening steatohepatitis model for the treatment of NASH and a long-term model to study the treatment efficacy for steatohepatitis, fibrosis, and tumor formation. Effect of energy restriction and physical exercise intervention on phenotypic flexibility as examined by transcriptomics analyses of mRNA from adipose tissue and whole body magnetic resonance imaging Sindre Lee, Frode Norheim, Torgrim M. Langleite, Hans J. Noreng, Trygve H. Storås, Lydia A. Afman, Gary Frost, Jimmy D. Bell, E. Louise Thomas, Kristoffer J. Kolnes, Daniel S. Tangen, Hans K. Stadheim, Gregor D. Gilfillan, Hanne L. Gulseth, Kåre I. Birkeland, Jørgen Jensen, Christian A. Drevon, Torgeir Holen, the NutriTech Consortium November 7, 2016 : e13019 DOI: 10.14814/phy2.13019 Both exercise and diet influence immune cell related gene expression in adipose tissue, although in different fashions. Exercise reduced M2-like macrophages and T cells, whereas diet increased M1-like macrophages. Arterio-venous anastomoses in isolated, perfused rat lungs Robert L. Conhaim, Gilad S. Segal, Kal E. Watson November 7, 2016 : e13023 DOI: 10.14814/phy2.13023 We show that arterio-venous shunt pathways exist within the pulmonary circulation that can accommodate latex particles ranging in size from 4 to 50 µm diameter. Shunt pathways for the smallest (4 µm) particles appear to be much more extensive than those for larger particles. This suggests that there is an extensive network of series and parallel perfusion pathways at the acinar level, and implies that the idea of sheet flow extends into the acini.

Corrigendum Corrigendum November 13, 2016 : e13035

DOI: 10.14814/phy2.13035 Corrigendum November 13, 2016 : e13036 DOI: 10.14814/phy2.13036

Original Research Glucocorticoids increase skeletal muscle NF-κB inducing kinase (NIK): links to muscle atrophy Christopher S. Fry, Syed Z. Nayeem, Edgar L. Dillon, Partha S. Sarkar, Batbayar Tumurbaatar, Randall J. Urban, Traver J. Wright, Melinda Sheffield-Moore, Ronald G. Tilton, Sanjeev Choudhary November 14, 2016 : e13014 DOI: 10.14814/phy2.13014 Glucocorticoids increase NF-kB inducing kinase (NIK) in skeletal muscle. Overexpressing NIK in mouse tibialis anterior mimics effects of glucocorticoids on muscle atrophy, loss of function, and expression of atrogenes. NIK overexpression in primary human skeletal muscle myotubes increases atrophy biomarkers while NIK knockdown significantly attenuates glucocorticoid-induced increase in Atrogin-1. These results indicate that NIK participates in glucocorticoid-induced skeletal muscle atrophy. Long-term exercise in mice has sex-dependent benefits on body composition and metabolism during aging Rachel C. McMullan, Scott A. Kelly, Kunjie Hua, Brian K. Buckley, James E. Faber, Fernando Pardo-Manuel de Villena, Daniel Pomp November 14, 2016 : e13011 DOI: 10.14814/phy2.13011 This study demonstrates that exercise prevents doubling of body fat, significant gains in body mass, and loss of lean mass during aging. It also provides evidence of the effect of sex on exercise, body mass, and body composition trajectories during aging. Thus, this study demonstrates that long-term exercise (starting in midlife) may be used as a preventive measure against age-related weight gain and changes in body composition. Desensitization of idiopathic pulmonary fibrosis fibroblasts to Alternaria alternata extract-mediated necrotic cell death Jintaek Im, Kyutae Kim, Ji Young Yhee, Scott M. O'Grady, Richard S. Nho November 15, 2016 : e13020 DOI: 10.14814/phy2.13020 Relatively low 7-AAD-positive cells were found in the majority of idiopathic pulmonary fibrosis (IPF) fibroblasts compared with that of control fibroblasts (Fig. 3B, left). Statistical analysis demonstrated that control fibroblasts showed a 1.9 fold greater 7-AAD-positive cell value compared to IPF fibroblasts (38.2 vs. 20.5% in Fig. 3B, right). Collectively, these results showed that the A. alternata extract promoted fibroblasts cell death via necrosis, and that IPF fibroblasts are resistant to A. alternata extract-induced necrotic cell death. A pathogenic role for the integrin CD103 in experimental allergic airways disease Vanessa S. Fear, Siew Ping Lai, Graeme R. Zosky, Kara L. Perks, Shelley Gorman, Fabian Blank, Christophe von Garnier, Philip A. Stumbles, Deborah H. Strickland November 15, 2016 : e13021 DOI: 10.14814/phy2.13021 This manuscript identifies an important pathogenic role for the integrin CD103 in controlling T-cell and dendritic cell migration in mice during induction of allergic airways disease on the genetically susceptible BALB/c background. Our data show that CD103 controls local migration of pathogenic CD4 T cells and allergen-laden dendritic cells into airways and onward to draining lymph nodes during induction of allergic airways disease, but does not regulate systemic allergen sensitization. Altered thermoregulatory responses in heart failure patients exercising in the heat Bryce N. Balmain, Ollie Jay, Surendran Sabapathy, Danielle Royston, Glenn M. Stewart, Rohan Jayasinghe, Norman R. Morris November 15, 2016 : e13022 DOI: 10.14814/phy2.13022 The purpose of this study was to examine thermoregulatory responses and human heat balance parameters in heart failure patients compared to control participants during exercise in a warm environment. Our data show that patients with heart failure appear to be limited in their ability to manage a thermal load during exercise in a warm environment, as evidenced by disrupted human heat balance secondary to impaired circulation to

the periphery. Lack of an apparent role for endothelin-1 in the prolonged reduction in renal perfusion following severe unilateral ischemia-reperfusion injury in the mouse Erika I. Boesen November 15, 2016 : e13027 DOI: 10.14814/phy2.13027 Renal perfusion, as assessed noninvasively by pulsed-wave Doppler ultrasound, remains significantly reduced following 45 min unilateral renal ischemia in male C57Bl/6 mice. The powerful vasoconstrictor endothelin-1 is rapidly upregulated in the renal vasculature by ischemia and reperfusion, however, blockade of the ETA  receptor or knockout of endothelin-1 from the endothelium do not improve recovery of renal perfusion or prevent atrophy of the injured kidney. Haploinsufficiency of the folliculin gene leads to impaired functions of lung fibroblasts in patients with Birt–Hogg–Dubé syndrome Yoshito Hoshika, Fumiyuki Takahashi, Shinsaku Togo, Muneaki Hashimoto, Takeshi Nara, Toshiyuki Kobayashi, Fariz Nurwidya, Hideyuki Kataoka, Masatoshi Kurihara, Etsuko Kobayashi, Hiroki Ebana, Mika Kikkawa, Katsutoshi Ando, Koichi Nishino, Okio Hino, Kazuhisa Takahashi, Kuniaki Seyama November 15, 2016 : e13025 DOI: 10.14814/phy2.13025 A state of FLCN haploinsufficiency may cause lung fibroblast dysfunction, thereby impairing tissue repair. These may reveal one mechanism of lung cyst formation and pneumothorax in BHDS patients. Intravital imaging of mouse urothelium reveals activation of extracellular signal-regulated kinase by stretch-induced intravesical release of ATP Takeshi Sano, Takashi Kobayashi, Hiromitsu Negoro, Atsushi Sengiku, Takuya Hiratsuka, Yuji Kamioka, Louis S. Liou, Osamu Ogawa, Michiyuki Matsuda November 15, 2016 : e13033 DOI: 10.14814/phy2.13033 Extracellular signal-regulated kinase (ERK) activity is observed in the whole bladder wall of live mice that express a Förster/fluorescence resonance energy transfer (FRET) biosensor by two-photon excitation microscopy. Elevated intravesical pressure activates ERK in the urothelium, but not in the detrusor smooth muscle. Increase in mechanical stretch, but not hydrostatic pressure, induces intravesical secretion of ATP and thereby activates ERK in the urothelium. The effect of iron deficiency on the temporal changes in the expression of genes associated with fat metabolism in the pregnant rat Susan M. Hay, Harry J. McArdle, Helen E. Hayes, Valerie J. Stevens, William D. Rees November 15, 2016 : e12908 DOI: 10.14814/phy2.12908 Iron is essential for the oxidative metabolism of lipids. In the pregnant rat iron deficiency produces changes in maternal lipid metabolism due to a reduction in beta-oxidation late in gestation. Beta-oxidation by the fetal liver was also reduced. Airway delivery of interferon-γ overexpressing macrophages confers resistance to Mycobacterium avium infection in SCID mice Rajamouli Pasula, Bradley E. Britigan, Banurekha Kesavalu, Maher Y. Abdalla, William J. Martin II November 17, 2016 : e13008 DOI: 10.14814/phy2.13008 Alveolar macrophages (AMs) represent the first line of host defense against infection in the lung. Interferon gamma (IFN-γ) activation of AMs enhances in vitro killing of pathogens such as M. avium. We hypothesized that airway delivery of AMs into the lungs of immunodeficient mice infected with M. avium will inhibit M. avium growth in the lung and that this macrophage function is in part IFN-γ dependent. In this study, normal BALB/c and BALB/c SCID mice received M. avium intratracheally while on mechanical ventilation. After 30 days, M. aviumnumbers increased in a concentration-dependent manner in SCID mice compared with normal BALB/c mice. Airway delivery of IFN-γ-activated BALB/c AMs or J774A.1 macrophages overexpressing IFN-γ into the lungs of SCID mice resulted in a significant decrease in M. avium growth (P