bluuebunny/crossref_metadata_2025 huggingface dataset:
Stem cell biomarker ALDH1A1 in breast cancer shows an association with prognosis and clinicopathological variables that is highly cut-off dependent
Authors: Sjöström Martin , Hartman Linda , Honeth Gabriella , Grabau Dorthe , Malmström Per , Hegardt Cecilia , Fernö Mårten , Niméus Emma
Published: July 2015

Aims

Aldehyde dehydrogenase family 1 member A1 (ALDH1A1) is a putative marker of breast cancer stem cells (CSCs) with prognostic implications when expressed in cancer or stroma. However, previous results are contradictory and we therefore aimed to further evaluate the impact of ALDH1A1 on distant disease-free survival (DDFS) and correlation with clinicopathological variables in breast cancer, specifically by evaluating different cut-offs.

Methods

Two breast cancer cohorts (N=216 and N=210) were evaluated with immunohistochemistry for ALDH1A1 on tissue microarrays with three different cut-offs in cancer cells and in stromal cells. The association of ALDH1A1 with DDFS and other clinicopathological variables was assessed. As further validation, gene expression levels of ALDH1A1 and association with survival were analysed in one of the cohorts and a separate cohort.

Results

ALDH1A1 expression in cancer cells was associated with either a better or a worse prognosis, depending on cut-off. Considering weakly stained cancer cells as positive, ALDH1A1+ was associated with a better prognosis in both cohorts. Considering only strongly stained cells as positive, ALDH1A1+ was associated with oestrogen receptor and progesterone receptor negativity in both cohorts and worse prognosis in one of the cohorts. Stromal ALDH1A1 staining was associated with improved DDFS in one cohort. Gene expression analysis showed that a high ALDH1A1 expression was associated with a better prognosis.

Conclusions

ALDH1A1 is associated with DDFS and clinicopathological variables, both in cancer cells and stroma, but is highly cut-off dependent. Only the strongly ALDH1A1-stained cells show a more aggressive phenotype typical for CSCs.
Food availability in spring affects smolting in brown trout (Salmo trutta)
Authors: Jones Douglas A. , Bergman Eva , Greenberg Larry
Published: July 2015

Prior to out-migration, salmonid fish typically undergo physiological and morphological changes — a process known as smolting. This study indicates that smolting in brown trout (Salmo trutta) is affected by feeding conditions in spring immediately prior to out-migration. This conclusion was reached after experimentally testing the effect of seasonal variation in food availability on smolt status in the spring. A migratory strain of trout was administered either high or low food rations in the autumn, winter, or spring prior to release in the spring. While fish growth or condition could be affected in any season, it was spring rationing that reduced growth and growth-related variables and that caused increased smolting. Our result supports the idea that smoltification and the decision to migrate is affected by spring food availability regardless of conditions in the previous autumn or winter.
FaRe: A Mathematica package for tensor reduction of Feynman integrals
Authors: Re Fiorentin Michele
Published: July 2015

In this paper, we present FaRe, a package for Mathematica that implements the decomposition of a generic tensor Feynman integral, with arbitrary loop number, into scalar integrals in higher dimension. In order for FaRe to work, the package FeynCalc is needed, so that the tensor structure of the different contributions is preserved and the obtained scalar integrals are grouped accordingly. FaRe can prove particularly useful when it is preferable to handle Feynman integrals with free Lorentz indices and tensor reduction of high-order integrals is needed. This can then be achieved with several powerful existing tools.
Pentavalent Symmetric Graphs of Order Twice a Prime Square
Authors: Pan Jiangmin , Liu Zhe , Yu Xiaofen
Published: July 2015

A classification of pentavalent symmetric graphs of order twice a prime square is given. It is proved that such a graph is a coset graph of ℤ3. A 6 (non-split extension), or a bi-coset graph of an extra-special group of order 125, or the standard double cover of a specific abelian Cayley digraph of order a prime square.
A Hua-like Theorem in Semirings
Authors: Pei Jun , Guo Yuqi , Shum K.P.
Published: July 2015

In this paper, we establish a Hua-Like theorem in some kind of semirings. This can be regarded as a generalized version of Hua's theorem from rings to semirings.
Recognizing the Semiprimitivity of ℕ-graded Algebras via Gröbner Bases
Authors: Li Huishi
Published: July 2015

Let K〈X〉=K〈X1,…,Xn〉 be the free K-algebra on X={X1,…,Xn} over a field K, which is equipped with a weight ℕ-gradation (i.e., each Xi is assigned a positive degree), and let [Formula: see text] be a finite homogeneous Gröbner basis for the ideal [Formula: see text] of K〈X〉 with respect to some monomial ordering ≺ on K〈X〉. It is shown that if the monomial algebra [Formula: see text] is semiprime, where [Formula: see text] is the set of leading monomials of [Formula: see text] with respect to ≺, then the ℕ-graded algebra A=K〈X〉 /I is semiprimitive in the sense of Jacobson. In the case that [Formula: see text] is a finite nonhomogeneous Gröbner basis with respect to a graded monomial ordering ≺ gr , and the ℕ-filtration FA of the algebra A=K〈X〉 /I induced by the ℕ-grading filtration FK〈X〉 of K〈X〉 is considered, if the monomial algebra [Formula: see text] is semiprime, then it is shown that the associated ℕ-graded algebra G(A) and the Rees algebra Ã of A determined by FA are all semiprimitive.
Self-Assembly of Gold Nanoparticles on Gold Core-Induced Polypyrrole Nanohybrids for Electrochemical Sensor of Dopamine
Authors: Ding Junwei , Zhang Kai , Xu Wei , Su Zhiqiang
Published: July 2015

Gold core-induced polypyrrole nanohybrids (Au–PPyNHs) were successfully synthesized via in situ chemical oxidation polymerization of pyrrole molecules, and their structure was directly confirmed and characterized by scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy and X-ray diffraction. Furthermore, gold nanoparticles (AuNPs) were assembled onto the as-prepared Au–PPyNHs by electrostatic interaction to fabricate the nanohybrids of Au–PPyNH–Au. The created Au–PPyNH–Au nanohybrids was immobilized onto glassy carbon electrode and applied to construct dopamine (DA) sensor. We found that the fabricated sensor with Au–PPyNH–Au nanohybrids is highly specific probe for sensing DA. The Au–PPyNH–Au based DA sensor has a linear detection range from 1[Formula: see text][Formula: see text]M to 0.321 mM and a detection limit of 0.32[Formula: see text][Formula: see text]M.
Exponential stability of memristor-based synchronous switching neural networks with time delays
Authors: Jiang Yinlu , Li Chuandong
Published: July 2015

In this paper, we study the existence, uniqueness and stability of memristor-based synchronous switching neural networks with time delays. Several criteria of exponential stability are given by introducing multiple Lyapunov functions. In comparison with the existing publications on simplice memristive neural networks or switching neural networks, we consider a system with a series of switchings, these switchings are assumed to be synchronous with memristive switching mechanism. Moreover, the proposed stability conditions are straightforward and convenient and can reflect the impact of time delay on the stability. Two examples are also presented to illustrate the effectiveness of the theoretical results.
Fetal endocrine and metabolic adaptations to hypoxia: the role of the hypothalamic-pituitary-adrenal axis
Authors: Newby Elizabeth A. , Myers Dean A. , Ducsay Charles A.
Published: July 2015

In utero, hypoxia is a significant yet common stress that perturbs homeostasis and can occur due to preeclampsia, preterm labor, maternal smoking, heart or lung disease, obesity, and high altitude. The fetus has the extraordinary capacity to respond to stress during development. This is mediated in part by the hypothalamic-pituitary-adrenal (HPA) axis and more recently explored changes in perirenal adipose tissue (PAT) in response to hypoxia. Obvious ethical considerations limit studies of the human fetus, and fetal studies in the rodent model are limited due to size considerations and major differences in developmental landmarks. The sheep is a common model that has been used extensively to study the effects of both acute and chronic hypoxia on fetal development. In response to high-altitude-induced, moderate long-term hypoxia (LTH), both the HPA axis and PAT adapt to preserve normal fetal growth and development while allowing for responses to acute stress. Although these adaptations appear beneficial during fetal development, they may become deleterious postnatally and into adulthood. The goal of this review is to examine the role of the HPA axis in the convergence of endocrine and metabolic adaptive responses to hypoxia in the fetus.
Prenatal alcohol exposure alters methyl metabolism and programs serotonin transporter and glucocorticoid receptor expression in brain
Authors: Ngai Ying Fai , Sulistyoningrum Dian C. , O'Neill Ryan , Innis Sheila M. , Weinberg Joanne , Devlin Angela M.
Published: July 2015

Prenatal alcohol exposure (PAE) programs the fetal hypothalamic-pituitary-adrenal (HPA) axis, resulting in HPA dysregulation and hyperresponsiveness to stressors in adulthood. Molecular mechanisms mediating these alterations are not fully understood. Disturbances in one-carbon metabolism, a source of methyl donors for epigenetic processes, contributes to alcoholic liver disease. We assessed whether PAE affects one-carbon metabolism (including Mtr, Mat2a, Mthfr, and Cbs mRNA) and programming of HPA function genes ( Nr3c1, Nr3c2, and Slc6a4) in offspring from ethanol-fed (E), pair-fed (PF), and ad libitum-fed control (C) dams. At gestation day 21, plasma total homocysteine and methionine concentrations were higher in E compared with C dams, and E fetuses had higher plasma methionine concentrations and lower whole brain Mtr and Mat2a mRNA compared with C fetuses. In adulthood (55 days), hippocampal Mtr and Cbs mRNA was lower in E compared with C males, whereas Mtr, Mat2a, Mthfr, and Cbs mRNA were higher in E compared with C females. We found lower Nr3c1 mRNA and lower nerve growth factor inducible protein A (NGFI-A) protein in the hippocampus of E compared with PF females, whereas hippocampal Slc6a4 mRNA was higher in E than C males. By contrast, hypothalamic Slc6a4 mRNA was lower in E males and females compared with C offspring. This was accompanied by higher hypothalamic Slc6a4 mean promoter methylation in E compared with PF females. These findings demonstrate that PAE is associated with alterations in one-carbon metabolism and has long-term and region-specific effects on gene expression in the brain. These findings advance our understanding of mechanisms of HPA dysregulation associated with PAE.
Aldo-keto reductase 1b7, a novel marker for renin cells, is regulated by cyclic AMP signaling
Authors: Lin Eugene E. , Pentz Ellen S. , Sequeira-Lopez Maria Luisa S. , Gomez R. Ariel
Published: July 2015

We previously identified aldo-keto reductase 1b7 (AKR1B7) as a marker for juxtaglomerular renin cells in the adult mouse kidney. However, the distribution of renin cells varies dynamically, and it was unknown whether AKR1B7 maintains coexpression with renin in response to different developmental, physiological, and pathological situations, and furthermore, whether similar factor(s) simultaneously regulate both proteins. We show here that throughout kidney development, AKR1B7 expression—together with renin—is progressively restricted in the kidney arteries toward the glomerulus. Subsequently, when formerly renin-expressing cells reacquire renin expression, AKR1B7 is reexpressed as well. This pattern of coexpression persists in extreme pathological situations, such as deletion of the genes for aldosterone synthase or Dicer. However, the two proteins do not colocalize within the same organelles: renin is found in the secretory granules, whereas AKR1B7 localizes to the endoplasmic reticulum. Interestingly, upon deletion of the renin gene, AKR1B7 expression is maintained in a pattern mimicking the embryonic expression of renin, while ablation of renin cells resulted in complete abolition of AKR1B7 expression. Finally, we demonstrate that AKR1B7 transcription is controlled by cAMP. Cultured cells of the renin lineage reacquire the ability to express both renin and AKR1B7 upon elevation of intracellular cAMP. In vivo, deleting elements of the cAMP-response pathway (CBP/P300) results in a stark decrease in AKR1B7- and renin-positive cells. In summary, AKR1B7 is expressed within the renin cell throughout development and perturbations to homeostasis, and AKR1B7 is regulated by cAMP levels within the renin cell.
Fetuin-A decrease induced by a low-protein diet enhances vascular calcification in uremic rats with hyperphosphatemia
Authors: Yamada Shunsuke , Tokumoto Masanori , Tsuruya Kazuhiko , Tatsumoto Narihito , Noguchi Hideko , Kitazono Takanari , Ooboshi Hiroaki
Published: July 2015

Although dietary phosphate restriction is important for treating hyperphosphatemia in patients with chronic kidney disease, it remains unclear whether a low-protein diet (LPD), which contains low phosphate, has beneficial effects on malnutrition, inflammation, and vascular calcification. The effects of LPD on inflammation, malnutrition, and vascular calcification were therefore assessed in rats. Rats were fed a normal diet or diets containing 0.3% adenine and low/normal protein and low/high phosphate. After 6 wk, serum and urinary biochemical parameters, systemic inflammation, and vascular calcification were examined. The protective effect of fetuin-A and albumin were assessed in cultured vascular smooth muscle cells. Rats fed the diet containing 0.3% adenine developed severe azotemia. LPD in rats fed high phosphate induced malnutrition (decreases in body weight, food intake, serum albumin and fetuin-A levels, and urinary creatinine excretion) and systemic inflammation (increases in serum tumor necrosis factor-α and urinary oxidative stress marker). LPD decreased the serum fetuin-A level and fetuin-A synthesis in the liver and increased serum calcium-phosphate precipitates. A high-phosphate diet increased aortic calcium content, which was enhanced by LPD. Reduced fetal calf serum in the medium of cultured vascular smooth muscle cells enhanced phosphate-induced formation of calcium-phosphate precipitates in the media and calcification of vascular smooth muscle cells, both of which were prevented by fetuin-A administration. Our results suggest that phosphate restriction by restricting dietary protein promotes vascular calcification by lowering the systemic fetuin-A level and increasing serum calcium-phosphate precipitates and induces inflammation and malnutrition in uremic rats fed a high-phosphate diet.
Gender, exercise training, and eNOS expression in porcine skeletal muscle arteries
Authors: Laughlin M. Harold , Welshons Wade V. , Sturek Michael , Rush James W. E. , Turk James R. , Taylor Julia A. , Judy Barbara M. , Henderson Kyle K. , Ganjam V. K.
Published: July 2015

Our purpose was to determine the effects of gender and exercise training on endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) protein content of porcine skeletal muscle arteries and to evaluate the role of 17β-estradiol (E2) in these effects. We measured eNOS and SOD content with immunoblots and immunohistochemistry in femoral and brachial arteries of trained and sedentary male and female pigs and measured estrogen receptor (ER) mRNA and α-ER and β-ER protein in aortas of male and female pigs. Results indicate that female arteries contain more eNOS than male arteries and that exercise training increases eNOS content independent of gender. Male and female pigs expressed similar levels of α-ER mRNA and protein and similar amounts β-ER protein in their arteries. E2 concentrations as measured by RIA were 180 ± 34 pg/ml in male sera and ∼5 pg/ml in female sera, and neither was changed by training. However, bioassay indicated that biologically active estrogen equivalent to only 35 ± 5 pg/ml was present in male sera. E2 in female pigs, whether measured by RIA or bioassay, was ∼24 pg/ml at peak estrous and 2 pg/ml on day 5 diestrus. The free fraction of E2 in sera did not explain the low measurements, relative to RIA, of E2. We conclude that 1) gender has significant influence on eNOS and SOD content of porcine skeletal muscle arteries; 2) the effects of gender and exercise training vary among arteries of different anatomic origin; 3) male sera contains compounds that cause RIA to overestimate circulating estrogenic activity; and 4) relative to human men, the male pig is not biologically estrogenized by high levels of E2 reported by RIA, whereas in female pigs E2 levels are lower than in the blood of human women.
Hypotensive effect of push-pull gravitational stress occurs after autonomic blockade
Authors: Sheriff Don D.
Published: July 2015

The “push-pull” effect denotes the reduced tolerance to +Gz (hypergravity) when +Gz stress is preceded by exposure to hypogravity, i.e., fractional, zero, or negative Gz. Previous studies have implicated autonomic reflexes as a mechanism contributing to the push-pull effect. The purpose of this study was to test the hypothesis that nonautonomic mechanisms can cause a push-pull effect, by using eye-level blood pressure as a measure of G tolerance. The approach was to impose control (30 s of 30° head-up tilt) and push-pull (30 s of 30° head-up tilt immediately preceded by 10 s of -15° headdown tilt) gravitational stress after administration of hexamethonium (10 mg/kg) to inhibit autonomic ganglionic neurotransmission in four dogs. The animals were chronically instrumented with arterial and venous catheters, an ascending aortic blood flow transducer, ventricular pacing electrodes, and atrioventicular block. The animals were paced at 75 beats/min throughout the experiment. The animals were sedated with acepromazine and lightly restrained in lateral recumbency on a tilt table. After the onset of head-up tilt, the magnitude of the fall in eye-level blood pressure from baseline was -27.6 ± 2.3 and -37.9 ± 2.7 mmHg for the control and push-pull trials, respectively ( P < 0.05). Cardiac output fell similarly in both conditions. Thus a push-pull effect attributable to a rise in total vascular conductance occurs when autonomic function is inhibited.
The first three minutes: smooth muscle contraction, cytoskeletal events, and soft glasses
Authors: Gunst Susan J. , Fredberg Jeffrey J.
Published: July 2015

Smooth muscle exhibits biophysical characteristics and physiological behaviors that are not readily explained by present paradigms of cytoskeletal and cross-bridge mechanics. There is increasing evidence that contractile activation of the smooth muscle cell involves an array of cytoskeletal processes that extend beyond cross-bridge cycling and the sliding of thick and thin filaments. We review here the evidence suggesting that the biophysical and mechanical properties of the smooth muscle cell reflect the integrated interactions of an array of highly dynamic cytoskeletal processes that both react to and transform the dynamics of cross-bridge interactions over the course of the contraction cycle. The activation of the smooth muscle cell is proposed to trigger dynamic remodeling of the actin filament lattice within cellular microdomains in response to local mechanical and pharmacological events, enabling the cell to adapt to its external environment. As the contraction progresses, the cytoskeletal lattice stabilizes, solidifies, and forms a rigid structure well suited for transmission of tension generated by the interaction of myosin and actin. The integrated molecular transitions that occur within the contractile cycle are interpreted in the context of microscale agitation mechanisms and resulting remodeling events within the intracellular microenvironment. Such an interpretation suggests that the cytoskeleton may behave as a glassy substance whose mechanical function is governed by an effective temperature.
Bradykinin causes hypotension by activating pulmonary sympathetic afferents in the rabbit
Authors: Wang Y. , Soukhova G. , Proctor M. , Walker J. , Yu J.
Published: July 2015

Bradykinin (BK) activates sympathetic afferents in the heart, intestine, and kidney, and it alters hemodynamics. However, we know little about the influence of pulmonary sympathetic afferents on circulation. Activation of pulmonary afferents by directly injecting stimulants into the lung parenchyma permits examination of reflexes that originate in the lung without confounding effects from the systemic circulation. In the present study, we tested the hypothesis that pulmonary sympathetic afferents exert a significant influence on hemodynamics. We examined reflex effects of injecting BK (1 μg/kg in 0.1 ml) into the lung parenchyma on circulation in anesthetized, open-chest, artificially ventilated rabbits. BK significantly decreased mean arterial blood pressure (BP) (27 ± 3 mmHg) and heart rate (19 ± 4 beats/min). Both effects remained after bilateral vagotomy. To rule out possible direct systemic vasodilation by BK, we examined renal sympathetic nerve activity (RSNA) in response to BK injection and examined BP responses to injection of ACh (0.1 ml of 10-4 M). BK suppressed the RSNA before and after vagotomy. ACh did not change BP when injected into the lung parenchyma, but it decreased BP (31 ± 3 mmHg) when injected into the right atrium. Our data indicate that activating pulmonary sympathetic afferents reflexly suppresses hemodynamics.
Validation of the doubly labeled water method under low and high humidity to estimate metabolic rate and water flux in a tropical snake (Boiga irregularis)
Authors: Anderson Nancy L. , Hetherington Thomas E. , Williams Joseph B.
Published: July 2015

This study uses indirect calorimetry to assess the effects of humidity on the accuracy of the doubly labeled water (DLW) technique to predict metabolic rate and water flux in brown treesnakes ( Boiga irregularis). The DLW technique accurately predicted total water efflux in brown treesnakes under low-humidity conditions and found that the total number of water molecules exchanged with the environment under humid conditions was not significantly different than maximum net total evaporative water loss under low humidity conditions plus fecal water loss. Because of changes of total body water of >12%, the DLW technique overestimated metabolic rate by a factor of 2.2 under low-humidity conditions. Under high-humidity conditions, the DLW technique overestimated metabolic rate in brown treesnakes by a factor of 4.6. Researchers using the DLW technique in humid or moist environments should be cautious because this study indicates that DLW estimates of metabolic rate may be inflated when large amounts of water vapor are exchanged through the skin or respiratory passages.
Effects of aerobic training on heart rate dynamics in sedentary subjects
Authors: Tulppo Mikko P. , Hautala Arto J. , Mäkikallio Timo H. , Laukkanen Raija T. , Nissilä Seppo , Hughson Richard L. , Huikuri Heikki V.
Published: July 2015

This study was designed to assess the effects of moderate- and high-volume aerobic training on the time domain and on spectral and fractal heart rate (HR) variability indexes. Sedentary subjects were randomized into groups with moderate-volume training ( n = 20), high-volume training ( n = 20), and controls ( n = 15). The training period was 8 wk, including 6 sessions/wk at an intensity of 70–80% of the maximum HR, lasting for 30 min/session in the moderate-volume group and 60 min/session in the high-volume group. Time domain, frequency domain, and short-term fractal scaling measures of HR variability were analyzed over a 24-h period. Mean HR decreased from 70 ± 7 to 64 ± 8 beats/min and from 67 ± 5 to 60 ± 6 beats/min ( P < 0.001 for both) for the moderate- and high-volume training groups, respectively. The normalized high-frequency spectral component increased in both groups ( P < 0.05). The normalized low-frequency component decreased significantly ( P < 0.05), resulting in a marked decrease in low frequency-to-high frequency ratio in both groups. In addition, short-term scaling exponent decreased in both groups ( P < 0.001). There were no significant differences in the changes of HR variability indexes between groups. Aerobic training in sedentary subjects results in altered autonomic regulation of HR toward vagal dominance. A moderate training volume is a sufficient intervention to induce these beneficial effects.
Active upper airway closure during induced central apneas in lambs is complete at the laryngeal level only
Authors: Fortier Pierre-Hugues , Reix Philippe , Arsenault Julie , Dorion Dominique , Praud Jean-Paul
Published: July 2015

We tested the hypotheses that active upper airway closure during induced central apneas in nonsedated lambs 1) is complete and occurs at the laryngeal level and 2) is not due to stimulation of the superior laryngeal nerves (SLN). Five newborn lambs were surgically instrumented to record thyroarytenoid (TA) muscle (glottal constrictor) electromyographic (EMG) activity with supra- and subglottal pressures. Hypocapnic and nonhypocapnic central apneas were induced before and after SLN sectioning in the five lambs. A total of 174 apneas were induced, 116 before and 58 after sectioning of the internal branch of the SLN (iSLN). Continuous TA EMG activity was observed in 88% of apneas before iSLN section and in 87% of apneas after iSLN section. A transglottal pressure different from zero was observed in all apneas with TA EMG activity, with a mean subglottal pressure of 4.3 ± 0.8 cmH2O before and 4.7 ± 0.7 cmH2O after iSLN section. Supraglottal pressure was consistently atmospheric. Sectioning of both iSLNs had no effects on the results. We conclude that upper airway closure during induced central apneas in lambs is active, complete, and occurs at the glottal level only. Consequently, a positive subglottal pressure is maintained throughout the apnea. Finally, this complete active glottal closure is independent from laryngeal afferent innervation.
Interaction between muscle metaboreflex and mechanoreflex modulation of arterial baroreflex sensitivity in exercise
Authors: Carrington C. A. , Ubolsakka C. , White M. J.
Published: July 2015

The effect of external calf compression on baroreflex sensitivity (BRS) during electrically evoked plantar flexion and postexercise circulatory occlusion (PECO) was studied. Subjects took part in two experimental trials: control and compression. In both trials, electrically evoked isometric plantarflexion (Stim) was performed at 30% maximum voluntary contraction force for 2 min. During compression, a cuff (inflated to 250 mmHg) was applied to the active calf during exercise and PECO. Sequence analysis carried out on the systolic blood pressure responses, and R-wave-R-wave intervals revealed a rightward shift of the regression line along the pressure axis during Stim in both trials. In the control experiment, BRS was significantly ( P < 0.01) increased from 10.37 ± 1.87 ms/mmHg during Stim to 12.79 ± 1.62 ms/mmHg during PECO. With external compression, BRS was unaltered between Stim (10.84 ± 1.86 ms/mmHg) and PECO (11.40 ± 1.54 ms/mmHg). Because the metabolic conditions were the same in both experiments, the results may best be explained by reactivation of muscle mechanoreceptor activity by external compression during PECO.
Effect of voluntary facilitation on the diaphragmatic response to transcranial magnetic stimulation
Authors: Sharshar Tarek , Ross Ewen , Hopkinson Nicholas S. , Dayer Mark , Nickol Annabel , Lofaso Frédéric , Moxham John , Similowski Thomas , Polkey Michael I.
Published: July 2015

We assessed recruitment curves of the surface diaphragm motor-evoked potential (MEP) after transcranial magnetic stimulation during relaxation and at three different levels of facilitation (20, 40, and 60% of maximal inspiratory esophageal pressure) in 10 healthy subjects (six young and four elderly). MEP amplitude recruitment curves varied between individuals during relaxation and at each level of facilitation. Amplitude recruitment curves during relaxation were reproducible in individual subjects. Inspiratory maneuvers caused a decrease in motor threshold and latency and an increase in MEP amplitude, positively correlated to the intensity of facilitation. These changes were similar in young and elderly subjects. The best fit for MEP amplitude recruitment curves for each condition was obtained with a Boltzmann model. The performance of repeated submaximal inspiratory maneuvers did not affect the amplitude recruitment curves of the relaxed diaphragm. We conclude that the recruitment curve of the diaphragm with transcranial magnetic stimulation is repeatable and changes consistently with facilitation and will, therefore, be a robust experimental tool for the investigation of supraspinal pathways to the diaphragm.
Relationship between pulmonary O2 uptake kinetics and muscle deoxygenation during moderate-intensity exercise
Authors: DeLorey Darren S. , Kowalchuk John M. , Paterson Donald H.
Published: July 2015

The temporal relationship between the kinetics of phase 2 pulmonary O2 uptake (V̇o2p) and deoxygenation of the vastus lateralis muscle was examined during moderate-intensity leg-cycling exercise. Young adults (5 men, 6 women; 23 ± 3 yr; mean ± SD) performed repeated transitions on 3 separate days from 20 W to a constant work rate corresponding to 80% of lactate threshold. Breath-by-breath V̇o2p was measured by mass spectrometer and volume turbine. Deoxyhemoglobin (HHb), oxyhemoglobin, and total hemoglobin and myoglobin were sampled each second by near-infrared spectroscopy (Hamamatsu NIRO-300). V̇o2p data were filtered, interpolated to 1 s, and averaged to 5-s bins; HHb data were averaged to 5-s bins. Phase 2 V̇o2p data were fit with a monoexponential model. For HHb, a time delay (TDHHb) from exercise onset to an increase in HHb was determined, and thereafter data were fit with a monoexponential model. The time constant for V̇o2p (30 ± 8 s) was slower ( P < 0.01) than that for HHb (10 ± 3 s). The TDHHb before an increase in HHb was 13 ± 2 s. The possible mechanisms of the TDHHb are discussed with reference to metabolic activation and matching of local muscle O2 delivery and O2 utilization. After this initial TDHHb, the kinetics of local muscle deoxygenation were faster than those of phase 2 V̇o2p (and presumably muscle O2 consumption), reflecting increased O2 extraction and a mismatch between local muscle O2 consumption and perfusion.
Upright LBPP application attenuates elevated postexercise resting thresholds for cutaneous vasodilation and sweating
Authors: Jackson Dwayne N. , Kenny Glen P.
Published: July 2015

We evaluated postexercise venous pooling as a factor leading to previously reported increases in the postexercise esophageal temperature threshold for cutaneous vasodilation (ThVD) and sweating (ThSW). Six subjects were randomly exposed to lower body positive pressure (LBPP) and to no LBPP after an exercise and no-exercise treatment protocol. The exercise treatment consisted of 15 min of upright cycling at 65% of peak oxygen consumption, and the no-exercise treatment consisted of 15 min upright seated rest. Immediately after either treatment, subjects donned a liquid-conditioned suit used to regulate mean skin temperature and then were positioned within an upright LBPP chamber. The suit was first perfused with 20°C water to control and stabilize skin and core temperature before whole body heating. Subsequently the skin was heated (∼4.0°C/h) until cutaneous vasodilation and sweating occurred. Forearm skin blood flow and arterial blood pressure were measured noninvasively and were used to calculate cutaneous vascular conductance during whole body heating. Sweat rate response was estimated from a 5.0-cm2 ventilated capsule placed on the upper back. Postexercise ThVD and ThSW were both significantly elevated (0.27 ± 0.04°C and 0.25 ± 0.04°C, respectively) compared with the no-exercise trial without LBPP ( P < 0.05). However, the postexercise increases in both ThVD and ThSW were reversed with the application of LBPP. Our results support the hypothesis that the postexercise warm thermal responses of cutaneous vasodilation and sweating are attenuated by baroreceptor modulation via lower body venous pooling.
Effects of physical training on cortical bone at midtibia assessed by peripheral QCT
Authors: Liu LiJing , Maruno Ryouko , Mashimo Tomoko , Sanka Kazunori , Higuchi Tai , Hayashi Kazuhiko , Shirasaki Yoshio , Mukai Naoki , Saitoh Shinichi , Tokuyama Kumpei
Published: July 2015

Effects of long-term exercise on volumetric bone mineral density (vBMD), bone mineral content, bone geometric properties, and the strength indexes of bone were examined in a cross-sectional study of athletes and controls. Tibias of 25 jumpers (13 women), 30 swimmers (15 women), and 25 controls (15 women), aged 18–23 yr, were scanned at midsite by using peripheral quantitative computed tomography. The cortical vBMD of female athletes was lower than that of the controls (2.00 ± 0.05, 1.90 ± 0.08, and 1.92 ± 0.12 g/cm3, respectively, for controls, swimmers, and jumpers). On the other hand, periosteal areas of male jumpers and female athletes were greater than that of controls (460 ± 50, 483 ± 46, and 512 ± 55 mm2, respectively, for male controls, swimmers, and jumpers, and 283 ± 52, 341 ± 73, and 378 ± 75 mm2, respectively, for female controls, swimmers, and jumpers). The endocortical area of female swimmers was greater than that of controls (103 ± 29, 148 ± 52, and 135 ± 54 mm2, respectively, for controls, swimmers, and jumpers). The polar moment of inertia and strength strain index of male jumpers and female athletes were significantly greater than those of controls, except for the difference in strength strain index between male jumpers and controls. We conclude that the improvement of mechanical properties of young adult bone in response to long-term exercise is related to geometric adaptation and not to vBMD.
Adaptation to chronic length change in explanted airway smooth muscle
Authors: Naghshin Jahanbakhsh , Wang Lu , Paré Peter D. , Seow Chun Y.
Published: July 2015

It has been shown that airway smooth muscle in vitro is able to maintain active force over a large length range by adaptation in the absence of periodic stimulations at 4°C (Wang L, Paré PD, and Seow CY. J Appl Physiol 90: 734–740, 2001). In this study, we show that such adaptation also takes place at body temperature and that long-term adaptation results in irreversible functional change in the muscle that could lead to airway hyperresponsiveness. Rabbit tracheal muscle explants were passively maintained at shortened and in situ length for 3 and 7–8 days in culture media; the length-tension relationship was then examined. The length associated with maximal force generation decreased by 10.5 ± 3.8% (SE) after 3 days and 37.7 ± 8.5% after 7 or 8 days of passive shortening. At day 3, the left shift in the length-tension curve due to adaptation at short lengths was reversible by readapting the muscle at a longer length. The shift was, however, not completely reversible after 7 days. The results suggest that long-term adaptation of airway smooth muscle could lead to increased muscle stiffness and force-generating ability at short lengths. Under in vivo condition, this could translate into resistance to stretch-induced relaxation and excessive airway narrowing.
Hormone-sensitive lipase activity and fatty acyl-CoA content in human skeletal muscle during prolonged exercise
Authors: Watt Matthew J. , Heigenhauser George J. F. , O'Neill Marcus , Spriet Lawrence L.
Published: July 2015

Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of intramuscular triacylglycerols (IMTGs), but HSL regulation is poorly understood in skeletal muscle. The present study measured human skeletal muscle HSL activity at rest and during 120 min of cycling at 60% of peak O2uptake. Several putative HSL regulators were also measured, including muscle long-chain fatty acyl-CoA (LCFA CoA) and free AMP contents and plasma epinephrine and insulin concentrations. HSL activity increased from resting levels by 10 min of exercise (from 2.09 ± 0.19 to 2.56 ± 0.22 mmol · min-1· kg dry mass-1, P < 0.05), increased further by 60 min (to 3.12 ± 0.27 mmol · min-1· kg dry mass-1, P < 0.05), and decreased to near-resting rates after 120 min of cycling. Skeletal muscle LCFA CoA increased ( P < 0.05) above rest by 60 min (from 15.9 ± 3.0 to 50.4 ± 7.9 μmol/kg dry mass) and increased further by 120 min. Estimated free AMP increased ( P < 0.05) from rest to 60 min and was ∼20-fold greater than that at rest by 120 min. Epinephrine was increased above rest ( P < 0.05) at 60 (1.47 ± 0.15 nM) and 120 min (4.87 ± 0.76 nM) of exercise. Insulin concentrations decreased rapidly and were lower than resting levels by 10 min and continued to decrease throughout exercise. In summary, HSL activity was increased from resting levels by 10 min, increased further by 60 min, and decreased to near-resting values by 120 min. The increased HSL activity at 60 min was associated with the stimulating effect of increased epinephrine and decreased insulin levels. After 120 min, the decreased HSL activity was associated with the proposed inhibitory effects of increased free AMP. The accumulation of LCFA CoA in the 2nd h of exercise may also have reduced the flux through HSL and accounted for the reduction in IMTG utilization previously observed late in prolonged exercise.
Heat balance precedes stabilization of body temperatures during cold water immersion
Authors: Tikuisis Peter
Published: July 2015

Certain previous studies suggest, as hypothesized herein, that heat balance (i.e., when heat loss is matched by heat production) is attained before stabilization of body temperatures during cold exposure. This phenomenon is explained through a theoretical analysis of heat distribution in the body applied to an experiment involving cold water immersion. Six healthy and fit men (mean ± SD of age = 37.5 ± 6.5 yr, height = 1.79 ± 0.07 m, mass = 81.8 ± 9.5 kg, body fat = 17.3 ± 4.2%, maximal O2 uptake = 46.9 ± 5.5 l/min) were immersed in water ranging from 16.4 to 24.1°C for up to 10 h. Core temperature (Tco) underwent an insignificant transient rise during the first hour of immersion, then declined steadily for several hours, although no subject's Tco reached 35°C. Despite the continued decrease in Tco, shivering had reached a steady state of ∼2 × resting metabolism. Heat debt peaked at 932 ± 334 kJ after 2 h of immersion, indicating the attainment of heat balance, but unexpectedly proceeded to decline at ∼48 kJ/h, indicating a recovery of mean body temperature. These observations were rationalized by introducing a third compartment of the body, comprising fat, connective tissue, muscle, and bone, between the core (viscera and vessels) and skin. Temperature change in this “mid region” can account for the incongruity between the body's heat debt and the changes in only the core and skin temperatures. The mid region temperature decreased by 3.7 ± 1.1°C at maximal heat debt and increased slowly thereafter. The reversal in heat debt might help explain why shivering drive failed to respond to a continued decrease in Tco, as shivering drive might be modulated by changes in body heat content.
Negative hemodynamic response in the cortex: evidence opposing neuronal deactivation revealed via optical imaging and electrophysiological recording
Authors: Hu Dewen , Huang Liangming
Published: July 2015

Functional brain imaging techniques depend on the relationship between regional hemodynamic responses and neural activity. The positive hemodynamic response (PHR) has widely been discussed and has generally been associated with an increase in neuronal signals. In contrast, the negative hemodynamic response (NHR) has not been investigated extensively, and its underlying nature is highly controversial. In the present study, we employed an optical imaging (OI) technique and microelectrode array (MEA) recordings in the rat cortex to examine the NHR to hindlimb electrical stimulation; we primarily focused on the NHR adjacent to a PHR region. We determined that the dynamics of the total blood volume signal in the NHR regions lagged slightly behind those in the PHR areas. Additionally, the deoxyhemoglobin signal in the PHR areas increased immediately after stimulation and the deoxyhemoglobin signal in the NHR regions remained unchanged or increased. Consistent with the change in the deoxyhemoglobin signal, the MEA recordings demonstrated that neural activity in the PHR regions was elevated and that activity in the NHR areas was unchanged or increased during stimulation, implying that the NHR occurred in the absence of neural deactivation. These results suggest that the NHR may be explained by purely hemodynamic contributions, specifically “blood stealing” or increased neural activity, and indicate that caution should be exercised when interpreting the NHR as a decrease in neural activity, especially when the NHR is adjacent to a PHR.
Corticosterone mediates the synaptic and behavioral effects of chronic stress at rat hippocampal temporoammonic synapses
Authors: Kvarta Mark D. , Bradbrook Keighly E. , Dantrassy Hannah M. , Bailey Aileen M. , Thompson Scott M.
Published: July 2015

Chronic stress is thought to impart risk for depression via alterations in brain structure and function, but contributions of specific mediators in generating these changes remain unclear. We test the hypothesis that stress-induced increases in corticosterone (CORT), the primary rodent glucocorticoid, are the key mediator of stress-induced depressive-like behavioral changes and synaptic dysfunction in the rat hippocampus. In rats, we correlated changes in cognitive and affective behavioral tasks (spatial memory consolidation, anhedonia, and neohypophagia) with impaired excitatory strength at temporoammonic-CA1 (TA-CA1) synapses, an archetypical stress-sensitive excitatory synapse. We tested whether elevated CORT was sufficient and necessary to generate a depressive-like behavioral phenotype and decreased excitatory signaling observed at TA-CA1 after chronic unpredictable stress (CUS). Chronic CORT administration induced an anhedonia-like behavioral state and neohypophagic behavior. Like CUS, chronic, but not acute, CORT generated an impaired synaptic phenotype characterized by reduced α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-preferring glutamate receptor-mediated excitation at TA-CA1 synapses, decreased AMPA-type glutamate receptor subunit 1 protein expression, and altered serotonin-1B receptor-mediated potentiation. Repeatedly blunting stress-induced increases of CORT during CUS with the CORT synthesis inhibitor metyrapone (MET) prevented these stress-induced neurobehavioral changes. MET also prevented the CUS-induced impairment of spatial memory consolidation. We conclude that corticosterone is sufficient and necessary to mediate glutamatergic dysfunction underlying stress-induced synaptic and behavioral phenotypes. Our results indicate that chronic excessive glucocorticoids cause specific synaptic deficits in the hippocampus, a major center for cognitive and emotional processing, that accompany stress-induced behavioral dysfunction. Maintaining excitatory strength at stress-sensitive synapses at key loci throughout corticomesolimbic reward circuitry appears critical for maintaining normal cognitive and emotional behavior.
Responses of the mammary transcriptome of dairy cows to altered photoperiod during late gestation
Authors: Bentley P. A. , Wall E. H. , Dahl G. E. , McFadden T. B.
Published: July 2015

Cows exposed to short day photoperiod (SD, 8L:16D) during the 60-day nonlactating period prior to parturition produce more milk in their subsequent lactation compared with cows exposed to long day photoperiod (LD, 16L:8D). Although this response is well established in dairy cows, the underlying mechanisms are not understood. We hypothesized that differential gene expression in cows exposed to SD or LD photoperiods during the dry period could be used to identify the functional basis for the subsequent increase in milk production during lactation. Pregnant, multiparous cows were maintained on an SD or LD photoperiod for 60 days prior to parturition. Mammary biopsies were obtained on days −24 and −9 relative to parturition and Affymetrix GeneChip Bovine Genome Arrays were used to quantify gene expression. Sixty-four genes were differentially expressed ( P ≤ 0.05 and fold-change ≥ |1.5|) between SD and LD treatments. Many of these genes were associated with cell growth and proliferation, or immune function. Ingenuity Pathway Analysis predicted upstream regulators to include TNF, TGF-β1, interferon-γ, and several interleukins. In addition, expression of 125 genes was significantly different between day −24 and day −9; those genes were associated with milk component metabolism and immune function. The interaction of photoperiod and time affected 32 genes associated with insulin-like growth factor I signaling. Genes differentially expressed in response to photoperiod were associated with mammary development and immune function consistent with the enhancement of milk yield in the ensuing lactation. Our results provide insight into the mechanisms by which photoperiod affects the mammary gland and subsequently lactation.
Polarized Calcium and Calmodulin Signaling in Secretory Epithelia
Authors: Ashby Michael C. , Tepikin Alexei V.
Published: July 2015

This review examines polarized calcium and calmodulin signaling in exocrine epithelial cells. The calcium ion is a simple, evolutionarily ancient, and universal second messenger. In exocrine epithelial cells, it regulates essential functions such as exocytosis, fluid secretion, and gene expression. Exocrine cells are structurally polarized, with the apical region usually dedicated to secretion. Recent advances in technology, in particular the development of videoimaging and confocal microscopy, have led to the discovery of polarized, subcellular calcium signals in these cell types. The properties of a rich variety of local and global calcium signals have now been described in secretory epithelial cells. Secretagogues stimulate apical-to-basal waves of calcium in many exocrine cell types, but there are some interesting exceptions to this rule. The shapes of intracellular calcium signals are determined by the distribution of calcium-releasing channels and mechanisms that limit calcium elevation. Polarized distribution of calcium-handling mechanisms also leads to transcellular calcium transport in exocrine epithelial cells. This transport can deliver considerable amounts of calcium into secreted fluids. Multicellular polarized calcium signals can coordinate the activity of many individual cells in epithelial secretory tissue. Certain particularly sensitive cells serve as pacemakers for initiation of intercellular calcium waves. Many calcium signaling pathways involve activation of calmodulin. This ubiquitous protein regulates secretion in exocrine cells and also activates interesting feedback interactions with calcium channels and transporters. Very recently it became possible to directly study polarized calcium-calmodulin reactions and to visualize the process of hormone-induced redistribution of calmodulin in live cells. The structural and functional polarity of secretory epithelia alongside the polarity of its calcium and calmodulin signaling present an interesting lesson in tissue organization.