bluuebunny/crossref_metadata_2025 huggingface dataset:
ON THE SHAPE OF RISK AVERSION AND ASSET ALLOCATION
Authors: SIX PIERRE
Published: December 2014

This paper demonstrates the simple incorporation of any shape of risk aversion into an asset allocation framework. Indeed, the relevant literature about risk aversion shows mixed evidence regarding the shape of this important but subjective variable. Our setting builds on, and can be compared with, the well-known constant relative risk aversion (CRRA) framework and mostly preserves the tractability of the affine-CRRA framework. Our numerical analysis exhibits some link between measures of risk aversions and empirical studies of asset allocation.
ON THE CREDIT RISK OF SECURED LOANS WITH MAXIMUM LOAN-TO-VALUE COVENANTS
Authors: Astic Fabian , Tourin Agnès
Published: December 2014

We propose a framework for analyzing the credit risk of secured loans with maximum loan-to-value covenants. Here, we do not assume that the collateral can be liquidated as soon as the maximum loan-to-value is breached. Closed-form solutions for the expected loss are obtained for nonrevolving loans. In the revolving case, we introduce a minimization problem with an objective function parameterized by a risk reluctance coefficient, capturing the trade-off between minimizing the expected loss incurred in the event of liquidation and maximizing the interest gain. Using stochastic control techniques, we derive the partial integro-differential equation satisfied by the value function, and solve it numerically with a finite difference scheme. The experimental results and their comparison with a standard loan-to-value-based lending policy suggest that stricter lending decisions would benefit the lender.
Investigation of Damages in RC Frames Under Near Field Earthquakes Using a Damage Index
Authors: Yazdi Seyed Morteza Zinati , Kazemi Mohammad Taghi
Published: December 2014

Heavy damages on structures caused by near field earthquakes in recent years has brought serious attention to this problem. An examination of previous records has shown significant differences for near field earthquakes, including a large energy pulse, unlike far field earthquakes. But as a general rule, the effects of near field earthquakes have been ignored in most building codes. The purpose of this paper is to investigate the effect of near field earthquakes on reinforced concrete (RC) moment frames. To achieve this goal, the Erduran damage index, an efficient way to calculate damage, was employed to analyze two 4- and 8-story RC moment frame buildings. The buildings with moderate and high ductility were designed by the strength criteria. Seven pairs of near field and far field earthquakes were scaled and used for dynamic nonlinear time history analysis. Using Erduran’s beam and column damage index, respectively, based on rotation and drift, the results from both near and far field earthquakes were compared. Moreover, for better assessment, 4-story buildings were evaluated from the performance based viewpoint of design. We observe from the results that most of the components of the structures under near field earthquakes sustained severe damages and in some cases even component failure. Components of the structures under near field earthquakes suffered from 30% more of damage, on average, than that under far field earthquakes.
Performance of Double-Angle Bolted Steel I-Beam to Hollow Square Column Connections Under Static and Cyclic Loadings
Authors: Song Qian-Yi , Heidarpour Amin , Zhao Xiao-Ling , Han Lin-Hai
Published: December 2014

Earthquake causes severe damage to buildings and infrastructure, due to not only the ground motion but also secondary actions, such as impact, blast and fire which would occur after an earthquake. In order to investigate the post-earthquake loading scenarios, it is important to assess the partial damage of structures caused by earthquake. This paper presents the behavior of double-angle bolted steel I-beam to hollow square tubular column connections under static and cyclic loading. A detailed experimental study is presented in which two groups of bolted steel connections with different column wall thickness are considered. The flexibility and strength of the connections are measured, while the damage phenomena and failure modes are explored in the tests. The connection damage under cyclic loading is found to be an accumulative developing process of fracture which leads to significant gradual degradation of the mechanical properties of the connections. Quantitative evaluations of the cyclic loading induced damage are carried out to investigate the damage level of connections according to different loading scenarios. The test results herein provide a detailed understanding of the behavior of the double-angle bolted connections under seismic loading, which would be useful for further investigations under post-earthquake actions.
A Hybrid Scheme of Synthesized Sliding Mode/Strain Rate Feedback Control Design for Flexible Spacecraft Attitude Maneuver Using Time Scale Decomposition
Authors: Shahravi Morteza , Azimi Milad
Published: December 2014

Presented herein is a new control approach for large angle attitude maneuver of flexible spacecraft. The singular perturbation theory (SPT) provides a useful tool for two time rate scale separation (mapping) of rigid and flexible body dynamics. The resulting slow and fast subsystems, enabling the use of two control approach for attitude (Modified Sliding Mode) and vibration Strain Rate Feedback (SRF) control of flexible spacecraft, respectively. An attractive feature of the present control approach is that the global stability of the entire system has been guaranteed while the controllers accomplished their tasks in coupled rigid/flexible dynamic domain without parasitic parameter interactions. Numerical simulations show the effectiveness of the present approach.
Corotational Formulation for Geometric Nonlinear Analysis of Shell Structures by ANDES Elements
Authors: Zhou Yi , Li Yuan-Qi , Shen Zu-Yan , Zhang Ying-Ying
Published: December 2014

The corotational (CR) kinematic description was a recent method for formulation of geometric nonlinear structural problems. Based on the consistent symmetrizable equilibrated (CSE) CR formulation, a linear triangular flat shell element with three translational and three rotational degrees of freedom (DOFs) at each of the three nodes was derived by the assumed natural deviatoric strain (ANDES) formulation, which can be used to the geometric nonlinear analysis of shell structures with large rotations and small strains. By taking variations of the internal energy with respect to nodal freedoms, the equations for the CR nonlinear finite element, including the tangent stiffness matrix and the internal force vector in the global coordinate system, were derived. The nonlinear equations were solved by using the generalized displacement control (GDC) method. It was shown through numerical examples that combing CR formulation and ANDES elements can accurately solve complex geometric nonlinear problems with large body motions. As revealed by the efficiency and reliability of the ANDES elements in tracing the nonlinear structural load–deflection response, it is demonstrated that some membrane elements and plate elements give better performance in the geometric nonlinear analysis of shell structures.
Macrocyclic dipyrrin dimer bridged by ethylene and dioxyphenylene linkers
Authors: Shin Ji-Young , Hiroto Satoru , Shinokubo Hiroshi
Published: December 2014

A tetrapyrrolic macrocycle containing ethenylene and dioxyphenylene bridges was obtained through the reaction of a dipyrrin-DDQ adduct with triethylamine. The structure of the macrocycle was elucidated by X-ray diffraction analysis. The macrocycle exhibited solvent-dependent absorption spectra due to intramolecular charge transfer interactions.
Preparation and characterization of a tungsten(V) corrole dichloride complex
Authors: Padilla Rosa , Buckley Heather L. , Ward Ashleigh L. , Arnold John
Published: December 2014

The first example of a tungsten(V) corrole complex, ( Mes 2(p- OMePh ) corrole ) WCl 2, has been prepared through a metathesis reaction of a lithium corrole ( Mes 2(p- OMePh ) corrole ) Li 3 ⋅ 6 THF and WCl 6. The product constitutes the first example of a tungsten(V) corrole complex synthesized under mild conditions and only the second example of a tungsten corrole complex.
APPLICATION OF COMPUTATIONAL INTELLIGENCE METHOD IN PETROLEUM GEOMECHANICS CHARACTERIZATION
Authors: ZHANG SHIKE , YUAN YUAN , XIAO JIANQING , YIN SHUNDE
Published: December 2014

Petroleum geomechanics characterization refers to the process of quantitatively assigning geomechanical parameters using all available field data. In this paper, an attempt is made to develop a computational intelligence method that integrates genetic algorithm (GA) and artificial neural network (ANN). Through this method, these geomechanical parameters such as horizontal in situ stresses, fracture aperture and joint spacing are determined based on the borehole displacements during drilling well. In the hybrid ANN–GA model, GA can automatically identify geomechanical parameters as neural inputs from monitored borehole displacements, and the ANN is trained to learn the complex relationship between geomechanical parameters and target borehole displacements. Data from numerical experiments on petroleum wells are used in verification of the proposed computational intelligence method for geomechanics characterization. The study of numerical experiment illustrates that the proposed computational intelligence method has the ability to generate reliable results.
Inhibitory motor neurons of the esophageal myenteric plexus are mechanosensitive
Authors: Dong Hui , Jiang Yanfen , Dong Jane , Mittal Ravinder K.
Published: December 2014

Mechanosensitivity of enteric neurons has been reported in the small intestine and colon, but not in the esophagus. Our earlier in vivo studies show that mechanical stretch of the esophagus in the axial direction induces neurally mediated relaxation of the lower esophageal sphincter, possibly through mechanosensitive motor neurons. However, this novel notion that the motor neurons are mechanosensitive has not been examined in isolated esophageal myenteric motor neurons. The goal of our present study was to examine the mechanosensitivity of esophageal motor neurons in primary culture and elucidate the underlying molecular mechanisms. Immmunocytochemical analysis revealed that >95% cells were positive for the neuronal marker protein gene product 9.5 and that 66% of these cells costained with protein gene product 9.5 and neuronal nitric oxide (NO) synthase. Hypotonic solution induced an increase in the cytoplasm volume in all cells that was independent of extracellular Ca2+. Hypotonic solution and mechanical stretch induced cytoplasmic free Ca2+ signaling in ∼65% of neurons in the presence, but not absence, of extracellular Ca2+. Neurons grown on the elastic membrane responded to mechanical stretch by an increase in neuronal size and Ca2+ signaling simultaneously. Hypotonic stretch-induced cytoplasmic free Ca2+ signaling was not affected by extracellular Mg2+, 5-nitro-2-(3-phenylpropylamino)benzoic acid, and nifedipine but was attenuated by 2-aminoethoxydiphenyl borate, Gd3+, and Grammostola mechanotoxin 4, blockers of the stretch-activated ion channels. In ∼57% of the neurons, hypotonic stretch also induced Ca2+-dependent cytoplasmic NO production, which was abolished by Grammostola mechanotoxin 4. These results prove that the esophageal inhibitory motor neurons possess a mechanosensitive property and also provide novel insights into the stretch-activated ion channel-Ca2+-NO signaling pathway in these neurons.
Characterization of slow waves generated by myenteric interstitial cells of Cajal of the rabbit small intestine
Authors: Kito Yoshihiko , Mitsui Retsu , Ward Sean M. , Sanders Kenton M.
Published: December 2014

Slow waves (slow wavesICC) were recorded from myenteric interstitial cells of Cajal (ICC-MY) in situ in the rabbit small intestine, and their properties were compared with those of mouse small intestine. Rabbit slow wavesICCconsisted of an upstroke depolarization followed by a distinct plateau component. Ni2+and nominally Ca2+-free solutions reduced the rate-of-rise and amplitude of the upstroke depolarization. Replacement of Ca2+with Sr2+enhanced the upstroke component but decreased the plateau component of rabbit slow wavesICC. In contrast, replacing Ca2+with Sr2+decreased both components of mouse slow wavesICC. The plateau component of rabbit slow wavesICCwas inhibited in low-extracellular-Cl−-concentration (low-[Cl−]o) solutions and by 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS), an inhibitor of Cl−channels, cyclopiazonic acid (CPA), an inhibitor of internal Ca2+pumps, or bumetanide, an inhibitor of Na+-K+-2Cl−cotransporter (NKCC1). Bumetanide also inhibited the plateau component of mouse slow wavesICC. NKCC1-like immunoreactivity was observed mainly in ICC-MY in the rabbit small intestine. Membrane depolarization with a high-K+solution reduced the upstroke component of rabbit slow wavesICC. In cells depolarized with elevated external K+, DIDS, CPA, and bumetanide blocked slow wavesICC. These results suggest that the upstroke component of rabbit slow wavesICCis partially mediated by voltage-dependent Ca2+influx, whereas the plateau component is dependent on Ca2+-activated Cl−efflux. NKCC1 is likely to be responsible for Cl−accumulation in ICC-MY. The results also suggest that the mechanism of the upstroke component differs in rabbit and mouse slow wavesICCin the small intestine.
The gastrointestinal microbiota and colorectal cancer
Authors: Keku Temitope O. , Dulal Santosh , Deveaux April , Jovov Biljana , Han Xuesong
Published: December 2014

The human gut is home to a complex and diverse microbiota that contributes to the overall homeostasis of the host. Increasingly, the intestinal microbiota is recognized as an important player in human illness such as colorectal cancer (CRC), inflammatory bowel diseases, and obesity. CRC in itself is one of the major causes of cancer mortality in the Western world. The mechanisms by which bacteria contribute to CRC are complex and not fully understood, but increasing evidence suggests a link between the intestinal microbiota and CRC as well as diet and inflammation, which are believed to play a role in carcinogenesis. It is thought that the gut microbiota interact with dietary factors to promote chronic inflammation and CRC through direct influence on host cell physiology, cellular homeostasis, energy regulation, and/or metabolism of xenobiotics. This review provides an overview on the role of commensal gut microbiota in the development of human CRC and explores its association with diet and inflammation.
Humans are more sensitive to the taste of linoleic and α-linolenic than oleic acid
Authors: Running Cordelia A. , Mattes Richard D.
Published: December 2014

Health concerns have led to recommendations to replace saturated fats with unsaturated fats. However, addition of unsaturated fatty acids may lead to changes in the way foods are perceived in the oral cavity. This study tested the taste sensitivity to and emulsion characteristics of oleic, linoleic, and α-linolenic acids. The hypothesis tested was that oral sensitivity to nonesterified fatty acids would increase with degree of unsaturation but that in vitro viscosities and particle sizes of these emulsions would not differ. Oral taste thresholds were obtained using the three-alternative, forced-choice, ascending method. Each participant was tested on each fat 7 times, for a total of 21 study visits, to account for learning effects. Viscosities were obtained for the blank solutions and all three emulsions. Results indicate lower oral thresholds to linoleic and α-linolenic than oleic acid. At higher shear rates, 5% oleic and linoleic acid were more viscous than other samples. More-dilute emulsions showed no significant differences in viscosity. Particle sizes of the emulsions increased very slightly with increasing unsaturation. Together, the emulsion characteristics and oral sensitivity data support a taste mechanism for nonesterified fatty acid detection.
Angiotensin II type 1a receptors in subfornical organ contribute towards chronic intermittent hypoxia-associated sustained increase in mean arterial pressure
Authors: Saxena Ashwini , Little Joel T. , Nedungadi T. Prashant , Cunningham J. Thomas
Published: December 2014

Sleep apnea is associated with hypertension. The mechanisms contributing to a sustained increase in mean arterial pressure (MAP) even during normoxic awake-state remain unknown. Rats exposed to chronic intermittent hypoxia for 7 days, a model of the hypoxemia associated with sleep apnea, exhibit sustained increases in MAP even during the normoxic dark phase. Activation of the renin-angiotensin system (RAS) has been implicated in chronic intermittent hypoxia (CIH) hypertension. Since the subfornical organ (SFO) serves as a primary target for the central actions of circulating ANG II, we tested the effects of ANG II type 1a receptor (AT1aR) knockdown in the SFO on the sustained increase in MAP in this CIH model. Adeno-associated virus carrying green fluorescent protein (GFP) and small-hairpin RNA against either AT1aR or a scrambled control sequence (SCM) was stereotaxically injected in the SFO of rats. After recovery, MAP, heart rate, respiratory rate, and activity were continuously recorded using radiotelemetry. In the normoxic groups, the recorded variables did not deviate from the baseline values. Both CIH groups exhibited significant increases in MAP during CIH exposures ( P < 0.05). During the normoxic dark phase in the CIH groups, only the SCM-injected group exhibited a sustained increase in MAP ( P < 0.05). The AT1aR-CIH group showed significant decreases in FosB/ΔFosB staining in the median preoptic nucleus and the paraventricular nuclei of the hypothalamus compared with the SCM-CIH group. Our data indicate that AT1aRs in the SFO are critical for the sustained elevation in MAP and increased FosB/ΔFosB expression in forebrain autonomic nuclei associated with CIH.
Macitentan reverses early obstructive pulmonary vasculopathy in rats: early intervention in overcoming the survivin-mediated resistance to apoptosis
Authors: Shinohara Tsutomu , Sawada Hirofumi , Otsuki Shoichiro , Yodoya Noriko , Kato Taichi , Ohashi Hiroyuki , Zhang Erquan , Saitoh Shinji , Shimpo Hideto , Maruyama Kazuo , Komada Yoshihiro , Mitani Yoshihide
Published: December 2014

It remains unknown whether current disease-targeting therapy can histologically reverse obstructive pulmonary vasculopathy and how the timing of the therapy influences the antiremodeling effects of the compound. We test the hypothesis that a novel endothelin receptor antagonist macitentan reverses the early and/or late stages of occlusive pulmonary vascular disease (PVD) in rats. Rats with pulmonary arterial hypertension (PAH), which were produced by combined exposure to a vascular endothelial growth factor receptor inhibitor Sugen 5416 and hypobaric hypoxia for 3 wk, were assigned to receive macitentan or vehicle during 3–5 wk (early study) or during 5–8 wk (late study) after Sugen injection. Compared with vehicle-treated PAH rats and PAH rats evaluated before treatment initiation, the macitentan-treated rats showed decreases in the proportion of occlusive lesions in the early study, a finding consistent with the reversal of right ventricular systolic pressure and indexes of right ventricular hypertrophy and medial wall thickness. Macitentan ameliorated but did not reverse the proportion of occlusive lesions in the late study. Although macitentan decreased the proportion of Ki67+ lesions in both studies, macitentan increased the proportion of cleaved caspase 3+ lesions and suppressed an antiapoptotic molecule survivin expression in the early study but not in the late study. In conclusion, macitentan reversed early but not late obstructive PVD in rats. This reversal was associated with the suppression of survivin-related resistance to apoptosis and proliferation of cells in PVD.
Asef mediates HGF protective effects against LPS-induced lung injury and endothelial barrier dysfunction
Authors: Meng Fanyong , Meliton Angelo , Moldobaeva Nurgul , Mutlu Gokhan , Kawasaki Yoshihiro , Akiyama Tetsu , Birukova Anna A.
Published: December 2014

Increased vascular endothelial permeability and inflammation are major pathological mechanisms of pulmonary edema and its life-threatening complication, the acute respiratory distress syndrome (ARDS). We have previously described potent protective effects of hepatocyte growth factor (HGF) against thrombin-induced hyperpermeability and identified the Rac pathway as a key mechanism of HGF-mediated endothelial barrier protection. However, anti-inflammatory effects of HGF are less understood. This study examined effects of HGF on the pulmonary endothelial cell (EC) inflammatory activation and barrier dysfunction caused by the gram-negative bacterial pathogen lipopolysaccharide (LPS). We tested involvement of the novel Rac-specific guanine nucleotide exchange factor Asef in the HGF anti-inflammatory effects. HGF protected the pulmonary EC monolayer against LPS-induced hyperpermeability, disruption of monolayer integrity, activation of NF-kB signaling, expression of adhesion molecules intercellular adhesion molecule-1 and vascular cell adhesion molecule-1, and production of IL-8. These effects were critically dependent on Asef. Small-interfering RNA-induced downregulation of Asef attenuated HGF protective effects against LPS-induced EC barrier failure. Protective effects of HGF against LPS-induced lung inflammation and vascular leak were also diminished in Asef knockout mice. Taken together, these results demonstrate potent anti-inflammatory effects by HGF and delineate a key role of Asef in the mediation of the HGF barrier protective and anti-inflammatory effects. Modulation of Asef activity may have important implications in therapeutic strategies aimed at the treatment of sepsis and acute lung injury/ARDS-induced gram-negative bacterial pathogens.
Lung matrix and vascular remodeling in mechanically ventilated elastin haploinsufficient newborn mice
Authors: Hilgendorff Anne , Parai Kakoli , Ertsey Robert , Navarro Edwin , Jain Noopur , Carandang Francis , Peterson Joanna , Mokres Lucia , Milla Carlos , Preuss Stefanie , Alcazar Miguel Alejandre , Khan Suleman , Masumi Juliet , Ferreira-Tojais Nancy , Mujahid Sana , Starcher Barry , Rabinovitch Marlene , Bland Richard
Published: December 2014

Elastin plays a pivotal role in lung development. We therefore queried if elastin haploinsufficient newborn mice ( Eln+/−) would exhibit abnormal lung structure and function related to modified extracellular matrix (ECM) composition. Because mechanical ventilation (MV) has been linked to dysregulated elastic fiber formation in the newborn lung, we also asked if elastin haploinsufficiency would accentuate lung growth arrest seen after prolonged MV of neonatal mice. We studied 5-day-old wild-type ( Eln+/+) and Eln+/− littermates at baseline and after MV with air for 8–24 h. Lungs of unventilated Eln+/− mice contained ∼50% less elastin and ∼100% more collagen-1 and lysyl oxidase compared with Eln+/+ pups. Eln+/− lungs contained fewer capillaries than Eln+/+ lungs, without discernible differences in alveolar structure. In response to MV, lung tropoelastin and elastase activity increased in Eln+/+ neonates, whereas tropoelastin decreased and elastase activity was unchanged in Eln+/− mice. Fibrillin-1 protein increased in lungs of both groups during MV, more in Eln+/− than in Eln+/+ pups. In both groups, MV caused capillary loss, with larger and fewer alveoli compared with unventilated controls. Respiratory system elastance, which was less in unventilated Eln+/− compared with Eln+/+ mice, was similar in both groups after MV. These results suggest that elastin haploinsufficiency adversely impacts pulmonary angiogenesis and that MV dysregulates elastic fiber integrity, with further loss of lung capillaries, lung growth arrest, and impaired respiratory function in both Eln+/+ and Eln+/− mice. Paucity of lung capillaries in Eln+/− newborns might help explain subsequent development of pulmonary hypertension previously reported in adult Eln+/− mice.
Impaired myogenic response and autoregulation of cerebral blood flow is rescued in CYP4A1 transgenic Dahl salt-sensitive rat
Authors: Fan Fan , Geurts Aron M. , Murphy Sydney R. , Pabbidi Mallikarjuna R. , Jacob Howard J. , Roman Richard J.
Published: December 2014

We have reported that a reduction in renal production of 20-HETE contributes to development of hypertension in Dahl salt-sensitive (SS) rats. The present study examined whether 20-HETE production is also reduced in the cerebral vasculature of SS rats and whether this impairs the myogenic response and autoregulation of cerebral blood flow (CBF). The production of 20-HETE, the myogenic response of middle cerebral arteries (MCA), and autoregulation of CBF were compared in SS, SS-5BNrats and a newly generated CYP4A1 transgenic rat. 20-HETE production was 6-fold higher in cerebral arteries of CYP4A1 and SS-5BNthan in SS rats. The diameter of the MCA decreased to 70 ± 3% to 65 ± 6% in CYP4A1 and SS-5BNrats when pressure was increased from 40 to 140 mmHg. In contrast, the myogenic response of MCA isolated from SS rats did not constrict. Administration of a 20-HETE synthesis inhibitor, HET0016, abolished the myogenic response of MCA in CYP4A1 and SS-5BNrats but had no effect in SS rats. Autoregulation of CBF was impaired in SS rats compared with CYP4A1 and SS-5BNrats. Blood-brain barrier leakage was 5-fold higher in the brain of SS rats than in SS-5BNand SS.CYP4A1 rats. These findings indicate that a genetic deficiency in the formation of 20-HETE contributes to an impaired myogenic response in MCA and autoregulation of CBF in SS rats and this may contribute to vascular remodeling and cerebral injury following the onset of hypertension.
Effect of bariatric surgery combined with medical therapy versus intensive medical therapy or calorie restriction and weight loss on glycemic control in Zucker diabetic fatty rats
Authors: Abegg Kathrin , Corteville Caroline , Docherty Neil G. , Boza Camilo , Lutz Thomas A. , Muñoz Rodrigo , le Roux Carel W.
Published: December 2014

Bariatric surgery rapidly improves Type 2 diabetes mellitus (T2DM). Our objective was to profile and compare the extent and duration of improved glycemic control following Roux-en-Y gastric (RYGB) bypass surgery and vertical sleeve gastrectomy (SG) and compare against calorie restriction/weight loss and medical combination therapy-based approaches using the Zucker diabetic fatty rat (ZDF) rodent model of advanced T2DM. Male ZDF rats underwent RYGB ( n = 15) or SG surgery ( n = 10) at 18 wk of age and received postsurgical insulin treatment, as required to maintain mid-light-phase glycemia within a predefined range (10–15 mmol/l). In parallel, other groups of animals underwent sham surgery with ad libitum feeding ( n = 6), with body weight ( n = 8), or glycemic matching ( n = 8) to the RYGB group, using food restriction or a combination of insulin, metformin, and liraglutide, respectively. Both bariatric procedures decreased the daily insulin dose required to maintain mid-light-phase blood glucose levels below 15 mmol/l, compared with those required by body weight or glycemia-matched rats ( P < 0.001). No difference was noted between RYGB and SG with regard to initial efficacy. SG was, however, associated with higher food intake, weight regain, and higher insulin requirements vs. RYGB at study end ( P < 0.05). Severe hypoglycemia occurred in several rats after RYGB. RYGB and SG significantly improved glycemic control in a rodent model of advanced T2DM. While short-term outcomes are similar, long-term efficacy appears marginally better after RYGB, although this is tempered by the increased risk of hypoglycemia.
Guanylin activates Cl−secretion into the lumen of seawater eel intestine via apical Cl−channel under simulated in vivo conditions
Authors: Ando Masaaki , Takei Yoshio
Published: December 2014

Guanylin (GN) action on seawater eel intestine was examined under simulated in vivo conditions, where isotonic luminal fluid has low NaCl and high MgSO4(MgSO4Ringer). In Ussing chamber, MgSO4Ringer induced serosa-negative potential difference (PD) even after bumetanide treatment, which is due to the higher paracellular Na+permeability over Cl−, as confirmed by the replacement by MgCl2(no Cl−gradient) or Na2SO4Ringer (no Na+gradient). Luminal GN reversed serosa-negative PD, probably by enhancing Cl−secretion into the lumen, as the GN effect was blocked by apical Cl−channel blockers [diphenylamine-2-carboxylic acid (DPC), 5-nitro-2-(3-phenylpropylamino) benzoic acid, glibenclamide but not cystic fibrosis transmembrane regulator (CFTR)inh-172] or replacement of luminal fluid by MgCl2Ringer. The blockers' effect was undetectable when normal Ringer was on both sides. In the sac preparation, NaCl secretion occurred into the lumen (Na+> Cl−), and GN further enhanced Cl−secretion (Cl−> Na+), resulting in water secretion. These GN effects were also blocked by DPC. Quantitative analyses showed that isotonic NaCl is absorbed when luminal fluid is normal Ringer, but, when luminal fluid is MgSO4Ringer, hypertonic NaCl, almost equivalent to seawater, is secreted into the lumen after GN. These results indicate that GN stimulates the secretion of hypertonic NaCl into the lumen of seawater eel intestine, like rectal gland of marine elasmobranchs, to get rid of excess NaCl although marine teleost intestine is thought to have only absorptive-type cells with a unique Na-K-Cl cotransport system. The secreted NaCl may activate the cotransport system and further help absorb water in the final segment of seawater eel intestine.
Peripheral oxytocin activates vagal afferent neurons to suppress feeding in normal and leptin-resistant mice: a route for ameliorating hyperphagia and obesity
Authors: Iwasaki Yusaku , Maejima Yuko , Suyama Shigetomo , Yoshida Masashi , Arai Takeshi , Katsurada Kenichi , Kumari Parmila , Nakabayashi Hajime , Kakei Masafumi , Yada Toshihiko
Published: December 2014

Oxytocin (Oxt), a neuropeptide produced in the hypothalamus, is implicated in regulation of feeding. Recent studies have shown that peripheral administration of Oxt suppresses feeding and, when infused subchronically, ameliorates hyperphagic obesity. However, the route through which peripheral Oxt informs the brain is obscure. This study aimed to explore whether vagal afferents mediate the sensing and anorexigenic effect of peripherally injected Oxt in mice. Intraperitoneal Oxt injection suppressed food intake and increased c-Fos expression in nucleus tractus solitarius to which vagal afferents project. The Oxt-induced feeding suppression and c-Fos expression in nucleus tractus solitarius were blunted in mice whose vagal afferent nerves were blocked by subdiaphragmatic vagotomy or capsaicin treatment. Oxt induced membrane depolarization and increases in cytosolic Ca2+ concentration ([Ca2+]i) in single vagal afferent neurons. The Oxt-induced [Ca2+]i increases were markedly suppressed by Oxt receptor antagonist. These Oxt-responsive neurons also responded to cholecystokinin-8 and contained cocaine- and amphetamine-regulated transcript. In obese diabetic db/db mice, leptin failed to increase, but Oxt increased [Ca2+]i in vagal afferent neurons, and single or subchronic infusion of Oxt decreased food intake and body weight gain. These results demonstrate that peripheral Oxt injection suppresses food intake by activating vagal afferent neurons and thereby ameliorates obesity in leptin-resistant db/db mice. The peripheral Oxt-regulated vagal afferent neuron provides a novel target for treating hyperphagia and obesity.
The effect of chronic treadmill exercise and acetaminophen on collagen and cross-linking in rat skeletal muscle and heart
Authors: Carroll Chad C. , Martineau Karl , Arthur Kathryn A. , Huynh Richard T. , Volper Brent D. , Broderick Tom L.
Published: December 2014

The purpose of this study was to determine whether exercise and/or acetaminophen (APAP) alter collagen and cross-linking in the rat gastrocnemius muscle, soleus muscle, and heart. Male Wistar rats ( n = 50; 8 wk old) were divided into placebo (PLA) or APAP groups and sedentary (SED) or exercised (RUN) groups. APAP (200 mg/kg) was administered daily by oral gavage. Exercised groups ran on a treadmill 5 days/wk for 8 wk with progression to 60 min/day, 20 m/min, and 8° incline. Tissues were assayed for collagen (hydroxyproline) and hydroxylyslpyridinoline (HP) and lysylpyridinoline (LP) cross-links by HPLC. Collagen content (μg/mg dry weight) was greater in both the gastrocnemius (SED-PLA: 114 ± 16 vs. RUN-PLA: 244 ± 32; P < 0.001) and soleus (SED-PLA: 51 ± 7 vs. RUN-PLA: 99 ± 27; P = 0.005) of exercised animals. In contrast, collagen content was not significantly greater in exercised animals treated with APAP (SED-APAP: 113 ± 16 vs. RUN-APAP: 145 ± 21) and soleus (SED-APAP: 55 ± 8 vs. RUN-APAP: 57 ± 10). HP cross-linking (mmol/mol collagen) in the gastrocnemius (SED-PLA: 126 ± 28, RUN-PLA: 50 ± 7, SED-APAP: 41 ± 7, and RUN-APAP: 30 ± 4) and soleus muscles (SED-PLA: 547 ± 107, RUN-PLA: 318 ± 92, SED-APAP: 247 ± 64, and RUN-APAP: 120 ± 17) was lower in exercised rats compared with sedentary rats ( P < 0.05). Cross-linking was further reduced in animals treated with APAP ( P < 0.05). Neither heart collagen nor cross-linking was influenced by exercise or APAP ( P > 0.05). Our findings suggest that exercise and APAP have tissue-specific effects on muscle collagen. Given the widespread use of APAP as an analgesic and antipyretic, further work in humans is warranted.
Chronic oxytocin administration inhibits food intake, increases energy expenditure, and produces weight loss in fructose-fed obese rhesus monkeys
Authors: Blevins James E. , Graham James L. , Morton Gregory J. , Bales Karen L. , Schwartz Michael W. , Baskin Denis G. , Havel Peter J.
Published: December 2014

Despite compelling evidence that oxytocin (OT) is effective in reducing body weight (BW) in diet-induced obese (DIO) rodents, studies of the effects of OT in humans and rhesus monkeys have primarily focused on noningestive behaviors. The goal of this study was to translate findings in DIO rodents to a preclinical translational model of DIO. We tested the hypothesis that increased OT signaling would reduce BW in DIO rhesus monkeys by inhibiting food intake and increasing energy expenditure (EE). Male DIO rhesus monkeys from the California National Primate Research Center were adapted to a 12-h fast and maintained on chow and a daily 15% fructose-sweetened beverage. Monkeys received 2× daily subcutaneous vehicle injections over 1 wk. We subsequently identified doses of OT (0.2 and 0.4 mg/kg) that reduced food intake and BW in the absence of nausea or diarrhea. Chronic administration of OT for 4 wk (0.2 mg/kg for 2 wk; 0.4 mg/kg for 2 wk) reduced BW relative to vehicle by 3.3 ± 0.4% (≈0.6 kg; P < 0.05). Moreover, the low dose of OT suppressed 12-h chow intake by 26 ± 7% ( P < 0.05). The higher dose of OT reduced 12-h chow intake by 27 ± 5% ( P < 0.05) and 8-h fructose-sweetened beverage intake by 18 ± 8% ( P < 0.05). OT increased EE during the dark cycle by 14 ± 3% ( P < 0.05) and was associated with elevations of free fatty acids and glycerol and reductions in triglycerides suggesting increased lipolysis. Together, these data suggest that OT reduces BW in DIO rhesus monkeys through decreased food intake as well as increased EE and lipolysis.
Effects of B-type natriuretic peptide on cardiovascular biomarkers in healthy volunteers
Authors: Resl M. , Vila G. , Grimm G. , Heinisch B. , Riedl M. , Dieplinger B. , Mueller T. , Luger A. , Clodi M.
Published: December 2014

Cardiovascular biomarkers provide independent prognostic information in the assessment of mortality and cardiovascular complications. However, little is known about possible interactions between these biomarkers. In the present study, we evaluated the influence of B-type natriuretic peptide (BNP) on midregional-proadrenomedullin (MR-proADM), C-terminal-proendothelin-1 (CT-proET-1), growth differentiation factor-15 (GDF-15), midregional-proatrial natriuretic peptide (MR-proANP), copeptin, and procalcitonin in healthy volunteers. Ten healthy male subjects (mean age 24 yr) participating in a randomized, placebo-controlled, single-blinded crossover study received placebo or 3.0 pmol·kg−1·min−1human BNP 32 during a continuous infusion lasting for 4 h. Effects of BNP on other cardiovascular biomarkers were assessed. BNP did not change concentrations of MR-proADM, copeptin, CT-proET1, GDF-15, or procalcitonin. In contrast, MR-proANP was significantly decreased during BNP infusion. BNP as an established cardiovascular biomarker did not affect plasma concentrations of other cardiovascular biomarkers in a model of healthy volunteers.
Role of the ovarian cycle on neural cardiovascular control in sleep-deprived women
Authors: Yang Huan , Durocher John J. , Larson Robert A. , Carter Jason R.
Published: December 2014

The midluteal (ML) phase of the ovarian cycle is often sympathoexcitatory compared with the early follicular (EF) phase. We recently reported that 24-h total sleep deprivation (TSD) augmented cardiovascular reactivity in both men and women, but that sex differences existed in resting muscle sympathetic nerve activity (MSNA) responses to TSD. In the present study, we hypothesized increased resting MSNA and augmented cardiovascular reactivity to acute laboratory stressors during the ML phase in sleep-deprived women. Heart rate (HR), mean arterial pressure (MAP), forearm vascular conductance (FVC), and MSNA were measured in 14 eumenorrheic women (age, 20 ± 1 yr) during 10 min supine rest, 5 min mental stress (MS) trial, and 2 min cold pressor test (CPT) trial. Subjects were tested twice after TSD: once during EF phase and once during ML phase (randomized, crossover design). Estradiol (29 ± 2 vs. 63 ± 8 pg/ml, P = 0.001) and progesterone (1.6 ± 0.2 vs. 4.4 ± 0.7 ng/ml, P = 0.002) were elevated during the ML phase. Resting supine MAP (75 ± 2 vs. 72 ± 1 mmHg, P = 0.042) was lower during the ML phase. In contrast, resting supine HR, MSNA, and FVC were not significantly different between EF and ML phases. MAP, HR and FVC reactivity to MS were not statistically different between the EF and ML phases. Similarly, MAP and HR reactivity to CPT were not different between the ovarian phases. Contrary to our original hypothesis, the ML phase was not associated with sympathoexcitation or exaggerated cardiovascular reactivity in sleep-deprived premenopausal women. However, our data reveal elevated resting blood pressure during the EF phase in sleep-deprived women.
Structure of the cortical cytoskeleton in fibers of postural muscles and cardiomyocytes of mice after 30-day 2-gcentrifugation
Authors: Ogneva Irina V. , Gnyubkin V. , Laroche N. , Maximova M. V. , Larina I. M. , Vico L.
Published: December 2014

Altered external mechanical loading during spaceflights causes negative effects on muscular and cardiovascular systems. The aim of the study was estimation of the cortical cytoskeleton statement of the skeletal muscle cells and cardiomyocytes. The state of the cortical cytoskeleton in C57BL6J mice soleus, tibialis anterior muscle fibers, and left ventricle cardiomyocytes was investigated after 30-day 2- g centrifugation (“2- g” group) and within 12 h after its completion (“2- g + 12-h” group). We used atomic force microscopy for estimating cell's transverse stiffness, Western blotting for measuring protein content, and RT-PCR for estimating their expression level. The transverse stiffness significantly decreased in cardiomyocytes (by 16%) and increased in skeletal muscles fibers (by 35% for soleus and by 29% for tibialis anterior muscle fibers) in animals of the 2-g group (compared with the control group). For cardiomyocytes, we found that, in the 2- g + 12-h group, α-actinin-1 content decreased in the membranous fraction (by 27%) and increased in cytoplasmic fraction (by 28%) of proteins (compared with the levels in the 2- g group). But for skeletal muscle fibers, similar changes were noted for α-actinin-4, but not for α-actinin-1. In conclusion, we showed that the different isoforms of α-actinins dissociate from cortical cytoskeleton under increased/decreased of mechanical load.
Postdinner resistance exercise improves postprandial risk factors more effectively than predinner resistance exercise in patients with type 2 diabetes
Authors: Heden Timothy D. , Winn Nathan C. , Mari Andrea , Booth Frank W. , Rector R. Scott , Thyfault John P. , Kanaley Jill A.
Published: December 2014

Abnormally elevated postprandial glucose and triacylglycerol (TAG) concentrations are risk factors for cardiovascular disease in type 2 diabetes. The most effective time to exercise to lower postprandial glucose and TAG concentrations is unknown. Thus the aim of this study was to determine what time is more effective, either pre- or postdinner resistance exercise (RE), at improving postprandial risk factors in patients with type 2 diabetes. Thirteen obese patients with type 2 diabetes completed three trials in a random order in which they consumed a dinner meal with 1) no RE (NoRE), 2) predinner RE (RE → M), and 3) postdinner RE beginning 45 min after dinner (M → RE). Clinical outcome measures included postprandial glucose and TAG concentrations. In addition, postprandial acetaminophen (gastric emptying), endocrine responses, free fatty acids, and β-cell function (mathematical modeling) were measured to determine whether these factors were related to changes in glucose and TAG. The TAG incremental area under the curve (iAUC) was ∼92% lower ( P ≤ 0.02) during M → RE compared with NoRE and RE → M, an effect due in part to lower very-low-density lipoprotein-1 TAG concentrations. The glucose iAUC was reduced ( P = 0.02) by ∼18 and 30% during the RE → M and M → RE trials, respectively, compared with NoRE, with no difference between RE trials. RE → M and M → RE reduced the insulin iAUC by 35 and 48%, respectively, compared with NoRE ( P < 0.01). The glucagon-like peptide-1 iAUC was ∼50% lower ( P ≤ 0.02) during M → RE compared with NoRE and RE → M. Given that predinner RE only improves postprandial glucose concentrations, whereas postdinner RE improves both postprandial glucose and TAG concentrations, postdinner RE may lower the risk of cardiovascular disease more effectively.
Instantaneous quantification of skeletal muscle activation, power production, and fatigue during cycle ergometry
Authors: Coelho A. C. , Cannon D. T. , Cao R. , Porszasz J. , Casaburi R. , Knorst M. M. , Rossiter H. B.
Published: December 2014

A rapid switch from hyperbolic to isokinetic cycling allows the velocity-specific decline in maximal power to be measured, i.e., fatigue. We reasoned that, should the baseline relationship between isokinetic power (Piso) and electromyography (EMG) be reproducible, then contributions to fatigue may be isolated from 1) the decline in muscle activation (muscle activation fatigue); and 2) the decline in Pisoat a given activation (muscle fatigue). We hypothesized that the EMG-Pisorelationship is linear, velocity dependent, and reliable for instantaneous fatigue assessment at intolerance during and following whole body exercise. Healthy participants ( n = 13) completed short (5 s) variable-effort isokinetic bouts at 50, 70, and 100 rpm to characterize baseline EMG-Piso. Repeated ramp incremental exercise tests were terminated with maximal isokinetic cycling (5 s) at 70 rpm. Individual baseline EMG-Pisorelationships were linear ( r2= 0.95 ± 0.04) and velocity dependent (analysis of covariance). Pisoat intolerance (two legs, 335 ± 88 W) was ∼45% less than baseline [630 ± 156 W, confidence interval of the difference (CIDifference) 211, 380 W, P < 0.05]. Following intolerance, Pisorecovered rapidly ( F = 44.1; P < 0.05; η2= 0.79): power was reduced ( P < 0.05) vs. baseline only at 0-min (CIDifference80, 201 W) and 1-min recovery (CIDifference13, 80 W). Activation fatigue and muscle fatigue (one leg) were 97 ± 55 and 60 ± 50 W, respectively. Mean bias ± limits of agreement for reproducibility were as follows: baseline Piso1 ± 30 W; Pisoat 0-min recovery 3 ± 35 W; and EMG at Piso3 ± 14%. EMG power is linear, velocity dependent, and reproducible. Deviation from this relationship at the limit of tolerance can quantify the “activation” and “muscle” related components of fatigue during cycling.
β-Alanine supplementation enhances human skeletal muscle relaxation speed but not force production capacity
Authors: Hannah Ricci , Stannard Rebecca Louise , Minshull Claire , Artioli Guilherme Giannini , Harris Roger Charles , Sale Craig
Published: December 2014

β-Alanine (BA) supplementation improves human exercise performance. One possible explanation for this is an enhancement of muscle contractile properties, occurring via elevated intramuscular carnosine resulting in improved calcium sensitivity and handling. This study investigated the effect of BA supplementation on in vivo contractile properties and voluntary neuromuscular performance. Twenty-three men completed two experimental sessions, pre- and post-28 days supplementation with 6.4 g/day of BA ( n = 12) or placebo (PLA; n = 11). During each session, force was recorded during a series of knee extensor contractions: resting and potentiated twitches and octet (8 pulses, 300 Hz) contractions elicited via femoral nerve stimulation; tetanic contractions (1 s, 1–100 Hz) via superficial muscle stimulation; and maximum and explosive voluntary contractions. BA supplementation had no effect on the force-frequency relationship, or the force responses (force at 25 and 50 ms from onset, peak force) of resting or potentiated twitches, and octet contractions ( P > 0.05). Resting and potentiated twitch electromechanical delay and time-to-peak tension were unaffected by BA supplementation ( P > 0.05), although half-relaxation time declined by 7–12% ( P < 0.05). Maximum and explosive voluntary forces were unchanged after BA supplementation. BA supplementation had no effect on evoked force responses, implying that altered calcium sensitivity and/or release are not the mechanisms by which BA supplementation influences exercise performance. The reduced half-relaxation time with BA supplementation might, however, be explained by enhanced reuptake of calcium, which has implications for the efficiency of muscle contraction following BA supplementation.
The effect of sensory feedback on crayfish posture and locomotion: I. Experimental analysis of closing the loop
Authors: Chung Bryce , Bacqué-Cazenave Julien , Cofer David W. , Cattaert Daniel , Edwards Donald H.
Published: December 2014

The effect of proprioceptive feedback on the control of posture and locomotion was studied in the crayfish Procambarus clarkii (Girard). Sensory and motor nerves of an isolated crayfish thoracic nerve cord were connected to a computational neuromechanical model of the crayfish thorax and leg. Recorded levator (Lev) and depressor (Dep) nerve activity drove the model Lev and Dep muscles to move the leg up and down. These movements released and stretched a model stretch receptor, the coxobasal chordotonal organ (CBCO). Model CBCO length changes drove identical changes in the real CBCO; CBCO afferent responses completed the feedback loop. In a quiescent preparation, imposed model leg lifts evoked resistance reflexes in the Dep motor neurons that drove the leg back down. A muscarinic agonist, oxotremorine, induced an active state in which spontaneous Lev/Dep burst pairs occurred and an imposed leg lift excited a Lev assistance reflex followed by a Lev/Dep burst pair. When the feedback loop was intact, Lev/Dep burst pairs moved the leg up and down rhythmically at nearly three times the frequency of burst pairs when the feedback loop was open. The increased rate of rhythmic bursting appeared to result from the positive feedback produced by the assistance reflex.