bluuebunny/crossref_metadata_2025 huggingface dataset:
IN SITU SYNTHESIS, CHARACTERIZATION AND FREQUENCY DEPENDENT AC CONDUCTIVITY OF POLYANILINE/CoFe2O4 NANOCOMPOSITES
Authors: PRASANNA G. D. , JAYANNA H. S.
Published: August 2011

The polyaniline (PANI)/ CoFe2O4 nanocomposites were prepared by an In Situ polymerization of aniline in an aqueous solution. The composites were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectrum,thermogravimetric analysis (TGA) and scanning electron micrograph (SEM). The AC conductivity and dielectric properties of these composites were investigated in the frequency range 1 kHz–10 MHz at room temperature. The AC conductivity was found to be constant up to 1 MHz and thereafter it increases steeply and it was observed maximum for the PANI with 60 wt% of CoFe2O4 nanocomposite. At lower frequencies the values of dielectric constant is maximum for pure CoFe2O4 nanoparticles.
IMPEDANCE SPECTROSCOPY AND AC CONDUCTIVITY STUDIES OF FERROELECTRIC (K0.5Na0.5)NbO3 CERAMICS
Authors: PALEI P. , KUMAR P.
Published: August 2011

Lead free (K0.5Na0.5)NbO3 (KNN) ceramics were prepared by conventional solid state reaction route. For single perovskite phase formation, calcination temperature was optimized at 850°C for 6 h, whereas for dense morphology the sintering of the ceramic was carried out at 1120°C for 4 h. X-ray diffraction XRD analysis confirmed the formation of single phase with orthorhombic structure at room temperature. Impedance analysis and AC conductivity studies of the KNN sample was carried out in the temperature range of 703–773 K. Impedance study showed the increase in conducting behavior at higher temperature. The temperature dependence of AC conductivity indicated that the conduction process is due to doubly ionized oxygen vacancies in the higher temperature region.
ATOMIC LAYER DEPOSITION HfO2 FILM USED AS BUFFER LAYER OF THE Pt/(Bi0.95Nd0.05)(Fe0.95Mn0.05)O3/HfO2/Si CAPACITORS FOR FeFET APPLICATION
Authors: XIE DAN , FENG TINGTING , LUO YAFENG , HAN XUEGUANG , REN TIANLING , BOSUND MARKUS , LI SHUO , AIRAKSINEN VELI-MATTI , LIPSANEN HARRI , HONKANEN SEPPO
Published: August 2011

Neodymium and manganese-doped BiFeO3 — (Bi0.95Nd0.05)(Fe0.95Mn0.05)O3(BNFMO) ferroelectric film and HfO2 layer with different thickness were fabricated using metal-organic decomposition and atomic layer deposition (ALD) method, respectively. Metal-ferroelectric-insulator-semiconductor (MFIS) capacitors with 200 nm thick BNFMO and 5 nm thick HfO2 layer on silicon substrate have been prepared and characterized. It is found that there is no distinct interdiffusion and reaction occurring at the interface between BNFMO/HfO2 and HfO2/Si . The capacitance–voltage (C–V) and leakage current properties of Pt/HfO2/Si capacitors with different HfO2 thickness were studied. The MFIS structure showed clockwise C–V hysteresis loops due to the ferroelectric polarization of BNFMO . The maximum memory window is 5 V. The leakage current of the Pt/BNFMO/HfO2/Si capacitor was about 2.1 × 10-6 A/cm2 at an applied voltage of 4 V.
EFFECTS OF ORDERING DOMAIN STRUCTURE ON DIELECTRIC PROPERTIES OF DOUBLE PEROVSKITE La2NiMnO6
Authors: LIN Y. Q. , WU S. Y. , CHEN X. M.
Published: August 2011

Two sets of La2NiMnO6 ceramics with different B-site ordering degree were prepared and evaluated. The valence states of Ni2+ and Mn4+ were confirmed, and the B-site ordering degree was estimated qualitatively using magnetic and Raman analysis. The ordering of Ni2+ and Mn4+ was the primary origin for the relaxor-like behavior of the present ceramics. The ordering degree of B-site ions greatly affected the dielectric properties, i.e., more ordered sample indicated higher dielectric constant. Meanwhile, the grain boundary layer capacitor (GBLC) effect was also activated but limited at the high temperatures and low frequencies.
ELECTRICAL CONDUCTIVITY AND PHASE TRANSITIONS IN KDP- AND ADP-POROUS GLASS NANOCOMPOSITES
Authors: SIERADZKI A. , CIZMAN A. , POPRAWSKI R. , MARCINISZYN T. , RYSIAKIEWICZ-PASEK E.
Published: August 2011

The results of dielectric and dilatometric measurements of ADP and KDP-porous glass composites are presented. We stated on dilatometric studies that in ADP-porous glass nanocomposites the phase transition temperature decreases with decreasing of average size of pores. The negative jump of volume at phase transition region in ADP-porous glasses is observed. It was found that for KDP embedded into porous glasses nonmonotonous dependence of phase transition temperature on pores sizes occurs. The conductivity of ADP/KDP composites is significantly higher than in bulk crystals. The obtained values of activation energies are typical for proton movement.
Fast food diet mouse: novel small animal model of NASH with ballooning, progressive fibrosis, and high physiological fidelity to the human condition
Authors: Charlton Michael , Krishnan Anuradha , Viker Kimberly , Sanderson Schuyler , Cazanave Sophie , McConico Andrea , Masuoko Howard , Gores Gregory
Published: August 2011

Although there are small animal platforms that recapitulate some of the histological features of nonalcoholic fatty liver disease, there are no small animal models of nonalcoholic steatohepatitis (NASH) with consistent hepatocellular ballooning and progressive fibrosis that also exhibit fidelity to the human condition physiologically. We examined the metabolic and histological effects of a diet on the basis of the composition of “fast food” (high saturated fats, cholesterol, and fructose). Mice ( n = 8 in each group) were assigned to diets as follows: 1) standard chow (SC), i.e., 13% energy as fat [1% saturated fatty acids (SFA)], 2) high fat (HF), i.e., 60% energy as fat (1% SFA), and 3) fast food (FF), i.e., 40% energy as fat (12% SFA, 2% cholesterol). All three diets were supplemented with high fructose. All diets produced obesity. The HF and FF diets produced insulin resistance. Liver histology was normal in animals fed the SC diet. Steatohepatitis with pronounced ballooning and progressive fibrosis (stage 2) was observed in mice fed the FF diet. Although the HF diet produced obesity, insulin resistance, and some steatosis; inflammation was minimal, and there was no increase in fibrosis. The FF diet produced a gene expression signature of increased fibrosis, inflammation, and endoplasmic reticulum stress and lipoapoptosis. A diet based on high cholesterol, high saturated fat, and high fructose recapitulates features of the metabolic syndrome and NASH with progressive fibrosis. This represents a novel small animal model of fibrosing NASH with high fidelity to the human condition. These results highlight the contribution of dietary composition to the development of nonalcoholic fatty liver disease and NASH.
Honokiol radiosensitizes colorectal cancer cells: enhanced activity in cells with mismatch repair defects
Authors: He Zhiyun , Subramaniam Dharmalingam , Ramalingam Satish , Dhar Animesh , Postier Russell G. , Umar Shahid , Zhang Youcheng , Anant Shrikant
Published: August 2011

DNA mismatch repair is required for correcting any mismatches that are created during replication and recombination, and a defective mismatch repair system contributes to DNA damage-induced growth arrest. The colorectal cancer cell line HCT116 is known to have a mutation in the hMLH1 mismatch repair gene resulting in microsatellite instability and defective mismatch repair. Honokiol is a biphenolic compound that has been used in traditional Chinese medicine for treating various ailments including cancer. This study was designed to test the hypothesis that honokiol enhances the radiosensitivity of cancer cells with mismatch repair defect (HCT116) compared with those that are mismatch repair proficient (HCT116-CH3). We first determined that the combination of honokiol and γ-irradiation treatment resulted in dose-dependent inhibition of proliferation and colony formation in both cell lines. However, the effects were more pronounced in HCT116 cells. Similarly, the combination induced higher levels of apoptosis (caspase 3 activation, Bax to Bcl2 ratio) in the HCT116 cells compared with HCT116-CH3 cells. Cell cycle analyses revealed higher levels of dead cells in HCT116 cells. The combination treatment reduced expression of cyclin A1 and D1 and increased phosphorylated p53 in both cell lines, although there were significantly lower amounts of phosphorylated p53 in the HCT116-CH3 cells, suggesting that high levels of hMLH1 reduce radiosensitivity. These data demonstrate that honokiol is highly effective in radiosensitizing colorectal cancer cells, especially those with a mismatch repair defect.
Urine sugars for in vivo gut permeability: validation and comparisons in irritable bowel syndrome-diarrhea and controls
Authors: Rao Archana S. , Camilleri Michael , Eckert Deborah J. , Busciglio Irene , Burton Duane D. , Ryks Michael , Wong Banny S. , Lamsam Jesse , Singh Ravinder , Zinsmeister Alan R.
Published: August 2011

Mucosal barrier dysfunction contributes to gastrointestinal diseases. Our aims were to validate urine sugar excretion as an in vivo test of small bowel (SB) and colonic permeability and to compare permeability in patients with irritable bowel syndrome-diarrhea (IBS-D) to positive and negative controls. Oral lactulose (L) and mannitol (M) were administered with 99mTc-oral solution, 111In-oral delayed-release capsule, or directly into the ascending colon (only in healthy controls). We compared L and M excretion in urine collections at specific times in 12 patients with IBS-D, 12 healthy controls, and 10 patients with inactive or treated ulcerative or microscopic colitis (UC/MC). Sugars were measured by high-performance liquid chromatography-tandem mass spectrometry. Primary endpoints were cumulative 0–2-h, 2–8-h, and 8–24-h urinary sugars. Radioisotopes in the colon at 2 h and 8 h were measured by scintigraphy. Kruskal-Wallis and Wilcoxon tests were used to assess the overall and pairwise associations, respectively, between group and urinary sugars. The liquid in the colon at 2 h and 8 h was as follows: health, 62 ± 9% and 89 ± 3%; IBS-D, 56 ± 11% and 90 ± 3%; and UC/MC, 35 ± 8% and 78 ± 6%, respectively. Liquid formulation was associated with higher M excretion compared with capsule formulation at 0–2 h (health P = 0.049; IBS-D P < 0.001) but not during 8–24 h. UC/MC was associated with increased urine L and M excretion compared with health (but not to IBS-D) at 8–24 h, not at 0–2 h. There were significant differences between IBS-D and health in urine M excretion at 0–2 h and 2–8 h and L excretion at 8–24 h. Urine sugars at 0–2 h and 8–24 h reflect SB and colonic permeability, respectively. IBS-D is associated with increased SB and colonic mucosal permeability.
Tspan-1 interacts with the thiamine transporter-1 in human intestinal epithelial cells and modulates its stability
Authors: Nabokina Svetlana M. , Senthilkumar Sundar Rajan , Said Hamid M.
Published: August 2011

The human thiamine transporter-1 (hTHTR-1) contributes to intestinal thiamine uptake, and its function is regulated at both the transcriptional and posttranscriptional levels. Nothing, however, is known about the protein(s) that may interact with hTHTR-1 and affects its cell biology and physiology. We addressed this issue in the present investigation using a bacterial two-hybrid system to screen a human intestinal cDNA library with the complete coding sequence of hTHTR-1 as a bait. Our results showed that a member of the tetraspanin family of proteins, Tspan-1, interacts with hTHTR-1. Coimmunoprecipitation and glutathione S-transferase (GST)-pulldown assays confirmed the existence of such an interaction between hTspan-1 and hTHTR-1 in human intestinal epithelial Caco-2 cells. Furthermore, live cell confocal imaging demonstrated that hTspan-1 and hTHTR-1 colocalize in human intestinal epithelial HuTu-80 cells. The importance of the interaction between hTspan-1 and hTHTR-1 for cell biology of the thiamine transporter was examined in HuTu-80 cells stably expressing hTHTR-1. Coexpression of hTspan-1 in these cells led to a significant decrease in the rate of degradation of hTHTR-1 compared with cells expressing the hTHTR-1 alone; in fact the half-life of the hTHTR-1 protein was twice longer in the former cell type compared with the latter cell type (12 h vs. 6 h, respectively). This finding was also confirmed at the functional level when a significantly higher thiamine uptake was observed in cycloheximide-treated (6 h) cells expressing hTHTR-1 together with hTspan-1 compared with those expressing hTHTR-1 alone. These studies demonstrate for the first time that Tspan-1 is an interacting partner with hTHTR-1 and that this interaction affects hTHTR-1 stability.
Transverse tubules are a common feature in large mammalian atrial myocytes including human
Authors: Richards M. A. , Clarke J. D. , Saravanan P. , Voigt N. , Dobrev D. , Eisner D. A. , Trafford A. W. , Dibb K. M.
Published: August 2011

Transverse (t) tubules are surface membrane invaginations that are present in all mammalian cardiac ventricular cells. The apposition of L-type Ca2+ channels on t tubules with the sarcoplasmic reticulum (SR) constitutes a “calcium release unit” and allows close coupling of excitation to the rise in systolic Ca2+. T tubules are virtually absent in the atria of small mammals, and therefore Ca2+ release from the SR occurs initially at the periphery of the cell and then propagates into the interior. Recent work has, however, shown the occurrence of t tubules in atrial myocytes from sheep. As in the ventricle, Ca2+ release in these cells occurs simultaneously in central and peripheral regions. T tubules in both the atria and the ventricle are lost in disease, contributing to cellular dysfunction. The aim of this study was to determine if the occurrence of t tubules in the atrium is restricted to sheep or is a more general property of larger mammals including humans. In atrial tissue sections from human, horse, cow, and sheep, membranes were labeled using wheat germ agglutinin. As previously shown in sheep, extensive t-tubule networks were present in horse, cow, and human atrial myocytes. Analysis shows half the volume of the cell lies within 0.64 ± 0.03, 0.77 ± 0.03, 0.84 ± 0.03, and 1.56 ± 0.19 μm of t-tubule membrane in horse, cow, sheep, and human atrial myocytes, respectively. The presence of t tubules in the human atria may play an important role in determining the spatio-temporal properties of the systolic Ca2+ transient and how this is perturbed in disease.
Caloric restriction: powerful protection for the aging heart and vasculature
Authors: Weiss Edward P. , Fontana Luigi
Published: August 2011

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. Research has shown that the majority of the cardiometabolic alterations associated with an increased risk of CVD (e.g., insulin resistance/type 2 diabetes, abdominal obesity, dyslipidemia, hypertension, and inflammation) can be prevented, and even reversed, with the implementation of healthier diets and regular exercise. Data from animal and human studies indicate that more drastic interventions, i.e., calorie restriction with adequate nutrition (CR), may have additional beneficial effects on several metabolic and molecular factors that are modulating cardiovascular aging itself (e.g., cardiac and arterial stiffness and heart rate variability). The purpose of this article is to review the current knowledge on the effects of CR on the aging of the cardiovascular system and CVD risk in rodents, monkeys, and humans. Taken together, research shows that CR has numerous beneficial effects on the aging cardiovascular system, some of which are likely related to reductions in inflammation and oxidative stress. In the vasculature, CR appears to protect against endothelial dysfunction and arterial stiffness and attenuates atherogenesis by improving several cardiometabolic risk factors. In the heart, CR attenuates age-related changes in the myocardium (i.e., CR protects against fibrosis, reduces cardiomyocyte apoptosis, prevents myosin isoform shifts, etc.) and preserves or improves left ventricular diastolic function. These effects, in combination with other benefits of CR, such as protection against obesity, diabetes, hypertension, and cancer, suggest that CR may have a major beneficial effect on health span, life span, and quality of life in humans.
microRNA-210 is upregulated in hypoxic cardiomyocytes through Akt- and p53-dependent pathways and exerts cytoprotective effects
Authors: Mutharasan R. Kannan , Nagpal Varun , Ichikawa Yoshihiko , Ardehali Hossein
Published: August 2011

microRNA-210 (miR-210) is upregulated in hypoxia, but its function in cardiomyocytes and its regulation in response to hypoxia are not well characterized. The purpose of this study was to identify upstream regulators of miR-210, as well as to characterize miR-210's function in cardiomyocytes. We first showed miR-210 is upregulated through both hypoxia-inducible factor (HIF)-dependent and -independent pathways, since aryl hydrocarbon nuclear translocator (ARNT) knockout mouse embryonic fibroblasts (MEF), lacking intact HIF signaling, still displayed increased miR-210 levels in hypoxia. To determine the mechanism for HIF-independent regulation of miR-210, we focused on p53 and protein kinase B (Akt). Overexpression of p53 in wild-type MEFs induced miR-210, whereas p53 overexpression in ARNT knockout MEFs did not, suggesting p53 regulates miR-210 in a HIF-dependent mechanism. Akt inhibition reduced miR-210 induction by hypoxia, whereas Akt overexpression increased miR-210 levels in both wild-type and ARNT knockout MEFs, indicating Akt regulation of miR-210 is HIF-independent. We then studied the effects of miR-210 in cardiomyocytes. Overexpression of miR-210 reduced cell death in response to oxidative stress and reduced reactive oxygen species (ROS) production both at baseline and after treatment with antimycin A. Furthermore, downregulation of miR-210 increased ROS after hypoxia-reoxygenation. To determine a mechanism for the cytoprotective effects of miR-210, we focused on the predicted target, apoptosis-inducing factor, mitochondrion-associated 3 (AIFM3), known to induce cell death. Although miR-210 reduced AIFM3 levels, overexpression of AIFM3 in the presence of miR-210 overexpression did not reduce cellular viability either at baseline or after hydrogen peroxide treatment, suggesting AIFM3 does not mediate miR-210's cytoprotective effects. Furthermore, HIF-3α, a negative regulator of HIF signaling, is targeted by miR-210, but miR-210 does not modulate HIF activity. In conclusion, we demonstrate a novel role for p53 and Akt in regulating miR-210 and demonstrate that, in cardiomyocytes, miR-210 exerts cytoprotective effects, potentially by reducing mitochondrial ROS production.
Src kinase integrates PI3K/Akt and MAPK/ERK1/2 pathways in T3-induced Na-K-ATPase activity in adult rat alveolar cells
Authors: Lei Jianxun , Ingbar David H.
Published: August 2011

We previously reported that the 3,5,3′-triiodo-l-thyronine (T3)-induced increase of Na-K-ATPase activity in rat alveolar epithelial cells (AECs) required activation of Src kinase, PI3K, and MAPK/ERK1/2. In the present study, we assessed the role of Akt in Na-K-ATPase activity and the interaction between the PI3K and MAPK in response to T3 by using MP48 cells, inhibitors, and constitutively active mutants in the MP48 (alveolar type II-like) cell line. The Akt inhibitor VIII blocked T3-induced increases in Na-K-ATPase activity and amount of plasma membrane Na-K-ATPase protein. The Akt inhibitor VIII also abolished the increase in Na-K-ATPase activity induced by constitutively active mutants of either Src kinase or PI3K. Moreover, constitutively active mutants of Akt increased Na-K-ATPase activity in the absence of T3. Thus activation of Akt was required for T3-induced Na-K-ATPase activity in AECs and is sufficient in the absence of T3. Inhibitors of Src kinase (PP1), PI3K (wortmannin), and ERK1/2 (U0126) all blocked the T3-induced Na-K-ATPase activity. PP1 blocked the activation of PI3K and also ERK1/2 by T3, whereas U0126 did not prevent T3 activation of Src kinase or PI3K activity. Wortmannin did not significantly alter T3-increased MAPK/ERK1/2 activity, suggesting that T3-activated PI3K/Akt and MAPK/ERK1/2 pathways acted downstream of the Src kinase. Furthermore, in the absence of T3, a constitutively active mutant of Src kinase increased activities of Na-K-ATPase, PI3K, and MAPK/ERK1/2. A constitutively active mutant of PI3K enhanced Na-K-ATPase activity but did not alter the MAPK/ERK1/2 activity significantly. In summary, in adult rat AECs T3-stimulated Src kinase activity can activate both PI3K/Akt and MAPK/ERK1/2, and activation of Akt is necessary for T3-induced Na-K-ATPase activity.
Electroacupuncture increased cerebral blood flow and reduced ischemic brain injury: dependence on stimulation intensity and frequency
Authors: Zhou Fei , Guo Jingchun , Cheng Jieshi , Wu Gencheng , Xia Ying
Published: August 2011

Stroke causes ischemic brain injury and is a leading cause of neurological disability and death. There is, however, no promising therapy to protect the brain from ischemic stress to date. Here we show an exciting finding that optimal electroacupuncture (EA) effectively protects the brain from ischemic injury. The experiments were performed on rats subjected to middle cerebral artery occlusion (MCAO) with continuous monitoring of cerebral blood flow. EA was delivered to acupoints of “Shuigou” (Du 26) and “Baihui” (Du 20) with different intensities and frequencies to optimize the stimulation parameters. The results showed that 1) EA at 1.0–1.2 mA and 5–20 Hz remarkably reduced ischemic infarction, neurological deficit, and death rate; 2) the EA treatment increased the blood flow by >100%, which appeared immediately after the initiation of EA and disappeared after the cessation of EA; 3) the EA treatment promoted the recovery of the blood flow after MCAO; 4) “nonoptimal” parameters of EA (e.g., <0.6 mA or >40 Hz) could not improve the blood flow or reduce ischemic injury; and 5) the same EA treatment with optimal parameters could not increase the blood flow in naive brains. These novel observations suggest that appropriate EA treatment protects the brain from cerebral ischemia by increasing blood flow to the ischemic brain region via a rapid regulation. Our findings have far-reaching impacts on the prevention and treatment of ischemic encephalopathy, and the optimized EA parameters may potentially be a useful clue for the clinical application of EA.
Lifetime sedentary living accelerates some aspects of secondary aging
Authors: Booth Frank W. , Laye Matthew J. , Roberts Michael D.
Published: August 2011

Lifetime physical inactivity interacts with secondary aging (i.e., aging caused by diseases and environmental factors) in three patterns of response. First, lifetime physical inactivity confers no apparent effects on a given set of physiological functions. Second, lifetime physical inactivity accelerates secondary aging (e.g., speeding the reduction in bone mineral density, maximal oxygen consumption, and skeletal muscle strength and power), but does not alter the primary aging of these systems. Third, a lifetime of physical activity to the age of ∼60–70 yr old totally prevents decrements in some age-associated risk factors for major chronic diseases, such as endothelial dysfunction and insulin resistance. The present review provides ample and compelling evidence that physical inactivity has a large impact in shortening average life expectancy. In summary, physical inactivity plays a major role in the secondary aging of many essential physiological functions, and this aging can be prevented through a lifetime of physical activity.
Activation of skeletal muscle calpain-3 by eccentric exercise in humans does not result in its translocation to the nucleus or cytosol
Authors: Murphy Robyn M. , Vissing Kristian , Latchman Heidy , Lamboley Cedric , McKenna Michael J. , Overgaard Kristian , Lamb Graham D.
Published: August 2011

The skeletal muscle-specific calpain-3 protease is likely involved in muscle repair, although the mechanism is not known. Physiological activation of calpain-3 occurs 24 h following eccentric exercise in humans. Functional consequences of calpain-3 activation are not known; however, calpain-3 has been suggested to be involved in nuclear signaling via NF-κB. To test this and help identify how/where calpain-3 acts, we investigated whether calpain-3 autolysis (hence, activation) following eccentric exercise results in translocation from its normal myofibrillar location to the nucleus or the cytosol. In resting human skeletal muscle, the majority (87%) of calpain-3 was present in myofibrillar fractions, with only a small proportion (<10%) in an autolyzed state. Enriched nuclear fractions contained ∼8% of the total calpain-3, which was present in a predominantly (>80%) autolyzed state. Using freshly dissected human muscle fibers to identify freely diffusible proteins, we showed that only ∼5% of the total calpain-3 pool was cytosolic. At 3 and 24 h following eccentric step exercise, there was an ∼70% increase in autolysis in whole muscle samples ( n = 11, P < 0.05, by 1-way ANOVA with repeated measures and Newman-Keuls post hoc analysis). This exercise-induced autolysis was attributed to myofibrillar-bound calpain-3, since neither the amount of calpain-3 nor the proportion autolyzed was significantly changed in enriched nuclear or cytosolic fractions following the exercise intervention. We present a model for calpain-3 localization at rest and following activation in human skeletal muscle and suggest that the functional importance of calpain-3 remains predominantly tightly associated with its localization within the myofibrillar compartment.
Automatic tracking of medial gastrocnemius fascicle length during human locomotion
Authors: Cronin Neil J. , Carty Christopher P. , Barrett Rod S. , Lichtwark Glen
Published: August 2011

During human locomotion lower extremity muscle-tendon units undergo cyclic length changes that were previously assumed to be representative of muscle fascicle length changes. Measurements in cats and humans have since revealed that muscle fascicle length changes can be uncoupled from those of the muscle-tendon unit. Ultrasonography is frequently used to estimate fascicle length changes during human locomotion. Fascicle length analysis requires time consuming manual methods that are prone to human error and experimenter bias. To bypass these limitations, we have developed an automatic fascicle tracking method based on the Lucas-Kanade optical flow algorithm with an affine optic flow extension. The aims of this study were to compare gastrocnemius fascicle length changes during locomotion using the automated and manual approaches and to determine the repeatability of the automated approach. Ultrasound was used to examine gastrocnemius fascicle lengths in eight participants walking at 4, 5, 6, and 7 km/h and jogging at 7 km/h on a treadmill. Ground reaction forces and three dimensional kinematics were recorded simultaneously. The level of agreement between methods and the repeatability of the automated method were quantified using the coefficient of multiple correlation (CMC). Regardless of speed, the level of agreement between methods was high, with overall CMC values of 0.90 ± 0.09 (95% CI: 0.86–0.95). Repeatability of the algorithm was also high, with an overall CMC of 0.88 ± 0.08 (95% CI: 0.79–0.96). The automated fascicle tracking method presented here is a robust, reliable, and time-efficient alternative to the manual analysis of muscle fascicle length during gait.
High intensity interval training alters substrate utilization and reduces oxygen consumption in the heart
Authors: Hafstad A. D. , Boardman N. T. , Lund J. , Hagve M. , Khalid A. M. , Wisløff U. , Larsen T. S. , Aasum E.
Published: August 2011

Aims: although exercise training induces hypertrophy with improved contractile function, the effect of exercise on myocardial substrate metabolism and cardiac efficiency is less clear. High intensity training has been shown to produce more profound effects on cardiovascular function and aerobic capacity than isocaloric low and moderate intensity training. The aim of the present study was to explore metabolic and mechanoenergetic changes in the heart following endurance exercise training of both high and moderate intensity. Methods and Results: C57BL/6J mice were subjected to 10 wk treadmill running, either high intensity interval training (HIT) or distance-matched moderate intensity training (MIT), where HIT led to a pronounced increase in maximal oxygen uptake. Although both modes of exercise were associated with a 10% increase in heart weight-to-body weight ratio, only HIT altered cardiac substrate utilization, as revealed by a 36% increase in glucose oxidation and a concomitant reduction in fatty acid oxidation. HIT also improved cardiac efficiency by decreasing work-independent myocardial oxygen consumption. In addition, it increased cardiac maximal mitochondrial respiratory capacity. Conclusion: This study shows that high intensity training is required for induction of changes in cardiac substrate utilization and energetics, which may contribute to the superior effects of high compared with moderate intensity training in terms of increasing aerobic capacity.
Caffeine intake improves intense intermittent exercise performance and reduces muscle interstitial potassium accumulation
Authors: Mohr Magni , Nielsen Jens Jung , Bangsbo Jens
Published: August 2011

The effect of oral caffeine ingestion on intense intermittent exercise performance and muscle interstitial ion concentrations was examined. The study consists of two studies (S1 and S2). In S1, 12 subjects completed the Yo-Yo intermittent recovery level 2 (Yo-Yo IR2) test with prior caffeine (6 mg/kg body wt; CAF) or placebo (PLA) intake. In S2, 6 subjects performed one low-intensity (20 W) and three intense (50 W) 3-min (separated by 5 min) one-legged knee-extension exercise bouts with (CAF) and without (CON) prior caffeine supplementation for determination of muscle interstitial K+ and Na+ with microdialysis. In S1 Yo-Yo IR2 performance was 16% better ( P < 0.05) in CAF compared with PLA. In CAF, plasma K+ at the end of the Yo-Yo IR2 test was 5.2 ± 0.1 mmol/l with no difference between the trials. Plasma free fatty acids (FFA) were higher ( P < 0.05) in CAF than PLA at rest and remained higher ( P < 0.05) during exercise. Peak blood glucose (8.0 ± 0.6 vs. 6.2 ± 0.4 mmol/l) and plasma NH3 (137.2 ± 10.8 vs. 113.4 ± 13.3 μmol/l) were also higher ( P < 0.05) in CAF compared with PLA. In S2 interstitial K+ was 5.5 ± 0.3, 5.7 ± 0.3, 5.8 ± 0.5, and 5.5 ± 0.3 mmol/l at the end of the 20-W and three 50-W periods, respectively, in CAF, which were lower ( P < 0.001) than in CON (7.0 ± 0.6, 7.5 ± 0.7, 7.5 ± 0.4, and 7.0 ± 0.6 mmol/l, respectively). No differences in interstitial Na+ were observed between CAF and CON. In conclusion, caffeine intake enhances fatigue resistance and reduces muscle interstitial K+ during intense intermittent exercise.
Exercise-induced adaptations of cardiac redox homeostasis and remodeling in heterozygous SOD2-knockout mice
Authors: Richters L. , Lange N. , Renner R. , Treiber N. , Ghanem A. , Tiemann K. , Scharffetter-Kochanek K. , Bloch W. , Brixius K.
Published: August 2011

A reduced expression of the manganese-dependent superoxide dismutase (SOD2) is characterized by increased cardiac oxidative stress. Oxidative stress has also been described in situations of physical exercise. We investigated the influence of physical exercise (EX; treadmill 1 h/day at 15 m/min, 5 days/wk, at an angle of 5° for a duration of 8 wk) on cardiac function [heart frequency (HF), echocardiography, morphometry], oxidative stress [reactive oxygen species (ROS)], and antioxidative defence capacity (peroxiredoxin 1–6) in male SOD2-knockout (SOD2_EX) and wild-type mice (WT_EX) compared with untrained age-matched animals (WT_CON; SOD2_CON). In SOD2_CON, heart weight, cardiomyocyte diameter, and cardiac ROS were significantly larger and peroxiredoxin isoforms 4–6 lower than in WT_CON. The vessel-to-cardiomyocyte ratio, cardiac VEGF-concentration, and cardiac function were similar in SOD2_CON and WT_CON. Both groups tolerated the exercise protocol well. In WT, exercise significantly increased vessel-to-cardiomyocyte ratio and ROS-generation and downregulated peroxiredoxin isoforms 4–6 and VEGF generation. The vessel-to-cardiomyocyte ratio, cardiac VEGF concentration, and cardiac ROS were not altered in SOD2_EX compared with SOD2_CON, but a significant upregulation of cardiac peroxiredoxin 1 and 4 was observed. Similar to the result observed in WT_EX, peroxiredoxin 3 was upregulated in SOD2_EX. Chronic exercise shifted the (mal)adaptive hypertrophic into a compensated dilated cardiac phenotype in SOD2_EX. In conclusion, downregulation of SOD2 induces a maladaptive cardiac hypertrophy. In this situation, physical exercise results in a further deterioration of cardiac remodeling despite an upregulation of the antioxidative defense system.
Dynamic Neural Control of Insect Muscle Metabolism Related to Motor Behavior
Authors: Pflüger Hans-Joachim , Duch Carsten
Published: August 2011

Skeletal muscle innervation differs between vertebrates and insects. Insect muscle fibers exhibit graded electrical potentials and are innervated by excitatory, inhibitory, and also neuromodulatory motoneurons. The latter form a unique class of unpaired neurons with bilaterally symmetrical axons that release octopamine to alter the efficacy of synaptic transmission and regulate muscle energy metabolism by activating glycolysis. Octopaminergic neurons that innervate muscles with a high energy demand, for example, flight muscles that move the wings of a locust up and down, are active during rest but are inhibited during flight and its preparatory phase, a jump. Therefore, it is argued that these neurons are involved in providing locusts with the necessary fuel at takeoff, but then may aid the switch to lipid oxidation during flight. In general, the octopaminergic system may switch the whole organism from a tonic to a dynamic state.
Protons and Ca2+: Ionic Allies in Tumor Progression?
Authors: Glitsch Maike
Published: August 2011

Ion channels and G-protein-coupled receptors (GPCRs) play a fundamental role in cancer progression by influencing Ca2+influx and signaling pathways in transformed cells. Transformed cells thrive in a hostile environment that is characterized by extracellular acidosis that promotes the pathological phenotype. The pathway(s) by which extracellular protons achieve this remain unclear. Here, a role for proton-sensing ion channels and GPCRs as mediators of the effects of extracellular protons in cancer cells is discussed.
Differentiation of Intercalated Cells in the Kidney
Authors: Al-Awqati Qais , Gao Xaio Bo
Published: August 2011

The intercalated cell of collecting ducts of the kidney is of two forms, the α form secretes acid, whereas the β form secretes HCO3. Here, we review recent work that shows that the α form is derived from the β form and that the pathway is mediated by an extracellular matrix protein called hensin/DMBT1.
Calorie Restriction: Is AMPK a Key Sensor and Effector?
Authors: Cantó Carles , Auwerx Johan
Published: August 2011

Dietary restriction can extend life span in most organisms tested to date, suggesting that mechanisms sensing nutrient and energy availability might regulate longevity. The AMP-activated protein kinase (AMPK) has emerged as a key energy sensor with the ability to transcriptionally reprogram the cell and metabolically adapt to external cues. In this review, we will discuss the possible role of AMPK in the beneficial effects of calorie restriction on health and life span.
Circadian Rhythms, Aging, and Life Span in Mammals
Authors: Froy Oren
Published: August 2011

Resetting the circadian clock leads to well being and increased life span, whereas clock disruption is associated with aging and morbidity. Increased longevity and improved health can be achieved by different feeding regimens that reset circadian rhythms and may lead to better synchrony in metabolism and physiology. This review focuses on recent findings concerning the relationships between circadian rhythms, aging attenuation, and life-span extension in mammals.
New Insights into HIV Assembly and Trafficking
Authors: Balasubramaniam Muthukumar , Freed Eric O.
Published: August 2011

Assembly and release of human immunodeficiency virus type 1 (HIV-1) particles is mediated by the viral Gag polyprotein precursor. Gag is synthesized in the cytosol and rapidly translocates to membrane to orchestrate particle production. The cell biology of HIV-1 Gag trafficking is currently one of the least understood aspects of HIV-1 replication. In this review, we highlight the current understanding of the cellular machinery involved in Gag trafficking and virus assembly.
Comparison of Increased Aromatase versus ERα in the Generation of Mammary Hyperplasia and Cancer
Authors: Díaz-Cruz Edgar S. , Sugimoto Yasuro , Gallicano G. Ian , Brueggemeier Robert W. , Furth Priscilla A.
Published: August 2011

Factors associated with increased estrogen synthesis increase breast cancer risk. Increased aromatase and estrogen receptor α (ERα) in both normal epithelium and ductal carcinoma in situ lesions are found in conjunction with breast cancer, leading to the idea that altered estrogen signaling pathways predispose the mammary gland to cancer development. Here, we developed a transgenic mouse that conditionally expresses aromatase in the mammary gland, and used it along with a deregulated ERα expression model to investigate the molecular pathways involved in the development of mammary gland preneoplasia and carcinoma. Both increased ERα and aromatase expression led to the development of preneoplasia, but increased preneoplasia, in addition to carcinoma, was found in aromatase overexpressing mice. Increased prevalence of mammary pathologic changes in mice expressing aromatase correlated with increased cyclin E and cyclin-dependent kinase 2 expression. Gain of both ERα and aromatase increased expression of ERα and progesterone receptor, but aromatase produced a higher increase than ERα, accompanied by higher levels of downstream target genes Ccnd1, Myc, and Tnfsf11. In summary, whereas gain of both ERα and aromatase activate abnormal growth pathways in the mammary gland, aromatase induced a wider range of abnormalities that was associated with a higher prevalence of mammary preneoplasia and cancer progression. Cancer Res; 71(16); 5477–87. ©2011 AACR.
Curcumin Modulates MicroRNA-203–Mediated Regulation of the Src-Akt Axis in Bladder Cancer
Authors: Saini Sharanjot , Arora Sumit , Majid Shahana , Shahryari Varahram , Chen Yi , Deng Guoren , Yamamura Soichiro , Ueno Koji , Dahiya Rajvir
Published: August 2011

Bladder cancer is often associated with recurrence and progression to invasive metastatic disease that have palliative therapeutic options. The use of traditional chemotherapeutic agents for bladder cancer management often suffers from toxicity and resistance concerns. This emphasizes the need for development of safer, natural, nontoxic compounds as chemotherapeutic/chemopreventive agents. Curcumin (diferuloylmethane) is a natural compound that has been known to possess anticancer properties in various cancers, including bladder cancer. However, the biological targets of curcumin are not well defined. Recently, it has been proposed that curcumin may mediate epigenetic modulation of expression of microRNAs (miRNA). In this article, we define for the first time, that curcumin directly induces a tumor-suppressive miRNA, miR-203, in bladder cancer. miR-203 is frequently downregulated in bladder cancer due to DNA hypermethylation of its promoter. We studied the functional significance of miR-203 in bladder cancer cell lines and found that miR-203 has tumor suppressive properties. Also, we define Akt2 and Src as novel miR-203 targets in bladder cancer. Curcumin induces hypomethylation of the miR-203 promoter and subsequent upregulation of miR-203 expression. This leads to downregulation of miR-203 target genes Akt2 and Src that culminates in decreased proliferation and increased apoptosis of bladder cancer cells. This is the first report that shows a direct effect of curcumin on inducing epigenetic changes at a miRNA promoter with direct biological consequences. Our study suggests that curcumin may offer a therapeutic advantage in the clinical management of refractory bladder cancer over other standard treatment modalities. Cancer Prev Res; 4(10); 1698–709. ©2011 AACR.
Associations between Oral HPV16 Infection and Cytopathology: Evaluation of an Oropharyngeal “Pap-Test Equivalent” in High-Risk Populations
Authors: Fakhry Carole , Rosenthal Barbara T. , Clark Douglas P. , Gillison Maura L.
Published: August 2011

Human papillomavirus (HPV) is responsible for the rising incidence of oropharyngeal squamous cell cancers (OSCC) in the United States, and yet, no screening strategies have been evaluated. Secondary prevention by means of HPV detection and cervical cytology has led to a decline in cervical cancer incidence in the United States. Here, we explored an analogous strategy by evaluating associations between HPV16 infection, cytopathology, and histopathology in two populations at elevated risk for OSCCs. In the first, a cross-sectional study population (PAP1), cytology specimens were collected by means of brush biopsy from patients presenting with oropharyngeal abnormalities. In the second (PAP2), a nested case–control study, bilateral tonsillar cytology samples were collected at 12-month intervals from HIV-infected individuals. The presence of cytopathologic abnormality in HPV16-positive tonsil brush biopsies (cases) was compared with HPV16-negative samples (controls) matched on age and gender. HPV16 was detected in samples by consensus primer PCR and/or type-specific PCR. Univariate logistic regression was used to evaluate associations. In PAP1, HPV16 alone (OR: 6.1, 95% CI: 1.6–22.7) or in combination with abnormal cytology (OR: 20, 95% CI: 4.2–95.4) was associated with OSCC. In PAP2, 4.7% (72 of 1,524) of tonsillar cytology specimens from HIV-infected individuals without oropharyngeal abnormalities were HPV16 positive. Tonsillar HPV16 infection was not associated with atypical squamous cells of unknown significance (ASCUS), the only cytologic abnormality identified. Therefore, HPV16 was associated with OSCCs among individuals with accessible oropharyngeal lesions but not with cytologic evidence of dysplasia among high-risk individuals without such lesions. An oropharyngeal Pap-test equivalent may not be feasible, likely due to limitations in sampling the relevant tonsillar crypt epithelium. Cancer Prev Res; 4(9); 1378–84. ©2011 AACR.
Fibrin Clot Structure and Function
Authors: Undas Anetta , Ariëns Robert A.S.
Published: August 2011

The formation of fibrin clots that are relatively resistant to lysis represents the final step in blood coagulation. We discuss the genetic and environmental regulators of fibrin structure in relation to thrombotic disease. In addition, we discuss the implications of fibrin structure for treatment of thrombosis. Fibrin clots composed of compact, highly branched networks with thin fibers are resistant to lysis. Altered fibrin structure has consistently been reported in patients with several diseases complicated by thromboembolic events, including patients with acute or prior myocardial infarction, ischemic stroke, and venous thromboembolism. Relatives of patients with myocardial infarction or venous thromboembolism display similar fibrin abnormalities. Low-dose aspirin, statins, lowering of homocysteine, better diabetes control, smoking cessation, and suppression of inflammatory response increase clot permeability and susceptibility to lysis. Growing evidence indicates that abnormal fibrin properties represent a novel risk factor for arterial and venous thrombotic events, particularly of unknown etiology in young and middle-aged patients.
Splicing of Histone Deacetylase 7 Modulates Smooth Muscle Cell Proliferation and Neointima Formation Through Nuclear β-Catenin Translocation
Authors: Zhou Boda , Margariti Andriana , Zeng Lingfang , Habi Ouassila , Xiao Qingzhong , Martin Daniel , Wang Gang , Hu Yanhua , Wang Xian , Xu Qingbo
Published: August 2011

Objective—

Vascular smooth muscle cell (SMC) proliferation has an indispensable role in the pathogenesis of vascular disease, but the mechanism is not fully elucidated. The epigenetic enzyme histone deacetylase 7 (HDAC7) is involved in endothelial homeostasis and SMC differentiation and could have a role in SMC proliferation. In this study, we sought to examine the effect of 2 HDAC7 isoforms on SMC proliferation and neointima formation.

Methods and Results—

We demonstrated that overexpression of unspliced HDAC7 (HDAC7u) could suppress SMC proliferation through downregulation of cyclin D1 and cell cycle arrest, whereas spliced HDAC7 (HDAC7s) could not. Small interfering RNA (siRNA)–mediated knockdown of HDAC7 increased SMC proliferation and induced nuclear translocation of β-catenin. Additional experiments showed that only HDAC7u could bind to β-catenin and retain it in the cytoplasm. Reporter gene assay and reverse transcription polymerase chain reaction revealed a reduction of β-catenin activity in cells overexpressing HDAC7u but not HDAC7s. Deletion studies indicated that the C-terminal region of HDAC7u is responsible for the interaction with β-catenin. However, the addition of amino acids to the N terminus of HDAC7u disrupted the binding, further strengthening our hypothesis that HDAC7s does not interact with β-catenin. The growth factor platelet-derived growth factor-BB increased the splicing of HDAC7 while simultaneously decreasing the expression of HDAC7u. Importantly, in an animal model of femoral artery wire injury, we demonstrated that knockdown of HDAC7 by siRNA aggravates neointima formation in comparison with control siRNA.

Conclusion—

Our findings demonstrate that splicing of HDAC7 modulates SMC proliferation and neointima formation through β-catenin nuclear translocation, which provides a potential therapeutic target in vascular disease.