bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex-allocation plasticity in hermaphrodites of sexually dimorphic Fragaria virginiana (Rosaceae)
Authors: Bishop Eric J. , Spigler Rachel B. , Ashman Tia-Lynn
Published: March 2010

Sex-allocation plasticity is thought to play an important role in the evolution of separate sexes in plants. Accordingly, much attention has been paid to environmentally induced variation in fruit and seed production in sexually dimorphic species, but we know little about whether this variation arises as a direct response to environmental variation or is instead an indirect consequence of changes in plant size. In this study, we characterize sex-allocation plasticity across a resource gradient for several reproductive traits in hermaphrodites of gyno(sub)dioecious Fragaria virginiana Duch. We find significant plasticity, on average, for flower number, proportion fruit set, ovule number, proportion seed set, and runner number in response to resource variation. Plasticity of most traits examined tended to be at least partially independent of variation in plant size, suggesting that it is not simply an indirect consequence of plant allometry. Moreover, we find genetic variation for plasticity of key reproductive traits. Comparisons of relative plasticities among traits reveal that F. virginiana hermaphrodites are more likely to adjust female investment via changes in fruit and seed set than ovule number, and most likely to adjust male investment via flower number rather than anther number or pollen per anther, although there is genotypic variation for plasticity in pollen per anther. Evidence of within-population variation can logically be extended to suggest that variation in hermaphrodite sex-expression seen among natural populations of F. virginiana may be due, at least in part, to sex-allocation plasticity.
Juvenile leaves of Rhus glabra have higher photosynthetic thermal tolerance than mature leaves
Authors: Snider John L. , Choinski John S. , Slaton William
Published: March 2010

We have previously shown that juvenile leaves of Rhus glabra  L. growing in a field setting were consistently 2–3 °C warmer than mature leaves during periods of high irradiance. An experiment was done to test the hypothesis that these differences in leaf temperature lead to increased photosynthetic temperature tolerance in juvenile leaves when compared with cooler, mature leaves. Significant differences were found between the leaf stages with detached juvenile leaves having a slightly higher T15 (the temperature causing a 15% drop in maximum photochemical efficiency) than mature leaves (43.5 vs. 41.1 °C). Additionally, measurement of the effect of temperature on actual quantum yield (ΦPSII) showed maximum activity at 35 °C for mature leaves, whereas juvenile leaves exhibited a broader temperature response with similar activities between 30 and 40 °C. The 2 °C difference in T15 roughly coincided with observed average differences between juvenile and mature leaf temperature we observed in the field, indicating that higher juvenile leaf temperature is a factor in promoting their enhanced temperature tolerance.
Pollination of an invasive orchid, Cyrtopodium polyphyllum (Orchidaceae), by an invasive oil-collecting bee, Centris nitida, in southern Florida
Authors: Liu Hong , Pemberton Robert
Published: March 2010

The lack of appropriate pollinators is believed to be an impediment to naturalization of orchids. We studied the self-compatibility and pollination of an invasive, showy, rewardless, terrestrial orchid ( Cyrtopodium polyphyllum (Vell.) Pabst ex F. Barrios) in southern Florida. Pollination treatments indicated that the orchid is self-compatible but not autogamous. Visitor observations indicated that the orchid is pollinated by an invasive specialist oil-collecting bee ( Centris nitida Smith). The presence of the invasive Centris nitida has probably contributed to the naturalization of this probable oil reward mimicking orchid in Florida. We contrasted our results in the orchid’s invasive range with those reported in two studies in the orchid’s native range. In the invasive range in Florida, the orchid experiences a lower inbreeding depression. In both areas, the orchid is pollinated by Centris species and the pollination of the orchid is apparently enhanced by the presence of oil-rewarding species of the Malpighiaceae.
GROWTH OF COPPER ZINC TIN SULFIDE NANO-RODS BY ELECTRODEPOSITION USING ANODIZED ALUMINUM AS THE GROWTH MASK
Authors: CHAN C. P. , LAM H. , LEUNG K. K. , SURYA C.
Published: March 2010

In this work, we report the growth of Copper Zinc Tin Sulfide (CZTS) nano-rods on CZTS thin films. The nano-structures were fabricated using an anodized aluminum oxide (AAO) growth mask. The metallic constituents of CZTS were co-electrodeposited within the AAO nano-pores using a choline-based ionic liquid as the electrolyte. Sulfurization was performed in elementary sulfur vapor environment at 450°C for 4 hours in nitrogen ambient. The properties of the CZTS thin film grown in the process were studied by X-ray diffraction (XRD) analysis. The results indicated that the film has a stannite structure with preferred grain orientation along (112). The nano-rods fabricated using this technique show that the diameters of the rods can be easily varied from 150–250 nm by changing the potential in the anodization process. The morphology and crystal structure of CZTS nano-rods were characterized by scanning electron microscopy (SEM) and transmission electron microscopy (TEM).
REALIZATION OF HOLOGRAPHIC STORAGE ON METAL FILM BY FEMTOSECOND LASER PULSES MICROMACHINING
Authors: GUO ZHONGYI , WANG HAIFENG , LIU ZHENGJUN , QU SHILIANG , DAI JINGMIN , LIU SHUTIAN
Published: March 2010

Optical information has been stored on the metal film by femtosecond laser pulses with the aid of the computer-generated hologram (CGH). The Fourier transform of an object is performed by a computer, and then the resulted complex amplitude distribution is encoded by the detour phase method. The resulted cell-oriented CGH is directly written on the metal film deposited on the glass substrate using femtosecond laser by selective ablation. The object wave has also been reconstructed with high fidelity by using a collimated He-Ne laser beam.
FLATBAND SLOW LIGHT PHOTONIC CRYSTAL WAVEGUIDE IN BOTH TE AND TM POLARIZATIONS
Authors: YU BO , ZHANG YUNDONG
Published: March 2010

The flatband slow light properties of a honeycomb photonic crystal waveguide in both TE and TM polarizations are discussed. By structure tuning, the waveguide may have obviously different group velocities for the TE and TM modes, which gives it the characteristics of a polarizer.
TIME DOMAIN DESCRIPTION OF THE GROUP VELOCITY MANIPULATION USING SEMICONDUCTOR QUANTUM DOTS
Authors: YANG QIGUANG , SEO JAETAE , TABIBI BAGHER , YU WILLIAM , TAN GUOLONG , TEMPLE DOYLE
Published: March 2010

The slow and fast propagation phenomena of optical pulses in a single semiconductor quantum dot have been investigated in the time domain. It was found that both the advancement and the slowdown of a pulse might be fulfilled by using the finite response nature of the semiconductor quantum dot.
SLOW LIGHT IN A TWO MICROSPHERE OPTICAL FIBER SYSTEM
Authors: ZHANG JING , ZHANG YUNDONG , ZHANG XUENAN , YU BO , WU DAN , TIAN HE , YUAN PING , WANG NAN , WANG JINFANG
Published: March 2010

The condition of being undercoupled and overcoupled for the lower microsphere is investigated respectively in two microspheres coupled with a fiber taper system. The effective phase shift curves which could occur in normal dispersion to generate slow light are different based on both situations. The influence of the loss coefficient and coupler parameter for each microsphere is interpreted in detail.
INFLUENCE OF THE INITIAL PHASE PROFILE ON THE ASYMPTOTIC SELF-SIMILAR PARABOLIC DYNAMICS
Authors: FINOT CHRISTOPHE , WU LEI
Published: March 2010

We describe the influence of the initial phase profile on the convergence toward the asymptotic self-similar parabolic shape. More precisely, based on numerical simulations, we discuss the impact of an initial linear chirp and a π phase shift. If the parabolic shape has been found to describe accurately the pulse envelope, dark structures can appear and also evolve self-similarly on the parabolic background.
PREMODULATION-FREE MICROWAVE FREQUENCY UP/DOWN-CONVERSION USING OPTICAL-FIBER-STIMULATED BRILLOUIN SCATTERING
Authors: GAO YING , GAO SHIMING
Published: March 2010

An all-optical premodulation-free microwave frequency up/down-conversion method is presented based on stimulated Brillouin scattering in optical fibers for bidirection radio-over-fiber systems. Through optical heterodyning between the modulated optical carrier and the Stokes light, the microwave signal of 1.5 GHz is up-converted to 9 and 12 GHz, and the microwave signal of 9 GHz is down-converted to 1.5 GHz. The unexpected microwaves are more than 7 dB suppressed by loading the signal to convert with the optical-carrier-suppressed modulation.
MALAKITE: AN AUTOMATIC TOOL FOR CHARACTERISATION OF STRUCTURE OF RELIABLE BLOCKS IN MULTIPLE ALIGNMENTS OF PROTEIN SEQUENCES
Authors: BURKOV BORIS , NAGAEV BORIS , SPIRIN SERGEI , ALEXEEVSKI ANDREI
Published: March 2010

It makes sense to speak of alignment of protein sequences only within the regions, where the sequences are related to each other. This simple consideration is often disregarded by programs of multiple alignment construction. A package for alignment analysis MAlAKiTE (Multiple Alignment Automatic Kinship Tiling Engine) is introduced. It aims to find the blocks of reliable alignment, which contain related regions only, within the whole alignment and allows for dealing with them. The validity of the detection of reliable blocks' was verified by comparison with structural data.
Improvement in Ferroelectric Fatigue Endurance of Poly(methyl metacrylate)-Blended Poly(vinylidene fluoride–trifluoroethylene)
Authors: Yoon Joo-Won , Yoon Sung-Min , Ishiwara Hiroshi
Published: March 2010

Ferroelectric poly(vinylidene fluoride–trifluoroethylene) [P(VDF–TrFE)] and poly(methyl metacrylate) (PMMA)-blended P(VDF–TrFE) thin films are deposited by spin coating on Pt/TiO2/SiO2/Si, and their fatigue endurance is investigated by forming metal–ferroelectrics–metla (MFM) capacitors. It has been found that fatigue endurance is significantly improved by blending PMMA into P(VDF–TrFE). Under the tested conditions, the best endurance for alternating voltage pulses is obtained in the 4 wt % PMMA blended P(VDF–TrFE) film.
LiF/Al Base Electrodes in Vertical Metal-Base Organic Transistors for Heat-Treatment-Free Process
Authors: Suzuki Fumito , Nakayama Ken-ichi , Pu Yong-Jin , Yokoyama Masaaki , Kido Junji
Published: March 2010

Clear current modulation and current amplification were observed in vertical metal-base organic transistors (MBOTs) without heat treatment in air that was previously essential. The devices, which use a LiF/Al base electrode and a C60 layer under it, were prepared without heat treatment and showed a large current modulation exceeding 114.5 mA cm-2 and a current amplification factor of 51.7 at a collector voltage of 5 V and a base voltage of 3 V. The LiF/Al base electrode and the C60 layer under it were found to contribute to the increase in on current and to the decrease in off current, respectively.
Low-Voltage Pentacene Field-Effect Transistors Fabricated on High-Dielectric-Constant Strontium Titanate Insulator
Authors: Yan Hu , Jo Toshihiko , Okuzaki Hidenori
Published: March 2010

A strontium titanate (SrTiO3) thin film on a heavily doped n-type silicon wafer prepared by sputtering was characterized by various means. The result indicated that the thin film mainly consisted of an 87-nm-thick amorphous SrTiO3 with a Sr:Ti:O ratio of 1:1.3:4.7, a dielectric constant of ε
r=12.1, and a leakage current density of 0.2 nA/cm2 at an electric field of 1 MV/cm. Pentacene field-effect transistors fabricated using the SrTiO3 thin film as an insulator, showed well-saturated output characteristics at low driving voltages (V
D=-3 V), and a hole mobility of 0.08 cm2 V-1 s-1, an on/off current ratio of 104, and threshold voltage of -0.7 V.
A Proposal of a Novel Gain Profile Model of Multi-Quantum-Well Semiconductor Optical Amplifiers
Authors: Shimizu Satoshi , Uenohara Hiroyuki
Published: March 2010

We introduce a novel model of the gain profile of multi-quantum-well semiconductor optical amplifiers (MQW-SOAs) that takes the variation of the gain spectrum with carrier density into detailed account. In this model, the gain spectrum is approximated by a cubic function and its peak gain, peak-gain wavelength, and polynomial coefficients are expressed by hyperbolic functions of carrier density. By using the proposed model, we calculated the static gain characteristics and dynamic response of cross gain modulation (XGM) of an SOA and compared them with the experimental results. Under both operation conditions, very good agreement with the experimental results was obtained.
Optimization of Active Layer Thickness in Planar Organic Solar Cells via Optical Simulation Methods
Authors: Boland Patrick , Namkoong Gon
Published: March 2010

A thin-film optical simulation modeling has been used to determine ideal active layer thicknesses for regioregular poly(3-hexylthiophene) and phenyl-C61/C71-butyric acid methyl ester (P3HT:PC61BM and P3HT:PC71BM) organic blends used as photoactive components in polymer solar cells. Solar cells are simulated based on their optical properties after varying such factors as active layer thickness, electron and hole mobilities, and the Langevin recombination efficiency. Our results indicate that optimizing device efficiency is strongly dependent on the simultaneous control of active layer thickness and the charge carrier mobilities.
LiNbO3Waveguide Quasi-Phase-Matched Highly Nondegenerate Twin Photon Generation Device for Heralded Single Photon Source
Authors: Kajita Shozo , Fujimura Masatoshi , Suhara Toshiaki
Published: March 2010

We designed, fabricated, and characterized a LiNbO3waveguide quasi-phase-matched highly nondegenerate twin photon generation device for a heralded single photon source. The power of the generated photon was nearly proportional to the pump power, as theoretically predicted. The temporal correlation of the generated twin photon was demonstrated by a photon coincidence counting experiment.
Development of a Total Reflection Zone Plate for Hard X-ray Focusing
Authors: Tsuji Takuya , Takano Hidekazu , Koyama Takahisa , Tsusaka Yoshiyuki , Kagoshima Yasushi
Published: March 2010

A total reflection zone plate (TRZP) was developed and fabricated as a hard X-ray focusing device. It consists of a Au zone pattern drawn on a flat SiO2 substrate. The reflection only from the zone pattern can be extracted by operating the TRZP with a grazing incident angle between critical angles of Au and SiO2. The effective zone size is fully reduced to the drawn zone size with a small reduction ratio below 1/100. A focusing test using 10 keV X-rays was performed at the “Hyogo-ID” beamline (BL24XU) of SPring-8, and a focusing beam with diffraction-limited size was achieved.
New Approach to Enhance Contrast Ratio at Normal Incidence by Controlling the Retardation of Optical Compensation Film in Vertically Aligned Liquid Crystal Displays
Authors: Ishiguro Makoto , Sekiguchi Megumi , Saitoh Yukito
Published: March 2010

We found that the light leakage at normal incidence of a vertically aligned liquid crystal display (VA-LCD) in black state is strongly affected by the polarization states of obliquely incident light. Experimental results were explained by a light scattering model of substrates on both sides of a liquid crystal layer. Applying this model, we found that the contrast ratio at normal incidence can be highly enhanced by controlling the retardation value of retardation films. This is a new, effective approach to enhancement of the contrast ratio in LCDs, different from the conventional approach of simply decreasing the depolarization of the scattering media.
Highly Stacked and High-Quality Quantum Dots Fabricated by Intermittent Deposition of InGaAs
Authors: Sugaya Takeyoshi , Amano Takeru , Mori Masahiko , Niki Shigeru , Kondo Michio
Published: March 2010

We report the successful fabrication of a highly stacked and well-aligned InGaAs quantum dot (QD) structure of over 50 layers without using a strain compensation technique by the intermittent deposition of InGaAs layers and an As2 source, resulting in no degradation in crystal quality. Intermittent deposition of InGaAs layers at relatively high temperature accounts for the formation of InGaAs QDs despite their small lattice mismatch with GaAs. The photoluminescence measurements indicate that the 50-stack InGaAs QD structures have high crystal quality, whereas the crystal quality of multistacked InAs QDs becomes much worse even with four-stack structures.
Stability and Indium Incorporation Processes on In0.25Ga0.75N Surfaces under Growth Conditions: First-Principles Calculations
Authors: Akiyama Toru , Yamashita Tomoki , Nakamura Kohji , Ito Tomonori
Published: March 2010

The structural stability and indium incorporation on In0.25Ga0.75N surfaces for various orientations are studied on the basis of first-principles total-energy calculations. The calculated surface phase diagrams as functions of temperature and pressure demonstrate that the (0001) and (2201) surfaces with bulk In concentration of 25% are stabilized for low temperature growth conditions. In contrast, the (1100) surface forms topmost Ga–N dimers over the wide range of growth conditions, and Ga atoms are preferentially adsorbed on the (1100) surfaces. These results imply that InGaN with In concentrations of ∼25% can be grown on c-plane and semipolar (2201) orientations.
Characteristics of Internal Inductively Coupled Plasma Source for Ultralarge-Area Plasma Processing
Authors: Lim Jong Hyeuk , Gweon Gwang Ho , Hong Seung Pyo , Kim Kyong Nam , Kim Yi Yeon , Yeom Geun Young
Published: March 2010

The capacitive–inductive (E–H) mode transition characteristics of an ultralarge-area (2,750×2,350 mm2) inductively coupled plasma (ICP) system with multiple internal U-type antennas have been investigated. When the electrical characteristics of the ICP antenna such as power transfer efficiency and ICP source impedance, were measured as a function of ICP power, a distinctive change from E to H mode was identified at an rf power of approximately 3 kW. When the power transfer mode was changed from capacitive to inductive for the multiple U-type antenna configuration, better plasma uniformity was obtained owing to the more uniform power deposition along the antenna line.
Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease
Authors: Wang Zhigang , Yao Tong , Pini Maria , Zhou Zhanxiang , Fantuzzi Giamila , Song Zhenyuan
Published: March 2010

Adipose tissue dysfunction, featured by insulin resistance and/or dysregulated adipokine production, plays a central role not only in disease initiation but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Promising beneficial effects of betaine supplementation on nonalcoholic fatty liver disease (NAFLD) have been reported in both clinical investigations and experimental studies; however, data related to betaine therapy in NAFLD are still limited. In this study, we examined the effects of betaine supplementation on hepatic fat accumulation and injury in mice fed a high-fat diet and evaluated mechanisms underlying its hepatoprotective effects. Male C57BL/6 mice weighing 25 ± 0.5 (SE) g were divided into four groups (8 mice/group) and started on one of four treatments: control diet, control diet supplemented with betaine, high-fat diet, and high-fat diet supplemented with betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Our results showed that long-term high-fat feeding caused NAFLD in mice, which was manifested by excessive neutral fat accumulation in the liver and elevated plasma alanine aminotransferase levels. Betaine supplementation alleviated hepatic pathological changes, which were concomitant with attenuated insulin resistance as shown by improved homeostasis model assessment of basal insulin resistance values and glucose tolerance test, and corrected abnormal adipokine (adiponectin, resistin, and leptin) productions. Specifically, betaine supplementation enhanced insulin sensitivity in adipose tissue as shown by improved extracellular signal-regulated kinases 1/2 and protein kinase B activations. In adipocytes freshly isolated from mice fed a high-fat diet, pretreatment of betaine enhanced the insulin signaling pathway and improved adipokine productions. Further investigation using whole liver tissues revealed that betaine supplementation alleviated the high-fat diet-induced endoplasmic reticulum stress response in adipose tissue as shown by attenuated glucose-regulated protein 78/C/EBP homologous protein (CHOP) protein abundance and c-Jun NH2-terminal kinase activation. Our findings suggest that betaine might serve as a safe and efficacious therapeutic tool for NAFLD by improving adipose tissue function.
Apical leptin induces chloride secretion by intestinal epithelial cells and in a rat model of acute chemotherapy-induced colitis
Authors: Hoda Raschid M. , Scharl Michael , Keely Stephen J. , McCole Declan F. , Barrett Kim E.
Published: March 2010

The purpose of this study was to investigate whether luminal leptin alters ion transport properties of the intestinal epithelium under acute inflammatory conditions. Monolayers of human intestinal T84 epithelial cells and a rat model of chemotherapy-induced enterocolitis were used. Cells were treated with leptin and mounted in Ussing chambers to measure basal and secretagogue-induced changes in transepithelial short-circuit current ( Isc). Furthermore, the role of MAPK and phosphatidylinositol 3-kinase (PI3K) signaling pathways in mediating responses to leptin was investigated. Acute colitis in Sprague-Dawley rats was induced by intraperitoneal injection of 40 mg/kg methotrexate. Leptin (100 ng/ml) induced a time-dependent increase in basal Isc in T84 intestinal epithelial cells ( P < 0.01). Moreover, pretreatment of T84 cells with leptin for up to 1 h significantly potentiated carbachol- and forskolin-induced increases in Isc. Pretreatment with an inhibitor of MAPK abolished the effect of leptin on basal, carbachol- and forskolin-induced chloride secretion ( P < 0.05). However, the PI3K inhibitor, wortmannin, only blunted the effect of leptin on forskolin-induced increases in Isc. Furthermore, leptin treatment evoked both ERK1/2 and Akt1 phosphorylation in T84 cells. In the rat model, luminal leptin induced significant increases in Isc across segments of proximal and, to a lesser extent, distal colon ( P < 0.05). We conclude that luminal leptin is likely an intestinal chloride secretagogue, particularly when present at elevated concentrations and/or in the setting of inflammation. Our findings may provide a mechanistic explanation, at least in part, for the clinical condition of secretory diarrhea both in hyperleptinemic obese patients and in patients with chemotherapy-induced intestinal inflammation.
Effect of indomethacin on bile acid-phospholipid interactions: implication for small intestinal injury induced by nonsteroidal anti-inflammatory drugs
Authors: Zhou Yong , Dial Elizabeth J. , Doyen Rand , Lichtenberger Lenard M.
Published: March 2010

The injurious effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in the small intestine was not appreciated until the widespread use of capsule endoscopy. Animal studies found that NSAID-induced small intestinal injury depends on the ability of these drugs to be secreted into the bile. Because the individual toxicity of amphiphilic bile acids and NSAIDs directly correlates with their interactions with phospholipid membranes, we propose that the presence of both NSAIDs and bile acids alters their individual physicochemical properties and enhances the disruptive effect on cell membranes and overall cytotoxicity. We utilized in vitro gastric AGS and intestinal IEC-6 cells and found that combinations of bile acid, deoxycholic acid (DC), taurodeoxycholic acid, glycodeoxycholic acid, and the NSAID indomethacin (Indo) significantly increased cell plasma membrane permeability and became more cytotoxic than these agents alone. We confirmed this finding by measuring liposome permeability and intramembrane packing in synthetic model membranes exposed to DC, Indo, or combinations of both agents. By measuring physicochemical parameters, such as fluorescence resonance energy transfer and membrane surface charge, we found that Indo associated with phosphatidylcholine and promoted the molecular aggregation of DC and potential formation of larger and isolated bile acid complexes within either biomembranes or bile acid-lipid mixed micelles, which leads to membrane disruption. In this study, we demonstrated increased cytotoxicity of combinations of bile acid and NSAID and provided a molecular mechanism for the observed toxicity. This mechanism potentially contributes to the NSAID-induced injury in the small bowel.
Cyclic AMP stimulates Mrp2 translocation by activating p38α MAPK in hepatic cells
Authors: Schonhoff Christopher M. , Webster Cynthia R. L. , Anwer M. Sawkat
Published: March 2010

Cyclic AMP (cAMP) induces translocation of multidrug resistant protein 2 (Mrp2) to the canalicular membrane and activates p38 MAPK in rat hepatocytes. In this study, we tested the hypothesis that cAMP-induced Mrp2 translocation may be mediated via p38 MAPK. Studies were conducted in rat hepatocytes and in a human hepatoma cell line, HuH-7. In rat hepatocytes, cAMP increased Mrp2 translocation and p38 MAPK activity. These effects of cAMP were inhibited by SB203580, an inhibitor of p38 MAPK. Wortmannin, a specific inhibitor of phosphoinositide-3-kinase (PI3K), did not inhibit cAMP induced activation of p38 MAPK, indicating PI3K-independent activation of p38 MAPK by cAMP. To further define the role of p38 MAPK, molecular approaches were used to up- or downregulate p38 MAPK activity in HuH-7 cells using constitutively active (CA) and dominant-negative (DN) MAPK kinase 3 and 6 (MKK3/6). MKK3/6 are upstream kinases responsible for the activation of p38 MAPK. Cells transfected with CAMKK6 showed increased p38 MAPK activity and MRP2 translocation compared with empty vector. cAMP-induced activation of p38 MAPK was inhibited in cells transfected with DNMKK3/6 and DNMKK3, but not with DNMKK6. DNMKK3/6 and DNMKK3 also inhibited cAMP-induced MRP2 translocation. cAMP selectively activated p38α MAPK in HuH-7 cells. Knockdown of p38α MAPK by short heterodimer RNA resulted in decreased level of p38 MAPK and failure of cAMP to stimulate MRP2 translocation. Taken together, these results suggest that cAMP-induced MRP2 translocation in hepatic cells is mediated via PI3K-independent and MKK3-mediated activation of p38α MAPK.
Bradykinin receptor blockade reduces sympathetic nerve response to muscle contraction in rats with ischemic heart failure
Authors: Koba Satoshi , Xing Jihong , Sinoway Lawrence I. , Li Jianhua
Published: March 2010

Previous animal and human studies have suggested that a muscle reflex engaged during contraction leads to heightened levels of sympathetic activity in congestive heart failure (CHF). The present experiment was designed to test the role for bradykinin, which is produced within contracting skeletal muscle and contributes to the muscle reflex through its action on kinin B2receptors located on the endings of thin fiber muscle afferents. CHF was induced in rats by myocardial infarction (MI) after coronary artery ligation. Echocardiography was performed to determine fractional shortening (FS), an index of the left ventricular function. In the decerebrate rats, we examined renal sympathetic nerve activity (RSNA) during 1 min intermittent (1 to 4 s stimulation to relaxation) contraction of left triceps surae muscles. RSNA responded synchronously as tension was developed, and the response was significantly ( P < 0.05) greater in MI rats [+39 ± 9% s−1(integrated RSNA over time); n = 16] with 20 ± 2% of FS than that in control healthy rats (+19 ± 2% s−1; n = 16) with 49 ± 2% of FS. Tension development did not differ significantly between the two groups of rats. Thirty minutes after intra-arterial injection into the hindlimb circulation of the kinin B2receptor antagonist, HOE-140 (2 μg/kg), the RSNA response to contraction was significantly reduced in the MI rats (+26 ± 7% s−1) but not in the control rats (+17 ± 2% s−1). These data suggest that bradykinin within contracting muscle is part of the exaggerated muscle reflex seen in CHF.
The myocardial infarct size-limiting effect of sitagliptin is PKA-dependent, whereas the protective effect of pioglitazone is partially dependent on PKA
Authors: Ye Yumei , Keyes Kyle T. , Zhang Congfang , Perez-Polo Jose R. , Lin Yu , Birnbaum Yochai
Published: March 2010

Pioglitazone (PIO) and glucagon-like peptide-1 (GLP-1) analogs limit infarct size (IS) in experimental models. The effects of the dipeptidyl-peptidase-IV inhibitors, which increase the endogenous levels of GLP-1, on myocardial protection, are unknown. We studied whether sitagliptin (SIT) and PIO have additive effects on IS limitation in the mouse. Mice received 3-day or 14-day oral SIT (300 mg·kg−1·day−1), PIO (5 mg·kg−1·day−1), SIT + PIO, or vehicle. In addition, mice received intravenous H-89 [20 mg/kg, a protein kinase A (PKA) inhibitor] or vehicle 1 h before ischemia. Rats underwent 30 min myocardial ischemia and 4 h reperfusion. SIT, PIO, and SIT + PIO for 3 days significantly reduced IS (24.3 ± 2.7, 23.0 ± 0.8, and 14.7 ± 0.9%) compared with controls (46.2 ± 2.8%). H-89 completely blocked the effect of SIT and partially blocked the PIO effect. SIT, but not PIO, increased cAMP levels. PKA activity was increased by PIO and to a greater extent by SIT. PIO, but not SIT, increased cytosolic phospholipase A2 and cyclooxygenase-2 activity. Accordingly, 6-keto-PGF1α and 15-deoxy-PGJ2 increased by PIO but not SIT. In contrast, SIT, and to a lesser extent PIO, increased 15-epi-lipoxin A4 levels. H-89 completely blocked the effect of SIT and PIO on 15-epi-lipoxin A4 levels. PIO, and to a greater extent SIT, increased endothelial nitric oxide synthase and cAMP response element-binding protein phosphorylation, an effect that was blocked by H-89. With a 14-day pretreatment experiment, IS was 46.4 ± 1.0% in the control group, 16.9 ± 0.6% in SIT ( P < 0.001), 19.1 ± 1.1% in PIO ( P = 0.014), and 12.9 ± 0.7% in SIT + PIO ( P < 0.001). We found that SIT and PIO limit IS using different pathways. The protective effect of SIT is via cAMP-dependent PKA activation, whereas PIO mediates its effects via both PKA-dependent and -independent pathways.
The calcineurin-myocyte enhancer factor 2c pathway mediates cardiac hypertrophy induced by endoplasmic reticulum stress in neonatal rat cardiomyocytes
Authors: Zhang Zhen-Ying , Liu Xiu-Hua , Hu Wei-Cheng , Rong Fei , Wu Xu-Dong
Published: March 2010

Endoplasmic reticulum (ER) stress (ERS) is involved in various cardiovascular diseases. Our previous study verified that ERS took part in the development of cardiac hypertrophy; however, its mechanism is still unclear. This study aimed to investigate the roles of the calcineurin (CaN) signal pathway in hypertrophy induced by the ERS inductor thapsigargin (TG) in neonatal cardiomyocytes from Sprague-Dawley rats. Investigation of ER chaperone expression, ER staining, and calreticulin immunoflourescence were used to detect the ERS response. mRNA expression of atrial natriuretic peptide and brain natriuretic peptide, total protein synthesis rate, and cell surface area were used to evaluate cardiac hypertrophy induced by TG. TG induced a significant ERS response along with hypertrophy in a dose- and time-dependent manner in cardiomyocytes, which was verified by treatment with tunicamycin, another ERS inducer. Furthermore, TG induced a significant elevation of the intracellular Ca2+level, CaN activation, and myocyte enhancer factor 2c (MEF2c) expression in a dose- and time-dependent manner in cardiomyocytes. Cyclosporine A, a CaN inhibitor, markedly suppressed MEF2c nuclear translocation and inhibited TG-induced hypertrophy. These results demonstrate that ERS induces cardiac hypertrophy and that the CaN-MEF2c pathway is involved in ERS-induced hypertrophy in cardiomyocytes.
Combined local ischemic postconditioning and remote perconditioning recapitulate cardioprotective effects of local ischemic preconditioning
Authors: Xin Ping , Zhu Wei , Li Jing , Ma Shixin , Wang Lixing , Liu Mingya , Li Jingbo , Wei Meng , Redington Andrew N.
Published: March 2010

Ischemic postconditioning (PostC) and perconditioning (PerC) provide practical methods for protecting the heart against ischemia-reperfusion (I/R) injury, but their combined effects have not been studied in detail. Using an in vivo rat I/R model, we tested 1) whether additive effects were produced when local PostC was preceded by varying doses of remote PerC, and whether the optimal PostC+PerC regime is additive to local ischemic preconditioning (IPC), and 2) how combined PostC+PerC alters the activity of the reperfusion injury salvage kinase pathway. The optimal combination of PerC and PostC therapy was produced by PerC delivered with four cycles of 5 min of limb ischemia followed by 5-min reperfusion. This resulted in lower infarct size (22.56 ± 4.45%) compared with rats with PostC alone (29.39 ± 3.66%) and PerC alone (33.49 ± 5.81%) and complementary differences in the generation of reactive oxygen species and apoptotic signaling. However, this optimal combination of PostC+PerC resulted in protection similar to local IPC alone (18.8 ± 2.54%, P = 0.13), and when added to IPC there was no additional protection (19.62 ± 2.89%, P = 0.675). Akt and ERK1/2 phosphorylation was induced by PostC and PerC and maximally by combined PostC+PerC treatment, and protection was abolished by phosphatidylinositol 3-kinase or ERK1/2 inhibitors. This study shows that neither PostC nor a maximized “dose” of PerC leads to optimal kinase signaling or cardioprotection compared with IPC alone. However, combined PostC+PerC may result in complementary effects on kinase signaling to recapitulate the effects of local IPC. Finally, combined PostC+PerC is not additive to IPC, suggesting that each works via a common pathway.
Epigenetics and cancer
Authors: Kanwal Rajnee , Gupta Sanjay
Published: March 2010

Epigenetic modifications are central to many human diseases, including cancer. Traditionally, cancer has been viewed as a genetic disease, and it is now becoming apparent that the onset of cancer is preceded by epigenetic abnormalities. Investigators in the rapidly expanding field of epigenetics have documented extensive genomic reprogramming in cancer cells, including methylation of DNA, chemical modification of the histone proteins, and RNA-dependent regulation. Recognizing that carcinogenesis involves both genetic and epigenetic alterations has led to a better understanding of the molecular pathways that govern the development of cancer and to improvements in diagnosing and predicting the outcome of various types of cancer. Studies of the mechanism(s) of epigenetic regulation and its reversibility have resulted in the identification of novel targets that may be useful in developing new strategies for the prevention and treatment of cancer.
Oxidative stress is required for mechanical ventilation-induced protease activation in the diaphragm
Authors: Whidden Melissa A. , Smuder Ashley J. , Wu Min , Hudson Matthew B. , Nelson W. Bradley , Powers Scott K.
Published: March 2010

Prolonged mechanical ventilation (MV) results in diaphragmatic weakness due to fiber atrophy and contractile dysfunction. Recent work reveals that activation of the proteases calpain and caspase-3 is required for MV-induced diaphragmatic atrophy and contractile dysfunction. However, the mechanism(s) responsible for activation of these proteases remains unknown. To address this issue, we tested the hypothesis that oxidative stress is essential for the activation of calpain and caspase-3 in the diaphragm during MV. Cause-and-effect was established by prevention of MV-induced diaphragmatic oxidative stress using the antioxidant Trolox. Treatment of animals with Trolox prevented MV-induced protein oxidation and lipid peroxidation in the diaphragm. Importantly, the Trolox-mediated protection from MV-induced oxidative stress prevented the activation of calpain and caspase-3 in the diaphragm during MV. Furthermore, the avoidance of MV-induced oxidative stress not only averted the activation of these proteases but also rescued the diaphragm from MV-induced diaphragmatic myofiber atrophy and contractile dysfunction. Collectively, these findings support the prediction that oxidative stress is required for MV-induced activation of calpain and caspase-3 in the diaphragm and are consistent with the concept that antioxidant therapy can retard MV-induced diaphragmatic weakness.
A new method to study in vivo protein synthesis in slow- and fast-twitch muscle fibers and initial measurements in humans
Authors: Dickinson J. M. , Lee J. D. , Sullivan B. E. , Harber M. P. , Trappe S. W. , Trappe T. A.
Published: March 2010

The aim of this study was to develop an approach to directly assess protein fractional synthesis rate (FSR) in isolated human muscle fibers in a fiber type-specific fashion. Individual muscle fibers were isolated from biopsies of the vastus lateralis (VL) and soleus (SOL) obtained from eight young men during a primed, continuous infusion of [5,5,5-2H3]leucine performed under basal conditions. To determine mixed protein FSR, a portion of each fiber was used to identify fiber type, fibers of the same type were pooled, and the [5,5,5-2H3]leucine enrichment was determined via GC-MS. Processing isolated slow-twitch [myosin heavy chain (MHC) I] and fast-twitch (MHC IIa) fibers for mixed protein bound [5,5,5-2H3]leucine enrichment yielded mass ion chromatographic peaks that were similar in shape, abundance, and measurement reliability as tissue homogenates. In the VL, MHC I fibers exhibited a 33% faster ( P < 0.05) mixed protein FSR compared with MHC IIa fibers (0.068 ± 0.006 vs. 0.051 ± 0.003%/h). MHC I fibers from the SOL (0.060 ± 0.005%/h) and MHC I fibers from the VL displayed similar ( P > 0.05) mixed protein FSR. Feasibility of processing isolated human muscle fibers for analysis of myofibrillar protein [5,5,5-2H3]leucine enrichment was also confirmed in non-fiber-typed pooled fibers from the VL. These methods can be applied to the study of fiber type-specific responses in human skeletal muscle. The need for this level of investigation is underscored by the different contributions of each fiber type to whole muscle function and the numerous distinct adaptive functional and metabolic changes in MHC I and MHC II fibers originating from the same muscle.
Changes in ventricular twist and untwisting with orthostatic stress: endurance athletes versus normally active individuals
Authors: Esch Ben T. , Scott Jessica M. , Haykowsky Mark J. , Paterson Ian , Warburton Darren E. R. , Cheng-Baron June , Chow Kelvin , Thompson Richard B.
Published: March 2010

Endurance-trained individuals exhibit larger reductions in left ventricular (LV) end-diastolic volume in response to lower body negative pressure (LBNP) compared with normally active individuals. However, the relationship between LV torsion and untwisting and the LV volume response to LBNP in endurance athletes is unknown. Eight endurance-trained athletes [maximal oxygen consumption (V̇o2max): 66.4 ± 7.2 ml·kg−1·min−1] and eight normally active individuals (V̇o2max: 41.9 ± 9.0 ml·kg−1·min−1) (all men) underwent two cardiac magnetic resonance imaging (MRI) assessments, the first during supine rest and the second during −30 mmHg LBNP. Right ventricular (RV) and LV volumes were assessed, myocardial tagging was applied in order to quantify LV peak torsion and peak untwisting rate, and filling rates were measured with phase-contrast MRI. In response to LBNP, endurance-trained individuals had greater reductions in RV and LV end-diastolic volume and stroke volume ( P < 0.05). Endurance athletes had reduced untwisting rates (20.3 ± 8.7°/s), while normally active individuals had increased untwisting rates (−16.2 ± 32.1°/s) in response to LBNP ( P < 0.05). Changes in peak untwisting rate were significantly correlated with change in peak torsion ( R = −0.87, P < 0.05), with the change in early filling rate and V̇o2max, but not with changes in end-diastolic or end-systolic volume ( P > 0.05). We conclude that increased untwisting rates in normally active subjects may mitigate the drop in early filling rate with LBNP and thus may be a compensatory mechanism for the reduction in stroke volume with volume unloading. The opposite response in athletes, who showed a decreased untwisting rate, may contribute to their larger reductions in LV end-diastolic and stroke volumes with volume unloading and their orthostatic intolerance.
Bismuth-Based First-Line Therapy for Helicobacter pylori Eradication in Type 2 Diabetes Mellitus Patients
Authors: Demir Mehmet , Göktürk Savaş , Öztürk Nevin Akçaer , Serin Ender , Yilmaz Uğur
Published: March 2010

Background/Aim: The primary aim of this study was to assess the efficacy of a bismuth-based quadruple regimen as first-line therapy for Helicobacter pylori (HP) eradication in diabetes mellitus (DM) patients. The secondary aim was to study the effect of HP eradication on dyspeptic symptoms in DM patients. Method: Eighty-nine consecutive type 2 DM and 48 non-diabetic age- and sex-matched patients were enrolled in this study. Diabetic patients were randomized to receive either pantoprazole (40 mg b.i.d.), clarithromycin (500 mg b.i.d.), and amoxicillin (1 g b.i.d., PCA-DM group) for 14 days, or pantoprazole (40 mg b.i.d.), bismuth citrate (400 mg b.i.d.), tetracycline (500 mg q.i.d.), and metronidazole (500 mg b.i.d., PBTM-DM group) for 14 days as the eradication regimen. All non-diabetic patients were treated by quadruple therapy (PBTM-non-DM group) for 14 days. We used the validated Leeds Dyspepsia Questionnaire (LDQ) to assess dyspeptic symptoms at baseline and 6 weeks after the end of treatment. Results: The HP eradication rates with intention-to-treat (ITT) and per-protocol (PP) analyses were 51% (for both) in the PCA-DM group; 81 and 85% in the PBTM-DM group, and 85 and 87% in the PBTM-non-DM group. The eradication rates are not different between the PBTM-DM and PBTM-non-DM groups (p > 0.05). The eradication rate was significantly lower in the PCA-DM group with both ITT and PP analysis than in the PBTM-DM and PBTM-non-DM groups (p < 0.05). LDQ score was 4.53 ± 7.7 in DM patients with successful eradication and 14.68 ± 5.9 in DM patients without successful eradication (p < 0.05). Conclusion: The bismuth-based quadruple eradication regimen as first-line therapy is safe, tolerable and achieves a high cure rate in patients with DM, and successful eradication may be beneficial on dyspeptic symptoms.
The Effect of External Beam Irradiation Timing on Skin Graft Survival
Authors: Kulahci Y. , Duman H. , Zor F. , Bozkurt M. , Guden M. , Gunhan O. , Celasun B. , Sengezer M.
Published: March 2010

Background: The purpose of this study was to evaluate skin graft integrity after external beam irradiation in a rat model. Methods: Forty-eight male Wistar rats were randomly assigned to 8 groups (A, B, C, D, Ac, Bc, Cc and Dc). A rectangular full-thickness skin graft was raised and reapplied to its original bed on the dorsum of each rat. Groups Ac, Bc, Cc and Dc were the control groups and were not given postoperative irradiation. After grafting, 25 Gy unfractioned cobalt60 irradiation was administered to groups A, B, C and D on postoperative days 10, 20, 30 and 40, respectively. Histological samples were obtained 8 weeks after grafting. Dermal and epidermal thickness were measured by the KS-400 image analysis program. Results: The difference in the epidermal and/or dermal thickness between the irradiated groups was not found to be significant. Furthermore, when histological features and the image analysis of the irradiated groups were compared with each other, there were no significant differences between the groups. Conclusions: Although we are aware that experimental results may not directly translate to the clinical setting, the present study indicates that external radiotherapy can be performed to skin-grafted areas as early as 10 days postoperatively.
Induction of Lymphocyte Apoptosis in Rat Liver Allograft by Adenoviral Gene Transfection of Human Interleukin-10
Authors: Li Jie-qun , Qi Hai-zhi , He Zhi-jun , Hu Wei , Si Zhong-zhou , Li Yi-ning
Published: March 2010

Background/Aims: Gene therapy can provide a possible avenue in organ transplantation to treat acute allograft rejection. This study was designed to investigate the effect of adenovirus-mediated human IL-10 (hIL-10) gene transfer on the apoptosis of infiltrating lymphocytes and examine the efficacy of hIL-10 gene transfer in combination with subtherapeutic doses of cyclosporine A (CsA) in a rat liver transplantation model. Methods: Inbred male DA and LEW rats were used for liver donors and recipients, respectively. The rats were divided into saline, Ad-lacZ, CsA, Ad-hIL-10 and Ad-hIL-10 + CsA groups. Graft survival, histopathological, enzyme-linked immunosorbent assay, reverse transcriptase-polymerase chain reaction and flow cytometry were performed in liver specimens obtained from different time points after transplantation in the 5 groups. Results: Ad-hIL-10 pretreatment inhibited allograft rejection, prolonged the survival of hepatic allografts, and downregulated the expression of IFN-γ and IL-2 mRNA, with simultaneous upregulation of IL-4 mRNA. In addition, Ad-hIL-10 pretreatment upregulated the expression of Fas mRNA in the isolated graft-infiltrating lymphocytes and induced graft-infiltrating lymphocyte apoptosis. A single subtherapeutic dose of CsA acted synergistically with it. Conclusion: hIL-10 gene therapy induced alloreactive lymphocyte apoptosis via Fas/FasL pathway. hIL-10 gene transfection in combination with subtherapeutic doses of CsA facilitates the long-term survival of liver grafts.