bluuebunny/crossref_metadata_2025 huggingface dataset:
Preserved protein synthesis in the heart in response to acute fasting and chronic food restriction despite reductions in liver and skeletal muscle
Authors: Yuan Celvie L. , Sharma Naveen , Gilge Danielle A. , Stanley William C. , Li Yi , Hatzoglou Maria , Previs Stephen F.
Published: April 2008

Whole body protein synthesis is reduced during the fed-to-fasted transition and in cases of chronic dietary restriction; however, less is known about tissue-specific alterations. We have assessed the extent to which protein synthesis in cardiac muscle responds to dietary perturbations compared with liver and skeletal muscle by applying a novel2H2O tracer method to quantify tissue-specific responses of protein synthesis in vivo. We hypothesized that protein synthesis in cardiac muscle would be unaffected by acute fasting or food restriction, whereas protein synthesis in the liver and gastrocnemius muscle would be reduced when there is a protein-energy deficit. We found that, although protein synthesis in liver and gastrocnemius muscle was significantly reduced by acute fasting, there were no changes in protein synthesis in the left ventricle of the heart for either the total protein pool or in isolated mitochondrial or cytosolic compartments. Likewise, a chronic reduction in calorie intake, induced by food restriction, did not affect protein synthesis in the heart, whereas protein synthesis in skeletal muscle and liver was decreased. The later observations are supported by changes in the phosphorylation state of two critical mediators of protein synthesis (4E-BP1 and eIF2α) in the respective tissues. We conclude that cardiac protein synthesis is maintained in cases of nutritional perturbations, in strong contrast to liver and gastrocnemius muscle, where protein synthesis is decreased by acute fasting or chronic food restriction.
Effect of ANG II on endothelial cell apoptosis and survival and its impact on skeletal muscle angiogenesis after electrical stimulation
Authors: de Resende Micheline M. , Greene Andrew S.
Published: April 2008

We have previously shown that skeletal muscle angiogenesis induced by electrical stimulation is significantly attenuated when SS-13BN/Mcwi rats are fed a high-salt diet. This effect was associated with a large increase in endothelial cell (EC) apoptosis. We hypothesized that the low levels of ANG II during high-salt diet would increase EC apoptosis and consequently diminish the angiogenic response. To test this hypothesis, a series of in vitro and in vivo studies was performed. EC apoptosis and viability were evaluated after incubation with ANG II under serum-free conditions. After 24 h of incubation, ANG II increased EC viability and Bcl-2-to-Bax ratio along with a dose-dependent decrease in EC apoptosis. This effect was blocked by the ANG II type 1 receptor antagonist losartan. To confirm our in vitro results, ANG II (3 ng·kg−1·min−1) was chronically infused in rats fed a high-salt diet (4% NaCl). ANG II decreased EC apoptosis and produced a significant increase (40%) in skeletal muscle angiogenesis after electrical stimulation. These in vivo results were in agreement with our in vitro results and demonstrate that the attenuation of ANG II levels during a high-salt diet may induce EC apoptosis and consequently block the angiogenic response induced by electrical stimulation. Furthermore, under normal conditions, ANG II increases EC viability and protects EC from apoptosis possibly by inactivation of the mitochondrial apoptotic pathway.
Estradiol accelerates endothelial healing through the retrograde commitment of uninjured endothelium
Authors: Filipe Cédric , Lam Shang Leen Lætitia , Brouchet Laurent , Billon Audrey , Benouaich Vincent , Fontaine Vincent , Gourdy Pierre , Lenfant Françoise , Arnal Jean-François , Gadeau Alain-Pierre , Laurell Henrik
Published: April 2008

Although the accelerative effect of 17β-estradiol (E2) on endothelial regrowth has been clearly demonstrated, the local cellular events accounting for this beneficial vascular action are still uncertain. In the present work, we compared the kinetics of endothelial healing of mouse carotid arteries after endovascular and perivascular injury. Both basal reendothelialization as well as the accelerative effect of E2 were similar in the two models. Three days after endothelial denudation, a regenerative area was observed in both models, characterized by similar changes in gene expression after injury, visualized by en face confocal microscopy (EFCM). A precise definition of the injury limits was only possible with the perivascular model, since it causes a complete and lasting decellularization of the media. Using this model, we demonstrated that the migration of uninjured endothelial cells precedes proliferation (bromodeoxyuridine incorporation) and that these events occur at earlier time points with E2 treatment. We have also identified an uninjured retrograde zone as an intimate component of the endothelial regeneration process. Thus, in the perivascular model, the regenerative area can be subdivided into a retrograde zone and a reendothelialized area. Importantly, both areas are significantly enlarged by E2. In conclusion, the combination of the electric perivascular injury model and EFCM is well adapted to the visualization of the endothelial monolayer and to investigate cellular events involved in reendothelialization. This process is accelerated by E2 as a consequence of the retrograde commitment of an uninjured endothelial zone to migrate and proliferate, contributing to an enlargement of the regenerative area.
Human neutrophil peptides upregulate expression of COX-2 and endothelin-1 by inducing oxidative stress
Authors: Syeda Farisa , Tullis Elizabeth , Slutsky Arthur S. , Zhang Haibo
Published: April 2008

Polymorphonuclear leukocytes (PMNs) play an important role during inflammation in cardiovascular diseases. Human neutrophil peptides (HNPs) are released from PMN granules upon activation and are conventionally involved in microbial killing. Recent studies suggested that HNPs may be involved in the pathogenesis of vascular abnormality by modulating inflammatory responses and vascular tone. Since HNPs directly interact with endothelium upon release from PMNs in the circulation, we tested the hypothesis that the stimulation with HNPs of endothelial cells modulates the expression of vasoactive by-products through altering cyclooxygenase (COX) activity. When human umbilical vein endothelial cells were stimulated with purified HNPs, we observed a time- and dose-dependent increase in the expression of COX-2, whereas COX-1 levels remained unchanged. Despite an increased expression of COX-2 at the protein level, HNPs did not significantly enhance the COX-2 activity, thus the production of the prostaglandin PGI2. HNPs significantly induced the release of endothelin-1 (ET-1) as well as the formation of nitrotyrosine. The HNP-induced COX-2 and ET-1 production was attenuated by the treatment with the oxygen free radical scavenger N-acetyl-l-cysteine and the inhibitors of p38 MAPK and NF-κB, respectively. The angiontensin II pathway did not seem to be involved in the HNP-induced upregulation of COX-2 and ET-1 since the use of the angiotensin-converting enzyme inhibitor enalapril had no effect in this context. In conclusion, HNP may play an important role in the pathogenesis of inflammatory cardiovascular diseases by activating endothelial cells to produce vasoactive by-products as a result of oxidative stress.
A cardioprotective role for platelet-activating factor through NOS-dependent S-nitrosylation
Authors: Leary Peter J. , Rajasekaran Surender , Morrison R. Ray , Tuomanen Elaine I. , Chin Thomas K. , Hofmann Polly A.
Published: April 2008

Controversy exists as to whether platelet-activating factor (PAF), a potent phospholipid mediator of inflammation, can actually protect the heart from postischemic injury. To determine whether endogenous activation of the PAF receptor is cardioprotective, we examined postischemic functional recovery in isolated hearts from wild-type and PAF receptor-knockout mice. Postischemic function was reduced in hearts with targeted deletion of the PAF receptor and in wild-type hearts treated with a PAF receptor antagonist. Furthermore, perfusion with picomolar concentrations of PAF improved postischemic function in hearts from wild-type mice. To elucidate the mechanism of a PAF-mediated cardioprotective effect, we employed a model of intracellular Ca2+ overload and loss of function in nonischemic ventricular myocytes. We found that PAF receptor activation attenuates the time-dependent loss of shortening and increases in intracellular Ca2+ transients in Ca2+-overloaded myocytes. These protective effects of PAF depend on nitric oxide, but not activation of cGMP. In addition, we found that reversible S-nitrosylation of myocardial proteins must occur in order for PAF to moderate Ca2+ overload and loss of myocyte function. Thus our data are consistent with the hypothesis that low-level PAF receptor activation initiates nitric oxide-induced S-nitrosylation of Ca2+-handling proteins, e.g., L-type Ca2+ channels, to attenuate Ca2+ overload during ischemia-reperfusion in the heart. Since inhibition of the PAF protective pathway reduces myocardial postischemic function, our results raise concern that clinical therapies for inflammatory diseases that lead to complete blockade of the PAF receptor may eliminate a significant, endogenous cardioprotective pathway.
Critical role of extracellular heat shock cognate protein 70 in the myocardial inflammatory response and cardiac dysfunction after global ischemia-reperfusion
Authors: Zou Ning , Ao Lihua , Cleveland Joseph C. , Yang Xiaoping , Su Xin , Cai Guang-Yun , Banerjee Anirban , Fullerton David A. , Meng Xianzhong
Published: April 2008

Previous studies showed that Toll-like receptor 4 (TLR4) modulates the myocardial inflammatory response to ischemia-reperfusion injury, and we recently found that cytokines link TLR4 to postischemic cardiac dysfunction. Although TLR4 can be activated in cultured cells by endogenous agents including heat shock protein 70, how it is activated during myocardial ischemia-reperfusion is unknown. In the present study, we examined 1) whether heat shock cognate protein 70 (HSC70), which is constitutively expressed in the myocardium, is released during ischemia-reperfusion; 2) whether extracellular HSC70 induces the myocardial inflammatory response and modulates cardiac function; and 3) whether HSC70 exerts these effects via TLR4. We subjected isolated mouse hearts to global ischemia-reperfusion via the Langendorff technique. Immunoblotting and immunostaining detected the release of HSC70 from the myocardium during reperfusion. Treatment with an antibody specific to HSC70 suppressed myocardial cytokine expression and improved cardiac functional recovery after ischemia-reperfusion. Recombinant HSC70 induced NF-κB activation and cytokine expression and depressed myocardial contractility in a TLR4-dependent manner. These effects required the substrate-binding domain of HSC70. Fluorescence resonance energy transfer analysis of isolated macrophages demonstrated that extracellular HSC70 interacts with TLR4. Therefore, this study demonstrates for the first time that 1) the myocardium releases HSC70 during ischemia-reperfusion, 2) extracellular HSC70 contributes to the postischemic myocardial inflammatory response and to cardiac dysfunction, 3) HSC70 exerts these effects through a TLR4-dependent mechanism, and 4) the substrate-binding domain of HSC70 is required to induce these effects. Thus extracellular HSC70 plays a critical role in regulating the myocardial innate immune response and cardiac function after ischemia-reperfusion.
Genomic deletion of estrogen receptors ERα and ERβ does not alter estrogen-mediated inhibition of Ca2+influx and contraction in murine cardiomyocytes
Authors: Ullrich Nina D. , Krust Andree , Collins Peter , MacLeod Kenneth T.
Published: April 2008

Estrogens modify contraction of vascular smooth muscle and cardiomyocytes, but suggestions that they confer protective effects on the cardiovascular system remain controversial. The negative inotropic effects of estrogens are a consequence of L-type Ca2+channel inhibition, but the underlying mechanisms remain elusive. We tested the hypothesis that membrane-associated estrogen receptors (ER)-α and -β are involved. We measured the effect of estrogens on Ca2+current ( ICaL) in isolated ventricular cardiomyocytes of wild-type (WT), ERα knockout (ERαKO), and ERβKO mice using the whole cell patch-clamp technique at 37°C. No differences in current densities or inactivation profiles of ICaLwere found under control conditions in WT, ERαKO, and ERβKO cardiomyocytes, suggesting that absence of either ER has no effect on functional properties of ICaL. In all groups, application of raloxifene (2 μM) or 17α- or 17β-estradiol (50 μM) reduced ICaL( P < 0.001). Raloxifene decreased ICaLby 44 ± 9% (mean ± SE) in WT ( n = 5), 34 ± 5% in ERαKO ( n = 5), and 30 ± 5% in ERβKO mice ( n = 8). 17α-Estradiol reduced ICaLby 41 ± 10% in WT ( n = 4), 34 ± 12% in ERαKO ( n = 7), and 38 ± 8% in ERβKO mice ( n = 7). 17β-Estradiol inhibited ICaLby 31 ± 4% in WT ( n = 4), 28 ± 6% in ERαKO ( n = 3), and 42 ± 3% in ERβKO mice ( n = 5). Decreases in cell shortening occurred in parallel with these findings. Our results suggest that inhibition of ICaLand the decrease in contraction by estrogens do not depend on ERα or ERβ.
Angiotensin II and tumor necrosis factor-α synergistically promote monocyte chemoattractant protein-1 expression: roles of NF-κB, p38, and reactive oxygen species
Authors: Takahashi Masao , Suzuki Etsu , Takeda Ryo , Oba Shigeyoshi , Nishimatsu Hiroaki , Kimura Kenjiro , Nagano Tetsuo , Nagai Ryozo , Hirata Yasunobu
Published: April 2008

We examined whether ANG II and TNF-α cooperatively induce vascular inflammation using the expression of monocyte chemoattractant protein (MCP)-1 as a marker of vascular inflammation. ANG II and TNF-α stimulated MCP-1 expression in a synergistic manner in vascular smooth muscle cells. ANG II-induced MCP-1 expression was potently inhibited to a nonstimulated basal level by blockade of the p38-dependent pathway but only partially inhibited by blockade of the NF-κB-dependent pathway. In contrast, TNF-α-induced MCP-1 expression was potently suppressed by blockade of NF-κB activation but only modestly suppressed by blockade of p38 activation. ANG II- and TNF-α-induced activation of NF-κB- and p38-dependent pathways was partially inhibited by pharmacological inhibitors of ROS production. Furthermore, ANG II- and TNF-α-stimulated MCP-1 expression was partially suppressed by ROS inhibitors. We also examined whether endogenous ANG II and TNF-α cooperatively promote vascular inflammation in vivo using a wire injury model of the rat femoral artery. Blockade of both ANG II and TNF-α further suppressed neointimal formation, macrophage infiltration, and MCP-1 expression in an additive manner compared with blockade of ANG II or TNF-α alone. These results suggested that ANG II and TNF-α synergistically stimulate MCP-1 expression via the utilization of distinct intracellular signaling pathways (p38- and NFκB-dependent pathways) and that these pathways are activated in ROS-dependent and -independent manners. These results also suggest that ANG II and TNF-α cooperatively stimulate vascular inflammation in vivo as well as in vitro.
Role of oxidative stress in high glucose-induced decreased expression of Giα proteins and adenylyl cyclase signaling in vascular smooth muscle cells
Authors: Li Yuan , Descorbeth Magda , Anand-Srivastava Madhu B.
Published: April 2008

We have recently shown that aorta from streptozotocin (STZ)-induced diabetic rats and A10 vascular smooth muscle cells (VSMCs) exposed to high glucose exhibited decreased levels of inhibitory guanine nucleotide regulatory protein (Gi)α proteins. In the present studies, we investigated the implication of oxidative stress in the hyperglycemia/diabetes-induced decreased expression of the Giα protein and adenylyl cyclase signaling in VSMCs by using antioxidants. The levels of Giα proteins were significantly decreased in A10 VSMCs exposed to high glucose and in aortic VSMCs from STZ-diabetic rats compared with control cells and were restored to control levels by antioxidants. In addition,111Mn-tetralis(benzoic acid porphyrin) and uric acid, scavengers of peroxynitrite, and NG-nitro-l-arginine methyl ester, an inhibitor of nitric oxide synthase but not catalase, also restored the high glucose-induced decreased expression of Giα proteins to the control levels in A10 VSMCs. Furthermore, the enhanced production of superoxide anion (O2−) and increased activity of NADPH oxidase in these cells were also restored to control levels by diphenyleneiodonium, an inhibitor of NADPH oxidase. In addition, the diminished inhibition of adenylyl cyclase activity by inhibitory hormones and forskolin-stimulated adenylyl cyclase activity by low concentrations of GTPγS as well as the enhanced stimulation of adenylyl cyclase by stimulatory agonists in hyperglycemic cells were restored to control levels by antioxidant treatments. These results suggest that high glucose-induced decreased levels of Giα proteins and associated signaling in A10 VSMCs may be attributed to the enhanced oxidative stress due to augmented levels of peroxynitrite and not to H2O2.
Mild inflammatory activation of mammary arteries in patients with acute coronary syndromes
Authors: Foglieni Chiara , Maisano Francesco , Dreas Lorella , Giazzon Alessio , Ruotolo Giacomo , Ferrero Elisabetta , Li Volsi Laura , Coli Stefano , Sinagra Gianfranco , Zingone Bartolo , Alfieri Ottavio , Becker Anton E. , Maseri Attilio
Published: April 2008

Acute coronary syndromes (ACS) are characterized by multiple unstable coronary plaques and elevated circulating levels of inflammatory biomarkers. The endothelium of internal mammary arteries (IMA), which are atherosclerosis resistant, is exposed to proinflammatory stimuli as vessels that develop atherosclerosis. Our study investigated the IMA endothelial expression of inflammatory molecules in patients with ACS or chronic stable angina (CSA). IMA demonstrated normal morphology, intact endothelial lining, and strong immunoreactivity for glucose transporter 1. E-selectin expression was observed more frequently in IMA of ACS patiention than CSA patients (ACS 61% vs. CSA 14%, P = 0.01). High fluorescence for major histocompatibility complex (MHC) was significantly more frequent on the luminal endothelium (ACS 66.7% vs. CSA 17.6%, P = 0.001 for class I; and ACS 66.7% vs. CSA 6.2%, P = 0.0003 for class II-DR) and on the vasa vasorum (ACS 92.9% vs. CSA 33.3% and 7.7%, P = 0.0007 and P < 0.0001 for class I and class II-DR, respectively) of ACS patients than CSA patients. ICAM-1, VCAM-1, Toll-like receptor 4, tissue factor, IL-6, inducible nitric oxide synthase, and TNF-α expression were not significantly different in ACS and CSA. Circulating C-reactive protein [ACS 4.8 (2.6–7.3) mg/l vs. CSA 1.8 (0.6–3.5) mg/l, P = 0.01] and IL-6 [ACS 4.0 (2.6–5.5) pg/ml vs. CSA 1.7 (1.4–4.0) pg/ml, P = 0.02] were higher in ACS than CSA, without a correlation with IMA inflammation. The higher E-selectin, MHC class I and MHC class II-DR on the endothelium and vasa vasorum of IMA from ACS patients suggests a mild, endothelial inflammatory activation in ACS, which can be unrelated to the presence of atherosclerotic coronary lesions. These findings indicated IMA as active vessels in coronary syndromes.
Increased transcription of cytokine genes in human lung epithelial cells through activation of a TRPM8 variant by cold temperatures
Authors: Sabnis Ashwini S. , Reilly Christopher A. , Veranth John M. , Yost Garold S.
Published: April 2008

Recognition of temperature is a critical element of sensory perception and allows mammals to evaluate both their external environment and internal status. The respiratory epithelium is constantly exposed to the external environment, and prolonged inhalation of cold air is detrimental to human airways. However, the mechanisms responsible for adverse effects elicited by cold air on the human airways are poorly understood. Transient receptor potential melastatin family member 8 (TRPM8) is a well-established cold- and menthol-sensing cation channel. We recently discovered a functional cold- and menthol-sensing variant of the TRPM8 ion channel in human lung epithelial cells. The present study explores the hypothesis that this TRPM8 variant mediates airway cell inflammatory responses elicited by cold air/temperatures. Here, we show that activation of the TRPM8 variant in human lung epithelial cells leads to increased expression of several cytokine and chemokine genes, including IL-1α, -1β, -4, -6, -8, and -13, granulocyte-macrophage colony-stimulating factor (GM-CSF), and TNF-α. Our results provide new insights into mechanisms that potentially control airway inflammation due to inhalation of cold air and suggest a possible role for the TRPM8 variant in the pathophysiology of asthma.
Pulmonary alveolar epithelial uptake of S-nitrosothiols is regulated by L-type amino acid transporter
Authors: Granillo Olivia M. , Brahmajothi Mulugu V. , Li Sheng , Whorton A. Richard , Mason S. Nicholas , McMahon Timothy J. , Auten Richard L.
Published: April 2008

Nitric oxide (NO) effects are often mediated via S-nitrosothiol (SNO) formation; SNO uptake has recently been shown to be mediated in some cell types via system L-type amino acid transporters (LAT-1, 2). Inhaled NO therapy may exert some biological effects via SNO formation. We therefore sought to determine if pulmonary epithelial SNO uptake depended on LAT or peptide transporter 2 (PEPT2). Both LAT-1 and PEPT2 proteins were detected by immunoblot and immunocytochemistry in L2 cells and rat lung. We tested SNO uptake through the transporters by exposing rat alveolar epithelial cells (L2 and type II) to RSNOs: S-nitrosoglutathione, S-nitrosocysteinylglycine (SNO-Cys-Gly), S-nitrosocysteine (CSNO), and to NO donor diethylamine NONOate (DEA-NONOate). SNO was detected in cell lysates by ozone chemiluminescence. NO uptake was detected by fluorescence in alveolar epithelial cells loaded with 4-amino-5-methylamino-2′,7′-difluorofluorescein (DAF-FM) diacetate cultured in submersion and exposed to RSNOs and DEA NONOate. Addition of l-Cys but not d-Cys to RSNOs or DEA NONOate increased SNO and DAF-FM signal that was inhibited by coincubation with LAT competitors. Incubation of cells with PEPT2 substrate SNO-Cys-Gly showed no increase in SNO or DAF-FM signal unless incubated with l-Cys. This was unaffected by PEPT2 inhibition. We conclude that RSNOs (thionitrites, S-nitrosothiols) and NO enter alveolar epithelial cells predominantly by S-nitrosation of l-Cys, which is then imported through LAT.
Metalloelastase in lungs and alveolar macrophages is modulated by extracellular substance P in mice
Authors: Xu J. , Xu F. , Barrett E.
Published: April 2008

Metalloelastase (MMP-12), mainly produced by macrophages, has been shown to play a key role in the pathogenesis of emphysema in animal models. Chronic cigarette smoke increases pulmonary MMP-12, which is closely correlated with an elevation of pulmonary substance P (SP). Because alveolar macrophages (AMs) contain the neurokinin-1 receptor (NK1R), we tested whether SP was able to trigger the upregulation of MMP-12 synthesis in AMs by acting on the NK1R. AMs isolated from bronchoalveolar lavage cells in C3H/HeN mice were cultured with control medium or SP that was coupled without or with NK1R antagonists (CP-99,994 or aprepitant) for 24 h. We found that SP significantly increased the mRNA of MMP-12 and NK1R by 11-fold and 82%, respectively, in AMs ( P < 0.05), and these responses were abolished by NK1R antagonists with little change in the cells' viability. Because pulmonary SP is primarily released by bronchopulmonary C-fibers (PCFs), we further asked whether destruction of PCFs would reduce SP and MMP-12. Two groups of mice were pretreated with vehicle and neonatal capsaicin (NCAP) to degenerate PCFs, respectively. Our results show that NCAP treatment significantly decreased mRNA and protein levels of SP associated with a reduction NK1R and MMP-12 in the lungs and AMs. These findings suggest that SP has a modulatory effect on pulmonary MMP-12 by acting on NK1R to trigger MMP-12 syntheses in the AMs.
EGF antagonizes TGF-β-induced tropoelastin expression in lung fibroblasts via stabilization of Smad corepressor TGIF
Authors: Yang Shenghong , Nugent Matthew A. , Panchenko Mikhail P.
Published: April 2008

We previously reported that neutrophil elastase (NE) downregulates transforming growth factor-β (TGF-β)-maintained tropoelastin mRNA levels in lung fibroblasts through transactivation of the epidermal growth factor (EGF) receptor (EGFR)/Mek/Erk pathway, which is dependent on the NE-initiated release of soluble EGFR ligands. In the present study, we investigated the mechanism by which EGF downregulates tropoelastin expression. We found that EGF downregulates tropoelastin expression through inhibition of TGF-β signaling. We show that EGF does not prevent the TGF-β-induced nuclear accumulation of Smad2/3; rather, EGF stabilizes the short-lived Smad transcriptional corepressor TG-interacting factor (TGIF) via EGFR/Mek/Erk-mediated phosphorylation of TGIF. Elevation of TGIF levels, either by TGIF overexpression or prevention of TGIF degradation, is sufficient to inhibit TGF-β-induced tropoelastin expression. Moreover, TGIF is essential for EGF-mediated downregulation of tropoelastin expression, inasmuch as small interfering RNA knockdown of TGIF blocked EGF-induced downregulation of tropoelastin. Finally, we demonstrated that NE treatment, which releases EGF-like growth factors, causes stabilization of TGIF through the EGFR/Mek/Erk pathway. These results suggest that EGFR/Mek/Erk signaling specifically antagonizes the proelastogenic action of TGF-β in lung fibroblasts by stabilizing the Smad transcriptional corepressor TGIF.
Glucocorticoid regulation of CD38 expression in human airway smooth muscle cells: role of dual specificity phosphatase 1
Authors: Kang Bit Na , Jude Joseph A. , Panettieri Reynold A. , Walseth Timothy F. , Kannan Mathur S.
Published: April 2008

The enzymatic activity of CD38, ADP-ribosyl cyclase, synthesizes the calcium mobilizing molecule cyclic ADP-ribose from β-NAD. In human airway smooth muscle (HASM) cells, CD38 expression is augmented by the inflammatory cytokine, TNF-α, causing increased intracellular calcium response to agonists. The transcriptional and posttranscriptional regulation of CD38 expression involves signaling through MAPKs and requires activation of NF-κB and activator protein-1 (AP-1). The cytokine-augmented CD38 expression is decreased by anti-inflammatory glucocorticoids due to inhibition of NF-κB activation and other mechanisms. In this study, we investigated glucocorticoid regulation of CD38 expression in HASM cells through the MKP-1. In HASM cells, dexamethasone and TNF-α induced MKP-1 expression (both mRNA and protein) rapidly. Dexamethasone decreased TNF-α-induced phosphorylation of the major MAPKs, i.e., ERK, p38, and JNK, and decreased the activation of NF-κB and AP-1. Dexamethasone also decreased CD38 expression induced by TNF-α, and part of this effect was attributable to decreased transcript stability. In cells transfected with MKP-1-specific small interfering RNAs (siRNAs), there was significant attenuation of MKP-1 expression and partial, but nonsignificant, reversal of dexamethasone inhibition of CD38 expression. These results indicate that regulation of CD38 expression in HASM cells by glucocorticoids involves decreased signaling through MAPKs and activation of transcription factors. The glucocorticoid effects on decreased CD38 expression and function result from regulation through transcription and transcript stability.
Superoxide dismutase protects against apoptosis and alveolar enlargement induced by ceramide
Authors: Petrache Irina , Medler Terry R. , Richter Amy T. , Kamocki Krzysztof , Chukwueke Ugonma , Zhen Lijie , Gu Yuan , Adamowicz Jeremy , Schweitzer Kelly S. , Hubbard Walter C. , Berdyshev Evgeny V. , Lungarella Giuseppe , Tuder Rubin M.
Published: April 2008

The molecular events leading to emphysema development include generation of oxidative stress and alveolar cell apoptosis. Oxidative stress upregulates ceramides, proapoptotic signaling sphingolipids that trigger further oxidative stress and alveolar space enlargement, as shown in an experimental model of emphysema due to VEGF blockade. As alveolar cell apoptosis and oxidative stress mutually interact to mediate alveolar destruction, we hypothesized that the oxidative stress generated by ceramide is required for its pathogenic effect on lung alveoli. To model the direct lung effects of ceramide, mice received ceramide intratracheally (Cer12:0or Cer8:0; 1 mg/kg) or vehicle. Apoptosis was inhibited with a general caspase inhibitor. Ceramide augmentation shown to mimic levels found in human emphysema lungs increased oxidative stress, and decreased, independently of caspase activation, the lung superoxide dismutase activity at 48 h. In contrast to their wild-type littermates, transgenic mice overexpressing human Cu/Zn SOD were significantly protected from ceramide-induced superoxide production, apoptosis, and air space enlargement. Activation of lung acid sphingomyelinase in response to ceramide treatment was abolished in the Cu/Zn SOD transgenic mice. Since cigarette smoke-induced emphysema in mice is similarly ameliorated by the Cu/Zn SOD overexpression, we hypothesized that cigarette smoke may induce ceramides in the mouse lung. Utilizing tandem mass spectrometry, we documented increased lung ceramides in adult mice exposed to cigarette smoke for 4 wk. In conclusion, ceramide-induced superoxide accumulation in the lung may be a critical step in ceramide's proapoptotic effect in the lung. This work implicates excessive lung ceramides as amplifiers of lung injury through redox-dependent mechanisms.
MAP kinases mediate interleukin-13 effects on calcium signaling in human airway smooth muscle cells
Authors: Moynihan Barry , Tolloczko Barbara , Michoud Marie-Claire , Tamaoka Meiyo , Ferraro Pasquale , Martin James G.
Published: April 2008

Interleukin-13 (IL-13) has been strongly implicated in the pathogenesis of allergic asthma through animal models that have shown that IL-13 is both necessary and sufficient to cause airway hyperresponsiveness (AHR). Airway smooth muscle (ASM) is a primary effector of AHR, and IL-13 increases the responsiveness of ASM, by increasing Ca2+release intracellularly, to bronchoconstrictors such as histamine. The mechanisms and signaling pathways mediating this effect are incompletely understood. We have investigated the pathways through which IL-13 regulates the Ca2+response to histamine in primary human ASM cell cultures. Functional IL-13 receptors were demonstrated by IL-13-mediated phosphorylation of signal transducer and activator of transcription 6 (STAT6) and mitogen-activated protein kinases (MAPKs). IL-13 increased Ca2+responses to histamine. The augmentation of Ca2+signaling was not affected by inhibition of STAT6 or p38 MAPK signaling but was prevented by concurrent inhibition of c-jun N-terminal kinase (JNK) and extracellular signal-related kinase (ERK) MAPKs. This inhibition did not affect the IL-13-induced increase in histamine receptors. We conclude that IL-13 induces potentiation of Ca2+responses to contractile agonists by affecting mechanisms downstream of receptors. JNK and ERK MAPKs modulate these mechanisms.
Utility of magnetic resonance imaging and nuclear magnetic resonance-based metabolomics for quantification of inflammatory lung injury
Authors: Serkova Natalie J. , Van Rheen Zachary , Tobias Meghan , Pitzer Joshua E. , Wilkinson J. Erby , Stringer Kathleen A.
Published: April 2008

Magnetic resonance imaging (MRI) and metabolic nuclear magnetic resonance (NMR) spectroscopy are clinically available but have had little application in the quantification of experimental lung injury. There is a growing and unfulfilled need for predictive animal models that can improve our understanding of disease pathogenesis and therapeutic intervention. Integration of MRI and NMR could extend the application of experimental data into the clinical setting. This study investigated the ability of MRI and metabolic NMR to detect and quantify inflammation-mediated lung injury. Pulmonary inflammation was induced in male B6C3F1 mice by intratracheal administration of IL-1β and TNF-α under isoflurane anesthesia. Mice underwent MRI at 2, 4, 6, and 24 h after dosing. At 6 and 24 h lungs were harvested for metabolic NMR analysis. Data acquired from IL-1β+TNF-α-treated animals were compared with saline-treated control mice. The hyperintense-to-total lung volume (HTLV) ratio derived from MRI was higher in IL-1β+TNF-α-treated mice compared with control at 2, 4, and 6 h but returned to control levels by 24 h. The ability of MRI to detect pulmonary inflammation was confirmed by the association between HTLV ratio and histological and pathological end points. Principal component analysis of NMR-detectable metabolites also showed a temporal pattern for which energy metabolism-based biomarkers were identified. These data demonstrate that both MRI and metabolic NMR have utility in the detection and quantification of inflammation-mediated lung injury. Integration of these clinically available techniques into experimental models of lung injury could improve the translation of basic science knowledge and information to the clinic.
Baroreflex control of lumbar and renal sympathetic nerve activity in conscious rats
Authors: Kanbar Roy , Chapuis Bruno , Oréa Valérie , Barrès Christian , Julien Claude
Published: April 2008

This study compared the baroreflex control of lumbar and renal sympathetic nerve activity (SNA) in conscious rats. Arterial pressure (AP) and lumbar and renal SNA were simultaneously recorded in six freely behaving rats. Pharmacological estimates of lumbar and renal sympathetic baroreflex sensitivity (BRS) were obtained by means of the sequential intravenous administration of sodium nitroprusside and phenylephrine. Sympathetic BRS was significantly ( P < 0.05) lower for lumbar [3.0 ± 0.4 normalized units (NU)/mmHg] than for renal (7.6 ± 0.6 NU/mmHg) SNA. During a 219-min baseline period, spontaneous lumbar and renal BRS were continuously assessed by computing the gain of the transfer function relating AP and SNA at heart rate frequency over consecutive 61.4-s periods. The transfer gain was considered only when coherence between AP and SNA significantly differed from zero, which was verified in 99 ± 1 and 96 ± 3% of cases for lumbar and renal SNA, respectively. When averaged over the entire baseline period, spontaneous BRS was significantly ( P < 0.05) lower for lumbar (1.3 ± 0.2 NU/mmHg) than for renal (2.3 ± 0.3 NU/mmHg) SNA. For both SNAs, spontaneous BRS showed marked fluctuations (variation coefficients were 26 ± 2 and 28 ± 2% for lumbar and renal SNA, respectively). These fluctuations were positively correlated in five of six rats ( R = 0.44 ± 0.06; n = 204 ± 8; P < 0.0001). We conclude that in conscious rats, the baroreflex control of lumbar and renal SNA shows quantitative differences but is modulated in a mostly coordinated way.
Shaping Appropriate Locomotive Motor Output Through Interlimb Neural Pathway Within Spinal Cord in Humans
Authors: Kawashima Noritaka , Nozaki Daichi , Abe Masaki O. , Nakazawa Kimitaka
Published: April 2008

Direct evidence supporting the contribution of upper limb motion on the generation of locomotive motor output in humans is still limited. Here, we aimed to examine the effect of upper limb motion on locomotor-like muscle activities in the lower limb in persons with spinal cord injury (SCI). By imposing passive locomotion-like leg movements, all cervical incomplete ( n = 7) and thoracic complete SCI subjects ( n = 5) exhibited locomotor-like muscle activity in their paralyzed soleus muscles. Upper limb movements in thoracic complete SCI subjects did not affect the electromyographic (EMG) pattern of the muscle activities. This is quite natural since neural connections in the spinal cord between regions controlling upper and lower limbs were completely lost in these subjects. On the other hand, in cervical incomplete SCI subjects, in whom such neural connections were at least partially preserved, the locomotor-like muscle activity was significantly affected by passively imposed upper limb movements. Specifically, the upper limb movements generally increased the soleus EMG activity during the backward swing phase, which corresponds to the stance phase in normal gait. Although some subjects showed a reduction of the EMG magnitude when arm motion was imposed, this was still consistent with locomotor-like motor output because the reduction of the EMG occurred during the forward swing phase corresponding to the swing phase. The present results indicate that the neural signal induced by the upper limb movements contributes not merely to enhance but also to shape the lower limb locomotive motor output, possibly through interlimb neural pathways. Such neural interaction between upper and lower limb motions could be an underlying neural mechanism of human bipedal locomotion.
On Possibilities of Synthesis of a Useful Model of Thick FilmComponents
Authors: Paszczyński Stanisław
Published: April 2008

The problems in forming a useful model of a thick film component have been analysed. The need for such a
model has been shown. Common features of thick film structures have been defined and, using the example of
resistive film models that have been presented by previous authors, the trends in thick film structure modelling
have been shown. Limitations of previous models have been described and, using the example of thick film
resistors, the components of structure which should be taken into consideration in a complete model have been
compiled. The problems in dealing with model verification, especially with regard to the choice of the criteria
of quality and also in the choice of the measuring methods for obtaining component characteristics together
with the values of the structural parameters, have been presented. Possible stages in the formation process of
such a model and also research directions which could improve the process have been suggested.
High Temperature Oxidized SnO2 Films Prepared by Reactive Sputtering
Authors: Beensh-Marchwicka G. , Król-Stępniewska L. , Misiuk A.
Published: April 2008

Undoped and Sb‐doped tin oxide films were prepared by d.c. reactive ion sputtering in an argon atmosphere
with oxygen partial pressures ranging from 0 to 50%. The films were anneled in oxygen in the temperature
range 360 ‐ 893℃. The effect of thermal annealing on the changes in electrical and structural properties is
described.
Realization of Solar Cells Based on Silicon/Oxide Junctions
Authors: Campet G. , Sun Z. W. , Keou P.
Published: April 2008

Transparent and conductive films of SrTiO3 , ITO, and Tl2O3 have been deposited by R.F. cathodic
sputtering and by anodic oxidation onto Si substrates in order to realize SIS cells. A photoconversion
efficiency of 8.8% has been obtained for Si/SiOx/Tl2O3 cells. On the other hand for Si/SiOx/SrTiO3(ITO)
the photoconversion efficiency is lower than 1% because of the too large thickness of the SiOx interfacial
layer.
Miniature Thick Film Resistors forMicrowave Integrated Circuits
Authors: Szczepański Zbigniew
Published: April 2008

In this paper the results of miniature thick film resistors designed as add‐on lumped resistors are
presented. A few resistor configurations have been elaborated and tested, and a specific trimming
resistance, which avoids parasitic trimming inductance was used. Some of the designed resistors were
used in isolators and directional couplers for the 2‐11 GHz band. The electrical parameters have been
presented and discussed. The assembly methods for these resistors to the microstrip lines have also
been given.
Influence of Thermal Treatment on The Electronic Properties of ITO Thin FilmsObtained by RF Cathodic Pulverization. Study of Solar Cells Based on Silicon/(RF Sputtered) ITO Junctions
Authors: Campet G. , Geoffroy C. , Wen S. J. , Portier J. , Keou P. , Salardenne J. , Sun Z. W.
Published: April 2008

ITO (Indium Tin Oxide) thin films obtained by R.F cathodic sputtering have been studied. The influence
of thermal treatment on the electronic properties of the films has been particularly investigated. Electrical
measurements were performed between 95 and 600 K. Free carriers concentration in the film were
measured by Hall effect coefficient. Optical indices were determined by computer drawing of charts
allowing to simplify Manifacier method.

Finally study of SIS tunnel solar cells, based on Si/(RF sputtered) ITO junctions is presented.
Superconducting Thick‐Films From a Y‐Ba‐Cu‐O Precursor
Authors: Sacchi Maurizio , Sirotti Fausto , Morten Bruno , Prudenziati Maria
Published: April 2008

We have prepared screen‐printed films of the Y‐Ba‐Cu‐O compound starting from a spray‐pyrolysis
precursor powder. BeO ceramic substrates are confirmed to be inert with respect to the film up to
about 1000ºC. Electrical properties of oxygen annealed films are investigated, evidencing excellent
superconducting behaviour, both in terms of Tc(≃91K)
and Jc (>102 A.cm-2 at 77 K).
Electrochromism and ElectrochromicWindows
Authors: Campet G. , Portier J. , Wen S. J. , Morel B. , Bourrel M. , Chabagno J. M.
Published: April 2008

The properties of electrochromic thin film materials, i.e., those that can be reversibly colored by the
passage of charge, are described. The application of some of these thin film compounds for the development
of electrochromic windows is discussed.
Thermoelectric Power of YBa2Cu3O7-X and YBa2Cu4O8 Under Pressure
Authors: Ramasesha Sheela K.
Published: April 2008

Thermoelectric power (TEP) of YBa2Cu3O7-X (123) and YBa2Cu4O8 (124) samples are measured as a function of pressure. The TEP of an as‐sintered 123 polycrystalline sample shows a broad maximum around 1.25 GPa whereas that of the cold‐pressed sample decreases steadily. The ab‐plane TEP of 123
single crystal decreases monotonically and the c‐axis TEP exhibits a maximum around 1.5 GPa. Disappearance
of the broad maximum in the polycrystalline sample upon cold‐pressing is interpreted in
terms of the crystallite orientation occurring under pressure. TEP of the 124 polycrystalline sample
decreases sharply up to 4.5 GPa and at a lower rate with further increase in pressure, a trend similar
to that is observed in the variation of Tc as a function of pressure.
Programmable OTA‐Based Multifunction Active Filter
Authors: Al-Ali Abdulrahman Khalaf , Abuelma′atti Muhammad Taher , Tiwana Rizwan Ali
Published: April 2008

A fully programmable multifunction filter is presented. The filter uses four operational transconductance
amplifiers and two capacitors. Analog switches are used to control the filter transfer function through
a microcontroller. The user is provided control over the cutoff (or centre) frequency of the filter by
controlling the auxiliary bias currents of the operational transconductance amplifiers via digital‐to‐analog
converters. The circuit can simultaneously provide three programmable transfer functions in a
single structure and can realize all the standard second‐order filters. The circuit is attractive for VLSI
implementation.
Small‐Signal and Noise Model Determination for Double Polysilicon Self‐Aligned Bipolar Transistors
Authors: Caddemi A. , Sannino M.
Published: April 2008

In this paper, noise characterization and modeling of a double polysilicon self‐aligned bipolar transistor
are presented. The device has been characterized in terms of noise and scattering parameters by means
of an original automatic noise figure measuring system only. Measurements have been performed over
the 1–4 GHz frequency range and at different bias conditions. The extracted model refers to the
performance of the chip device since the package and bond parasitics have been accurately de‐embedded
by proper calibration techniques.
Universal Current‐Conveyor‐BasedCurrent‐Mode Filter with Single Input and Five Outputs
Authors: Abuelma′atti Muhammad Taher , Farooqui Aamir Alam
Published: April 2008

A new universal active current‐mode filter with single input and five outputs is presented. The
proposed filter avoids the use of external feedback in any part of the circuit and uses grounded
resistors. The proposed circuit can simultaneously realize lowpass, highpass, bandpass, allpass, and
notch biquadratic filter functions.
Voltage and Current Boost Techniques
Authors: Virani H.
Published: April 2008

The stability requirements for the current boosted are discussed in this paper.

Both internal and external compensation techniques are shown, along with necessary heatsink
design information and typical circuits, including a self‐oscillating switching regulator,
and a voltage boost circuit.
Simulation of Open Circuit Voltage Decay for Solar Cell Determination of the Base Minority Carrier Lifetime and the Back Surface Recombination Velocity
Authors: Affour B. , Mialhe P.
Published: April 2008

The Open Circuit Voltage Decay (OCVD) method for the determination of the base minority carrier lifetime (τ) and the back surface recombination velocity (S) of silicon solar cells has been investigated at constant illumination level. The validity of the method has been discussed through a simulation study by considering the mathematical solution of the continuity equation. Extracted values of τ and S are compared to their input values in order to evaluate the performances of our method and the precision with regard to cell structural parameters, namely the base width and the base doping level. Deviations in lifetime values remain lower than 7% for almost all the cell configurations while recombination velocity deviations are shown to be dependent on cell structure parameters and experimental procedure.
Time Domain Response of Uniform RC Lines with RC Termination at Both Ends
Authors: Abuelma′atti Muhammad Taher
Published: April 2008

The time domain response of uniform RC lines with RC termination at both ends is obtained from the approximate poles of the transfer function. A simple model is developed for the URC line. The model consists of three passive elements only and can be easily implemented for computer‐aided analysis of URC lines with RC termination at both ends.
New CFOA‐Based Grounded‐Capacitor Single‐Element‐ControlledSinusoidal Oscillator
Authors: Abuelma′atti Muhammad Taher , Al-Shahrani Sa′ad Muhammad
Published: April 2008

A new grounded‐capacitor single‐element‐controlled CFOA‐based sinusoidal oscillator circuit
is presented. The circuit exploits to advantage the internal pole of a general CFOA and
uses externally connected three resistors and two grounded capacitors. The frequency of
oscillation and the condition of oscillation of the proposed circuit can be independently
controlled. Experimental results are included.
Correlations Between the Thermoelectric Power and Hall Effect of SN‐ or GE‐Doped IN2O3 Polycrystalline Ceramics
Authors: Marcel C. , Salardenne J. , Huang S. Y. , Campet G. , Portier J.
Published: April 2008

The thermoelectric power and Hall effect of Sn‐or Ge‐doped In2O3 ceramics are investigated based on a comparative study. The metal‐type conductivity in both the samples occurs when the carrier concentration exceeds ~1019 cm-3. The carrier mobility is found to be higher for Ge‐doped samples. The relation between the <> of the dopant element and its scattering cross section is also presented.
Fabrication of AlGaInP/GaInP Laser Diodes by Molecular Beam Epitaxy
Authors: Wu K. K.
Published: April 2008

Room temperature pulse operation for AlGaInP/GalnP visible laser diodes prepared by gas source molecular beam epitaxy (GSMBE) have been successfully fabricated and demonstrated. In this report, two kinds of laser structures, the lattice‐matched quantum well double heterostructure (DH) and the grade‐index separate‐ confinement heterostructure (GRIN‐SCH) stained quantum well structure are characterized. Measurements of photoluminescence (PL) intensity, L‐I curves and wavelength spectra of these two structures all exhibit lasing properties. At room temperature, it is found that induced lasing phenomena has a full width half maximum (FWHM) of 2.1 nm and 0.5 nm, respectively. The emitting wavelengths range from 6500 Å to 6850 Å.