bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Smoking during Pregnancy on Peripheral Tissue Oxygenation in Term Neonates
Authors: Pichler Gerhard , Heinzinger Julia , Klaritsch Philipp , Zotter Heinz , Müller Wilhelm , Urlesberger Berndt
Published: September 2007

Background: Smoking during pregnancy is associated with higher blood pressure in neonates. Objective: To analyze whether smoking during pregnancy has an influence on peripheral tissue oxygenation in healthy term neonates within the first days after delivery. Methods: In a prospective cohort study, 15 healthy term neonates of mothers who had smoked during pregnancy (smoking group) were matched for gestational age, actual weight and postnatal age to 15 healthy term neonates of mothers who had not smoked during pregnancy (non-smoking group). Peripheral oxygenation was measured by near-infrared spectroscopy in combination with the venous occlusion method on the left forearm. Measurements were performed within the first 2 days after delivery. Tissue oxygenation index (TOI), fractional oxygen extraction (FOE), oxygen delivery (DO2) and oxygen consumption (VO2) were analyzed. Results: In neonates measured within the first day after delivery, TOI was significantly lower and FOE was significantly higher (63.5 ± 5.5; 0.37 ± 0.04) in the smoking group compared to the non-smoking group (69.2 ± 2.9; 0.30 ± 0.04). DO2 tended to be lower and VO2 tended to be higher in the smoking group. In neonates measured on the second day after delivery, no significant differences were observed between the groups. Conclusions: Smoking during pregnancy reduced TOI and increased FOE in otherwise healthy neonates on the first day of life with normalization on the second day of life.
Progression of Fibrosis in Usual Interstitial Pneumonia: Serial Evaluation of the Native Lung after Single Lung Transplantation
Authors: Grgic Aleksandar , Lausberg Henning , Heinrich Marc , Koenig Jochem , Uder Michael , Sybrecht Gerhard W. , Wilkens Heinrike
Published: September 2007

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a poor prognosis. Usual interstitial pneumonia (UIP) is the histopathological pattern identifying patients with the clinical entity of IPF. Despite aggressive immunosuppressive therapy the clinical course is usually dismal. For selected patients only lung transplantation improves prognosis and quality of life. After lung transplantation patients often receive a potent cyclosporine-based immunosuppressive therapy. Some reports suggest that cyclosporine has the potential to prevent progression of fibrosis. Objective: In patients with single lung transplantation (sLTx) for UIP we evaluated the effect of cyclosporine-based immunosuppressive therapy on progression of fibrosis using a high-resolution computed tomography (HRCT) scoring system. Methods: This retrospective observational study included 13 patients (24–64 years old) with histologically confirmed UIP who had HRCT scans preceding and following sLTx and who survived at least 6 months after sLTx. All patients were initially treated with cyclosporin A, prednisone and azathioprine. Three radiologists analyzed HRCT scans by setting a score regarding fibrosis [fibrosis score (FS); range 0–5 for each lobe] and ground-glass opacity [ground-glass score (GGS); range 0–5 for each lobe]. A comparison of serial changes (interval: 12–96 months posttransplant, 2–4 HRCT examinations/patient) was performed with the sign test. Results: Mean pretransplant FS and GGS of the nontransplanted lung were 1.80 and 1.61, respectively. Comparing pre- and posttransplant HRCT scans, mean lung FS significantly increased (0.35 ± 0.15/year; p = 0.00024), while GGS tended to decrease (0.06 ± 0.26/year; p = 0.5). Conclusion: A cyclosporin A based triple immunosuppressive regimen following sLTx does not seem to prevent progression of the fibrotic changes of the native lung in patients with IPF.
PNAS-2: A Novel Gene Probably Participating in Leukemogenesis
Authors: Wang Hai-Rong , Gu Chun-Hong , Zhu Jian-Yi , Han Jie-Yin , Zhong Hua , Chen Fang-Yuan , OuYang Ren-Rong
Published: September 2007

Objective:As4S4 is an effective drug for the treatment of acute promyelocytic leukemia but its mechanism of action remains largely unknown. In a previous study, we identified PNAS-2, a human apoptosis-related protein gene, using gene expression profiling. In this study, we tried to clarify the role of PNAS-2 in apoptosis and leukemogenesis. Methods: NB4 and U937 leukemia cell lines and serial clinical samples were studied. RNA interference (RNAi) and RNA overexpression were used to address the potential role of PNAS-2 in apoptosis. PNAS-2 expression was examined using Northern blot in multiple tissues, and real-time PCR was applied to analyze PNAS-2 expression in various patient samples. Results: Functional analyses of PNAS-2 by RNAi and RNA overexpression indicate PNAS-2 is an anti-apoptosis gene. PNAS-2 expression is significantly increased in de novo or relapsed acute leukemia, but in patients in complete remission PNAS-2 levels decrease to levels comparable to those found in normal controls. In carcinomas, PNAS-2 expression was not upregulated, indicating that PNAS-2 overexpression was specific for leukemia. Conclusion: Based on the preliminary data, we suggest that the PNAS-2 gene functions as an anti-apoptotic gene and probably participates in leukemogenesis.
Local Overexpression of Toll-Like Receptors at the Vessel Wall Induces Atherosclerotic Lesion Formation
Authors: Shinohara Masakazu , Hirata Ken-ichi , Yamashita Tomoya , Takaya Tomofumi , Sasaki Naoto , Shiraki Rio , Ueyama Tomomi , Emoto Noriaki , Inoue Nobutaka , Yokoyama Mitsuhiro , Kawashima Seinosuke
Published: September 2007

Objective—

Atherosclerosis is now considered as a chronic inflammatory disease, and inflammation is closely related to immune systems, which consist of innate-immunity and adaptive-immunity. Recently, toll-like receptors (TLRs) have been identified as key components of innate-immunity. We examined the role of local expressions of TLRs at the vessel wall in atherosclerosis.

Methods and Results—

We transfected cDNA encoding human TLR2 and TLR4 into the carotid arterial vessel wall of rabbits fed high-cholesterol diets with the use of HVJ-liposome. The rabbits were transfected with (1) pCMV-β-gal, (2) empty vector, (3) TLR2, (4) TLR4, (5) TLR2+4. X-gal staining and immunohistochemical analysis showed that the transfected plasmids were mainly expressed in the media. Neither TLR2 nor TLR4 transfection induced significant augmentation of atherosclerosis. Transfection of TLR2- and TLR4-containing HVJ synergistically accelerated atherosclerosis and increased expressions of vascular cell adhesion molecule 1, intercellular adhesion molecule 1, and MCP-1. Moreover, transfection of TLR2 and TLR4 resulted in synergistic activation of NF-κB at the vessel wall in vivo, and in vascular smooth muscle cells in vitro.

Conclusions—

Expressions of both TLR2 and TLR4 at the vessel wall synergistically accelerated atherosclerosis. The present study revealed the role of TLRs expressed locally at the vessel wall in the early stage of atherosclerosis.
Pathway for Differentiation of Human Embryonic Stem Cells to Vascular Cell Components and Their Potential for Vascular Regeneration
Authors: Sone Masakatsu , Itoh Hiroshi , Yamahara Kenichi , Yamashita Jun K. , Yurugi-Kobayashi Takami , Nonoguchi Akane , Suzuki Yutaka , Chao Ting-Hsing , Sawada Naoki , Fukunaga Yasutomo , Miyashita Kazutoshi , Park Kwijun , Oyamada Naofumi , Sawada Naoya , Taura Daisuke , Tamura Naohisa , Kondo Yasushi , Nito Shinji , Suemori Hirofumi , Nakatsuji Norio , Nishikawa Shin-Ichi , Nakao Kazuwa
Published: September 2007

Objective—

We demonstrated previously that mouse embryonic stem (ES) cell–derived vascular endothelial growth factor receptor-2 (VEGF-
R
2)–positive cells can differentiate into both vascular endothelial cells and mural cells. This time, we investigated kinetics of differentiation of human ES cells to vascular cells and examined their potential as a source for vascular regeneration.

Methods and Results—

Unlike mouse ES cells, undifferentiated human ES cells already expressed VEGF-
R
2, but after differentiation, a VEGF-
R
2-positive but tumor rejection antigen 1-60 (TRA1-60)–negative population emerged. These VEGF-
R
2-positive but tumor rejection antigen 1-60–negative cells were also positive for platelet-derived growth factor receptor α and β chains and could be effectively differentiated into both VE-cadherin
+
endothelial cell and α-smooth muscle actin
+
mural cell. VE-cadherin
+
cells, which were also CD34
+
and VEGF-
R
2
+
and thought to be endothelial cells in the early differentiation stage, could be expanded while maintaining their maturity. Their transplantation to the hindlimb ischemia model of immunodeficient mice contributed to the construction of new blood vessels and improved blood flow.

Conclusions—

We could identify the differentiation process from human ES cells to vascular cell components and demonstrate that expansion and transplantation of vascular cells at the appropriate differentiation stage may constitute a novel strategy for vascular regenerative medicine.
Esculeogenin A, a New Tomato Sapogenol, Ameliorates Hyperlipidemia and Atherosclerosis in ApoE-Deficient Mice by Inhibiting ACAT
Authors: Fujiwara Yukio , Kiyota Naoko , Hori Masaharu , Matsushita Sayaka , Iijima Yoko , Aoki Koh , Shibata Daisuke , Takeya Motohiro , Ikeda Tsuyoshi , Nohara Toshihiro , Nagai Ryoji
Published: September 2007

Objective—

We recently identified esculeoside A, a new spirosolane-type glycoside, with a content in tomatoes that is 4-fold higher than that of lycopene. In the present study, we examined the effects of esculeoside A and esculeogenin A, a new aglycon of esculeoside A, on foam cell formation in vitro and atherogenesis in apoE-deficient mice.

Methods and Results—

Esculeogenin A significantly inhibited the accumulation of cholesterol ester (CE) induced by acetylated low density lipoprotein (acetyl-LDL) in human monocyte-derived macrophages (HMDM) in a dose-dependent manner without inhibiting triglyceride accumulation, however, it did not inhibit the association of acetyl-LDL to the cells. Esculeogenin A also inhibited CE formation in Chinese hamster ovary cells overexpressing acyl-coenzymeA (CoA): cholesterol acyl-transferase (ACAT)-1 or ACAT-2, suggesting that esculeogenin A suppresses the activity of both ACAT-1 and ACAT-2. Furthermore, esculeogenin A prevented the expression of ACAT-1 protein, whereas that of SR-A and SR-BI was not suppressed. Oral administration of esculeoside A to apoE-deficient mice significantly reduced the levels of serum cholesterol, triglycerides, LDL-cholesterol, and the areas of atherosclerotic lesions without any detectable side effects.

Conclusions—

Our study provides the first evidence that purified esculeogenin A significantly suppresses the activity of ACAT protein and leads to reduction of atherogenesis.
Silencing of a Targeted Protein in In Vivo Platelets Using a Lentiviral Vector Delivering Short Hairpin RNA Sequence
Authors: Ohmori Tsukasa , Kashiwakura Yuji , Ishiwata Akira , Madoiwa Seiji , Mimuro Jun , Sakata Yoichi
Published: September 2007

Objective—

Because platelets are anucleate cells having a limited life span, direct gene manipulation cannot in principle be used to investigate the involvement of a specific signal transduction pathway in platelet activation. In this study, we examined whether the expression of a short hairpin RNA (shRNA) sequence in hematopoietic stem cells is maintained during megakaryocyte differentiation, thus resulting in inhibition of targeted protein in platelets.

Methods and Results—

To identify platelets derived from transduced stem cells, we generated a lentiviral vector that simultaneously expresses the shRNA sequence driven by the U6 promoter and GFP under the control of the glycoprotein (GP) Ibα promoter. Transplantation of mouse bone marrow cells transduced with the vector facilitated specifically mark platelets derived from the transduced cells. Transplantation of cells transduced with shRNA sequence targeting integrin αIIb caused a significant reduction of integrin αIIbβ3 (αIIbβ3) expression in GFP-positive platelets. It also inhibited αIIbβ3 activation assessed by the binding of JON/A, an antibody that recognizes activated αIIbβ3. Talin-1 silencing by the same method resulted in normal αIIbβ3 expression but deficient inside-out αIIbβ3 signaling.

Conclusions—

shRNA expression driven by the U6 promoter is preserved during megakaryopoiesis. This method facilitates functional analysis of targeted protein in platelet activation.
Pioglitazone Stimulates Apolipoprotein A-I Production Without Affecting HDL Removal in HepG2 Cells
Authors: Qin Shucun , Liu Tianjiao , Kamanna Vaijinath S. , Kashyap Moti L.
Published: September 2007

Objective—

Pioglitazone, an antihyperglycemic drug, increases plasma high-density lipoprotein (HDL)-cholesterol in patients with type 2 diabetes. The mechanisms by which pioglitazone regulate HDL levels are not clear. This study examined the effect of pioglitazone on hepatocyte apolipoprotein AI (apoA-I) and apoA-II production and HDL-protein/cholesterol ester uptake.

Methods and Results—

In human hepatoblastoma (HepG2) cells, pioglitazone, dose-dependently (0.5 to 10 μmol/L), increased the de novo synthesis (up to 45%), secretion (up to 44%), and mRNA expression (up to 59%) of apoA-I. Pioglitazone also increased apoA-II de novo synthesis (up to 73%) and mRNA expression (up to 129%). Pioglitazone did not affect the uptake of HDL
3
-protein or HDL
3
-cholesterol ester in HepG2 cells. The pioglitazone-induced apoA-I lipoprotein particles increased cholesterol efflux from THP-1 macrophages. The pioglitazone-induced apoA-I secretion or mRNA expression by the HepG2 cells was abrogated with the suppression of PPAR-α by small interfering RNA or a specific inhibitor of PPAR-α, MK886.

Conclusions—

The data indicate that pioglitazone increases HDL by stimulating the de novo hepatic synthesis of apoA-I without affecting hepatic HDL-protein or HDL-cholesterol removal. We suggest that pioglitazone-mediated hepatic activation of PPAR-α may be one of the mechanisms of action of pioglitazone to raise hepatic apoA-I and HDL.
4-Hydroxy-2-Nonenal Increases Superoxide Anion Radical in Endothelial Cells via Stimulated GTP Cyclohydrolase Proteasomal Degradation
Authors: Whitsett Jennifer , Picklo Matthew J. , Vasquez-Vivar Jeannette
Published: September 2007

Objective—

4-Hydroxy-2-nonenal (4-HNE) is an abundant electrophilic lipid that mediates oxidative stress in endothelium by mechanisms that remain controversial. This study examines the effects of 4-HNE on nitric oxide (NO) and superoxide levels in bovine aorta endothelial cells (BAECs).

Methods and Results—

Exposure of BAECs to 4-HNE caused a dose-dependent inhibition of NO that correlated with losses of hsp90 and phosphorylated eNOS-serine1179 but not eNOS protein levels. 4-HNE failed to inhibit NO production in sepiapterin and ascorbate supplemented cells suggesting that tetrahydrobiopterin (BH
4
) is a limiting factor in non supplemented cells. This was verified by quantification of BH
4
by high-performance liquid chromatography analysis with electrochemical detection and by examining GTP cyclohydrolase I (GTPCH) protein levels and activity all of which were diminished by 4-HNE treatment. Analysis of 2-hydroxyethidium indicated that 4-HNE increased superoxide release in BAECs. The effects of 4-HNE on GTPCH and hsp90 were efficiently counteracted by proteasomal inhibition, indicating that depletion of BH
4
by 4-HNE is attributable to specific mechanisms involving protein degradation.

Conclusions—

4-HNE by altering BH
4
homeostasis mediates eNOS-uncoupling and superoxide generation in BAECs. By also decreasing phosphorylation of eNOS-serine 1179 4-HNE may specifically regulate NO/reactive oxygen species fluxes in the endothelium with important consequences to redox signaling.
Ets-1 Is a Critical Transcriptional Regulator of Reactive Oxygen Species and p47

phox

Gene Expression in Response to Angiotensin II
Authors: Ni Weihua , Zhan Yumei , He Huamei , Maynard Elizabeth , Balschi James A. , Oettgen Peter
Published: September 2007

Angiotensin (Ang) II is a potent mediator of vascular inflammation. A central mechanism by which Ang II promotes inflammation is through the generation of reactive oxygen species (ROS). In the current study, we investigated the role of the transcription factor Ets-1 in regulating Ang II–induced ROS generation. ROS generation was measured in the thoracic aorta of Ets-1
−/−
mice compared with littermate controls after continuous infusion of Ang II. H
2
O
2
and superoxide anion (O
2
−
) production were significantly blunted in the Ets-1
−/−
mice. Inhibition of Ets-1 expression by small interfering RNA in primary human aortic smooth muscle cells also potently inhibited ROS production and the induction of the NAD(P)H oxidase subunit p47
phox
in response to Ang II. To evaluate the therapeutic potential of inhibiting Ets-1 in wild-type mice, dominant negative Ets-1 membrane-permeable peptides were administered systemically. Ang II–induced ROS production and medial hypertrophy in the thoracic aorta were markedly diminished as a result of blocking Ets-1. In summary, Ets-1 functions as a critical downstream transcriptional mediator of Ang II ROS generation by regulating the expression of NAD(P)H oxidase subunits such as
p47

phox

.
Acid-Sensing Ion Channels Contribute to Transduction of Extracellular Acidosis in Rat Carotid Body Glomus Cells
Authors: Tan Zhi-Yong , Lu Yongjun , Whiteis Carol A. , Benson Christopher J. , Chapleau Mark W. , Abboud Francois M.
Published: September 2007

Carotid body chemoreceptors sense hypoxemia, hypercapnia, and acidosis and play an important role in cardiorespiratory regulation. The molecular mechanism of pH sensing by chemoreceptors is not clear, although it has been proposed to be mediated by a drop in intracellular pH of carotid body glomus cells, which inhibits a K
+
current. Recently, pH-sensitive ion channels have been described in glomus cells that respond directly to extracellular acidosis. In this study, we investigated the possible molecular mechanisms of carotid body pH sensing by recording the responses of glomus cells isolated from rat carotid body to rapid changes in extracellular pH using the whole-cell patch-clamping technique. Extracellular acidosis evoked transient inward current in glomus cells that was inhibited by the acid-sensing ion channel (ASIC) blocker amiloride, absent in Na
+
-free bathing solution, and enhanced by either Ca
2+
-free buffer or addition of lactate. In addition, ASIC1 and ASIC3 were shown to be expressed in rat carotid body by quantitative PCR and immunohistochemistry. In the current-clamp mode, extracellular acidosis evoked both a transient and sustained depolarizations. The initial transient component of depolarization was blocked by amiloride, whereas the sustained component was eliminated by removal of K
+
from the pipette solution and partially blocked by the TASK (tandem-p-domain, acid-sensitive K
+
channel) blockers anandamide and quinidine. The results provide the first evidence that ASICs may contribute to chemotransduction of low pH by carotid body chemoreceptors and that extracellular acidosis directly activates carotid body chemoreceptors through both ASIC and TASK channels.
Increased Atherosclerotic Lesion Calcification in a Novel Mouse Model Combining Insulin Resistance, Hyperglycemia, and Hypercholesterolemia
Authors: Heinonen Suvi E. , Leppänen Pia , Kholová Ivana , Lumivuori Henri , Häkkinen Sanna-Kaisa , Bosch Fatima , Laakso Markku , Ylä-Herttuala Seppo
Published: September 2007

No mouse model is currently available where the induction of type 2 diabetes on an atherosclerotic background could be achieved without significant concomitant changes in plasma lipid levels. We crossbred 2 genetically modified mouse strains to achieve a model expressing both atherosclerosis and characteristics of type 2 diabetes. For atherosclerotic background we used low-density lipoprotein receptor–deficient mice synthetizing only apolipoprotein B100 (LDLR
−/−
ApoB
100/100
). Diabetic background was obtained from transgenic mice overexpressing insulin-like growth factor-II (IGF-II) in pancreatic beta cells. Thorough phenotypic characterization was performed in 6- and 15-month-old mice on both normal and high-fat Western diet. Results indicated that IGF-II transgenic LDLR
−/−
ApoB
100/100
mice demonstrated insulin resistance, hyperglycemia, and mild hyperinsulinemia compared with hypercholesterolemic LDLR
−/−
ApoB
100/100
controls. In addition, old IGF-II/LDLR
−/−
ApoB
100/100
mice displayed significantly increased lesion calcification, which was more related to insulin resistance than glucose levels, and significantly higher baseline expression in aorta of several genes related to calcification and inflammation. Lipid levels of IGF-II/LDLR
−/−
ApoB
100/100
mice did not differ from LDLR
−/−
ApoB
100/100
controls at any time. In conclusion, type 2 diabetic factors induce increased calcification and lesion progression without any lipid changes in a new mouse model of diabetic macroangiopathy.
Overexpression of FK-506–Binding Protein 12.0 Modulates Excitation–Contraction Coupling in Adult Rabbit Ventricular Cardiomyocytes
Authors: Seidler Tim , Loughrey Christopher M. , Zibrova Darya , Kettlewell Sarah , Teucher Nils , Kögler Harald , Hasenfuss Gerd , Smith Godfrey L.
Published: September 2007

The effect of the 12-kDa isoform of FK-506–binding protein (FKBP)12.0 on cardiac excitation–contraction coupling was studied in adult rabbit ventricular myocytes after transfection with a recombinant adenovirus coding for human FKBP12.0 (Ad-FKBP12.0). Western blots confirmed overexpression (by 2.6±0.4 fold, n=5). FKBP12.0 association with rabbit cardiac ryanodine receptor (RyR2) was not detected by immunoprecipitation. However, glutathione
S
-transferase pull-down experiments indicated FKBP12.0–RyR2 binding to proteins isolated from human and rabbit but not dog myocardium. Voltage-clamp experiments indicated no effects of FKBP12.0 overexpression on L-type Ca
2+
current (
I
Ca,L
) or Ca
2+
efflux rates via the Na
+
/Ca
2+
exchanger. Ca
2+
transient amplitude was also not significantly different. However, sarcoplasmic reticulum Ca
2+
load was ≈25% higher in myocytes in the Ad-FKBP12.0 group. The reduced ability of
I
Ca,L
to initiate sarcoplasmic reticulum Ca
2+
release was observed over a range of values of sarcoplasmic reticulum Ca
2+
content, indicating that overexpression of FKBP12.0 reduces the sensitivity of RyR2 to Ca
2+
. Ca
2+
spark morphology was measured in β-escin–permeabilized cardiomyocytes. Ca
2+
spark amplitude and duration were significantly increased, whereas frequency was decreased in cells overexpressing FKBP12.0. These changes were accompanied by an increased sarcoplasmic reticulum Ca
2+
content. In summary, the effects of FKBP12.0 overexpression on intact and permeabilized cells were similar to those of tetracaine, a drug known to reduce RyR2 Ca
2+
sensitivity and distinctly different from the effects of overexpression of the FKBP12.6 isomer. In conclusion, FKBP12.0-RyR2 interaction can regulate the gain of excitation–contraction coupling.
Transient Receptor Potential Channel 6–Mediated, Localized Cytosolic [Na
+
] Transients Drive Na
+
/Ca
2+
Exchanger–Mediated Ca
2+
Entry in Purinergically Stimulated Aorta Smooth Muscle Cells
Authors: Poburko Damon , Liao Chiu-Hsiang , Lemos Virginia S. , Lin Eric , Maruyama Yoshiaki , Cole William C. , van Breemen Cornelis
Published: September 2007

The Na
+
/Ca
2+
exchanger (NCX) is increasingly recognized as a physiological mediator of Ca
2+
influx and significantly contributes to salt-sensitive hypertension. We recently reported that Ca
2+
influx by the NCX (1) is the primary mechanism of Ca
2+
entry in purinergically stimulated rat aorta smooth muscle cells and (2) requires functional coupling with transient receptor potential channel 6 nonselective cation channels. Using the Na
+
indicator CoroNa Green, we now directly observed and characterized the localized cytosolic [Na
+
] ([Na
+
]
i
) elevations that have long been hypothesized to underlie physiological NCX reversal but that have never been directly shown. Stimulation of rat aorta smooth muscle cells caused both global and monotonic [Na
+
]
i
elevations and localized [Na
+
]
i
transients (LNats) at the cell periphery. Inhibition of nonselective cation channels with SKF-96365 (50 μmol/L) and 2-amino-4-phosphonobutyrate (75 μmol/L) reduced both global and localized [Na
+
]
i
elevations in response to ATP (1 mmol/L). This effect was mimicked by expression of a dominant negative construct of transient receptor potential channel 6. Selective inhibition of NCX-mediated Ca
2+
entry with KB-R7943 (10 μmol/L) enhanced the LNats, whereas the global cytosolic [Na
+
] signal was unaffected. Inhibition of mitochondrial Na
+
uptake with CGP-37157 (10 μmol/L) increased both LNats and global cytosolic [Na
+
] elevations. These findings directly demonstrate NCX regulation by LNats, which are restricted to subsarcolemmal, cytoplasmic microdomains. Analysis of the LNats, which facilitate Ca
2+
entry via NCX, suggests that mitochondria limit the cytosolic diffusion of LNats generated by agonist-mediated activation of transient receptor potential channel 6–containing channels.
Sphingosine 1-Phosphate Receptor 2 Negatively Regulates Neointimal Formation in Mouse Arteries
Authors: Shimizu Takuya , Nakazawa Tatsu , Cho Aesim , Dastvan Frank , Shilling Dustin , Daum Günter , Reidy Michael A.
Published: September 2007

Neointimal lesion formation was induced in sphingosine 1-phosphate (S1P) receptor 2 (S1P
2
)-null and wild-type mice by ligation of the left carotid artery. After 28 days, large neointimal lesions developed in S1P
2
-null but not in wild-type arteries. This was accompanied with a significant increase in both medial and intimal smooth muscle cell (SMC) replication between days 4 to 28, with only minimal replication in wild-type arteries. S1P
2
-null SMCs showed a significant increase in migration when stimulated with S1P alone and together with platelet-derived growth factor, whereas both wild-type and null SMCs migrated equally well to platelet-derived growth factor. S1P increased Rho activation in wild-type but not in S1P
2
-null SMCs, and inhibition of Rho activity promoted S1P-induced SMC migration. Plasma S1P levels were similar and did not change after surgery. These results suggest that activation of S1P
2
normally acts to suppress SMC growth in arteries and that S1P is a regulator of neointimal development.
Myofibroblasts Induce Ectopic Activity in Cardiac Tissue
Authors: Miragoli Michele , Salvarani Nicolò , Rohr Stephan
Published: September 2007

Focal ectopic activity in cardiac tissue is a key factor in the initiation and perpetuation of tachyarrhythmias. Because myofibroblasts as present in fibrotic remodeled myocardia and infarct scars depolarize cardiomyocytes by heterocellular electrotonic interactions via gap junctions in vitro, we investigated using strands of cultured ventricular cardiomyocytes coated with myofibroblasts, whether this interaction might give rise to depolarization-induced abnormal automaticity. Whereas uncoated cardiomyocyte strands were invariably quiescent, myofibroblasts induced synchronized spontaneous activity in a density dependent manner. Activations appeared at spatial myofibroblast densities >15.7% and involved more than 80% of the preparations at myofibroblast densities of 50%. Spontaneous activity was based on depolarization-induced automaticity as evidenced by: (1) suppression of activity by the sarcolemmal K
ATP
channel opener P-1075; (2) induction of activity in current-clamped single cardiomyocytes undergoing depolarization to potentials similar to those induced by myofibroblasts in cardiomyocyte strands; and (3) induction of spontaneous activity in cardiomyocyte strands coated with connexin 43 transfected Hela cells but not with communication deficient HeLa wild-type cells. Apart from unveiling the mechanism underlying the hallmark of monolayer cultures of cardiomyocytes, ie, spontaneous electromechanical activity, these findings open the perspective that myofibroblasts present in structurally remodeled myocardia following pressure overload and infarction might contribute to arrhythmogenesis by induction of ectopic activity.
The UN Commission on Sustainable Development: Which Mechanisms Explain Its Accomplishments?
Authors: Kaasa Stine Madland
Published: September 2007

The UN Commission on Sustainable Development (CSD) has been criticized for lack of effectiveness since its establishment in 1993. The main objective of this article is to describe and explain the mechanisms that affect the work of the CSD, in order to understand how it would be possible to enhance the potential for effectiveness. The study aims to apply the perspectives of “distribution of capabilities” and “institutional design” to evaluate the CSD's accomplishments during its fırst ten-year period. I conclude that the CSD has achieved some results in monitoring and reviewing the process on the implementation of Agenda 21 and promoting dialogue and building partnerships for sustainable development, due to the role of the secretariat and nongovernmental organizations. However, the member states' positions and interests have contributed to the CSD's low goal attainment, especially in the area of policy guidance.
Implementing Multilateral Environmental Agreements: An Analysis of EU Directives
Authors: Perkins Richard , Neumayer Eric
Published: September 2007

While a number of different theoretical models have been advanced to explain why states implement—or, indeed, do not implement—multilateral environmental agreements (MEAs), very little empirical work has been undertaken to validate their predictions. With a view to narrowing this gap, the present article adopts a large-N, econometric approach to test the explanatory power of four distinct models of compliance—domestic adjustment, reputational, constructivist and managerial—in the context of European Union (EU) environmental policy. Using data on the number of ofıcial infringements received by 15 member states for non-implementation of environmental directives over the period 1979–2000, we ınd that all four models make a statistically signiıcant contribution to explaining spatio-temporal differences in legal implementation. Thus, our results suggest that the implementation of MEAs is shaped by a combination of rational calculations of domestic compliance costs and reputational damage, domestically institutionalized normative obligations, and legal and political constraints. We conclude by suggesting a greater need for multi-causal theoretical models of supranational legal compliance.
Oil Companies and Climate Change: Inconsistencies between Strategy Formulation and Implementation?
Authors: Sæverud Ingvild Andreassen , Skjærseth Jon Birger
Published: September 2007

This article examines major oil companies in terms of climate strategies and their implementation. More specifıcally, it takes a critical look at Shell, BP, and ExxonMobil, and the relationship between rhetoric and action regarding investments in climate-friendly activities. Empirical evidence indicates a generally high degree of consistency between what these companies say and what they do, but interesting differences are also found: ExxonMobil has done somewhat more than its climate strategy formulations would suggest; Shell has done somewhat less; whereas BP's activities are mainly in line with its statements. Factors at three levels contribute to explaining these differences: (1) the company level, 2) the political framework conditions in the various regions where the companies operate, 3) international climate cooperation. The fındings and explanations, although restricted to the three oil companies with regard to climate change, provide insight into the relationship between corporate strategies and implementation more generally. They offer understanding and analytical categories for assessing how well and why such multinational entities put into practice stated objectives.
Coalition Politics and Chemicals Management in a Regulatory Ambitious Europe
Authors: Selin Henrik
Published: September 2007

The European Union (EU) has greatly expanded its environmental legislation over the past two decades. This article analyzes the recent development of the REACH (Registration, Evaluation and Authorization of Chemicals) regulation. It uses a process-tracing technique to explore the question of how REACH was created despite signifıcant resistance from influential and well-organized industry interests and misgivings from leading European politicians and policy-makers. Examining developing coalition politics within the EU, it is argued that a relatively small coalition of green actors from EU organizations, member states, and environmental and public health advocacy groups succeeded in ensuring the development and adoption of REACH largely because the coalition included influential members from all major EU policy-making centers (the European Commission, the Council of Ministers, and the European Parliament). In addition, it is argued that the implementation of REACH can have important ramiıcations for international chemical politics and policy-making outside the EU.
Pretend Play of Brazilian Children
Authors: Gosso Yumi , e Morais Maria de Lima Salum , Otta Emma
Published: September 2007

This study compared pretend play of Brazilian children (41 girls and 35 boys, 4 to 6 years old) of five different cultural groups: (a) Indians, (b) seashore, (c) low socioeconomic status (SES) urban, (d) high SES urban, and (e) mixed SES urban. This cross-cultural investigation was based in naturalistic observation and conducted within a methodological framework that considered the content and the meaning of symbolic transformation and its structure. Although pretend play occurred in all groups, high and mixed SES urban children engaged in more pretending than the others. In accordance with the theoretical claim that make believe is a universal phenomenon, the differences among cultural groups were expressed more in the content than in the structure of pretend play.
Social Dominance Orientation and Ideological Asymmetry in Relation To Interracial Dating and Transracial Adoption in Canada
Authors: Lalonde Richard N. , Giguère Benjamin , Fontaine Marsha , Smith Andrea
Published: September 2007

This study examines the relation between social dominance orientation (SDO) and three hierarchy-attenuating beliefs (attitude toward and openness to personally engaging in interracial dating and attitude toward transracial adoption) and two hierarchy-enhancing beliefs (stereotyping of interracial relationships and racial identity concerns in transracial adoption). Participants were 77 Black and 142 White Canadians from the Toronto area. SDO was significantly negatively related to the three hierarchy-attenuating beliefs and positively to the two hierarchy-enhancing beliefs for Whites, whereas no significant relationships were found for Blacks. The relation between SDO and the outcome variables for Blacks and Whites differed significantly with the exception of openness to interracial dating. Interracial dating experience moderated the relation between race, SDO, and openness to become personally involved in interracial dating. Results support and extend previous research by Fang, Sidanius, and Pratto. Their social implications are discussed.
Cultural Validation of the Multidimensional Peer Victimization Scale in Nigerian Children
Authors: Balogun Shyngle Kolawole , Olapegba Peter Olamakinde
Published: September 2007

This study attempted cultural validation of the Multidimensional Peer Victimization Scale for use with Nigerian children. In it, 240 primary school pupils in Grades 4 and 5 (131 boys and 109 girls; age 7 to 12) purposively selected from five nursery/primary schools in Ibadan, Nigeria, participated. The Multidimensional Peer Victimization Scale was administered, and analysis yielded Cronbach's alpha of .78 for internal consistency and split-half reliability of .76. Principal component analysis identified four factors with Eigenvalues greater than 1.00, with all items loading above .49. Gender and age effects were not significant on total peer victimization score, although significant gender and age differences were observed on some subscales. The scale correlated significantly with the Buss and Durkee Aggression Scale. Results suggest the Multidimensional Peer Victimization Scale can be used to measure Nigerian children's experience of peer victimization and provide an initial step toward further cross-cultural work on peer victimization.
Social Relationships and Sexism in the United States and Taiwan
Authors: Lee I-Ching , Pratto Felicia , Li Mei-Chih
Published: September 2007

This research examines the cultural origins of sexism and how it is enacted within cultures. The harmonious tenor of Taiwanese collectivism and the competitive individualism of American culture are hypothesized to afford benevolent sexism and hostile sexism, respectively. Whereas hostile sexism was expected to affect Americans' bias in favor of men more than benevolent sexism, benevolent sexism should affect Taiwanese bias favoring men more than hostile sexism. Deferential family norms and support for hierarchical intergroup relationships (social dominance orientation) were hypothesized to increase support of sexism in both cultures. Two studies within each culture confirmed the aforementioned hypotheses. The cultural roots of legitimizing ideologies and the cultural origins of different forms of sexism are discussed.
Police-Run Brothels in Republican Kunming
Authors: Remick Elizabeth J.
Published: September 2007

Breaking from practice in the rest of China, local officials in Republican Kunming selected an unusual strategy for controlling prostitution: police-managed brothel compounds called jiyuan. In the face of social resistance from many groups, the jiyuan subjected prostitutes to unusually high levels of surveillance and state intervention, as a local state bureaucracy was created to monitor the brothels. This phenomenon is theoretically significant because it illustrates how apparently “private” gender systems result in distinct local state formations.
On the Mid Range
Authors: Rappert Brian
Published: September 2007

Many efforts to establish concepts and theories of the middle range have sought to find an appropriate balance between theoretical abstraction and the desire to remain faithful to the empirical complexity of phenomenon. As with other forms of expertise, those analyzing socio-technical life face acute tensions in attempting to reconcile the general and the specific in a manner which is regarded as credible. Through a consideration of the self-referential implications of STS critiques of traditional notions of science as well as attempts to establish rules for the acceptability of coercive force, this article develops a sense of what is at stake in attempts by actors and analysts to grasp the general and the specific together. Instead of seeking to identify a point of resolution for the two, it advocates and exemplifies the need to attend to the dilemmas associated with the movement between the general and the specific. The middle range concept of “disposal strategies” is offered both as an aid to the study of socio-technical life and as an example of attending to the movement between the general and specific.
STS and the City
Authors: Coutard Olivier , Guy Simon
Published: September 2007

Many recent studies on network technologies and cities share an alarmist view of the impact of technological or regulatory change in utility sectors on the social and spatial fabric of cities, pointing to growing discrimination and inequalities, alienation, enhanced social exclusion and urban “splintering” on a universal scale.

A science and technology study (STS) perspective on these matters is helpful in moving beyond this “universal alarmism” by emphasizing the ambivalence inherent to all technologies, the significant potential of contestation of, and resistance, to technology-supported forms of discrimination, and the deeply contingent nature of the process of appropriation of new technologies and, as a consequence, of the social “effects” of technologies. Adopting this perspective would mean actively searching for and exploring these context-dependent and often conflictive appropriation processes. For it is in these spaces that we might begin to identify urban technological politics that break free from an intellectually and politically disabling technological pessimism.
Buckling Behavior of Laminated Composite Plates
Authors: Baba B. O.
Published: September 2007

In this study, the influence of boundary conditions on the buckling load for rectangular plates of various cutout shape, length/thickness ratio, and ply orientation is examined. Boundary conditions consisting of clamped, pinned, and their combinations are considered. Numerical and experimental studies are conducted to investigate the effect of boundary conditions, cutout shape, length/thickness ratio, and ply orientation on the buckling behavior of E-glass/epoxy composite plates under in-plane compression load. Buckling analysis of the laminated composites is performed by using finite element analysis software ANSYS. Tests have been carried out on laminated composites with circular and semicircular cutouts under various boundary conditions. Comparisons are made between the test results and predictions based on finite element analysis. The results show a complex interaction between plate orthotropy and boundary conditions.
Effects of Material and Test Parameters on the Wear Behavior of Particulate Filled Composites Part 2: Cu-Epoxy and A1-Epoxy Composites
Authors: Bhagyashekar M.S. , Rao R.M.V.G.K.
Published: September 2007

Studies were carried out on a RT-cure epoxy (LY556 + HY951) composite system filled with the Al and Cu particles. Results showed that the wear loss and COF of both the composites increased with sliding distance and contact load for the range of filler content considered. Further, it was observed that the Cu-Epoxy composite exhibited superior wear resistance compared to the Al-Epoxy composites. From the experimental data, a ``wear endurance index'' was identified which can serve as a parameter to assess the long term wear life (residual wear life) of these composites.
Degradation Studies of Coir Fiber/Polyester and Glass Fiber/Polyester Composites under Different Conditions
Authors: Sindhu K. , Joseph Kuruvilla , Joseph Jasmine Maria , Mathew Thomas V.
Published: September 2007

The influence of different conditions on the mechanical properties of short coir fiber reinforced polymer composites as well as glass fiber reinforced polymer composites have been analyzed and compared. Fiber length of 20 mm was found to be optimum for the best result. It is observed that the filler loading of 30 phr was most suitable for best results. Degradation studies were carried out in different solvents like 10% NaOH, 1 N HCl, and 10% NaCl and water. The effect of these solvents and water on the mechanical properties of the composites was studied in detail. The deterioration of mechanical properties of the coir/PE and glass/PE composites by environmental weathering was also studied.
Effects of Some Injection Molding Process Parameters on Fiber Orientation Tensor of Short Glass Fiber Polystyrene Composites (SGF/PS)
Authors: SadAbadi Hamid , Ghasemi Masood
Published: September 2007

Calculation of fiber orientation distribution is the reference standard for determining the numerous physical and mechanical properties of injection molded short fiber reinforced thermoplastics. On the other hand, most of the properties of these composites depend on their fiber orientation pattern, which can be represented by tensorial notation, aij. This work focuses on numerical calculation of a fiber orientation tensor of an injection molded short glass fiber polystyrene (SGF-PS) composite part, shaped as a rectangular plate. In this study, the effects of some parameters of the injection molding process including injection flow rate, mold wall temprature, packing pressure and also fiber content on the changes of fiber orientations of this specimen are investigated. Our studies are concentrated on determining the changes of the first orientation tensor component in the flow direction due to different injection parameters. In addition, the changes on tensile modulus of the injected part are simulated in every condition. The simulations show how these molding parameters can influence both fiber orientation and tensile modulus of injection molded parts. At the first step, in order to be confident about the software results, they are validated by experimental data in two cases.
Factors Influencing the Motivation of Turkey's Community Volunteers
Authors: Boz Ismet , Palaz Serap
Published: September 2007

Although Turkish society has traditionally valued volunteering, it has not fully utilized the potential of such contributions. This is because the country lacks professional volunteer organizations, and limited research has evaluated Turkish volunteers. The main aims of the current study were to describe the personal characteristics of Turkey's community volunteers and to determine the influence of various motivational factors on their decision to serve in the Community Volunteer Foundation. The participants were a randomly selected sample of 175 community volunteers from different regions of Turkey. Findings showed that the average community volunteer was a 22-year-old, male college student pursuing a career in engineering, economics, or business. The most important motivational factors for volunteering were altruism, a filiation, and personal improvement (in that order). Completing an orientation course before working as a volunteer was considered useful. Recognition, by contrast, was not considered to be a vital factor.
Immigrant Nonprofit Organizations in U.S. Metropolitan Areas
Authors: Hung Chi-Kan Richard
Published: September 2007

This article provides an overview of existing immigrant nonprofits formed and maintained by Asian-American or Hispanic-Latino community leaders in the largest metropolitan areas in the United States. Although some of these organizations date back to the 1940s, the majority of them were formed in the last three decades in a more open and accommodating society. For both of these immigrant groups, organizing to form and maintain religious organizations started early and continued to significantly affect the respective community. While Asian-American communities tend to focus on maintaining their heritage by forming numerous cultural organizations, the larger Hispanic-Latino population started early to form service agencies—aided possibly by alternative means to maintain cultural identity. Immigrant religious organizations tend to be older and located in suburban middle-class communities with a diverse ethnic population. Immigrant secular organizations are generally younger, located in central city communities with a more homogeneous ethnic population. Older immigrant nonprofits also tend to be financially stronger and more stable.
Do Antipoverty Nonprofits Locate Where People Need Them? Evidence From a Spatial Analysis of Phoenix
Authors: Peck Laura R.
Published: September 2007

This work explores the spatial connections between nonprofit organizations that have an antipoverty focus and poor residents in the greater Phoenix, Arizona, metropolitan area. Substantial population and service growth occurred in Phoenix between 1990 and 2000, with almost twice the number of organizations and almost three times the amount of expenditures in 2000 than in 1990. Empirical evidence supports that these nonprofits locate in areas of greater need, but evidence that those organizations affect neighborhood poverty is weak, suggesting that the government should not retract services and that further nonprofit organizational growth may be necessary. The comprehensive measure of accessibility and two-way causal analysis are proposed for future replication.