bluuebunny/crossref_metadata_2025 huggingface dataset:
Phenolic Acid-Mediated Regulation of the
padC
Gene, Encoding the Phenolic Acid Decarboxylase of
Bacillus subtilis
Authors: Tran Ngoc Phuong , Gury Jerôme , Dartois Véronique , Nguyen Thi Kim Chi , Seraut Hélène , Barthelmebs Lise , Gervais Patrick , Cavin Jean-François
Published: March 2008

In
Bacillus subtilis
, several phenolic acids specifically induce expression of
padC
, encoding a phenolic acid decarboxylase that converts these antimicrobial compounds into vinyl derivatives.
padC
forms an operon with a putative coding sequence of unknown function,
yveFG
, and this coding sequence does not appear to be involved in the phenolic acid stress response (PASR). To identify putative regulators involved in the PASR, random transposon mutagenesis, combined with two different screens, was performed. PadR, a negative transcriptional regulator of
padC
expression, was identified.
padR
is not located in the vicinity of
padC
, and the expression of
padR
is low and appears constitutive. This is in contrast with what occurs in other gram-positive bacteria, in which
padR
is autoregulated and induced by phenolic acids. Further screening of the transposon library failed to identify genes other than
padR
involved in the PASR. Modest inactivation of
padR
by phenolic acids was obtained in recombinant
Escherichia coli
expressing
padC
and
padR
, and this translates into induction of decarboxylase activity. Gel shift promoter binding assays performed with and without MgCl
2
, and with and without phenolic acids, demonstrated that phenolic acids were able to abolish the binding of PadR to the
yveFG
-
padC
promoter in the absence of MgCl
2
. Altogether, our results indicate that (i) PadR is inactivated directly by phenolic acids in vitro, (ii) inhibition of PadR in response to phenolic acids may occur without the need for a sensor-like effector in
B. subtilis
, and (iii) phenolic acids are able to modulate PadR activity in
E. coli
in the absence of any additional effector.
Characterization of the
Streptomyces lividans
PspA Response
Authors: Vrancken Kristof , Van Mellaert Lieve , Anné Jozef
Published: March 2008

Phage shock protein (Psp) is induced by extracytoplasmic stress that may reduce the energy status of the cell. It is encoded in
Escherichia coli
by the phage shock protein regulon consisting of
pspABCDE
and by
pspF
and
pspG
. The phage shock protein system is highly conserved among a large number of gram-negative bacteria. However, many bacterial genomes contain only a
pspA
homologue but no homologues of the other genes of the Psp system. This conservation indicates that PspA alone might play an important role in these bacteria. In
Streptomyces lividans
, a soil-borne gram-positive bacterium, the phage shock protein system consists only of the
pspA
gene. In this report, we showed that
pspA
encodes a 28-kDa protein that is present in both the cytoplasmic and the membrane fractions of the
S. lividans
mycelium. We demonstrated that the
pspA
gene is strongly induced under stress conditions that attack membrane integrity and that it is essential for growth and survival under most of these conditions. The data reported here clearly show that PspA plays an important role in
S. lividans
under stress conditions despite the absence of other
psp
homologues, suggesting that PspA may be more important in most bacteria than previously thought.
Enterococcus faecalisPcfC, a Spatially Localized Substrate Receptor for Type IV Secretion of the pCF10 Transfer Intermediate
Authors: Chen Yuqing , Zhang Xiaolin , Manias Dawn , Yeo Hye-Jeong , Dunny Gary M. , Christie Peter J.
Published: March 2008

Upon sensing of peptide pheromone,Enterococcus faecalisefficiently transfers plasmid pCF10 through a type IV secretion (T4S) system to recipient cells. The PcfF accessory factor and PcfG relaxase initiate transfer by catalyzing strand-specific nicking at the pCF10 origin of transfer sequence (oriT). Here, we present evidence that PcfF and PcfG spatially coordinate docking of the pCF10 transfer intermediate with PcfC, a membrane-bound putative ATPase related to the coupling proteins of gram-negative T4S machines. PcfC and PcfG fractionated with the membrane and PcfF with the cytoplasm, yet all three proteins formed several punctate foci at the peripheries of pheromone-induced cells as monitored by immunofluorescence microscopy. A PcfC Walker A nucleoside triphosphate (NTP) binding site mutant (K156T) fractionated with theE. faecalismembrane and also formed foci, whereas PcfC deleted of its N-terminal putative transmembrane domain (PcfCΔN103) distributed uniformly throughout the cytoplasm. Native PcfC and mutant proteins PcfCK156T and PcfCΔN103 bound pCF10 but notpcfGor ΔoriTmutant plasmids as shown by transfer DNA immunoprecipitation, indicating that PcfC binds only the processed form of pCF10 in vivo. Finally, purified PcfCΔN103 bound DNA substrates and interacted with purified PcfF and PcfG in vitro. Our findings support a model in which (i) PcfF recruits PcfG tooriTto catalyze T-strand nicking, (ii) PcfF and PcfG spatially position the relaxosome at the cell membrane to stimulate substrate docking with PcfC, and (iii) PcfC initiates substrate transfer through the pCF10 T4S channel by an NTP-dependent mechanism.
The Early Kinetics of Cytomegalovirus-Specific CD8+T-Cell Responses Are Not Affected by Antigen Load or the Absence of Perforin or Gamma Interferon
Authors: Andrews Daniel M. , Andoniou Christopher E. , Fleming Peter , Smyth Mark J. , Degli-Esposti Mariapia A.
Published: March 2008

Both innate and adaptive immune responses participate in the control of murine cytomegalovirus (mCMV) infection. In some mouse strains, like BALB/c, the control of infection relies on the activities of CD8+T cells. mCMV-specific CD8+T-cell responses are unusual in that, even after mCMV has been controlled in the periphery, the numbers of circulating virus-specific CD8+T cells remain high compared to those observed in other viral infections. To better understand the generation and maintenance of mCMV-specific CD8+T-cell responses, we evaluated how antigen load and effector molecules, such as perforin (Prf) and gamma interferon (IFN-γ), influence these responses during acute infection in vivo. Viral burden affected the magnitude, but not the early kinetics, of antigen-specific CD8+T-cell responses. Similarly, the magnitude of virus-specific CD8+T-cell expansion was affected by Prf and IFN-γ, but contraction of antigen-specific responses occurred normally in both Prf- and IFN-γ-deficient mice. These data indicate that control of mCMV-specific CD8+T-cell expansion and contraction is more complex than anticipated and, despite the role of Prf or IFN-γ in controlling viral replication, a full program of T-cell expansion and contraction can occur in their absence.
Polyomavirus Middle T Antigen Induces the Transcription of Osteopontin, a Gene Important for the Migration of Transformed Cells
Authors: Whalen Kerry A. , Weber Georg F. , Benjamin Thomas L. , Schaffhausen Brian S.
Published: March 2008

Middle T antigen (MT) is the principal oncoprotein of murine polyomavirus. Experiments on the acute immediate effects of MT expression on cellular RNA levels showed that expression of osteopontin (OPN) was strongly induced by MT expression. Osteopontin is a protein known to be associated with cancer. It has a role in tumor progression and invasion. Protein analysis confirmed that MT induced the secretion of OPN into the extracellular medium. Expression of antisense OPN RNA had no effect on the growth of MT-transformed cells. However, it had a strong effect on the ability of MT transformants to migrate or to fill a wound. Analysis of MT mutants implicated both the SHC and phosphatidylinositol 3-kinase pathways in OPN induction. Reporter assays showed that MT regulated the OPN promoter through two of its PEA3 (
p
olyoma
e
nhancer
a
ctivator
3
) sites. As critical PEA3 sites are also part of the polyomavirus enhancer, the same signaling important for viral replication also contributes to virally induced metastatic potential.
Contractile regulation by overexpressed ETArequires intact T tubules in adult rat ventricular myocytes
Authors: Chung Ka Young , Kang Misuk , Walker Jeffery W.
Published: March 2008

Endothelin (ET)-1 regulates the contractility and growth of the heart by binding G protein-coupled receptors of the ET type A receptor (ETA)/ET type B (ETB) receptor family. ETA, the predominant ET-1 receptor subtype in myocardium, is thought to localize preferentially within cardiac T tubules, but the consequences of mislocalization are not fully understood. Here we examined the effects of the overexpression of ETAin conjunction with T-tubule loss in cultured adult rat ventricular myocytes. In adult myocytes cultured for 3 to 4 days, the normally robust positive inotropic effect (PIE) of ET-1 was lost in parallel with T-tubule degeneration and a decline in ETAprotein levels. In these T tubule-compromised myocytes, an overexpression of ETAusing an adenoviral vector did not rescue the responsiveness to ET-1, despite the robust expression in the surface sarcolemma. The inclusion of the actin polymerization inhibitor cytochalasin D (CD) during culture prevented gross morphological changes including a loss of T tubules and a rounding of intercalated discs, but CD alone did not rescue the responsiveness to ET-1 or prevent ETAdownregulation. The rescue of a normal PIE in 3- to 4-day cultured myocytes required both an increased expression of ETAand intact T tubules (preserved with CD). Therefore, the activation of ETAlocalized in T tubules was associated with a strong PIE, whereas the activation of ETAin surface sarcolemma was not. The results provide insight into the pathological cardiac conditions in which ETAis upregulated and T-tubule morphology is altered.
Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats
Authors: Ungvari Zoltan , Labinskyy Nazar , Gupte Sachin , Chander Praveen N. , Edwards John G. , Csiszar Anna
Published: March 2008

Mitochondrial biogenesis is involved in the control of cell metabolism, signal transduction, and regulation of mitochondrial reactive oxygen species (ROS) production. Despite the central role of mitochondria in cellular aging and endothelial physiology, there are no studies extant investigating age-related alterations in mitochondrial biogenesis in blood vessels. Electronmicroscopy and confocal microscopy (en face Mitotracker staining) revealed that in aortas of F344 rats, a decline in mitochondrial biogenesis occurs with aging. In aged vessels, the expression of the mitochondrial biogenesis factors (including mitochondrial transcription factor A and peroxisome proliferator-activated receptor-γ coactivator-1) was decreased. The vascular expression of complex I, III, and IV significantly declined with age, whereas aging did not alter the expression of complex II and V. Cytochrome c oxidase (COX) expression/activity exhibited the greatest age-related decline, which was associated with increased mitochondrial ROS production in the aged vessels. In cultured coronary arterial endothelial cells, a partial knockdown of COX significantly increased mitochondrial ROS production. In conclusion, vascular aging is characterized by a decline in mitochondrial mass in the endothelial cells and an altered expression of components of the mitochondrial electron transport chain likely due to a dysregulation of mitochondrial biogenesis factors. We posit that impaired mitochondrial biogenesis and downregulation of COX may contribute to the increased mitochondrial oxidative stress in aged endothelial cells.
Nitric oxide generation by endothelial cells exposed to shear stress in glass tubes perfused with red blood cell suspensions: role of aggregation
Authors: Yalcin Ozlem , Ulker Pinar , Yavuzer Ugur , Meiselman Herbert J. , Baskurt Oguz K.
Published: March 2008

Endothelial function is modulated by wall shear stress acting on the vessel wall, which is determined by fluid velocity and the local viscosity near the vessel wall. Red blood cell (RBC) aggregation may affect the local viscosity by favoring axial migration. The aim of this study was to investigate the role of RBC aggregation, with or without altered plasma viscosity, in the mechanically induced nitric oxide (NO)-related mechanisms of endothelial cells. Human umbilical vein endothelial cells (HUVEC) were cultured on the inner surface of cylindrical glass capillaries that were perfused with RBC suspensions having normal and increased aggregation at a nominal shear stress of 15 dyn/cm2. RBC aggregation was enhanced by two different approaches: 1) poloxamer-coated RBC suspended in normal, autologous plasma, resulting in enhanced aggregation but unchanged plasma viscosity and 2) normal RBC suspended in autologous plasma containing 0.5% dextran (mol mass 500 kDa), with a similar level of RBC aggregation but higher plasma viscosity. Compared with normal cells in unmodified plasma, perfusion with suspensions of poloxamer-coated RBC in normal plasma resulted in decreased levels of NO metabolites and serine 1177 phosphorylation of endothelial nitric oxide synthase (eNOS). Perfusion with normal RBC in plasma containing dextran resulted in a NO level that remained elevated, whereas only a modest decrease of phosphorylated eNOS level was observed. The results of this study suggest that increases of RBC aggregation tendency affect endothelial cell functions by altering local blood composition, especially if the alterations of RBC aggregation are due to modified cellular properties and not to plasma composition changes.
Erectile dysfunction in the type II diabetic db/db mouse: impaired venoocclusion with altered cavernosal vasoreactivity and matrix
Authors: Luttrell Ian P. , Swee Mei , Starcher Barry , Parks William C. , Chitaley Kanchan
Published: March 2008

The number of men with type II diabetes-associated erectile dysfunction (ED) continues to grow rapidly; however, the majority of basic science studies has examined mechanisms of ED in animal models of type I diabetes. In this study, we first establish an in vivo mouse model of type II diabetic ED using the leptin receptor mutated db/ db and wild-type control BKS mouse. Furthermore, we hypothesized that dual mechanistic impairments contribute to the impaired erectile function in the type II diabetic mouse, altered vasoreactivity, and venoocclusive disorder. In vivo erectile function was measured as intracavernosal pressure (ICP) normalized to mean arterial pressure (MAP) following electrical stimulation of the cavernosal nerve. Venoocclusion was assessed by the maintenance of elevated in vivo ICP following intracorporal saline infusion. Vasoreactivity of isolated cavernosum in response to contractile and dilatory stimulation was examined in vitro by myography. Collagen and elastin content were evaluated by quantification of hydroxyproline and desmosine, respectively, as well as by quantitative PCR and histological analysis of isolated cavernosum. Erectile function was significantly decreased in db/ db vs. BKS mice in a manner consistent with impairments in venoocclusive ability and decreased inflow. Heightened vasoconstriction and attenuated dilation in cavernosum of db/ db vs. BKS mice suggest an overall lowered relaxation ability and thus impaired filling of the cavernosal spaces. A decrease in desmosine and hydroxyproline as well as lowered mRNA levels for tropoelastin, fibrillin-1, and α1(I) collagen were detected. These vasoreactive and sinusoidal matrix alterations may alter tissue compliance dispensability, preventing the normal expansion necessary for erection.
Effects of ischemia and reperfusion on isolated ventricular myocytes from young adult and aged Fischer 344 rat hearts
Authors: O'Brien J. Darcy , Ferguson Jessica H. , Howlett Susan E.
Published: March 2008

This study examined the impact of age on contractile function, Ca2+homeostasis, and cell viability in isolated myocytes exposed to simulated ischemia and reperfusion. Ventricular myocytes were isolated from anesthetized young adult (3 mo) and aged (24 mo) male Fischer 344 rats. Cells were field-stimulated at 4 Hz (37°C), exposed to simulated ischemia, and reperfused with Tyrode solution. Cell shortening and intracellular Ca2+were measured simultaneously with an edge detector and fura-2. Cell viability was assessed by Trypan blue exclusion. Ischemia (20–45 min) depressed amplitudes of contraction equally in isolated myocytes from young adult and aged animals. The degree of postischemic contractile depression (stunning) was comparable in both groups. Ca2+transient amplitudes were depressed in early reperfusion in young adult and aged cells and then recovered to preischemic levels in both groups. Cell viability also declined equally in reperfusion in both groups. In short, some cellular responses to simulated ischemia and reperfusion were similar in both groups. Even so, aged myocytes exhibited a much greater and more prolonged accumulation of diastolic Ca2+in ischemia and in early reperfusion compared with myocytes from younger animals. In addition, the degree of mechanical alternans in ischemia increased significantly with age. The observation that there is an age-related increase in accumulation of diastolic Ca2+in ischemia and early reperfusion may account for the increased sensitivity to ischemia and reperfusion injury in the aging heart. The occurrence of mechanical alternans in ischemia may contribute to contractile dysfunction in ischemia in the aging heart.
Increased shear stress with upregulation of VEGF-A and its receptors and MMP-2, MMP-9, and TIMP-1 in venous stenosis of hemodialysis grafts
Authors: Misra Sanjay , Fu Alex A. , Puggioni Alessandra , Karimi Kamran M. , Mandrekar Jaywant N. , Glockner James F. , Juncos Luis A. , Anwer Bilal , McGuire Antonio M. , Mukhopadhyay Debabrata
Published: March 2008

Venous injury and subsequent venous stenosis formation are responsible for hemodialysis graft failure. Our hypothesis is that these pathological changes are in part related to changes in wall shear stress (WSS) that results in the activation of matrix regulatory proteins causing subsequent venous stenosis formation. In the present study, we examined the serial changes in WSS, blood flow, and luminal vessel area that occur subsequent to the placement of a hemodialysis graft in a porcine model of chronic renal insufficiency. We then determined the corresponding histological, morphometric, and kinetic changes of several matrix regulatory proteins including VEGF-A, its receptors, matrix metalloproteinase (MMP)-2, MMP-9, tissue inhibitor of matrix metalloproteinase (TIMP)-1, and TIMP-2. WSS was estimated by obtaining blood flow and luminal vessel area by performing phase-contrast MRI with magnetic resonance angiography in 21 animals at 1 day after graft placement and prior to death on day 3 ( n = 7), day 7 ( n = 7), and day 14 ( n = 7). At all time points, the mean WSS at the vein-to-graft anastomosis was significantly higher than that at the control vein ( P < 0.05). WSS had a bimodal distribution with peaks on days 1 and 7 followed by a significant reduction in WSS by day 14 ( P < 0.05 compared with day 7) and a decrease in luminal vessel area compared with control vessels. By day 3, there was a significant increase in VEGF-A and pro-MMP-9 followed by, on day 7, increased pro-MMP-2, active MMP-2, and VEGF receptor (VEGFR)-2 ( P < 0.05) and, by day 14, increased VEGFR-1 and TIMP-1 ( P < 0.05) at the vein-to-graft anastomosis compared with control vessels. Over time, the neointima thickened and was composed primarily of α-smooth muscle actin-positive cells with increased cellular proliferation. Our data suggest that hemodialysis graft placement leads to early increases in WSS, VEGF-A, and pro-MMP-9 followed by subsequent increases in pro-MMP-2, active MMP-2, VEGFR-1, VEGFR-2, and TIMP-1, which may contribute to the development of venous stenosis.
Deficient renal 20-HETE release in the diabetic rat is not the result of oxidative stress
Authors: Chen Yu-Jung , Li Jing , Quilley John
Published: March 2008

We confirmed that release of 20-hydroxyeicosatetraenoic acid (20-HETE) from the isolated perfused kidney of diabetic rats is greatly reduced compared with age-matched control rats. The present studies were undertaken to examine potential mechanisms for the deficit in renal 20-HETE in rats with streptozotocin-induced diabetes of 3–4 wk duration. A role for oxidative stress was excluded, inasmuch as treatment of diabetic rats with tempol, an SOD mimetic, for 4 wk did not affect the renal release of 20-HETE. Similarly, chronic inhibition of nitric oxide formation with nitro-l-arginine methyl ester or aldose reductase with zopolrestat failed to alter the release of 20-HETE from the diabetic rat kidney. Inasmuch as 20-HETE may be metabolized by cyclooxygenase (COX), the expression/activity of which is increased in diabetes, we included indomethacin in the perfusate of the isolated kidney to inhibit COX but found no effect on 20-HETE release. Diabetic rats were treated for 3 wk with fenofibrate to increase expression of cytochrome P-450 (CYP4A) in an attempt to find an intervention that would restore release of 20-HETE from the diabetic rat kidney. However, fenofibrate reduced 20-HETE release in diabetic and control rat kidneys but increased expression of CYP4A. Only insulin treatment of diabetic rats for 2 wk to reverse the hyperglycemia and maintain blood glucose levels at <200 mg/dl reversed the renal deficit in 20-HETE. We conclude that oxidative stress, increased aldose reductase activity, or increased COX activity does not contribute to the renal deficit of 20-HETE in diabetes, which may be directly related to insulin deficiency.
Local prostaglandin blockade attenuates muscle mechanoreflex-mediated renal vasoconstriction during muscle stretch in humans
Authors: Momen Afsana , Cui Jian , McQuillan Patrick , Sinoway Lawrence I.
Published: March 2008

During exercise, muscle mechanoreflex-mediated sympathoexcitation evokes renal vasoconstriction. Animal studies suggest that prostaglandins generated within the contracting muscle sensitize muscle mechanoreflexes. Thus we hypothesized that local prostaglandin blockade would attenuate renal vasoconstriction during ischemic muscle stretch. Eleven healthy subjects performed static handgrip before and after local prostaglandin blockade (6 mg ketorolac tromethamine infused into the exercising forearm) via Bier block. Renal blood flow velocity (RBV; Duplex Ultrasound), mean arterial pressure (MAP; Finapres), and heart rate (HR; ECG) were obtained during handgrip, post-handgrip muscle ischemia (PHGMI) followed by PHGMI with passive forearm muscle stretch (PHGMI + stretch). Renal vascular resistance (RVR, calculated as MAP/RBV) was increased from baseline during all paradigms except during PHGMI + stretch after the ketorolac Bier block trial where RVR did not change from baseline. Before Bier block, RVR rose more during PHGMI + stretch than during PHGMI alone ( P < .01). Similar results were found after a saline Bier block trial (Δ53 ± 13% vs. Δ35 ± 10%; P < 0.01). However, after ketorolac Bier block, RVR was not greater during PHGMI + stretch than during PHGMI alone [Δ39 ± 8% vs. Δ40 ± 12%; P = not significant (NS)]. HR and MAP responses were similar during PHGMI and PHGMI + stretch ( P = NS). Passive muscle stretch during ischemia augments renal vasoconstriction, suggesting that ischemia sensitizes mechanically sensitive afferents. Inhibition of prostaglandin synthesis eliminates this mechanoreceptor sensitization-mediated constrictor responses. Thus mechanoreceptor sensitization in humans is linked to the production of prostaglandins.
Sexual dimorphism in rabbit aortic endothelial function under acute hyperglycemic conditions and gender-specific responses to acute 17β-estradiol
Authors: Goel Aditya , Thor Der , Anderson Leigh , Rahimian Roshanak
Published: March 2008

Epidemiological data suggest that hyperglycemia abrogates the gender-based cardiovascular protection possibly associated with estrogens. This study was designed to investigate 1) whether rabbit aortic rings show gender differences in the development of abnormal endothelium-dependent vasodilation (EDV) under acute hyperglycemic conditions, 2) the potential role of PKC isoforms and superoxide (O2−) in acute hyperglycemia-induced vascular dysfunction, and 3) the effect of acute estrogen administration on hyperglycemia-induced endothelial dysfunction in male and female rabbits. EDV to ACh was determined before and after 3 h of treatment with high glucose (HG) in phenylephrine-precontracted aortic rings from male and female New Zealand White rabbits. Similar experiments were conducted in the presence of inhibitors of PKC-α, PKC-β, and PKC-δ or an O2−scavenger. The effect of acute estrogen administration was evaluated in the presence and absence of HG. Finally, mRNA expression of PKC isoforms was measured by real-time PCR. We found that 1) 3 h of incubation with HG impairs EDV to a greater extent in female than male aorta, 2) inhibition of PKC-β or O2−prevents HG-induced impairment of EDV in female aorta, 3) acute 17β-estradiol aggravates HG-induced endothelial dysfunction in female, but not male, aorta, and 4) PKC-α and PKC-β expression are significantly higher in female than male aorta. This study reveals the predisposition of female rabbit aorta to vascular injury under hyperglycemic conditions, possibly via activation of PKC-β and O2−production. Furthermore, it suggests that, under hyperglycemic conditions, acute estrogen treatment is detrimental to endothelial function in female rabbits.
Relationships between regional myocardial wall stress and bioenergetics in hearts with left ventricular hypertrophy
Authors: Feygin Julia , Hu Qinsong , Swingen Cory , Zhang Jianyi
Published: March 2008

This study utilized porcine models of postinfarction left ventricular (LV) remodeling [myocardial infarction (MI); n = 8] and concentric LV hypertrophy secondary to aortic banding (AoB; n = 8) to examine the relationships between regional myocardial contractile function (tagged MRI), wall stress (MRI and LV pressure), and bioenergetics (31P-magnetic resonance spectroscopy). Physiological assessments were conducted at a 4-wk time point after MI or AoB surgery. Comparisons were made with size-matched normal animals (normal; n = 8). Both MI and AoB instigated significant LV hypertrophy. Ejection fraction was not significantly altered in the AoB group, but significantly decreased in the MI group ( P < 0.01 vs. normal and AoB). Systolic and diastolic wall stresses were approximately two times greater than normal in the infarct region and border zone. Wall stress in the AoB group was not significantly different from that in normal hearts. The infarct border zone demonstrated profound bioenergetic abnormalities, especially in the subendocardium, where the ratio of PCr/ATP decreased from 1.98 ± 0.16 (normal) to 1.06 ± 0.30 (MI; P < 0.01). The systolic radial thickening fraction and the circumferential shortening fraction in the anterior wall were severely reduced (MI, P < 0.01 vs. normal). The radial thickening fraction and circumferential shortening fraction in the AoB group were not significantly different from normal. The severely elevated wall stress in the infarct border zone was associated with a significant increase in chemical energy demand and abnormal myocardial energy metabolism. Such severe metabolic perturbations cannot support normal cardiac function, which may explain the observed regional contractile abnormalities in the infarct border zone.
Role of gp91phox-containing NADPH oxidase in left ventricular remodeling induced by intermittent hypoxic stress
Authors: Hayashi Tetsuya , Yamashita Chika , Matsumoto Chika , Kwak Chol-Jun , Fujii Kiwako , Hirata Tomoko , Miyamura Masatoshi , Mori Tatsuhiko , Ukimura Akira , Okada Yoshikatsu , Matsumura Yasuo , Kitaura Yasushi
Published: March 2008

Intermittent hypoxia due to sleep apnea syndrome is associated with cardiovascular diseases. However, the precise mechanisms by which intermittent hypoxic stress accelerates cardiovascular diseases are largely unclear. The aim of this study was to investigate the role of gp91 phox-containing NADPH oxidase in the development of left ventricular (LV) remodeling induced by intermittent hypoxic stress in mice. Male gp91 phox-deficient (gp91−/−) mice ( n = 26) and wild-type ( n = 39) mice at 7–12 wk of age were exposed to intermittent hypoxia (30 s of 4.5–5.5% O2 followed by 30 s of 21% O2 for 8 h/day during daytime) or normoxia for 10 days. Mean blood pressure and LV systolic and diastolic function were not changed by intermittent hypoxia in wild-type or gp91−/− mice, although right ventricular systolic pressure tended to be increased. In wild-type mice, intermittent hypoxic stress significantly increased the diameter of cardiomyocytes and interstitial fibrosis in LV myocardium. Furthermore, intermittent hypoxic stress increased superoxide production, 4-hydroxy-2-nonenal protein, TNF-α and transforming growth factor-β mRNA, and NF-κB binding activity in wild-type, but not gp91−/−, mice. These results suggest that gp91 phox-containing NADPH oxidase plays a crucial role in the pathophysiology of intermittent hypoxia-induced LV remodeling through an increase of oxidative stress.
Effect of muscle metaboreflex activation on carotid-cardiac baroreflex function in humans
Authors: Fisher James P. , Young Colin N. , Fadel Paul J.
Published: March 2008

Whether the activation of metabolically sensitive skeletal muscle afferents (i.e., muscle metaboreflex) influences cardiac baroreflex responsiveness remains incompletely understood. A potential explanation for contrasting findings of previous reports may be related to differences in the magnitude of muscle metaboreflex activation utilized. Therefore, the present study was designed to investigate the influence of graded intensities of muscle metaboreflex activation on cardiac baroreflex function. In eight healthy subjects (24 ± 1 yr), the graded isolation of the muscle metaboreflex was achieved by post-exercise ischemia (PEI) following moderate- (PEI-M) and high- (PEI-H) intensity isometric handgrip performed at 35% and 45% maximum voluntary contraction, respectively. Beat-to-beat heart rate (HR) and blood pressure were measured continuously. Rapid pulse trains of neck pressure and neck suction (+40 to −80 Torr) were applied to derive carotid baroreflex stimulus-response curves. Mean blood pressure increased significantly from rest during PEI-M (+13 ± 3 mmHg) and was further augmented during PEI-H (+26 ± 4 mmHg), indicating graded metaboreflex activation. However, the operating point gain and maximal gain (−0.51 ± 0.09, −0.48 ± 0.13, and −0.49 ± 0.12 beats·min−1·mmHg−1 for rest; PEI-M and PEI-H) of the carotid-cardiac baroreflex function curve were unchanged from rest during PEI-M and PEI-H ( P > 0.05 vs. rest). Furthermore, the carotid-cardiac baroreflex function curve was progressively reset rightward from rest to PEI-M to PEI-H, with no upward resetting. These findings suggest that the muscle metaboreflex contributes to the resetting of the carotid baroreflex control of HR; however, it would appear not to influence carotid-cardiac baroreflex responsiveness in humans, even with high-intensity activation during PEI.
Pericardial delivery of omega-3 fatty acid: a novel approach to reducing myocardial infarct sizes and arrhythmias
Authors: Xiao Yong-Fu , Sigg Daniel C. , Ujhelyi Michael R. , Wilhelm Joshua J. , Richardson Eric S. , Iaizzo Paul A.
Published: March 2008

Basic and clinical evidence suggests that omega-3 (n-3) polyunsaturated fatty acids (PUFAs) decrease fatal arrhythmias and infarct sizes. This study investigated if pericardial delivery of n-3 PUFAs would protect the myocardium from ischemic damages and arrhythmias. Acute myocardial infarctions were induced in 23 pigs with either 45 min balloon inflations or clamp occlusions of the left anterior descending coronary arteries and 180 min reperfusion. Docosahexaenoic acid (C22:6n-3, DHA, 45 mg), one of the main n-3 PUFAs in fish oil, was infused within the pericardial space only during the 40-min stabilizing phase, 45 min ischemia and initial 5 min reperfusion. Hemodynamics and cardiac functions were very similar between the DHA-treated and control groups. However, DHA therapy significantly reduced infarct sizes from 56.8 ± 4.9% for controls ( n = 12) to 28.8 ± 7.9% ( P < 0.01) for DHA-treated animals ( n = 11). Compared with controls, DHA-treated animals significantly decreased heart rates and reduced ventricular arrhythmia scores during ischemia. Furthermore, three (25%) control animals experienced eight episodes of ventricular fibrillation (VF), and two died subsequent to unsuccessful defibrillation. In contrast, only 1 (9%) of 11 DHA-treated pigs elicited one episode of VF that was successfully converted via defibrillation to normal rhythm; thus, mortality was reduced from 17% in the controls to 0% in the DHA-treated animals. These data demonstrate that pericardial infusion of n-3 PUFA DHA can significantly reduce both malignant arrhythmias and infarct sizes in a porcine infarct model. Pericardial administration of n-3 PUFAs could represent a novel approach to treating or preventing myocardial infarctions.
The critical role of the intrinsic VSMC proliferation and death programs in injury-induced neointimal hyperplasia
Authors: Mnjoyan Zakar H. , Doan Dennis , Brandon Jimi Lynn , Felix Kumar , Sitter Christy L. , Rege Ajay A. , Brock Tommy A. , Fujise Ken
Published: March 2008

Postangioplasty and in-stent restenosis remain ominous problems in percutaneous coronary intervention where good animal models of restenosis proneness and resistance are needed. We accidentally discovered that the carotid arteries (CAs) of the Harlan and Sasco substrains of Sprague-Dawley rats display drastically different restenosis phenotypes following balloon-induced endothelial denudation. When subjected to balloon injury, Sasco CAs exhibited significantly larger neointimal mass than did Harlan CAs at both days 14 and 32, as evidenced by a higher intima-to-media ratio and a greater number of intimal cells in Sasco CAs. This was due to a greater cell proliferation and to a less vigorous apoptosis of Sasco neointima, as assessed by 5-bromo-2′-deoxyuridine and terminal deoxynucleotidyl transferase-deoxyuridine nick-end labeling staining, respectively. At a cellular level, whereas vascular smooth muscle cells (VSMCs) isolated from Sasco and Harlan CAs were identical in morphology and in propensity to migrate, Sasco VSMCs proliferated more robustly and died far less, suggesting that under the exact same microenvironment, Sasco and Harlan VSMCs respond to growth and noxious stimuli in a drastically different fashion and that Sasco's significantly more robust neointimal proliferation after vascular injury in vivo can be accounted for by these intrinsic differences in VSMCs of these substrains in vitro. Sasco and Harlan Sprague-Dawley rats as well as VSMCs from these rats will prove to be powerful tools to study genes involved in the pathogenesis of restenosis.
Alveolar macrophage activation and an emphysema-like phenotype in adiponectin-deficient mice
Authors: Summer R. , Little F. F. , Ouchi N. , Takemura Y. , Aprahamian T. , Dwyer D. , Fitzsimmons K. , Suki B. , Parameswaran H. , Fine A. , Walsh K.
Published: March 2008

Adiponectin is an adipocyte-derived collectin that acts on a wide range of tissues including liver, brain, heart, and vascular endothelium. To date, little is known about the actions of adiponectin in the lung. Herein, we demonstrate that adiponectin is present in lung lining fluid and that adiponectin deficiency leads to increases in proinflammatory mediators and an emphysema-like phenotype in the mouse lung. Alveolar macrophages from adiponectin-deficient mice spontaneously display increased production of tumor necrosis factor-α (TNF-α) and matrix metalloproteinase (MMP-12) activity. Consistent with these observations, we found that pretreatment of alveolar macrophages with adiponectin leads to TNF-α and MMP-12 suppression. Together, our findings show that adiponectin leads to macrophage suppression in the lung and suggest that adiponectin-deficient states may contribute to the pathogenesis of inflammatory lung conditions such as emphysema.
Reduced spontaneous relaxation in immature guinea pig airway smooth muscle is associated with increased prostanoid release
Authors: Wang Lu , Pozzato Valeria , Turato Graziella , Madamanchi Aasakiran , Murphy Thomas M. , Chitano Pasquale
Published: March 2008

Airway smooth muscle (ASM) from infant guinea pigs has less spontaneous relaxation during stimulation than ASM from adults. Inhibition of cyclooxygenase (COX), which catalyzes the production of prostanoids, increases this relaxation in infant ASM and abolishes age differences, thus suggesting that prostanoids reduce relaxation in infant ASM. In this study, we investigated whether leukotrienes are also involved in reducing spontaneous relaxation; whether the two COX isoforms, COX-1 and COX-2, differentially regulate spontaneous relaxation; and whether prostanoid release is developmentally regulated in guinea pig ASM. In different age groups, we measured relaxation during and after electrical stimulation in tracheal strips as well as prostanoid release from tracheal segments. Relaxation was studied in the absence and in the presence of a lipoxygenase inhibitor, a cysteinyl leukotriene receptor-1 antagonist, a COX-1 inhibitor, or a COX-2 inhibitor. We found that inhibition of lipoxygenase or cysteinyl leukotriene receptor-1 antagonism did not increase spontaneous relaxation at any age, thus excluding a role for leukotrienes in this phenomenon. Inhibition of COX-2, but not COX-1, promoted spontaneous relaxation. The basal release of prostanoids was more abundant in tissue from infant animals and decreased significantly with age. Thromboxane B2 was the most abundant metabolite released at all ages. Electrical stimulation and epithelium removal did not affect the age difference in prostanoid release. We conclude that increased basal prostanoid release contributes to the reduced spontaneous relaxation in immature guinea pig ASM compared with older animals. By regulating ASM relaxation, prostanoids may play a role in the airway hyperresponsiveness at a young age.
Contributions of nitric oxide synthase isoforms to pulmonary oxygen toxicity, local vs. mediated effects
Authors: Demchenko Ivan T. , Atochin Dmitriy N. , Gutsaeva Diana R. , Godfrey Ryan R. , Huang Paul L. , Piantadosi Claude A. , Allen Barry W.
Published: March 2008

Reactive species of oxygen and nitrogen have been collectively implicated in pulmonary oxygen toxicity, but the contributions of specific molecules are unknown. Therefore, we assessed the roles of several reactive species, particularly nitric oxide, in pulmonary injury by exposing wild-type mice and seven groups of genetically altered mice to >98% O2at 1, 3, or 4 atmospheres absolute. Genetically altered animals included knockouts lacking either neuronal nitric oxide synthase (nNOS−/−), endothelial nitric oxide synthase (eNOS−/−), inducible nitric oxide synthase (iNOS−/−), extracellular superoxide dismutase (SOD3−/−), or glutathione peroxidase 1 (GPx1−/−), as well as two transgenic variants (S1179A and S1179D) having altered eNOS activities. We confirmed our earlier finding that normobaric hyperoxia (NBO2) and hyperbaric hyperoxia (HBO2) result in at least two distinct but overlapping patterns of pulmonary injury. Our new findings are that the role of nitric oxide in the pulmonary pathophysiology of hyperoxia depends both on the specific NOS isozyme that is its source and on the level of hyperoxia. Thus, iNOS predominates in the etiology of lung injury in NBO2, and SOD3 provides an important defense. But in HBO2, nNOS is a major contributor to pulmonary injury, whereas eNOS is protective. In addition, we demonstrated that nitric oxide derived from nNOS is involved in a neurogenic mechanism of HBO2-induced lung injury that is linked to central nervous system oxygen toxicity through adrenergic/cholinergic pathways.
Substance P acts via the neurokinin receptor 1 to elicit bronchoconstriction, oxidative stress, and upregulated ICAM-1 expression after oil smoke exposure
Authors: Li Ping-Chia , Chen Wen-Chung , Chang Li-Ching , Lin Shao-Chieh
Published: March 2008

This study aimed to 1) assess whether substance P (SP) acts via neurokinin (NK)-1 and NK-2 receptors to stimulate neurogenic inflammation (indicated by formation of ICAM-1 expression and oxidative stress) following oil smoke exposure (OSE) in rats; and 2) determine if pretreatment with antioxidants ameliorates the deleterious effects of OSE. Rats were pretreated with NK-1 receptor antagonist CP-96345, NK-2 receptor antagonist SR-48968, vitamin C, or catechins. OSE was for 30–120 min. Rats were killed 0–8 h later. Total lung resistance ( RL), airway smooth muscle activity (ASMA), lung ICAM-1 expression, neurogenic plasma extravasation (via India ink and Evans blue dye), bronchoalveolar lavage fluid SP concentrations, and reactive oxygen species formation [via lucigenin- and luminal-amplified chemiluminescence (CL)] were assessed. Lung histology was performed. SP concentrations increased significantly in nonpretreated rats following OSE in a dose-dependent manner. RLand total ASMA increased over time after OSE. Vitamin C and catechin pretreatments were associated with significantly reduced lucigenin CL 2 and 4 h after OSE. Pretreatment with catechins significantly reduced luminal CL counts 4 and 8 h after OSE. Evans blue levels were significantly reduced following 60 and 120 min of OSE in catechin- and CP-96345-pretreated rats. ICAM-1 protein expression was significantly decreased in all pretreatment groups after OSE. Thickening of the alveolar capillary membrane, focal hemorrhaging, interstitial pneumonitis, and peribronchiolar inflammation were apparent in OSE lungs. These findings suggest that SP acts via the NK-1 receptor to provoke neurogenic inflammation, oxidative stress, and ICAM-1 expression after OSE in rats.
Effects of gastric distension on the cardiovascular system in rainbow trout (Oncorhynchus mykiss)
Authors: Seth Henrik , Sandblom Erik , Holmgren Susanne , Axelsson Michael
Published: March 2008

When animals feed, blood flow to the gastrointestinal tract increases to ensure an adequate oxygen supply to the gastrointestinal tissue and an effective absorption of nutrients. In mammals, this increase depends on the chemical properties of the food, as well as, to some extent, on the mechanical distension of the stomach wall. By using an inflatable nitrile balloon positioned in the stomach, we investigated the cardiovascular responses to mechanical stretch of the stomach wall in rainbow trout ( Oncorhynchus mykiss). Distension with a volume equivalent to a meal of 2% of the body mass increased dorsal aortic blood pressure by up to 29%, and central venous blood pressure increased transiently nearly fivefold. The increase in arterial pressure was mediated by an increased vascular resistance of both the systemic and the intestinal circulation. Cardiac output, heart rate, and stroke volume (SV) did not change, and only transient changes in gut blood flow were observed. The increase in arterial pressure was abolished by the α-adrenergic antagonist prazosin, indicating an active adrenergic vasoconstriction, whereas the venous pressor response could be the consequence of a passive increase in intraperitoneal pressure. Our results show that mechanical distension of the stomach causes an instantaneous increase in general vascular resistance, which may facilitate a redistribution of blood to the gastrointestinal tract when chemical stimuli from a meal induce vasodilation in the gut circulation. The normal postprandial increase in gut blood flow in teleosts is, therefore, most likely partly dependent on mechanical stimuli, as well as on chemical stimuli.
Generation of Length Distribution, Length Diagram, Fibrogram, and Statistical Characteristics by Weight of Cotton Blends
Authors: Azzouz B. , Hassen M. Ben , Sakli F.
Published: March 2008

The textile fibre mixture as a multicomponent blend of variable fibres imposes regarding the proper method to predict the characteristics of the final blend. The length diagram and the fibrogram of cotton are generated. Then the length distribution, the length diagram, and the fibrogram of a blend of different categories of cotton are determined. The length distributions by weight of five different categories of cotton (Egyptian, USA (Pima), Brazilian, USA (Upland), and Uzbekistani) are measured by AFIS. From these distributions, the length distribution, the length diagram, and the fibrogram by weight of four binary blends are expressed. The length parameters of these cotton blends are calculated and their variations are plotted against the mass fractionxof one component in the blend .These calculated parameters are compared to those of real blends. Finally, the selection of the optimal blends using the linear programming method, based on the hypothesis that the cotton blend parameters vary linearly in function of the components rations, is proved insufficient.
Stability Guaranteed Active Fault‐Tolerant Control of Networked Control Systems
Authors: Li Shanbin , Sauter Dominique , Aubrun Christophe , Yamé Joseph
Published: March 2008

The stability guaranteed active fault‐tolerant control against actuators failures and plant uncertainties in networked control systems (NCSs) is addressed. A detailed design procedure is formulated as a convex optimization
problem which can be efficiently solved by existing software. An illustrative example
is given to show the efficiency of the proposed method for network‐based
control for uncertain systems.
Structural, Elastic, and Electronic Properties of ReB2: A First‐Principles Calculation
Authors: Long Run , Dai Ying , Jin Hao , Huang Baibiao
Published: March 2008

The structural, elastic, and electronic properties of the hard material ReB2 have been investigated by means of density functional theory. The calculated equilibrium structural parameters of ReB2
are in agreement with the experimental results. Our result of bulk modulus shows that it is a low compressible material. Furthermore, the elastic anisotropy is discussed by investigating the elastic stiffness constants. The charge density and the electronic properties indicate that the covalent bonding of Re‐B and B‐B plays an important role in formation of a hard material. The good metallicity and hardness of
ReB2 might serve as hard conductors.
Cationic Porphyrin Induced a Telomeric DNA to G‐Quadruplex Form in Water
Authors: Murashima Takashi , Sakiyama Daichi , Miyoshi Daisuke , Kuriyama Masanori , Yamada Takashi , Miyazawa Toshifumi , Sugimoto Naoki
Published: March 2008

The formation of the DNA G‐quadruplex is induced by the addition of a novel porphyrin carrying four cationic tethers. Circular dichroism spectroscopy reveals that the porphyrin binds to Tetrahymena telomeric repeat to form G‐quadruplex under stabilizing‐cation‐deficient and no buffer conditions.
On the Continuity Properties of the Attainable Sets of Nonlinear Control Systems with Integral Constraint on Controls
Authors: Guseinov Khalik G. , Nazlipinar Ali S.
Published: March 2008

The attainable sets of the nonlinear control systems with integral constraint on the
control functions are considered. It is assumed that the behavior of control system is described by
differential equation which is nonlinear with respect to phase‐state vector and control vector. The
admissible control functions are chosen from the closed ball centered at the origin with radius μ0 in Lp([t0, θ]; ℝm) (p ∈ (1, +∞)). Precompactness of the solutions set is specified, and dependence of the attainable sets on the initial conditions and on the parameters of the control system is studied.