bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in DivL and CckA Rescue a
divJ
Null Mutant of
Caulobacter crescentus
by Reducing the Activity of CtrA
Authors: Pierce Deanne L. , O'Donnol Danielle S. , Allen Rebecca C. , Javens June W. , Quardokus Ellen M. , Brun Yves V.
Published: March 2006

Polar development and cell division in
Caulobacter crescentus
are controlled and coordinated by multiple signal transduction proteins.
divJ
encodes a histidine kinase. A null mutation in
divJ
results in a reduced growth rate, cell filamentation, and mislocalized stalks. Suppressor analysis of
divJ
identified mutations in genes encoding the tyrosine kinase (
divL
) and the histidine kinase (
cckA
). The
divL
and
cckA
suppressor alleles all have single amino acid substitutions, some of which confer a temperature-sensitive phenotype, particularly in a wild-type background. Analysis of transcription levels from several positively regulated CtrA-dependent promoters reveals high expression in the
divJ
mutant, suggesting that DivJ normally serves to reduce CtrA activity. The
divL
and
cckA
suppressors reduce the amount of transcription from promoters positively regulated by CtrA, indicating that the mutations in
divL
and
cckA
are suppressing the defects of the
divJ
mutant by reducing the abnormally high level of CtrA activity. Immunoblotting showed no major perturbations in the CtrA protein level in any of these strains, suggesting that the high amount of CtrA activity seen in the
divJ
mutant and the reduced amount of activity in the suppressors are regulated at the level of activation and not transcription, translation, or degradation. In vivo phosphorylation assays confirmed that
divJ
mutants have elevated levels of CtrA phosphorylation and that this level is reduced in the suppressors with mutations in
divL
.
Coenzyme B12 Controls Transcription of the
Streptomyces
Class Ia Ribonucleotide Reductase
nrdABS
Operon via a Riboswitch Mechanism
Authors: Borovok Ilya , Gorovitz Batia , Schreiber Rachel , Aharonowitz Yair , Cohen Gerald
Published: March 2006

Ribonucleotide reductases (RNRs) catalyze the conversion of ribonucleotides to deoxyribonucleotides and are essential for de novo DNA synthesis and repair. Streptomycetes contain genes coding for two RNRs. The class Ia RNR is oxygen dependent, and the class II RNR is oxygen independent and requires coenzyme B12. Either RNR is sufficient for vegetative growth. We show here that the
Streptomyces coelicolor
M145
nrdABS
genes encoding the class Ia RNR are regulated by coenzyme B12. The 5′-untranslated region of
nrdABS
contains a 123-nucleotide B12 riboswitch. Similar B12 riboswitches are present in the corresponding regions of eight other
S. coelicolor
genes. The effect of B12 on growth and
nrdABS
transcription was examined in a mutant in which the
nrdJ
gene, encoding the class II RNR, was deleted. B12 concentrations of just 1 μg/liter completely inhibited growth of the NrdJ mutant strain. Likewise, B12 significantly reduced
nrdABS
transcription. To further explore the mechanism of B12 repression, we isolated in the
nrdJ
deletion strain mutants that are insensitive to B12 inhibition of growth. Two classes of mutations were found to map to the B12 riboswitch. Both conferred resistance to B12 inhibition of
nrdABS
transcription and are likely to affect B12 binding. These results establish that B12 regulates overall RNR expression in reciprocal ways, by riboswitch regulation of the class Ia RNR
nrdABS
genes and by serving as a cofactor for the class II RNR.
Analysis of
Escherichia coli
Global Gene Expression Profiles in Response to Overexpression and Deletion of CspC and CspE
Authors: Phadtare Sangita , Tadigotla Vasisht , Shin Weon-Hye , Sengupta Anirvan , Severinov Konstantin
Published: March 2006

The
Escherichia coli
cold shock protein CspA family consists of nine proteins (CspA to CspI), of which two, CspE and CspC, are constitutively produced at 37°C and are involved in regulation of expression of genes encoding stress response proteins but can also perform an essential function during cold acclimation. In this study, we analyzed global transcript profiles of cells lacking
cspE
and
cspC
as well as cells individually overexpressing these proteins or a CspE mutant that is unable to melt nucleic acids and is defective in cold acclimation. The analysis reveals sets of genes whose expression (i) is regulated by CspC and CspE at physiological temperature or cold shock conditions and (ii) depends on the nucleic acid melting function of CspE. Bioinformatic analysis of the latter group reveals that many of those genes contain promoter-proximal sequences that can block transcript elongation and may be targeted by the nucleic acid melting function of CspE.
Identification of RamA, a Novel LuxR-Type Transcriptional Regulator of Genes Involved in Acetate Metabolism of
Corynebacterium glutamicum
Authors: Cramer Annette , Gerstmeir Robert , Schaffer Steffen , Bott Michael , Eikmanns Bernhard J.
Published: March 2006

In
Corynebacterium glutamicum
, the acetate-activating enzymes phosphotransacetylase and acetate kinase and the glyoxylate cycle enzymes isocitrate lyase and malate synthase are coordinately up-regulated in the presence of acetate in the growth medium. This regulation is due to transcriptional control of the respective
pta-ack
operon and the
aceA
and
aceB
genes, brought about at least partly by the action of the negative transcriptional regulator RamB. Using cell extracts of
C. glutamicum
and employing DNA affinity chromatography, mass spectrometry, and peptide mass fingerprinting, we identified a LuxR-type transcriptional regulator, designated RamA, which binds to the
pta-ack
and
aceA/aceB
promoter regions. Inactivation of the
ramA
gene in the genome of
C. glutamicum
resulted in mutant RG2. This mutant was unable to grow on acetate as the sole carbon and energy source and, in comparison to the wild type of
C. glutamicum
, showed very low specific activities of phosphotransacetylase, acetate kinase, isocitrate lyase, and malate synthase, irrespective of the presence of acetate in the medium. Comparative transcriptional
cat
fusion experiments revealed that this deregulation takes place at the level of transcription. By electrophoretic mobility shift analysis, purified His-tagged RamA protein was shown to bind specifically to the
pta-ack
and the
aceA/aceB
promoter regions, and deletion and mutation studies revealed in both regions two binding motifs each consisting of tandem A/C/TG
4-6
T/C or AC
4-5
A/G/T stretches separated by four or five arbitrary nucleotides. Our data indicate that RamA represents a novel LuxR-type transcriptional activator of genes involved in acetate metabolism of
C. glutamicum
.
Product Repression of Alkane Monooxygenase Expression in
Pseudomonas butanovora
Authors: Doughty D. M. , Sayavedra-Soto L. A. , Arp D. J. , Bottomley P. J.
Published: March 2006

Physiological and regulatory mechanisms that allow the alkane-oxidizing bacterium
Pseudomonas butanovora
to consume C
2
to C
8
alkane substrates via butane monooxygenase (BMO) were examined. Striking differences were observed in response to even- versus odd-chain-length alkanes. Propionate, the downstream product of propane oxidation and of the oxidation of other odd-chain-length alkanes following β-oxidation, was a potent repressor of BMO expression. The transcriptional activity of the BMO promoter was reduced with as little as 10 μM propionate, even in the presence of appropriate inducers. Propionate accumulated stoichiometrically when 1-propanol and propionaldehyde were added to butane- and ethane-grown cells, indicating that propionate catabolism was inactive during growth on even-chain-length alkanes. In contrast, propionate consumption was induced (about 80 nmol propionate consumed · min
−1
· mg protein
−1
) following growth on the odd-chain-length alkanes, propane and pentane. The induction of propionate consumption could be brought on by the addition of propionate or pentanoate to the growth medium. In a reporter strain of
P. butanovora
in which the BMO promoter controls β-galactosidase expression, only even-chain-length alcohols (C
2
to C
8
) induced β-galactosidase following growth on acetate or butyrate. In contrast, both even- and odd-chain-length alcohols (C
3
to C
7
) were able to induce β-galactosidase following the induction of propionate consumption by propionate or pentanoate.
Molecular and Physiological Effects of Mycobacterial
oxyR
Inactivation
Authors: Pagán-Ramos Eileen , Master Sharon S. , Pritchett Christopher L. , Reimschuessel Renate , Trucksis Michele , Timmins Graham S. , Deretic Vojo
Published: March 2006

The majority of slow-growing mycobacteria have a functional
oxyR
, the central regulator of the bacterial oxidative stress response. In contrast, this gene has been inactivated during the evolution of
Mycobacterium tuberculosis
. Here we inactivated the
oxyR
gene in
Mycobacterium marinum
, an organism used to model
M. tuberculosis
pathogenesis. Inactivation of
oxyR
abrogated induction of
ahpC
, a gene encoding alkylhydroperoxide reductase, normally activated upon peroxide challenge. The absence of
oxyR
also resulted in increased sensitivity to the front-line antituberculosis drug isoniazid. Inactivation of
oxyR
in
M. marinum
did not affect either virulence in a fish infection model or survival in human macrophages. Our findings demonstrate, at the genetic and molecular levels, a direct role for OxyR in
ahpC
regulation in response to oxidative stress. Our study also indicates that
oxyR
is not critical for virulence in
M. marinum
. However,
oxyR
inactivation confers increased sensitivity to isonicotinic acid hydrazide, suggesting that the natural loss of
oxyR
in the tubercle bacillus contributes to the unusually high sensitivity of
M. tuberculosis
to isoniazid.
CRITICAL BEHAVIOUR IN STATISTICAL QCD
Authors: SATZ HELMUT
Published: March 2006

We survey the critical behaviour of strongly interacting matter, as determined in finite temperature lattice QCD.
A Review of Pentaquark Calculations on the Lattice
Authors: Liu Keh-Fei , Mathur Nilmani
Published: March 2006

We review lattice calculations of pentaquarks and discuss issues pertaining to interpolation fields, distinguishing the signal of pentaquarks from those of the KN scattering states, chiral symmetry, and ghost state contaminations.
Vector Manifestation and the Hidden Local Symmetry
Authors: Harada Masayasu
Published: March 2006

In this write-up, I summarize the key ingredients of the vector manifestaion formulated in the hidden local symmetry theory, in which the ρ meson becomes massless degenerated with the pion at the chiral phase transition point.
BERRY PHASE CORRECTION TO ELECTRON DENSITY IN SOLIDS AND "EXOTIC" DYNAMICS
Authors: DUVAL C. , HORVÁTH Z. , HORVÁTHY P. A. , MARTINA L. , STICHEL P. C.
Published: March 2006

Recent results on the semiclassical dynamics of an electron in a solid are explained using techniques developed for "exotic" Galilean dynamics. The system is indeed Hamiltonian and Liouville's theorem holds for the symplectic volume form. Suitably defined quantities satisfy hydrodynamic equations.
COUPLING EULER AND VLASOV EQUATIONS IN THE CONTEXT OF SPRAYS: THE LOCAL-IN-TIME, CLASSICAL SOLUTIONS
Authors: BARANGER CÉLINE , DESVILLETTES LAURENT
Published: March 2006

Sprays are complex flows made of liquid droplets surrounded by a gas. They can be modeled by introducing a system coupling a kinetic equation (for the droplets) of Vlasov type and a (Euler-like) fluid equation for the gas. In this paper, we prove that, for the so-called thin sprays, this coupled model is well-posed, in the sense that existence and uniqueness of classical solutions holds for small time, provided the initial data are sufficiently smooth and their support have suitable properties.
FINITE DIFFERENCE SCHEMES WITH CROSS DERIVATIVES CORRECTORS FOR MULTIDIMENSIONAL PARABOLIC SYSTEMS
Authors: BOUCHUT FRANÇOIS , FRID HERMANO
Published: March 2006

We propose finite difference schemes for multidimensional quasilinear parabolic systems whose main feature is the introduction of correctors which control the second-order terms with mixed derivatives. We show that with these correctors the schemes inherit physically relevant properties present at the continuous level, such as the existence of invariant domains and/or the nonincrease of the total amount of entropy. The analysis is performed with some general tools that could be used also in the analysis of finite volume methods based on flux vector splitting for first-order hyperbolic problems on unstructured meshes. Applications to the compressible Navier–Stokes system are given.
COUPLING OF MULTIDIMENSIONAL PARABOLIC AND HYPERBOLIC EQUATIONS
Authors: AGUILAR GLORIA , LÉVI LAURENT , MADAUNE-TORT MONIQUE
Published: March 2006

This paper deals with the mathematical analysis of a quasilinear parabolic-hyperbolic problem in a multidimensional bounded domain Ω. In a region Ωp a diffusion-advection-reaction type equation is set, while in the complementary Ωh ≡ Ω\Ωp, only advection-reaction terms are taken into account. To begin we provide a definition of a weak solution through an entropy inequality on the whole domain. Since the interface ∂Ωp ∩ ∂Ωh contains outward characteristics for the first-order operator in Ωh, the uniqueness proof starts by considering first the hyperbolic zone and then the parabolic one. The existence property uses the vanishing viscosity method and to pass to the limit on the hyperbolic zone, we refer to the notion of process solution.
PRIMITIVE ROOTS IN QUADRATIC FIELDS
Authors: COHEN JOSEPH
Published: March 2006

We consider an analogue of Artin's primitive root conjecture for units in real quadratic fields. Given such a nontrivial unit, for a rational prime p which is inert in the field the maximal order of the unit modulo p is p + 1. An extension of Artin's conjecture is that there are infinitely many such inert primes for which this order is maximal. This is known at present only under the Generalized Riemann Hypothesis. Unconditionally, we show that for any choice of 7 units in different real quadratic fields satisfying a certain simple restriction, there is at least one of the units which satisfies the above version of Artin's conjecture.
Neuronal basis of Hammel's model for set-point thermoregulation
Authors: Boulant Jack A.
Published: March 2006

In 1965, H. T. Hammel proposed a neuronal model to explain set-point thermoregulation. His model was based on a synaptic network encompassing four different types of hypothalamic neurons: i.e., warm-sensitive and temperature-insensitive neurons and heat loss and heat production effector neurons. Although some modifications to this model are suggested, recent electrophysiological and morphological studies support many of the model's major tenets. Hypothalamic warm-sensitive neurons integrate core and peripheral thermal information. These neurons sense changes in hypothalamic temperature, and they orient their dendrites medially and laterally to receive ascending afferent input from cutaneous thermoreceptors. Temperature-insensitive neurons have a different dendritic orientation and may provide constant reference signals, which are important in determining thermoregulatory set points. In Hammel's model, temperature-sensitive and -insensitive neurons send mutually antagonistic synaptic inputs to effector neurons controlling various thermoregulatory responses. The model predicts that warm-sensitive neurons synaptically excite heat loss effector neurons and inhibit heat production effector neurons. In recent studies, one counterpart of these effector neurons may be “excitatory postsynaptic potential-driven neurons,” the activity of which is dependent on synaptic excitation from nearby cells. Excitatory postsynaptic potential-driven neurons have sparse dendrites that appear to be specifically oriented, either medially or laterally, presumably to receive selective synaptic input from a discrete source. Another counterpart of effector neurons may be “silent neurons,” which have extensive dendritic branches that may receive synaptic excitation from remote sources. Because some silent neurons receive synaptic inhibition from nearby warm-sensitive neurons, Hammel's model would predict that they have a role in heat production or heat retention responses.
Light source-detector spacing of near-infrared-based tissue oximeters and the influence of skin blood flow
Authors: Ferrari Marco , Cettolo Valentina , Quaresima Valentina
Published: March 2006

Near-infrared (NIR) spectroscopy is a noninvasive optical technique that is increasingly used to assess muscle oxygenation during exercise with the assumption that the contribution of skin blood flow to the NIR signal is minor or nonexistent. We tested this assumption in humans by monitoring forearm tissue oxygenation during selective cutaneous vasodilation induced by locally applied heat ( n = 6) or indirect whole body heating (i.e., heating subject but not area surrounding NIR probes; n = 8). Neither perturbation has been shown to cause a measurable change in muscle blood flow or metabolism. Local heating (∼41°C) caused large increases in the NIR-derived tissue oxygenation signal [before heating = 0.82 ± 0.89 optical density (OD), after heating = 18.21 ± 2.44 OD; P < 0.001]. Similarly, whole body heating (increase internal temperature 0.9°C) also caused large increases in the tissue oxygenation signal (before heating = −0.31 ± 1.47 OD, after heating = 12.48 ± 1.82 OD; P < 0.001). These increases in the tissue oxygenation signal were closely correlated with increases in skin blood flow during both local heating (mean r = 0.95 ± 0.02) and whole body heating (mean r = 0.89 ± 0.04). These data suggest that the contribution of skin blood flow to NIR measurements of tissue oxygenation can be significant, potentially confounding interpretation of the NIR-derived signal during conditions where both skin and muscle blood flows are elevated concomitantly (e.g., high-intensity and/or prolonged exercise).
Mitochondrial respiration in creatine-loaded muscle: is there 31P-MRS evidence of direct effects of phosphocreatine and creatine in vivo?
Authors: Kemp Graham
Published: March 2006

Recent human isolated muscle fiber studies suggest that phosphocreatine (PCr) and creatine (Cr) concentrations play a role in the regulation of mitochondrial respiration rate. To determine whether similar regulatory mechanisms are present in vivo, this study examined the relationship between skeletal muscle mitochondrial respiration rate and end-exercise PCr, Cr, PCr-to-Cr ratio (PCr/Cr), ADP, and pH by using 31P-magnetic resonance spectroscopy in 16 men and women (36.9 ± 4.6 yr). The initial PCr resynthesis rate and time constant (Tc) were used as indicators of mitochondrial respiration after brief (10–12 s) and exhaustive (1–4 min) dynamic knee extension exercise performed in placebo and creatine-supplemented conditions. The results show that the initial PCr resynthesis rate has a strong relationship with end-exercise PCr, Cr, and PCr/Cr ( r > 0.80, P < 0.001), a moderate relationship with end-exercise ADP ( r = 0.77, P < 0.001), and no relationship with end-exercise pH ( r = −0.14, P = 0.34). The PCr Tc was not as strongly related to PCr, Cr, PCr/Cr, and ADP ( r < 0.77, P < 0.001–0.18) and was significantly influenced by end-exercise pH ( r = −0.43, P < 0.01). These findings suggest that end-exercise PCr and Cr should be taken into consideration when PCr recovery kinetics is used as an indicator of mitochondrial respiration and that the initial PCr resynthesis rate is a more reliable indicator of mitochondrial respiration compared with the PCr Tc.
What can be concluded regarding water versus sports drinks from the Vrijens-Reher experiments?
Authors: Weschler Louise B.
Published: March 2006

This study assessed whether replacing sweat losses with sodium-free fluid can lower the plasma sodium concentration and thereby precipitate the development of hyponatremia. Ten male endurance athletes participated in one 1-h exercise pretrial to estimate fluid needs and two 3-h experimental trials on a cycle ergometer at 55% of maximum O2 consumption at 34°C and 65% relative humidity. In the experimental trials, fluid loss was replaced by distilled water (W) or a sodium-containing (18 mmol/l) sports drink, Gatorade (G). Six subjects did not complete 3 h in trial W, and four did not complete 3 h in trial G. The rate of change in plasma sodium concentration in all subjects, regardless of exercise time completed, was greater with W than with G (−2.48 ± 2.25 vs. −0.86 ± 1.61 mmol·l−1·h−1, P = 0.0198). One subject developed hyponatremia (plasma sodium 128 mmol/l) at exhaustion (2.5 h) in the W trial. A decrease in sodium concentration was correlated with decreased exercise time ( R = 0.674; P = 0.022). A lower rate of urine production correlated with a greater rate of sodium decrease ( R = −0.478; P = 0.0447). Sweat production was not significantly correlated with plasma sodium reduction. The results show that decreased plasma sodium concentration can result from replacement of sweat losses with plain W, when sweat losses are large, and can precipitate the development of hyponatremia, particularly in individuals who have a decreased urine production during exercise. Exercise performance is also reduced with a decrease in plasma sodium concentration. We, therefore, recommend consumption of a sodium-containing beverage to compensate for large sweat losses incurred during exercise.
Pharmacogenetics and Regulation of Human CytochromeP450 1B1: Implications in Hormone-Mediated Tumor Metabolism and a Novel Target for Therapeutic Intervention
Authors: Sissung Tristan M. , Price Douglas K. , Sparreboom Alex , Figg William D.
Published: March 2006

Several of the hormone-mediated cancers (breast, endometrial, ovarian, and prostate) represent major cancers in both incidence and mortality rates. The etiology of these cancers is in large part modulated by the hormones estrogen and testosterone. As advanced disease develops, the common treatment for these cancers is chemotherapy. Thus, genes that can alter tissue response to hormones and alter clinical response to chemotherapy are of major interest. The cytochrome P450 1B1 (CYP1B1) may be involved in disease progression and modulate the treatment in the above hormone-mediated cancers. This review will focus on the pharmacogenetics of CYP1B1 in relation to hormone-mediated cancers and provide an assessment of cancer risk based on CYP1B1 polymorphisms and expression. In addition, it will provide a summary of CYP1B1 gene regulation and expression in normal and neoplastic tissue. (Mol Cancer Res 2006;4(3):1–16)
Central Venous Line-Related Thrombosis in Children
Authors: Revel-Vilk Shoshana
Published: March 2006

Central venous lines are used in critically ill children and in children with chronic conditions for the administration of intravenous therapy, such as fluids, medications, total parenteral nutrition and blood products. Although the use of central venous lines has greatly improved the quality of care in these children, these catheters may cause serious mechanical, infectious and thrombotic complications. The reported frequency of catheter thrombosis in children is low as 5% in studies including only symptomatic cases and high as 50% in studies where patients are systematically screened for catheter-related thrombosis. The risk factors for catheter-related thrombosis in children are associated with the methods used for catheter insertion and with individual patient characteristics, underlying diagnosis and treatment. The management of catheter-related thrombosis is largely dependent on the requirement of the catheter. If no longer required or nonfunctioning the catheter should be removed. If access is still required and the catheter is functioning, treatment with anticoagulation is recommended in the absence of contraindications. The management of radiographically detected asymptomatic thrombosis in children is less clear. Clinical studies of prophylaxis for catheter-related thrombosis are inconclusive and no definitive recommendations for prophylaxis in adults or in children with central venous thrombosis can be made. Properly designed studies are needed to assess the role of prophylactic anticoagulation for preventing catheter-related thrombosis.
Effects of Dopexamine in a Rat Model of Supracoeliac Aortic Cross-Clamping and Declamping
Authors: Studer W. , Wu X. , Siegemund M. , Seeberger M. , Filipovic M.
Published: March 2006

This experimental study in rats was designed to demonstrate effects of dopexamine (3 µg kg–1 min–1, n = 6) or physiologic saline solution (n = 6) on systemic as well as regional perfusion during 30 min of supracoeliac aortic cross-clamping and during 180 min of reperfusion following declamping. Rats were surgically instrumented with arterial, right atrial and portal venous catheters, ultrasonic flow probes around the abdominal aorta, superior mesenteric and carotid artery, and a paediatric tonometer for intestinal mucosal PCO2 measurement. During 120 min of reperfusion, fluid resuscitation was titrated to keep abdominal aortic blood flow above 80% of baseline values. We found that during cross-clamping, values of arterial lactate (p = 0.002) and intestinal tonometric PCO2 (p = 0.018) were higher in the dopexamine group than in the control group.
Apelin and Cardiac Function in Hemodialyzed Patients: Possible Relations?
Authors: Małyszko Jolanta , Małyszko Jacek S. , Koźminski Piotr , Myśliwiec Michał
Published: March 2006

Background: Apelin, a newly discovered adipocytokine, is produced by white adipose tissue and is also expressed in the kidney and heart. Increasing evidence suggests a role for apelin in the pathology of the cardiovascular system. Cardiovascular disease is a major contributor to the mortality and morbidity in patients with chronic renal failure. The aim of this study was to assess associations between apelin, coronary artery disease (CAD) and echocardiographic parameters in hemodialyzed patients. Patients and Methods: We investigated plasma apelin levels (using commercially available kits) in 81 nondiabetic, clinically stable hemodialyzed patients (38 females, 43 males) with and without CAD. Results: Patients with CAD were significantly older, with significantly increased left ventricular internal end-diastolic dimension (LVIDd), left ventricular internal end-systolic dimension (LVISd), right ventricle (RV), left atrium (LA), interventricular septum in diastole, left ventricle posterior wall in diastole (LVPW), aorta, pulmonary artery, significantly lower ejection fraction and apelin than patients without CAD. We observed statistically significant correlations between apelin and echocardiographic parameters: LVIDd, LVISd, RV, LA, right atrium, LVPW, aorta, and serum lipids: cholesterol, LDL, triglycerides. In multiple logistic regression analysis, the only associate of apelin was LVIDd. Conclusions: Apelin level was significantly lower in dialyzed patients with CAD and it was associated with cardiac function. Apelin might be involved in the pathophysiology of cardiovascular disease in chronic renal failure. Since apelin is an inotrope in normal and failing hearts, this finding may have clinical implications for future use of apelin as a novel inotropic agent also for patients with uremic cardiomyopathy.
12/15 Lipoxygenase Mediates Monocyte Adhesion to Aortic Endothelium in Apolipoprotein E–Deficient Mice Through Activation of RhoA and NF-κB
Authors: Bolick David T. , Srinivasan Suseela , Whetzel Angela , Fuller Lauren C. , Hedrick Catherine C.
Published: March 2006

Objectives—12/15 lipoxygenase (12/15LO) has been implicated as a mediator of inflammation and atherosclerosis. In the current study, we identified mechanisms through which 12/15LO mediates monocyte:endothelial interactions in vivo in apolipoprotein E-deficient mice (apoEKO), a well-characterized mouse model of atherosclerosis.

Methods and Results—In apoEKO mice that are also deficient in 12/15LO (doubleKO), monocyte adhesion to aorta in vivo was reduced by 95% in doubleKO mice compared with apoEKO mice. Inhibition of 12/15LO in apoEKO mice in vivo using CDC (Cinnamyl-3,4-Dihydroxy-a-Cyanocinnamate) prevented monocyte adhesion to aortic endothelium in apoEKO mice. Aortic endothelium of apoEKO mice had significant activation of rhoA compared with doubleKO aortic endothelium. Further, apoEKO aorta displayed significant activation of NF-κB. DoubleKO aorta displayed little nuclear localization of NF-κB. Finally, we found significant upregulation of intercellular adhesion molecule-1 (ICAM-1) on apoEKO aortic endothelium compared with doubleKO endothelium. Inhibition of rhoA and PKCα significantly reduced NF-κB activation, ICAM-1 induction, and monocyte adhesion to aorta.

Conclusions—We conclude that 12/15LO products activate endothelial rhoA and PKCα. Activation of rhoA and PKCα cause activation and translocation of NF-κB to the nucleus, which, in turn, results in induction of ICAM-1. Induction of ICAM-1 on aortic endothelium stimulates monocyte:endothelial adhesion in vivo in apoEKO mice.
Diabetic Cardiomyopathy
Authors: Poornima Indu G. , Parikh Pratik , Shannon Richard P.
Published: March 2006

Although diabetes is recognized as a potent and prevalent risk factor for ischemic heart disease, less is known as to whether diabetes causes an altered cardiac phenotype independent of coronary atherosclerosis. Left ventricular systolic and diastolic dysfunction, left ventricular hypertrophy, and alterations in the coronary microcirculation have all been observed, although not consistently, in diabetic cardiomyopathy and are not fully explained by the cellular effects of hyperglycemia alone. The recent recognition that diabetes involves more than abnormal glucose homeostasis provides important new opportunities to examine and understand the impact of complex metabolic disturbances on cardiac structure and function.
Focal Adhesions
Authors: Romer Lewis H. , Birukov Konstantin G. , Garcia Joe G.N.
Published: March 2006

The vascular wall contains intimal endothelium and medial smooth muscle that act as contiguous tissues with tight spatial and functional coordination in response to tonic and episodic input from the bloodstream and the surrounding parenchyma. Focal adhesions are molecular bridges between the intracellular and extracellular spaces that integrate a variety of environmental stimuli and mediate 2-way crosstalk between the extracellular matrix and the cytoskeleton. Focal adhesion components are targets for biochemical and mechanical stimuli that evoke crucial developmental and injury response mechanisms including cell growth, movement, and differentiation, and tailoring of the extracellular microenvironment. Focal adhesions provide the vascular wall constituents with flexible and specific tools for exchanging cues in a complex system. The molecular mechanisms that underlie these vital communications are detailed in this review with the goal of defining future targets for vascular tissue engineering and for the therapeutic modulation of disordered vascular growth, inflammation, thrombosis, and angiogenesis.
Endothelial Dysfunction and Hypertension in Rats Transduced With CYP4A2 Adenovirus
Authors: Wang Ji-Shi , Singh Harpreet , Zhang Frank , Ishizuka Tsuneo , Deng Huan , Kemp Rowena , Wolin Michael S. , Hintze Thomas H. , Abraham Nader G. , Nasjletti Alberto , Laniado-Schwartzman Michal
Published: March 2006

Vascular cytochrome P450 (CYP) 4A enzymes catalyze the synthesis of 20-hydroxyeicosatetraenoic acid (20-HETE), an eicosanoid which participates in the regulation of vascular tone by sensitizing the smooth muscle cells to constrictor and myogenic stimuli. This study was undertaken to investigate the consequences of CYP4A overexpression on blood pressure and endothelial function in rats treated with adenoviral vectors carrying the CYP4A2 construct. Intravenous injection of Adv-CYP4A2 increased blood pressure (from 114±1 to 133±1 mm Hg,P<0.001), and interlobar renal arteries from these rats displayed decreased relaxing responsiveness to acetylcholine, which was offset by treatment with an inhibitor of CYP4A. Relative to data in control rats, arteries from Adv-CYP4A2–transduced rats produced more 20-HETE (129±10 versus 97±7 pmol/mg protein,P<0.01) and less nitric oxide (NO; 4.2±1.6 versus 8.4±1 nmol nitrite+nitrate/mg;P<0.05). They also displayed higher levels of oxidative stress as measured by increased generation of superoxide anion and increased expression of nitrotyrosine and gp91phox. Collectively, these findings demonstrate that augmentation in vascular 20-HETE promotes the development of hypertension and causes endothelial dysfunction, a condition characterized by decreased NO synthesis and/or bioavailability, imbalance in the relative contribution of endothelium-derived relaxing and contracting factors, and enhanced endothelial activation.
Positive Inotropic Effects by Uridine Triphosphate (UTP) and Uridine Diphosphate (UDP) via P2Y2and P2Y6Receptors on Cardiomyocytes and Release of UTP in Man During Myocardial Infarction
Authors: Wihlborg Anna-Karin , Balogh Johanna , Wang Lingwei , Borna Catharina , Dou Ying , Joshi Bhalchandra V. , Lazarowski Eduardo , Jacobson Kenneth A. , Arner Anders , Erlinge David
Published: March 2006

The aim of this study was to examine a possible role for extracellular pyrimidines as inotropic factors for the heart. First, nucleotide plasma levels were measured to evaluate whether UTP is released in patients with coronary heart disease. Then, inotropic effects of pyrimidines were examined in isolated mouse cardiomyocytes. Finally, expression of pyrimidine-selective receptors (a subgroup of the P2 receptors) was studied in human and mouse heart, using real time polymerase chain reaction, Western blot, and immunohistochemistry. Venous plasma levels of UTP were increased (57%) in patients with myocardial infarction. In electrically stimulated cardiomyocytes the stable P2Y2/4agonist UTPγS increased contraction by 52%, similar to β1-adrenergic stimulation with isoproterenol (65%). The P2Y6-agonist UDPβS also increased cardiomyocyte contraction (35%), an effect abolished by the P2Y6-blocker MRS2578. The phospholipase C inhibitor U73122 inhibited both the UDPβS and the UTPγS-induced inotropic effect, indicating an IP3-mediated effect via P2Y6receptors. The P2Y14agonist UDP-glucose was without effect. Quantification of mRNA with real time polymerase chain reaction revealed P2Y2as the most abundant pyrimidine receptor expressed in cardiomyocytes from man. Presence of P2Y6receptor mRNA was detected in both species and confirmed at protein level with Western blot and immunohistochemistry in man. In conclusion, UTP levels are increased in humans during myocardial infarction, giving the first evidence for UTP release in man. UTP is a cardiac inotropic factor most likely by activation of P2Y2receptors in man. For the first time we demonstrate inotropic effects of UDP, mediated by P2Y6receptors via an IP3-dependent pathway. Thus, the extracellular pyrimidines (UTP and UDP) could be important inotropic factors involved in the development of cardiac disease.
Entertainment Education and Social Change The Communicative Dynamics of Social Capital*
Authors: Singhal, Arvind , Papa, Michael J. , Sharma, Devendra , Pant, Saumya , Worrell, Tracy , Muthuswamy Nithya , Witte Kim
Published: March 2006

This study explored processes of social change initiated by an entertainment education radio programme in India, Taru, which led to certain socially desirable effects in four villages in Bihar state. Data was collected primarily in the form of in-depth individual and focus group interviews, participant observation, and the design and implementation of a participatory theatre production by the respondents. We discovered that a media programme facilitates social change by stimulating the development of social capital in communities. Social capital was displayed through the development of: (a) relationships based on trust; (b) norms of reciprocity; and (c) communication networks. The existence of social capital contributed to educational programmes for lower-caste children, the improvement of community health, the stopping of a number of child marriages, and the promotion of gender equality. We also discovered, however, that social capital can initiate forces of both support and resistance towards social change. Furthermore, negative social capital may contribute to excluding certain people from participation in pro-social action, restricting individual freedom, placing excessive demands on group members, and downward levelling norms.
Self-injurious Behavior to the Lower Extremities Among Children With Atypical Development: A Diagnostic and Treatment Algorithm
Authors: Russell Paul Swamidhas Sudhakar
Published: March 2006

Self-injurious behavior is a devastating and persistent condition that results in severe tissue damage, permanent impairment, or, occasionally, death. This aberrant behavior seen in specific childhood syndromes is compounded when the lower limbs are injured. Secondary complications are more frequent, depending on the site of the injury, resulting in significant morbidity and depletion of hospital resources. A substantial body of empirical evidence indicates that this deviant behavior is partly learned and partly of biologic origin. Therefore, this article presents a case study and reviews the components of a biopsychosocial paradigm of treatment for self-inflicted wounds to the lower extremity and formulates a prototypical algorithm for its diagnosis and management.
The Evidence Supporting the Use of Honey as a Wound Dressing
Authors: Molan P. C.
Published: March 2006

Some clinicians are under the impression that there is little or no evidence to support the use of honey as a wound dressing. To allow sound decisions to be made, this seminar article has covered the various reports that have been published on the clinical usage of honey. Positive findings on honey in wound care have been reported from 17 randomized controlled trials involving a total of 1965 participants, and 5 clinical trials of other forms involving 97 participants treated with honey. The effectiveness of honey in assisting wound healing has also been demonstrated in 16 trials on a total of 533 wounds on experimental animals. There is also a large amount of evidence in the form of case studies that have been reported. It has been shown to give good results on a very wide range of types of wound. It is therefore mystifying that there appears to be a lack of universal acceptance of honey as a wound dressing. It is recommended that clinicians should look for the clinical evidence that exists to support the use of other wound care products to compare with the evidence that exists for honey.
Cecropia peltata L(Cecropiaceae) Has Wound-Healing Potential: A Preclinical Study in a Sprague Dawley Rat Model
Authors: Nayak B. Shivananda
Published: March 2006

The plant Cecropia peltata is used in traditional medicine to treat a variety of disorders. The objective of the study presented in this report was to screen the extracts of this plant leaf for its wound-healing properties based on its traditional use for wound healing. Aqueous and ethanol extracts were prepared for topical and oral administration. The dose studied was 150 mgkg-1day-1for 10 days, using the excision wound model in rats. Carboxymethyl cellulose (1%) was used as control in topical and oral route studies. Animals were randomized to treatment or control, the experiment being done with prior ethical approval from the university. Wound areas were measured. On day 11, tissue was excised to determine the contents of protein, hydroxyproline, and hexosamine. Wound areas reduced statistically significantly in all treatment groups compared to respective controls (P < .001). Biochemistry and tissue histology outcomes were consistent with changes in the treatment groups. No differences were detected within the treatment groups. The study permits the conclusion that Crecopia peltata has wound-healing potential.
The Citizen Factor
Authors: Simms Michele
Published: March 2006

Teaching an MBA ethics course, Management and the Social Environment, prompted the focus of this article on citizenship and the work of social entrepreneurs— those individuals involved in a worldwide mobilization of transnational organizations called the citizen sector. The first part presents an overviewon citizenship, ethics, and the role of liberal education in management courses. The second part outlines the practice and integration of these concepts to class curriculum and their particular relevance as taught at an Hispanic-serving institution.
Assessing Social Support in Mexican and Mexican American High School Students
Authors: López Eric J. , Salas Loretta
Published: March 2006

This study is a means of validating the Harter's Social Support Scale for Children on a sample of Mexican and Mexican American ninth-grade students to assist researchers and practitioners to more accurately assess this variable on this specific Latino group. The psychometric information was obtained through intercorrelations and Cronbach's alpha. Results indicated that the scale was an adequate measure of perceived social support from parents, teachers, close friends, and classmates for the assessed sample.
Teaching Spanish Caribbean History Through In the Time of the Butterflies
Authors: Martínez Elizabeth Coonrod
Published: March 2006

This manuscript presents a proposal for teaching Latino Caribbean heritag using as principal focus the novel and film In the Time of the Butterflies. It discusses terms of literary works and their readings, the foundation of a Spanish caste system, African immigration, and political and economic aspects affecting Dominican American identity and culture. It is geared to teaching in the undergraduate classroom and from the perspectives of race, gender, and transnationalism, with examples to engage critical thinking.
Petrology of forearc peridotite from the Hahajima Seamount, the Izu-Bonin arc, with special reference to chemical characteristics of chromian spinel
Authors: Okamura H. , Arai S. , Kim Y.-U.
Published: March 2006

Forearc peridotite is generally characterized by low Mg# (= Mg/[Mg + Fe2+] atomic ratio) at a given Cr# (= Cr/[Cr + Al] atomic ratio) of chromian spinel compared to common abyssal peridotite. This may be due to (1) smaller modal abundance of spinel and/or (2) lower equilibrium temperature, for the forearc peridotite. Forearc peridotite has the same amount of spinel as abyssal peridotite, eliminating the first possibility. Spinel in harzburgite and dunite from the Hahajima Seamount at the Izu-Bonin forearc, has a large Cr#, >0.57, and the Mg# is slightly variable towards low values at a given Cr#. The Mg# of spinel cores decreases strongly with a decrease in size. This is due to cooling along with hydration, which gave rise to a compositional variation of Ca-amphibole, from edenitic hornblende (high-temperature) to tremolite (low-temperature) in the Hahajima peridotite. The average two- pyroxene temperature of the Hahajima peridotite, 921°C, is less than that of the abyssal peridotite (1138°C), which is not consistent with a size-dependent Mg# of spinel for the latter. Forearc peridotite has been cooled effectively by H2O released from the subducted slab, causing a small Mg# of their spinels.
Detrital chrome-spinel grains in heavy-mineral sand deposits from southeast Africa
Authors: Pownceby M. , Bourne P.
Published: March 2006

Detrital chrome-spinels are contaminant grains within ilmenite concentrates produced from heavy-mineral deposits along the coast of southeast Africa. The presence of even minor levels of chromia in the predominantly ilmenite-rich concentrates, downgrades their market value as potential feedstocks for the production of titania pigment. An understanding of their composition can assist in their removal from the ilmenite concentrates.

Compositions from a database of close to 900 chrome-spinel analyses shows the major element components and their ranges (in wt.%) are: Cr: 0.4-45.3, Al: 0.0-31.0, Fe: 8.5-69.6 and Mg: 0.0-12.2. Minor components include Ti: 0.1-11.4 and Zn: 0.0-13.7.

The chrome-spinel data fall into two compositionally distinct groups. The first group of spinels is dominated by a strong trend reflecting the mutual substitution between Al3+ and Cr3+ in the spinel structure. The second group of spinels is characterized by compositions containing abundant Fe3O4magnetite component. The clear division between chrome-spinel compositional types indicates the grains are derived from at least two chemically dissimilar provenances.

The compositional differences between the chrome-spinel groups has a positive impact on subsequent ilmenite upgrading treatments as the spinels which contain the highest magnetite component are easily removed via low-intensity magnetic separation procedures.
Platinum-group mineral assemblages in the Platreef at the Sandsloot Mine, northern Bushveld Complex, South Africa
Authors: Holwell D. A. , McDonald I. , Armitage P. E. B.
Published: March 2006

Platinum group mineral (PGM) assemblages in the Platreef at Sandsloot, northern Bushveld Complex, in a variety of lithologies reveal a complex multi-stage mineralization history. During crystallization of the Platreef pyroxenites, platinum group elements (PGE) and base-metal sulphides (BMS) were distributed thoughout the interstitial liquid forming a telluride-dominant assemblage devoid of PGE sulphides. Redistribution of PGE into the metamorphic footwall by hydrothermal fluids has formed arsenide-, alloy- and antimonide-dominant assemblages, indicating a significant volatile influence during crystallization. Serpentinization of the footwall has produced an antimonide-dominant PGM assemblage. Parts of the igneous reef were subjected to alteration by a late-stage, Fe-rich fluid, producing ultramafic zones where the telluride-dominant assemblage has been recrystallized to an alloy-dominant one, particularly rich in Pt-Fe and Pd-Pb alloys. A thin, small-volume zone of PGE-BMS mineralization along the base of the hangingwall contains a primary PGM assemblage that is locally altered to one dominated by Pt/Pd germanides. This is thought to have formed when the new pulse of Main Zone magma entered the chamber, and scavenged PGE from the underlying Platreef pyroxenites. That each major rock type at Sandsloot contains a distinctive PGM assemblage reflects the importance of syn- and post-emplacement fluid and magmatic processes on the development of Platreef mineralization.