bluuebunny/crossref_metadata_2025 huggingface dataset:
Functional Analysis of Subunit e of the F
1
F
o
-ATP Synthase of the Yeast
Saccharomyces cerevisiae
: Importance of the N-Terminal Membrane Anchor Region
Authors: Everard-Gigot Valerie , Dunn Cory D. , Dolan Brigid M. , Brunner Susanne , Jensen Robert E. , Stuart Rosemary A.
Published: February 2005

Mitochondrial F
1
F
o
-ATP synthase complexes do not exist as physically independent entities but rather form dimeric and possibly oligomeric complexes in the inner mitochondrial membrane. Stable dimerization of two F
1
F
o
-monomeric complexes involves the physical association of two membrane-embedded F
o
-sectors. Previously, formation of the ATP synthase dimeric-oligomeric network was demonstrated to play a critical role in modulating the morphology of the mitochondrial inner membrane. In
Saccharomyces cerevisiae
, subunit e (Su e) of the F
o
-sector plays a central role in supporting ATP synthase dimerization. The Su e protein is anchored to the inner membrane via a hydrophobic region located at its N-terminal end. The hydrophilic C-terminal region of Su e resides in the intermembrane space and contains a conserved coiled-coil motif. In the present study, we focused on characterizing the importance of these regions for the function of Su e. We created a number of C-terminal-truncated derivatives of the Su e protein and expressed them in the Su e null yeast mutant. Mitochondria were isolated from the resulting transformant strains, and a number of functions of Su e were analyzed. Our results indicate that the N-terminal hydrophobic region plays important roles in the Su e-dependent processes of mitochondrial DNA maintenance, modulation of mitochondrial morphology, and stabilization of the dimer-specific F
o
subunits, subunits g and k. Furthermore, we show that the C-terminal coiled-coil region of Su e functions to stabilize the dimeric form of detergent-solubilized ATP synthase complexes. Finally, we propose a model to explain how Su e supports the assembly of the ATP synthase dimers-oligomers in the mitochondrial membrane.
Activation of an AP1-Like Transcription Factor of the Maize Pathogen
Cochliobolus heterostrophus
in Response to Oxidative Stress and Plant Signals
Authors: Lev Sophie , Hadar Ruthi , Amedeo Paolo , Baker Scott E. , Yoder O. C. , Horwitz Benjamin A.
Published: February 2005

Redox sensing is a ubiquitous mechanism regulating cellular activity. Fungal pathogens face reactive oxygen species produced by the host plant's oxidative burst in addition to endogenous reactive oxygen species produced during aerobic metabolism. An array of preformed and induced detoxifying enzymes, including superoxide dismutase, catalases, and peroxidases, could allow fungi to infect plants despite the oxidative burst. We isolated a gene (
CHAP1
) encoding a redox-regulated transcription factor in
Cochliobolus heterostrophus
, a fungal pathogen of maize. CHAP1 is a bZIP protein that possesses two cysteine-rich domains structurally and functionally related to
Saccharomyces cerevisiae
YAP1. Deletion of
CHAP1
in
C. heterostrophus
resulted in decreased resistance to oxidative stress caused by hydrogen peroxide and menadione, but the virulence of
chap1
mutants was unaffected. Upon activation by oxidizing agents or plant signals, a green fluorescent protein (GFP)-CHAP1 fusion protein became localized in the nucleus. Expression of genes encoding antioxidant proteins was induced in the wild type but not in
chap1
mutants. Activation of CHAP1 occurred from the earliest stage of plant infection, in conidial germ tubes on the leaf surface, and persisted during infection. Late in the course of infection, after extensive necrotic lesions were formed, GFP-CHAP1 redistributed to the cytosol in hyphae growing on the leaf surface. Localization of CHAP1 to the nucleus may, through changes in the redox state of the cell, provide a mechanism linking extracellular cues to transcriptional regulation during the plant-pathogen interaction.
Gene Discovery and Expression Profile Analysis through Sequencing of Expressed Sequence Tags from Different Developmental Stages of the Chytridiomycete
Blastocladiella emersonii
Authors: Ribichich Karina F. , Salem-Izacc Silvia M. , Georg Raphaela C. , Vêncio Ricardo Z. N. , Navarro Luci D. , Gomes Suely L.
Published: February 2005

Blastocladiella emersonii
is an aquatic fungus of the chytridiomycete class which diverged early from the fungal lineage and is notable for the morphogenetic processes which occur during its life cycle. Its particular taxonomic position makes this fungus an interesting system to be considered when investigating phylogenetic relationships and studying the biology of lower fungi. To contribute to the understanding of the complexity of the
B. emersonii
genome, we present here a survey of expressed sequence tags (ESTs) from various stages of the fungal development. Nearly 20,000 cDNA clones from 10 different libraries were partially sequenced from their 5′ end, yielding 16,984 high-quality ESTs. These ESTs were assembled into 4,873 putative transcripts, of which 48% presented no matches with existing sequences in public databases. As a result of Gene Ontology (GO) project annotation, 1,680 ESTs (35%) were classified into biological processes of the GO structure, with transcription and RNA processing, protein biosynthesis, and transport as prevalent processes. We also report full-length sequences, useful for construction of molecular phylogenies, and several ESTs that showed high similarity with known proteins, some of which were not previously described in fungi. Furthermore, we analyzed the expression profile (digital Northern analysis) of each transcript throughout the life cycle of the fungus using Bayesian statistics. The in silico approach was validated by Northern blot analysis with good agreement between the two methodologies.
Impact of heart failure on quality of sleep
Authors: Rao A , Gray D
Published: February 2005

Chronic heart failure is an important health problem associated with a high mortality and morbidity. Appropriate treatment reduces mortality and leads to improved exercise tolerance but many patients report poor quality of sleep. Sleep studies of patients with heart failure suggest that sleep disordered breathing is experienced in 50% of patients and is a powerful predictor of poor prognosis. Sleep disordered breathing broadly comprises obstructive sleep apnoea, when upper airway instability causes mechanical obstruction to breathing; and central sleep apnoea, characterised by an absence of ventilatory effort. Sleep disordered breathing occurring in patients with heart failure is in most part attributable to central sleep apnoea and reflects uncompensated instability of the ventilatory feedback mechanism.
Use of humour in primary care: different perceptions among patients and physicians
Authors: Granek-Catarivas M , Goldstein-Ferber S , Azuri Y , Vinker S , Kahan E
Published: February 2005

Purpose

(1) To explore the frequency with which humorous behaviour and statements occur in family medicine practice in Israel, and (2) to quantitatively assess the correlation between the subjective perceptions of humour in medical encounters between patients and physicians.

Method

In a cross sectional study, two populations (doctors and patients) were surveyed with paired structured questionnaires completed immediately after primary care practice visits. Two hundred and fifty consecutive encounters from 15 practices were sampled. The physician questionnaire was self administered, and patient questionnaire was administered by a trained research assistant.

Results

A mean of 16.7 questionnaires was completed per physician (range 6–20). The physicians reported having used some humour in only 95 encounters (38%), whereas almost 60% of patients agreed with the statement, “The doctor used some humour during the visit”. At the same time, for specific encounters, the agreement between patients’ perception and physicians’ perceptions on the use of humour, although not completely by chance (p = 0.04), is low (κ = 0.115). Patient characteristics (age, education, gender, family status, mother tongue, self perceived heath status, stress, mood, and expectations) were not related to the degree of agreement between the patients’ and physicians’ perceptions.

Conclusion

Humour was used in a large proportion of encounters, independently of patient characteristics. Patients seem to be more sensitised to humour than physicians, probably because of their high stress level during medical encounters. Cultural differences may also play a part. Physicians should be made aware of this magnifying effect, and the issue should be discussed in medical schools.
Low grade B cell gastric mucosa associated lymphoma presenting as upper gastrointestinal bleeding from non-healing stomal ulcers
Authors: Misra S P , Misra V , Dwivedi M
Published: February 2005

Primary gastric lymphoma is a rare tumour. It is thought that low grade gastric mucosa associated lymphoid tissue lymphoma has not been previously reported to occur in a patient with gastrojejunostomy. This report describes such a case. The patient presented with bleeding from non-healing stomal ulcers. The ulcers healed and there was regression of the tumour after eradication of Helicobacter pylori.
Urinary tract infections: new insights into a common problem
Authors: Kucheria R , Dasgupta P , Sacks S H , Khan M S , Sheerin N S
Published: February 2005

This review discusses recent advances in the understanding of how the common pathogen, uropathogenic Escherichia coli, interacts with the host to lead to infection.
HOW PAIRS OF PARTNERS EMERGE IN AN INITIALLY FULLY CONNECTED SOCIETY
Authors: KARPIŃSKA J. , MALARZ K. , KUŁAKOWSKI K.
Published: February 2005

A social group is represented by a graph, where each pair of nodes is connected by two oppositely directed links. At the beginning, a given amount p(i) of resources is assigned randomly to each node i. Also, each link r(i,j) is initially represented by a random positive value, which means the percentage of resources of node i which is offered to node j. Initially, the graph is fully connected, i.e., all nondiagonal matrix elements r(i,j) are different from zero. During the simulation, the amounts of resources p(i) change according to the balance equation. The nodes reorganize their activity with time to give more resources to those which give them more. This is the rule of varying the coefficients r(i,j). The result is that after some transient time, only some pairs (m,n) of nodes survive with nonzero p(m) and p(n), each pair with symmetric and positive r(m,n)=r(n,m). Other coefficients r(m,i≠n) vanish. Unpaired nodes remain with no resources, i.e., their p(i)=0, and they cease to be active as they have nothing to offer. The percentage of survivors (i.e., those with p(i) positive) increases with the velocity of varying the numbers r(i,j), and it slightly decreases with the size of the group. The picture and the results can be interpreted as a description of a social algorithm leading to marriages.
FRUSTRATION EFFECTS ON SMALL-WORLD NETWORKS
Authors: CAMPOS PAULO R. A. , DE OLIVEIRA VIVIANE M. , MOREIRA F. G. BRADY
Published: February 2005

We investigate the frustration effects on small-world networks by studying antiferromagnetic Ising model in two dimensions. When the rewiring is constrained to those sites such that the interaction still occurs between spins in distinct sublattices and frustration does not take place, we observe that the system behaves as in previous investigations of ferromagnetic Ising model. However, when the rewiring procedure does not only produce interactions between spins in distinct sublattices, small-world configurations can effectively produce geometrical frustration and we attain a different critical behavior. In the frustrated case, the critical temperature decreases with the augment of the rewiring probability and the magnetic ordering presents two different regimes for low and high p.
THE TIME EVALUATION OF RESISTANCE PROBABILITY OF A CLOSED COMMUNITY AGAINST OCCUPATION IN A SZNAJD-LIKE MODEL WITH SYNCHRONOUS UPDATING: A NUMERICAL STUDY
Authors: AYDINER EKREM
Published: February 2005

In the present paper, we have briefly reviewed Sznajd's sociophysics model and its variants, and we also have proposed a simple Sznajd-like sociophysics model based on Ising spin system to explain the time evaluation of resistance probability of a closed community against occupation. Using a numerical method, we have shown that the time evaluation of resistance probability of community has a nonexponential character, which decays as stretched exponential, independent of the number of soldiers in one-dimensional model. Furthermore, it has been astonishingly found that our simple sociophysics model belongs to the same universality class of random walk process on the trapping space.
Toward Predictive Models of Mammalian Cells
Authors: Ma'ayan Avi , Blitzer Robert D. , Iyengar Ravi
Published: February 2005

▪ Abstract  Progress in experimental and theoretical biology is likely to provide us with the opportunity to assemble detailed predictive models of mammalian cells. Using a functional format to describe the organization of mammalian cells, we describe current approaches for developing qualitative and quantitative models using data from a variety of experimental sources. Recent developments and applications of graph theory to biological networks are reviewed. The use of these qualitative models to identify the topology of regulatory motifs and functional modules is discussed. Cellular homeostasis and plasticity are interpreted within the framework of balance between regulatory motifs and interactions between modules. From this analysis we identify the need for detailed quantitative models on the basis of the representation of the chemistry underlying the cellular process. The use of deterministic, stochastic, and hybrid models to represent cellular processes is reviewed, and an initial integrated approach for the development of large-scale predictive models of a mammalian cell is presented.
Toroidal DNA Condensates: Unraveling the Fine Structure and the Role of Nucleation in Determining Size
Authors: Hud Nicholas V. , Vilfan Igor D.
Published: February 2005

▪ Abstract  Toroidal DNA condensates have attracted the attention of biophysicists, biochemists, and polymer physicists for more than thirty years. In the biological community, the quest to understand DNA toroid formation has been motivated by its relevance to gene packing in certain viruses and by the potential use of DNA toroids in artificial gene delivery (e.g., gene therapy). In the physical sciences, DNA toroids are appreciated as a superb model system for studying particle formation by the collapse of a semiflexible, polyelectrolyte polymer. This review focuses on experimental studies from the past few years that have significantly increased our understanding of DNA toroid structure and the mechanism of their formation. Highlights include structural studies that show the DNA strands within toroids to be packed in an ideal hexagonal lattice, and also in regions with a nonhexagonal lattice that are required by the topological constraints associated with winding DNA into a toroid. Recent studies of DNA toroid formation have also revealed that toroid size limits result from a complex interplay between kinetic and thermodynamic factors that govern both toroid nucleation and growth. The work discussed in this review indicates that it will ultimately be possible to obtain substantial control over DNA toroid dimensions.
Urinary Neopterin Levels in the Different Stages of Pregnancy
Authors: Boyunağa Hakan , Bayram Merih , Keleş Hatice , Yücel Aykan , Sağsöz Nevin , Özer Güler , Erbil M. Kemal , Akgül Emin Özgür
Published: February 2005

Background/Aims: Neopterin is a biochemical marker of activated cell-mediated immune response which increases in pathological conditions associated with cellular immune activation as well as in pregnancy where cellular immune response is predominant. The aim of this study was to determine the urinary neopterin level in each trimester of pregnancy and to determine if it can be used as a marker. Methods: 104 healthy pregnant women (mean age 22.10 ± 4.39 years; 36 in the first, 30 in the second and 38 in the third trimester) and 16 non-pregnant healthy women (mean age 20.94 ± 4.48 year) were included. Results: The mean urinary neopterin concentration of all pregnant women was higher than that of non-pregnant women (166.4 ± 31.7 and 103.1 ± 27.5 µmol/mol creatinine respectively, p < 0.01). The mean urinary neopterin levels in each trimester and non-pregnant women were 139.8 ± 49.6, 131 ± 40.2, 227.9 ± 86.5 and 103.1 ± 27.5 µmol/mol creatinine, respectively. Urinary neopterin levels were not significantly different between non-pregnant, first and second trimester groups, but were significantly higher in the third trimester than each of these groups (p < 0.05, p < 0.01 and p < 0.01 respectively). Conclusion: Urinary neopterin levels increase significantly in the third trimester probably due to more predominated cellular immunity. The pathologies causing cellular immune activation, especially in the first two trimesters can be predicted with urinary neopterin levels.
Investigation of Vascular Responses in Endothelial Nitric Oxide Synthase/Cyclooxygenase-1 Double-Knockout Mice
Authors: Scotland Ramona S. , Madhani Melanie , Chauhan Sharmila , Moncada Salvador , Andresen Jørgen , Nilsson Holger , Hobbs Adrian J. , Ahluwalia Amrita
Published: February 2005

Background—

Endothelium-dependent dilatation is mediated by 3 principal vasodilators: nitric oxide (NO), prostacyclin (PGI
2
), and endothelium-derived hyperpolarizing factor (EDHF). To determine the relative contribution of these factors in endothelium-dependent relaxation, we have generated mice in which the enzymes required for endothelial NO and PGI
2
production, endothelial NO synthase (eNOS) and cyclooxygenase-1 (COX-1), respectively, have been disrupted (eNOS
−/−
and COX-1
−/−
mice).

Methods and Results—

In female mice, the absence of eNOS and COX-1 had no effect on mean arterial blood pressure (BP), whereas BP was significantly elevated in eNOS
−/−
/COX-1
−/−
males compared with wild-type controls. Additionally, endothelium-dependent relaxation remained intact in the resistance vessels of female mice and was associated with vascular smooth muscle hyperpolarization; however, these responses were profoundly suppressed in arteries of male eNOS
−/−
/COX-1
−/−
animals. Similarly, the endothelium-dependent vasodilator bradykinin produced dose-dependent hypotension in female eNOS
−/−
/COX-1
−/−
animals in vivo but had no effect on BP in male mice.

Conclusions—

These studies indicate that EDHF is the predominant endothelium-derived relaxing factor in female mice, whereas NO and PGI
2
are the predominant mediators in male mice. Moreover, the gender-specific prevalence of EDHF appears to underlie the protection of female eNOS
−/−
/COX-1
−/−
mice against hypertension.
Retinoids and Pulmonary Hypertension
Authors: Preston Ioana R. , Tang Guangwen , Tilan Jason U. , Hill Nicholas S. , Suzuki Yuichiro J.
Published: February 2005

Background—

Retinoic acid has antimitogenic effects on smooth muscle cells. Studies on the systemic circulation suggest that it may reduce vascular thickening. Relationships between retinoids and pulmonary hypertension/pulmonary vascular remodeling, however, have not been explored. Thus, the present study examined retinoid levels in plasma of patients with idiopathic pulmonary arterial hypertension and the effects of retinoic acid on human pulmonary artery smooth muscle cell growth.

Methods and Results—

We measured retinoid levels by gas chromatograph–mass spectrometer technique in plasma of idiopathic pulmonary arterial hypertension patients and in age- and sex-matched healthy control subjects. Patients had significantly lower levels of all-
trans
retinoic acid and 13-
cis
retinoic acid than control subjects but similar 9-
cis
retinoic acid and retinol levels. In cultured human pulmonary artery smooth muscle cells, all-
trans
retinoic acid suppressed serotonin-induced cell growth. These cells were found to express the retinoid acid receptors RARα, RARβ, RARγ, RXRα, and RXRβ. Gene array analysis showed that retinoic acid induces the expression of GADD45A, a known cell growth suppressor. Contrary to expectations, plasma from pulmonary hypertension patients suppressed cell growth, likely influenced by factors other than retinoids.

Conclusions—

Idiopathic pulmonary arterial hypertension patients have reduced retinoic acid levels, and retinoic acid treatment can elicit growth-inhibitory signals in pulmonary artery smooth muscle cells in vitro. Thus, retinoic acid may influence pulmonary vascular remodeling in humans.
Early and Mid-Term Results of Drug-Eluting Stent Implantation in Unprotected Left Main
Authors: Chieffo Alaide , Stankovic Goran , Bonizzoni Erminio , Tsagalou Eleftheria , Iakovou Ioannis , Montorfano Matteo , Airoldi Flavio , Michev Iassen , Sangiorgi Massimo Giuseppe , Carlino Mauro , Vitrella Giancarlo , Colombo Antonio
Published: February 2005

Background—

The safety and efficacy of percutaneous coronary intervention in unprotected left main (ULM) coronary arteries are still a matter of debate.

Methods and Results—

All consecutive patients who had a sirolimus-eluting stent (Cypher, Cordis, Johnson and Johnson Co) or a paclitaxel-eluting stent (Taxus, Boston Scientific) electively implanted in de novo lesions on unprotected left main were analyzed. Patients treated with a drug-eluting stent (DES) were compared with the historical group of consecutive patients treated with bare metal stent (BMS). Eighty-five patients were treated with DES; 64 had BMS implantation. Patients treated with DES had lower ejection fractions (51.1±11% versus 57.4±13%,
P
=0.002) and were more often diabetics (21.2% versus 10.9%,
P
=0.12) with more frequent distal left main involvement (81.2% versus 57.8%,
P
=0.003). Furthermore, in the DES group, smaller vessels (3.33±0.6 versus 3.7±0.7 mm, respectively;
P
=0.0001) with more lesions (2.94±1.6 versus 2.25±1.3,
P
=0.004) and vessels (2.03±0.69 versus 1.8±0.72,
P
=0.05) were treated with longer stents (24.3±12 versus 15.8±8.6 mm,
P
=0.0001). Despite the higher-risk patients and lesion profiles in the DES group, the incidence of major cardiac events at a 6-month clinical follow-up was lower in the DES than in the BMS group (20.0% versus 35.9%, respectively;
P
=0.039). Moreover, cardiac deaths occurred in 3 DES patients (3.5%), as compared with 6 (9.3%) in the BMS group (
P
=0.17).

Conclusions—

In this early experience with DES in unprotected left main, this procedure appears safe with favorable and improved clinical results as compared with historical control subjects with a BMS. A randomized study comparing surgery appears justified at present.
Neurocirculatory Abnormalities in Chronic Orthostatic Intolerance
Authors: Goldstein David S. , Eldadah Basil , Holmes Courtney , Pechnik Sandra , Moak Jeffrey , Sharabi Yehonatan
Published: February 2005

Background—

Chronic orthostatic intolerance (COI) occurs in postural tachycardia syndrome (POTS) and in some individuals with repeated neurocardiogenic syncope/presyncope (NCS), without POTS. This study addressed whether patients with COI and POTS or NCS have neurocirculatory abnormalities during supine rest.

Methods and Results—

Adult patients referred for COI who had POTS (n=90, mean±SEM age 40±1 years, 86% women) or NCS (n=36, 41±2 years old, 78% women) underwent measurements of plasma levels of catecholamines and forearm hemodynamics. Comparison data were obtained from 32 age- and gender-matched normal volunteers (39±2 years old, 81% women). The POTS group had a relatively fast mean heart rate (79±2 bpm) during supine rest compared with the NCS group (69±1.6 bpm,
P
=0.03) and normal volunteers (66±3 bpm,
P
=0.0004). The POTS group also had higher mean arterial norepinephrine (1.61±0.11 nmol/L, n=37) and epinephrine (0.39±0.03 nmol/L, n=37) concentrations than the NCS group (1.03±0.12 nmol/L, n=20,
P
=0.0012; 0.21±0.03 nmol/L, n=20,
P
=0.0005) and normal volunteers (1.13±0.11 nmol/L, n=20,
P
=0.006; 0.17±0.03 nmol/L, n=15,
P
=0.0001). The NCS group had higher mean forearm vascular resistance (52±6 U) than the POTS group (36±2 U,
P
=0.003).

Conclusions—

Overall, POTS features increased heart rate and sympathetic nervous and adrenomedullary hormonal system outflows during supine rest. Increased sympathetic outflow may contribute to the relative tachycardia in POTS. NCS features forearm vasoconstriction during supine rest but not sympathoneural or adrenomedullary activation.
Renal Denervation Abolishes Hypertension in Low-Birth-Weight Offspring From Pregnant Rats With Reduced Uterine Perfusion
Authors: Alexander Barbara T. , Hendon Andrew E. , Ferril Geoffrey , Dwyer Terry M.
Published: February 2005

Low birth weight is a risk factor for the subsequent development of hypertension in humans. We previously reported that reduced uterine perfusion in the pregnant rat results in growth-restricted offspring predisposed to the development of hypertension. The purpose of this study was to determine whether the sympathetic nervous system plays a role in mediating hypertension in this model of low birth weight. Weight at birth was significantly decreased in male growth-restricted offspring (5.9±0.1 grams) as compared with male control offspring (6.5±0.2 grams;
P
<0.05). At 10 weeks of age, growth-restricted offspring and control offspring were randomly assigned to either an intact group (sham-denervated) or a group subjected to bilateral renal denervation. For sham-denervated offspring, mean arterial pressure was significantly elevated in growth-restricted offspring (145±4 mm Hg; n=7) as compared with control offspring (134±3 mm Hg;
P
<0.05; n=9) at 12 weeks of age. Bilateral renal denervation resulted in a marked reduction in arterial pressure in growth-restricted offspring (125±3 mm Hg;
P
<0.01; difference of 20 mm Hg versus sham growth-restricted; n=8) but no significant decrease in control offspring (127±3 mm Hg; difference of 7 mm Hg versus sham control; n=9). Adequacy of renal denervation was verified by >90% reduction in renal norepinephrine content. Therefore, these findings indicate the renal nerves play an important role in mediating hypertension in adult growth-restricted offspring.
14,15-Epoxyeicosatrienoic Acid Represents a Transferable Endothelium-Dependent Relaxing Factor in Bovine Coronary Arteries
Authors: Gauthier Kathryn M. , Edwards Erik M. , Falck John R. , Reddy Dendi S. , Campbell William B.
Published: February 2005

Bradykinin causes arterial relaxation and hyperpolarization, which is mediated by a transferable endothelium-derived hyperpolarizing factor (EDHF). In coronary arteries, epoxyeicosatrienoic acids (EETs) are involved in the EDHF response. However, the role of EETs as transferable mediators of EDHF-dependent relaxation remains poorly defined. Two small bovine coronary arteries were cannulated and perfused in tandem in the presence of the nitric oxide synthase inhibitor, nitro-
l
-arginine (30 μmol/L), and the cyclooxygenase inhibitor, indomethacin (10 μmol/L). Luminal perfusate from donor arteries with intact endothelium perfused endothelium-denuded detector arteries. Detector arteries were constricted with U46619 and diameters were monitored. Bradykinin (10 nmol/L) added to detector arteries did not induce dilation (5±2%), whereas bradykinin addition to donor arteries dilated detector arteries by 26.5±7% (
P
<0.05). These dilations were blocked by donor artery endothelium removal and detector artery treatment with the EET-selective antagonist, 14,15-epoxyeicosa-5(Z)-monoenoic acid (14,15-EEZE; 10 μmol/L, −5±6%) but not 14,15-EEZE treatment of donor arteries (20±5%). 14,15-EET (0.1 to 10 μmol/L) added to detector arteries induced maximal dilations of 82±5% that were inhibited 50% by detector artery treatment with 14,15-EEZE (32±12%) but not donor artery treatment with 14,15-EEZE. Liquid chromatography–electrospray ionization mass spectrometry analysis verified the presence of 14,15-EET in the perfusate from an endothelium-intact but not denuded artery. These results show that bradykinin stimulates donor artery 14,15-EET release that dilates detector arteries. 14,15-EEZE blocked the donor artery, endothelium-dependent, bradykinin-induced relaxations, and attenuated relaxations to 14,15-EET. These results suggest that EETs are transferable EDHFs in coronary arteries.
Superoxide Mediates Angiotensin II–Induced Influx of Extracellular Calcium in Neural Cells
Authors: Zimmerman Matthew C. , Sharma Ram V. , Davisson Robin L.
Published: February 2005

We recently demonstrated that superoxide (O
2
•−
) is a key signaling intermediate in central angiotensin II (Ang II)-elicited blood pressure and drinking responses, and that hypertension caused by systemic Ang II infusion involves oxidative stress in cardiovascular nuclei of the brain. Intracellular Ca
2+
is known to play an important role in Ang II signaling in neurons, and it is also linked to reactive oxygen species mechanisms in neurons and other cell types. However, the potential cross-talk between Ang II, O
2
•−
, and Ca
2+
in neural cells remains unknown. Using mouse neuroblastoma Neuro-2A cells, we tested the hypothesis that O
2
•−
radicals are involved in the Ang II–induced increase in intracellular Ca
2+
concentration ([Ca
2+
]
i
) in neurons. Ang II caused a rapid time-dependent increase in [Ca
2+
]
i
that was abolished in cells bathed in Ca
2+
-free medium or by pretreatment with the nonspecific voltage-gated Ca
2+
channel blocker CdCl
2
, suggesting that voltage-sensitive Ca
2+
channels are the primary source of Ang II–induced increases in [Ca
2+
]
i
in this cell type. Overexpression of cytoplasm-targeted O
2
•−
dismutase via an adenoviral vector (AdCuZnSOD) efficiently scavenged Ang II–induced increases in intracellular O
2
•−
and markedly attenuated the increase in [Ca
2+
]
i
caused by this peptide. Furthermore, adenoviral-mediated expression of a dominant-negative isoform of Rac1 (AdN17Rac1), a critical component for NADPH oxidase activation and O
2
•−
production, significantly inhibited the increase in [Ca
2+
]
i
after Ang II stimulation. These data provide the first evidence that O
2
•−
is involved in the Ang II–stimulated influx of extracellular Ca
2+
in neural cells and suggest a potential intracellular signaling mechanism involved in Ang II–mediated oxidant regulation of central neural control of blood pressure.
Cardiovascular Genomics and Oxidative Stress
Authors: Dominiczak Anna F. , Graham Delyth , McBride Martin W. , Brain Nick J.R. , Lee Wai Kwong , Charchar Fadi J. , Tomaszewski Maciej , Delles Christian , Hamilton Carlene A.
Published: February 2005

The majority of modifiable cardiovascular risk factors are complex, polygenic, or at least oligogenic traits, with genetic and environmental determinants playing important roles in disease risk and its phenotypic expression. The Human Genome Project and subsequent mouse and rat genome data have provided powerful tools to commence the dissection of genetic determinants of hypertension and other cardiovascular risk factors. Despite several new methodologies such as genome-wide scans, genome-wide gene expression profiling, and proteomic screens, it is fair to say that the progress of genetic studies designed as nonhypothesis driven has been relatively slow. On the other hand, several interesting candidate pathways have been identified, where investigators allowed for hypothesis-driven functional studies. One example of such pathway is vascular oxidative stress with its extensive network of genes and proteins, many with proven contributions to cardiovascular disease. Therefore, in parallel to genome-wide or proteome-wide studies, it will be constructive to pursue “pathwayomics” defined here as functional studies of a candidate pathway for disease pathogenesis.
Nitric Oxide–Dependent and Nitric Oxide–Independent Transcriptional Responses to High Shear Stress in Endothelial Cells
Authors: Braam Branko , de Roos Remmert , Bluyssen Hans , Kemmeren Patrick , Holstege Frank , Joles Jaap A. , Koomans Hein
Published: February 2005

Shear stress modulates gene expression in endothelial cells (ECs) partly through nitric oxide (NO), acting via enhanced cGMP formation by guanylyl cyclase (GC). We addressed non-cGMP–mediated transcriptional responses to shear stress in human umbilical ECs subjected to high-laminar shear stress (25 dyn/cm
2
; 150 minutes). RNA was isolated, reverse-transcribed, Cy3/5-labeled, and hybridized to 19 K human microarrays. High shear (n=6), high shear with 100 μmol/L
l
-NAME (n=3), and high shear with 10 μmol/L ODQ (GC inhibitor) in the perfusate (n=3) was compared with samples not subjected to flow. Among genes responding to high shear were HMOX1 (up) and PPARG (down). A high percentage of gene expression modulation by shear was absent during concomitant
l
-NAME or ODQ. Several transcriptional modulators were found (up: SOX5, SOX25, ZNF151, HOXD10; down: SOX11); a number of genes were regulated by shear and by shear with ODQ, but not regulated during
l
-NAME, indicating a nitric oxide synthase (NOS)–dependent, guanylyl cyclase (GC)–independent pathway. Several genes only responded to shear stress during
l
-NAME, others only responded to shear during ODQ. Upstream binding site analysis indicated shear stress and NO-dependent regulation of transcription via SOX5 and SOX9. Although NO importantly modulated the effect of shear stress on EC transcription, HMOX1 was consistently induced by shear stress, but not dependent on NOS or GC. Using bio-informatics software and databases, a promoter analysis identified SOX5 and SOX9 as potential, novel, shear-sensitive, and NO-dependent transcriptional regulators. The role of HMOX1 as a potential backup for NOS and the downstream role of SOXes should be explored.
Endurance Exercise Training in Orthostatic Intolerance
Authors: Winker Robert , Barth Alfred , Bidmon Daniela , Ponocny Ivo , Weber Michael , Mayr Otmar , Robertson David , Diedrich André , Maier Richard , Pilger Alex , Haber Paul , Rüdiger Hugo W.
Published: February 2005

Orthostatic intolerance is a syndrome characterized by chronic orthostatic symptoms of light-headedness, fatigue, nausea, orthostatic tachycardia, and aggravated norepinephrine levels while standing. The aim of this study was to assess the protective effect of exercise endurance training on orthostatic symptoms and to examine its usefulness in the treatment of orthostatic intolerance. 2768 military recruits were screened for orthostatic intolerance by questionnaire. Tilt-table testing identified 36 cases of orthostatic intolerance out of the 2768 soldiers. Subsequently, 31 of these subjects with orthostatic intolerance entered a randomized, controlled trial. The patients were allocated randomly to either a “training” (3 months jogging) or a “control” group. The influence of exercise training on orthostatic intolerance was assessed by determination of questionnaire scores and tilt-table testing before and after intervention. After training, only 6 individuals of 16 still had orthostatic intolerance compared with 10 of 11 in the control group. The Fisher exact test showed a highly significant difference in diagnosis between the 2 groups (
P
=0.008) at the end of the study. Analysis of the questionnaire-score showed significant interaction between time and group (
P
=0.001). The trained subjects showed an improvement in the average symptom score from 1.79±0.4 to 1.04±0.4, whereas the control subjects showed no significant change in average symptom score (2.09±0.6 and 2.14±0.5, respectively). Our data demonstrate that endurance exercise training leads to an improvement of symptoms in the majority of patients with orthostatic intolerance. Therefore, we suggest that endurance training should be considered in the treatment of orthostatic intolerance patients.
Nonlinear Relations of Blood Pressure to Cognitive Function
Authors: Waldstein Shari R. , Giggey Paul P. , Thayer Julian F. , Zonderman Alan B.
Published: February 2005

This investigation examined cross-sectional and longitudinal relations, both linear and nonlinear, of blood pressure (BP) and its interaction with demographic and lifestyle variables to a broad spectrum of cognitive functions. Eight hundred forty-seven participants (503 men and 344 women) from the Baltimore Longitudinal Study of Aging completed tests of verbal and nonverbal memory, attention, perceptuo-motor speed, executive functions, and confrontation naming, and clinical assessment of BP on 1 to 7 occasions over 11 years. Mixed-effects regression models, adjusted for age, education, gender, alcohol consumption, smoking status, depression scores, and use of antihypertensive medications, revealed nonlinear relations of systolic BP with longitudinal change on tests of nonverbal memory and confrontation naming; cognitive decline was apparent among older (80 years) individuals with higher systolic BP. Cross-sectional findings, across testing sessions, indicated moderated U- and J-shaped relations between BP and cognitive function. Both high and low diastolic BP were associated with poorer performance on tests of executive function and confrontation naming among less-educated persons; with tests of perceptuo-motor speed and confrontation naming among nonmedicated (antihypertensives) individuals; and with executive function among older individuals. Cross-sectional linear relations included higher systolic BP and poorer nonverbal memory in nondrinkers, and higher diastolic BP and poorer working memory among less-educated individuals. Results indicate that cross-sectional and longitudinal relations of BP to cognitive function are predominantly nonlinear and moderated by age, education, and antihypertensive medications. Careful monitoring and treatment of both high and low BP levels may be critical to the preservation of cognitive function.
Long-Term Effectiveness of Extended-Release Nitrate for the Treatment of Systolic Hypertension
Authors: Stokes Gordon S. , Bune Alexandra J , Huon Natasha , Barin Edward S.
Published: February 2005

Isosorbide mononitrate (ISMN) is effective in the short-term for decreasing systolic blood pressure, pulse pressure, and pulse wave reflection in patients with systolic hypertension. To determine whether tolerance negates the efficacy of this nitrate in the long-term, a placebo-controlled study was performed in which ISMN was withdrawn briefly in a group of patients (n=16) who had received extended-release ISMN 60 to 120 mg once daily for 16 to 109 months. Blood pressure and wave reflection were determined by 24-hour ambulatory recorder and tonometer, respectively. During a 4-hour delay of the regular morning dose of ISMN, mean systolic blood pressure was higher than with the regular ISMN dosing schedule (
P
<0.0001). The maximum placebo-active difference was 16±4 mm Hg. The corresponding difference in augmentation index (a measure of pulse wave reflection) corrected for heart rate was 25±4% (
P
<0.001). The difference in pulse pressure was 13±3 mm Hg (
P
<0.001). There was no significant difference in diastolic blood pressure. For a subgroup (n=12) in which the effects of a single ISMN dose had been determined at the initiation of regular ISMN therapy, the mean change in augmentation index was of similar magnitude to that observed in their initial study. Thus, tolerance does not seriously diminish the antihypertensive efficacy of ISMN used as adjunct therapy in the chronic treatment of systolic hypertension. This agent lowers systolic blood pressure sufficiently to achieve therapeutic goal in some patients refractory to conventional treatment regimens.
Correction Method for RS80-A Humicap Humidity Profiles and Their Validation by Lidar Backscattering Profiles in Tropical Cirrus Clouds
Authors: Leiterer Ulrich , Dier Horst , Nagel Dagmar , Naebert Tatjana , Althausen Dietrich , Franke Kathleen , Kats Alexandre , Wagner Frank
Published: February 2005

Routine radiosonde relative humidity (RH) measurements are not reliable as they are presently used in the global upper-air network. The new Lindenberg measuring and evaluation method, which provides RH profile measurements with an accuracy of ±1% RΗ in the temperature range from 35° to −70°C near the tropical tropopause is described. This Standardized Frequencies (FN) method uses a thin-film capacitive polymer sensor of a modified RS90-H Humicap radiosonde. These research humidity reference radiosondes (FN sondes) are used to develop a correction method for operational RS80-A Humicap humidity profiles. All steps of correction and quality control for RS80-A radiosondes are shown: ground-check correction, time-lag and temperature-dependent correction, and the recognition of icing during the ascent. The results of a statistical comparison between FN sondes and RS80-A sondes are presented. Corrected humidity data of operational RS80-A sondes used in Lindenberg (4 times daily) show no bias when compared to FN radiosondes and have an uncertainty of about ±3% RH at the 1 σ or 68% confidence level from 1000 to about 150 hPa. Only a small dry bias of at most −2% RH remains in the lowest part of the boundary layer (up to 500-m height). Finally, some examples of corrected RS80-A RH profiles in cirrus clouds validated by lidar backscattering profiles in a region of the intertropical convergence (Maldive Islands) are demonstrated. The soundings indicate that ice-saturated and ice-supersaturated air above 10-km height were connected with cirrus clouds in all 47 investigated cases, and, second, that the corrected RS80-A RH profiles also provide good quality information on water vapor in the upper troposphere.
Motion Correction for Shipborne Turbulence Sensors
Authors: Schulz E. W. , Sanderson B. G. , Bradley E. F.
Published: February 2005

A method for removing ship motion from wind measurements using a simple and inexpensive strap-down system of accelerometers is described and analyzed. In slight seas, error analysis indicates that mean root-mean-square uncertainties associated with the motion correction are 0.03 and 0.006 m s−1 for the horizontal and vertical wind, respectively, for all runs analyzed. The mean uncertainty in the wind stress due to motion correction is 8 × 10−4 N m−2. In a shallow coastal sea setting, ship motion appears to almost always be successfully detected and removed from the vertical component of the observed wind. The horizontal wind components appear to be successfully corrected in 86% of the runs analyzed. Motion correction is shown to have a significant influence on the covariance-calculated wind stress. In approximately half of the runs analyzed the wind stress changes by more than 15%. Motion correction has a smaller effect on the heat fluxes.
Lagrangian Data Assimilation in Multilayer Primitive Equation Ocean Models
Authors: Molcard Anne , Griffa Annalisa , Özgökmen Tamay M.
Published: February 2005

Because of the increases in the realism of OGCMs and in the coverage of Lagrangian datasets in most of the world's oceans, assimilation of Lagrangian data in OGCMs emerges as a natural avenue to improve ocean state forecast with many potential practical applications, such as environmental pollutant transport, biological, and naval-related problems.

In this study, a Lagrangian data assimilation method, which was introduced in prior studies in the context of single-layer quasigeostrophic and primitive equation models, is extended for use in multilayer OGCMs using statistical correlation coefficients between velocity fields in order to project the information from the data-containing layer to the other model layers. The efficiency of the assimilation scheme is tested using a set of twin experiments with a three-layer model, as a function of the layer in which the floats are launched and of the assimilation sampling period normalized by the Lagrangian time scale of motion.

It is found that the assimilation scheme is effective provided that the correlation coefficient between the layer that contains the data and the others is high, and the data sampling period Δt is smaller than the Lagrangian time scale TL. When the assimilated data are taken in the first layer, which is the most energetic and is characterized by the fastest time scale, the assimilation is very efficient and gives relatively low errors also in the other layers (≈ 40% in the first 120 days) provided that Δt is small enough, Δt << TL. The assimilation is also efficient for data released in the third layer (errors < 60%), while the dependence on Δt is distinctively less marked for the same range of values, since the time scales of the deeper layer are significantly longer. Results for the intermediate layer show a similar insensitivity to Δt, but the errors are higher (exceeding 70%), because of the lower correlation with the other layers. These results suggest that the assimilation of deep-layer data with low energetics can be very effective, but it is strongly dependent on layer correlation. The methodology also remains quite robust to large deviations from geostrophy.
Socio-Economic Changes, Collective Insecurity and New Forms of Religious Expression
Authors: Chekroun Mohammed
Published: February 2005

English

Many economic and social factors lie behind the changes Moroccan society has undergone since the late 1970s. A new ethics and new forms of religious expression appear to correspond to these phenomena. The author attempts to elucidate the significance of strategies that social actors, particularly the young and women, have employed in the space-time in their immediate control. Through disparate but nonetheless convergent responses, new social and affective circumstances have formed, not initially the result of the external action of Islamist groups wanting to exert an 'influence'. Cleavages in religious sensitivities and values that were accentuated in the course of the first two decades after independence, notably between the new middle classes and the working classes due to mobility and social advancement, are shrinking today. This rapprochement is particularly evident when it comes to certain practices with high social visibility, such as group prayer for men and wearing the 'hijab' for women.

French

Plusieurs faits économiques et sociaux sont à l'origine des mutations que connaît la société marocaine depuis la fin des années soixante-dix. A ces phénomènes semblent correspondre une nouvelle éthique et de nouvelles formes d'expression religieuse. L'auteur tente d'élucider la signification des stratégies que les acteurs sociaux, plus particulièrement les jeunes et les femmes, déploient à partir des espaces temps immédiats qu'ils contrôlent. Au travers de réactions dispersées, mais néanmoins convergentes, se constitue une conjoncture socio-affective nouvelle, qui n'est pas d'abord le résultat d'une action externe de groupes islamistes ayant une intention 'd'influence'. Les clivages des sensibilités et des valeurs religieuses qui s'étaient accentués au cours des deux premières décennies après l'indépendance, notamment entre les nouvelles classes moyennes et les classes populaires du fait de la mobilité et de la promotion sociales, se réduisent aujourd'hui. Ce rapprochement est particulièrement évident en ce qui concerne certaines pratiques à forte visibilité sociale comme la prière collective pour les hommes et le port du 'hijab' pour les femmes.