bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental effort of American kestrels: the role of variation in brood size
Authors: Dawson Russell D , Bortolotti Gary R
Published: June 2003

Brood size has the potential to determine the allocation of resources between parents and offspring, as well as influence the relative contributions of each sex to parental effort. However, it is unclear whether brood size is the proximate determinant of parental effort, or conversely whether parental effort is the proximate factor to which brood size is adjusted. If brood size determines parental effort, then theory suggests that parental effort should vary with experimental changes in brood size. In contrast, if parental effort determines brood size, then parental effort is expected to be independent of experimental variation in brood size. To distinguish between these hypotheses, we experimentally reduced brood sizes of American kestrels (Falco sparverius). Our results suggest that male parents responded to brood-size variation and adjusted their provisioning behaviour accordingly. Conversely, female parents did not adjust provisioning in response to brood size, and as a result, offspring in reduced broods received more food on a per-nestling basis. However, condition and survival of offspring were similar in reduced broods and control young, which may have been the result of larger food requirements of small broods, owing to increased thermoregulatory costs compared with control broods. Female parents with reduced broods also did not brood offspring more often, further suggesting that females do not respond to variation in brood size. We conclude that the proximate determinants of parental effort are sex-specific in American kestrels: for males, brood size determines behaviour, whereas for females, behaviour may be a proximate factor determining brood size.
An experimental study of carbon-isotope fractionation between diet, hair, and feces of mammalian herbivores
Authors: Sponheimer Matt , Robinson Todd , Ayliffe Linda , Passey Ben , Roeder Beverly , Shipley Lisa , Lopez Elvia , Cerling Thure , Dearing Denise , Ehleringer Jim
Published: June 2003

The carbon-isotope composition of hair and feces offers a glimpse into the diets of mammalian herbivores. It is particularly useful for determining the relative consumption of browse and graze in tropical environments, as these foods have strongly divergent carbon-isotope compositions. Fecal δ13C values reflect the last few days consumption, whereas hair provides longer term dietary information. Previous studies have shown, however, that some fractionation occurs between dietary δ13C values and those of hair and feces. Accurate dietary reconstruction requires an understanding of these fractionations, but few controlled-feeding studies have been undertaken to investigate these fractionations in any mammalian taxa, fewer still in large mammalian herbivores. Here, we present data from the first study of carbon-isotope fractionation between diet, hair, and feces in multiple herbivore taxa. All taxa were fed pure alfalfa (Medicago sativa) diets for a minimum period of 6 months, at which point recently grown hair was shaved and analyzed for carbon isotopes. The mean observed diethair fractionation was +3.2, with a range of +2.7 to +3.5. We also examined dietfeces fractionation for herbivores on alfalfa and bermudagrass (Cynodon dactylon) feeds. The mean dietfeces fractionation for both diets was 0.8, with less fractionation for alfalfa (0.6) than bermudagrass (1.0). Fecal carbon turnover also varies greatly between taxa. When diets were switched, horse (Equus caballus) feces reflected the new diet within 60 h, but alpaca (Lama pacos) feces did not equilibrate with the new diet for nearly 200 h. Thus, fecal carbon isotopes provide far greater dietary resolution for hindgut-fermenting horses than foregut-fermenting alpacas.
Distribution and habitat features associated with remnant populations of New England cottontails in Maine
Authors: Litvaitis J A , Johnson B , Jakubas W , Morris K
Published: June 2003

We investigated the distribution and habitat associations of New England cottontails (Sylvilagus transitionalis; NEC) at the northern edge of their historic range (state of Maine) during the winters of 19992000 and 20002001. We compared features of regions ([Formula: see text]100 km2), landscapes (multiple home ranges of NEC within 1 km of suitable habitat), and patches (usually <0.1 km2) among sites that were occupied by NEC, occupied by a potential competitor (snowshoe hares, Lepus americanus), or vacant. The current range of NEC in Maine is approximately 1600 km2 versus a recent historic range of 9400 km2 (83% decline). Loss of early-successional forests may explain the decline in abundance but does not explain the pattern of range contraction. Patches occupied by NEC were larger, had a greater density of understory vegetation, and were more frequently associated with idle agricultural lands than vacant patches. Habitats occupied by snowshoe hares were characterized by a greater proportion of forest and a lower density of roads in the surrounding landscape, were more often associated with recent clearcuts, and had a lower density of understory vegetation than sites occupied by NEC. Based on current land-use patterns, remaining populations of NEC in Maine are vulnerable to extirpation.
Offspring sex ratios in subcolonies of Audouin's gull, Larus audouinii, with differential breeding performance
Authors: Genovart Meritxell , Jover Lluís , Ruiz Xavier , Oro Daniel
Published: June 2003

At the Ebro River delta colony in the western Mediterranean Sea, Audouin's gull, Larus audouinii, breeds in discrete aggregations called subcolonies, which showed strong differences in breeding parameters such as egg volume or breeding success. Egg parameters (such as size of both eggs and clutches) are strongly influenced by food availability. As all subcolonies are in the same area, differences in egg parameters might reflect different individuals' foraging efficiency. We measured mean clutch volumes in different subcolonies and chose those subcolonies that showed the greatest differences in this measure, which should indicate differences in parental body condition. Between these subcolonies we would expect, in turn, differences in offspring sex ratios. We took blood samples at hatching and fledging from chicks at these subcolonies and compared offspring sex ratios by means of molecular sexing. The proportions of young breeders differed between these subcolonies, and the subcolony with the greater proportion of young breeders produced smaller eggs and had lower breeding success. However, we did not detect any bias in progeny sex ratio, which probably indicates that if parental condition is not extremely reduced, selective pressures are insufficient to overcome the constraints imposed by Mendelian segregation of chromosomes.
Rapid female multiple mating in red flour beetles (Tribolium castaneum)
Authors: Pai Aditi , Yan Guiyun
Published: June 2003

Many female insects mate with multiple males within a single fertile period despite costs such as expenditure of energy and time and contraction of sexually transmitted diseases. In the red flour beetle, Tribolium castaneum, females remate with different males within minutes of the first copulation. If rapid multiple mating is adaptive then multiply mated females should have higher fitness than singly mated females. In this study, we determined the remating frequency of female beetles, characterized female mating behavior, and examined the fitness consequences of female multiple mating. We found that female T. castaneum mated, on average, with 46 nonvirgin males within a 1-h observation period. The number of males present in a mating arena did not significantly affect copulation frequency or the intermating interval. However, number of males present significantly affected the length of a single copula as a result of disturbance by rival males when more males were present. Female mating with multiple males in 24 h did not significantly improve egg production, F1-adult production, egg-to-adult viability, fertility retention, and female survivorship. Thus, multiple mating did not enhance long-term female fitness. Polyandrous mating behavior may have evolved through other mechanisms such as fertility assurance and increased offspring genetic diversity or fitness.
The gut microenvironment of helicid snails (Gastropoda: Pulmonata): in-situ profiles of pH, oxygen, and hydrogen determined by microsensors
Authors: Charrier Maryvonne , Brune Andreas
Published: June 2003

In-situ profiles of pH, oxygen, and hydrogen were measured in isolated guts of starved terrestrial gastropods belonging to four species, Cornu aspersum (syn. Helix aspersa), Elona quimperiana, Helix pomatia, and Helix lucorum (excepted pH), using Clark-type oxygen and hydrogen microsensors and liquid-ion-exchanger pH microelectrodes. The pH profiles in the two phyllophagous species, H. pomatia and C. aspersum, increased by 0.9 and 1.4 from the crop to the distal intestine (pH 6.4 and 7.4, respectively). In the saprophagous E. quimperiana, as in H. pomatia, the pH along the gut axis remained acidic (5.16.6), suggesting saprophagous habits in the latter. In all four species, no oxygen was detected in the gut lumen. Nevertheless, steep oxygen gradients around the gut epithelium indicated high oxygen-uptake rates. The estimated respiratory activity of the intestine ranged between 6.5 (E. quimperiana) and 13.1 (H. lucorum) μmol O2·g fresh mass1·h1. Hydrogen accumulated in the intestine and digestive gland of all snails tested, with the highest values in E. quimperiana and H. pomatia (58 and 78 μM, respectively). These results provide the basis for a better understanding of the microbial and biochemical processes involved in digestion.
Does habitat complexity influence the ability of fathead minnows to learn heterospecific chemical alarm cues?
Authors: Pollock M S , Chivers D P
Published: June 2003

Numerous aquatic animals release chemical cues when attacked by a predator. These cues "warn" other individuals of danger and have been termed alarm cues. Cross-species responses to alarm cues are common and in some cases result from learned recognition. However, little is known about the ecological factors that could influence this learned recognition. The current study focuses on the role of habitat complexity in the learning of heterospecific alarm cues. We introduced brook stickleback (Culaea inconstans) into outdoor pools containing fathead minnows (Pimephales promelas) naïve to stickleback. The pools all contained a predatory fish (northern pike, Esox lucius) but varied in habitat characteristics. Pools representing high-complexity habitats had a large amount of structure to obscure the visual environment, while pools representing low-complexity habitats had minimal structure. After 8 days, fish were removed from the pools and behavioural assays were conducted in the laboratory. We tested the minnows for a response to either stickleback skin extract (experimental) or swordtail (Xiphophorus helleri) skin extract (control) and found that minnows conditioned in pools with little structure had learned to recognize stickleback alarm cues, while those from pools with complex structure did not recognize stickleback alarm cues.
Escalated aggression in interpopulation brook trout dyads: evidence for behavioural divergence
Authors: Dunbrack Robert , Clarke Lynn
Published: June 2003

The "communication-failure" hypothesis states that individuals whose agonistic displays deviate from the population norm are selected against because of the greater likelihood of their becoming involved in escalated contests. A corollary of this hypothesis is that the level of aggression in dyadic (pairwise) contests over resources is predicted to be higher the greater the behavioural divergence between the two contestants. Display divergence between two contestants from different populations should exceed that in intrapopulation dyads, consequently this prediction can be tested by comparing levels of aggression in contests between interpopulation dyads with those in contests between intra population dyads. We carried out such a test using brook trout (Salvelinus fontinalis) from two isolated populations in eastern Newfoundland. In initial encounters, the nipping rate (a measure of aggressiveness) of individuals from one of these populations was significantly higher in interpopulation dyads than in intrapopulation dyads. These results are consistent with the communication-failure hypothesis, as well as with the view that behavioural assessment, using low-cost stereotypic displays, reduces the cost of interactions over resources for both contestants.
Effects of vegetation structure and edge habitat on the density and distribution of white-footed mice (Peromyscus leucopus) in small and large forest patches
Authors: Anderson Christine S , Cady Alan B , Meikle Douglas B
Published: June 2003

We tested the hypothesis that if the quality or quantity of vegetation in small forest patches is greater than in large patches, then vegetation attributes may contribute to greater densities of white-footed mice (Peromyscus leucopus) in smaller patches. We trapped more mice per hectare in small (range 59 ha) than in large (range 110150 ha) patches, as has been reported by other investigators. The difference appeared to be due primarily to the disproportionately high densities of P. leucopus in the edge habitat of small patches. While the greater edge-to-interior ratio in small patches could contribute to greater overall densities of mice in small patches, we trapped the same relative amount of edge and interior habitats in each of the six study patches. The structural complexity of understory vegetation was much greater in small than in large patches and also in edge than in interior habitats across the six patches. Thus, we trapped the most mice in the most structurally complex vegetation (i.e., edges of small patches). However, while vegetation at the edge of large patches was more complex than in the interior, we did not capture relatively high densities of P. leucopus in edge habitat of large patches. Hence, understory vegetation may differentially influence the distribution of P. leucopus between edge and interior habitats in forest patches of different sizes.
EFFICIENT PAIRING FUNCTIONS — AND WHY YOU SHOULD CARE
Authors: ROSENBERG ARNOLD L.
Published: June 2003

This paper provides a short guided tour through the world of pairing functions—bijections between [Formula: see text] and [Formula: see text] —as models for computational "situations." After a short discussion of the computationally simplest pairing functions—the Cauchy-Cantor "diagonal" polynomials—we describe in detail two specific computational situations where pairing functions give an unexpectedly simple handle on apparently complex systems-related problems. (1) We discuss the use of pairing functions as storage mappings for rectangular arrays/tables that are extendible, in the sense that the programmer may expand and shrink them dynamically. (2) We discuss the use of pairing functions as the basis for a mechanism for instilling accountability into Web-computing projects, by linking remote "volunteers" to the tasks they compute.
PROBABILISTIC REWRITING P SYSTEMS
Authors: MADHU MUTYAM
Published: June 2003

In this paper we define a variant of P systems, namely, probabilistic rewriting P systems, where the selection of rewriting rules is probabilistic. We show that, with non-zero cut-point, probabilistic rewriting P systems with/without priorities generate only finite languages, but with zero cut/point and without priorities, probabilistic rewriting P systems of degree 1 characterize the family of languages generated by matrix grammars. We also prove that probabilistic rewriting P systems of degree 1 with zero cut-point and priorities characterize recursively enumerable languages.
CHAOTIC SOLUTIONS OF THE DIRICHLET PROBLEMS FOR THE FORCED NAGUMO EQUATION
Authors: ABDEL-GAWAD H. I. , ABDUSALAM H. A.
Published: June 2003

Using an approach developed by one of the authors, approximate solutions of the null-Dirichlet problem for the forced Nagumo equation are obtained. It is shown that these solutions are chaotic whatever the values of the control parameter in this equation. It is also shown that in the absence of the external force the solutions are chaotic for negative values of the control parameter. However, these solutions are quasi-periodic for large time scales.
EXPERT SYSTEM FOR THRESHOLD SPECTRA ANALYSIS
Authors: PETROVIĆ VIOLETA , BOČVARSKI VALERIJ
Published: June 2003

In this paper, an expert system is presented that was developed with the aim to analyze threshold spectra experimentally obtained using backward chaining method of inference. With this way the process of spectra analysis was speeded up and automated. The spectrum usefulness, energy scale calibration, identification of peaks in spectrum, as well as identification of peaks by resonant influence was made possible with this expert system.
SYMMETRIC SELF-ORGANIZATION IN A CELLULAR AUTOMATON REQUIRING AN ESSENTIALLY RANDOM FEEDBACK: OBSERVATIONS, CONJECTURES, QUESTIONS
Authors: BARBÉ ANDRÉ , VON HAESELER FRITZ
Published: June 2003

A triangular cellular array whose cell-states satisfy the local rule of the cellular automaton that generates Pascal's triangle modulo 2 is subjected to a feedback inspired by conditions for rotational symmetry of its state-pattern. We discuss observations and conjectures about the fact that, in order to stabilize effectively in a rotationally symmetric pattern, the underlying recursion (feedback) procedure must have an essentially random nature.
NONLINEAR IDENTIFICATION USING PRIOR KNOWLEDGE OF FIXED POINTS: A MULTIOBJECTIVE APPROACH
Authors: NEPOMUCENO ERIVELTON G. , TAKAHASHI RICARDO H. C. , AMARAL GLEISON F. V. , AGUIRRE LUIS A.
Published: June 2003

This paper is devoted to the problem of model building from data produced by a nonlinear dynamical system. Unlike most published works that address the problem from a black-box perspective, in the present paper a procedure is developed that permits the use of prior knowledge about the location of fixed-points in addition to the data thus resulting in a gray-box approach. Numerical results using Chua's double-scroll attractor and the sine map are presented. As discussed, the suggested procedure is useful as a means to partially compensate for the loss of information due to noise and to improve dynamical performance in the presence of model structure mismatches. Preliminary results have indicated that the procedure outlined in this paper is a systematic way of searching for models in the vicinity of the black-box solution. This could have important consequences not only in model building but also in model validation.
CROSSING NUMBER OF LINKS FORMED BY EDGES OF A TRIANGULATION
Authors: KING SIMON A.
Published: June 2003

We study the crossing number of links that are formed by edges of a triangulation [Formula: see text] of S3 with n tetrahedra. We show that the crossing number is bounded from above by an exponential function of n2. In general, this bound can not be replaced by a subexponential bound. However, if [Formula: see text] is polytopal (resp. shellable) then there is a quadratic (resp. biquadratic) upper bound in n for the crossing number. In our proof, we use a numerical invariant [Formula: see text], called polytopality, introduced by the author.
DIAGRAM GROUPS, BRAID GROUPS, AND ORDERABILITY
Authors: WIEST BERT
Published: June 2003

We prove that all diagram groups (in the sense of Guba and Sapir) are left-orderable. The proof is in two steps: firstly, it is proved that all diagram groups inject in a certain braid group on infinitely many strings, and secondly, this group is then shown to be left-orderable.
TREE LEVEL LIE ALGEBRA STRUCTURES OF PERTURBATIVE INVARIANTS
Authors: HABEGGER NATHAN , PITSCH WOLFGANG
Published: June 2003

We study two different Lie algebra structures on the space of Feynman diagrams at tree level. We show that each such structure arises naturally from a tower of automorphism groups of nilpotent quotients of a free group.
DISCRIMINATION BY MULTIFRACTAL SPECTRUM ESTIMATION OF HUMAN HEARTBEAT INTERVAL DYNAMICS
Authors: MEYER M. , STIEDL O. , KERMAN B.
Published: June 2003

The complexity of the cardiac rhythm is demonstrated to exhibit self-affine multifractal variability. The dynamics of heartbeat interval time series was analyzed by application of the multifractal formalism based on the Cramer theory of large deviations. The continuous multifractal large deviation spectrum uncovers the nonlinear fractal properties in the dynamics of heart rate and presents a useful diagnostic framework for discrimination and classification of patients with cardiac disease, e.g. congestive heart failure. The characteristic multifractal spectral pattern in heart transplant recipients or chronic heart disease highlights the importance of neuroautonomic control mechanisms regulating the fractal dynamics of the cardiac rhythm.
AN EXPERIMENTAL STUDY OF STOCHASTIC PHASE SYNCHRONIZATION IN VERTICAL CAVITY LASERS
Authors: BARBAY SYLVAIN , GIACOMELLI GIOVANNI , LEPRI STEFANO , ZAVATTA ALESSANDRO
Published: June 2003

The response of a bistable vertical cavity surface emitting laser to a periodic input signal display all the hallmarks of stochastic resonance. Accurate experimental measurements show the occurrence of noise-induced frequency and effective phase locking characterized by a plateau of the mean output switching rate and a minimum of the relative–phase diffusion constant, respectively.
SEGREGATION OF PARTICLES USING CHAOTIC RATCHETS
Authors: MATEOS JOSE L.
Published: June 2003

We address the problem of the chaotic transport of particles in an asymmetric periodic ratchet potential. We consider the case of deterministic rocking ratchets and analyze different regimes for the amplitude of rocking. When the inertial term is taken into account, the dynamics can be chaotic and modify the transport properties. We compare the dynamics of point particles and extended objects under the action of the ratchet potential and show that we can segregate particles according to its size.
Low-Level Endotoxin Induces Potent Inflammatory Activation of Human Blood Vessels
Authors: Rice James B. , Stoll Lynn L. , Li Wei-Gen , Denning Gerene M. , Weydert Jamie , Charipar Elizabeth , Richenbacher Wayne E. , Miller Francis J. , Weintraub Neal L.
Published: June 2003

Background—Low-level endotoxemia (ie, ≥50 pg/mL) in apparently healthy subjects was recently identified as a powerful, independent risk factor for atherosclerosis.

Methods and Results—We treated human saphenous veins (HSVs) with low levels of endotoxin. Release of the proinflammatory chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) was measured by ELISA. Superoxide was determined by using the fluorescent probe dihydroethidium (HE), and monocyte binding was assessed with calcein-labeled U-937 cells. Three- to 4-fold increases in MCP-1 and IL-8 release were observed at endotoxin concentrations of 100 pg/mL; these increases were inhibited by the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor atorvastatin. Studies in cultured endothelial cells suggest that the mechanism is related to inhibition of isoprenylation (ie, geranylgeranylation) rather than cholesterol formation. Endotoxin produced dose-dependent increases in HE fluorescence that were inhibited by the superoxide dismutase mimics Tiron and MnTBAP. Endotoxin potently induced U-937 cell binding to HSV; binding was inhibited by both Tiron and atorvastatin. Toll-like receptor-4 expression was detected in cultured HSV endothelial and smooth muscle cells and in intact HSV.

Conclusions—Clinically relevant levels of endotoxin, as reported in ambulatory populations, have profound inflammatory effects on intact HSV. Inhibition of endotoxin-induced vascular inflammation might contribute to the beneficial effects of statins in treating atherosclerosis.
Caveolin-1 Can Regulate Vascular Smooth Muscle Cell Fate by Switching Platelet-Derived Growth Factor Signaling From a Proliferative to an Apoptotic Pathway
Authors: Peterson Timothy E. , Guicciardi Maria E. , Gulati Rajiv , Kleppe Laurel S. , Mueske Cheryl S. , Mookadam Martina , Sowa Grzegorz , Gores Gregory J. , Sessa William C. , Simari Robert D.
Published: June 2003

Background—

Caveolin-1 is a regulator of signaling events originating from plasma membrane microdomains termed caveolae. This study was performed to determine the regulatory role of caveolin-1 on the proliferative events induced by platelet-derived growth factor (PDGF) in vascular smooth muscle cells (VSMCs).

Methods and Results—

Treatment of VSMCs with PDGF for 24 hours resulted in a loss of caveolin-1 protein expression and plasma membrane–associated caveolae, despite a 3-fold increase in caveolin-1 mRNA. Pretreatment of VSMCs with chloroquine, an inhibitor of lysosomal function, inhibited the PDGF-induced loss of caveolin-1. These studies demonstrated that caveolin-1 was a target of PDGF signaling events. Adenoviral overexpression of caveolin-1 was associated with a switch in PDGF-induced signaling events from a proliferative response to an apoptotic response. This overexpression inhibited PDGF-induced expression of cyclin D1 in the presence of unaffected mitogen-activated protein kinase activation.

Conclusions—

Taken together, these studies suggest that caveolin-1 is an inhibitor of PDGF proliferative responses and might be capable of transforming PDGF-induced proliferative signals into death signals.
Effects of Insulin Resistance and Obesity on Lipoproteins and Sensitivity to Egg Feeding
Authors: Knopp Robert H. , Retzlaff Barbara , Fish Brian , Walden Carolyn , Wallick Shari , Anderson Melissa , Aikawa Keiko , Kahn Steven E.
Published: June 2003

Objective—

This study was undertaken to determine if insulin resistance without and with obesity influences LDL response to dietary cholesterol and saturated fat.

Methods and Results—

We fed 0, 2, and 4 egg yolks per day to 197 healthy subjects in a 4-week, double-blind, randomized, crossover design. Subjects were dichotomized on body mass index (<27.5 and ≥27.5 kg/m
2
) and insulin sensitivity (insulin-sensitivity index ≥4.2×1.0
−4
and <4.2×1.0
−4
min
−1
μU/mL), yielding insulin-sensitive (IS, n=65), insulin-resistant (IR, n=75), and obese insulin-resistant (OIR, n=58) subjects. Mean fasting baseline LDL cholesterol (LDL-C) levels were higher in IR and OIR subjects (3.44±0.67 and 3.32±0.80 mol/L) than in IS subjects (2.84±0.75 mmol/L) (
P
<0.001). Progressive triglyceride elevations and HDL-C decreases were seen across the 3 groups. Ingesting 4 eggs daily yielded significant LDL-C increases of 7.8±13.7% (IS) and 3.3±13.2% (IR) (both
P
<0.05) compared with 2.4±12.6% for OIR (NS). HDL-C increases were 8.8±10.4%, 5.2±10.4%, and 3.6±9.4% in IS, IR, and OIR, respectively (all
P
<0.01).

Conclusions—

Insulin resistance without and with obesity is associated with elevated LDL-C as well as elevated triglyceride and low HDL-C. The elevated LDL-C cannot be explained by dietary sensitivity, because the LDL-C rise with egg feeding is less in IR persons regardless of obesity status, probably attributable to diminished cholesterol absorption. The results suggest that dietary management of insulin resistance and obesity can focus more on restricting calories and less on restricting dietary fat.
Oral Infection With a Periodontal Pathogen Accelerates Early Atherosclerosis in Apolipoprotein E–Null Mice
Authors: Lalla Evanthia , Lamster Ira B. , Hofmann Marion A. , Bucciarelli Loredana , Jerud Adrienne P. , Tucker Sid , Lu Yan , Papapanou Panos N. , Schmidt Ann Marie
Published: June 2003

Objective—Because recent epidemiologic evidence suggests that periodontal infections may increase the risk of atherosclerosis and related events in humans, we assessed the impact of oral inoculation with the periodontal pathogenPorphyromonas gingivalison atherogenesis in hypercholesterolemic apolipoprotein E–null mice.

Methods and Results—In the absence of alterations in distinct risk factors,P gingivalisinfection exacerbated the early stages of atherogenesis in this model. Infected animals displayed evidence of local periodontal infection, as the severity of alveolar bone loss, the hallmark of periodontitis, was increased. Generalized activation of host inflammatory responses was evident in infected mice, as demonstrated by serum IgG response toP gingivalisand elevated levels of interleukin-6.P gingivalisDNA was localized in the aortic tissue from a limited number of infected mice but not in any noninfected controls. Infected mice displayed enhanced vascular activation, as suggested by increased aortic expression of vascular cell adhesion molecule-1 and tissue factor.

Conclusions—Oral infection withP gingivalisaccelerates early atherosclerosis. Thus, uncovering the underlying mechanisms is critical for the design of preventive and therapeutic strategies targeting atherosclerotic vascular disease and its sequelae.
Association Between a Novel 11–Base Pair Deletion Mutation in the Promoter Region of the Scavenger Receptor Class B Type I Gene and Plasma HDL Cholesterol Levels in Taiwanese Chinese
Authors: Hsu Lung-An , Ko Yu-Lin , Wu Semon , Teng Ming-Sheng , Peng Tsui-Yi , Chen Chun-Fei , Chen Chin-Fen , Lee Ying-Shiung
Published: June 2003

Objective—

Scavenger receptor class B type I (SR-BI) is a multiligand cell-surface receptor that mediates the selective uptake of lipid from HDL cholesterol (HDL-C) into cells. This study hypothesized an association between functional variants in the promoter region of SR-BI gene and HDL-C levels.

Methods and Results—

We identified 2 novel mutations in the SR-BI gene promoter region by using single-strand conformation polymorphism. One mutation was an 11-bp
CCCCGCCC

C

GT deletion mutation from positions −140 to −150 relative to the transcription start site, corresponding to an Sp1 binding site; the other was a
C
→
T
substitution at position −142. Twenty-six of 690 unrelated subjects were heterozygous for the −140 to −150 deletion mutation, and the allele frequency in this population was 0.02. This study showed that the deletion variant prevented binding of Sp1 to this region of the SR-BI promoter and effectively reduced transcriptional activities in HepG2 cells. Notably, the −140 to −150 deletion mutation was significantly associated with increased HDL-C levels and explained ≈0.5% of the variation in HDL-C levels in this population.

Conclusions—

A genetic variant at the SR-BI gene promoter region might explain a significant proportion of individual differences in HDL-C levels among Taiwanese Chinese. Our results require further replication in an independent population.
Dominant Expression of the CysLT2Receptor Accounts for Calcium Signaling by Cysteinyl Leukotrienes in Human Umbilical Vein Endothelial Cells
Authors: Sjöström Mattias , Johansson Anne-Sofie , Schröder Oliver , Qiu Hong , Palmblad Jan , Haeggström Jesper Z.
Published: June 2003

Objective—The objective of the present study was to identify and characterize the cell-surface receptors on human umbilical vein endothelial cells (HUVECs) that transduce calcium transients elicited by cysteinyl leukotrienes (CysLTs), potent spasmogenic and proinflammatory agents with profound effects on the cardiovascular system.

Methods and Results—Using quantitative reverse transcription–polymerase chain reaction, we found that HUVECs abundantly express CysLT2R mRNA in vast excess (>4000-fold) of CysLT1R mRNA. Lipopolysaccharide, tumor necrosis factor-α, or interleukin-1β caused a rapid (within 30 minutes) and partially reversible suppression of CysLT2R mRNA levels. Challenge of HUVECs with BAY u9773, a specific CysLT2R agonist, triggered diagnostic Ca2+transients. LTC4and LTD4are equipotent agonists, and their actions can be blocked by the dual-receptor antagonist BAY u9773, but not by the CysLT1R-selective antagonist MK571.

Conclusions—HUVECs almost exclusively express the CysLT2R. Furthermore, Ca2+fluxes elicited by CysLT in these cells emanate from perturbation of the CysLT2R, rather than the expected CysLT1R. Hence, signaling events involving CysLT2R might trigger functional responses involved in the critical components of LT-dependant vascular reactions, which in turn have implications for ischemic heart disease and myocardial infarction.
Differential Leukotriene Receptor Expression and Calcium Responses in Endothelial Cells and Macrophages Indicate 5-Lipoxygenase–Dependent Circuits of Inflammation and Atherogenesis
Authors: Lötzer Katharina , Spanbroek Rainer , Hildner Markus , Urbach Anja , Heller Regine , Bretschneider Ellen , Galczenski Helen , Evans Jilly F. , Habenicht Andreas J.R.
Published: June 2003

Objective—

Inflammatory infiltrates and atherosclerotic lesions emerge when monocytes adhere to endothelial cells (ECs), migrate into the subendothelial space, and become macrophages (MΦs). Leukotrienes (LTs), products of 5-lipoxygenase, are powerful inflammatory mediators. 5-lipoxygenase
+
MΦs have been shown to increase during atherogenesis, and LT receptor (LT-R) transcripts were identified in diseased arteries. To investigate LT-Rs in cells involved in inflammation and atherogenesis, we used the in vitro models of human umbilical vein ECs (HUVECs) and monocyte-derived MΦs.

Methods and Results—

HUVECs primarily expressed transcripts of the cysteinyl (cys) LT
2
-R, which was strongly upregulated by interleukin-4. By contrast, MΦs predominantly expressed transcripts of the cysLT
1
-R. Calcium responses toward LTs revealed differential cysLT-R utilization by both cell types: HUVECs responded to both cysLTs, whereas MΦs preferentially responded to LTD
4
; HUVECs, but not MΦs, were resistant toward a cysLT
1
-R antagonist, montelukast; cysLTs generated regular calcium oscillations in HUVECs that lasted >60 minutes, resulting in >500 oscillations per cell. By contrast, calcium elevations in MΦs returned to baseline within seconds and were nonoscillatory.

Conclusions—

Our data raise the possibility that MΦ-derived LTs differentially activate cysLT
2
-Rs via paracrine stimulation and cysLT
1
-Rs via autocrine and paracrine stimulation during inflammation and atherogenesis.
Platelet-Activating Factor Acetylhydrolase Is Mainly Associated With Electronegative Low-Density Lipoprotein Subfraction
Authors: Benítez Sonia , Sánchez-Quesada José Luis , Ribas Vicent , Jorba Oscar , Blanco-Vaca Francisco , González-Sastre Francesc , Ordóñez-Llanos Jordi
Published: June 2003

Background—

Electronegative LDL [LDL(−)], a modified subfraction of LDL present in plasma, induces the release of interleukin-8 and monocyte chemotactic protein-1 from cultured endothelial cells.

Methods and Results—

We demonstrate that platelet-activating factor acetylhydrolase (PAF-AH) is mainly associated with LDL(−). LDL(−) had 5-fold higher PAF-AH activity than the nonelectronegative LDL subfraction [LDL(+)] in both normolipemic and familial hypercholesterolemic subjects. Western blot analysis after SDS-PAGE confirmed these results, because a single band of 44 kDa corresponding to PAF-AH appeared in LDL(−) but not in LDL(+). Nondenaturing polyacrylamide gradient gel electrophoresis demonstrated that PAF-AH was bound to LDL(−) regardless of LDL size. In accordance with the above findings, nonesterified fatty acids, a cleavage product of PAF-AH, were increased in LDL(−) compared with LDL(+).

Conclusions—

The high PAF-AH activity observed in LDL(−) could be related to the proinflammatory activity of these lipoproteins toward cultured endothelial cells.
Catheter Ablation of Paroxysmal Atrial Fibrillation Initiated by Non–Pulmonary Vein Ectopy
Authors: Lin Wei-Shiang , Tai Ching-Tai , Hsieh Ming-Hsiung , Tsai Chin-Feng , Lin Yung-Kuo , Tsao Hsuan-Ming , Huang Jin-Long , Yu Wen-Chung , Yang Shih-Ping , Ding Yu-An , Chang Mau-Song , Chen Shih-Ann
Published: June 2003

Background—

Most of the ectopic beats initiating paroxysmal atrial fibrillation (PAF) originate from the pulmonary vein (PV). However, only limited data are available on PAF originating from the non-PV areas.

Methods and Results—

Two hundred forty patients with a total of 358 ectopic foci initiating PAF were included. Sixty-eight (28%) patients had AF initiated by ectopic beats (73 foci, 20%) from the non-PV areas, including the left atrial posterior free wall (28, 38.3%), superior vena cava (27, 37.0%), crista terminalis (10, 3.7%), ligament of Marshall (6, 8.2%), coronary sinus ostium (1, 1.4%), and interatrial septum (1, 1.4%). Catheter ablation eliminated AF with acute success rates of 63%, 96%, 100%, 50%, 100%, and 0% in left atrial posterior free wall, superior vena cava, crista terminalis, ligament of Marshall, coronary sinus ostium, and interatrial septum, respectively. During a follow-up period of 22±11 months, 43 patients (63.2%) were free of antiarrhythmic drugs without AF recurrence.

Conclusions—

Ectopic beats initiating PAF can originate from the non-PV areas, and catheter ablation of the non-PV ectopy has a moderate efficacy in treatment of PAF.
Basal Pulmonary Vascular Resistance and Nitric Oxide Responsiveness Late After Fontan-Type Operation
Authors: Khambadkone S. , Li J. , de Leval M.R. , Cullen S. , Deanfield J.E. , Redington A.N.
Published: June 2003

Background—

The pulsatile nature of pulmonary blood flow is important for shear stress–mediated release of endothelium-derived nitric oxide (NO) and lowering pulmonary vascular resistance (PVR) by passive recruitment of capillaries. Normal pulsatile flow is lost or markedly attenuated after Fontan-type operations, but to date, there are no data on basal pulmonary vascular resistance and its responsiveness to exogenous NO at late follow-up in these patients.

Methods and Results—

We measured indexed PVR (PVRI) using Fick principle to calculate pulmonary blood flow, with respiratory mass spectrometry to measure oxygen consumption, in 15 patients (median age, 12 years; range, 7 to 17 years; 12 male, 3 female) at a median of 9 years after a Fontan-type operation (6 atriopulmonary connections, 7 lateral tunnels, 2 extracardiac conduits). The basal PVRI was 2.11±0.79 Wood unit (WU) times m
2
(mean±SD) and showed a significant reduction to 1.61±0.48 (
P
=0.016) after 20 ppm of NO for 10 minutes. The patients with nonpulsatile group in the pulmonary circulation dropped the PVRI from 2.18±0.34 to 1.82±0.55 (
P
<0.05) after NO inhalation.

Conclusions—

PVR falls with exogenous NO late after Fontan-type operation. These data suggest pulmonary endothelial dysfunction, related in some part to lack of pulsatility in the pulmonary circulation because of altered flow characteristics. Therapeutic strategies to enhance pulmonary endothelial NO release may have a role in these patients.
Timing of Antioxidant Vitamin Ingestion Alters Postprandial Proatherogenic Serum Markers
Authors: Carroll Mary F. , Schade David S.
Published: June 2003

Background—

This study was designed to determine the optimal timing of vitamins E and C to prevent oxidative stress induced by a high-fat evening meal in type 2 diabetes.

Methods and Results—

Eleven subjects were admitted on 4 occasions. Euglycemia was maintained for 24 hours by insulin infusion. Participants were fed a high-fat test supper equivalent to a McDonald’s Big Mac Meal. Blood was drawn for measurement of C-reactive protein (CRP), interleukin 6 (IL-6), plasminogen activator inhibitor-1 (PAI-1), malonyldialdehyde (MDA), and total radical antioxidant parameter (TRAP) before and during the 4 hours after the test meal. Studies were performed in random sequence with vitamin E 800 IU and vitamin C 1 g given either before breakfast or before supper in a double-blind manner on the day of the test meal. Control studies were performed with no vitamins and no test meal administered. There was a significant rise in CRP and PAI-1 after the test supper (
P
<0.05 compared with “no meal”). Either presupper or prebreakfast vitamins E and C prevented the meal-induced rise in CRP (
P
=0.03), although presupper vitamins were more effective (
P
=0.03 compared with prebreakfast vitamins). Only prebreakfast vitamins prevented the meal-induced rise in PAI-1 (
P
=0.006). There were no significant meal-related changes in the concentrations of IL-6, MDA, or TRAP.

Conclusions—

The timing of administration of antioxidant vitamins has variable effects on markers of meal-induced inflammation and fibrinolysis. This observation may be one reason why cardiovascular disease prevention trials using these vitamins have reported conflicting results.
Inhibition of Granulation Tissue Cell Apoptosis During the Subacute Stage of Myocardial Infarction Improves Cardiac Remodeling and Dysfunction at the Chronic Stage
Authors: Hayakawa Kenji , Takemura Genzou , Kanoh Motoo , Li Yiwen , Koda Masahiko , Kawase Yukinori , Maruyama Rumi , Okada Hideshi , Minatoguchi Shinya , Fujiwara Takako , Fujiwara Hisayoshi
Published: June 2003

Background—

Granulation tissue cells at the subacute stage of myocardial infarction (MI) are eliminated by apoptosis to finally make a scar at the chronic stage. We hypothesized that postinfarct inhibition of apoptosis might preserve myofibroblasts and endothelial cells in granulation and modulate chronic left ventricular (LV) remodeling and heart failure.

Methods and Results—

A pancaspase inhibitor, Boc-Asp-fmk (BAF, 10 μmol/kg per day), or vehicle (control) was given to rats with experimental large MI. The treatment was started on the third day after MI and continued until 4-week-old MI. Two weeks later, the apoptosis of granulation tissue cells was significantly reduced and conversely, the cell population was greater in BAF. Twelve weeks later, BAF showed significantly greater survival rates (84% versus 42%) with significantly smaller LV cavity, lower LV end-diastolic pressure and central venous pressure, and higher LV dP/dt, which indicated improvement of LV remodeling and dysfunction. A scar was established in old infarct of control subjects, but in BAF, the infarct wall was thicker because of greater old infarct area, which contained abundant myofibroblasts and vessels. Surprisingly, many of the α-smooth muscle actin–positive myofibroblast-like cells in BAF, making bundles and running parallel to the survived cardiomyocytes, were ultrastructurally mature smooth muscle cells with contractile phenotype. Cardiomyocyte apoptosis in the infarct area was equally rare in each group.

Conclusions—

The postinfarct treatment with BAF improved LV remodeling and dysfunction through inhibition of granulation tissue cell apoptosis. These findings imply a new therapeutic strategy against postinfarct heart failure.
Mapping a Locus for Familial Thoracic Aortic Aneurysms and Dissections (
TAAD2
) to 3p24–25
Authors: Hasham Sumera N. , Willing Marcia C. , Guo Dong-chuan , Muilenburg Ann , He Rumin , Tran Van T. , Scherer Steven E. , Shete Sanjay S. , Milewicz Dianna M.
Published: June 2003

Background—

Familial thoracic aortic aneurysms and dissections (TAAD) occur as part of known syndromes such as Marfan syndrome but can also be inherited in families in an autosomal dominant manner as an isolated condition. Previous studies have mapped genes causing nonsyndromic familial TAAD to 5q13–15 (
TAAD1
) and 11q23.2-q24 (
FAA1
). Further genetic heterogeneity for the condition was evident by the presence of TAAD in some families not linked to these known loci.

Methods and Results—

A 4-generation family with dominant mode of inheritance of TAAD was studied. Affected status was determined by dilation of the ascending aorta, surgical repair of an aneurysm or dissection, or death as the result of aortic dissection. None of the family members evaluated met the diagnostic criteria for Marfan syndrome. After exclusion of known loci for familial TAAD, a genome-wide scan was carried out to map the defective gene causing the disease in the family. A locus was mapped to a 25-cM region on 3p24–25 with a maximum multipoint logarithm of the odds score of 4.28.

Conclusions—

A third locus for nonsyndromic TAAD was mapped to 3p24–25 and termed the
TAAD2
locus. This locus overlaps a previously mapped second locus for Marfan syndrome, termed the
MFS2
locus. Future characterization of the
TAAD2
gene will determine if
TAAD2
is allelic to
MFS2
. In addition, identification of the
TAAD2
gene will improve the presymptomatic diagnosis of individuals with this life-threatening genetic syndrome and provide information concerning the pathogenesis of the disease.
Predictors of Subacute Stent Thrombosis
Authors: Cheneau Edouard , Leborgne Laurent , Mintz Gary S. , Kotani Jun-ichi , Pichard Augusto D. , Satler Lowell F. , Canos Daniel , Castagna Marco , Weissman Neil J. , Waksman Ron
Published: June 2003

Background—

Factors leading to subacute stent thrombosis after percutaneous coronary intervention (PCI) have not been well established. We assessed the pre- and post-PCI intravascular ultrasound (IVUS) characteristics of subacute stent thrombosis.

Methods and Results—

We analyzed 7484 consecutive patients without acute myocardial infarction who were treated with PCI and stenting and underwent IVUS imaging during the intervention. Twenty-seven (0.4%) had angiographically documented subacute closure <1 week after PCI (median time to subacute closure, 24 hours). Subacute closure lesions were compared with a control group (selected to be 3 times the abrupt closer group) matched by procedure date (within 6 months), age, gender, stable or unstable angina, lesion location, and additional treatment (balloon angioplasty or atherectomy). Postintervention IVUS did not identify a cause in 22% and did identify at least 1 cause for abrupt closure in 78% of patients (versus 33% in matched lesions,
P
=0.0002). In 48% of the patients, there were multiple causes in 48% (versus 3% in matched lesions,
P
<0.0001). Causes included dissection (17%), thrombus (4%), and tissue protrusion within the stent struts leading to lumen compromise lumen (4%). A total of 83% of patients with >1 of these abnormal morphologies also had reduced lumen dimensions post-PCI (final lumen <80% reference lumen). Preprocedural lesion characteristics were not different from matched lesions.

Conclusions—

Subacute stent thrombosis is infrequently related to the preintervention lesion characteristics. Inadequate postprocedure lumen dimensions, alone or in combination with other procedurally related abnormal lesion morphologies (dissection, thrombus, or tissue prolapse), contribute to this phenomenon.