bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantitative Analysis of Spatial-Temporal Correlations during Germination of Spores of Bacillus Species
Authors: Zhang Jinqiao , Garner Will , Setlow Peter , Yu Ji
Published: May 2011

Bacteria of
Bacillus
species sporulate upon starvation, and the resultant dormant spores germinate when the environment appears likely to allow the resumption of vegetative growth. Normally, the rates of germination of individual spores in populations are very heterogeneous, and the current work has investigated whether spore-to-spore communication enhances the synchronicity of germination. In order to do this work, time-lapse optical images of thousands of individual spores were captured during germination, and an image analysis algorithm was developed to do the following: (i) measure the positions and germination rates of many thousands of individual spores and (ii) compute pairwise correlations of their germination. This analysis showed that an individual spore's germination rate was dependent on its distance from other spores, especially at short distances. Thus, spores that were within a few micrometers exhibited an increased synchronicity in germination, suggesting that there is a mechanism for short-range communication between such spores during germination. However, two molecules known to be germinants that are released during germination,
l
-alanine and the 1:1 chelate of Ca
2+
and dipicolinic acid, did not mediate spore-to-spore communication during germination.
Complete Genome Sequence of Lactobacillus buchneri NRRL B-30929, a Novel Strain from a Commercial Ethanol Plant
Authors: Liu Siqing , Leathers Timothy D. , Copeland Alex , Chertkov Olga , Goodwin Lynne , Mills David A.
Published: May 2011

Lactobacillus buchneri
strain NRRL B-30929 was a contaminant obtained from a commercial ethanol fermentation. This facultative anaerobe is unique because of its rapid growth on xylose and simultaneous fermentation of xylose and glucose. The strain utilizes a broad range of carbohydrate substrates and possesses a high tolerance to ethanol and other stresses, making it an attractive candidate for bioconversion of biomass substrates to various bioproducts. The genome sequence of NRRL B-30929 will provide insight into the unique properties of this lactic acid bacterium.
Complete Genome Sequence of Bordetella pertussis CS, a Chinese Pertussis Vaccine Strain
Authors: Zhang Shumin , Xu Yinghua , Zhou Zhemin , Wang Shaojing , Yang Ruifu , Wang Junzhi , Wang Lei
Published: May 2011

Bordetella pertussis
is the causative agent of pertussis. Here, we report the genome sequence of
Bordetella pertussis
strain CS, isolated from an infant patient in Beijing and widely used as a vaccine strain for production of an acellular pertussis vaccine in China.
Phosphorylation of Spo0A by the Histidine Kinase KinD Requires the Lipoprotein Med in Bacillus subtilis
Authors: Banse Allison V. , Hobbs Errett C. , Losick Richard
Published: May 2011

The response regulatory protein Spo0A of
Bacillus subtilis
is activated by phosphorylation by multiple histidine kinases via a multicomponent phosphorelay. Here we present evidence that the activity of one of the kinases, KinD, depends on the lipoprotein Med, a mutant of which has been known to cause a cannibalism phenotype. We show that the absence of Med impaired and the overproduction of Med stimulated the transcription of two operons (
sdp
and
skf
) involved in cannibalism whose transcription is known to depend on Spo0A in its phosphorylated state (Spo0A∼P). Further, these effects of Med were dependent on KinD but not on kinases KinA, KinB, and KinC. Additionally, we show that deletion or overproduction of Med impaired or enhanced, respectively, biofilm formation and that these effects, too, depended specifically on KinD. Finally, we report that overproduction of Med bypassed the dominant negative effect on transcription of
sdp
of a truncated KinD retaining the transmembrane segments but lacking the kinase domain. We propose that Med directly or indirectly interacts with KinD in the cytoplasmic membrane and that this interaction is required for KinD-dependent phosphorylation of Spo0A.
Genome Sequence of Pseudomonas sp. Strain S9, an Extracellular Arylsulfatase-Producing Bacterium Isolated from Mangrove Soil
Authors: Long Mengxian , Ruan Lingwei , Yu Ziniu , Xu Xun
Published: May 2011

Pseudomonas
sp. strain S9 was originally isolated from mangrove soil in Xiamen, China. It is an aerobic bacterium which shows extracellular arylsulfatase activity. Here, we describe the 4.8-Mb draft genome sequence of
Pseudomonas
sp. S9, which exhibits novel cysteine-type sulfatases.
Complete Genome Sequence of the Universal Killer Salmonella enterica Serovar Typhimurium UK-1 (ATCC 68169)
Authors: Luo Yingqin , Kong Qingke , Yang Jiseon , Golden Greg , Wanda Soo-Young , Jensen Roderick V. , Ernst Peter B. , Curtiss Roy
Published: May 2011

The
Salmonella enterica
serovar Typhimurium strain UK-1 exhibits the highest invasion and virulence attributes among the most frequently studied strains.
S.
Typhimurium UK-1 has been used as the foundation for developing recombinant vaccines and has been used extensively on virulence and colonization studies in chickens and mice. We describe here the complete genome sequence of
S.
Typhimurium UK-1. Comparative genomics of
Salmonella
Typhimurium will provide insight into factors that determine virulence and invasion.
Genome Sequence of the Algicidal Bacterium Kordia algicida OT-1
Authors: Lee Hyun Sook , Kang Sung Gyun , Kwon Kae Kyoung , Lee Jung-Hyun , Kim Sang-Jin
Published: May 2011

Kordia algicida
OT-1 is an algicidal bacterium against the bloom-forming microalgae. The genome sequence of
K. algicida
revealed a number of interesting features, including the degradation of macromolecules, the biosynthesis of carotenoid pigment and secondary metabolites, and the capacity for gliding motility, which might facilitate the understanding of algicidal mechanisms.
Complete Genome Sequence of
Pusillimonas
sp. T7-7, a Cold-Tolerant Diesel Oil-Degrading Bacterium Isolated from the Bohai Sea in China
Authors: Cao Boyang , Ma Ting , Ren Yan , Ren Yi , Li Guoqiang , Li Ping , Guo Xi , Ding Peng , Feng Lu
Published: May 2011

Pusillimonas
sp. T7-7 is a diesel oil-degrading cold-tolerant bacterium isolated from the benthal mud of a petroleum-contaminated site in Bohai Sea, China. We present here the complete genome sequence of T7-7. Genome analysis revealed many features of typical marine bacteria, including the absence of intact sugar metabolic pathways, the presence of glyoxylate and gluconeogenesis pathways, and the abilities for nitrate assimilation and denitrification, as well as sulfate reduction and sulfite oxidation. The presence of novel genes for the degradation of diesel oils was suggested.
Draft Genome Sequence of Bacteroides vulgatus PC510, a Strain Isolated from Human Feces
Authors: Cuív Páraic Ó , Klaassens Eline S. , Durkin A. Scott , Harkins Derek M. , Foster Les , McCorrison Jamison , Torralba Manolito , Nelson Karen E. , Morrison Mark
Published: May 2011

Although
Bacteroides vulgatus
is one of the most prevalent microorganisms in the human gastrointestinal tract, little is known about the genetic potential of this species. Here, we describe the annotated draft genome sequence of
B. vulgatus
PC510 isolated from human feces.
Genome Sequence of Rhodobacter sphaeroides Strain WS8N
Authors: Porter Steven L. , Wilkinson David A. , Byles Elaine D. , Wadhams George H. , Taylor Stephen , Saunders Nigel J. , Armitage Judith P.
Published: May 2011

Rhodobacter sphaeroides
is a metabolically diverse photosynthetic alphaproteobacterium found ubiquitously in soil and freshwater habitats. Here we present the annotated genome sequence of
R. sphaeroides
WS8N.
Genome Sequences of the Zoonotic Pathogens Chlamydia psittaci 6BC and Cal10
Authors: Grinblat-Huse Valerie , Drabek Elliott F. , Creasy Heather Huot , Daugherty Sean C. , Jones Kristine M. , Santana-Cruz Ivette , Tallon Luke J. , Read Timothy D. , Hatch Thomas P. , Bavoil Patrik , Myers Garry S. A.
Published: May 2011

Chlamydia psittaci
is a highly prevalent avian pathogen and the cause of a potentially lethal zoonosis, causing life-threatening pneumonia in humans. We report the genome sequences of
C. psittaci
6BC, the prototype strain of the species, and
C. psittaci
Cal10, a widely used laboratory strain.
Genome Sequence of the Vertebrate Gut Symbiont Lactobacillus reuteri ATCC 53608
Authors: Heavens Darren , Tailford Louise E. , Crossman Lisa , Jeffers Faye , MacKenzie Donald A. , Caccamo Mario , Juge Nathalie
Published: May 2011

Lactobacillus reuteri
, inhabiting the gastrointestinal tracts of a range of vertebrates, is a true symbiont with effects established as beneficial to the host. Here we describe the draft genome of
L. reuteri
ATCC 53608, isolated from a pig. The genome sequence provides important insights into the evolutionary changes underlying host specialization.
Newcastle Disease Virus-Vectored Rabies Vaccine Is Safe, Highly Immunogenic, and Provides Long-Lasting Protection in Dogs and Cats
Authors: Ge Jinying , Wang Xijun , Tao Lihong , Wen Zhiyuan , Feng Na , Yang Songtao , Xia Xianzhu , Yang Chinglai , Chen Hualan , Bu Zhigao
Published: June 2011

Effective, safe, and affordable rabies vaccines are still being sought. Newcastle disease virus (NDV), an avian paramyxovirus, has shown promise as a vaccine vector for mammals. Here, we generated a recombinant avirulent NDV La Sota strain expressing the rabies virus glycoprotein (RVG) and evaluated its potential to serve as a vaccine against rabies. The recombinant virus, rL-RVG, retained its high-growth property in chicken eggs, with titers of up to 10
9.8
50% egg infective doses (EID
50
)/ml of allantoic fluid. RVG expression enabled rL-RVG to spread from cell to cell in a rabies virus-like manner, and RVG was incorporated on the surface of the rL-RVG viral particle. RVG incorporation did not alter the trypsin-dependent infectivity of the NDV vector in mammalian cells. rL-RVG and La Sota NDV showed similar levels of sensitivity to a neutralization antibody against NDV and similar levels of resistance to a neutralization antibody against rabies virus. Animal studies demonstrated that rL-RVG is safe in several species, including cats and dogs, when administered as multiple high doses of recombinant vaccine. Intramuscular vaccination with rL-RVG induced a substantial rabies virus neutralization antibody response and provided complete protection from challenge with circulating rabies virus strains. Most importantly, rL-RVG induced strong and long-lasting protective neutralization antibody responses to rabies virus in dogs and cats. A low vaccine dose of 10
8.3
EID
50
completely protected dogs from challenge with a circulating strain of rabies virus for more than a year. This is the first study to demonstrate that immunization with an NDV-vectored vaccine can induce long-lasting, systemic protective immunity against rabies.
Structure of the Three N-Terminal Immunoglobulin Domains of the Highly Immunogenic Outer Capsid Protein from a T4-Like Bacteriophage
Authors: Fokine Andrei , Islam Mohammad Z. , Zhang Zhihong , Bowman Valorie D. , Rao Venigalla B. , Rossmann Michael G.
Published: June 2011

The head of bacteriophage T4 is decorated with 155 copies of the highly antigenic outer capsid protein (Hoc). One Hoc molecule binds near the center of each hexameric capsomer. Hoc is dispensable for capsid assembly and has been used to display pathogenic antigens on the surface of T4. Here we report the crystal structure of a protein containing the first three of four domains of Hoc from bacteriophage RB49, a close relative of T4. The structure shows an approximately linear arrangement of the protein domains. Each of these domains has an immunoglobulin-like fold, frequently found in cell attachment molecules. In addition, we report biochemical data suggesting that Hoc can bind to
Escherichia coli
, supporting the hypothesis that Hoc could attach the phage capsids to bacterial surfaces and perhaps also to other organisms. The capacity for such reversible adhesion probably provides survival advantages to the bacteriophage.
Herpes Simplex Virus Immediate-Early Protein ICP0 Is Targeted by SIAH-1 for Proteasomal Degradation
Authors: Nagel Claus-Henning , Albrecht Nina , Milovic-Holm Kristijana , Mariyanna Lakshmikanth , Keyser Britta , Abel Bettina , Weseloh Britta , Hofmann Thomas G. , Eibl Martha M. , Hauber Joachim
Published: June 2011

Herpes simplex virus (HSV) immediate-early protein ICP0 is a transcriptional activator with E3 ubiquitin ligase activity that induces the degradation of ND10 proteins, including the promyelocytic leukemia protein (PML) and Sp100. Moreover, ICP0 has a role in the derepression of viral genomes and in the modulation of the host interferon response to virus infection. Here, we report that ICP0 interacts with SIAH-1, a cellular E3 ubiquitin ligase that is involved in multiple cellular pathways and is itself capable of mediating PML degradation. This novel virus-host interaction profoundly stabilized SIAH-1 and recruited this cellular E3 ligase into ICP0-containing nuclear bodies. Moreover, SIAH-1 mediated the polyubiquitination of HSV ICP0
in vitro
and
in vivo
. After infection of SIAH-1 knockdown cells with HSV, higher levels of ICP0 were produced, ICP0 was less ubiquitinated, and the half-life of this multifunctional viral regulatory protein was increased. These results indicate an inhibitory role of SIAH-1 during lytic infection by targeting ICP0 for proteasomal degradation.
Shared Ancestry between a Newfound Mole-Borne Hantavirus and Hantaviruses Harbored by Cricetid Rodents
Authors: Kang Hae Ji , Bennett Shannon N. , Hope Andrew G. , Cook Joseph A. , Yanagihara Richard
Published: June 2011

Discovery of genetically distinct hantaviruses in multiple species of shrews (order Soricomorpha, family Soricidae) and moles (family Talpidae) contests the conventional view that rodents (order Rodentia, families Muridae and Cricetidae) are the principal reservoir hosts and suggests that the evolutionary history of hantaviruses is far more complex than previously hypothesized. We now report on Rockport virus (RKPV), a hantavirus identified in archival tissues of the eastern mole (
Scalopus aquaticus
) collected in Rockport, TX, in 1986. Pairwise comparison of the full-length S, M, and L genomic segments indicated moderately low sequence similarity between RKPV and other soricomorph-borne hantaviruses. Phylogenetic analyses, using maximum-likelihood and Bayesian methods, showed that RKPV shared a most recent common ancestor with cricetid-rodent-borne hantaviruses. Distributed widely across the eastern United States, the fossorial eastern mole is sympatric and syntopic with cricetid rodents known to harbor hantaviruses, raising the possibility of host-switching events in the distant past. Our findings warrant more-detailed investigations on the dynamics of spillover and cross-species transmission of present-day hantaviruses within communities of rodents and moles.
Economic burden of injuries in South Korea
Authors: Lim Seung-Ji , Chung Woo-Jin , Cho Woo-Hyun
Published: May 2011

Background

Studies on the cost of injury are useful in setting research and policy priorities and it is valuable to observe differences in the economic burden of injuries across countries.

Objective

To estimate the treated prevalence rate, economic burden and gender- and age-specific costs of injuries in Korea in 2006.

Design

Annual direct healthcare costs associated with injuries were estimated from the National Health Insurance, Medical Aid and Automobile Insurance databases. Annual direct non-health costs were estimated for transport and caregiver's costs. Indirect costs were estimated for premature death, absence from work and disability. Costs were adjusted to 2006 levels using the healthcare component of the Consumer Price Index.

Main outcome measures

Prevalence-based direct costs, incidence-based indirect costs and total costs for injuries, stratified by gender, age group and type of injury.

Results

The treated prevalence rate of injury in 2006 of the Korean population was 26.5 per 100, resulting in an annual economic burden of $39 837 million ($4703 million in direct and $35 134 million in indirect costs). The cost of medical treatment associated with injuries accounted for 9.5% of the total health expenditure in Korea. The cost of premature death was the largest contributor to the total and automobile-related injuries accounted for 30.3% of total costs.

Conclusions

The estimates were considerably understated because they did not include losses in household production and quality of life. Nevertheless, the size and main components of the injury burden were identified; this information should aid decision-making about research priorities and improve monitoring of the effects of policy initiatives.
A qualitative investigation of selecting surrogate decision-makers
Authors: Edwards Sarah J L , Brown Patrick , Twyman Matt Amon , Christie Deborah , Rakow Tim
Published: May 2011

Background

Empirical studies of surrogate decision-making tend to assume that surrogates should make only a 'substituted judgement'—that is, judge what the patient would want if they were mentally competent.

Objectives

To explore what people want in a surrogate decision-maker whom they themselves select and to test the assumption that people want their chosen surrogate to make only a substituted judgement.

Methods

30 undergraduate students were recruited. They were presented with a hypothetical scenario about their expected loss of mental capacity in the future and asked to answer some questions about their choice of surrogate. These data were analysed qualitatively using thematic content analysis.

Results

Most respondents talked about choosing someone who was caring and competent in certain ways, giving interesting evidence for their judgements. Surprisingly few highlighted how well they thought their chosen surrogate knew their preferences and would be able to make a substituted judgement. Moreover, few specified that their chosen surrogate had similar attitudes and values to their own and so would make a similar decision to theirs in the circumstances presented. Some respondents also referred to the social role of their chosen surrogate or the social dynamics of their situation which influenced their choices, as well as to ideas of reciprocity and characteristics of honesty and loyalty.

Conclusion

In the event that they lose mental capacity, many people will not select a surrogate to decide about medical treatments on their behalf solely on the basis that they expect their surrogate to make a substituted judgement.
Aptamer selection for the detection ofEscherichia coliK88
Authors: Li Hua , Ding Xinghua , Peng Zhihui , Deng Le , Wang Dan , Chen Hui , He Qizhi
Published: June 2011

In this study, the first group of single-stranded DNA aptamers that are highly specific to enterotoxigenic Escherichia coli (ETEC) K88 was obtained from an enriched oligonucleotide pool by the SELEX (Systematic Evolution of Ligands by Exponential Enrichment) procedure, during which the K88 fimbriae protein was used as the target and bovine serum albumin as counter targets. These aptamers were applied successfully in the detection of ETEC K88. They were then grouped under different families based on the similarity of their secondary structure and the homology of their primary sequence. Four sequences from different families were deliberately chosen for further characterization by fluorescence analysis. Having the advantage of high sensitivity, fluorescence photometry was selected as single-stranded DNA quantification method during the SELEX process. Aptamers with the highest specificity and affinity were analyzed to evaluate binding ability with E. coli. Since ETEC K88 is the only type of bacterium that expressed abundant K88 fimbriae, the selected aptamers against the K88 fimbriae protein were able to specifically identify ETEC K88 among other bacteria. This method of detecting ETEC K88 by aptamers can also be applied to bacteria other than ETEC K88.
Phosphatidylinositol phospholipase C mediates carbon sensing and vegetative nuclear duplication rates inAspergillus nidulans
Authors: Vanzela Ana Paula de Figueiredo Conte , Said Suraia , Prade Rolf Alexander
Published: June 2011

In this work, we disrupted one of three putative phosphatidylinositol phospholipase C genes of Aspergillus nidulans and studied its effect on carbon source sensing linked to vegetative mitotic nuclear division. We showed that glucose does not affect nuclear division rates during early vegetative conidial germination (6–7 h) in either the wild type or the plcA-deficient mutant. Only after 8 h of cultivation on glucose did the mutant strain present some decrease in nuclear duplication. However, decreased nuclear division rates were observed in the wild type when cultivated in media amended with polypectate, whereas our plcA-deficient mutant did not show slow nuclear duplication rates when grown on this carbon source, even though it requires induction and secretion of multiple pectinolytic enzymes to be metabolized. Thus, plcA appears to be directly linked to high-molecular-weight carbon source sensing.
TWO-DIMENSIONAL STATIONARY DYADIC WAVELET TRANSFORM, DECIMATED DYADIC DISCRETE WAVELET TRANSFORM AND THE FACE RECOGNITION APPLICATION
Authors: SUN YANKUI , CHEN YONG , FENG HAO
Published: June 2011

Currently, two-dimensional dyadic wavelet transform (2D-DWT) is habitually considered as the one presented by Mallat, which is defined by an approximation component, two detail components in horizontal and vertical directions. This paper is to introduce a new type of two-dimensional dyadic wavelet transform and its application so that dyadic wavelet can be studied and used widely furthermore. (1) Two-dimensional stationary dyadic wavelet transform (2D-SDWT) is proposed, it is defined by approximation coefficients, detail coefficients in horizontal, vertical and diagonal directions, which is essentially the extension of two-dimensional stationary wavelet transform for orthogonal/biorthogonal wavelet filters. (2) ε-decimated dyadic discrete wavelet transform (DDWT) is introduced and its relation with 2D-SDWT is given, where ε is a sequence of 0's and 1's. (3) Mallat decomposition algorithm based on dyadic wavelet is introduced as a special case of ε-decimated DDWT, and so a face recognition algorithm based on dyadic wavelet is proposed, and experimental results are given to show its effectiveness.
ON BIORTHOGONAL WAVELETS RELATED TO THE WALSH FUNCTIONS
Authors: FARKOV YU. A. , MAKSIMOV A. YU. , STROGANOV S. A.
Published: June 2011

In this paper, we describe an algorithm for computing biorthogonal compactly supported dyadic wavelets related to the Walsh functions on the positive half-line ℝ+. It is noted that a similar technique can be applied in very general situations, e.g., in the case of Cantor and Vilenkin groups. Using the feedback-based approach, some numerical experiments comparing orthogonal and biorthogonal dyadic wavelets with the Haar, Daubechies, and biorthogonal 9/7 wavelets are prepared.
DYNAMICAL PROPERTIES OF A STOCHASTIC TWO-SPECIES SCHOENER'S COMPETITIVE MODEL
Authors: LV JINGLIANG , WANG KE , LIU MENG
Published: June 2011

A stochastic two-species Schoener's competitive model is proposed and investigated. Sufficient conditions for the existence of global positive solutions, boundedness, uniform continuity, global attractivity, stochastic permanence and extinction are obtained. Moreover, the upper-growth rate and the average in time of the sample paths of solutions are also estimated. Finally, some figures are introduced to illustrate the main results.
Abdominal surgery inhibits circulating acyl ghrelin and ghrelin-O-acyltransferase levels in rats: role of the somatostatin receptor subtype 2
Authors: Stengel Andreas , Goebel-Stengel Miriam , Wang Lixin , Shaikh Almaas , Lambrecht Nils W. G. , Rivier Jean , Taché Yvette
Published: June 2011

Clinical studies are evaluating the efficacy of synthetic ghrelin agonists in postoperative ileus management. However, the control of ghrelin secretion under conditions of postoperative gastric ileus is largely unknown. Peripheral somatostatin inhibits ghrelin secretion in animals and humans. We investigated the time course of ghrelin changes postsurgery in fasted rats and whether somatostatin receptor subtype 2 (sst2) signaling is involved. Abdominal surgery (laparotomy and 1-min cecal palpation) induced a rapid and long-lasting decrease in plasma acyl ghrelin levels as shown by the 64, 67, and 59% reduction at 0.5, 2, and 5 h postsurgery, respectively, compared with sham (anesthesia alone for 10 min, P < 0.05). Levels were partly recovered at 7 h and fully restored at 24 h. The percentage of acyl ghrelin reduction was significantly higher than that of desacyl ghrelin at 2 h postsurgery and not at any other time point. This was associated with a 48 and 23% decrease in gastric and plasma ghrelin- O-acyltransferase protein concentrations, respectively ( P < 0.001). Ghrelin-positive cells in the oxyntic mucosa expressed sst2a receptor and the sst2 agonist S-346-011 inhibited fasting acyl ghrelin levels by 64 and 77% at 0.5 and 2 h, respectively. The sst2 antagonist S-406-028 prevented the abdominal surgery-induced decreased circulating acyl ghrelin but not the delayed gastric emptying assessed 0.5 h postinjection. These data show that activation of sst2 receptor located on gastric X/A-like cells plays a key role in the rapid inhibition of circulating acyl ghrelin induced by abdominal surgery while not being primarily involved in the early phase of postoperative gastric ileus.
Ascorbate improves circulation in postural tachycardia syndrome
Authors: Stewart Julian M. , Ocon Anthony J. , Medow Marvin S.
Published: May 2011

Low flow postural tachycardia syndrome (LFP) is associated with vasoconstriction, reduced cardiac output, increased plasma angiotensin II, reduced bioavailable nitric oxide (NO), and oxidative stress. We tested whether ascorbate would improve cutaneous NO and reduce vasoconstriction when delivered systemically. We used local cutaneous heating to 42°C and laser Doppler flowmetry to assess NO-dependent conductance (%CVCmax) to sodium ascorbate and the systemic hemodynamic response to ascorbic acid in 11 LFP patients and in 8 control subjects (aged 23 ± 2 yr). We perfused intradermal microdialysis catheters with sodium ascorbate (10 mM) or Ringer solution. Predrug heat response was reduced in LFP, particularly the NO-dependent plateau phase (56 ± 6 vs. 88 ± 7%CVCmax). Ascorbate increased baseline skin flow in LFP and control subjects and increased the LFP plateau response (82 ± 6 vs. 92 ± 6 control). Systemic infusion experiments used Finometer and ModelFlow to estimate relative cardiac index (CI) and forearm and calf venous occlusion plethysmography to estimate blood flows, peripheral arterial and venous resistances, and capacitance before and after infusing ascorbic acid. CI increased 40% after ascorbate as did peripheral flows. Peripheral resistances were increased (nearly double control) and decreased by nearly 50% after ascorbate. Calf capacitance and venous resistance were decreased compared with control but normalized with ascorbate. These data provide experimental support for the concept that oxidative stress and reduced NO possibly contribute to vasoconstriction and venoconstriction of LFP.
Repeated sauna therapy attenuates ventricular remodeling after myocardial infarction in rats by increasing coronary vascularity of noninfarcted myocardium
Authors: Sobajima Mitsuo , Nozawa Takashi , Shida Takuya , Ohori Takashi , Suzuki Takayuki , Matsuki Akira , Inoue Hiroshi
Published: May 2011

Repeated sauna therapy (ST) increases endothelial nitric oxide synthase (eNOS) activity and improves cardiac function in heart failure as well as peripheral blood flow in ischemic limbs. The present study investigates whether ST can increase coronary vascularity and thus attenuate cardiac remodeling after myocardial infarction (MI). We induced MI by ligating the left coronary artery of Wistar rats. The rats were placed in a far-infrared dry sauna at 41°C for 15 min and then at 34°C for 20 min once daily for 4 wk. Cardiac hemodynamic, histopathological, and gene analyses were performed. Despite the similar sizes of MI between the ST and non-ST groups (51.4 ± 0.3 vs. 51.1 ± 0.2%), ST reduced left ventricular (LV) end-diastolic (9.7 ± 0.4 vs. 10.7 ± 0.5 mm, P < 0.01) and end-systolic (8.6 ± 0.5 vs. 9.6 ± 0.6 mm, P < 0.01) dimensions and attenuated MI-induced increases in LV end-diastolic pressure. Cross-sectional areas of cardiomyocytes were smaller in ST rats and associated with a significant reduction in myocardial atrial natriuretic peptide mRNA levels. Vascular density was reduced in the noninfarcted myocardium of non-ST rats, and the density of cells positive for CD31 and for α-smooth muscle actin was decreased. These decreases were attenuated in ST rats compared with non-ST rats and associated with increases in myocardial eNOS and vascular endothelial growth factor mRNA levels. In conclusion, ST attenuates cardiac remodeling after MI, at least in part, through improving coronary vascularity in the noninfarcted myocardium. Repeated ST might serve as a novel noninvasive therapy for patients with MI.
Assessment of coronary microcirculation in a swine animal model
Authors: Zhang Zhang , Takarada Shigeho , Molloi Sabee
Published: May 2011

Coronary microvascular dysfunction has important prognostic implications. Several hemodynamic indexes, such as coronary flow reserve (CFR), microvascular resistance, and zero-flow pressure (Pzf), were used to establish the most reliable index to assess coronary microcirculation. Fifteen swine were instrumented with a flow probe, and a pressure wire was advanced into the distal left anterior descending artery. Adenosine was used to produce maximum hyperemia. Microspheres were used to create microvascular dysfunction. An occluder was used to produce stenosis. Blood flow from the probe (Q̇p), aortic pressure, distal coronary pressure, and right atrium pressure were recorded. Angiographic flow (Q̇a) was calculated using a time-density curve. Flow probe-based CFR and angiographic CFR were calculated using Q̇p and Q̇a, respectively. Flow probe-based (NMRqh) and angiographic normalized microvascular resistance (NMRah) were determined using Q̇p and Q̇a, respectively, during hyperemia. Pzf was calculated using Q̇p and distal coronary pressure. Two series of receiver operating characteristic curves were generated: normal epicardial artery model (N model) and stenosis model (S model). The areas under the receiver operating characteristic curves for flow probe-based CFR, angiographic CFR, NMRqh, NMRah, and Pzf were 0.855, 0.836, 0.976, 0.956, and 0.855 in N model and 0.737, 0.700, 0.935, 0.889, and 0.698 in S model. Both NMRqh and NMRah were significantly more reliable than CFR and Pzf in detecting the microvascular deterioration. Compared with CFR and Pzf, NMR provided a more accurate assessment of microcirculation. This improved accuracy was more prevalent when stenosis existed. Moreover, NMRah is potentially a less invasive method for assessing coronary microcirculation.
Biochemical and myofilament responses of the right ventricle to severe pulmonary hypertension
Authors: Walker Lori A. , Walker John S. , Glazier Amelia , Brown Dale R. , Stenmark Kurt R. , Buttrick Peter M.
Published: May 2011

Right ventricular (RV) failure is one of the strongest predictors of mortality both in the presence of left ventricular decompensation and in the context of pulmonary vascular disease. Despite this, there is a limited understanding of the biochemical and mechanical characteristics of the pressure-overloaded RV at the level of the cardiac myocyte. To better understand this, we studied ventricular muscle obtained from neonatal calves that were subjected to hypobaric atmospheric conditions, which result in profound pulmonary hypertension. We found that RV pressure overload resulted in significant changes in the phosphorylation of key contractile proteins. Total phosphorylation of troponin I was decreased with pressure overload, predominantly reflecting changes at the putative PKA site at Ser22/23. Similarly, both troponin T and myosin light chain 2 showed a significant decline in phosphorylation. Desmin was unchanged, and myosin-binding protein C (MyBP-C) phosphorylation was apparently increased. However, the apparent increase in MyBP-C phosphorylation was not due to phosphorylation but rather to an increase in MyBP-C total protein. Importantly, these findings were seen in all regions of the RV and were paralleled by reduced Ca2+ sensitivity with preserved maximal Ca2+ saturated developed force normalized to cross-sectional area in isolated skinned right ventricular myocyte fragments. No changes in total force or cooperativity were seen. Taken together, these results suggest that RV failure is mechanistically unique from left ventricular failure.
Rho-kinase: important new therapeutic target in cardiovascular diseases
Authors: Satoh Kimio , Fukumoto Yoshihiro , Shimokawa Hiroaki
Published: May 2011

Rho-kinase (ROCKs) belongs to the family of serine/threonine kinases and is an important downstream effector of the small GTP-binding protein RhoA. There are two isoforms of Rho-kinase, ROCK1 and ROCK2, and they have different functions with ROCK1 for circulating inflammatory cells and ROCK2 for vascular smooth muscle cells. It has been demonstrated that the RhoA/Rho-kinase pathway plays an important role in various fundamental cellular functions, including contraction, motility, proliferation, and apoptosis, leading to the development of cardiovascular disease. The important role of Rho-kinase in vivo has been demonstrated in the pathogenesis of vasospasm, arteriosclerosis, ischemia-reperfusion injury, hypertension, pulmonary hypertension, stroke, and heart failure. Furthermore, the beneficial effects of fasudil, a selective Rho-kinase inhibitor, have been demonstrated for the treatment of several cardiovascular diseases in humans. Thus the Rho-kinase pathway is an important new therapeutic target in cardiovascular medicine.
Both AT1and AT2receptors mediate proliferation and migration of porcine vascular smooth muscle cells
Authors: Louis Sherif , Saward Laura , Zahradka Peter
Published: May 2011

Angiotensin receptor antagonists have shown clinical promise in modulating vascular disease, in part by limiting smooth muscle cell proliferation and migration. The majority of studies examining the contribution of these receptors have been undertaken in cells derived from rat aorta, which primarily express the ANG II type 1 (AT1) receptor. This investigation studied the relative contribution of AT1and ANG II type 2 (AT2) receptors to the mitogenic program of porcine smooth muscle cells. Smooth muscle cells were derived from porcine coronary artery explants. The presence of both AT1and AT2receptors was demonstrated through ligand binding and RT-PCR analysis. Biochemical and cellular markers of proliferation were monitored in the presence of selective receptor antagonists. Smooth muscle cell migration was measured using both wound healing and Boyden chamber migration assays. Visualization of the AT1and AT2receptors in growing and quiescent porcine smooth muscle cells with epifluorescence microscopy demonstrated that their subcellular distribution varied with growth state. An examination with several growth assays revealed that both AT1-specific losartan and AT2-specific PD-123319 receptor antagonists inhibited ANG II-stimulated RNA and DNA synthesis, PCNA expression, and hyperplasia. ANG II induced both directional and nondirectional cell migration. AT1receptor antagonist treatment significantly decreased ANG II-induced directional migration only, whereas AT2receptor antagonist treatment significantly reduced both modes of migration. Interestingly, the focal adhesion kinase inhibitor PF-573228 also blocked migration but not proliferation. Furthermore, focal adhesion kinase activation in response to ANG II was prevented only by PD-123319, indicating that this activation is downstream of the AT2receptor. The observed role of the AT2receptor in ANG II-induced migration was confirmed with smooth muscle cells depleted of the AT2receptor with short hairpin RNA treatment.
Cardiac remodeling caused by transgenic overexpression of a corn Rac gene
Authors: Elnakish Mohammad T. , Awad Mohamed M. , Hassona Mohamed D. H. , Alhaj Mazin A. , Kulkarni Aditi , Citro Lucas A. , Sayyid Muzzammil , Abouelnaga Zeinb A. , El-Sayed Osama , Kuppusamy Periannan , Moldovan Leni , Khan Mahmood , Hassanain Hamdy H.
Published: May 2011

Rac1-GTPase activation plays a key role in the development and progression of cardiac remodeling. Therefore, we engineered a transgenic mouse model by overexpressing cDNA of a constitutively active form of Zea maize Rac gene (ZmRacD) specifically in the hearts of FVB/N mice. Echocardiography and MRI analyses showed cardiac hypertrophy in old transgenic mice, as evidenced by increased left ventricular (LV) mass and LV mass-to-body weight ratio, which are associated with relative ventricular chamber dilation and systolic dysfunction. LV hypertrophy in the hearts of old transgenic mice was further confirmed by an increased heart weight-to-body weight ratio and histopathology analysis. The cardiac remodeling in old transgenic mice was coupled with increased myocardial Rac-GTPase activity (372%) and ROS production (462%). There were also increases in α1-integrin (224%) and β1-integrin (240%) expression. This led to the activation of hypertrophic signaling pathways, e.g., ERK1/2 (295%) and JNK (223%). Pravastatin treatment led to inhibition of Rac-GTPase activity and integrin signaling. Interestingly, activation of ZmRacD expression with thyroxin led to cardiac dilation and systolic dysfunction in adult transgenic mice within 2 wk. In conclusion, this is the first study to show the conservation of Rho/Rac proteins between plant and animal kingdoms in vivo. Additionally, ZmRacD is a novel transgenic model that gradually develops a cardiac phenotype with aging. Furthermore, the shift from cardiac hypertrophy to dilated hearts via thyroxin treatment will provide us with an excellent system to study the temporal changes in cardiac signaling from adaptive to maladaptive hypertrophy and heart failure.
Validation of a patient-specific one-dimensional model of the systemic arterial tree
Authors: Reymond Philippe , Bohraus Yvette , Perren Fabienne , Lazeyras Francois , Stergiopulos Nikos
Published: May 2011

The aim of this study is to develop and validate a patient-specific distributed model of the systemic arterial tree. This model is built using geometric and hemodynamic data measured on a specific person and validated with noninvasive measurements of flow and pressure on the same person, providing thus a patient-specific model and validation. The systemic arterial tree geometry was obtained from MR angiographic measurements. A nonlinear viscoelastic constitutive law for the arterial wall is considered. Arterial wall distensibility is based on literature data and adapted to match the wave propagation velocity of the main arteries of the specific subject, which were estimated by pressure waves traveling time. The intimal shear stress is modeled using the Witzig-Womersley theory. Blood pressure is measured using applanation tonometry and flow rate using transcranial ultrasound and phase-contrast-MRI. The model predicts pressure and flow waveforms in good qualitative and quantitative agreement with the in vivo measurements, in terms of wave shape and specific wave features. Comparison with a generic one-dimensional model shows that the patient-specific model better predicts pressure and flow at specific arterial sites. These results obtained let us conclude that a patient-specific one-dimensional model of the arterial tree is able to predict well pressure and flow waveforms in the main systemic circulation, whereas this is not always the case for a generic one-dimensional model.
Impact of elevated uric acid on ventricular remodeling in infarcted rats with experimental hyperuricemia
Authors: Chen Chien-Chang , Hsu Yu-Jung , Lee Tsung-Ming
Published: May 2011

Hyperuricemia is associated with cardiovascular disease, but it is usually considered a marker rather than a risk factor. Previous studies using uric acid-lowering drugs in normouricemic animals are not suitable to answer the effect of hyperuricemia on ventricular remodeling after myocardial infarction. The purpose of this study was to determine whether hyperuricemia adversely affects ventricular remodeling in infarcted rats with elevated uric acid. Male Wistar rats aged 8 wk were randomly assigned into either vehicle, oxonic acid, oxonic acid + allopurinol, oxonic acid + benzbromarone, oxonic acid + ABT-627, or oxonic acid + tempol for 4 wk starting 24 h after ligation. Postinfarction was associated with increased oxidant production, as measured by myocardial superoxide, isoprostane, xanthine oxidase activity, and dihydroethidium staining. Compared with normouricemic infarcted rats, hyperuricemic infarcted rats had a significant increase of superoxide production (1.7×) and endothelin-1 protein (1.2×) and mRNA (1.4×) expression, which was associated with increased left ventricular dysfunction and enhanced myocardial hypertrophy and fibrosis. These changes were all prevented by treatment with allopurinol. For similar levels of urate lowering, the uricosuric agent benzbromarone had no effect on ventricular remodeling. In spite of equivalent hyperuricemia, the ability of both ABT-627 and tempol to attenuate ventricular remodeling suggested involvement of endothelin-1 and redox pathways. Hyperuricemia is associated with unfavorable ventricular remodeling probably through a superoxide and endothelin-1-dependent pathway. Uric acid lowering without inhibition of superoxide and endothelin-1 may not have an effect on remodeling. Chronic administration of allopurinol, ABT-627, and tempol is associated with attenuated ventricular remodeling.
Increasing dihydrobiopterin causes dysfunction of endothelial nitric oxide synthase in rats in vivo
Authors: Noguchi Katsuhiko , Hamadate Naobumi , Matsuzaki Toshihiro , Sakanashi Mayuko , Nakasone Junko , Uchida Taro , Arakaki Kumiko , Kubota Haruaki , Ishiuchi Shogo , Masuzaki Hiroaki , Sugahara Kazuhiro , Ohya Yusuke , Sakanashi Matao , Tsutsui Masato
Published: May 2011

An elevation of oxidized forms of tetrahydrobiopterin (BH4), especially dihydrobiopterin (BH2), has been reported in the setting of oxidative stress, such as arteriosclerotic/atherosclerotic disorders, where endothelial nitric oxide synthase (eNOS) is dysfunctional, but the role of BH2in the regulation of eNOS activity in vivo remains to be evaluated. This study was designed to clarify whether increasing BH2concentration causes endothelial dysfunction in rats. To increase vascular BH2levels, the BH2precursor sepiapterin (SEP) was intravenously given after the administration of the specific dihydrofolate reductase inhibitor methotrexate (MTX) to block intracellular conversion of BH2to BH4. MTX/SEP treatment did not significantly affect aortic BH4levels compared with control treatment. However, MTX/SEP treatment markedly augmented aortic BH2levels (291.1 ± 29.2 vs. 33.4 ± 6.4 pmol/g, P < 0.01) in association with moderate hypertension. Treatment with MTX alone did not significantly alter blood pressure or BH4levels but decreased the BH4-to-BH2ratio. Treatment with MTX/SEP, but not with MTX alone, impaired ACh-induced vasodilator and depressor responses compared with the control treatment (both P < 0.05) and also aggravated ACh-induced endothelium-dependent relaxations ( P < 0.05) of isolated aortas without affecting sodium nitroprusside-induced endothelium-independent relaxations. Importantly, MTX/SEP treatment significantly enhanced aortic superoxide production, which was diminished by NOS inhibitor treatment, and the impaired ACh-induced relaxations were reversed with SOD ( P < 0.05), suggesting the involvement of eNOS uncoupling. These results indicate, for the first time, that increasing BH2causes eNOS dysfunction in vivo even in the absence of BH4deficiency, demonstrating a novel insight into the regulation of endothelial function.
Aerobic exercise reverses arterial inflammation with aging in mice
Authors: Lesniewski Lisa A. , Durrant Jessica R. , Connell Melanie L. , Henson Grant D. , Black Alexander D. , Donato Anthony J. , Seals Douglas R.
Published: May 2011

We tested the hypothesis that regular aerobic exercise reverses arterial inflammation with aging. When compared with young controls (6.2 ± 0.4 mo; n = 7), old (31.3 ± 0.5 mo; n = 11) male B6D2F1 cage-restricted mice demonstrated increased arterial activation of the proinflammatory transcription factor NF-κB, as indicated by greater aortic phosphorylation of both the inhibitor of NF-κB kinase (IKK) and the p65 subunit of NF-κB (both P < 0.05). Similarly, aortic expression of the proinflammatory cytokines IL-1 and IL-6, IFN-γ, and TNF-α were greater in the old mice (all P < 0.05). Macrophage and T lymphocyte abundance was unchanged with age in the aortic intima and media but was markedly increased in the adventitia and perivascular fat tissue of old mice (all P < 0.05). This proinflammatory arterial phenotype with aging was associated with vascular dysfunction, as reflected by impaired nitric oxide-mediated endothelium-dependent dilation. Voluntary wheel running (10–14 wk) normalized aortic IKK-NF-κB activation, cytokine expression, adventitial and perivascular macrophage infiltration, and vascular function in old mice (32.4 ± 0.3 mo; n = 8) while having no consistent effects in young mice. Short-term voluntary wheel running started late in life reverses arterial inflammation with aging in mice possibly via outside-in actions. These anti-inflammatory effects may play an important role in the amelioration of age-associated vascular dysfunction by regular aerobic exercise.
Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy
Authors: Zhang Yixuan , Janssens Stefan P. , Wingler Kirstin , Schmidt Harald H. H. W. , Moens An L.
Published: May 2011

The pathogenesis of many cardiovascular diseases is associated with reduced nitric oxide (NO) bioavailability and/or increased endothelial NO synthase (eNOS)-dependent superoxide formation. These findings support that restoring and conserving adequate NO signaling in the heart and blood vessels is a promising therapeutic intervention. In particular, modulating eNOS, e.g., through increasing the bioavailability of its substrate and cofactors, enhancing its transcription, and interfering with other modulators of eNOS pathway, such as netrin-1, has a high potential for effective treatments of cardiovascular diseases. This review provides an overview of the possibilities for modulating eNOS and how this may be translated to the clinic in addition to describing the genetic models used to study eNOS modulation.