bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome of Horsepox Virus
Authors: Tulman E. R. , Delhon G. , Afonso C. L. , Lu Z. , Zsak L. , Sandybaev N. T. , Kerembekova U. Z. , Zaitsev V. L. , Kutish G. F. , Rock D. L.
Published: August 2006

Here we present the genomic sequence of horsepox virus (HSPV) isolate MNR-76, an orthopoxvirus (OPV) isolated in 1976 from diseased Mongolian horses. The 212-kbp genome contained 7.5-kbp inverted terminal repeats and lacked extensive terminal tandem repetition. HSPV contained 236 open reading frames (ORFs) with similarity to those in other OPVs, with those in the central 100-kbp region most conserved relative to other OPVs. Phylogenetic analysis of the conserved region indicated that HSPV is closely related to sequenced isolates of vaccinia virus (VACV) and rabbitpox virus, clearly grouping together these VACV-like viruses. Fifty-four HSPV ORFs likely represented fragments of 25 orthologous OPV genes, including in the central region the only known fragmented form of an OPV ribonucleotide reductase large subunit gene. In terminal genomic regions, HSPV lacked full-length homologues of genes variably fragmented in other VACV-like viruses but was unique in fragmentation of the homologue of VACV strain Copenhagen B6R, a gene intact in other known VACV-like viruses. Notably, HSPV contained in terminal genomic regions 17 kbp of OPV-like sequence absent in known VACV-like viruses, including fragments of genes intact in other OPVs and approximately 1.4 kb of sequence present only in cowpox virus (CPXV). HSPV also contained seven full-length genes fragmented or missing in other VACV-like viruses, including intact homologues of the CPXV strain GRI-90 D2L/I4R CrmB and D13L CD30-like tumor necrosis factor receptors, D3L/I3R and C1L ankyrin repeat proteins, B19R kelch-like protein, D7L BTB/POZ domain protein, and B22R variola virus B22R-like protein. These results indicated that HSPV contains unique genomic features likely contributing to a unique virulence/host range phenotype. They also indicated that while closely related to known VACV-like viruses, HSPV contains additional, potentially ancestral sequences absent in other VACV-like viruses.
Translocation of
Tomato Bushy Stunt Virus
P19 Protein into the Nucleus by ALY Proteins Compromises Its Silencing Suppressor Activity
Authors: Canto Tomas , Uhrig Joachim F. , Swanson Maud , Wright Kathryn M. , MacFarlane Stuart A.
Published: August 2006

The P19 protein of
Tomato bushy stunt virus
is a potent suppressor of RNA silencing and, depending on the host species, is required for short- and long-distance virus movement and symptom production. P19 interacts with plant ALY proteins and relocalizes a subset of these proteins from the nucleus to the cytoplasm. Here we showed that coexpression by agroinfiltration in
Nicotiana benthamiana
of P19 and the subset of ALY proteins that are not relocalized from the nucleus interfered with the ability of P19 to suppress RNA silencing. We demonstrated that this interference correlates with the relocation of P19 from the cytoplasm into the nucleus, and by constructing and analyzing chimeric ALY genes, we showed that the C-terminal part of the central, RNA recognition motif of ALY is responsible for interaction with P19, relocalization or nonrelocalization of ALY, and inhibition of silencing suppression by P19. We studied the interaction of ALY and P19 by using the technique of bimolecular fluorescence complementation to show that these proteins associate physically in the nucleus but not detectably in the cytoplasm, and we present a model to explain the dynamics of this interaction.
Complete Genome Sequence of the Broad Host Range Single-Stranded RNA Phage PRR1 Places It in the
Levivirus
Genus with Characteristics Shared with Alloleviviruses
Authors: Ruokoranta Tanja M. , Grahn A. Marika , Ravantti Janne J. , Poranen Minna M. , Bamford Dennis H.
Published: August 2006

Single-stranded RNA (ssRNA) bacteriophages of the family
Leviviridae
infect gram-negative bacteria. They are restricted to a single host genus. Phage PRR1 is an exception, having a broad host range due to the promiscuity of the receptor encoded by the IncP plasmid. Here we report the complete genome sequence of PRR1. Three proteins homologous with those of other ssRNA phages, i.e., maturation, coat, and replicase proteins, were identified. A fourth protein has a lysis function. Comparison of PRR1 with other members of the
Leviviridae
family places PRR1 in the genus
Levivirus
with some characteristics more similar to those of members of the genus
Allolevivirus
.
The Virion Host Shutoff Protein (U
L
41) of Herpes Simplex Virus 1 Is an Endoribonuclease with a Substrate Specificity Similar to That of RNase A
Authors: Taddeo Brunella , Roizman Bernard
Published: August 2006

Earlier, our laboratory reported that purified glutathione
S
-transferase-virion host shutoff (GST-
vhs
) protein exhibited endoribonucleolytic activity in in vitro assays using as substrates in vitro-transcribed regions of IEX-1 mRNA. Here, we report that studies of the cleavage patterns of synthetic RNA oligonucleotides defined the activity of GST-
vhs
as being similar to that of RNase A. Thus, GST-
vhs
cleaved the RNA at the 3′ end of single-stranded cytidine and uridine residues. Since the GST-m
vhs
nuclease-defective mutant protein failed to cleave the synthetic RNAs, the results unambiguously attribute the activity to
vhs
.
Vaccinia Virus Entry into Cells via a Low-pH-Dependent Endosomal Pathway
Authors: Townsley Alan C. , Weisberg Andrea S. , Wagenaar Timothy R. , Moss Bernard
Published: August 2006

Previous studies established that vaccinia virus could enter cells by fusion with the plasma membrane at neutral pH. However, low pH triggers fusion of vaccinia virus-infected cells, a hallmark of viruses that enter by the endosomal route. Here, we demonstrate that entry of mature vaccinia virions is accelerated by brief low-pH treatment and severely reduced by inhibitors of endosomal acidification, providing evidence for a predominant low-pH-dependent endosomal pathway. Entry of vaccinia virus cores into the cytoplasm, measured by expression of firefly luciferase, was increased more than 10-fold by exposure to a pH of 4.0 to 5.5. Furthermore, the inhibitors of endosomal acidification bafilomycin A1, concanamycin A, and monensin each lowered virus entry by more than 70%. This reduction was largely overcome by low-pH-induced entry through the plasma membrane, confirming the specificities of the drugs. Entry of vaccinia virus cores with or without brief low-pH treatment was visualized by electron microscopy of thin sections of immunogold-stained cells. Although some virus particles fused with the plasma membrane at neutral pH, 30 times more fusions and a greater number of cytoplasmic cores were seen within minutes after low-pH treatment. Without low-pH exposure, the number of released cores lagged behind the number of virions in vesicles until 30 min posttreatment, when they became approximately equal, perhaps reflecting the time of endosome acidification and virus fusion. The choice of two distinct pathways may contribute to the ability of vaccinia virus to enter a wide range of cells.
Crystal Structure of the Receptor-Binding Protein Head Domain from
Lactococcus lactis
Phage bIL170
Authors: Ricagno Stefano , Campanacci Valérie , Blangy Stéphanie , Spinelli Silvia , Tremblay Denise , Moineau Sylvain , Tegoni Mariella , Cambillau Christian
Published: August 2006

Lactococcus lactis
, a gram-positive bacterium widely used by the dairy industry, is subject to lytic phage infections. In the first step of infection, phages recognize the host saccharidic receptor using their receptor binding protein (RBP). Here, we report the 2.30-Å-resolution crystal structure of the RBP head domain from phage bIL170. The structure of the head monomer is remarkably close to those of other lactococcal phages, p2 and TP901-1, despite any sequence identity with them. The knowledge of the three-dimensional structures of three RBPs gives a better insight into the module exchanges which have occurred among phages.
Poxvirus Tumor Necrosis Factor Receptor (TNFR)-Like T2 Proteins Contain a Conserved Preligand Assembly Domain That Inhibits Cellular TNFR1-Induced Cell Death
Authors: Sedger Lisa M. , Osvath Sarah R. , Xu Xiao-Ming , Li Grace , Chan Francis K.-M. , Barrett John W. , McFadden Grant
Published: August 2006

The poxvirus tumor necrosis factor receptor (TNFR) homologue T2 has immunomodulatory properties; secreted myxoma virus T2 (M-T2) protein binds and inhibits rabbit TNF-α, while intracellular M-T2 blocks virus-induced lymphocyte apoptosis. Here, we define the antiapoptotic function as inhibition of TNFR-mediated death via a highly conserved viral preligand assembly domain (vPLAD). Jurkat cell lines constitutively expressing M-T2 were generated and shown to be resistant to UV irradiation-, etoposide-, and cycloheximide-induced death. These cells were also resistant to human TNF-α, but M-T2 expression did not alter surface expression levels of TNFRs. Previous studies indicated that T2's antiapoptotic function was conferred by the N-terminal region of the protein, and further examination of this region revealed a highly conserved N-terminal vPLAD, which is present in all poxvirus T2-like molecules. In cellular TNFRs and TNF-α-related apoptosis-inducing ligand (TRAIL) receptors (TRAILRs), PLAD controls receptor signaling competency prior to ligand binding. Here, we show that M-T2 potently inhibits TNFR1-induced death in a manner requiring the M-T2 vPLAD. Furthermore, we demonstrate that M-T2 physically associates with and colocalizes with human TNFRs but does not prevent human TNF-α binding to cellular receptors. Thus, M-T2 vPLAD is a species-nonspecific dominant-negative inhibitor of cellular TNFR1 function. Given that the PLAD is conserved in all known poxvirus T2-like molecules, we predict that it plays an important function in each of these proteins. Moreover, that the vPLAD confers an important antiapoptotic function confirms this domain as a potential target in the development of the next generation of TNF-α/TNFR therapeutics.
Herpes Simplex Virus Type 1 Latently Infected Neurons Differentially Express Latency-Associated and ICP0 Transcripts
Authors: Maillet Séverine , Naas Thierry , Crepin Sophie , Roque-Afonso Anne-Marie , Lafay Florence , Efstathiou Stacey , Labetoulle Marc
Published: August 2006

During the latent phase of herpes simplex virus type 1 (HSV-1) infection, the latency-associated transcripts (LATs) are the most abundant viral transcripts present in neurons, but some immediate-early viral transcripts, such as those encoding ICP0, have also been reported to be transcribed in latently infected mouse trigeminal ganglia (TG). A murine oro-ocular model of herpetic infection was used to study
ICP0
gene expression in the major anatomical sites of HSV-1 latency, including the TG, superior cervical ganglion, spinal cord, and hypothalamus. An HSV-1 recombinant strain, SC16 110LacZ, revealed ICP0 promoter activity in several neurons in latently infected ganglia, and following infection with wild-type HSV-1 strain SC16, in situ hybridization analyses identified ICP0 transcripts in the nuclei of neurons at times consistent with the establishment of latency. Reverse transcription (RT)-PCR assays performed on RNA extracted from latently infected tissues indicated that ICP0 transcripts were detected in all anatomical sites of viral latency. Furthermore, quantitative real-time RT-PCR showed that neurons differentially expressed the LATs and ICP0 transcripts, with splicing of ICP0 transcripts being dependent on the anatomical location of latency. Finally, TG neurons were characterized by high-level expression of LATs and detection of abundant unspliced ICP0 transcripts, a pattern markedly different from those of other anatomical sites of HSV-1 latency. These results suggest that LATs might be involved in the maintenance of HSV-1 latency through the posttranscriptional regulation of ICP0 in order to inhibit expression of this potent activator of gene expression during latency.
Rhesus Macaque Polyclonal and Monoclonal Antibodies Inhibit Simian Immunodeficiency Virus in the Presence of Human or Autologous Rhesus Effector Cells
Authors: Forthal Donald N. , Landucci Gary , Cole Kelly Stefano , Marthas Marta , Becerra Juan C. , Van Rompay Koen
Published: August 2006

Although antibodies can prevent or modulate lentivirus infections in nonhuman primates, the biological functions of antibody responsible for such effects are not known. We sought to determine the role of antibody-dependent cell-mediated virus inhibition (ADCVI), an antibody function that inhibits virus yield from infected cells in the presence of Fc receptor-bearing effector cells, in preventing or controlling SIVmac251 infection in rhesus macaques (Macaca mulatta). Using CEMx174 cells infected with simian immunodeficiency virus mac251 (SIVmac251), both polyclonal and monoclonal anti-SIV antibodies were capable of potent virus inhibition in the presence of human peripheral blood mononuclear cell (PBMC) effector cells. In the absence of effector cells, virus inhibition was generally very poor. PBMCs from healthy rhesus macaques were also capable of mediating virus inhibition either against SIVmac251-infected CEMx174 cells or against infected, autologous rhesus target cells. We identified both CD14+cells and, to a lesser extent, CD8+cells as the effector cell population in the rhesus PBMCs. Finally, pooled, nonneutralizing SIV-antibody-positive serum, shown in a previous study to prevent infection of neonatal macaques after oral SIVmac251 challenge, had potent virus-inhibitory activity in the presence of effector cells; intact immunoglobulin G, rather than F(ab′)2, was required for such activity. This is the first demonstration of both humoral and cellular ADCVI functions in the macaque-SIV model. ADCVI activity in nonneutralizing serum that prevents SIV infection suggests that ADCVI may be a protective immune function. Finally, our data underscore the potential importance of Fc-Fc receptor interactions in mediating biological activities of antibody.
Use of Stents to Treat Intracranial Cerebrovascular Disease
Authors: Meyers Philip M. , Schumacher H. Christian , Tanji Kurenai , Higashida Randall T. , Caplan Louis R.
Published: August 2006

Intracranial atherosclerosis is a common cause of stroke. Although it has been recognized for decades, the lack of successful treatment strategies has limited clinical interest until recently. We review the natural history and pathophysiology of intracranial atherosclerosis. Vascular biomechanics are important to define differences between cerebral arteries and extracranial vessels and partly explain the technical challenges facing cerebral artery revascularization as compared with revascularization of coronary arteries. Pharmacological interventions to prevent stroke have had limited success, but technological developments offer improved methods for endovascular revascularization of symptomatic and asymptomatic cerebral artery stenosis. Identification of appropriate candidates for treatment also remains a challenge, and our knowledge about the natural history of the disease is limited. At this time, patients with significant intracranial stenosis should receive information on the benefits and risks of revascularization therapy. Determining which patients should undergo revascularization procedures will require carefully planned, randomized clinical trials.
mTOR Pathway as a Target in Tissue Hypertrophy
Authors: Lee Chung-Han , Inoki Ken , Guan Kun-Liang
Published: August 2006

Recent work has shown that the mTOR (mammalian target of rapamycin) pathway is an integral cell growth regulator. The mTOR pathway involves two functional complexes, TORC1 and TORC2, which have been defined by both their association with raptor or rictor, respectively, and their sensitivity to short-term rapamycin inhibition. Loss of tumor suppressors TSC1 or TSC2 leads to aberrant activation of TORC1, which has been implicated in the control of cell size. As a result, both physiologic and pathologic tissue hypertrophy are associated with TORC1 activation. Some clinical examples include skeletal and cardiac muscle hypertrophy, vascular restenosis, and compensatory nephrotic hypertrophy. Clarification of the mTOR pathway may lead to increased understanding of both the etiology and consequences of aberrant cell size regulation. This review covers some of the biochemical regulation of the mTOR pathway that may be important to the regulation of cell size, and it will present several potential clinical applications where the control of cell size may be biologically significant.
Ketogenic HMGCS2 Is a c-Myc Target Gene Expressed in Differentiated Cells of Human Colonic Epithelium and Down-Regulated in Colon Cancer
Authors: Camarero Nuria , Mascaró Cristina , Mayordomo Cristina , Vilardell Felip , Haro Diego , Marrero Pedro F.
Published: August 2006

HMGCS2, the gene that regulates ketone body production, is expressed in liver and several extrahepatic tissues, such as the colon. In CaCo-2 colonic epithelial cells, the expression of this gene increases with cell differentiation. Accordingly, immunohistochemistry with specific antibodies shows that HMGCS2 is expressed mainly in differentiated cells of human colonic epithelium. Here, we used a chromatin immunoprecipitation assay to study the molecular mechanism responsible for this expression pattern. The assay revealed that HMGCS2 is a direct target of c-Myc, which represses HMGCS2 transcriptional activity. c-Myc transrepression is mediated by blockade of the transactivating activity of Miz-1, which occurs mainly through a Sp1-binding site in the proximal promoter of the gene. Accordingly, the expression of human HMGCS2 is down-regulated in 90% of Myc-dependent colon and rectum tumors. HMGCS2 protein expression is down-regulated preferentially in moderately and poorly differentiated carcinomas. In addition, it is also down-regulated in 80% of small intestine Myc-independent tumors. Based on these findings, we propose that ketogenesis is an undesirable metabolic characteristic of the proliferating cell, which is down-regulated through c-Myc-mediated repression of the key metabolic gene HMGCS2. (Mol Cancer Res 2006;4(9):645–53)
Protein Kinase-ζ Inhibits Collagen I–Dependent and Anchorage-Independent Growth and Enhances Apoptosis of Human Caco-2 Cells
Authors: Mustafi Reba , Cerda Sonia , Chumsangsri Anusara , Fichera Alessandro , Bissonnette Marc
Published: August 2006

Colonic carcinogenesis is accompanied by abnormalities in multiple signal transduction components, including alterations in protein kinase C (PKC). The expression level of PKC-ζ, an atypical PKC isoform, increases from the crypt base to the luminal surface and parallels crypt cell differentiation in normal colon. In prior studies in the azoxymethane model of colon cancer, we showed that PKC-ζ was down-regulated in rat colonic tumors. In this study, we showed that PKC-ζ is expressed predominantly in colonic epithelial and not stromal cells, and loss of PKC-ζ occurs as early as the adenoma stage in human colonic carcinogenesis. To assess the regulation of growth and differentiation by PKC-ζ, we altered this isoform in human Caco-2 colon cancer cells using stable constitutive or inducible expression vectors, specific peptide inhibitors or small interfering RNA. In ecdysone-regulated transfectants grown on collagen I, ponasterone A significantly induced PKC-ζ expression to 135% of empty vector cells, but did not alter nontargeted PKC isoforms. This up-regulation was accompanied by a 2-fold increase in basal and 4-fold increase in insulin-stimulated PKC-ζ biochemical activity. Furthermore, PKC-ζ up-regulation caused >50% inhibition of cell proliferation on collagen I (P < 0.05). Increased PKC-ζ also significantly enhanced Caco-2 cell differentiation, nearly doubling alkaline phosphatase activity, while inducing a 3-fold increase in the rate of apoptosis (P < 0.05). In contrast, knockdown of this isoform by small interfering RNA or kinase inhibition by myristoylated pseudosubstrate significantly and dose-dependently increased Caco-2 cell growth on collagen I. In transformation assays, constitutively up-regulated wild-type PKC-ζ significantly inhibited Caco-2 cell growth in soft agar, whereas a kinase-dead mutant caused a 3-fold increase in soft agar growth (P < 0.05). Taken together, these studies indicate that PKC-ζ inhibits colon cancer cell growth and enhances differentiation and apoptosis, while inhibiting the transformed phenotype of these cells. The observed down-regulation of this growth-suppressing PKC isoform in colonic carcinogenesis would be predicted to contribute to tumorigenesis. (Mol Cancer Res 2006;4(9):683–94)
Angiotensin II Type 1 Receptor Blockade Attenuates In-Stent Restenosis by Inhibiting Inflammation and Progenitor Cells
Authors: Ohtani Kisho , Egashira Kensuke , Ihara Yoshiko , Nakano Kaku , Funakoshi Kouta , Zhao Gang , Sata Masataka , Sunagawa Kenji
Published: August 2006

The precise mechanism by which angiotensin II type 1 receptor blocker reduces in-stent restenosis in clinical trials is unclear. We, therefore, investigated the mechanism of in-stent neointima formation. Male cynomolgus monkeys and rabbits were fed a high-cholesterol diet and were allocated to untreated control and type 1 receptor blocker groups. Five days after grouping, multilink stents were implanted in the iliac artery. The type 1 receptor blocker reduced the development of in-stent neointima formation by ≈30% in rabbits and monkeys. To investigate potential mechanisms, we examined the expression of renin-angiotensin system markers, all of which increased in monocytes and smooth muscle-like cells in the neointima and media within 7 days. The type 1 receptor blocker attenuated increased oxidative stress, the enhanced expression of markers of the rennin-angiotensin system and monocyte chemoattractant protein-1, and macrophage infiltration. The effects of type 1 receptor blocker on the differentiation of peripheral blood mononuclear cells into vascular progenitor cells were also examined. Treatment with type 1 receptor blocker suppressed the enhanced differentiation to smooth muscle progenitor cells induced by stenting. The type 1 receptor blocker attenuated in-stent neointima formation by inhibiting redox-sensitive inflammatory changes and by reducing recruitment of the progenitor cells. These potential actions of type 1 receptor blocker on inflammation and progenitor cells constitute a novel mechanism of suppression of in-stent restenosis by type 1 receptor blocker.
Endothelial NO Synthase Gene Polymorphisms and Hypertension
Authors: Zintzaras Elias , Kitsios Georgios , Stefanidis Ioannis
Published: August 2006

Studies investigated the association between endothelial NO synthase gene polymorphisms and hypertension-reported contradicted or nonconclusive results. A meta-analysis of 35 genetic association studies that examined the relation between hypertension and the G894T, 4a/b, T786C, and G23T polymorphisms of the endothelial nitric oxide synthase gene was carried out. Subgroup analysis by ethnicity and potential sources of heterogeneity and bias were explored. The meta-analysis included genotype data on 7779/10 498, 2216/3222, 2491/3913, and 833/587 cases/controls for G894T, 4b/a, T786C, and G23T, respectively. For the 4b/a polymorphism, overall, the heterogeneity between studies was not significant (
P
=0.82), and the allele b was associated with a 15% decreased risk of hypertension relative to allele a (odds ratio: 0.85; 95% CI: 0.74 to 0.98). Overall and in whites, the recessive model for allele b produced significant results (odds ratios: 0.78; 95% CI: 0.68 to 0.90 and OR: 0.76 95% CI: 0.62 to 0.92, respectively), whereas the dominant model produced nonsignificant results. In studies involved East Asians and blacks, an association was not demonstrated. Regarding the G894T, T768C, and G23T polymorphisms, in no case (ie, overall, in whites, or in East Asians) was a statistically significant association and heterogeneity found. There was no substantial source of bias in the selected studies. In conclusion, there is evidence of association only between 4b/a polymorphism and hypertension; however, studies exploring combinations of the polymorphisms may help us better understand the genetics of hypertension.
Hypertension Produced by Reductions in Uterine Perfusion in the Pregnant Rat
Authors: Gadonski Giovani , LaMarca B. Babbette D. , Sullivan Elizabeth , Bennett William , Chandler Derrick , Granger Joey P.
Published: August 2006

The purpose of this study was to determine the role of interleukin (IL) 6 in mediating the increase in arterial pressure (AP) in response to chronic reductions in uterine perfusion pressure (RUPP) in pregnant rats. AP was higher in RUPP rats (138±1 mm Hg) than in normal pregnant (NP) rats (104±1 mm Hg). Serum IL-6 levels in the RUPP rats were 104.5±28.6 pg/mL as compared with 36.6±7.4 pg/mL in NP rats. To determine the long-term effects of a 2- to 3-fold elevation in plasma IL-6 on renal function and AP in pregnant rats, we infused IL-6 for 5 days (2.5 ng/day) in NP rats starting at day 14 of gestation. Five days later, serum IL-6 levels were 55.5±6.5 pg/mL in the control NP rats and 157.0±36.1 pg/mL in the IL-6–treated NP rats. AP was higher in the IL-6–treated NP rats (115±3 mm Hg) as compared with NP controls (101±1 mm Hg) at day 19 of gestation. Renal plasma flow and GFR were lower in the IL-6–treated NP rats than in the NP group. IL-6 increased plasma renin activity but did not affect endothelin in IL-6–treated NP rats. In contrast to the NP rats, IL-6 had no effect on AP or renal hemodynamics in virgin rats. In summary, these data indicate that plasma IL-6 is elevated in response to chronic reductions in uterine perfusion in pregnant rats and that a comparable elevation in plasma IL-6 increases AP and reduces renal function in pregnant rats.
Endothelial Function Is Associated With Pulse Pressure, Pulse Wave Velocity, and Augmentation Index in Healthy Humans
Authors: McEniery Carmel M. , Wallace Sharon , Mackenzie Isla S. , McDonnell Barry , Yasmin  , Newby David E. , Cockcroft John R. , Wilkinson Ian B.
Published: August 2006

Arterial stiffness is an independent predictor of mortality and is regulated by a number of factors, including vascular smooth muscle tone. However, the relationship between endothelial function and definitive measures of arterial stiffness and wave reflections has not been described in healthy individuals. Therefore, we tested the hypothesis that endothelial function is inversely correlated with aortic pulse wave velocity (PWV), central pulse pressure, and augmentation index in healthy individuals. Peripheral and central pulse pressure and augmentation index were determined at rest, and global endothelial function was measured using pulse wave analysis and administration of sublingual nitroglycerin and inhaled albuterol. Aortic PWV was also determined at baseline in a subset of 89 subjects. In a separate group of subjects (n=89), aortic PWV was measured and brachial artery flow-mediated dilatation assessed as a measure of conduit artery endothelial function. Global endothelial function was significantly and inversely correlated with aortic PWV (
r
=−0.69;
P
<0.001), augmentation index (
r
=−0.59;
P
<0.001), and central (
r
=−0.34;
P
<0.001) and peripheral pulse pressure (
r
=−0.15;
P
=0.03). Moreover, there was a stronger correlation between central rather than peripheral pulse pressure. After adjusting for potential confounders, global endothelial function remained independently and inversely associated with aortic PWV and augmentation index. There was also a significant, inverse relationship between conduit artery endothelial function and aortic PWV (
r
=0.39,
P
<0.001), which remained independent after adjusting for confounding factors. In healthy individuals, a decline in endothelial function is associated with increased large artery stiffness, wave reflections, and central pulse pressure.
Familial Sudden Death Is an Important Risk Factor for Primary Ventricular Fibrillation
Authors: Dekker Lukas R.C. , Bezzina Connie R. , Henriques José P.S. , Tanck Michael W. , Koch Karel T. , Alings Marco W. , Arnold Alfred E.R. , de Boer Menko-Jan , Gorgels Anton P.M. , Michels H. Rolf , Verkerk Agnes , Verheugt Freek W.A. , Zijlstra Felix , Wilde Arthur A.M.
Published: August 2006

Background—

Primary ventricular fibrillation (VF) accounts for the majority of deaths during the acute phase of myocardial infarction. Identification of patients at risk for primary VF remains very poor.

Methods and Results—

We performed a case-control study in patients with a first ST-elevation myocardial infarction (STEMI) to identify independent risk factors for primary VF. A total of 330 primary VF survivors (cases) and 372 controls were included; patients with earlier infarcts or signs of structural heart disease were excluded. Baseline characteristics, including age, gender, drug use, and ECG parameters registered well before the index infarction, as well as medical history, were not different. Infarct size and location, culprit coronary artery, and presence of multivessel disease were similar between groups. Analysis of ECGs performed at hospital admission for the index STEMI revealed that cumulative ST deviation was significantly higher among cases (OR per 10-mm ST deviation 1.59, 95% CI 1.25 to 2.02). Analysis of medical histories among parents and siblings showed that the prevalence of cardiovascular disease was similar between cases and controls (73.1% and 73.0%, respectively); however, familial sudden death occurred significantly more frequently among cases than controls (43.1% and 25.1%, respectively; OR 2.72, 95% CI 1.84 to 4.03).

Conclusions—

In a population of STEMI patients, the risk of primary VF is determined by cumulative ST deviation and family history of sudden death.
B-Type Natriuretic Peptide Predicts Adverse Cardiovascular Events in Pediatric Outpatients With Chronic Left Ventricular Systolic Dysfunction
Authors: Price Jack F. , Thomas Anne K. , Grenier Michelle , Eidem Benjamin W. , Smith E. O’Brian , Denfield Susan W. , Towbin Jeffrey A. , Dreyer William J.
Published: August 2006

Background—

Plasma B-type natriuretic peptide (BNP) levels are elevated in adults with heart failure and correlate with functional classification and prognosis. The range and predictive power of BNP concentrations in children with chronic heart failure, however, are not known.

Methods and Results—

Whole blood BNP concentrations were measured in 53 consecutive patients with chronic left ventricular (LV) systolic dysfunction (biventricular hearts, ejection fraction <50%, >3 months since diagnosis). Children who had been hospitalized within 3 months before potential enrollment and those <2 months or >21 years of age were excluded. BNP concentrations were measured with the Triage assay (Biosite Diagnostics, Inc, San Diego, Calif). Echocardiographers and clinicians were blinded to BNP levels. An adverse cardiovascular event was defined as cardiac death, cardiac-related hospitalization, or listing for cardiac transplantation. The median age of patients with LV dysfunction was 9.3 years (interquartile range [IQR], 2.7 to 15.1 years). BNP levels were elevated in children with LV dysfunction compared with healthy controls (median, 78 pg/mL [IQR, 22 to 551 pg/mL] versus median, 7 pg/mL [IQR, 5 to 11 pg/mL];
P
<0.0001). Whole blood BNP concentrations were increased in patients who had a 90-day adverse cardiovascular event compared with those who did not (median, 735 pg/mL [IQR, 685 to 1510 pg/mL] versus median, 37 pg/mL [IQR, 14 to 92 pg/mL];
P
<0.001). Patients with a BNP concentration ≥300 pg/mL were at increased risk of death, hospitalization, or listing for cardiac transplantation (adjusted hazard ratio, 63.6;
P
<0.0001).

Conclusions—

BNP concentrations are elevated in children with chronic LV systolic dysfunction and predict the 90-day composite end point of death, hospitalization, or listing for cardiac transplantation.
Both Hepatic and Extrahepatic ABCA1 Have Discrete and Essential Functions in the Maintenance of Plasma High-Density Lipoprotein Cholesterol Levels In Vivo
Authors: Singaraja Roshni R. , Van Eck Miranda , Bissada Nagat , Zimetti Francesca , Collins Heidi L. , Hildebrand Reeni B. , Hayden Anna , Brunham Liam R. , Kang Martin H. , Fruchart Jean-Charles , Van Berkel Theo J.C. , Parks John S. , Staels Bart , Rothblat George H. , Fiévet Catherine , Hayden Michael R.
Published: August 2006

Background—

Extrahepatic tissues have long been considered critical contributors of cholesterol to nascent HDL particles in the reverse cholesterol transport pathway, in which ABCA1 plays the crucial role. Recent studies, however, including both overexpression and deletion of ABCA1 selectively in the liver, have highlighted the primary role of the liver in the maintenance of HDL levels in vivo.

Methods and Results—

The availability of mice with complete deletion of ABCA1 (total knockout [TKO]) and with liver-specific deletion of ABCA1 (LSKO) has enabled us to dissect the discrete roles of hepatic relative to extrahepatic ABCA1 in HDL biogenesis. Delivery of adenoviral ABCA1 resulted in selective expression of physiological levels of ABCA1 in the livers of both LSKO and TKO mice, resulting in increased HDL cholesterol (HDL-C). Expression of ABCA1 in the liver of LSKO mice resulted in plasma HDL-C levels that were similar to those in wild-type mice and significantly above those seen in similarly treated TKO mice. HDL particles from ABCA1-expressing LSKO mice were larger and contained significantly increased cholesterol compared with TKO mice. Infusion of human apolipoprotein A-I/phospholipid reconstituted HDL particles normalized plasma HDL-C levels in LSKO mice but had no effect on HDL-C levels in TKO mice.

Conclusions—

Although hepatic ABCA1 appears crucial for phospholipid transport, extrahepatic tissues play an important role in cholesterol transfer to nascent HDL particles. These data highlight the discrete and specific roles of both liver and extrahepatic ABCA1 in HDL biogenesis in vivo and indicate that ABCA1 shows lipid cargo selectivity depending on its site of expression.
AVE0118, Blocker of the Transient Outward Current (
I
to
) and Ultrarapid Delayed Rectifier Current (
I
Kur
), Fully Restores Atrial Contractility After Cardioversion of Atrial Fibrillation in the Goat
Authors: de Haan Sunniva , Greiser Maura , Harks Erik , Blaauw Yuri , van Hunnik Arne , Verheule Sander , Allessie Maurits , Schotten Ulrich
Published: August 2006

Background—

The loss of atrial contractile function after cardioversion of atrial fibrillation (AF) contributes to the thromboembolic risk associated with AF. The newly developed blocker of the transient outward current (
I
to
) and ultrarapid delayed rectifier current (
I
Kur
) AVE0118 prolongs atrial action potential duration and might therefore enhance atrial contractility. We compared the ability of AVE0118 to restore atrial contraction after cardioversion of AF with the efficacy of conventional positive inotropic compounds in the goat model of AF.

Methods and Results—

Eighteen goats were chronically instrumented with epicardial electrodes, a pressure transducer in the right atrium, and piezoelectric crystals to measure right atrial diameter. Atrial contractility and refractoriness and QT duration were measured before and after 1 week (3 to 8 days) of AF induced by repetitive burst pacing. The measurements were repeated after administration of digoxin (0.02 mg/kg), dobutamine (5 μg · kg
−1
· min
−1
), the Ca
2+
sensitizer EMD57033 (1 mg · kg
−1
· min
−1
), the L-type Ca
2+
channel agonist BayY5959 (0.1 mg · kg
−1
· min
−1
), and AVE0118 (0.01 to 0.2 mg · kg
−1
· min
−1
). The effect of AVE0118 on the configuration of atrial monophasic action potentials was determined for comparison. After 1 week of AF, atrial contractility during sinus rhythm or slow atrial pacing was reduced to <10%. Digoxin and dobutamine failed to increase atrial contractility. EMD57033 restored 41% and BayY5959 restored 48% of atrial contractility at baseline. BayY5959 significantly prolonged QT duration by 24.7%. AVE0118 enhanced atrial contraction to 156% of the baseline value. The positive inotropic effect was accompanied by a pronounced prolongation of atrial action potential duration and refractoriness, whereas QT duration remained unchanged.

Conclusions—

Conventional positive inotropic drugs showed limited effect on atrial contractility after cardioversion of AF or produced QT prolongation. In contrast, the
I
to
/
I
Kur
blocker AVE0118 fully restored atrial contraction without proarrhythmic effects on the ventricle.
Community Attachments as Predictors of Local Environmental Concern
Authors: Brehm Joan M. , Eisenhauer Brian W. , Krannich Richard S.
Published: August 2006

This article conceptualizes two distinct dimensions of community attachment—socially based attachment and attachment to a community’s natural environment—and examines their connections with attitudes about local environmental issues. The findings indicate that the two dimensions of attachment are distinct and relate differently to environmental concern. In cases where the social attachment dimension is a statistically significant predictor of attitudes toward local environmental issues, the issues are representative of community culture and identity or health. In contrast, when natural environment attachment is a statistically significant predictor of local environmental concern, the topics reflect issues involving resource protection. Building on the previous work of Vorkinn and Riese, this study further clarifies that community-focused factors may be more useful variables for understanding attitudes toward environmental issues than sociodemographic ones.
Sharing the Rangelands, Competing for Sense of Place
Authors: Wulfhorst J. D. , Rimbey Neil , Darden Tim
Published: August 2006

The rural-urban interface in southwestern Idaho has experienced rapid population growth since 1990. That burgeoning population sits on the frontier of more than 3.5 million acres of open space—public rangelands in Owyhee County—managed for multiple use by the Bureau of Land Management. The remote areas of Owyhee County have long-standing ranching operations as their social structure and basis for community, but recreational use continues to increase from the adjacent metropolitan population. The related changing social landscape and environmental impacts affect sense of place for many. This analysis uses qualitative and quantitative data to analyze relationships and impacts associated with the emergence of sense of place among different groups for the same region and concludes multiple groups claiming a sense of place to the same general locations can affect traditional community structures at the same time a competing sense of place may foster expanded and more diverse social interactions.
Understanding Place Attachment Among Second Home Owners
Authors: Stedman Richard C.
Published: August 2006

Many high amenity rural communities are growing rapidly and have high rates of seasonal residence, with concomitant “impacts” on longer term permanent residents. The de facto stance that seasonal residents are “outsiders” marginalizes their experience and treats as givens questions that should remain open to empirical scrutiny. This article compares seasonal and year-round resident attachment to such a landscape. Counter to popular assumptions, seasonal residents exhibit higher levels of attachment, but its creation and meaning base varies: Year-rounder attachment is rooted in social networks and community meanings, whereas seasonal attachment is fostered through meanings of environmental quality and escape from day-to-day cares.
The Relevance of Community Sentiments to Australian Rural Youths’ Intention to Stay in Their Home Communities
Authors: Pretty Grace , Bramston Paul , Patrick Jeff , Pannach Wendy
Published: August 2006

This study explores whether community sentiment factors can mediate structural disadvantage factors in rural youths’ intentions to stay in their home communities. In total, 3,023 Australians ages 13 to 18 years responded to items assessing community sentiment (belonging, sense of community, and social support) and subjective quality of life. Structural disadvantage was represented by population size. Participants responded to “If I could get a job here or go to University/College here, I would choose to stay in this town for the foreseeable future.” Findings indicate all factors had a positive relationship with intention to stay; however, only belonging partially mediates the effect of size of community. The combined effects for all factors account for 19% more of the variability in intention to stay than the size of community alone. Discussion considers how focus on structural factors alone restricts the understanding of push-pull dynamics facing rural youth.
“What’s a Mother To Do?”
Authors: DeSena Judith N.
Published: August 2006

Investigating the dynamics of gentrification in Greenpoint, Brooklyn, a community in New York City, this article examines the actions of gentrifiers and the ways in which the process of gentrification affects ordinary people in their everyday lives. The focus is on school selection for children, documenting the strategies used by women, on behalf of their gentry families, to gain admission of their children to public schools outside the neighborhood. This behavior is contrasted with that of working-class and low-income residents whose children attend local schools. The rejection of local social/physical space by the gentry creates a dynamic whereby social relations between gentrifiers and lower income residents are segregated and stratified. Using participant observation and interviews, with a sample made up primarily of women, this article examines “women’s work” in the process of gentrification.
Child vocabulary across the second year: Stability and continuity for reporter comparisons and a cumulative score
Authors: Bornstein Marc H. , Putnick Diane L. , De Houwer Annick
Published: August 2006

Mothers, fathers and caregivers in 29 families completed the Infant and Toddler Forms of Dutch adaptations of the MacArthur Communicative Development Inventories (CDI) for the same children at 1;1 and 1;8, respectively. We computed CDI Cumulative Scores, which credit the child with the best score for each item on the CDI as checked by any single reporter. We then computed comprehension and production scores for each reporter and for the cumulative score. Different reporters assess a particular child's communicative abilities differently. Mothers', fathers' and caregivers' comprehension scores intercorrelated, as did their production scores. Reporters' comprehension and production scores were lower than their respective cumulative comprehension and production scores. For all reporters and the cumulative score, we found significant stability in comprehension and production from 1;1 to 1;8 and significant increases in average comprehension and production.
The Veiled Women and Masked Men of Chechnya
Authors: Struckman Sara
Published: August 2006

This article analyzes gender representations of Chechen veiled women and masked men in the Terror in Moscow documentary, an account of the October 2002 Chechen rebel siege of a Moscow theater. Because the documentary is novel in its use of original footage recorded during the siege, it provides several issues to discuss related to objective accounts versus constructed reality in nonfiction films and how gender representations fit into mediated reality. As part of the “circuit of culture,” the documentary follows dominant notions of what it means to be feminine and masculine in the media. By deconstructing the documentary's structure and analyzing the ideological representations of gender, the analysis reveals that film represents female and male rebels differently by questioning and attempting to explain women's involvement while accepting men's involvement as “natural.”
Political Violence and Journalism in a Multiethnic State
Authors: Brooten Lisa
Published: August 2006

Debates about the role of media in situations of political violence call into question whether journalists should focus on “objective” reporting or instead facilitate conflict resolution. Yet an increasingly problematic assumption is that journalists are outsiders to the communities in conflict, especially as aid agencies increase their funding for media development and journalism training in conflicted areas. By focusing on the situation facing journalists from Burma (Myanmar) living in exile in Thailand, this article explores the consequences of political violence on the development of indigenous journalism in a multiethnic state. Although influenced by the recent surge in foreign funding, these journalists struggle to develop a context-specific model for their work, calling into question the relevance of the dominant U.S. approach to “objectivity.” The contested nature of concepts such as unity, independence, and censorship in these often high-risk areas suggests the need for a more complex model of media development in contexts of political violence.
“Fatwa on the Bunny”
Authors: Vultee Fred
Published: August 2006

How did fatwa, once an unambiguous, simple term for a ruling on a question of Islamic religious law, come to mean “death sentence” in U.S. news language and popular culture? This article uses content and discourse analyses to trace this newly created meaning through a series of gatekeeping failures to a position from which its more ominous meaning is easily inferred—not simply in references to political violence but in discussions of baseball and literature or in advertisements featuring the ubiquitous “Energizer bunny.” The shared meanings it reflects are the underpinnings of the Orientalism that Said described in the 1970s and 1980s, a “pervasive Western discourse” built around a fundamental “ideology of difference.”
Case management and Think First completion
Authors: Davies Keith
Published: August 2006

This article considers the findings of a small-scale study of the practice of case managers supervising offenders required to attend the Think First Group. It explores the interface between one-to-one and group-based work within multi-modal programmes of supervision and seeks to identify those practices that support individuals in completing a group.
Towards a model regime for Approved Premises
Authors: Cherry Sally , Cheston Len
Published: August 2006

This article, based on a review of the literature both from Britain and North America and findings from the Approved Premises pathfinder, will explore the key issues in establishing a model regime for Approved Premises. It will suggest that face-to-face work with residents is an essential component for Approved Premises, and that there is a danger of this vital work being pushed into a secondary function by the need for surveillance and monitoring. The article will argue that working in a rehabilitative manner with residents assists in their risk management.