bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin-Like Growth Factor-1 Receptor Expression Masks the Antiinflammatory and Glucose Uptake Capacity of Insulin in Vascular Smooth Muscle Cells
Authors: Engberding Niels , San Martín Alejandra , Martin-Garrido Abel , Koga Mitsuhisa , Pounkova Lily , Lyons Erin , Lassègue Bernard , Griendling Kathy K.
Published: January 2009

Objective—

Insulin resistance of vascular smooth muscle cells (VSMCs) has been linked to accelerated atherosclerosis in diabetes; however, the effects of insulin on VSMCs remain controversial. Most VSMC insulin receptors are sequestered into insulin-insensitive hybrids with insulin-like growth factor-1 receptors (IGF1Rs). Thus we hypothesized that regulation of IGF1R expression may impact cellular insulin sensitivity.

Methods and Results—

IGF1R expression was increased in aortas from diabetic mice. IGF1R overexpression in VSMCs impaired insulin-induced Akt phosphorylation. Conversely, IGF1R downregulation by siRNA allowed assembly of insulin holoreceptors, enhanced insulin-induced phosphorylation of its receptor, Akt, Erk1/2, and further augmented insulin-induced glucose uptake. IGF1R downregulation uncovered an insulin-induced reduction in activation of NF-κB and inhibition of MCP-1 upregulation in response to TNF-α.

Conclusions—

Downregulation of IGF1R increases the fraction of insulin receptors organized in holoreceptors, which leads to enhanced insulin signaling and unmasks potential antiinflammatory properties of insulin in VSMCs. Therefore, IGF1R, which is susceptible to feedback regulation by its own ligand, may represent a novel target for interventions designed to treat insulin resistance in the vasculature.
Prognostic Utility of ApoB/AI, Total Cholesterol/HDL, Non-HDL Cholesterol, or hs-CRP as Predictors of Clinical Risk in Patients Receiving Statin Therapy After Acute Coronary Syndromes
Authors: Ray Kausik K. , Cannon Christopher P. , Cairns Richard , Morrow David A. , Ridker Paul M , Braunwald Eugene
Published: January 2009

Objectives—

The purpose of this study was to compare the prognostic utility of apoB/AI, total cholesterol/HDL (TC/HDL) ratio, non-HDL cholesterol (non–HDL-C), or hs-CRP as predictors of clinical risk among patients receiving statin therapy after acute coronary syndromes (ACS).

Methods and Results—

Patients with ACS were randomized in the PROVE IT–TIMI 22 trial to either pravastatin 40 mg or atorvastatin 80 mg. Cox regression models adjusting for confounders were used to assess the relationship between on-treatment lipids or hs-CRP and risk of death or acute coronary events. At 4 months a 1 SD increment in apoB/AI (HR 1.10, 95% CI 1.01 to 1.20), TC/HDL (HR 1.12, 95% CI 1.01 to 1.24), and non–HDL-C (HR 1.20, 95% CI 1.07 to 1.35) predicted events to a similar extent as LDL-C (HR 1.20, 95% CI 1.07 to 1.35) with neither apoB/AI, TC/HDL, nor non–HDL-C improving risk prediction models which included LDL-C. In contrast, the addition of hs-CRP significantly improved risk prediction models irrespective of the lipid parameters included, with a 29% to 30% increased risk observed per 1 SD increment in log CRP.

Conclusion—

In the present study of ACS patients receiving statin therapy, on-treatment apoB/AI, TC/HDL, and non–HDL-C offered similar prognostic information to LDL-C. However, the addition of hs-CRP to lipid-based measurements significantly improved risk prediction. On treatment CRP measurement may therefore offer additive prognostic information to lipids in ACS patients.
I
K1
Heterogeneity Affects Genesis and Stability of Spiral Waves in Cardiac Myocyte Monolayers
Authors: Sekar Rajesh B. , Kizana Eddy , Cho Hee C. , Molitoris Jared M. , Hesketh Geoffrey G. , Eaton Brett P. , Marbán Eduardo , Tung Leslie
Published: January 2009

Previous studies have postulated an important role for the inwardly rectifying potassium current (
I
K1
) in controlling the dynamics of electrophysiological spiral waves responsible for ventricular tachycardia and fibrillation. In this study, we developed a novel tissue model of cultured neonatal rat ventricular myocytes (NRVMs) with uniform or heterogeneous Kir2.1expression achieved by lentiviral transfer to elucidate the role of
I
K1
in cardiac arrhythmogenesis. Kir2.1-overexpressed NRVMs showed increased
I
K1
density, hyperpolarized resting membrane potential, and increased action potential upstroke velocity compared with green fluorescent protein–transduced NRVMs. Opposite results were observed in Kir2.1-suppressed NRVMs. Optical mapping of uniformly Kir2.1 gene-modified monolayers showed altered conduction velocity and action potential duration compared with nontransduced and empty vector-transduced monolayers, but functional reentrant waves could not be induced. In monolayers with an island of altered Kir2.1 expression, conduction velocity and action potential duration of the locally transduced and nontransduced regions were similar to those of the uniformly transduced and nontransduced monolayers, respectively, and functional reentrant waves could be induced. The waves were anchored to islands of Kir2.1 overexpression and remained stable but dropped in frequency and meandered away from islands of Kir2.1 suppression. In monolayers with an inverse pattern of
I
K1
heterogeneity, stable high frequency spiral waves were present with
I
K1
overexpression, whereas lower frequency, meandering spiral waves were observed with
I
K1
suppression. Our study provides direct evidence for the contribution of
I
K1
heterogeneity and level to the genesis and stability of spiral waves and highlights the potential importance of
I
K1
as an antiarrhythmia target.
The Ca
V
3.2 T-Type Ca
2+
Channel Is Required for Pressure Overload–Induced Cardiac Hypertrophy in Mice
Authors: Chiang Chien-Sung , Huang Ching-Hui , Chieng Hockling , Chang Ya-Ting , Chang Dory , Chen Ji-Jr , Chen Yong-Cyuan , Chen Yen-Hui , Shin Hee-Sup , Campbell Kevin P. , Chen Chien-Chang
Published: January 2009

Voltage-gated T-type Ca
2+
channels (T-channels) are normally expressed during embryonic development in ventricular myocytes but are undetectable in adult ventricular myocytes. Interestingly, T-channels are reexpressed in hypertrophied or failing hearts. It is unclear whether T-channels play a role in the pathogenesis of cardiomyopathy and what the mechanism might be. Here we show that the α
1H
voltage-gated T-type Ca
2+
channel (Ca
v
3.2) is involved in the pathogenesis of cardiac hypertrophy via the activation of calcineurin/nuclear factor of activated T cells (NFAT) pathway. Specifically, pressure overload–induced hypertrophy was severely suppressed in mice deficient for Ca
v
3.2 (Ca
v
3.2
−/−
) but not in mice deficient for Ca
v
3.1 (Ca
v
3.1
−/−
). Angiotensin II–induced cardiac hypertrophy was also suppressed in Ca
v
3.2
−/−
mice. Consistent with these findings, cultured neonatal myocytes isolated from Ca
v
3.2
−/−
mice fail to respond hypertrophic stimulation by treatment with angiotensin II. Together, these results demonstrate the importance of Ca
v
3.2 in the development of cardiac hypertrophy both in vitro and in vivo. To test whether Ca
v
3.2 mediates the hypertrophic response through the calcineurin/NFAT pathway, we generated Ca
v
3.2
−/−
, NFAT-luciferase reporter mice and showed that NFAT-luciferase reporter activity failed to increase after pressure overload in the Ca
v
3.2
−/−
/NFAT-Luc mice. Our results provide strong genetic evidence that Ca
v
3.2 indeed plays a pivotal role in the induction of calcineurin/NFAT hypertrophic signaling and is crucial for the activation of pathological cardiac hypertrophy.
The Antiangiogenic Activity of rPAI-1
23
Inhibits Vasa Vasorum and Growth of Atherosclerotic Plaque
Authors: Drinane Mary , Mollmark Jessica , Zagorchev Lyubomir , Moodie Karen , Sun Baiming , Hall Amy , Shipman Samantha , Morganelli Peter , Simons Michael , Mulligan-Kehoe Mary Jo
Published: January 2009

Plaque vascularity has been implicated in its growth and stability. However, there is a paucity of information regarding the origin of plaque vasculature and the role of vasa vasorum in plaque growth. To inhibit growth of vasa vasorum in atherogenic mice and assess its effect on plaque growth, we used a truncated plasminogen activator inhibitor (PAI)-1 protein, rPAI-1
23
, that has significant antiangiogenic activity. Female LDLR
−/−
ApoB-48–deficient mice fed Paigen’s diet without cholate for 20 weeks received rPAI-1
23
treatment (n=21) for the last 6 weeks. Plaque size and vasa vasorum density were compared to 2 controls: mice fed Paigen’s diet and treated with saline for the last 6 weeks (n=16) and mice fed Paigen’s diet until the onset of treatment (n=14). The rPAI-1
23
treatment significantly reduced plaque area and plaque cholesterol in the descending aorta and plaque area in the innominate artery. Measurements of reconstructed confocal microscopy images of vasa vasorum demonstrate that rPAI-1
23
treatment decreased vasa vasorum area and length, which was supported by microCT images. Confocal images provide evidence for vascularized plaque in the saline-treated group but not in rPAI-1
23
–treated mice. The increased vessel density in saline-treated mice is attributable, in part, to upregulated fibroblast growth factor-2 expression, which is inhibited by rPAI-1
23
. In conclusion, rPAI-1
23
inhibits growth of vasa vasorum, as well as vessels within the adjacent plaque and vessel wall, through inhibition of fibroblast growth factor-2, leading to reduced plaque growth in atherogenic female LDLR
−/−
ApoB-48–deficient mice.
Induction of Prostacyclin by Steady Laminar Shear Stress Suppresses Tumor Necrosis Factor-α Biosynthesis via Heme Oxygenase-1 in Human Endothelial Cells
Authors: Di Francesco Luigia , Totani Licia , Dovizio Melania , Piccoli Antonio , Di Francesco Andrea , Salvatore Tania , Pandolfi Assunta , Evangelista Virgilio , Dercho Ryan A. , Seta Francesca , Patrignani Paola
Published: January 2009

Cyclooxygenase (COX)-2 is among the endothelial genes upregulated by uniform laminar shear stress (LSS), characteristically associated with atherosclerotic lesion-protected areas. We have addressed whether the induction of COX-2–dependent prostanoids in endothelial cells by LSS plays a role in restraining endothelial tumor necrosis factor (TNF)-α generation, a proatherogenic cytokine, through the induction of heme oxygenase-1 (HO)-1, an antioxidant enzyme. In human umbilical vein endothelial cells (HUVECs) exposed to steady LSS of 10 dyn/cm2for 6 hours, COX-2 protein was significantly induced, whereas COX-1 and the downstream synthases were not significantly modulated. This was associated with significant (P<0.05) increase of 6-keto-prostaglandin (PG)F1α(the hydrolysis product of prostacyclin), PGE2, and PGD2. In contrast, TNF-α released in the medium in 6 hours (3633±882 pg) or detected in cells lysates (1091±270 pg) was significantly (P<0.05) reduced versus static condition (9100±2158 and 2208±300 pg, respectively). Coincident induction of HO-1 was detected. The finding that LSS-dependent reduction of TNF-α generation and HO-1 induction were abrogated by the selective inhibitor of COX-2 NS-398, the nonselective COX inhibitor aspirin, or the specific prostacyclin receptor (IP) antagonist RO3244794 illuminates the central role played by LSS-induced COX-2–dependent prostacyclin in restraining endothelial inflammation. Carbacyclin, an agonist of IP, induced HO-1. Similarly to inhibition of prostacyclin biosynthesis or activity, the novel imidazole-based HO-1 inhibitor QC15 reversed TNF-α reduction by LSS. These findings suggest that inhibition of COX-2–dependent prostacyclin might contribute to acceleration of atherogenesis in patients taking traditional nonsteroidal antiinflammatory drugs (NSAIDs) and NSAIDs selective for COX-2 through downregulation of HO-1, which halts TNF-α generation in human endothelial cells.
Mysteries of the Nile? Joseph Scaliger and Ancient Egypt Les mystères du Nil? Joseph Scaliger et l'Égypte ancienne
Authors: Dijkstra Jitse
Published: January 2009

L'humaniste et savant Joseph Scaliger (1540–1609) est bien connu pour ses œuvres d'astronomie et de chronologies anciennes. Elles contiennent, notamment, des développements consacrés à ces domaines pour ce qui concerne l'Égypte ancienne. Cet article traite de la perspective adoptée par Scaliger sur l'Égypte ancienne, Dans quelle mesure cette perspective fut-elle influencée par l'“Égyptomanie” qui caractérise cette époque? En se fondant sur les œuvres et la correspondance de Scaliger, il s'agit de montrer que, même si son intérêt pour l'Égypte devait beaucoup à ses études en matière de chronologie et d'astronomie, il ne s'est pas limité à ces sujets. De fait, certains passages dans des lettres écrites par lui ou adressées à lui montrent que ses intérêts allaient au-delà. En raison de son approche philologique et de son érudition, ce savant s'est trouvé porté à considérer l'Égypte au même titre que n'importe quel autre pays de l'Antiquité. Aussi s'est-il trouvé en mesure de développer plusieurs idées originales sur l'Égypte ancienne, qui étaient très en avance sur son temps.
From Swedenborg's Spiritual World to Kant's Kingdom of Ends Von der geistigen Welt Swedenborgs zu Kants Reich der Zwecke
Authors: Johnson Gregory
Published: January 2009

In diesem Beitrag wird die These aufgestellt, dass Immanuel Kants Konzept des “Reiches der Zwecke” von Emanuel Swedenborgs Konzept der geistigen Welt abgeleitet ist, welches Swedenborg in seinem Werk Arcana Coelestia (“Geheimnisse des Himmels”, 1749–1756) ebenfalls als “Reich der Zwecke” (regnum finium) beschreibt. Der Artikel argumentiert, dass Kant Swedenborgs Arcana Coelestia kurz nach 1760 gelesen hat und dass die Konzeption der geistigen Welt, wie Kant sie in seiner Abhandlung Träume eines Geistersehers von 1766 vorstellt, von Swedenborg abhängig ist. Nimmt man ferner zu Kants veröffentlichten Werken Notizen von Studenten zu seinen Vorlesungen über Metaphysik und Ethik hinzu, zeigt sich im Hinblick auf die geistige Welt eine direkte Linie von den Träumen eines Geistersehers zur Grundlegung zur Metaphysik der Sitten von 1785, in der erstmals der Ausdruck “Reich der Zwecke” im Druck erscheint.
Starvation‐Induced Proximal Gut Mucosal Atrophy Diminished With Aging
Authors: Song Juquan , Wolf Steven E. , Wu Xiao‐Wu , Finnerty Celeste C. , Gauglitz Gerd G. , Herndon David N. , Jeschke Marc G.
Published: January 2009

Background: Starvation induces small bowel atrophy with increased intestinal epithelial apoptosis and decreased proliferation. The authors examined these parameters after starvation in aged animals. Methods: Sixty‐four 6‐week‐old and 26‐month‐old C57BL/6 mice were randomly assigned to either an ad libitum fed or fasted group. The small bowel was harvested at 12, 48, and 72 hours following starvation. Proximal gut mucosal height was measured and epithelial cells counted. Apoptosis was identified by terminal deoxynucleotidyl transferase‐mediated dUTP nick end labeling (TUNEL) staining. Proliferation was determined by immunohistochemical staining for proliferating cell nuclear antigen. Comparison of fed vs fasted and adult vs old groups was done by one‐way ANOVA with Tukey's test and unpaired Student's t test. Significance was accepted at P < .05. Results: Aged mice had higher proximal gut weights, mucosal heights, and cell numbers at baseline compared with the adult group (P < .05). The rate of apoptosis was lower in the aged (P < .05), but proliferation was not different between groups before starvation. After starvation, proximal gut wet weight decreased only in adult mice (P < .05). Gut mucosal height and mucosal cell number decreased more in adult than in aged mice (P < .05). This was related to decreased proliferation only in the adult group (P < .05). The fold of epithelial apoptosis that increased was higher in the aged group than in the adult group after starvation (P < .05). Conclusions: Gut mucosal kinetics change with age and have lower rates of apoptosis and greater mucosal mass; the character of starvation‐induced atrophy is diminished with aging.
The Relationship between Depression and Body Dissatisfaction across Pregnancy and the Postpartum
Authors: Clark Abigail , Skouteris Helen , Wertheim Eleanor H. , Paxton Susan J. , Milgrom Jeannette
Published: January 2009

The overall aim of this study was to examine the relationship between depression and body dissatisfaction across pregnancy and the first 12 months postpartum. During pregnancy, women's ( N = 116) perceived attractiveness and strength/fitness remained stable, while feeling fat and salience of weight/shape decreased in late pregnancy. During the postpartum, feeling fat and salience of weight/shape increased. Depression and body dissatisfaction scores were correlated with each other concurrently and across multiple time points. However, in baseline-controlled prospective analyses, only a model of greater depression late in pregnancy predicting body dissatisfaction at six weeks postpartum and feeling fat throughout the postpartum was supported.
Social Representations of Female Orgasm
Authors: Lavie-Ajayi Maya , Joffe Hélène
Published: January 2009

This study examines women's social representations of female orgasm. Fifty semi-structured interviews were conducted with British women. The data were thematically analysed and compared with the content of female orgasm-related writing in two women's magazines over a 30-year period. The results indicate that orgasm is deemed the goal of sex with emphasis on its physiological dimension. However, the women and the magazines graft onto this scientifically driven representation the importance of relational and emotive aspects of orgasm. For the women, particularly those who experience themselves as having problems with orgasm, the scientifically driven representations induce feelings of failure, but are also resisted. The findings highlight the role played by the social context in women's subjective experience of their sexual health.
A first-generation microsatellite-based genetic linkage map of the Siberian jay (Perisoreus infaustus): insights into avian genome evolution
Authors: Jaari Sonja , Li Meng-Hua , Merilä Juha
Published: January 2009

Background

Genomic resources for the majority of free-living vertebrates of ecological and evolutionary importance are scarce. Therefore, linkage maps with high-density genome coverage are needed for progress in genomics of wild species. The Siberian jay (Perisoreus infaustus; Corvidae) is a passerine bird which has been subject to lots of research in the areas of ecology and evolutionary biology. Knowledge of its genome structure and organization is required to advance our understanding of the genetic basis of ecologically important traits in this species, as well as to provide insights into avian genome evolution.

Results

We describe the first genetic linkage map of Siberian jay constructed using 117 microsatellites and a mapping pedigree of 349 animals representing five families from a natural population breeding in western Finland from the years 1975 to 2006. Markers were resolved into nine autosomal and a Z-chromosome-specific linkage group, 10 markers remaining unlinked. The best-position map with the most likely positions of all significantly linked loci had a total sex-average size of 862.8 cM, with an average interval distance of 9.69 cM. The female map covered 988.4 cM, whereas the male map covered only 774 cM. The Z-chromosome linkage group comprised six markers, three pseudoautosomal and three sex-specific loci, and spanned 10.6 cM in females and 48.9 cM in males. Eighty-one of the mapped loci could be ordered on a framework map with odds of >1000:1 covering a total size of 809.6 cM in females and 694.2 cM in males. Significant sex specific distortions towards reduced male recombination rates were revealed in the entire best-position map as well as within two autosomal linkage groups. Comparative mapping between Siberian jay and chicken anchored 22 homologous loci on 6 different linkage groups corresponding to chicken chromosomes Gga1, 2, 3, 4, 5, and Z. Quite a few cases of intra-chromosomal rearrangements within the autosomes and three cases of inter-chromosomal rearrangement between the Siberian jay autosomal linkage groups (LG1, LG2 and LG3) and the chicken sex chromosome GgaZ were observed, suggesting a conserved synteny, but changes in marker order, within autosomes during about 100 million years of avian evolution.

Conclusion

The constructed linkage map represents a valuable resource for intraspecific genomics of Siberian jay, as well as for avian comparative genomic studies. Apart from providing novel insights into sex-specific recombination rates and patterns, the described maps – from a previously genomically uncharacterized superfamily (Corvidae) of passerine birds – provide new insights into avian genome evolution. In combination with high-resolution data on quantitative trait variability from the study population, they also provide a foundation for QTL-mapping studies.
Asymmetrical distribution of non-conserved regulatory sequences at PHOX2B is reflected at the ENCODE loci and illuminates a possible genome-wide trend
Authors: McGaughey David M , Stine Zachary E , Huynh Jimmy L , Vinton Ryan M , McCallion Andrew S
Published: January 2009

Background

Transcriptional regulatory elements are central to development and interspecific phenotypic variation. Current regulatory element prediction tools rely heavily upon conservation for prediction of putative elements. Recent in vitro observations from the ENCODE project combined with in vivo analyses at the zebrafish phox2b locus suggests that a significant fraction of regulatory elements may fall below commonly applied metrics of conservation. We propose to explore these observations in vivo at the human PHOX2B locus, and also evaluate the potential evidence for genome-wide applicability of these observations through a novel analysis of extant data.

Results

Transposon-based transgenic analysis utilizing a tiling path proximal to human PHOX2B in zebrafish recapitulates the observations at the zebrafish phox2b locus of both conserved and non-conserved regulatory elements. Analysis of human sequences conserved with previously identified zebrafish phox2b regulatory elements demonstrates that the orthologous sequences exhibit overlapping regulatory control. Additionally, analysis of non-conserved sequences scattered over 135 kb 5' to PHOX2B, provides evidence of non-conserved regulatory elements positively biased with close proximity to the gene. Furthermore, we provide a novel analysis of data from the ENCODE project, finding a non-uniform distribution of regulatory elements consistent with our in vivo observations at PHOX2B. These observations remain largely unchanged when one accounts for the sequence repeat content of the assayed intervals, when the intervals are sub-classified by biological role (developmental versus non-developmental), or by gene density (gene desert versus non-gene desert).

Conclusion

While regulatory elements frequently display evidence of evolutionary conservation, a fraction appears to be undetected by current metrics of conservation. In vivo observations at the PHOX2B locus, supported by our analyses of in vitro data from the ENCODE project, suggest that the risk of excluding non-conserved sequences in a search for regulatory elements may decrease as distance from the gene increases. Our data combined with the ENCODE data suggests that this may represent a genome wide trend.
Alcohol consumption is associated with an increased risk of erosive esophagitis and Barrett's epithelium in Japanese men
Authors: Akiyama Tomoyuki , Inamori Masahiko , Iida Hiroshi , Mawatari Hironori , Endo Hiroki , Hosono Kunihiro , Yoneda Kyoko , Fujita Koji , Yoneda Masato , Takahashi Hirokazu , Goto Ayumu , Abe Yasunobu , Kobayashi Noritoshi , Kubota Kensuke , Saito Satoru , Nakajima Atsushi
Published: January 2009

Background

Evidence regarding the association between alcohol consumption and the gastro-esophageal reflux disease (GERD) spectrum has been conflicting. We examined the association between alcohol consumption and erosive esophagitis and Barrett's epithelium in Japanese men.

Methods

The study population comprised 463 men subjects who had undergone an upper endoscopy at the Gastroenterology Division of Yokohama City University Hospital between August 2005 and July 2006. The presence of erosive esophagitis and Barrett's epithelium was diagnosed based on the Los Angeles Classification and the Prague C and M Criteria, respectively. We divided the study population into four groups: never drinkers, light drinkers (less than 25.0 g of ethanol per day), moderate drinkers (25.0 to 50.0 g of ethanol per day), and heavy drinkers (more than 50.0 g of ethanol per day). A linear regression of the logistic regression analysis was used to analyze the dose-response trends.

Results

Compared with never drinkers, light drinkers (less than 25.0 g ethanol per day), moderate drinkers (25.0 to 50.0 g per day), and heavy drinkers (more than 50.0 g per day) had ORs for erosive esophagitis of 1.110 (95% CI: 0.553 – 2.228, p = 0.7688), 1.880 (95% CI: 1.015 – 3.484, p = 0.0445) and 1.988 (95% CI: 1.120 – 3.534, p = 0.0190), respectively. These groups had ORs for Barrett's epithelium of 1.278 (95% CI: 0.752 – 2.170, p = 0.3643), 1.458 (95% CI: 0.873 – 2.433, p = 0.1500), and 1.912 (95% CI: 1.185 – 3.086, p = 0.0079), respectively. The odds ratios/grams (alcohol)/day of dose response trends for erosive esophagitis and Barrett's epithelium were 1.015 (95% CI: 1.004–1.026, p = 0.0066) and 1.012 (95% CI: 1.003–1.021, p = 0.0079), respectively.

Conclusion

These findings suggest that alcohol consumption in Japanese men tends to be associated with an increased risk of erosive esophagitis and Barrett's epithelium.
Water aerobics II: maternal body composition and perinatal outcomes after a program for low risk pregnant women
Authors: Cavalcante Sergio R , Cecatti Jose G , Pereira Rosa I , Baciuk Erica P , Bernardo Ana L , Silveira Carla
Published: January 2009

Background

To evaluate the effectiveness and safety of water aerobics during pregnancy.

Methods

A randomized controlled trial carried out in 71 low-risk sedentary pregnant women, randomly allocated to water aerobics or no physical exercise. Maternal body composition and perinatal outcomes were evaluated. For statistical analysis Chi-square, Fisher's or Student's t-tests were applied. Risk ratios and their 95% CI were estimated for main outcomes. Body composition was evaluated across time using MANOVA or Friedman multiple analysis.

Results

There were no significant differences between the groups regarding maternal weight gain, BMI or percentage of body fat during pregnancy. Incidence of preterm births (RR = 0.84; 95%CI:0.28–2.53), vaginal births (RR = 1.24; 95%CI:0.73–2.09), low birthweight (RR = 1.30; 95%CI:0.61–2.79) and adequate weight for gestational age (RR = 1.50; 95%CI:0.65–3.48) were also not significantly different between groups. There were no significant differences in systolic and diastolic blood pressure and heart rate between before and immediately after the water aerobics session.

Conclusion

Water aerobics for sedentary pregnant women proved to be safe and was not associated with any alteration in maternal body composition, type of delivery, preterm birth rate, neonatal well-being or weight.
Production of recombinant AAV vectors encoding insulin-like growth factor I is enhanced by interaction among AAV rep regulatory sequences
Authors: Shi Shuiliang , Mercer Scott A , Dilley Robert , Trippel Stephen B
Published: January 2009

Background

Adeno-associated virus (AAV) vectors are promising tools for gene therapy. Currently, their potential is limited by difficulties in producing high vector yields with which to generate transgene protein product. AAV vector production depends in part upon the replication (Rep) proteins required for viral replication. We tested the hypothesis that mutations in the start codon and upstream regulatory elements of Rep78/68 in AAV helper plasmids can regulate recombinant AAV (rAAV) vector production. We further tested whether the resulting rAAV vector preparation augments the production of the potentially therapeutic transgene, insulin-like growth factor I (IGF-I).

Results

We constructed a series of AAV helper plasmids containing different Rep78/68 start codon in combination with different gene regulatory sequences. rAAV vectors carrying the human IGF-I gene were prepared with these vectors and the vector preparations used to transduce HT1080 target cells. We found that the substitution of ATG by ACG in the Rep78/68 start codon in an AAV helper plasmid (pAAV-RC) eliminated Rep78/68 translation, rAAV and IGF-I production. Replacement of the heterologous sequence upstream of Rep78/68 in pAAV-RC with the AAV2 endogenous p5 promoter restored translational activity to the ACG mutant, and restored rAAV and IGF-I production. Insertion of the AAV2 p19 promoter sequence into pAAV-RC in front of the heterologous sequence also enabled ACG to function as a start codon for Rep78/68 translation. The data further indicate that the function of the AAV helper construct (pAAV-RC), that is in current widespread use for rAAV production, may be improved by replacement of its AAV2 unrelated heterologous sequence with the native AAV2 p5 promoter.

Conclusion

Taken together, the data demonstrate an interplay between the start codon and upstream regulatory sequences in the regulation of Rep78/68 and indicate that selective mutations in Rep78/68 regulatory elements may serve to augment the therapeutic value of rAAV vectors.
Mental hospital reform in Asia: the case of Yuli Veterans Hospital, Taiwan
Authors: Lin Chih-Yuan , Huang Ai-Ling , Minas Harry , Cohen Alex
Published: January 2009

Background

Yuli Veterans Hospital (YVH) has been the largest mental hospital for the patients with chronic and severe mental illness in Taiwan for the past 50 years. While this hospital used to be a symbol of hopelessness among patients and their families and an unspoken shame among Taiwan psychiatry and mental health circles it now represents an example of how an old, custodial hospital can be transformed into a very different institution. In this case study we will describe the features of this transformation, which, over the past 20 years, has aimed to help extended stay inpatients with severe mental illness to integrate into the local community of Yuli even though it is not their original home.

Methods

Using historical documents and oral narratives from Yuli inhabitants, workers and patients of YVH, we will offer a case study of the Yuli model.

Results

There are four main components of the Yuli model: holistic medical support, vocational rehabilitation, case management, and the residential program. The four components help patients recover two essential features of their lives: vocational life and ordinary daily routines. As the process of recovery evolves, patients gradually regain inner stability, dignity, self-confidence, and a sense of control. The four components are critical to rebuild the structure and order of life of the patients and are indispensable and interdependent parts of one service package. They operate simultaneously to benefit the patients to the greatest degree possible.

Discussion

There are many challenges to the further development and financial viability of the model of services developed at YVH. There are also important questions concerning the replicability of the Yuli model in other sociocultural and service system contexts.

Conclusion

This case study reveals the possibility of transforming a custodial mental hospital into a hospital providing high quality care. Hospital and community are not in opposition. They are part of a continuum of care for the patients. We reinterpret and redefine the boundary and function of hospital and community, and thereby create a new service model, the Yuli Model, to help patients to reintegrate into the community. The Yuli model, which particularly focuses on the needs of people with long-standing illness and prolonged hospital stay, illustrates one approach to linking hospital and community in a creative and constructive manner.
Complex nature of SNP genotype effects on gene expression in primary human leucocytes
Authors: Heap Graham A , Trynka Gosia , Jansen Ritsert C , Bruinenberg Marcel , Swertz Morris A , Dinesen Lotte C , Hunt Karen A , Wijmenga Cisca , vanHeel David A , Franke Lude
Published: January 2009

Background

Genome wide association studies have been hugely successful in identifying disease risk variants, yet most variants do not lead to coding changes and how variants influence biological function is usually unknown.

Methods

We correlated gene expression and genetic variation in untouched primary leucocytes (n = 110) from individuals with celiac disease – a common condition with multiple risk variants identified. We compared our observations with an EBV-transformed HapMap B cell line dataset (n = 90), and performed a meta-analysis to increase power to detect non-tissue specific effects.

Results

In celiac peripheral blood, 2,315 SNP variants influenced gene expression at 765 different transcripts (< 250 kb from SNP, at FDR = 0.05, cis expression quantitative trait loci, eQTLs). 135 of the detected SNP-probe effects (reflecting 51 unique probes) were also detected in a HapMap B cell line published dataset, all with effects in the same allelic direction. Overall gene expression differences within the two datasets predominantly explain the limited overlap in observed cis-eQTLs. Celiac associated risk variants from two regions, containing genes IL18RAP and CCR3, showed significant cis genotype-expression correlations in the peripheral blood but not in the B cell line datasets. We identified 14 genes where a SNP affected the expression of different probes within the same gene, but in opposite allelic directions. By incorporating genetic variation in co-expression analyses, functional relationships between genes can be more significantly detected.

Conclusion

In conclusion, the complex nature of genotypic effects in human populations makes the use of a relevant tissue, large datasets, and analysis of different exons essential to enable the identification of the function for many genetic risk variants in common diseases.
On the Correlation Structure of a Lévy-Driven Queue
Authors: Es-Saghouani Abdelghafour , Mandjes Michel
Published: January 2009

In this paper we consider a single-server queue with Lévy input and, in particular, its workload process (Qt)t≥0, with a focus on the correlation structure. With the correlation function defined asr(t) := cov(Q0,Qt) / var(Q0) (assuming that the workload process is in stationarity at time 0), we first determine its transform ∫0∞r(t)e-ϑtdt. This expression allows us to prove thatr(·) is positive, decreasing, and convex, relying on the machinery of completely monotone functions. We also show thatr(·) can be represented as the complementary distribution function of a specific random variable. These results are used to compute the asymptotics ofr(t), for larget, for the cases of light-tailed and heavy-tailed Lévy inputs.
Stability of a Processor-Sharing Queue with Varying Throughput
Authors: Moyal Pascal
Published: January 2009

In this paper we present a stability criterion for processor-sharing queues, in which the throughput may depend on the number of customers in the system (such as in the case of interferences between users). Such a system is represented by a point measure-valued stochastic recursion keeping track of the remaining processing times of the customers.
How Nearly do Arriving Customers See Time-Average Behavior?
Authors: Peköz Erol A. , Ross Sheldon M. , Seshadri Sridhar
Published: January 2009

Customers arriving at a queue do not usually see its time-average behavior unless arrivals occur according to a Poisson process. In this article we study how nearly customers see time-average behavior. We give total variation error bounds for comparing the distance between the time- and customer-average distributions of a queueing system in terms of properties of the interarrival distribution. Some refinements are given for special cases and numerical computations are used to demonstrate the performance of the inequalities.
Some Blackwell-Type Renewal Theorems for Weighted Renewal Functions
Authors: Lin Jianxi
Published: January 2009

In this paper, a new approach is proposed to investigate Blackwell-type renewal theorems for weighted renewal functions systematically according to which of the tails of weighted renewal constants or the underlying distribution is asymptotically heavier. Some classical results are improved considerably.
Ranking of Weighted Majority Rules
Authors: Berend Daniel , Chernyavsky Yuri , Sapir Luba
Published: January 2009

A decision-making body may utilize a wide variety of different strategies when required to make a collective decision. In principle, we would like to use the most effective decision rule, that is, the rule yielding the highest probability of making the correct decision. However, in reality we often have to choose a decision rule out of some restricted family of rules. Therefore, it is important to be able to rank various families of rules. In this paper we consider three classes of decision rules: (i) balanced expert rules, (ii) the so-called single expert rules, and (iii) restricted majority rules. For the first two classes, we show that, as we deviate from the best rule in the family, the effectiveness of the decision rule decreases. For the last class, we obtain a very different phenomenon: any inner ranking is possible.
A Random Permutation Model Arising in Chemistry
Authors: Brown Mark , Peköz Erol A. , Ross Sheldon M.
Published: January 2009

We study a model arising in chemistry where n elements numbered 1, 2, …, n are randomly permuted and if i is immediately to the left of i + 1 then they become stuck together to form a cluster. The resulting clusters are then numbered and considered as elements, and this process keeps repeating until only a single cluster is remaining. In this article we study properties of the distribution of the number of permutations required.
A Stochastic Volatility Alternative to SABR
Authors: Rogers L. C. G. , Veraart L. A. M.
Published: January 2009

We present two new stochastic volatility models in which option prices for European plain-vanilla options have closed-form expressions. The models are motivated by the well-known SABR model, but use modified dynamics of the underlying asset. The asset process is modelled as a product of functions of two independent stochastic processes: a Cox-Ingersoll-Ross process and a geometric Brownian motion. An application of the models to options written on foreign currencies is studied.
Mixture Representations of Residual Lifetimes of Used Systems
Authors: Navarro Jorge , Balakrishnan N. , Samaniego Francisco J.
Published: January 2009

The representation of the reliability function of the lifetime of a coherent system as a mixture of the reliability function of order statistics associated with the lifetimes of its components is a very useful tool to study the ordering and the limiting behaviour of coherent systems. In this paper, we obtain several representations of the reliability functions of residual lifetimes of used coherent systems under two particular conditions on the status of the components or the system in terms of the reliability functions of residual lifetimes of order statistics.
Conditional Ordering ofk-out-of-nSystems with Independent But Nonidentical Components
Authors: Zhao Peng , Li Xiaohu , Balakrishnan N.
Published: January 2009

By consideringk-out-of-nsystems with independent and nonidentically distributed components, we discuss stochastic monotone properties of the residual life and the inactivity time. We then present some stochastic comparisons of two systems based on the residual life and inactivity time.
A Note on Embedding Certain Bernoulli Sequences in Marked Poisson Processes
Authors: Holst Lars
Published: January 2009

A sequence of independent Bernoulli random variables with success probabilities a / (a + b + k − 1), k = 1, 2, 3, …, is embedded in a marked Poisson process with intensity 1. Using this, conditional Poisson limits follow for counts of failure strings.
The birth of cloning: an interview with John Gurdon
Authors: Kain Kristin
Published: January 2009

Sir John Gurdon used nuclear transplantation and cloning to show that the nucleus of a differentiated somatic cell retains the totipotency necessary to form a whole organism. Here, he discusses model organisms, the future implications for his early work on medicine and his thoughts about scientific publishing.
Subcellular localization and dimerization of APLP1 are strikingly different from APP and APLP2
Authors: Kaden Daniela , Voigt Philipp , Munter Lisa-Marie , Bobowski Karolina D. , Schaefer Michael , Multhaup Gerd
Published: January 2009

The molecular association between APP and its mammalian homologs has hardly been explored. In systematically addressing this issue, we show by live cell imaging that APLP1 mainly localizes to the cell surface, whereas APP and APLP2 are mostly found in intracellular compartments. Homo- and heterotypic cis interactions of APP family members could be detected by FRET and co-immunoprecipitation analysis and occur in a modular mode. Only APLP1 formed trans interactions, supporting the argument for a putative specific role of APLP1 in cell adhesion. Deletion mutants of APP family members revealed two highly conserved regions as important for the protein crosstalk. In particular, the N-terminal half of the ectodomain was crucial for APP and APLP2 interactions. By contrast, multimerization of APLP1 was only partially dependent on this domain but strongly on the C-terminal half of the ectodomain. We further observed that coexpression of APP with APLP1 or APLP2 leads to diminished generation of Aβ42. The current data suggest that this is due to the formation of heteromeric complexes, opening the way for novel therapeutic strategies targeting these complexes.
Connexin mutation that causes dominant congenital cataracts inhibits gap junctions, but not hemichannels, in a dominant negative manner
Authors: Banks Eric A. , Toloue Masoud M. , Shi Qian , Zhou Zifei Jade , Liu Jialu , Nicholson Bruce J. , Jiang Jean X.
Published: January 2009

The connexin (Cx) 50, E48K, mutation is associated with a human dominant congenital cataract; however, the underlying molecular mechanism has not been characterized. The glutamate (E) residue at position 48 is highly conserved across animal species and types of connexins. When expressed in paired Xenopus oocytes, human (h) and chicken (ch) Cx50 E48K mutants showed no electrical coupling. In addition, this mutation acts in a dominant negative manner when paired hetero-typically or hetero-merically with wild-type Cx50, but has no such effect on Cx46, the other lens fiber connexin. A similar loss-of-function and dominant negative effect was observed using dye transfer assays in the same system. By using two different dye transfer methods, with two different tracer dyes, we found chCx50 E48K expressed in chicken lens embryonic fibroblast cells by retroviral infection similarly failed to induce dye coupling, and prevented wild-type chCx50 from forming functional gap junctions. In contrast to its effect on gap junctions, the E48K mutation has no effect on hemichannel activity when assayed using electrical conductance in oocytes, and mechanically induced dye uptake in cells. Cx50 is functionally involved in cell differentiation and lens development, and the E48K mutant promotes primary lens cell differentiation indistinguishable from wild-type chCx50, despite its lack of junctional channel function. Together the data show that mutations affecting gap junctions but not hemichannel function of Cx50 can lead to dominant congenital cataracts in humans. This clearly supports the model of intercellular coupling of fiber cells creating a microcirculation of nutrients and metabolites required for lens transparency.
Sequential lineup presentation: Patterns and policy
Authors: Lindsay R. C. L. , Mansour Jamal K. , Beaudry Jennifer L. , Leach Amy‐May , Bertrand Michelle I.
Published: January 2009

Sequential lineups were offered as an alternative to the traditional simultaneous lineup. Sequential lineups reduce incorrect lineup selections; however, the accompanying loss of correct identifications has resulted in controversy regarding adoption of the technique. We discuss the procedure and research relevant to (1) the pattern of results found using sequential versus simultaneous lineups; (2) reasons (theory) for differences in witness responses; (3) two methodological issues; and (4) implications for policy decisions regarding the adoption of sequential lineups.
The Groningen Protocol: Is it necessary? Is it scientific? Is it ethical?
Authors: Chervenak Frank A. , McCullough Laurence B. , Arabin Birgit
Published: January 2009

Aim:To explore whether the Groningen Protocol is clinically necessary, scientific, and ethically justified.

Results:The Groningen Protocol is clinically unnecessary because the withdrawal of life-sustaining treatment from seriously ill infants is already ethically accepted globally without the need for the Protocol and because spina bifida, to which the Protocol has been most often applied, can be detected by ultrasound before viability, affording pregnant women the opportunity of termination of pregnancy. The Groningen Protocol is unscientific because it does not meet the accepted standards of evidence-based reasoning concerning the four clinical criteria for its application. The Groningen Protocol is unethical because it does not meet the standards of argument-based ethics in defining its four clinical criteria.

Conclusions:The Groningen Protocol is clinically unnecessary, unscientific, and unethical. Physicians should condemn its use. The Dutch Association of Paediatrics should revoke its approval and adoption of the Groningen Protocol.
A Computer-based Safety Assessment for Flight Evacuation: SAFE
Authors: Shively Robert J.
Published: January 2009

Recently, the U.S. emergency medical services (EMS) industry has received a great deal of negative publicity concerning its safety record. It has been noted that the EMS industry has an accident rate that is five times that of the rest of the helicopter industry (Harvey and Jensen, 1987; Harvey, 1986. While it is true that during 1987 and early 1988 the safety record has improved, the industry cannot become complacent. The National Transportation and Safety Board recently conducted a study of the EMS industry and returned specific recommendations for the FAA and NASA. One of the critical factors in EMS missions is the pilot's decision accept or reject a mission. This can often be influenced by such factors as the urgency of the care required. This, along with other factors, may prompt a pilot to accept a mission of unacceptable risk. The present paper presents a computer- based decision aid, based upon earlier work by the Army and Coas Guard, to assist the pilot in objective assessment of the probable risk of an EMS mission. Data for validation of this technique will be collected at an EMS operator and from the EMS Safety Reporting Service.
Development of Subjective Data for Performance Prediction
Authors: Meister David
Published: January 2009

The point is made that in the absence of other human performance data sources, the use of subjective estimates is justifiable and, even more, necessary. The most common methods of eliciting these estimates are described.