bluuebunny/crossref_metadata_2025 huggingface dataset:
Quantifying the Importance of Galactofuranose in Aspergillus nidulans Hyphal Wall Surface Organization by Atomic Force Microscopy
Authors: Paul Biplab C. , El-Ganiny Amira M. , Abbas Mariam , Kaminskyj Susan G. W. , Dahms Tanya E. S.
Published: February 2011

The fungal wall mediates cell-environment interactions. Galactofuranose (Gal
f
), the five-member ring form of galactose, has a relatively low abundance in
Aspergillus
walls yet is important for fungal growth and fitness.
Aspergillus nidulans
strains deleted for Gal
f
biosynthesis enzymes UgeA (UDP-glucose-4-epimerase) and UgmA (UDP-galactopyranose mutase) lacked immunolocalizable Gal
f
, had growth and sporulation defects, and had abnormal wall architecture. We used atomic force microscopy and force spectroscopy to image and quantify cell wall viscoelasticity and surface adhesion of
ugeA
Δ and
ugmA
Δ strains. We compared the results for
ugeA
Δ and
ugmA
Δ strains with the results for a wild-type strain (AAE1) and the
ugeB
deletion strain, which has wild-type growth and sporulation. Our results suggest that UgeA and UgmA are important for cell wall surface subunit organization and wall viscoelasticity. The
ugeA
Δ and
ugmA
Δ strains had significantly larger surface subunits and lower cell wall viscoelastic moduli than those of AAE1 or
ugeB
Δ hyphae. Double deletion strains (
ugeA
Δ
ugeB
Δ and
ugeA
Δ
ugmA
Δ) had more-disorganized surface subunits than single deletion strains. Changes in wall surface structure correlated with changes in its viscoelastic modulus for both fixed and living hyphae. Wild-type walls had the largest viscoelastic modulus, while the walls of the double deletion strains had the smallest. The
ugmA
Δ strain and particularly the
ugeA
Δ
ugmA
Δ double deletion strain were more adhesive to hydrophilic surfaces than the wild type, consistent with changes in wall viscoelasticity and surface organization. We propose that Gal
f
is necessary for full maturation of
A. nidulans
walls during hyphal extension.
Crystal Structure of the Autochaperone Region from the Shigella flexneri Autotransporter IcsA
Authors: Kühnel Karin , Diezmann Dagmar
Published: February 2011

The IcsA (
i
ntra
c
ellular
s
pread gene
A
) autotransporter from
Shigella flexneri
is a key virulence factor. We identified a stable fragment comprising residues 591 to 758, which corresponds to the autochaperone region of the IcsA passenger domain. We showed that thermal unfolding of the autochaperone region is reversible and determined its crystal structure at 2.0-Å resolution.
Elucidation of the Regulon and
cis
-Acting Regulatory Element of HrpB, the AraC-Type Regulator of a Plant Pathogen-Like Type III Secretion System in Burkholderia pseudomallei
Authors: Lipscomb Lyla , Schell Mark A.
Published: February 2011

The human pathogen
Burkholderia pseudomallei
possesses multiple type III secretion system (T3SS) gene clusters. One of these, the
B. pseudomallei
T3SS2 (T3SS2
bp
) gene cluster, which apparently plays no role in animal virulence, is also found in six additional
Burkholderia
spp. and is very similar to T3SSs found in phytopathogenic
Xanthomonas
spp. and
Ralstonia solanacearum
. The T3SS2
bp
gene cluster also encodes an AraC-type regulatory protein (HrpB
bp
) that is an ortholog of HrpB, the master regulator of the
R. solanacearum
T3SS (T3SS
rso
) and its secreted effectors. Transcriptome analysis showed that HrpB
bp
activates the expression of T3SS2
bp
genes, as well as their orthologs in
R. solanacearum
. In addition to activating T3SS2
bp
, HrpB
bp
also upregulates the expression of ∼30 additional
B. pseudomallei
genes, including some that may confer production of adhesive pili, a polyketide toxin, several putative T3SS2
bp
-secreted effectors, and components of a regulatory cascade. T3SS2
bp
promoter regions were found to contain a conserved DNA motif (p2
bp
box) identical in sequence and position to the hrp
II
box required for HrpB-dependent T3SS
rso
transcription activation. The p2
bp
box is also present in the promoter regions of the essentially identical T3SS found in the very closely related species
Burkholderia thailandensis
(T3SS2
bt
). Analysis of p2
bp
box mutants showed that it is essential for HrpB
bp
-mediated transcription activation in both species. Although it has been suggested that T3SS2
bp
and T3SS2
bt
may function in phytopathogenicity, we were unable to demonstrate a phytopathogenic phenotype for
B. thailandensis
in three different plant hosts.
The Regulatory C-Terminal Domain of Subunit ε of F
o
F
1
ATP Synthase Is Dispensable for Growth and Survival of Escherichia coli
Authors: Taniguchi Naohiro , Suzuki Toshiharu , Berney Michael , Yoshida Masasuke , Cook Gregory M.
Published: February 2011

The C-terminal domain of subunit ε of the bacterial F
o
F
1
ATP synthase is reported to be an intrinsic inhibitor of ATP synthesis/hydrolysis activity
in vitro
, preventing wasteful hydrolysis of ATP under low-energy conditions. Mutants defective in this regulatory domain exhibited no significant difference in growth rate, molar growth yield, membrane potential, or intracellular ATP concentration under a wide range of growth conditions and stressors compared to wild-type cells, suggesting this inhibitory domain is dispensable for growth and survival of
Escherichia coli
.
A UDP-HexNAc:Polyprenol-P GalNAc-1-P Transferase (WecP) Representing a New Subgroup of the Enzyme Family
Authors: Merino Susana , Jimenez Natalia , Molero Raquel , Bouamama Lamiaa , Regué Miguel , Tomás Juan M.
Published: February 2011

The
Aeromonas hydrophila
AH-3 WecP represents a new class of UDP-HexNAc:polyprenol-P HexNAc-1-P transferases. These enzymes use a membrane-associated polyprenol phosphate acceptor (undecaprenyl phosphate [Und-P]) and a cytoplasmic UDP-
d
-
N
-acetylhexosamine sugar nucleotide as the donor substrate. Until now, all the WecA enzymes tested were able to transfer UDP-GlcNAc to the Und-P. In this study, we present
in vitro
and
in vivo
proofs that
A. hydrophila
AH-3 WecP transfers GalNAc to Und-P and is unable to transfer GlcNAc to the same enzyme substrate. The molecular topology of WecP is more similar to that of WbaP (UDP-Gal polyprenol-P transferase) than to that of WecA (UDP-GlcNAc polyprenol-P transferase). WecP is the first UDP-HexNAc:polyprenol-P GalNAc-1-P transferase described.
Health and human rights: an area of neglect in the core curriculum?
Authors: Fitchett Joseph Robert , Ferran Elena , Footer Katherine , Ahmed Natasha
Published: February 2011

Medical ethics and law education in the UK is undergoing continuous transformation. In parallel, human rights teaching with respect to health is expanding as a distinct field. Yet a resistance to the inclusion of human rights in the medical ethics and law curriculum persists. In response to Stirrat and colleagues, this article seeks to highlight the mutual benefit that could be derived from an integration of human rights into the already established medical ethics and law teaching in medical schools. It proposes that incorporating human rights into the curriculum would add value to traditional medical ethics and law teaching and provide a promising opportunity to enhance the interest from the student body.
On the relevance of personal responsibility in priority setting: a cross-sectional survey among Norwegian medical doctors
Authors: Bringedal Berit , Feiring Eli
Published: February 2011

The debate on responsibility for health takes place within political philosophy and in policy setting. It is increasingly relevant in the context of rationing scarce resources as a substantial, and growing, proportion of diseases in high-income countries is attributable to lifestyle. Until now, empirical studies of medical professionals' attitudes towards personal responsibility for health as a component of prioritisation have been lacking. This paper explores to what extent Norwegian physicians find personal responsibility for health relevant in prioritisation and what type of risk behaviour they consider relevant in such decisions. The proportion who agree that it should count varies from 17.1% (‘Healthcare priority should depend on the patient's responsibility for the disease’) to 26.9% (‘Access to scarce organ transplants should depend on the patient's responsibility for the disease’). Higher age and being male is positively correlated with acceptance. The doctors are more willing to consider substance use in priority setting decisions than choices on food and exercise. The findings reveal that a sizeable proportion have beliefs that conflict with the norms stated in the Norwegian Patient Act. It may be possible that the implementation of legal regulations can be hindered by the opposing attitudes among doctors. A further debate on the role personal responsibility should play in priority setting seems warranted. However, given the deep controversies about the concept of health responsibility and its application, it would be wise to proceed with caution.

Design

Nationally representative cross-sectional study.

Setting

Panel-data.

Participants

1072 respondents, response rate 65%.
Economic costs attributable to smoking in China: update and an 8-year comparison, 2000–2008
Authors: Yang Lian , Sung Hai-Yen , Mao Zhengzhong , Hu Teh-wei , Rao Keqin
Published: February 2011

Objective

To estimate the health-related economic costs attributable to smoking in China for persons aged 35 and older in 2003 and in 2008 and to compare these costs with the respective results from 2000.

Methods

A prevalence-based, disease-specific approach was used to estimate smoking-attributable direct and indirect economic costs. The primary data source was the 2003 and 2008 China National Health Services Survey, which contains individual participant's smoking status, healthcare use and expenditures.

Results

The total economic cost of smoking in China amounted to $17.1 billion in 2003 and $28.9 billion in 2008 (both measured in 2008 constant US$). Direct smoking-attributable healthcare costs in 2003 and 2008 were $4.2 billion and $6.2 billion, respectively. Indirect economic costs in 2003 and 2008 were $12.9 billion and $22.7 billion, respectively. Compared to 2000, the direct costs of smoking rose by 72% in 2003 and 154% in 2008, while the indirect costs of smoking rose by 170% in 2003 and 376% in 2008.

Conclusions

The economic burden of cigarette smoking has increased substantially in China during the past decade and is expected to continue to increase as the national economy and the price of healthcare services grow. Stronger intervention measures against smoking should be taken without delay to reduce the health and financial losses caused by smoking.
The Bending of Long H-Section Piles
Authors: Hanna Thomas H
Published: February 2011

During a pile-testing program at the site of Ontario Hydro's new Lambton generating station, three H-section piles were instrumented to determine whether they drove straight and were subsequently load tested. Very large deflections that occurred about the weak axis of the piles were measured. The practical implications of pile bending are treated in detail, the causes of pile bending discussed, and a general hypothesis put forward to explain pile bending.
NEUROMA OF THE RADIAL DIGITAL NERVE OF THE MIDDLE FINGER FOLLOWING TRIGGER RELEASE
Authors: Sreedharan S. , Teoh L. C. , Chew W. Y. C.
Published: February 2011

Trigger digit release is a common surgical procedure with a low complication rate. One of the potential complications is digital nerve injury. Though uncommon, digital nerve injury can be significantly symptomatic to the patient. We report a case of radial digital nerve neuroma formation following trigger release of the middle finger, which is considered to be safe, in terms of risk of digital nerve injury. We discuss our management of the complication, possible pitfalls which may have resulted in the complication in our case and offer possible means of overcoming these pitfalls.
Using external aggregate ratings for improving individual recommendations
Authors: Umyarov Akhmed , Tuzhilin Alexander
Published: February 2011

This article describes an approach for incorporating externally specified aggregate ratings information into certain types of recommender systems, including two types of collaborating filtering and a hierarchical linear regression model. First, we present a framework for incorporating aggregate rating information and apply this framework to the aforementioned individual rating models. Then we formally show that this additional aggregate rating information provides more accurate recommendations of individual items to individual users. Further, we experimentally confirm this theoretical finding by demonstrating on several datasets that the aggregate rating information indeed leads to better predictions of unknown ratings. We also propose scalable methods for incorporating this aggregate information and test our approaches on large datasets. Finally, we demonstrate that the aggregate rating information can also be used as a solution to the cold start problem of recommender systems.
SeDiM
Authors: Flores Carlos , Grace Paul , Blair Gordon S.
Published: February 2011

Service Discovery Protocols (SDPs) provide mechanisms that allow networked devices and applications to advertise and locate services with minimum or no human intervention. For fixed networked devices, SDPs such as SLP, Bonjour, and UPnP have been proposed. For more dynamic networked environments such as ad hoc, sensor, and wireless networks, a set of discovery technologies have been designed to operate optimally in such conditions; these include protocols like Ariadne, Allia, GSD, and UDDI. Hence, it is possible to advertise and discover services in diverse network types using one of a suite of technologies. Importantly, there are differences between individual protocols in terms of: (i) service description language, (ii) message format, (iii) directory architecture, (iv) discovery protocol behavior, (v) network communication, and (vi) nonfunctional features. These differences mean it is not possible to discover services with one protocol that is advertised by another and vice versa; we characterize this as
service discovery protocol heterogeneity
. In this article, we propose SeDiM, a dynamic middleware solution to allow heterogeneous discovery protocols within and across different domains to interoperate with one another. SeDiM is evaluated within a case study that demonstrates transparent interoperation of protocols including SLP and Bonjour in highly heterogeneous environments.
Aging attenuates the vasodilator response to relaxin
Authors: van Drongelen Joris , Ploemen Ivo H. J. , Pertijs Jeanne , Gooi Jonathan H. , Sweep Fred C. G. J. , Lotgering Frederik K. , Spaanderman Marc E. A. , Smits Paul
Published: February 2011

Relaxin, an insulin-like growth factor peptide, increases endothelium-dependent vasodilation and vascular compliance and decreases myogenic reactivity. These vascular effects significantly contribute to the physiological circulatory adaptations in pregnancy, particularly in the mesentery and kidney. Aging predisposes to vascular maladaptation and gestational hypertensive disease. We hypothesized that mild aging reduces the vascular responses to relaxin. In 20 young (10–12 wk) and 20 middle-aged (40–46 wk) female Wistar Hannover rats, vascular responses to chronic exposure of relaxin vs. placebo (5 days) were quantified in isolated mesenteric arteries and kidney. Vascular responses were evaluated using pressure-perfusion myograph, wire myograph, and an isolated perfused rat kidney model. Rxfp1 (relaxin family peptide) gene expression was determined by quantitative polymerase chain reaction. In young rats, relaxin stimulated nitric oxide (NO)-dependent flow-mediated vasodilation (2.67-fold, from 48 ± 9 to 18 ± 4 μl/min), reduced myogenic reactivity (from −1 ± 2 to 7 ± 3 μm/10 mmHg), and decreased mesenteric sensitivity to (28%, from 1.39 ± 0.08 to 1.78 ± 0.10 μM) but did not change compliance and renal perfusion flow (RPFF). In aged rats, relaxin did not affect any of the analyzed mesenteric or renal parameters. In aged compared with young placebo-treated rats, all mesenteric characteristics were comparable, while RPFF was lower (17%, from 6.9 ± 0.2 to 5.7 ± 0.1 ml·min−1·100 g−1) even though NO availability was comparable. Rxfp1 expression was not different among young and aged rats. Our findings suggest that moderate aging involves normal endothelial function but blunts the physiological endothelium-dependent and -independent vasodilator response to relaxin.
Eicosapentaenoic acid prevents atrial fibrillation associated with heart failure in a rabbit model
Authors: Kitamura Kazuhisa , Shibata Rei , Tsuji Yukiomi , Shimano Masayuki , Inden Yasuya , Murohara Toyoaki
Published: February 2011

Atrial fibrillation (AF) is associated with morbidity and mortality of heart failure. Eicosapentaenoic acid (EPA), which is contained in fish oil, was shown to reduce the risk of cardiovascular diseases. We investigated the effects of EPA on AF associated with heart failure in a rabbit model. Rabbits were subjected to ventricular tachypacing (VTP) for 4 wk with or without EPA treatment. Continuous VTP induced heart failure status in these rabbits. The duration of AF (DAF) induced by burst pacing was analyzed by electrophysiological studies. VTP resulted in increased DAF following burst pacing. EPA treatment attenuated increased DAF. Atrial fibrosis increased in response to VTP, accompanied by extracellular signal-regulated kinase (ERK) phosphorylation and transforming growth factor-β1 (TGF-β1) expression in the atrium. Treatment with EPA attenuated atrial fibrosis, ERK phosphorylation, and TGF-β1 expression in response to VTP. EPA treatment increased adiponectin as an anti-inflammatory adipokine and decreased tumor necrosis factor-α as a proinflammatory adipokine in the atrium and epicardial adipose tissues. EPA attenuated VTP-induced AF promotion and atrial remodeling, which was accompanied by modulating the profiles of adipokine production from epicardial adipose tissue. EPA may be useful for prevention and treatment of AF associated with heart failure.
Ferritin as a reporter gene for in vivo tracking of stem cells by 1.5-T cardiac MRI in a rat model of myocardial infarction
Authors: Campan Manuela , Lionetti Vincenzo , Aquaro Giovanni D. , Forini Francesca , Matteucci Marco , Vannucci Laura , Chiuppesi Flavia , Di Cristofano Claudio , Faggioni Michela , Maioli Margherita , Barile Lucio , Messina Elisa , Lombardi Massimo , Pucci Angela , Pistello Mauro , Recchia Fabio A.
Published: February 2011

The methods currently utilized to track stem cells by cardiac MRI are affected by important limitations, and new solutions are needed. We tested human ferritin heavy chain (hFTH) as a reporter gene for in vivo tracking of stem cells by cardiac MRI. Swine cardiac stem/progenitor cells were transduced with a lentiviral vector to overexpress hFTH and cultured to obtain cardiospheres (Cs). Myocardial infarction was induced in rats, and, after 45 min, the animals were subjected to intramyocardial injection of ∼200 hFTH-Cs or nontransduced Cs or saline solution in the border zone. By employing clinical standard 1.5-Tesla MRI scanner and a multiecho T2* gradient echo sequence, we localized iron-accumulating tissue only in hearts treated with hFTH-Cs. This signal was detectable at 1 wk after infarction, and its size did not change significantly after 4 wk (6.33 ± 3.05 vs. 4.41 ± 4.38 mm2). Cs transduction did not affect their cardioreparative potential, as indicated by the significantly better preserved left ventricular global and regional function and the 36% reduction in infarct size in both groups that received Cs compared with control infarcts. Prussian blue staining confirmed the presence of differentiated, iron-accumulating cells containing mitochondria of porcine origin. Cs-derived cells displayed CD31, α-smooth muscle, and α-sarcomeric actin antigens, indicating that the differentiation into endothelial, smooth muscle and cardiac muscle lineage was not affected by ferritin overexpression. In conclusion, hFTH can be used as a MRI reporter gene to track dividing/differentiating stem cells in the beating heart, while simultaneously monitoring cardiac morpho-functional changes.
Role of M1, M3, and M5 muscarinic acetylcholine receptors in cholinergic dilation of small arteries studied with gene-targeted mice
Authors: Gericke Adrian , Sniatecki Jan J. , Mayer Veronique G. A. , Goloborodko Evgeny , Patzak Andreas , Wess Jürgen , Pfeiffer Norbert
Published: February 2011

Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of vasorelaxing agents from the endothelium. The purpose of the present study was to determine the role of M1, M3, and M5 muscarinic acetylcholine receptors in vasodilation of small arteries using gene-targeted mice deficient in either of the three receptor subtypes (M1R−/−, M3R−/−, or M5R−/− mice, respectively). Muscarinic receptor gene expression was determined in murine cutaneous, skeletal muscle, and renal interlobar arteries using real-time PCR. Moreover, respective arteries from M1R−/−, M3R−/−, M5R−/−, and wild-type mice were isolated, cannulated with micropipettes, and pressurized. Luminal diameter was measured using video microscopy. mRNA for all five muscarinic receptor subtypes was detected in all three vascular preparations from wild-type mice. However, M3 receptor mRNA was found to be most abundant. Acetylcholine produced dose-dependent dilation in all three vascular preparations from M1R−/−, M5R−/−, and wild-type mice. In contrast, cholinergic dilation was virtually abolished in arteries from M3R−/− mice. Deletion of either M1, M3, or M5 receptor genes did not affect responses to nonmuscarinic vasodilators, such as substance P and nitroprusside. These findings provide the first direct evidence that M3 receptors mediate cholinergic vasodilation in cutaneous, skeletal muscle, and renal interlobar arteries. In contrast, neither M1 nor M5 receptors appear to be involved in cholinergic responses of the three vascular preparations tested.
Low circulating insulin-like growth factor I increases atherosclerosis in ApoE-deficient mice
Authors: Shai Shaw-Yung , Sukhanov Sergiy , Higashi Yusuke , Vaughn Charlotte , Rosen Clifford J. , Delafontaine Patrice
Published: February 2011

Some clinical studies have suggested that lower IGF-I levels may be associated with an increased risk of ischemic heart disease. We generated atherosclerosis-prone apolipoprotein E-deficient (ApoE−/−) mice with 6T alleles (6T/ApoE−/− mice) with a 20% decline in circulating IGF-I and fed these mice and control ApoE−/− mice with normal chow or a Western diet for 12 wk to evaluate the effect of low serum IGF-I on atherosclerosis progression. We found that the 6T/ApoE−/− phenotype was characterized by an increased atherosclerotic burden, elevated plaque macrophages, and increased proinflammatory cytokine TNF-α levels compared with ApoE−/− controls. 6T/ApoE−/− mice had similar body weight, blood pressure, serum total cholesterol levels, total plaque and smooth muscle cell apoptosis rates, and circulating levels of endothelial progenitor cells as ApoE−/− mice. 6T/ApoE−/− mice fed with normal chow had reduced vascular endothelial nitric oxide synthase mRNA levels and a trend to increased aortic expression of chemokine (C-C motif) receptor (CCR)1, CCR2, and monocyte chemoattractant protein-1/chemokine (C-C motif) ligand 2. Western diet-fed 6T/ApoE−/− mice had a trend to increased expression of macrophage scavenger receptor-1/scavenger receptor-A, osteopontin, ATP-binding cassette (subfamily A, member 1), and angiotensin-converting enzyme and elevated circulating levels of the neutrophil chemoattractant chemokine (C-X-C motif) ligand 1 (KC). Our data establish a link between lower circulating IGF-I and increased atherosclerosis that has important clinical implications.
Mammalian enabled (Mena) is a critical regulator of cardiac function
Authors: Aguilar Frédérick , Belmonte Stephen L. , Ram Rashmi , Noujaim Sami F. , Dunaevsky Olga , Protack Tricia L. , Jalife Jose , Todd Massey H. , Gertler Frank B. , Blaxall Burns C.
Published: February 2011

Mammalian enabled (Mena) of the Drosophila enabled/vasodilator-stimulated phosphoprotein gene family is a cytoskeletal protein implicated in actin regulation and cell motility. Cardiac Mena expression is enriched in intercalated discs (ICD), the critical intercellular communication nexus between adjacent muscle cells. We previously identified Mena gene expression to be a key predictor of human and murine heart failure (HF). To determine the in vivo function of Mena in the heart, we assessed Mena protein expression in multiple HF models and characterized the effects of genetic Mena deletion on cardiac structure and function. Immunoblot analysis revealed significant upregulation of Mena protein expression in left ventricle tissue from patients with end-stage HF, calsequestrin-overexpressing mice, and isoproterenol-infused mice. Characterization of the baseline cardiac function of adult Mena knockout mice (Mena−/−) via echocardiography demonstrated persistent cardiac dysfunction, including a significant reduction in percent fractional shortening compared with wild-type littermates. Electrocardiogram PR and QRS intervals were significantly prolonged in Mena−/−mice, manifested by slowed conduction on optical mapping studies. Ultrastructural analysis of Mena−/−hearts revealed disrupted organization and widening of ICD structures, mislocalization of the gap junction protein connexin 43 (Cx43) to the lateral borders of cardiomyoycytes, and increased Cx43 expression. Furthermore, the expression of vinculin (an adherens junction protein) was significantly reduced in Mena−/−mice. We report for the first time that genetic ablation of Mena results in cardiac dysfunction, highlighted by diminished contractile performance, disrupted ICD structure, and slowed electrical conduction.
Oxidative stress impairs insulin signal in skeletal muscle and causes insulin resistance in postinfarct heart failure
Authors: Ohta Yukihiro , Kinugawa Shintaro , Matsushima Shouji , Ono Taisuke , Sobirin Mochamad A. , Inoue Naoki , Yokota Takashi , Hirabayashi Kagami , Tsutsui Hiroyuki
Published: February 2011

Insulin resistance has been shown to occur as a consequence of heart failure. However, its exact mechanisms in this setting remain unknown. We have previously reported that oxidative stress is enhanced in the skeletal muscle from mice with heart failure after myocardial infarction (MI) ( 30 ). This study is aimed to investigate whether insulin resistance in postinfarct heart failure is due to the impairment of insulin signaling in the skeletal muscle caused by oxidative stress. Mice were divided into four groups: sham operated (sham); sham treated with apocynin, an inhibitor of NAD(P)H oxidase activation (10 mmol/l in drinking water); MI; and MI treated with apocynin. After 4 wk, intraperitoneal insulin tolerance tests were performed, and skeletal muscle samples were obtained for insulin signaling measurements. MI mice showed left ventricular dilation and dysfunction by echocardiography and increased left ventricular end-diastolic pressure and lung weight. The decrease in glucose level after insulin load significantly attenuated in MI compared with sham. Insulin-stimulated serine phosphorylation of Akt and glucose transporter-4 translocation were decreased in MI mice by 61 and 23%, respectively. Apocynin ameliorated the increase in oxidative stress and NAD(P)H oxidase activities measured by the lucigenin assay in the skeletal muscle after MI. It also improved insulin resistance and inhibited the decrease of Akt phosphorylation and glucose transporter-4 translocation. Insulin resistance was induced by the direct impairment of insulin signaling in the skeletal muscle from postinfarct heart failure, which was associated with the enhanced oxidative stress via NAD(P)H oxidase.
Protecting against vascular disease in brain
Authors: Faraci Frank M.
Published: February 2011

Endothelial cells exert an enormous influence on blood vessels throughout the circulation, but their impact is particularly pronounced in the brain. New concepts have emerged recently regarding the role of this cell type and mechanisms that contribute to endothelial dysfunction and vascular disease. Activation of the renin-angiotensin system plays a prominent role in producing these abnormalities. Both oxidative stress and local inflammation are key mechanisms that underlie vascular disease of diverse etiology. Endogenous mechanisms of vascular protection are also present, including antioxidants, anti-inflammatory molecules, and peroxisome proliferator-activated receptor-γ. Despite their clear importance, studies of mechanisms that underlie cerebrovascular disease continue to lag behind studies of vascular biology in general. Identification of endogenous molecules and pathways that protect the vasculature may result in targeted approaches to prevent or slow the progression of vascular disease that causes stroke and contributes to the vascular component of dementia and Alzheimer's disease.
Inflammatory signatures for eosinophilic vs. neutrophilic allergic pulmonary inflammation reveal critical regulatory checkpoints
Authors: Bogaert Pieter , Naessens Thomas , De Koker Stefaan , Hennuy Benoit , Hacha Jonathan , Smet Muriel , Cataldo Didier , Di Valentin Emmanuel , Piette Jacques , Tournoy Kurt G. , Grooten Johan
Published: February 2011

Contrary to the T-helper (Th)-2 bias and eosinophil-dominated bronchial inflammation encountered in most asthmatic subjects, other patients may exhibit neutrophil-predominant asthma subphenotypes, along with Th-1 and Th-17 cells. However, the etiology of many neutrophil-dominated asthma subphenotypes remains ill-understood, in part due to a lack of appropriate experimental models. To better understand the distinct immune-pathological features of eosinophilic vs. neutrophilic asthma types, we developed an ovalbumin (OVA)-based mouse model of neutrophil-dominated allergic pulmonary inflammation. Consequently, we probed for particular inflammatory signatures and checkpoints underlying the immune pathology in this new model, as well as in a conventional, eosinophil-dominated asthma model. Briefly, mice were OVA sensitized using either aluminum hydroxide (alum) or complete Freund's adjuvants, followed by OVA aerosol challenge. T-cell, granulocyte, and inflammatory mediator profiles were determined, along with alveolar macrophage genomewide transcriptome profiling. In contrast to the Th-2-dominated phenotype provoked by alum, OVA/ complete Freund's adjuvants adjuvant-based sensitization, followed by allergen challenge, elicited a pulmonary inflammation that was poorly controlled by dexamethasone, and in which Th-1 and Th-17 cells additionally participated. Analysis of the overall pulmonary and alveolar macrophage inflammatory mediator profiles revealed remarkable similarities between both models. Nevertheless, we observed pronounced differences in the IL-12/IFN-γ axis and its control by IL-18 and IL-18 binding protein, but also in macrophage arachidonic acid metabolism and expression of T-cell instructive ligands. These differential signatures, superimposed onto a generic inflammatory signature, denote distinctive inflammatory checkpoints potentially involved in orchestrating neutrophil-dominated asthma.
p53 Gene deficiency promotes hypoxia-induced pulmonary hypertension and vascular remodeling in mice
Authors: Mizuno Shiro , Bogaard Herman J. , Kraskauskas Donatas , Alhussaini Aysar , Gomez-Arroyo Jose , Voelkel Norbert F. , Ishizaki Takeshi
Published: February 2011

Chronic hypoxia induces pulmonary arterial remodeling, resulting in pulmonary hypertension and right ventricular hypertrophy. Hypoxia has been implicated as a physiological stimulus for p53 induction and hypoxia-inducible factor-1α (HIF-1α). However, the subcellular interactions between hypoxic exposure and expression of p53 and HIF-1α remain unclear. To examine the role of p53 and HIF-1α expression on hypoxia-induced pulmonary arterial remodeling, wild-type (WT) and p53 knockout (p53KO) mice were exposed to either normoxia or hypoxia for 8 wk. Following chronic hypoxia, both genotypes demonstrated elevated right ventricular pressures, right ventricular hypertrophy as measured by the ratio of the right ventricle to the left ventricle plus septum weights, and vascular remodeling. However, the right ventricular systolic pressures, the ratio of the right ventricle to the left ventricle plus septum weights, and the medial wall thickness of small vessels were significantly greater in the p53KO mice than in the WT mice. The p53KO mice had lower levels of p21 and miR34a expression, and higher levels of HIF-1α, VEGF, and PDGF expression than WT mice following chronic hypoxic exposure. This was associated with a higher proliferating cell nuclear antigen expression of pulmonary artery in p53KO mice. We conclude that p53 plays a critical role in the mitigation of hypoxia-induced small pulmonary arterial remodeling. By interacting with p21 and HIF-1α, p53 may suppress hypoxic pulmonary arterial remodeling and pulmonary arterial smooth muscle cell proliferation under hypoxia.
Emerging themes of cAMP regulation of the pulmonary endothelial barrier
Authors: Sayner Sarah L.
Published: February 2011

The presence of excess fluid in the interstitium and air spaces of the lung presents severe restrictions to gas exchange. The pulmonary endothelial barrier regulates the flux of fluid and plasma proteins from the vascular space into the underlying tissue. The integrity of this endothelial barrier is dynamically regulated by transitions in cAMP (3′,5′-cyclic adenosine monophosphate), which are synthesized in discrete subcellular compartments. Cyclic AMP generated in the subplasma membrane compartment acts through PKA and Epac (exchange protein directly activated by cAMP) to tighten cell adhesions, strengthen cortical actin, reduce actomyosin contraction, and decrease permeability. Confining cAMP within the subplasma membrane space is critical to its barrier-protective properties. When cAMP escapes the near membrane compartment and gains access to the cytosolic compartment, or when soluble adenylyl cyclases generate cAMP within the cytosolic compartment, this second messenger activates established cytosolic cAMP signaling cascades to perturb the endothelial barrier through PKA-mediated disruption of microtubules. Thus the concept of cAMP compartmentalization in endothelial barrier regulation is gaining momentum and new possibilities are being unveiled for cytosolic cAMP signaling with the emergence of the bicarbonate-regulated mammalian soluble adenylyl cyclase (sAC or AC10).
Atomistic Simulation of High‐Density Uranium Fuels
Authors: Garcés Jorge Eduardo , Bozzolo Guillermo
Published: February 2011

We apply an atomistic modeling approach to deal with interfacial phenomena in high‐density uranium fuels. The effects of Si, as additive to Al or as U‐Mo‐particles coating, on the behavior of the Al/U‐Mo interface is modeled by using the Bozzolo‐Ferrante‐Smith (BFS) method for alloys. The basic experimental features characterizing the real system are identified, via simulations and atom‐by‐atom analysis. These include (1) the trend indicating formation of interfacial compounds, (2) much reduced diffusion of Al into U‐Mo solid solution due to the high Si concentration, (3) Si depletion in the Al matrix, (4) an unexpected interaction between Mo and Si which inhibits Si diffusion to deeper layers in the U‐Mo solid solution, and (5) the minimum amount of Si needed to perform as an effective diffusion barrier. Simulation results related to alternatives to Si dispersed in the Al matrix, such as the use of C coating of U‐Mo particles or Zr instead of the Al matrix, are also shown. Recent experimental results confirmed early theoretical proposals, along the lines of the results reported in this work, showing that atomistic computational modeling could become a valuable tool to aid the experimental work in the development of nuclear fuels.
Scale Space Methods for Analysis of Type 2 Diabetes Patients′ Blood Glucose Values
Authors: Skrøvseth Stein Olav , Godtliebsen Fred
Published: February 2011

We describe how scale space methods can be used for quantitative analysis of blood glucose
concentrations from type 2 diabetes patients. Blood glucose values were recorded voluntarily
by the patients over one full year as part of a self‐management process, where the time
and frequency of the recordings are decided by the patients. This makes a unique dataset
in its extent, though with a large variation in reliability of the recordings. Scale space and
frequency space techniques are suited to reveal important features of unevenly sampled data,
and useful for identifying medically relevant features for use both by patients as part of their
self‐management process, and provide useful information for physicians.
Chemopreventive Potential of Synergy1 and Soybean in Reducing Azoxymethane-Induced Aberrant Crypt Foci in Fisher 344 Male Rats
Authors: Gourineni V. P. , Verghese M. , Boateng J. , Shackelford L. , Bhat K. N
Published: February 2011

Synergy1, a prebiotic composed of Inulin and Oligofructose (1 : 1). Soybean meal is a natural source of isoflavones. The objective was to investigate the effects of feeding Synergy1 and SM on the incidence of azoxymethane- (AOM-) induced aberrant crypt foci (ACF) in Fisher 344 male rats. Rats (54) were randomly assigned to 9 groups (n=6). Control group (C) was fed AIN-93G and treatment groups Syn1 and SM at 5% and 10% singly and in combinations. Rats were injected with two s/c injections of AOM at 7 and 8 weeks of age at 16 mg/kg body weight and killed at 17 weeks by CO2asphyxiation. Colonic ACF enumeration and hepatic enzyme activities were measured. Reductions (%) in total ACF among treatment groups fed combinations were higher (67–77) compared to groups fed singly (52–64). Synergistic mechanisms among phytochemicals may be responsible suggesting protective role in colon carcinogenesis with implications in food product development.
Expression Profiling of Liposarcoma Yields a Multigene Predictor of Patient Outcome and Identifies Genes That Contribute to Liposarcomagenesis
Authors: Gobble Ryan M. , Qin Li-Xuan , Brill Elliott R. , Angeles Christina V. , Ugras Stacy , O'Connor Rachael B. , Moraco Nicole H. , DeCarolis Penelope L. , Antonescu Cristina , Singer Samuel
Published: February 2011

Liposarcomas are the most common type of soft tissue sarcoma but their genetics are poorly defined. To identify genes that contribute to liposarcomagenesis and serve as prognostic candidates, we undertook expression profiling of 140 primary liposarcoma samples, which were randomly split into training set (n = 95) and test set (n = 45). A multigene predictor for distant recurrence-free survival (DRFS) was developed by the supervised principal component method. Expression levels of the 588 genes in the predictor were used to calculate a risk score for each patient. In validation of the predictor in the test set, patients with low risk score had a 3-year DRFS of 83% versus 45% for high risk score patients (P = 0.001). The HR for high versus low score, adjusted for histologic subtype, was 4.42 (95% CI, 1.26–15.55; P = 0.021). The concordance probability for risk score was 0.732. In contrast, the concordance probability for histologic subtype, which had been considered the best predictor of outcome in liposarcoma, was 0.669. Genes related to adipogenesis, DNA replication, mitosis, and spindle assembly checkpoint control were all highly represented in the multigene predictor. Three genes from the predictor, TOP2A, PTK7, and CHEK1, were found to be overexpressed in liposarcoma samples of all five subtypes and in liposarcoma cell lines. RNAi-mediated knockdown of these genes in liposarcoma cell lines reduced proliferation and invasiveness and increased apoptosis. Taken together, our findings identify genes that seem to be involved in liposarcomagenesis and have promise as therapeutic targets, and support the use of this multigene predictor to improve risk stratification for individual patients with liposarcoma. Cancer Res; 71(7); 2697–705. ©2011 AACR.
Prevalence of Possible Occupational Asthma in Hairdressers Working in Hair Salons for Women
Authors: Espuga M. , Muñoz X. , Plana E. , Ramón M.A. , Morell F. , Sunyer J. , Cruz M.J.
Published: February 2011

Background: The aim of this study was to determine the prevalence of possible occupational asthma (OA) in hairdressers. Methods: A telephone questionnaire (Q1) was administered to 1,334 individuals from a total of 1,875 hairdressers working in hair salons for women in Barcelona (response rate 71%) to identify those with respiratory symptoms. Multiple correspondence analysis showed 5 specific questions for assessing symptoms of asthma. Individuals who gave a positive response to 1 of these questions (n = 251) were given a second validated questionnaire (Q2) to identify those with suspected OA. OA was defined according to a classification tree based on the response to queries on nasal itching, daily symptoms throughout the week at work, nasal secretions, voice loss, wheezing, and sputum production as reported previously. Moreover, we calculated the prevalence of OA according to the conventional criteria of improvement and/or worsening of symptoms in relation to exposure at work and during off-work time on weekends and during vacations. Results: Asthma was present in 9.5% of hairdressers. From Q2 data, 72 were classified as having possible OA, yielding a prevalence of OA from 5.4 (72/1,334) to 7.8% according to the classification tree previously described. A prevalence from 4.6 (62/1,334) to 6.7% was obtained using conventional criteria. Rhinitis or dermatitis (OR 7.80), as well as exacerbation of symptoms at work and persistence of symptoms on weekends (OR 2.99) were associated with the development of OA. Conclusions: Hairdressing employment can induce asthma. Episodes of rhinitis or dermatitis seem to be risk factors for the development of OA in this population.
Involvement of Residues Asp8, Asn13, Glu145, Asp168, and Thr173 in the Chaperone Activity of a Recombinant DnaK from Bacillus licheniformis
Authors: Lin Min-Guan , Liang Wan-Chi , Chen Bo-En , Chou Wei-Mou , Lin Long-Liu
Published: February 2011

Based on the sequence homology, we have modeled the three-dimensional structure of Bacillus licheniformis DnaK (BlDnaK), a counterpart of Hsp70, and identified five different amino acids that might be responsible for maintaining ADP-Mg2+-Pi in the correct configuration at the ATP-binding cleft of the protein. As compared with wild-type BlDnaK, site-directed mutant proteins D8A, N13D, E145A, D168A, and T173A had a dramatic reduction in their chaperone activities. Complementation test revealed that the mutant proteins lost completely the ability to rescue the temperature-sensitive growth defect of Escherichia colidnaK756-ts. Wild-type BlDnak assisted the refolding of denatured firefly luciferase, whereas a significant decrease in this ability was observed for the mutant proteins. Simultaneous addition of B. licheniformis DnaJ, BlGrpE, and NR-peptide, did not synergistically stimulate the ATPase activity of D8A, E145A, D168A and T173A. Circular dichroism spectra were nearly identical for wild-type and mutant proteins, and they, except D8A, also exhibited a similar sensitivity towards temperature-induced denaturation. These results suggest that the selected residues are critical for the proper function of BlDnaK.
Relationship between Radar-Estimated Precipitation and Synoptic Weather Patterns in the European Alps
Authors: Rudolph James V. , Friedrich Katja , Germann Urs
Published: February 2011

A 9-yr (2000–08) analysis of precipitation characteristics for the central and western European Alps has been generated from ground-based operational weather radar data provided by the Swiss radar network. The radar-based precipitation analysis focuses on the relationship between synoptic-scale weather patterns and mesoscale precipitation distribution over complex alpine terrain. The analysis divides the Alps into six regions (each approximately 200 × 200 km2in size)—one on the northern side, two each on the western and southern sides of the Alps, and one in the Massif Central—representing various orographic aspects and localized climates within the radar coverage area. For each region, estimated precipitation rate derived from radar data is analyzed on a seasonal basis for total daily precipitation and frequency of high-precipitation-rate events. The summer season has the highest total daily precipitation for all regions in the study, whereas median values of daily precipitation in winter are less than one-half of median daily precipitation for summer. For all regions, high-precipitation-rate events occur most frequently in the summer. Daily synoptic-scale weather patterns are associated with total daily precipitation and frequency of high precipitation rate to show that an advective synoptic-scale pattern with southerly midtropospheric flow results in the highest median and 90th-quantile values for total daily precipitation and that a convective synoptic-scale pattern results in elevated frequency of extreme-precipitation-rate events.
How do Former Inmates Perform in the Community? A Survival Analysis of Rearrests, Reconvictions, and Technical Parole Violations
Authors: Ostermann Michael
Published: February 2011

This study provides insight into the postrelease performance of all former inmates with available data who were released from a prison in New Jersey in 2006 ( N = 12,187). Three indicators of recidivism are considered: (a) an arrest for a new crime, (b) a conviction for a new crime, and (c) a technical parole violation. Individuals are categorized into groups according to the release mechanism that they experienced: discretionary parole, mandatory parole, or unconditional release. Multivariate analyses utilize Cox proportional hazards survival tests. Results indicate that after approximately 3 years of follow-up time, those released to supervision were generally less involved in new crimes when compared with those who were released unconditionally. However, a high proportion of those who were paroled recidivated shortly after release, and the predicted probability that a former inmate would recidivate did not substantially differ between release groups in the presence of statistical controls.
Reconceptualizing Victimization and Victimization Responses
Authors: Zaykowski Heather
Published: February 2011

Research consistently demonstrates that severity, often measured by victim injury, is the most influential factor to predict reporting crimes to the police. However, less is known with regard to how the victim’s perception of the incident or their involvement in offending behavior inhibits this decision. The current study examines how traditional indicators (i.e., victim, offender and incident characteristics), the victim’s offending behavior, and perceptual measures influence police awareness of criminal victimization. Results suggest that victim injury and offending status does not significantly predict police awareness when subjective measures are controlled. However, multiple offenders, community crime, and parental knowledge significantly increased the odds that the police were aware that the victimization occurred.