bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bmper Inhibits Endothelial Expression of Inflammatory Adhesion Molecules and Protects Against Atherosclerosis
Authors: Pi Xinchun , Lockyer Pamela , Dyer Laura A. , Schisler Jonathan C. , Russell Brooke , Carey Stephen , Sweet Daniel Timothy , Chen Zhongming , Tzima Ellie , Willis Monte S. , Homeister Jonathon W. , Moser Martin , Patterson Cam 
Published: July 2012

Objective—
Bone morphogenetic proteins (Bmps) are important mediators of inflammation and atherosclerosis, though their mechanism of action is not fully understood. To better understand the contribution of the Bmp signaling pathway in vascular inflammation, we investigated the role of Bmper (Bmp endothelial cell precursor–derived regulator), an extracellular Bmp modulator, in an induced in vivo model of inflammation and atherosclerosis.

Methods and Results—

We crossed apolipoprotein E–deficient (ApoE
−/−
) mice with mice missing 1 allele of Bmper (Bmper
+/−
mice used in the place of Bmper
−/−
mice that die at birth) and measured the development of atherosclerosis in mice fed a high-fat diet. Bmper haploinsufficiency in ApoE
−/−
mice (Bmper
+/−
;ApoE
−/−
mice) led to a more severe phenotype compared with Bmper
+/+
;ApoE
−/−
mice. Bmper
+/−
;ApoE
−/−
mice also exhibited increased Bmp activity in the endothelial cells in both the greater and lesser curvatures of the aortic arch, suggesting a role for Bmper in regulating Bmp-mediated inflammation associated with laminar and oscillatory shear stress. Small interfering RNA knockdown of Bmper in human umbilical vein endothelial cells caused a dramatic increase in the inflammatory markers intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 at rest and after exposure to oscillatory and laminar shear stress.

Conclusion—
We conclude that Bmper is a critical regulator of Bmp-mediated vascular inflammation and that the fine-tuning of Bmp and Bmper levels is essential in the maintenance of normal vascular homeostasis.
Enhancement of 26S Proteasome Functionality Connects Oxidative Stress and Vascular Endothelial Inflammatory Response in Diabetes Mellitus
Authors: Liu Hongtao , Yu Shujie , Xu Wenjia , Xu Jian 
Published: July 2012

Objective—
Although the connection of oxidative stress and inflammation has been long recognized in diabetes mellitus, the underlying mechanisms are not fully elucidated. This study defined the role of 26S proteasomes in promoting vascular inflammatory response in early diabetes mellitus.

Methods and Results—

The 26S proteasome functionality, markers of autophagy, and unfolded protein response were assessed in (1) cultured 26S proteasome reporter cells and endothelial cells challenged with high glucose, (2) transgenic reporter (Ub
G76V
–green fluorescence protein) and wild-type (C57BL/6J) mice rendered diabetic, and (3) genetically diabetic (Akita and OVE26) mice. In glucose-challenged cells, and also in aortic, renal, and retinal tissues from diabetic mice, enhanced 26S proteasome functionality was observed, evidenced by augmentation of proteasome (chymotrypsin-like) activities and reduction in 26S proteasome reporter proteins, accompanied by increased nitrotyrosine-containing proteins. Also, whereas inhibitor of the nuclear factor κ-light-chain-enhancer of activated B cells α proteins were decreased, an increase was found in nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) nucleus translocation, which enhanced the NF-κB–mediated proinflammatory response, without affecting markers of autophagy or unfolded protein response. Importantly, the alterations were abolished by MG132 administration, small interfering RNA knockdown of PA700 (proteasome activator protein complex), or superoxide scavenging in vivo.

Conclusion—
Early hyperglycemia enhances 26S proteasome functionality, not autophagy or unfolded protein response, through peroxynitrite/superoxide-mediated PA700-dependent proteasomal activation, which elevates NF- ĸB-mediated endothelial inflammatory response in early diabetes mellitus.
Hyperbilirubinemia, Augmentation of Endothelial Function, and Decrease in Oxidative Stress in Gilbert Syndrome
Authors: Maruhashi Tatsuya , Soga Junko , Fujimura Noritaka , Idei Naomi , Mikami Shinsuke , Iwamoto Yumiko , Kajikawa Masato , Matsumoto Takeshi , Kihara Yasuki , Chayama Kazuaki , Noma Kensuke , Nakashima Ayumu , Tomiyama Hirofumi , Takase Bonpei , Yamashina Akira , Higashi Yukihito 
Published: July 2012

Background—
Patients with Gilbert syndrome have mild unconjugated hyperbilirubinemia. It has been shown that bilirubin is an endogenous antioxidant. We evaluated the role of oxidative stress in endothelial function in patients with Gilbert syndrome under normal conditions without cardiovascular risk factors.

Methods and Results—

A total of 108 young men with Gilbert syndrome without cardiovascular risk factors and 108 age-matched healthy men (normal controls) were enrolled in this study. Serum concentrations of bilirubin were higher in patients with Gilbert syndrome than in control subjects (29.2±11.6 versus 9.4±2.7 μmol/L;
P
<0.001). Serum concentrations of malondialdehyde-modified low-density lipoprotein and urinary excretion of 8-hydroxy-2′-deoxyguanosine (8-OHdG), as indices of oxidative stress, were lower in patients with Gilbert syndrome than in control subjects (61.8±24.5 versus 72.5±21.8 U/L,
P
=0.034; 7.8±2.4 versus 10.4±3.2 ng/mg creatinine,
P
=0.001, respectively). Flow-mediated vasodilation was greater in patients with Gilbert syndrome than in normal control subjects (7.2±2.2% versus 5.9±1.7%;
P
<0.001). Vascular responses to nitroglycerine were not significantly different between the 2 groups. Flow-mediated vasodilation correlated with serum concentration of bilirubin (
r
=0.44,
P
<0.001), malondialdehyde-modified low-density lipoprotein (
r
=−0.25,
P
=0.01), and urinary excretion of 8-OHdG (
r
=−0.27,
P
=0.004) in patients with Gilbert syndrome but not in control subjects. In addition, serum concentration of bilirubin correlated with malondialdehyde-modified low-density lipoprotein (
r
=−0.20,
P
=0.04) and 8-OHdG (
r
=−0.21,
P
=0.02) in patients with Gilbert syndrome but not in control subjects.

Conclusions—
Patients with Gilbert syndrome had low levels of oxidative stress associated with hyperbilirubinemia and enhancement of endothelium-dependent vasodilation.

Clinical Trial Registration—

URL:
http://www.umin.ac.jp
. Unique identifier: UMIN000003409.
Stratification of Heterogeneous Diffusion MRI Ischemic Lesion With Kurtosis Imaging
Authors: Cheung Jerry S. , Wang Enfeng , Lo Eng H , Sun Phillip Zhe 
Published: July 2012

Background and Purpose—
Ischemic tissue damage is heterogeneous, resulting in complex patterns in the widely used diffusion-weighted MRI. Our study examined the spatiotemporal characteristics of diffusion kurtosis imaging in an animal model of transient middle cerebral artery occlusion.

Methods—

Adult male Wistar rats (N=18) were subjected to 90 minutes middle cerebral artery occlusion. Multiparametric MR images were obtained during middle cerebral artery occlusion and 20 minutes after reperfusion with diffusion-weighted MRI obtained using 8 b-values from 250 to 3000 s/mm
2
in 6 diffusion gradient directions. Diffusion and kurtosis lesions were outlined in shuffled images by 2 investigators independently. T
2
MRI was obtained 24 hours after middle cerebral artery occlusion to evaluate stroke outcome.

Results—
Mean diffusion lesion (23.5%±8.1%, percentage of the brain slice) was significantly larger than mean kurtosis lesion (13.2%±2.0%) during middle cerebral artery occlusion. Mean diffusion lesion decreased significantly after reperfusion (13.8%±4.3%), whereas mean kurtosis lesion showed little change (13.0%±2.5%) with their lesion size difference being insignificant.

Conclusions—
We demonstrated that mean diffusion/mean kurtosis mismatch recovered reasonably well on reperfusion, whereas regions with concurrent mean diffusion and mean kurtosis deficits showed poor recovery. Diffusion kurtosis imaging may help stratify heterogeneous diffusion-weighted MRI lesions for enhanced characterization of ischemic tissue injury.
Brain-Derived Neurotrophic Factor Val66Met Polymorphism Predicts Worse Functional Outcome After Surgery in Patients With Unruptured Brain Arteriovenous Malformation
Authors: Westbroek Erick M. , Pawlikowska Ludmila , Lawton Michael T. , McCulloch Charles E. , Young William L. , Kim Helen 
Published: July 2012

Background and Purpose—
The Val66Met polymorphism of brain-derived neurotrophic factor is associated with decreased brain-derived neurotrophic factor secretion and poor outcome after acute neurological injury. We hypothesized that the Met allele is associated with worsening of functional outcome after brain arteriovenous malformation resection.

Methods—
Three hundred forty-one surgically treated patients with brain arteriovenous malformation with outcome data were genotyped for Val66Met. Outcome was change in modified Rankin Scale preoperatively versus postoperatively, dichotomized into poor (change >0) or good outcome (change ≤0). Likelihood ratio tests for interactions and logistic regression analysis were performed.

Results—

A significant interaction (
P
=0.03) of Val66Met genotype and hemorrhagic presentation existed; thus, ruptured and unruptured patients were considered separately. The Met allele was associated with increased risk of poor outcome among patients presenting unruptured (OR, 2.15; 95% CI, 1.02–4.55;
P
=0.045) but not ruptured (OR, 0.54; 95% CI, 0.19–1.53;
P
=0.25), adjusting for covariates.

Conclusions—
The Val66Met polymorphism is associated with worsened surgical outcome in patients with unruptured brain arteriovenous malformation, a group that currently has no good risk predictors. Further studies replicating these findings are needed.
Mortality and antioxidant responses in the planarian (Dugesia japonica) after exposure to copper
Authors: Zhang Xiufang , Zhang Bowen , Yi Hongyang , Zhao Bosheng 
Published: July 2012

The planarians ( Dugesia japonica) are distributed widely in China, Japan, Korea, and southern Siberia. In this study, the acute toxicity of copper on D. japonica was evaluated using mortality and the activity of the enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), and reactive oxygen species (ROS) as endpoints. Acute toxicity tests were conducted according to the American Society for Testing and Materials guidelines. The 24-, 48-, 72-, and 96-h median lethal concentration that killed 50% of individuals (LC50) were calculated as 8.70, 6.31, 4.48, and 4.23 mg Cu2+/L, respectively, based on measured copper concentrations. When compared with different phyla or classes of freshwater animals, the rank of D. japonica in species sensitivity was in the range of 25–26 for 96-h LC50. The antioxidant enzymes SOD and CAT were determined in D. japonica exposed to two copper concentrations (50 and 100 μg Cu2+/L) with a short-term exposure (15 days). They all attained peak value and then reduced during the experimental period. The GPx activities were activated only for 100 μg/L treatments at days 3 and 6 and then renewed to the original level. Meanwhile, copper significantly increased the levels of ROS in D. japonica. Our study suggests that the adult D. japonica was less sensitive to copper than most other aquatic species. Copper may induce oxidative stress and interfere with the antioxidant defense system of the D. japonica, including SOD and CAT. GPx might be an insusceptible antioxidant enzyme in the metabolic detoxification processes in adult D. japonica.
Patterns of hypnotic medication use for sleep disturbance amongst hospital inpatients
Authors: Rankin Katherine , Brakoulias Vlasios 
Published: July 2012

Objective: The objective of this article is to examine patterns of temazepam prescribing amongst inpatients at a Sydney teaching hospital. Method: The study involved a retrospective file audit of 98.8% ( n=410) of patients discharged from psychiatry, medical, surgical and obstetric and gynaecology wards of Nepean Hospital during a one-week period. Data was collected on patient demographics, temazepam and other sedative-hypnotic use, falls risk and analgesia use. Results: Sixteen per cent ( n=64) of patients were prescribed temazepam during their stay. All patients from the psychiatry wards had been prescribed temazepam. Fifteen per cent ( n=6) of falls risk patients had been prescribed temazepam. Temazepam prescription was associated with an increased length of stay, psychiatry and surgical wards, and higher use of analgesia. Conclusions: Temazepam continues to be a frequently prescribed medication in the acute psychiatry setting. Its frequent prescription to patients in surgical wards and to those prescribed analgesic agents indicates that it still has a role in settling patients to sleep in the hospital setting.
Analysis of the importance of family in the development of sense of coherence during adolescence
Authors: García-Moya Irene , Rivera Francisco , Moreno Carmen , Lindström Bengt , Jiménez-Iglesias Antonia 
Published: July 2012

Aims: The aim of this work was to study the influence of several family dimensions on sense of coherence (SOC) in adolescence, controlling the possible effects from the demographic variables, gender and age. Methods: The sample consisted of 7580 adolescents between the ages of 13 and 18, who had taken part in the 2010 edition of the WHO Health Behaviour in School-aged Children study in Spain. Results: The results showed that there were no significant gender differences in SOC levels. However, age had a significant influence on SOC. Higher levels of SOC were found in adolescents aged 13 and 14 compared to older participants. Family variables explained 18% of SOC variability, with affection, easy communication with parents, and parental knowledge as the most outstanding variables. In addition, positive relationships between parents and family affluence had a significant role in explaining SOC levels. Conclusions: The results suggest that the family context plays an important role in providing meaningful experiences for the development of a strong SOC in adolescence.
Megakaryocyte pathology and bone marrow fibrosis: the lysyl oxidase connection
Authors: Papadantonakis Nikolaos , Matsuura Shinobu , Ravid Katya 
Published: July 2012

AbstractMegakaryocytes (MKs), the platelet precursors, are capable of accumulating DNA greater than a diploid content as part of their cell cycle. MKs have been recognized as mediating fibrosis in a subset of hematologic malignancies, including acute megakaryoblastic leukemia and a subset of myeloproliferative neoplasms. The mechanisms responsible for fibrosis remain only partially understood. Past studies highlighted the role of growth factors in such pathologies, and recently, the protein lysyl oxidase (LOX) has been implicated in proliferation of MKs, ploidy and deposition of fibers. LOX was initially characterized as a protein responsible for the intermolecular cross-linking of elastin and collagen, and in recent years it has been identified as regulator of various pathologies, such as cancer and inflammation. Here, we review recent advances in the understanding of the contribution of MKs to the progression of myelofibrosis, highlighting the newly identified role of LOX.
Syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet secretion
Authors: Ye Shaojing , Karim Zubair A. , Al Hawas Rania , Pessin Jeffery E. , Filipovich Alexandra H. , Whiteheart Sidney W. 
Published: July 2012

AbstractThe platelet release reaction plays a critical role in thrombosis and contributes to the events that follow hemostasis. Previous studies have shown that platelet secretion is mediated by Soluble NSF Attachment Protein Receptor (SNARE) proteins from granule and plasma membranes. The SNAREs form transmembrane complexes that mediate membrane fusion and granule cargo release. Although VAMP-8 (v-SNARE) and SNAP-23 (a t-SNARE class) are important for platelet secretion, the identity of the functional syntaxin (another t-SNARE class) has been controversial. Previous studies using anti-syntaxin Abs in permeabilized platelets have suggested roles for both syntaxin-2 and syntaxin-4. In the present study, we tested these conclusions using platelets from syntaxin-knockout mouse strains and from a Familial Hemophagocytic Lymphohistiocytosis type 4 (FHL4) patient. Platelets from syntaxin-2 and syntaxin-4 single- or double-knockout mice had no secretion defect. Platelets from a FHL4 patient deficient in syntaxin-11 had a robust defect in agonist-induced secretion although their morphology, activation, and cargo levels appeared normal. Semiquantitative Western blotting showed that syntaxin-11 is the more abundant syntaxin in both human and murine platelets. Coimmunoprecipitation experiments showed that syntaxin-11 can form SNARE complexes with both VAMP-8 and SNAP-23. The results of the present study indicate that syntaxin-11, but not syntaxin-2 or syntaxin-4, is required for platelet exocytosis.
Orthogonally additive-additive and orthogonally quadratic-quadratic functional equation in orthogonality spaces
Authors: Park Choonkil , Kim Gwang Hui , Lee Jung Rye , Shin Dong Yun 
Published: July 2012

Abstract
Using fixed point method, we prove the Hyers-Ulam stability of the orthogonally additive-additive and orthogonally quadratic-quadratic functional equation

f

x
+
y
+
z

2

+
f

x
+
y
-
z

2

+
f

x
-
y
+
z

2

+
f

y
+
z
-
x

2

=
f

(

x

)

+
f

(

y

)

+
f

(

z

)

for all x, y, z with x ⊥ y, in orthogonality Banach spaces and in non-Archimedean orthogonality Banach spaces.

Mathematics Subject Classification (2010): Primary 39B55, 46S10, 39B72, 39B52, 54E40, 47H10, 47S10, 26E30, 12J25, 46H25.
Health facility-based malaria surveillance: The effects of age, area of residence and diagnostics on test positivity rates
Authors: Francis Damon , Gasasira Anne , Kigozi Ruth , Kigozi Simon , Nasr Sussann , Kamya Moses R , Dorsey Grant 
Published: July 2012

Abstract

Background
The malaria test positivity rate (TPR) is increasingly used as an indicator of malaria morbidity because TPR is based on laboratory-confirmed cases and is simple to incorporate into existing surveillance systems. However, temporal trends in TPR may reflect changes in factors associated with malaria rather than true changes in malaria morbidity. This study examines the effects of age, area of residence and diagnostic test on TPR at two health facilities in regions of Uganda with differing malaria endemicity.

Methods
The analysis included data from diagnostic blood smears performed at health facilities in Walukuba and Aduku between January 2009 and December 2010. The associations between age and time and between age and TPR were evaluated independently to determine the potential for age to confound temporal trends in TPR. Subsequently, differences between observed TPR and TPR adjusted for age were compared to determine if confounding was present. A similar analysis was performed for area of residence. Temporal trends in observed TPR were compared to trends in TPR expected using rapid diagnostic tests, which were modelled based upon sensitivity and specificity in prior studies.

Results
Age was independently associated with both TPR and time at both sites. At Aduku, age-adjusted TPR increased relative to observed TPR due to the association between younger age and TPR and the gradual increase in age distribution. At Walukuba, there were no clear differences between observed and age-adjusted TPR. Area of residence was independently associated with both TPR and time at both sites, though there were no clear differences in temporal trends in area of residence-adjusted TPR and observed TPR at either site. Expected TPR with pLDH- and HRP-2-based rapid diagnostic tests (RDTs) was higher than observed TPR at all time points at both sites.

Conclusions
Adjusting for potential confounders such as age and area of residence can ensure that temporal trends in TPR due to confounding are not mistakenly ascribed to true changes in malaria morbidity. The potentially large effect of diagnostic test on TPR can be accounted for by calculating and adjusting for the sensitivity and specificity of the test used.
Effect of obesity reduction on preservation of heart function and attenuation of left ventricular remodeling, oxidative stress and inflammation in obese mice
Authors: Wang Hui-Ting , Liu Chu-Feng , Tsai Tzu-Hsien , Chen Yung-Lung , Chang Hsueh-Wen , Tsai Ching-Yen , Leu Steve , Zhen Yen-Yi , Chai Han-Tan , Chung Sheng-Ying , Chua Sarah , Yen Chia-Hung , Yip Hon-Kan 
Published: July 2012

Abstract

Background
Obesity is an important cardiovascular risk factor. This study tested the effect of obesity reduction on preserving left ventricular ejection fraction (LVEF) and attenuating inflammation, oxidative stress and LV remodeling in obese mice.

Methods and results
Eight-week-old C57BL/6 J mice (n=24) were equally divided into control (fed a control diet for 22 weeks), obesity (high-fat diet, 22 weeks), and obese reduction (OR) (high-fat diet, 14 weeks; then control diet, 8 weeks). Animals were sacrificed at post 22-week high-fat diet and the LV myocardium collected. Heart weight, body weight, abdominal-fat weight, total cholesterol level and fasting blood glucose were higher in obesity than in control and OR (all p<0.001). Inflammation measured by mRNA expressions of IL-6, MMP-9, PAI-1 and leptin and protein expression of NF-κB was higher, whereas anti-inflammation measured by mRNA expressions of adiponectin and INF-γ was lower in obesity than in control and OR (all p<0.003). Oxidative protein expressions of NOX-1, NOX-2 and oxidized protein were higher, whereas expression of anti-oxidant markers HO-1 and NQO-1 were lower (all p<0.01); and apoptosis measured by Bax and caspase 3 was higher, whereas anti-apoptotic Bcl-2 was lower in obesity as compared with control and OR (all p<0.001). The expressions of fibrotic markers phosphorylated Smad3 and TGF-β were higher, whereas expression of anti-fibrotic phosphorylated Smad1/5 and BMP-2 were lower (all p<0.02); and LVEF was lower, whereas the LV remodeling was higher in obesity than in control and OR (all p<0.001).

Conclusion
Impaired LVEF, enhanced LV remodeling, inflammation, fibrosis, oxidative stress and apoptosis were reversed by reduction in mouse obesity.
GWIDD: a comprehensive resource for genome-wide structural modeling of protein-protein interactions
Authors: Kundrotas Petras J , Zhu Zhengwei , Vakser Ilya A 
Published: July 2012

Abstract
Protein-protein interactions are a key component of life processes. The knowledge of the three-dimensional structure of these interactions is important for understanding protein function. Genome-Wide Docking Database (http://gwidd.bioinformatics.ku.edu) offers an extensive source of data for structural studies of protein-protein complexes on genome scale. The current release of the database combines the available experimental data on the structure and characteristics of protein interactions with structural modeling of protein complexes for 771 organisms spanned over the entire universe of life from viruses to humans. The interactions are stored in a relational database with user-friendly interface that includes various search options. The search results can be interactively previewed; the structures, downloaded, along with the interaction characteristics.