bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factor VIIa bound to endothelial cell protein C receptor activates protease activated receptor-1 and mediates cell signaling and barrier protection
Authors: Sen Prosenjit , Gopalakrishnan Ramakrishnan , Kothari Hema , Keshava Shiva , Clark Curtis A. , Esmon Charles T. , Pendurthi Usha R. , Rao L. Vijaya Mohan 
Published: January 2011

Abstract
Recent studies have shown that factor VIIa (FVIIa) binds to the endothelial cell protein C receptor (EPCR), a cellular receptor for protein C and activated protein C, but the physiologic significance of this interaction is unclear. In the present study, we show that FVIIa, upon binding to EPCR on endothelial cells, activates endogenous protease activated receptor-1 (PAR1) and induces PAR1-mediated p44/42 mitogen-activated protein kinase (MAPK) activation. Pretreatment of endothelial cells with FVIIa protected against thrombin-induced barrier disruption. This FVIIa-induced, barrier-protective effect was EPCR dependent and did not involve PAR2. Pretreatment of confluent endothelial monolayers with FVIIa before thrombin reduced the development of thrombin-induced transcellular actin stress fibers, cellular contractions, and paracellular gap formation. FVIIa-induced p44/42 MAPK activation and the barrier-protective effect are mediated via Rac1 activation. Consistent with in vitro findings, in vivo studies using mice showed that administration of FVIIa before lipopolysaccharide (LPS) treatment attenuated LPS-induced vascular leakage in the lung and kidney. Overall, our present data provide evidence that FVIIa bound to EPCR on endothelial cells activates PAR1-mediated cell signaling and provides a barrier-protective effect. These findings are novel and of great clinical significance, because FVIIa is used clinically for the prevention of bleeding in hemophilia and other bleeding disorders.
Shb deficient mice display an augmented TH2 response in peripheral CD4+ T cells
Authors: Gustafsson Karin , Calounova Gabriela , Hjelm Fredrik , Kriz Vitezslav , Heyman Birgitta , Grönvik Kjell-Olov , Mostoslavsky Gustavo , Welsh Michael 
Published: January 2011

AbstractBackgroundShb, a ubiquitously expressed Src homology 2 domain-containing adaptor protein has previously been implicated in the signaling of various tyrosine kinase receptors including the TCR. Shb associates with SLP76, LAT and Vav, all important components in the signaling cascade governing T cell function and development. AShbknockout mouse was recently generated and the aim of the current study was to address the importance ofShbdeficiency on T cell development and function.ResultsShbknockout mice did not display any major changes in thymocyte development despite an aberrant TCR signaling pattern, including increased basal activation and reduced stimulation-induced phosphorylation. The loss of Shb expression did however affect peripheral CD4+ THcells resulting in an increased proliferative response to TCR stimulation and an elevated IL-4 production of naïve THcells. This suggests a TH2 skewing of theShbknockout immune system, seemingly caused by an altered TCR signaling pattern.ConclusionOur results indicate that Shb appears to play an important modulating role on TCR signaling, thus regulating the peripheral CD4+ TH2 cell response.
Autoreactive marginal zone B cells enter the follicles and interact with CD4+ T cells in lupus-prone mice
Authors: Zhou Zhenhai , Niu Haitao , Zheng Ying-Yi , Morel Laurence 
Published: January 2011

AbstractBackgoundMarginal zone B cells have been implicated in the production of autoantibodies in murine models of lupus. It has been suggested that they contribute to lupus immunopathogenesis through their enhanced effector functions and their repertoire that is biased toward autoreactive specificities. In the B6.NZM2410.Sle.Sle2.Sle3(B6.TC) model of lupus, the majority of marginal zone B cells are located outside the marginal zone and inside the follicles. Genetic alterations of this strain have shown a correlation between autoimmune pathogenesis and the presence of intrafollicular marginal zone B cells. This study was designed first to strengthen our original observations and to determine how the marginal zone B cells from the lupus-prone mice respond to stimulations and interact with T cells.ResultsThe intrafollicular location of B6.TC MZB cells starts before disease manifestations and puts MZB cells in direct contact with CD4+T cells. Two different autoreactive B cell receptor (BCR) transgenic models showed that the expression of theSlesusceptibility loci enhances the presence of MZB cells inside the follicles.In vitro, B6.TC MZB cells were better effectors than B6 MZB cells with enhanced proliferation and antibody (Ab) production, including anti-DNA Ab, in response to stimulation with TLR ligands, immune complexes or anti-CD40. Furthermore, B6.TC MZB and CD4+T cells showed a reciprocally enhanced activation, which indicated that their contacts inside B6.TC follicles have functional consequences that suggest an amplification loop between these two cell types.ConclusionsThese results showed that the NZM2410 susceptibility loci induce MZB cells to locate into the follicles, and that this breach of follicular exclusion occurs early in the development of the autoimmune pathogenesis. The enhanced responses to stimulation and increased effector functions of MZB cells from lupus-prone mice as compare to non-autoimmune MZB cells provide a mechanism by which the failure of MZB cell follicular exclusion contributes to the autoimmune process.
Characterization of cp3 reveals a new bri1 allele, bri1-120, and the importance of the LRR domain of BRI1 mediating BR signaling
Authors: Shang Yun , Lee Myeong Min , Li Jianming , Nam Kyoung Hee 
Published: January 2011

Abstract

Background
Since the identification of BRI1 (BRASSINOSTEROID-INSENSITIVE1), a brassinosteroids (BRs) receptor, most of the critical roles of BR in plant development have been assessed using various bri1 mutant alleles. The characterization of individual bri1 mutants has shown that both the extracellular and cytoplasmic domains of BRI1 are important to its proper functioning. Particularly, in the extracellular domain, regions near the 70-amino acid island are known to be critical to BR binding. In comparison, the exact function of the leucine rich-repeats (LRR) region located before the 70-amino acid island domain in the extracellular cellular portion of BRI1 has not yet been described, due to a lack of specific mutant alleles.

Results
Among the mutants showing altered growth patterns compared to wild type, we further characterized cp3, which displayed defective growth and reduced BR sensitivity. We sequenced the genomic DNA spanning BRI1 in the cp3 and found that cp3 has a point mutation in the region encoding the 13th LRR of BRI1, resulting in a change from serine to phenylalanine (S399F). We renamed it bri1-120. We also showed that overexpression of the wild type BRI1 protein rescued the phenotype of bri1-120. Using a GFP-tagged bri1-120 construct, we detected the bri1-120 protein in the plasma membrane, and showed that the phenotypic defects in the rosette leaves of bri1-301, a kinase-inactive weak allele of BRI1, can be restored by the overexpression of the bri1-120 proteins in bri1-301. We also produced bri1-301 mutants that were wild type in appearance by performing a genetic cross between bri1-301 and bri1-120 plants.

Conclusions
We identified a new bri1 allele, bri1-120, whose mutation site has not yet been found or characterized. Our results indicated that the extracellular LRR regions before the 70-amino acid island domain of BRI1 are important for the appropriate cellular functioning of BRI1. Also, we confirmed that a successful interallelic complementation occurs between the extracellular domain mutant allele and the cytoplasmic kinase-inactive mutant allele of BRI1 in vivo.
A 3D Freehand Ultrasound System for Multi-view Reconstructions from Sparse 2D Scanning Planes
Authors: Yu Honggang , Pattichis Marios S , Agurto Carla , Beth Goens M 
Published: January 2011

Abstract

Background
A significant limitation of existing 3D ultrasound systems comes from the fact that the majority of them work with fixed acquisition geometries. As a result, the users have very limited control over the geometry of the 2D scanning planes.

Methods
We present a low-cost and flexible ultrasound imaging system that integrates several image processing components to allow for 3D reconstructions from limited numbers of 2D image planes and multiple acoustic views. Our approach is based on a 3D freehand ultrasound system that allows users to control the 2D acquisition imaging using conventional 2D probes.
For reliable performance, we develop new methods for image segmentation and robust multi-view registration. We first present a new hybrid geometric level-set approach that provides reliable segmentation performance with relatively simple initializations and minimum edge leakage. Optimization of the segmentation model parameters and its effect on performance is carefully discussed. Second, using the segmented images, a new coarse to fine automatic multi-view registration method is introduced. The approach uses a 3D Hotelling transform to initialize an optimization search. Then, the fine scale feature-based registration is performed using a robust, non-linear least squares algorithm. The robustness of the multi-view registration system allows for accurate 3D reconstructions from sparse 2D image planes.

Results
Volume measurements from multi-view 3D reconstructions are found to be consistently and significantly more accurate than measurements from single view reconstructions. The volume error of multi-view reconstruction is measured to be less than 5% of the true volume. We show that volume reconstruction accuracy is a function of the total number of 2D image planes and the number of views for calibrated phantom. In clinical in-vivo cardiac experiments, we show that volume estimates of the left ventricle from multi-view reconstructions are found to be in better agreement with clinical measures than measures from single view reconstructions.

Conclusions
Multi-view 3D reconstruction from sparse 2D freehand B-mode images leads to more accurate volume quantification compared to single view systems. The flexibility and low-cost of the proposed system allow for fine control of the image acquisition planes for optimal 3D reconstructions from multiple views.
Synthetic arylquinuclidine derivatives exhibit antifungal activity against Candida albicans, Candida tropicalis and Candida parapsilopsis
Authors: Ishida Kelly , Fernandes Rodrigues Juliany Cola , Cammerer Simon , Urbina Julio A , Gilbert Ian , de Souza Wanderley , Rozental Sonia 
Published: January 2011

Abstract

Background
Sterol biosynthesis is an essential pathway for fungal survival, and is the biochemical target of many antifungal agents. The antifungal drugs most widely used to treated fungal infections are compounds that inhibit cytochrome P450-dependent C14α-demethylase (CYP51), but other enzymes of this pathway, such as squalene synthase (SQS) which catalyses the first committed step in sterol biosynthesis, could be viable targets. The aim of this study was to evaluate the antifungal activity of SQS inhibitors on Candida albicans, Candida tropicalis and Candida parapsilopsis strains.

Methods
Ten arylquinuclidines that act as SQS inhibitors were tested as antiproliferative agents against three ATCC strains and 54 clinical isolates of Candida albicans, Candida tropicalis and Candida parapsilopsis. Also, the morphological alterations induced in the yeasts by the experimental compounds were evaluated by fluorescence and transmission electron microscopy.

Results
The most potent arylquinuclidine derivative (3-[1'-{4'-(benzyloxy)-phenyl}]-quinuclidine-2-ene) (WSP1267) had a MIC50 of 2 μg/ml for all species tested and MIC90 varying from 4 μg/ml to 8 μg/ml. Ultrathin sections of C. albicans treated with 1 μg/ml of WSP1267 showed several ultrastructural alterations, including (a) loss of cell wall integrity, (b) detachment of the plasma membrane from the fungal cell wall, (c) accumulation of small vesicles in the periplasmic region, (d) presence of large electron-dense vacuoles and (e) significantly increased cell size and cell wall thickness. In addition, fluorescence microscopy of cells labelled with Nile Red showed an accumulation of lipid droplets in the cytoplasm of treated yeasts. Nuclear staining with DAPI revealed the appearance of uncommon yeast buds without a nucleus or with two nuclei.

Conclusion
Taken together, our data demonstrate that arylquinuclidine derivatives could be useful as lead compounds for the rational synthesis of new antifungal drugs.
The impact of plasma triglyceride and apolipoproteins concentrations on high-density lipoprotein subclasses distribution
Authors: Tian Li , Xu Yanhua , Fu Mingde , Peng Tao , Liu Yinghui , Long Shiyin 
Published: January 2011

Abstract

Objective
To investigate the effect of triglyceride (TG) integrates with plasma major components of apolipoproteins in HDL subclasses distribution and further elicited the TG-apolipoproteins (apos) interaction in the processes of high density lipoprotein (HDL) mature metabolic and atherosclerosis related diseases.

Methods
Contents of plasma HDL subclasses were quantities by two-dimensional gel electrophoresis associated with immunodetection in 500 Chinese subjects.

Results
Contents of preβ1-HDL, HDL3a, and apoB-100 level along with apoB-100/A-I ratio were significantly increased, whereas there was a significant reduction in the contents of HDL2, apoA-I level as well as apoC-III/C-II ratio with increased TG concentration. Moreover, preβ1-HDL contents is elevated about 9 mg/L and HDL2b contents can be reduced 21 mg/L for 0.5 mmol/L increment in TG concentration. Moreover, with increase of apoA-I levels, HDL2b contents were marginally elevated in any TG concentration group. Furthermore, despite of in the apoB-100/A-I < 0.9 group, the contents of preβ1-HDL increased, and those of HDL2b decreased significantly for subjects in both high and very high TG levels compared to that in normal TG levels. Similarly, in the apoB-100/A-I ≥ 0.9 group, the distribution of HDL subclasses also showed abnormality for subjects with normal TG levels.

Conclusions
The particle size of HDL subclasses tend to small with TG levels increased which indicated that HDL maturation might be impeded and efficiency of reverse cholesterol transport(RCT) might be weakened. These data suggest that TG levels were not only significantly associated with but liner with the contents of preβ1-HDL and HDL2b. They also raise the possibility that the TG levels effect on HDL maturation metabolism are subjected to plasma apolipoproteins and apolipoproteins ratios.
Modification of fatty acids composition in erythrocytes lipids in arterial hypertension associated with dyslipidemia
Authors: Novgorodtseva Tatyana P , Kantur Tatyana A , Karaman Yulia K , Antonyuk Marina V , Zhukova Natalia V 
Published: January 2011

Abstract

Background
Modification of fatty acids (FA) composition in erythrocytes lipids as an early indicator of the development of arterial hypertension (AH) and lipid disorders.

Methods
We included 34 patients with arterial hypertension and 11 healthy individuals. Each patient was examined the lipid composition of serum. From erythrocytes by gas chromatography were identified fatty acids. The quantitative composition of the erythrocyte lipids FA in patients with AH presented with saturated and polyunsaturated monoenic acids with carbon chain lengths from C12 to C22.

Results
In all hypertensive patients is disturbed lipid FA composition of erythrocytes. The patients with a normal level of serum lipids revealed deficiency of polyunsaturated acids n6-linoleic (18:2 n6), arachidonic (20:4 n6), dokozatetraenic 14,4% (22:4 n6). The patients with dislipidemia installed more profound restructuring of the lipid matrix of the membrane of erythrocytes. A decrease in polyunsaturated fatty acids family n3: dokozapentaenovoy (22:5 n3), docosahexaenoic PUFA (22:6 n3), the total value of n3 PUFA in 1,3 times was revealed.

Conclusion
Thus, modification of erythrocyte FA are fairly subtle indicator of pathology of lipid metabolism, which manifest themselves much earlier than changes in the lipoprotein of blood plasma.
Hepatitis G Virus associated aplastic anemia: A recent case from Pakistan
Authors: Riaz Shah Shahida Amjad , Idrees Muhammad , Hussain Abrar 
Published: January 2011

Abstract

Background
Aplastic anemia (AA) is a serious and rare disorder characterized by a hypocellular bone marrow. Hepatitis associated aplastic anemia (HAAA) is a variant of aplastic anemia in which aplastic anemia follows an acute attack of hepatitis. Several reports have noted an association between HGV and hepatitis-associated aplastic anemia besides other hepatitis causing viruses.

Case presentation
A female girl of age 11 year with a history of loose motion for one month, vomiting for last 15 days and poor oral intake for last few days is reported here. The physical examination presents fever, pallor whereas bleeding, hepatomegaly, Splenomegaly and bruising were absent, abdominal ultrasonography confirmed the absence of hepatomegaly, Splenomegaly and lymphodenopathy. The laboratory investigation parameters were: haemoglobin 6.2 g/L, total leucocytes count 1.51, neutrophils 0.47%, absolute reticulocyte count 0.5%, Monocytes 0.16%, red cell count 3.2 mil/uL, Picked cell volume (PCV) 30.13%, Mean Corpuscular Volume (MCV) 78 fL, Mean Corpuscular Hemoglobin (MCH) 26.3 pg. The liver enzymes were alanine aminotransferease (ALT) 98 IU/L, aspartate aminotransferase (AST) 114 IU/L. Serologic and molecular tests for hepatitis A, B, C, D, E, TTV, B19 were negative, whereas HGV RNA PCR test was found positive for hepatitis G virus. The bone marrow aspirate and trephine biopsy examination revealed hypo- cellularity, erythropoiesis, myelopoiesis and megakaryopoiesis.

Conclusion
HAAA is an uncommon but severe condition, which may occur following idiopathic cases of acute hepatitis. Our finding suggests the involvement of HGV in the development of aplastic anemia. In patients presenting with pancytopenia after an episode of acute hepatitis, the definitive diagnosis should be considered and confirmed by RT-PCR and if possible by bone marrow biopsy.
Coating carbon nanotubes with a polystyrene-based polymer protects against pulmonary toxicity
Authors: Tabet Lyes , Bussy Cyrill , Setyan Ari , Simon-Deckers Angélique , Rossi Michel J , Boczkowski Jorge , Lanone Sophie 
Published: January 2011

Abstract

Background
carbon nanotubes (CNT) can have adverse effects on health. Therefore, minimizing the risk associated with CNT exposure is of crucial importance. The aim of this work was to evaluate if coating multi-walled CNT (MWCNT) with polymers could modify their toxicity, thus representing a useful strategy to decrease adverse health effects of CNT. We used industrially-produced MWCNT uncoated (NT1) or coated (50/50 wt%) with acid-based (NT2) or polystyrene-based (NT3) polymer, and exposed murine macrophages (RAW 264.7 cell line) or Balb/c mice by intratracheal administration. Biological experiments were performed both in vitro and in vivo, examining time- and dose-dependent effects of CNT, in terms of cytotoxicity, expression of genes and proteins related to oxidative stress, inflammation and tissue remodeling, cell and lung tissue morphology (optical and transmission electron microscopy), and bronchoalveolar lavage fluid content analysis.

Results
extensive physico-chemical characterization of MWCNT was performed, and showed, although similar dimensions for the 3 MWCNT, a much smaller specific surface area for NT2 and NT3 as compared to NT1 (54.1, 34 and 227.54 m2/g respectively), along with different surface characteristics. MWCNT-induced cytotoxicity, oxidative stress, and inflammation were increased by acid-based and decreased by polystyrene-based polymer coating both in vitro in murine macrophages and in vivo in lung of mice monitored for 6 months.

Conclusions
these results demonstrate that coating CNT with polymers, without affecting their intrinsic structure, may constitute a useful strategy for decreasing CNT toxicity, and may hold promise for improving occupational safety and that of general the user.
The value of shoe size for prediction of the timing of the pubertal growth spurt
Authors: Busscher Iris , Kingma Idsart , Wapstra Frits Hein , Bulstra Sjoerd K , Verkerke Gijsbertus J , Veldhuizen Albert G 
Published: January 2011

Abstract

Background
Knowing the timing of the pubertal growth spurt of the spine, represented by sitting height, is essential for the prognosis and therapy of adolescent idiopathic scoliosis. There are several indicators that reflect growth or remaining growth of the patient. For example, distal body parts have their growth spurt earlier in adolescence, and therefore the growth of the foot can be an early indicator for the growth spurt of sitting height. Shoe size is a good alternative for foot length, since patients can remember when they bought new shoes and what size these shoes were. Therefore the clinician already has access to some longitudinal data at the first visit of the patient to the outpatient clinic.
The aim of this study was to describe the increase in shoe size during adolescence and to determine whether the timing of the peak increase could be an early indicator for the timing of the peak growth velocity of sitting height.

Methods
Data concerning shoe sizes of girls and boys were acquired from two large shoe shops from 1991 to 2008. The longitudinal series of 242 girls and 104 boys were analysed for the age of the "peak increase" in shoe size, as well as the age of cessation of foot growth based on shoe size.

Results
The average peak increase in shoe size occurred at 10.4 years (SD 1.1) in girls and 11.5 years (SD 1.5) in boys. This was on average 1.3 years earlier than the average peak growth velocity of sitting height in girls, and 2.5 years earlier in boys. The increase in shoe size diminishes when the average peak growth velocity of sitting height takes place at respectively 12.0 (SD 0.8) years in girls, and 13.7 (SD 1.0) years in boys.

Conclusions
Present data suggest that the course of the shoe size of children visiting the outpatient clinic can be a useful first tool for predicting the timing of the pubertal growth spurt of sitting height, as a representative for spinal length.
This claim needs verification by direct comparison of individual shoe size and sitting height data and than a step forward can be made in clinical decision making regarding adolescent idiopathic scoliosis.