bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mice With Cardiac Overexpression of Peroxisome Proliferator–Activated Receptor γ Have Impaired Repolarization and Spontaneous Fatal Ventricular Arrhythmias
Authors: Morrow John P. , Katchman Alexander , Son Ni-Huiping , Trent Chad M. , Khan Raffay , Shiomi Takayuki , Huang Haiyan , Amin Vaibhav , Lader Joshua M. , Vasquez Carolina , Morley Gregory E. , D'Armiento Jeanine , Homma Shunichi , Goldberg Ira J. , Marx Steven O. 
Published: November 2011

Background—
Diabetes mellitus and obesity, which confer an increased risk of sudden cardiac death, are associated with cardiomyocyte lipid accumulation and altered cardiac electric properties, manifested by prolongation of the QRS duration and QT interval. It is difficult to distinguish the contribution of cardiomyocyte lipid accumulation from the contribution of global metabolic defects to the increased incidence of sudden death and electric abnormalities.

Methods and Results—
In order to study the effects of metabolic abnormalities on arrhythmias without the complex systemic effects of diabetes mellitus and obesity, we studied transgenic mice with cardiac-specific overexpression of peroxisome proliferator–activated receptor γ 1 (PPARγ1) via the cardiac α-myosin heavy-chain promoter. The PPARγ transgenic mice develop abnormal accumulation of intracellular lipids and die as young adults before any significant reduction in systolic function. Using implantable ECG telemeters, we found that these mice have prolongation of the QRS and QT intervals and spontaneous ventricular arrhythmias, including polymorphic ventricular tachycardia and ventricular fibrillation. Isolated cardiomyocytes demonstrated prolonged action potential duration caused by reduced expression and function of the potassium channels responsible for repolarization. Short-term exposure to pioglitazone, a PPARγ agonist, had no effect on mortality or rhythm in WT mice but further exacerbated the arrhythmic phenotype and increased the mortality in the PPARγ transgenic mice.

Conclusions—
Our findings support an important link between PPARγ activation, cardiomyocyte lipid accumulation, ion channel remodeling, and increased cardiac mortality.
Cell type-dependent gene regulation by Staufen2 in conjunction with Upf1
Authors: Miki Takashi , Kamikawa Yasunao , Kurono Sadamu , Kaneko Yuka , Katahira Jun , Yoneda Yoshihiro 
Published: November 2011

Abstract

Background
Staufen2 (Stau2), a double-stranded RNA-binding protein, is a component of neuronal RNA granules, which are dendritic mRNA transport machines. Although Stau2 is thought to be involved in the dendritic targeting of several mRNAs in neurons, the mechanism whereby Stau2 regulates these mRNAs is unknown. To elucidate the functions of Stau2, we screened for novel binding partners by affinity purification of GST-tagged Stau2 from 293F cells.

Results
Three RNA helicases, RNA helicase A, Upf1 and Mov10, were identified in Stau2-containing complexes. We focused our studies on Upf1, a key player in nonsense-mediated mRNA decay. Stau2 was found to bind directly to Upf1 in an RNA-independent manner in vitro. Tethering Stau2 to the 3'-untranslated region (UTR) of a reporter gene had little effect on its expression in HeLa cells. In contrast, when the same tethering assay was performed in 293F cells, we observed an increase in reporter protein levels. This upregulation of protein expression by Stau2 turned out to be dependent on Upf1. Moreover, we found that in 293F cells, Stau2 upregulates the reporter mRNA level in an Upf1-independent manner.

Conclusions
These results indicate that the recruitment of Stau2 alone or in combination with Upf1 differentially affects the fate of mRNAs. Moreover, the results suggest that Stau2-mediated fate determination could be executed in a cell type-specific manner.
Multiallelic epistatic model for an out-bred cross and mapping algorithm of interactive quantitative trait loci
Authors: Tong Chunfa , Zhang Bo , Wang Zhong , Xu Meng , Pang Xiaoming , Si Jingna , Huang Minren , Wu Rongling 
Published: November 2011

Abstract

Background
Genetic mapping has proven to be powerful for studying the genetic architecture of complex traits by characterizing a network of the underlying interacting quantitative trait loci (QTLs). Current statistical models for genetic mapping were mostly founded on the biallelic epistasis of QTLs, incapable of analyzing multiallelic QTLs and their interactions that are widespread in an outcrossing population.

Results
Here we have formulated a general framework to model and define the epistasis between multiallelic QTLs. Based on this framework, we have derived a statistical algorithm for the estimation and test of multiallelic epistasis between different QTLs in a full-sib family of outcrossing species. We used this algorithm to genomewide scan for the distribution of mul-tiallelic epistasis for a rooting ability trait in an outbred cross derived from two heterozygous poplar trees. The results from simulation studies indicate that the positions and effects of multiallelic QTLs can well be estimated with a modest sample and heritability.

Conclusions
The model and algorithm developed provide a useful tool for better characterizing the genetic control of complex traits in a heterozygous family derived from outcrossing species, such as forest trees, and thus fill a gap that occurs in genetic mapping of this group of important but underrepresented species.
Selective targeted delivery of the TNF-alpha receptor p75 and uteroglobin to the vasculature of inflamed tissues: a preliminary report
Authors: Ventura Elisa , Balza Enrica , Borsi Laura , Tutolo Giorgia , Carnemolla Barbara , Castellani Patrizia , Zardi Luciano 
Published: November 2011

Abstract

Background
Ligand-targeted approaches have proven successful in improving the therapeutic index of a number of drugs. We hypothesized that the specific targeting of TNF-alpha antagonists to inflamed tissues could increase drug efficacy and reduce side effects.

Results
Using uteroglobin (UG), a potent anti-inflammatory protein, as a scaffold, we prepared a bispecific tetravalent molecule consisting of the extracellular ligand-binding portion of the human TNF-alpha receptor P75 (TNFRII) and the scFv L19. L19 binds to the ED-B containing fibronectin isoform (B-FN), which is expressed only during angiogenesis processes and during tissue remodeling. B-FN has also been demonstrated in the pannus in rheumatoid arthritis. L19-UG-TNFRII is a stable, soluble homodimeric protein that maintains the activities of both moieties: the immuno-reactivity of L19 and the capability of TNFRII to inhibit TNF-alpha. In vivo bio-distribution studies demonstrated that the molecule selectively accumulated on B-FN containing tissues, showing a very fast clearance from the blood but a very long residence time on B-FN containing tissues. Despite the very fast clearance from the blood, this fusion protein was able to significantly improve the severe symptomatology of arthritis in collagen antibody-induced arthritis (CAIA) mouse model.

Conclusions
The recombinant protein described here, able to selectively deliver the TNF-alpha antagonist TNFRII to inflamed tissues, could yield important contributions for the therapy of degenerative inflammatory diseases.
Hypercholesterolemia promotes early renal dysfunction in apolipoprotein E-deficient mice
Authors: Balarini Camille M , Oliveira Mariana ZT , Pereira Thiago MC , Silva Nyam F , Vasquez Elisardo C , Meyrelles Silvana S , Gava Agata L 
Published: November 2011

Abstract

Background
Aging and dyslipidemia are processes which can lead to deleterious consequences to renal function. Therefore, the aim of this study was to determine the effects of both hypercholesterolemia and aging on renal function in mice.

Methods
Male hypercholesterolemic apolipoprotein E-deficient mice (ApoE, n = 13) and age-matched C57BL/6 control mice (C57, n = 15) were studied at 2 (young) and 8 (adult) month-old. At each time point, animals were placed in metabolic cages for 24 hours to urine volume and urinary creatinine quantification. Blood samples were collected for serum cholesterol, urea and creatinine measurements. Glomerular filtration rate (GFR) was estimated through creatinine clearance determination. Mesangial expansion was evaluated by Periodic Acid Schiff staining, renal fibrosis was determined through Masson's trichrome staining and neuronal nitric oxide synthase (nNOS) expression in the kidney was performed by Western Blotting. To statistical analysis two-way ANOVA followed by Fisher's post hoc test was used.

Results
Total plasma cholesterol was increased about 5-fold in ApoE mice at both time points compared to C57 animals. At 2-month-old, GFR was already markedly reduced in ApoE compared to C57 mice (187 ± 28 vs 358 ± 92 μL/min, p < 0.05). Adult C57 (-77%) and ApoE (-50%) mice also presented a significant reduction of GFR. In addition, serum urea was significantly increased in young ApoE animals compared to C57 mice (11 ± 1.3 vs 7 ± 0.9 mmol/L, p < 0.01). A significant mesangial expansion was observed at 2-month old ApoE mice compared to C57 mice (35 ± 0.6 vs 30 ± 0.9%, respectively, p < 0.05), which was aggravated at 8-month old animals (40 ± 3 and 35 ± 3%, respectively). Tubulointersticial fibrosis was augmented at both young (17 ± 2%, p < 0.05) and adult (20 ± 1%, p < 0.05) ApoE mice compared to respective C57 age controls (8 ± 1 and 12 ± 2%, respectively). The expression of nNOS was markedly reduced in a time-dependent manner in both strains.

Conclusions
These data show that both hypercholesterolemia and aging contribute to the loss of renal function in mice.
Effect of route of delivery on heterologous protection against HCV induced by an adenovirus vector carrying HCV structural genes
Authors: Guan Jie , Wen Bo , Deng Yao , Zhang Ke , Chen Hong , Wu Xiaobing , Ruan Li , Tan Wenjie 
Published: November 2011

Abstract

Background
An effective vaccine and new therapeutic methods for hepatitis C virus (HCV) are needed, and a potent HCV vaccine must induce robust and sustained cellular-mediated immunity (CMI). Research has indicated that adenoviral and vaccinia vectors may have the ability to elicit strong B and T cell immune responses to target antigens.

Results
A recombinant replication-defective adenovirus serotype 5 (rAd5) vector, rAd5-CE1E2, and a recombinant Tian Tan vaccinia vector, rTTV-CE1E2, were constructed to express the HCV CE1E2 gene (1-746 amino acid HCV 1b subtype). Mice were prime-immunised with rAd5-CE1E2 delivered via intramuscular injection (i.m.), intranasal injection (i.n.), or intradermal injection (i.d.) and boosted using a different combination of injection routes. CMI was evaluated via IFN-γ ELISPOT and ICS 2 weeks after immunisation, or 16 weeks after boost for long-term responses. The humoral response was analysed by ELISA. With the exception of priming by i.n. injection, a robust CMI response against multiple HCV antigens (core, E1, E2) was elicited and remained at a high level for a long period (16 weeks post-vaccination) in mice. However, i.n. priming elicited the highest anti-core antibody levels. Priming with i.d. rAd5-CE1E2 and boosting with i.d. rTTV-CE1E2 carried out simultaneously enhanced CMI and the humoral immune response, compared to the homologous rAd5-CE1E2 immune groups. All regimens demonstrated equivalent cross-protective potency in a heterologous surrogate challenge assay based on a recombinant HCV (JFH1, 2a) vaccinia virus.

Conclusions
Our data suggest that a rAd5-CE1E2-based HCV vaccine would be capable of eliciting an effective immune response and cross-protection. These findings have important implications for the development of T cell-based HCV vaccine candidates.
Pilose antler polypeptides promote chondrocyte proliferation via the tyrosine kinase signaling pathway
Authors: Lin Jian-Hua , Deng Ling-Xiao , Wu Zhao-Yang , Chen Lei , Zhang Li 
Published: November 2011

Abstract

Background
Pilose antler polypeptides (PAP) have been reported to promote chondrocyte proliferation. However, the underlying mechanism remains unclear. The present study was to investigate the effects of PAP on the proliferation of chondrocytes and its underlying mechanism.

Methods
Chondrocytes isolated from the knee of Zealand white rabbits were cultured. The second generation chondrocytes were collected and identified using safranin-O staining. The chondrocytes were divided into the following 4 groups including serum-free, PAP, genistein (an inhibitor of tyrosine kinases), and PAP plus genistein group. Cell viability was analyzed using the MTT assay. The cell cycle distribution of the chondrocytes was analyzed by flow cytometry. The expression levels of cyclin A was detected using immunocytochemical staining.

Results
No significant difference was observed between serum-free and genistein group. Treatment of the cultures with PAP produced a significant dose-dependent increase in cell viability, the percentage proportion of chondrocytes in the S phase and Cyclin A expression as well. However, the promoting effect of PAP on chondrocyte proliferation were dose-dependently inhibited by genistein, whereas genistein alone had no effect on proliferation of isolated chondrocytes.

Conclusions
The data demonstrate that PAP promotes chondrocyte proliferation with the increased cell number, percentage proportion of chondrocytes in S phase and expression of protein cyclin A via the TK signaling pathway.
Perceptions of environmental changes and Lethargic crab disease among crab harvesters in a Brazilian coastal community
Authors: Firmo Angélica MS , Tognella Mônica MP , Có Walter LO , Barboza Raynner RD , Alves Rômulo RN 
Published: November 2011

Abstract
Background
Lethargic Crab Disease (LCD) has caused significant mortalities in the population of Ucides cordatus crabs in the Mucuri estuary in Bahia State, Brazil, and has brought social and economic problems to many crab-harvesting communities that depend on this natural resource. The present work examined the perceptions of members of a Brazilian crab harvesting community concerning environmental changes and the Lethargic Crab Disease.

Methods
Field work was undertaken during the period between January and April/2009, with weekly or biweekly field excursions during which open and semi-structured interviews were held with local residents in the municipality of Mucuri, Bahia State, Brazil. A total of 23 individuals were interviewed, all of whom had at least 20 years of crab-collecting experience in the study region. Key-informants (more experienced crab harvesters) were selected among the interviewees using the "native specialist" criterion.

Results
According to the collectors, LCD reached the Mucuri mangroves between 2004 and 2005, decimating almost all crab population in the area, and in 2007, 2008 and 2009 high mortalities of U. cordatus were again observed as a result of recurrences of this disease in the region. In addition to LCD, crabs were also suffering great stock reductions due to habitat degradation caused by deforestation, landfills, sewage effluents, domestic and industrial wastes and the introduction of exotic fish in the Mucuri River estuary. The harvesting community was found to have significant ecological knowledge about the functioning of mangrove swamp ecology, the biology of crabs, and the mass mortality that directly affected the economy of this community, and this information was largely in accordance with scientific knowledge.

Conclusions
The study of traditional knowledge makes it possible to better understand human interactions with the environment and aids in the elaboration of appropriate strategies for natural resource conservation.
Association screening for genes with multiple potentially rare variants: an inverse-probability weighted clustering approach
Authors: Liu Ying , Huang Chien Hsun , Hu Inchi , Lo Shaw-Hwa , Zheng Tian 
Published: November 2011

Abstract
Both common variants and rare variants are involved in the etiology of most complex diseases in humans. Developments in sequencing technology have led to the identification of a high density of rare variant single-nucleotide polymorphisms (SNPs) on the genome, each of which affects only at most 1% of the population. Genotypes derived from these SNPs allow one to study the involvement of rare variants in common human disorders. Here, we propose an association screening approach that treats genes as units of analysis. SNPs within a gene are used to create partitions of individuals, and inverse-probability weighting is used to overweight genotypic differences observed on rare variants. Association between a phenotype trait and the constructed partition is then evaluated. We consider three association tests (one-way ANOVA, chi-square test, and the partition retention method) and compare these strategies using the simulated data from the Genetic Analysis Workshop 17. Several genes that contain causal SNPs were identified by the proposed method as top genes.
A weighted accumulation test for associating rare genetic variation with quantitative phenotypes
Authors: Xing Chuanhua , Satten Glen A , Allen Andrew S 
Published: November 2011

Abstract
Currently there is a great deal of interest in developing methods for testing the role that rare variation plays in disease development. Here we propose a weighted association test that accumulates genetic variation across a signaling pathway. We evaluate our approach by analyzing simulated phenotype data from an exome sequencing study of 697 unrelated individuals from the Genetic Analysis Workshop 17 (GAW17) data set. Although our weighted approach identifies several interesting pathways associated with phenotype Q1, so does an alternative unweighted accumulation approach. Such a result is not unexpected because there is no systematic relationship between the allele frequency of a variant and its effect on phenotype in the GAW17 simulation model.
Evaluation of association tests for rare variants using simulated data sets in the Genetic Analysis Workshop 17 data
Authors: Chen Wenan , Gao Xi , Wang Jiexun , Sun Chuanyu , Wan Wen , Zhi Degui , Liu Nianjun , Chen Xiangning , Gao Guimin 
Published: November 2011

Abstract
We evaluate four association tests for rare variants—the combined multivariate and collapsing (CMC) method, two weighted-sum methods, and a variable threshold method—by applying them to the simulated data sets of unrelated individuals in the Genetic Analysis Workshop 17 (GAW17) data. The family-wise error rate (FWER) and average power are used as criteria for evaluation. Our results show that when all nonsynonymous SNPs (rare variants and common variants) in a gene are jointly analyzed, the CMC method fails to control the FWER; when only rare variants (single-nucleotide polymorphisms with minor allele frequency less than 0.05) are analyzed, all four methods can control FWER well. All four methods have comparable power, which is low for the analysis of the GAW17 data sets. Three of the methods (not including the CMC method) involve estimation of p-values using permutation procedures that either can be computationally intensive or generate inflated FWERs. We adapt a fast permutation procedure into these three methods. The results show that using the fast permutation procedure can produce FWERs and average powers close to the values obtained from the standard permutation procedure on the GAW17 data sets. The standard permutation procedure is computationally intensive.
Impact of Body Mass Index on Survival After Colorectal Cancer Diagnosis: The Cancer Prevention Study-II Nutrition Cohort
Authors: Campbell Peter T. , Newton Christina C. , Dehal Ahmed N. , Jacobs Eric J. , Patel Alpa V. , Gapstur Susan M. 
Published: November 2011

Purpose The impact of body mass index (BMI) on survival after colorectal cancer diagnosis is poorly understood. This study assessed the association of pre- and postdiagnosis BMI with all-cause and cause-specific survival among men and women diagnosed with colorectal cancer in a prospective cohort. Patients and Methods Participants in the Cancer Prevention Study-II Nutrition Cohort reported weight and other risk factor information via a self-administered questionnaire at baseline in 1992 to 1993. Updated information on current weight and incident cancer was reported via periodic follow-up questionnaires. This analysis includes 2,303 cohort participants who were diagnosed with nonmetastatic colorectal cancer between baseline and mid 2007 and were observed for mortality from diagnosis through December 2008. Results A total of 851 participants with colorectal cancer died during the 16-year follow-up period, including 380 as a result of colorectal cancer and 153 as a result of cardiovascular disease (CVD). In analyses of prediagnosis BMI (weight reported at baseline in 1992 to 1993; mean, 7 years before colorectal cancer diagnosis), obese BMI (≥ 30 kg/m2) relative to normal BMI (18.5 to 24.9 kg/m2) was associated with higher risk of mortality resulting from all causes (relative risk [RR], 1.30; 95% CI, 1.06 to 1.58), colorectal cancer (RR, 1.35; 95% CI, 1.01 to 1.80), and CVD (RR, 1.68; 95% CI, 1.07 to 2.65). Postdiagnosis BMI (based on weight reported; mean, 1.5 years after diagnosis) was not associated with all-cause or cause-specific mortality. Conclusion This study suggests that prediagnosis BMI, but not postdiagnosis BMI, is an important predictor of survival among patients with nonmetastatic colorectal cancer.
Effect of pilot hole diameter and tapping on insertion torque and axial pullout strength of 4.0-mm cancellous bone screws
Authors: Kunkel Kevin A. R. , Suber Jonathan T. , Gerard Patrick D. , Kowaleski Michael P. 
Published: November 2011

Abstract
Objective—To evaluate the effects of pilot hole diameter and tapping on insertion torque and axial pullout strength of 4.0-mm cancellous bone screws in a synthetic canine cancellous bone substitute.
Sample—75 synthetic cancellous bone blocks (15 blocks/group).
Procedures—For groups 1 through 5, screw size-pilot hole diameter combinations were 3.5–2.5 mm (cortical screws), 4.0–2.5 mm, 4.0–2.5 mm, 4.0–2.0 mm, and 4.0–2.0 mm, respectively. Holes were tapped in groups 1, 2, and 4 only (tap diameter, 3.5, 4.0, and 4.0 mm, respectively). One 70-mm-long screw was inserted into each block; in a servohydraulic materials testing machine, the screw was extracted (rate, 5 mm/min) until failure. Mean group values of maximum insertion torque, axial pullout strength, yield strength, and stiffness were determined.
Results—Mean maximum insertion torque differed significantly among the 5 groups; the group 5 value was greatest, followed by group 3, 4, 2, and 1 values. Group 3, 4, and 5 axial pullout strengths were similar and significantly greater than the group 2 value; all values were significantly greater than that for group 1. Group 5 and 4 yield strengths were similar and significantly greater than the group 3, 2, and 1 values. Stiffness in group 3 was similar to group 4 and 2 values but significantly greater than the group 5 value; all values were significantly greater than that for group 1.
Conclusions and Clinical Relevance—These synthetic cancellous bone model findings suggested that tapping a 2.0-mm-diameter pilot hole when placing a 4.0-mm screw is the optimal insertion technique.