bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of Different Methods for Measuring Lateral Tibial Slope Using Magnetic Resonance Imaging
Authors: Lipps David B. , Wilson Annie M. , Ashton-Miller James A. , Wojtys Edward M. 
Published: October 2012

Background: Since lateral tibial slope (LTS) affects the amount of anterior tibial translation and anterior cruciate ligament (ACL) strain during a dynamic maneuver, accurate measurements of LTS may be beneficial in screening people at a higher risk for ACL injury. Methods for measuring LTS on magnetic resonance imaging (MRI) scans of the proximal tibia include the midpoint and circle methods. No current studies have validated different LTS measurement methods using a proximal tibia MRI scan. Hypothesis: We tested the null hypotheses that (1) LTS measurements were independent of the length of tibia imaged using the midpoint method, and (2) LTS measurements calculated from different methods (midpoint, circle, and full tibia) would not differ significantly. Study Design: Controlled laboratory study. Methods: Blinded observers measured LTS from 3-tesla, 3-dimensional MRIs from 40 size-matched donors according to 1 circle method and 3 midpoint methods. Outcomes were then compared with the full-tibial anatomic axis (line connecting the center of 2 circles fit within the proximal and distal tibia) in 11 donors. Bonferroni-corrected paired t tests (significance, P < .005) were used to compare the 5 methods. Results: The circle and full-tibia methods had the lowest interobserver and intraobserver variability, whereas the midpoint method with 10-cm tibia was the most variable. The midpoint method with 10-cm and 15-cm proximal tibia closely resembled LTS measurements with the full-tibial anatomic axis. The circle method, although repeatable, provided smaller numerical LTS measurements than the full-tibia and midpoint methods. Conclusion: Although LTS measurements using the midpoint method can resemble measurements made using the full tibia, the reliability of the midpoint method depends on the length of proximal tibia used. The circle method may be the preferred method for future studies since it was the most repeatable method and is independent of proximal tibial length. Clinical Relevance: LTS measurements vary depending on the method used.
Ulinastatin reduces pathogenesis of phosgene-induced acute lung injury in rats
Authors: Shen Jie , Gan Zhengyi , Zhao Jie , Zhang Liming , Xu Guoxiong 
Published: October 2012

Phosgene (CG) is an industrial chemical used to make plastics, rubbers, dyestuff, and pesticides. Although the inhalation of CG is relatively uncommon, its accidental exposure can lead to acute lung injury (ALI). Ulinastatin, a urinary trypsin inhibitor, has been emerged to use for the treatment of acute inflammatory state of a number of organs including the lung. In this study, we examined the pathogenic changes in the lungs after the inhalation of CG gas and also examined the effect of ulinastatin treatment in reversing these changes in rats. We found that the rats exposed to CG gas at a dose of 5.0 g/m3 for 5 min led to ALI after 6 h. The signs of lung injury include pulmonary edema, hemorrhage, and cellular infiltration in pulmonary alveoli. In addition, interleukin-15 (IL-15) and intercellular adhesion molecule-1 (ICAM-1) were significantly increased in CG-inhaled animals. Ulinastatin administration at 1 h postexposure significantly reduced the intensity of all the pathological changes in the lungs of these CG-exposed animals. Ulinastatin at a dose of 400 U/g was shown to decrease the total number of cells in bronchoalveolar lavage fluid and the levels of IL-15 and ICAM-1 in the serum. We also found that the structure of the lung was protected by ulinastatin treatment. Thus, our data suggest that ulinastatin can be used as an effective drug for the treatment of CG-induced ALI. The serum levels of IL-15 and ICAM-1 can be used as the markers of lung injury after exposure to CG and may also serve as useful therapeutic targets at an early stage. The effects of long-term treatment of ulinastatin and the mechanisms by which ulinastatin decreases the infiltration of blood cells and reduces cytokines need further investigation.
Manufacturing and thermal and mechanical properties of advanced 3-aminophenoxyphthalonitrile/bisphthalonitrile composite laminates
Authors: Chen Zhiran , Guo Heng , Yang Jian , Zhao Rui , Liu Xiaobo 
Published: October 2012

The 3-aminophenoxyphthalonitrile (3-APN) was used as a comonomer and coreactive curing agent to modify the 2,2-bis[4-(3,4)-dicyanophenoxyphenyl] (BAPh) resin by blending technology. First, the 3-APN/BAPh matrices were characterized using differential scanning calorimetry, dynamic rheological analysis and thermogravimetric analysis (TGA). The curing and rheological behaviors of the blends and prepolymers of 3-APN/BAPh matrix were studied. The results revealed that the blends and prepolymers exhibited the polymerization reaction controlled by the 3-APN content and had large processing window with low melt viscosity. The TGA data revealed that the 3-APN/BAPh matrix copolymers showed excellent thermal and thermal-oxidative stabilities. Moreover, the continuous glass fiber (GF)-reinforced 3-APN/BAPh (GF/3-APN/BAPh) composite laminates were manufactured and the mechanical and thermal properties were studied. The GF/3-APN/BAPh composite laminates exhibited flexural strength (500–766 MPa) and flexural modulus (21–27 GPa) by maintaining high thermal performances. In addition, scanning electron microscopy was utilized to investigate the fracture surfaces of the GF/3-APN/BAPh composite laminates, which had the effective interfacial interaction between the GFs and the matrix. Herein, the 3-APN/BAPh matrix can be a good candidate matrix for high-performance polymeric materials and the advanced laminate can be used in a high-temperature environment.
Comparison between the effect of glibenclamide and captopril on experimentally induced diabetic nephropathy in rats
Authors: Akbar Daad H , Hagras Magda M , Amin Hanan A , Khorshid Omayma A 
Published: October 2012

Hypothesis: This study aimed to elucidate the role of glibenclamide in the prevention of diabetic nephropathy and to compare it with a reference drug captopril in rats. Materials and methods: There were two main groups of rats. Control group (I) was subdivided into four subgroups which received distilled water, vehicle of streptozotocin, glibenclamide or captopril. The streptozotocin-diabetic Group (II) was subdivided into three subgroups: untreated, glibenclamide or captopril treated. Measurement of arterial blood pressure, serum glucose and creatinine levels, 24 h urinary protein and albumin/creatinine ratio, kidney weight and its histological examination were done after 1, 2, 4, 8, 12 and 16 weeks of treatment. Results: In treated diabetic rats captopril reduced blood pressure significantly, while no significant change in the mean arterial blood pressure or blood glucose level was recorded with glibenclamide treatment. Glibenclamide and captopril-treated diabetic rats showed significant decrease in serum creatinine level, urine volume, urinary protein excretion, albumin:creatinine ratio and kidney:body weight ratio compared with the diabetic non-treated group. Histological examination of diabetic kidneys treated with either glibenclamide or captopril showed reduced glomerular hypertrophy, glomerulosclerosis, tubular degeneration and interstitial fibrosis compared with untreated diabetic rats. Conclusion: Glibenclamide attenuated some biochemical and histological changes produced by diabetic nephropathy, despite persistent hyperglycemia and hypertension.
Association between angiotensin-converting enzyme insertion/deletion gene polymorphism and end-stage renal disease susceptibility
Authors: Zhou Tian-Biao , Yin Sheng-Sheng , Qin Yuan-Han 
Published: October 2012

Background and objective: The association between angiotensin-converting enzyme (ACE) insertion/deletion (I/D) gene polymorphism and end-stage renal disease (ESRD) risk is still controversial. A meta-analysis was performed to evaluate the association between ACE I/D gene polymorphism and ESRD susceptibility. Method: A predefined literature search and selection of eligible relevant studies were performed to collect data from electronic databases. Results: Thirty-four articles were identified for the analysis of an association between ACE I/D gene polymorphism and ESRD risk. Both D allele and DD genotype were associated with ESRD susceptibility in overall populations (D: OR = 1.20, 95% CI: 1.06–1.36, p = 0.003, DD: OR = 1.47, 95% CI: 1.20–1.78, p = 0.0001) and in East Asians (D: OR = 1.34, 95% CI: 1.06–1.69, p = 0.01, DD: OR = 2.01, 95% CI: 1.29–3.12, p = 0.002). Only the DD genotype had a positive association with ESRD susceptibility in Caucasians (OR = 1.20, 95% CI: 1.01–1.43, p = 0.03). The result from sensitivity analysis in overall populations or Caucasians was similar to those in non-sensitivity analysis, but not among East Asians. Conclusions: The results of our study support the idea that D allele or DD genotype was associated with increased risk of ESRD susceptibility in the overall populations, and DD genotype was associated with ESRD susceptibility in Caucasians.
Magnetic Resonance Imaging as a Predictor of Return to Play Following Syndesmosis (High) Ankle Sprains in Professional Football Players
Authors: Howard Daniel R. , Rubin David A. , Hillen Travis J. , Nissman Daniel B. , Lomax James , Williams Tyler , Scott Reggie , Cunningham Byron , Matava Matthew J. 
Published: October 2012

Background: Syndesmosis ankle sprains cause greater disability and longer duration of recovery than lateral ankle sprains. Objective: To describe the severity of syndesmosis sprains using several accepted magnetic resonance imaging (MRI) criteria and to assess the interrater reliability of diagnosing syndesmosis injury using these same criteria in professional American football players. Hypothesis: There is a high degree of interrater reliability of MRI findings in American football players with syndesmosis ankle sprains. These radiographic findings will correlate with time lost to injury, indicating severity of the sprain. Study Design: Uncontrolled retrospective review. Methods: Player demographics and time lost to play were recorded among professional football players who had sustained a syndesmosis ankle sprain and underwent standardized ankle MRI. Each image was independently read by 3 blinded musculoskeletal radiologists. Results: Seventeen players met study criteria. There was almost perfect agreement among the radiologists for diagnosing injury to the syndesmotic membrane; substantial agreement for diagnosing injury to the posterior inferior tibiofibular ligament (PITFL) and in determining the proximal extent of syndesmotic edema/injury; but only fair agreement for diagnosing injury to the anterior inferior tibiofibular ligament and in determining the width of syndesmotic separation. There was a significant correlation between the width of syndesmotic separation and time lost, but no significant correlation between individual syndesmotic ligament injury or proximal extent of syndesmotic edema/injury and time lost. Conclusion: While ankle MRI can identify syndesmotic disruption with a high degree of interobserver agreement, no association was demonstrated between the extent of injury on MRI and the time to return to play following a high ankle sprain. Clinical Relevance: In athletes with suspected high ankle sprains, MRI may help confirm diagnosis or suggest alternative diagnoses when the syndesmotic supporting structures are intact. However, the severity of ligamentous and syndesmotic disruption on MRI cannot help predict recovery times.
Transforming Asia: Realizing the Asian Century through Good Governance
Authors: Nag Rajat M. 
Published: October 2012

As developing Asia seeks to cement the gains from a decades-long economic boom and sustain its growth momentum, it will need to take bold action to address the plethora of governance challenges facing the region. Failure to address these challenges will lead to widened governance deficit in government, businesses and institutions. Policy prescriptions for good governance abound, but true change will need to come from within the region. There is no short-cut to building good governance. We believe that endogenous factors—changing demographics, increasing urbanization, an expanding middle class—will drive demand for good governance in the region. It is hoped that the new aspirations accompanying the prospect of realizing the Asian Century and attaining higher living standards as well quality of life will transform governance across the region.
The high Nrf2 expression in human acute myeloid leukemia is driven by NF-κB and underlies its chemo-resistance
Authors: Rushworth Stuart A. , Zaitseva Lyubov , Murray Megan Y. , Shah Niraj M. , Bowles Kristian M. , MacEwan David J. 
Published: October 2012

AbstractNF-E2–related factor 2 (Nrf2) transcription factor regulates a range of cytoprotective transcriptional responses, preventing further cellular injury by removing biochemical damage and renewing tissue. Here we show that acute myeloid leukemia (AML) cells possess greater constitutive nuclear levels of Nrf2 than normal control CD34+ cells because of an imbalance between mRNA expression levels of Nrf2 and its inhibitor Keap1 but not through their somatic mutation. Elevated Nrf2 was reduced by NF-κB inhibitors. Using promoter assays, ChIP and siRNA knockdown, we demonstrated NF-κB subunits p50 and p65 induce transcription of Nrf2 in AML cells at a specific promoter κB-site and that long-term lentiviral miRNA-knockdown of Nrf2 significantly reduced clonogenicity of AML patient cells and improved their chemotherapeutic responsiveness. Normal physiologic Nrf2 protects cells from damage, but here we have exposed aberrant continuous nuclear activation of Nrf2 in AML that allows cell survival, even against cytotoxic chemotherapeutics. We show for the first time that Nrf2, an important regulator of several biologic processes involved in the progression of cancer, has abnormal NF-κB–driven constitutive expression in AML. Such a mechanism allows for a greater cytoprotective response in human AML cells and encourages their evasion of chemotherapy-induced cytotoxicity, which is necessary for improved clinical outcomes.
Identification of functionally important residues in TFPI Kunitz domain 3 required for the enhancement of its activity by protein S
Authors: Ahnström Josefin , Andersson Helena M. , Hockey Verity , Meng Yiran , McKinnon Thomas A. J. , Hamuro Tsutomu , Crawley James T. B. , Lane David A. 
Published: October 2012

AbstractProtein S is a cofactor for tissue factor pathway inhibitor (TFPI) that critically reduces the inhibition constant for FXa to below the plasma concentration of TFPI. TFPI Kunitz domain 3 is required for this enhancement to occur. To delineate the molecular mechanism underlying enhancement of TFPI function, in the present study, we produced a panel of Kunitz domain 3 variants of TFPI encompassing all 12 surface-exposed charged residues. Thrombin-generation assays in TFPI-depleted plasma identified a novel variant, TFPI E226Q, which exhibited minimal enhancement by protein S. This was confirmed in purified FXa inhibition assays in which no protein S enhancement of TFPI E226Q was detected. Surface plasmon resonance demonstrated concentration-dependent binding of protein S to wild-type TFPI, but almost no binding to TFPI E226Q. We conclude that the TFPI Kunitz domain 3 residue Glu226 is essential for TFPI enhancement by protein S.
Frat2 mediates the oncogenic activation of Rac by MLL fusions
Authors: Walf-Vorderwülbecke Vanessa , de Boer Jasper , Horton Sarah J. , van Amerongen Renée , Proost Natalie , Berns Anton , Williams Owen 
Published: October 2012

Abstract
Mixed lineage leukemia (MLL) fusion genes arise from chromosomal translocations and induce acute myeloid leukemia through a mechanism involving transcriptional deregulation of differentiation and self-renewal programs. Progression of MLL-rearranged acute myeloid leukemia is associated with increased activation of Rac GTPases. Here, we demonstrate that MLL fusion oncogenes maintain leukemia-associated Rac activity by regulating Frat gene expression, specifically Frat2. Modulation of FRAT2 leads to concomitant changes in Rac activity, and transformation of Frat knockout hematopoietic progenitor cells by MLL fusions results in leukemias displaying reduced Rac activation and increased sensitivity to chemotherapeutic drugs. FRAT2 activates Rac through a signaling mechanism that requires glycogen synthase kinase 3 and DVL. Disruption of this pathway abrogates the leukemogenic activity of MLL fusions. This suggests a rationale for the paradoxical requirement of canonical Wnt signaling and glycogen synthase kinase 3 activity for MLL fusion oncogenicity and identifies novel therapeutic targets for this disease.
The biology of nematode- and IL4Rα-dependent murine macrophage polarization in vivo as defined by RNA-Seq and targeted lipidomics
Authors: Thomas Graham D. , Rückerl Dominik , Maskrey Benjamin H. , Whitfield Phillip D. , Blaxter Mark L. , Allen Judith E. 
Published: October 2012

Abstract
Alternatively activated macrophages (AAMφ) are a major component of the response to helminth infection; however, their functions remain poorly defined. To better understand the helminth-induced AAMφ phenotype, we performed a systems-level analysis of in vivo derived AAMφ using an established mouse model. With next-generation RNA sequencing, we characterized the transcriptomes of peritoneal macrophages from BALB/c and IL4Rα−/− mice elicited by the nematode Brugia malayi, or via intraperitoneal thioglycollate injection. We defined expression profiles of AAMφ-associated cytokines, chemokines, and their receptors, providing evidence that AAMφ contribute toward recruitment and maintenance of eosinophilia. Pathway analysis highlighted complement as a potential AAMφ-effector function. Up-regulated mitochondrial genes support in vitro evidence associating mitochondrial metabolism with alternative activation. We mapped macrophage transcription start sites, defining over-represented cis-regulatory motifs within AAMφ-associated promoters. These included the binding site for PPAR transcription factors, which maintain mitochondrial metabolism. Surprisingly PPARγ, implicated in the maintenance of AAMφ, was down-regulated on infection. PPARδ expression, however, was maintained. To explain how PPAR-mediated transcriptional activation could be maintained, we used lipidomics to quantify AAMφ-derived eicosanoids, potential PPAR ligands. We identified the PPARδ ligand PGI2 as the most abundant AAMφ-derived eicosanoid and propose a PGI2-PPARδ axis maintains AAMφ during B malayi implantation.
Unique small RNA signatures uncovered in the tammar wallaby genome
Authors: Lindsay James , Carone Dawn M , Brown Judy , Hall Laura , Qureshi Sohaib , Mitchell Sarah E , Jannetty Nicholas , Hannon Greg , Renfree Marilyn , Pask Andrew , O’Neill Michael , O’Neill Rachel 
Published: October 2012

Abstract

Background
Small RNAs have proven to be essential regulatory molecules encoded within eukaryotic genomes. These short RNAs participate in a diverse array of cellular processes including gene regulation, chromatin dynamics and genome defense. The tammar wallaby, a marsupial mammal, is a powerful comparative model for studying the evolution of regulatory networks. As part of the genome sequencing initiative for the tammar, we have explored the evolution of each of the major classes of mammalian small RNAs in an Australian marsupial for the first time, including the first genome-scale analysis of the newest class of small RNAs, centromere repeat associated short interacting RNAs (crasiRNAs).

Results
Using next generation sequencing, we have characterized the major classes of small RNAs, micro (mi) RNAs, piwi interacting (pi) RNAs, and the centromere repeat associated short interacting (crasi) RNAs in the tammar. We examined each of these small RNA classes with respect to the newly assembled tammar wallaby genome for gene and repeat features, salient features that define their canonical sequences, and the constitution of both highly conserved and species-specific members. Using a combination of miRNA hairpin predictions and co-mapping with miRBase entries, we identified a highly conserved cluster of miRNA genes on the X chromosome in the tammar and a total of 94 other predicted miRNA producing genes. Mapping all miRNAs to the tammar genome and comparing target genes among tammar, mouse and human, we identified 163 conserved target genes. An additional nine genes were identified in tammar that do not have an orthologous miRNA target in human and likely represent novel miRNA-regulated genes in the tammar. A survey of the tammar gonadal piRNAs shows that these small RNAs are enriched in retroelements and carry members from both marsupial and tammar-specific repeat classes. Lastly, this study includes the first in-depth analyses of the newly discovered crasiRNAs. These small RNAs are derived largely from centromere-enriched retroelements, including a novel SINE.

Conclusions
This study encompasses the first analyses of the major classes of small RNAs for the newly completed tammar genome, validates preliminary annotations using deep sequencing and computational approaches, and provides a foundation for future work on tammar-specific as well as conserved, but previously unknown small RNA progenitors and targets identified herein. The characterization of new miRNA target genes and a unique profile for crasiRNAs has allowed for insight into multiple RNA mediated processes in the tammar, including gene regulation, species incompatibilities, centromere and chromosome function.
Enhancement of carotenoid production by disrupting the C22-sterol desaturase gene (CYP61) in Xanthophyllomyces dendrorhous
Authors: Loto Iris , Gutiérrez María Soledad , Barahona Salvador , Sepúlveda Dionisia , Martínez-Moya Pilar , Baeza Marcelo , Cifuentes Víctor , Alcaíno Jennifer 
Published: October 2012

Abstract

Background

Xanthophyllomyces dendrorhous is a basidiomycetous yeast that synthesizes astaxanthin, which is a carotenoid with a great biotechnological impact. The ergosterol and carotenoid synthesis pathways are derived from the mevalonate pathway, and in both pathways, cytochrome P450 enzymes are involved.

Results
In this study, we isolated and described the X. dendrorhous CYP61 gene, which encodes a cytochrome P450 involved in ergosterol biosynthesis. This gene is composed of nine exons and encodes a 526 amino acid polypeptide that shares significant percentages of identity and similitude with the C22-sterol desaturase, CYP61, from other fungi. Mutants derived from different parental strains were obtained by disrupting the CYP61 gene with an antibiotic selection marker. These mutants were not able to produce ergosterol and accumulated ergosta-5,8,22-trien-3-ol and ergosta-5,8-dien-3-ol. Interestingly, all of the mutants had a more intense red color phenotype than their respective parental strains. The carotenoid composition was qualitatively and quantitatively analyzed by RP-HPLC, revealing that the carotenoid content was higher in the mutant strains without major changes in their composition. The expression of the HMGR gene, which encodes an enzyme involved in the mevalonate pathway (3-hydroxy-3-methylglutaryl-CoA reductase), was analyzed by RT-qPCR showing that its transcript levels are higher in the CYP61 mutants.

Conclusions
These results suggest that in X. dendrorhous, ergosterol regulates HMGR gene expression by a negative feedback mechanism and in this way; it contributes in the regulation of the carotenoid biosynthesis.