bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of resveratrol on the amelioration of insulin resistance in KKAy mice
Authors: Chen Sifan , Li Jinghua , Zhang Zili , Li Wenxue , Sun Yanshuang , Zhang Quanxin , Feng Xiang , Zhu Wei 
Published: February 2012

Resveratrol (Res) has attracted great interest regarding its effects related to metabolic syndrome, especially for lipid metabolic disorder or insulin resistance; however, the underlying mechanisms remain elusive. To explore the effects of Res on insulin sensitivity and the underlying mechanism, insulin-resistant KKAy mice were treated with 2 and 4 g/kg diets of Res for 12 weeks. After the treatment, blood glucose, serum insulin, glucose tolerance, and insulin tolerance, as well as other indices such as adiponectin mRNA in epididymal adipose tissues, silent information regulator 1 (Sirt1), AMP-activated protein kinase (AMPK), insulin receptor substrate 1 (IRS1), and phosphorylated protein kinase B (PKB/AKT) proteins in liver and soleus muscles, were investigated. The results indicate that Res intervention reduces blood glucose and serum insulin levels, improves insulin and glucose tolerance, increases serum adiponectin and adiponectin mRNA levels in epididymal adipose tissues, and more importantly, elevates Sirt1, p-AMPK, p-IRS1, and p-AKT levels in liver and soleus muscles. In conclusion, Res could improve insulin sensitivity and ameliorate insulin resistance in KKAy mice, which may be associated with the upregulation of Sirt1 protein in liver and soleus muscles and consequent AMPK activation, as well as insulin-signaling related proteins.
Folic acid supplementation attenuates high fat diet induced hepatic oxidative stress via regulation of NADPH oxidase
Authors: Sarna Lindsei K. , Wu Nan , Wang Pengqi , Hwang Sun-Young , Siow Yaw L. , O Karmin 
Published: February 2012

Diets high in saturated fat and cholesterol facilitate weight gain, a predisposing factor that contributes to the onset of obesity and metabolic disorders. Hepatic oxidative stress is commonly reported in various animal models of obesity and has been associated with enhanced expression of NADPH oxidase. We have previously reported several antioxidant mechanisms through which folic acid confers protection during hyperhomocysteinemia-induced oxidative stress. The objective of the present study was to investigate whether folic acid supplementation ameliorates high-fat diet induced oxidative stress in the liver, and to identify the underlying mechanisms. Male C57BL/6J mice were fed a control diet, a high-fat diet, or a high-fat diet supplemented with folic acid for 12 weeks. A high-fat diet led to increased body mass, hepatic lipid peroxidation, and liver injury. There was a significant increase in hepatic NADPH oxidase activity, which was associated with enhanced expression of several NADPH-oxidase subunits. Folic acid supplementation had a protective effect against high-fat diet induced hepatic oxidative stress and liver injury. Further analysis revealed that the antioxidant effect of folic acid was attributed, in part, to transcriptional regulation of NADPH oxidase. These results suggested that folic acid supplementation may be hepatoprotective from liver injury associated with a high-fat diet.
Activation of proteolytic enzymes and depression of the sarcolemmal Na+/K+-ATPase in ischemia–reperfused heart may be mediated through oxidative stress
Authors: Singh Raja B. , Hryshko Larry , Freed Darren , Dhalla Naranjan S. 
Published: February 2012

We tested whether the activation of proteolytic enzymes, calpain, and matrix metalloproteinases (MMPs) during ischemia–reperfusion (I/R) is mediated through oxidative stress. For this purpose, isolated rat hearts were subjected to a 30 min global ischemia followed by a 30 min reperfusion. Cardiac function was monitored and the activities of Na+/K+-ATPase, Mg2+-ATPase, calpain, and MMP were measured. Depression of cardiac function and Na+/K+-ATPase activity in I/R hearts was associated with increased calpain and MMP activities. These alterations owing to I/R were similar to those observed in hearts perfused with hypoxic medium, H2O2 and xanthine plus xanthine oxidase. The I/R-induced changes were attenuated by ischemic preconditioning as well as by perfusing the hearts with N-acetylcysteine or mercaptopropionylglycine. Inhibition of MMP activity in hearts treated with doxycycline depressed the I/R-induced changes in cardiac function and Na+/K+-ATPase activity without affecting the calpain activation. On the other hand, inhibition of calpain activity upon treatment with leupeptin or MDL 28170 significantly reduced the MMP activity in addition to attenuating the I/R-induced alterations in cardiac function and Na+/K+-ATPase activity. These results suggest that the I/R-induced depression in Na+/K+-ATPase and cardiac function may be a consequence of the increased activities of both calpain and MMP because of oxidative stress in the heart.
Genetic Determinants of Statin-Induced Low-Density Lipoprotein Cholesterol Reduction
Authors: Chasman Daniel I. , Giulianini Franco , MacFadyen Jean , Barratt Bryan J. , Nyberg Fredrik , Ridker Paul M 
Published: February 2012

Background—
In statin trials, each 20 mg/dL reduction in cholesterol results in a 10–15% reduction of annual incidence rates for vascular events. However, interindividual variation in low-density lipoprotein cholesterol (LDL-C) response to statins is wide and may partially be determined on a genetic basis.

Methods and Results—

A genome-wide association study of LDL-C response was performed among a total of 6989 men and women of European ancestry who were randomly allocated to either rosuvastatin 20 mg daily or placebo. Single nucleotide polymorphisms (SNPs) for genome-wide association (
P
<5×10
−8
) with LDL-C reduction on rosuvastatin were identified at
ABCG2
,
LPA
, and
APOE
, and a further association at
PCSK9
was genome-wide significant for baseline LDL-C and locus-wide significant for LDL-C reduction. Median LDL-C reductions on rosuvastatin were 40, 48, 51, 55, 60, and 64 mg/dL, respectively, among those inheriting increasing numbers of LDL-lowering alleles for SNPs at these 4 loci (
P
trend=6.2×10
−20
), such that each allele approximately doubled the odds of percent LDL-C reduction greater than the trial median (odds ratio, 1.9; 95% confidence interval, 1.8–2.1;
P
=5.0×10
−41
). An intriguing additional association with sub–genome-wide significance (
P
<1×10
-6
) was identified for statin related LDL-C reduction at
IDOL
, which mediates posttranscriptional regulation of the LDL receptor in response to intracellular cholesterol levels. In candidate analysis, SNPs in
SLCO1B1
and
LDLR
were confirmed as associated with LDL-C lowering, and a significant interaction was observed between SNPs in
PCSK9
and
LDLR
.

Conclusions—
Inherited polymorphisms that predominantly relate to statin pharmacokinetics and endocytosis of LDL particles by the LDL receptor are common in the general population and influence individual patient response to statin therapy.
Evaluation of TRMM Rain Estimates Using Ground Measurements over Central Florida
Authors: Wang Jianxin , Wolff David B. 
Published: February 2012

AbstractThis study evaluates space-based rain estimates from the Tropical Rainfall Measuring Mission (TRMM) satellite using ground-based measurements from the radar (GR) and tipping-bucket rain gauges (TG) over the TRMM Ground Validation (GV) site at Melbourne, Florida. The satellite rain products are derived from the TRMM Microwave Imager (TMI), precipitation radar (PR), and combined (COM) rain algorithms using observations from both instruments. The TRMM satellite and GV rain products are spatiotemporally matched and are intercompared at multiple time scales over the 12-yr period from 1998 to 2009. On monthly and yearly scales, the TG agree excellently with the GR because the GR rain rates are generated using the TG data as a constraint on a monthly basis. However, large disagreements exist between the GR and TG at shorter time scales because of their significantly different spatial and temporal sampling modes. The yearly biases relative to the GR for the PR and TMI are generally negative, with a few exceptions. The COM bias fluctuates from year to year over the 12-yr period. The PR, TMI, and COM are in good overall agreement with the GR in the lower range of rain rates, but the agreement is notably worse at higher rain rates. The diurnal cycle of rainfall is captured well by all products, but the peak satellite-derived rainfall (PR, TMI, and COM) lags the peak from the ground measurements (GR and TG) by ~1 h.
Contributions of Downstream Eddy Development to the Teleconnection between ENSO and the Atmospheric Circulation over the North Atlantic
Authors: Li Ying , Lau Ngar-Cheung 
Published: February 2012

AbstractThe spatiotemporal evolution of various meteorological phenomena associated with El Niño–Southern Oscillation (ENSO) in the North Pacific–North American–North Atlantic sector is examined using both NCEP–NCAR reanalyses and output from a 2000-yr integration of a global coupled climate model. Particular attention is devoted to the implications of downstream eddy developments on the relationship between ENSO and the atmospheric circulation over the North Atlantic.The El Niño–related persistent events are characterized by a strengthened Pacific subtropical jet stream and an equatorward-shifted storm track over the North Pacific. The wave packets that populate the storm tracks travel eastward through downstream development. The barotropic forcing of the embedded synoptic-scale eddies is conducive to the formation of a flow that resembles the negative phase of the North Atlantic Oscillation (NAO). The more frequent and higher persistence of those episodes during El Niño winters contribute to the prevalence of negative NAO conditions.The above processes are further delineated by conducting a case study for the 2009/10 winter season, in which both El Niño and negative NAO conditions prevailed. It is illustrated that the frequent and intense surface cyclone development over North America and the western Atlantic throughout that winter are associated with upper-level troughs propagating across North America, which in turn are linked to downstream evolution of wave packets originating from the Pacific storm track.
An Automated Cirrus Cloud Detection Method for a Ground-Based Cloud Image
Authors: Yang Jun , Lu Weitao , Ma Ying , Yao Wen 
Published: February 2012

Abstract
Cloud detection is a basic research for achieving cloud-cover state and other cloud characteristics. Because of the influence of sunlight, the brightness of sky background on the ground-based cloud image is usually nonuniform, which increases the difficulty for cirrus cloud detection, and few detection methods perform well for thin cirrus clouds. This paper presents an effective background estimation method to eliminate the influence of variable illumination conditions and proposes a background subtraction adaptive threshold method (BSAT) to detect cirrus clouds in visible images for the small field of view and mixed clear–cloud scenes. The BSAT algorithm consists of red-to-blue band operation, background subtraction, adaptive threshold selection, and binarization. The experimental results show that the BSAT algorithm is robust for all types of cirrus clouds, and the quantitative evaluation results demonstrate that the BSAT algorithm outperforms the fixed threshold (FT) and adaptive threshold (AT) methods in cirrus cloud detection.
Development and validation of a real-time quantification assay to detect and monitor BRAFV600E mutations in hairy cell leukemia
Authors: Schnittger Susanne , Bacher Ulrike , Haferlach Torsten , Wendland Nicole , Ulke Madlen , Dicker Frank , Grossmann Vera , Haferlach Claudia , Kern Wolfgang 
Published: February 2012

Abstract
The BRAFV600E mutation was recently detected in hairy cell leukemia (HCL) by whole exome sequencing. To make use of this new marker for diagnosis and follow-up of HCL, we developed a BRAFV600Emut-specific quantitative real-time PCR assay and validated it in 117 HCL patients and 102 non-HCL/BRAFwt patients. The cut-off level to discriminate BRAFV600E-positive/-negative cases was set at 0.023% BRAFV600E/BRAFwt. A total of 115 of 117 HCL (98.3%) demonstrated percentage BRAFV600E/BRAFwt above the cut-off (mean, 29.6 ± 41.1). The remaining 2 of 117 HCL with lower percentage BRAFV600E/BRAFwt ratios were also BRAFwt by deep-sequencing technology. Sixteen HCL-variant patients showed percentage BRAFV600E/BRAFwt values corresponding to “non-HCL.” Follow-up studies in 19 HCL cases demonstrated a decrease of percentage BRAFV600E/BRAFwt during therapy. The log-reductions as determined by RT-PCR and immunophenotyping correlated significantly (P < .001). In conclusion, we confirmed BRAFmut as a useful marker in HCL, its absence in HCL variant, and developed an RT-PCR-based assay to monitor minimal residual disease in HCL.
Fractionated breath condensate sampling: H2O2 concentrations of the alveolar fraction may be related to asthma control in children
Authors: Trischler Jordis , Merkel Nick , Könitzer Stephanie , Müller Christina-Maria , Unverzagt Susanne , Lex Christiane 
Published: February 2012

Abstract

Background
Asthma is a chronic inflammatory disease of the airways but recent studies have shown that alveoli are also subject to pathophysiological changes. This study was undertaken to compare hydrogen peroxide (H2O2) concentrations in different parts of the lung using a new technique of fractioned breath condensate sampling.

Methods
In 52 children (9-17 years, 32 asthmatic patients, 20 controls) measurements of exhaled nitric oxide (FENO), lung function, H2O2 in exhaled breath condensate (EBC) and the asthma control test (ACT) were performed. Exhaled breath condensate was collected in two different fractions, representing mainly either the airways or the alveoli. H2O2 was analysed in the airway and alveolar fractions and compared to clinical parameters.

Results
The exhaled H2O2 concentration was significantly higher in the airway fraction than in the alveolar fraction comparing each single pair (p = 0.003, 0.032 and 0.040 for the whole study group, the asthmatic group and the control group, respectively). Asthma control, measured by the asthma control test (ACT), correlated significantly with the H2O2 concentrations in the alveolar fraction (r = 0.606, p = 0.004) but not with those in the airway fraction in the group of children above 12 years. FENO values and lung function parameters did not correlate to the H2O2 concentrations of each fraction.

Conclusion
The new technique of fractionated H2O2 measurement may differentiate H2O2 concentrations in different parts of the lung in asthmatic and control children. H2O2 concentrations of the alveolar fraction may be related to the asthma control test in children.
The diversity and evolution of chelicerate hemocyanins
Authors: Rehm Peter , Pick Christian , Borner Janus , Markl Jürgen , Burmester Thorsten 
Published: February 2012

Abstract

Background
Oxygen transport in the hemolymph of many arthropod species is facilitated by large copper-proteins referred to as hemocyanins. Arthropod hemocyanins are hexamers or oligomers of hexamers, which are characterized by a high O2 transport capacity and a high cooperativity, thereby enhancing O2 supply. Hemocyanin subunit sequences had been available from horseshoe crabs (Xiphosura) and various spiders (Araneae), but not from any other chelicerate taxon. To trace the evolution of hemocyanins and the emergence of the large hemocyanin oligomers, hemocyanin cDNA sequences were obtained from representatives of selected chelicerate classes.

Results
Hemocyanin subunits from a sea spider, a scorpion, a whip scorpion and a whip spider were sequenced. Hemocyanin has been lost in Opiliones, Pseudoscorpiones, Solifugae and Acari, which may be explained by the evolution of trachea (i.e., taxon Apulmonata). Bayesian phylogenetic analysis was used to reconstruct the evolution of hemocyanin subunits and a relaxed molecular clock approach was applied to date the major events. While the sea spider has a simple hexameric hemocyanin, four distinct subunit types evolved before Xiphosura and Arachnida diverged around 470 Ma ago, suggesting the existence of a 4 × 6mer at that time. Subsequently, independent gene duplication events gave rise to the other distinct subunits in each of the 8 × 6mer hemocyanin of Xiphosura and the 4 × 6mer of Arachnida. The hemocyanin sequences were used to infer the evolutionary history of chelicerates. The phylogenetic trees support a basal position of Pycnogonida, a sister group relationship of Xiphosura and Arachnida, and a sister group relationship of the whip scorpions and the whip spiders.

Conclusion
Formation of a complex hemocyanin oligomer commenced early in the evolution of euchelicerates. A 4 × 6mer hemocyanin consisting of seven subunit types is conserved in most arachnids since more than 400 Ma, although some entelegyne spiders display selective subunit loss and independent oligomerization. Hemocyanins also turned out to be a good marker to trace chelicerate evolution, which is, however, limited by the loss of hemocyanin in some taxa. The molecular clock calculations were in excellent agreement with the fossil record, also demonstrating the applicability of hemocyanins for such approach.
Orthologous genes identified by transcriptome sequencing in the spider genus Stegodyphus
Authors: Mattila Tiina M , Bechsgaard Jesper S , Hansen Troels T , Schierup Mikkel H , Bilde Trine 
Published: February 2012

Abstract

Background
The evolution of sociality in spiders involves a transition from an outcrossing to a highly inbreeding mating system, a shift to a female biased sex ratio, and an increase in the reproductive skew among individuals. Taken together, these features are expected to result in a strong reduction in the effective population size. Such a decline in effective population size is expected to affect population genetic and molecular evolutionary processes, resulting in reduced genetic diversity and relaxed selective constraint across the genome. In the genus Stegodyphus, permanent sociality and regular inbreeding has evolved independently three times from periodic-social (outcrossing) ancestors. This genus is therefore an ideal model for comparative studies of the molecular evolutionary and population genetic consequences of the transition to a regularly inbreeding mating system. However, no genetic resources are available for this genus.

Results
We present the analysis of high throughput transcriptome sequencing of three Stegodyphus species. Two of these are periodic-social (Stegodyphus lineatus and S.tentoriicola) and one is permanently social (S. mimosarum). From non-normalized cDNA libraries, we obtained on average 7,000 putative uni-genes for each species. Three-way orthology, as predicted from reciprocal BLAST, identified 1,792 genes that could be used for cross-species comparison. Open reading frames (ORFs) could be deduced from 1,345 of the three-way alignments. Preliminary molecular analyses suggest a five- to ten-fold reduction in heterozygosity in the social S. mimosarum compared with the periodic-social species. Furthermore, an increased ratio of non-synonymous to synonymous polymorphisms in the social species indicated relaxed efficiency of selection. However, there was no sign of relaxed selection on the phylogenetic branch leading to S. mimosarum.

Conclusions
The 1,792 three-way ortholog genes identified in this study provide a unique resource for comparative studies of the eco-genomics, population genetics and molecular evolution of repeated evolution of inbreeding sociality within the Stegodyphus genus. Preliminary analyses support theoretical expectations of depleted heterozygosity and relaxed selection in the social inbreeding species. Relaxed selection could not be detected in the S. mimosarum lineage, suggesting that there has been a recent transition to sociality in this species.
Reference genome-independent assessment of mutation density using restriction enzyme-phased sequencing
Authors: Monson-Miller Jennifer , Sanchez-Mendez Diana C , Fass Joseph , Henry Isabelle M , Tai Thomas H , Comai Luca 
Published: February 2012

Abstract

Background
The availability of low cost sequencing has spurred its application to discovery and typing of variation, including variation induced by mutagenesis. Mutation discovery is challenging as it requires a substantial amount of sequencing and analysis to detect very rare changes and distinguish them from noise. Also challenging are the cases when the organism of interest has not been sequenced or is highly divergent from the reference.

Results
We describe the development of a simple method for reduced representation sequencing. Input DNA was digested with a single restriction enzyme and ligated to Y adapters modified to contain a sequence barcode and to provide a compatible overhang for ligation. We demonstrated the efficiency of this method at SNP discovery using rice and arabidopsis. To test its suitability for the discovery of very rare SNP, one control and three mutagenized rice individuals (1, 5 and 10 mM sodium azide) were used to prepare genomic libraries for Illumina sequencers by ligating barcoded adapters to NlaIII restriction sites. For genome-dependent discovery 15-30 million of 80 base reads per individual were aligned to the reference sequence achieving individual sequencing coverage from 7 to 15×. We identified high-confidence base changes by comparing sequences across individuals and identified instances consistent with mutations, i.e. changes that were found in a single treated individual and were solely GC to AT transitions. For genome-independent discovery 70-mers were extracted from the sequence of the control individual and single-copy sequence was identified by comparing the 70-mers across samples to evaluate copy number and variation. This de novo "genome" was used to align the reads and identify mutations as above. Covering approximately 1/5 of the 380 Mb genome of rice we detected mutation densities ranging from 0.6 to 4 per Mb of diploid DNA depending on the mutagenic treatment.

Conclusions
The combination of a simple and cost-effective library construction method, with Illumina sequencing, and the use of a bioinformatic pipeline allows practical SNP discovery regardless of whether a genomic reference is available.
The tyrosyl-tRNA synthetase like gene located in the tyramine biosynthesis cluster of Enterococcus duransis transcriptionally regulated by tyrosine concentration and extracellular pH
Authors: Linares Daniel M , Fernández Maria , Del-Río Beatriz , Ladero Victor , Martin Maria Cruz , Alvarez Miguel A 
Published: February 2012

Abstract

Background
The tyramine producer Enterococcus durans IPLA655 contains all the necessary genes for tyramine biosynthesis, grouped in the TDC cluster. This cluster includes tyrS, an aminoacyl-tRNA synthetase like gene.

Results
This work shows that tyrS was maximally transcribed in absence of tyrosine at acidic pH, showing a greater than 10-fold induction in mRNA levels over levels occurring in presence of tyrosine. Mapping of the tyrS transcriptional start site revealed an unusually long untranslated leader region of 322 bp, which displays the typical features of the T box transcriptional attenuation mechanism. The tyrosine concentration regulation of tyrS was found to be mediated by a transcription antitermination system, whereas the specific induction at acidic pH was regulated at transcription initiation level.

Conclusions
The expression of the tyrS gene present in the TDC cluster of E. durans is transcriptionally regulated by tyrosine concentration and extracelular pH. The regulation is mediated by both an antitermination system and the promoter itself.