bluuebunny/crossref_metadata_2025_split huggingface dataset:
Farnesoid X receptor protects human and murine gastric epithelial cells against inflammation-induced damage
Authors: Lian Fan , Xing Xiangbin , Yuan Gang , Schäfer Claus , Rauser Sandra , Walch Axel , Röcken Christoph , Ebeling Martin , Wright Matthew B. , Schmid Roland M. , Ebert Matthias P. A. , Burgermeister Elke 
Published: July 2011

Bile acids from duodenogastric reflux promote inflammation and increase the risk for gastro-oesophageal cancers. FXR (farnesoid X receptor/NR1H4) is a transcription factor regulated by bile acids such as CDCA (chenodeoxycholic acid). FXR protects the liver and the intestinal tract against bile acid overload; however, a functional role for FXR in the stomach has not been described. We detected FXR expression in the normal human stomach and in GC (gastric cancer). FXR mRNA and protein were also present in the human GC cell lines MKN45 and SNU5, but not in the AGS cell line. Transfection of FXR into AGS cells protected against TNFα (tumour necrosis factor α)-induced cell damage. We identified K13 (keratin 13), an anti-apoptotic protein of desmosomes, as a novel CDCA-regulated FXR-target gene. FXR bound to a conserved regulatory element in the proximal human K13 promoter. Gastric expression of K13 mRNA was increased in an FXR-dependent manner by a chow diet enriched with 1% (w/w) CDCA and by indomethacin (35 mg/kg of body weight intraperitoneal) in C57BL/6 mice. FXR-deficient mice were more susceptible to indomethacin-induced gastric ulceration than their WT (wild-type) littermates. These results suggest that FXR increases the resistance of human and murine gastric epithelial cells to inflammation-mediated damage and may thus participate in the development of GC.
Radiosensitization in human breast carcinoma cells by thymoquinone: role of cell cycle and apoptosis
Authors: Velho‐Pereira Reelma , Kumar Amit , Pandey Badri N. , Jagtap Aarti G. , Mishra Kaushala P. 
Published: July 2011

AbstractTQ (thymoquinone), the bioactive constituent of black seed (Nigella sativa), has been shown to inhibit the growth of various human cancers both in vitro and in vivo. This study reports the radiosensitizing effect of TQ on human breast carcinoma cells (MCF7 and T47D). TQ in combination with single dose of ionizing radiation (2.5 Gy) was found to exert supra‐additive cytotoxic effects on both the carcinomas as measured by cell proliferation and colony‐formation assays. Annexin V binding and FACS analysis revealed the role of enhanced apoptosis and cell cycle modulation in the mechanism of TQ‐mediated radiosensitization, thus supporting TQ as an adjuvant for preclinical testing in cancer chemo‐radiotherapy.
Curvature factor and membrane solubilization, with particular reference to membrane rafts
Authors: Mrówczyńska Lucyna , Salzer Ulrich , Iglič Aleš , Hägerstrand Henry 
Published: July 2011

AbstractThe composition of membrane rafts (cholesterol/sphingolipid‐rich domains) cannot be fully deduced from the analysis of a detergent‐resistant membrane fraction after solubilization in Triton X‐100 at 4°C. It is hypothesized that the membrane curvature‐dependent lateral distribution of membrane components affects their solubilization. The stomatocytogenic, Triton X‐100, cannot effectively solubilize membrane components, especially with regard to the outward membrane curvature.
Plasma proprotein convertase subtilisin kexin type 9 is a heritable trait of familial combined hyperlipidaemia
Authors: Brouwers Martijn C.G.J. , van Greevenbroek Marleen M.J. , Troutt Jason S. , Bonner Freeman Angela , Lu Ake , Schaper Nicolaas C. , Konrad Robert J. , Stehouwer Coen D.A. 
Published: July 2011

The aim of the present study was to investigate the relationship between circulating PCSK9 (proprotein convertase subtilisin kexin type 9) and FCHL (familial combined hyperlipidaemia) and, when positive, to determine the strength of its heritability. Plasma PCSK9 levels were measured in FCHL patients (n=45), NL (normolipidaemic) relatives (n=139) and their spouses (n=72). In addition, 11 FCHL patients were treated with atorvastatin to study the response in PCSK9 levels. PCSK9 levels were higher in FCHL patients compared with NL relatives and spouses: 96.1 compared with 78.7 and 82.0 ng/ml (P=0.004 and P=0.002 respectively). PCSK9 was significantly associated with both TAG (triacylglycerol) and apolipoprotein B levels (P&lt;0.001). The latter relationship was accounted for by LDL (low-density lipoprotein)–apolipoprotein B (r=0.31, P=0.02), not by VLDL (very-low-density lipoprotein)–apolipoprotein B (r=0.09, P=0.49) in a subgroup of subjects (n=59). Heritability calculations for PCSK9 using SOLAR and FCOR software yielded estimates of 67–84% respectively (P&lt;0.0001). PCSK9 increased from 122 to 150 ng/ml in 11 FCHL patients treated with atorvastatin (40 mg) once daily for 8 weeks (P=0.018). In conclusion, plasma PCSK9 is a heritable trait associated with both FCHL diagnostic hallmarks. These results, combined with the significant rise in PCSK9 levels after statin therapy, warrant further studies in order to unravel the exact role of PCSK9 in the pathogenesis and treatment of this highly prevalent genetic dyslipidaemia.
Acute simvastatin increases endothelial nitric oxide synthase phosphorylation via AMP-activated protein kinase and reduces contractility of isolated rat mesenteric resistance arteries
Authors: Rossoni Luciana V. , Wareing Mark , Wenceslau Camilla F. , Al-Abri Mahmood , Cobb Chris , Austin Clare 
Published: July 2011

Statins can have beneficial cholesterol-independent effects on vascular contractility, which may involve increases in the bioavailability of NO (nitric oxide) as a result of phosphorylation of eNOS (endothelial NO synthase). Although this has been attributed to phosphorylation of Akt (also known as protein kinase B), studies in cultured cells have shown that statins can phosphorylate AMPK (AMP-activated protein kinase); it is unknown whether this has functional effects in intact arteries. Thus we investigated the acute effects of simvastatin on resistance arterial contractile function, evaluating the involvement of NO, Akt and AMPK. Isolated rat mesenteric resistance arteries were mounted on a wire myograph. The effects of incubation (1 and 2 h) with simvastatin (0.1 or 1 μM) on contractile responses were examined in the presence and absence of L-NNA (N-nitro-L-arginine; 10 μM) or mevalonate (1 mM). Effects on eNOS, phospho-eNOS (Ser1177), and total and phospho-Akt and -AMPK protein expression were investigated using Western blotting. The effect of AMPK inhibition (compound C, 10 μM) on eNOS phosphorylation and contractile responses were also studied. Simvastatin (1 μM, 2 h) significantly reduced constriction to U46619 and phenylephrine and enhanced dilations to ACh (acetylcholine) in depolarized, but not in U46619-pre-constricted arteries. These effects were completely and partially prevented by L-NNA and mevalonate respectively. Simvastatin increased eNOS and AMPKα phosphorylation, but had no effect on Akt protein expression and phosphorylation after 2 h incubation. Compound C prevented the effects of simvastatin on eNOS phosphorylation and contractility. Thus simvastain can acutely modulate resistance arterial contractile function via mechanisms that involve the AMPK/phospho-eNOS (Ser1177)/NO-dependent pathway.
Influence of lower leg muscle fatigue on the centre of pressure in a static upright posture
Authors: Noda Masahiro , Demura Shin‐Ichi 
Published: July 2011

AbstractWe examined the influence of fatigue in the lower leg muscles on the centre of pressure sway during a static upright posture. Twelve healthy young men and women completed the exercise stress test on the triceps surae muscle and continued the exercise until their muscles were fatigued. A centre of pressure sway of 1 min was carried out in a Romberg posture at rest and at different instants after fatiguing exercise: immediately after, 5 min after, and 10 min after exercise. Blood lactate concentration was measured from fingertip samples taken before and immediately after exercise. To evaluate body sway, the following four centre of pressure sway factors were selected: unit time sway, front–back sway, left–right sway, and high‐frequency band power spectrum. The measurement device used was an Anima stabilometer (G5500). The data sampling frequency was 20 Hz. After exercise, blood lactate concentration was increased. Significant differences were observed in unit time sway, front–back sway, and high‐frequency band power spectrum immediately after exercise. These values eventually returned to baseline levels 5 min after fatiguing exercise.
TotalReCaller: improved accuracy and performance via integrated alignment and base-calling
Authors: Menges Fabian , Narzisi Giuseppe , Mishra Bud 
Published: July 2011

AbstractMotivation: Currently, re-sequencing approaches use multiple modules serially to interpret raw sequencing data from next-generation sequencing platforms, while remaining oblivious to the genomic information until the final alignment step. Such approaches fail to exploit the full information from both raw sequencing data and the reference genome that can yield better quality sequence reads, SNP-calls, variant detection, as well as an alignment at the best possible location in the reference genome. Thus, there is a need for novel reference-guided bioinformatics algorithms for interpreting analog signals representing sequences of the bases ({A, C, G, T}), while simultaneously aligning possible sequence reads to a source reference genome whenever available.Results: Here, we propose a new base-calling algorithm, TotalReCaller, to achieve improved performance. A linear error model for the raw intensity data and Burrows–Wheeler transform (BWT) based alignment are combined utilizing a Bayesian score function, which is then globally optimized over all possible genomic locations using an efficient branch-and-bound approach. The algorithm has been implemented in soft- and hardware [field-programmable gate array (FPGA)] to achieve real-time performance. Empirical results on real high-throughput Illumina data were used to evaluate TotalReCaller's performance relative to its peers—Bustard, BayesCall, Ibis and Rolexa—based on several criteria, particularly those important in clinical and scientific applications. Namely, it was evaluated for (i) its base-calling speed and throughput, (ii) its read accuracy and (iii) its specificity and sensitivity in variant calling.Availability: A software implementation of TotalReCaller as well as additional information, is available at: http://bioinformatics.nyu.edu/wordpress/projects/totalrecaller/Contact: fabian.menges@nyu.edu
Tissue-specific prediction of directly regulated genes
Authors: McLeay Robert C. , Leat Chris J. , Bailey Timothy L. 
Published: July 2011

Abstract
Direct binding by a transcription factor (TF) to the proximal promoter of a gene is a strong evidence that the TF regulates the gene. Assaying the genome-wide binding of every TF in every cell type and condition is currently impractical. Histone modifications correlate with tissue/cell/condition-specific (‘tissue specific’) TF binding, so histone ChIP-seq data can be combined with traditional position weight matrix (PWM) methods to make tissue-specific predictions of TF–promoter interactions.
Results: We use supervised learning to train a naïve Bayes predictor of TF–promoter binding. The predictor's features are the histone modification levels and a PWM-based score for the promoter. Training and testing uses sets of promoters labeled using TF ChIP-seq data, and we use cross-validation on 23 such datasets to measure the accuracy. A PWM+histone naïve Bayes predictor using a single histone modification (H3K4me3) is substantially more accurate than a PWM score or a conservation-based score (phylogenetic motif model). The naïve Bayes predictor is more accurate (on average) at all sensitivity levels, and makes only half as many false positive predictions at sensitivity levels from 10% to 80%. On average, it correctly predicts 80% of bound promoters at a false positive rate of 20%. Accuracy does not diminish when we test the predictor in a different cell type (and species) from training. Accuracy is barely diminished even when we train the predictor without using TF ChIP-seq data.
Availability: Our tissue-specific predictor of promoters bound by a TF is called Dr Gene and is available at http://bioinformatics.org.au/drgene.
Contact: t.bailey@imb.uq.edu.au
Supplementary information: Supplementary data are available at Bioinformatics online.
An examination of information‐processing skills among inhalant‐using adolescents
Authors: Scott K. D. , Scott A. A. 
Published: July 2011

AbstractBackground  This study investigates the association between inhalant use and information processing (IP) in adjudicated polysubstance users. Polysubstance users who used inhalants (n= 158) were compared with polysubstance users who did not use inhalants (n= 303). Hispanic Americans comprised 72% of the participants; European Americans, African Americans and Asian Americans comprised 28% of the participants.Method  Standardized intelligence and achievement tests were used to assess information‐processing constructs of working memory and processing speed. Psychosocial and substance abuse standardized surveys were used to assess drug use severity and psychosocial problems associated with substance use.Results  Polysubstance users who used inhalants (PSI users) were younger, used more drugs more frequently and had more psychiatric admissions than non‐inhalant polysubstance users (PSO users). Statistical analysis also shows that PSI users performed worse on measures of IP selected tests in comparison with the PSO users.Conclusion  Inhalant users begin abusing substances at a younger age and suffer from more verbal and non‐verbal processing, behavioural, language and memory problems than non‐inhalant users.
Increased prevalence of impaired fasting glucose in MEN1 gene mutation carriers
Authors: van Wijk J. P. H. , Dreijerink K. M. A. , Pieterman C. R. C. , Lips C. J. M. , Zelissen P. M. J. , Valk G. D. 
Published: July 2011

SummaryObjective  Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome characterized by parathyroid, gastroenteropancreatic, pituitary and adrenal tumours. Cardiovascular disease has been identified as an important cause of death in MEN1 patients. Menin, the product of the MEN1 gene, is a co‐activator for peroxisome proliferator‐activated receptor‐γ and the vitamin D receptor, which are involved in glucose metabolism. We aimed to compare insulin sensitivity and prevalence of impaired fasting glucose and diabetes mellitus between MEN1 patients and controls.Design  Cross‐sectional study.Patients  Sixty‐three MEN1 gene mutation carriers (44% men, mean age 41 years) from 22 kindreds and 126 unrelated controls matched for gender, age and BMI.Measurements  Fasting glucose levels were categorized and compared using WHO criteria. Homeostasis model assessment (HOMA) was used as a measure of insulin resistance.Results  Homeostasis model assessment was significantly increased in MEN1 patients compared with controls (3·0 ± 2·0 vs 2·0 ± 1·0, P < 0·05). In MEN1 patients, HOMA was associated with BMI, but not with age, calcium and gastrin levels. Using logistic regression analysis, the presence of hyperparathyroidism, pancreatic lesions and various other manifestations was not associated with HOMA. Impaired fasting glucose was more prevalent in MEN1 compared with controls (17%vs 6%, P < 0·05). Three MEN1 patients (5%) compared with four controls (3%) were diabetic (not significant).Conclusions  Multiple endocrine neoplasia type 1 patients had decreased insulin sensitivity and higher prevalence of impaired fasting glucose compared with controls, which was unrelated to MEN1 manifestations. Impaired glucose metabolism may result in increased risk of cardiovascular disease in MEN1 patients.
Job satisfaction, occupational commitment and intent to stay among Chinese nurses: a cross‐sectional questionnaire survey
Authors: Wang Lin , Tao Hong , Ellenbecker Carol H , Liu Xiaohong 
Published: July 2011

Wang L, Tao H, Ellenbecker CH & Liu X (2012) Job satisfaction, occupational commitment and intent to stay among Chinese nurses: a cross‐sectional questionnaire survey. Journal of Advanced Nursing68(3), 539–549.AbstractAim.  This study was designed to identify the level of nurses’ job satisfaction, occupational commitment and intent to stay among mainland Chinese nurses, to explore the relationship among them.Background.  Little is known about the magnitude of Chinese nurses’ intent to stay. Understanding the association among demographic characteristics and job satisfaction, occupational commitment and intent to stay among Chinese nurses is most important in a time of nurse shortages.Methods.  A descriptive correlation design was used to examine the relationship among variables related to intent to stay. Data were collected by a self‐administered survey questionnaire from 560 nurses working in four large hospital facilities in Shanghai in 2009.Results.  The mean scores for nurses’ job satisfaction, occupational commitment and intent to stay were 3·25(0·48), 3·11(0·40) and 3·56(0·65), respectively. Job satisfaction and occupational commitment were significantly related to intent to stay. A statistically significant positive correlation was found between occupational commitment and job satisfaction. Age and job position were significantly related to job satisfaction, occupational commitment and intent to stay.Conclusion.  Levels of job satisfaction, occupational commitment and intent to stay reported by nurses in this study can be improved. Suggested strategies for improvement are: increasing salaries, decreasing workloads, modifying task structure, cultivating work passion and creating more professional opportunity for nurses’ personal growth development and promotion. Enhancing nurses’ job satisfaction and occupational commitment are vital to improve nurses’ intent to stay and for strategies to address the nursing shortage.
‘New to Forensic’; implementing a problem‐based introductory educational programme for forensic practitioners in Scotland
Authors: WALKER H. , LANGTON D. , THOMSON L. 
Published: July 2011

Accessible summary
An introductory education programme entitled ‘New to Forensic’ has been developed for staff working in and across existing range of forensic services. The programme allows staff to learn about the processes and methods of working with people who become part of the forensic service, who are often described as mentally disordered offenders. This is the first forensic education programme of its kind in Scotland.
The process of development and implementation as part of the first programme in the new School of Forensic Mental Health (SoFMH) is described, and includes a summary of the numbers of people involved in the project.
A formal evaluation was undertaken as part of this initiative and early findings are described. Results from questionnaires issued before and after using the programme indicate that people who have completed it feel much more confident in their knowledge of forensic‐related issues.
AbstractThe New to Forensic educational programme has been developed for use across all forensic services in Scotland. It is designed to meet the needs of all staff who are both new to and already working within forensic mental health services. Its objectives are targeted to both clinical and non‐clinical staff. The programme follows the patient's journey through the mental health and criminal justice systems. It covers mental disorder, legislation, psychiatric defences, assessment and treatment, risk of harm to others, services, attitudes and boundaries, multidisciplinary working, users and carers, community, learning disability, and prison services. It is self‐directed and practice based, and uses a problem‐based approach. Over a 3‐year period, trainers and mentors have been trained to deliver the programme by members of the School of Forensic Mental Health http://www.forensicnetwork.scot.nhs.uk/ and all services have adopted the programme as a core educational initiative. Initial findings from the programme evaluation indicate a significant improvement in learning following engagement in the initiative.
Geochemistry of Holocene salt marsh and tidal flat sediments on a barrier island in the southern North Sea (Langeoog, North‐west Germany)
Authors: KOLDITZ KERSTIN , DELLWIG OLAF , BARKOWSKI JAN , BAHLO RAINER , LEIPE THOMAS , FREUND HOLGER , BRUMSACK HANS‐JÜRGEN 
Published: July 2011

AbstractThe barrier islands of the southern North Sea were formed during the Holocene sea‐level rise. These islands form part of a highly dynamic environment whose evolution continues today. Subjected to sea‐level changes, tides and storm events, the sedimentary record reflects processes occurring under varying energy conditions. This article presents geochemical, mineralogical and diatom investigations carried out in the salt marsh of the East Frisian barrier island of Langeoog, which is re‐exposed to a rising sea‐level due to de‐embankment. The major aim of this study is to improve the knowledge of the sedimentological and geochemical development of these deposits under the influence of sea‐level rise, with a special focus on the geochemistry and distribution of heavy mineral‐associated elements. Correlation diagrams between FeO, TiO2 and MnO, as well as ternary plots (Al2O3–SiO2–Zr or TiO2), clearly indicate the variable appearance of heavy minerals in different lithological facies, comprising marsh soil, mixed and sand flat, and relocated beach sands. A dominating abundance of ilmenite followed by zircon, garnets and some other heavy minerals is evidenced by Scanning Electron Microscope‐Energy Dispersive X‐ray measurements. The data presented here suggests that these geochemical proxies are useful tools for characterizing depositional energy conditions. Increasing depositional energy is evident for the lithological units in the following order: marsh soil, mixed flat, sand flat and relocated beach sand. The energetic conditions during sediment deposition, as well as the sedimentary history, are confirmed by diatom analyses as an additional independent indicator. Depending on source rock composition, the geochemical parameters used in this study may also help to investigate depositional energy regimes of other siliciclastic sedimentary systems.