bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Sphingosine-1-phospate receptor 1 mediates S1P action during cardiac development
Authors: Poulsen Ryan R , McClaskey Carolyn M , Rivkees Scott A , Wendler Christopher C 
Published: June 2011

Abstract

Background
Sphingosine-1-phosophate (S1P) is a biologically active sphingolipid metabolite that influences cellular events including differentiation, proliferation, and migration. S1P acts through five distinct cell surface receptors designated S1P1-5R, with S1P1R having the highest expression level in the developing heart. S1P1R is critical for vascular maturation, with its loss leading to embryonic death by E14.5; however, its function during early cardiac development is not well known. Our previous studies demonstrated that altered S1P levels adversely affects atrioventricular (AV) canal development in vitro, with reduced levels leading to cell death and elevated levels inhibiting cell migration and endothelial to mesenchymal cell transformation (EMT).

Results
We determined, by real-time PCR analysis, that S1P1R was expressed at least 10-fold higher than other S1P receptors in the developing heart. Immunohistochemical analysis revealed S1P1R protein expression in both endothelial and myocardial cells in the developing atrium and ventricle. Using AV canal cultures, we observed that treatment with either FTY720 (an S1P1,3,4,5R agonist) or KRP203 (an S1P1R-specific agonist) caused similar effects on AV canal cultures as S1P treatment, including induction of cell rounding, inhibition of cell migration, and inhibition of EMT. In vivo, morphological analysis of embryonic hearts at E10.5 revealed that S1P1R-/- hearts were malformed with reduced myocardial tissue. In addition to reduced myocardial tissue, E12.5 S1P1R-/- hearts had disrupted morphology of the heart wall and trabeculae, with thickened and disorganized outer compact layer and reduced fibronectin (FN) deposition compared to S1P1R+/+ littermates. The reduced myocardium was accompanied by a decrease in cell proliferation but not an increase in apoptosis.

Conclusions
These data indicate that S1P1R is the primary mediator of S1P action in AV canal cultures and that loss of S1P1R expression in vivo leads to malformed embryonic hearts, in part due to reduced fibronectin expression and reduced cell proliferation.
Characterization of single-nucleotide variation in Indian-origin rhesus macaques (Macaca mulatta)
Authors: Fawcett Gloria L , Raveendran Muthuswamy , Deiros David Rio , Chen David , Yu Fuli , Harris Ronald Alan , Ren Yanru , Muzny Donna M , Reid Jeffrey G , Wheeler David A , Worley Kimberly C , Shelton Steven E , Kalin Ned H , Milosavljevic Aleksandar , Gibbs Richard , Rogers Jeffrey 
Published: June 2011

AbstractBackgroundRhesus macaques are the most widely utilized nonhuman primate model in biomedical research. Previous efforts have validated fewer than 900 single nucleotide polymorphisms (SNPs) in this species, which limits opportunities for genetic studies related to health and disease. Extensive information about SNPs and other genetic variation in rhesus macaques would facilitate valuable genetic analyses, as well as provide markers for genome-wide linkage analysis and the genetic management of captive breeding colonies.ResultsWe used the available rhesus macaque draft genome sequence, new sequence data from unrelated individuals and existing published sequence data to create a genome-wide SNP resource for Indian-origin rhesus monkeys. The original reference animal and two additional Indian-origin individuals were resequenced to low coverage using SOLiD™ sequencing. We then used three strategies to validate SNPs: comparison of potential SNPs found in the same individual using two different sequencing chemistries, and comparison of potential SNPs in different individuals identified with either the same or different sequencing chemistries. Our approach validated approximately 3 million SNPs distributed across the genome. Preliminary analysis of SNP annotations suggests that a substantial number of these macaque SNPs may have functional effects. More than 700 non-synonymous SNPs were scored by Polyphen-2 as either possibly or probably damaging to protein function and these variants now constitute potential models for studying functional genetic variation relevant to human physiology and disease.ConclusionsResequencing of a small number of animals identified greater than 3 million SNPs. This provides a significant new information resource for rhesus macaques, an important research animal. The data also suggests that overall genetic variation is high in this species. We identified many potentially damaging non-synonymous coding SNPs, providing new opportunities to identify rhesus models for human disease.
Identification of CRISPR and riboswitch related RNAs among novel noncoding RNAs of the euryarchaeon Pyrococcus abyssi
Authors: Phok Kounthéa , Moisan Annick , Rinaldi Dana , Brucato Nicolas , Carpousis Agamemnon J , Gaspin Christine , Clouet-d'Orval Béatrice 
Published: June 2011

Abstract

Background
Noncoding RNA (ncRNA) has been recognized as an important regulator of gene expression networks in Bacteria and Eucaryota. Little is known about ncRNA in thermococcal archaea except for the eukaryotic-like C/D and H/ACA modification guide RNAs.

Results
Using a combination of in silico and experimental approaches, we identified and characterized novel P. abyssi ncRNAs transcribed from 12 intergenic regions, ten of which are conserved throughout the Thermococcales. Several of them accumulate in the late-exponential phase of growth. Analysis of the genomic context and sequence conservation amongst related thermococcal species revealed two novel P. abyssi ncRNA families. The CRISPR family is comprised of crRNAs expressed from two of the four P. abyssi CRISPR cassettes. The 5'UTR derived family includes four conserved ncRNAs, two of which have features similar to known bacterial riboswitches. Several of the novel ncRNAs have sequence similarities to orphan OrfB transposase elements. Based on RNA secondary structure predictions and experimental results, we show that three of the twelve ncRNAs include Kink-turn RNA motifs, arguing for a biological role of these ncRNAs in the cell. Furthermore, our results show that several of the ncRNAs are subjected to processing events by enzymes that remain to be identified and characterized.

Conclusions
This work proposes a revised annotation of CRISPR loci in P. abyssi and expands our knowledge of ncRNAs in the Thermococcales, thus providing a starting point for studies needed to elucidate their biological function.
A species independent universal bio-detection microarray for pathogen forensics and phylogenetic classification of unknown microorganisms
Authors: Shallom Shamira J , Weeks Jenni N , Galindo Cristi L , McIver Lauren , Sun Zhaohui , McCormick John , Adams L Garry , Garner Harold R 
Published: June 2011

AbstractBackgroundThe ability to differentiate a bioterrorist attack or an accidental release of a research pathogen from a naturally occurring pandemic or disease event is crucial to the safety and security of this nation by enabling an appropriate and rapid response. It is critical in samples from an infected patient, the environment, or a laboratory to quickly and accurately identify the precise pathogen including natural or engineered variants and to classify new pathogens in relation to those that are known. Current approaches for pathogen detection rely on prior genomic sequence information. Given the enormous spectrum of genetic possibilities, a field deployable, robust technology, such as a universal (any species) microarray has near-term potential to address these needs.ResultsA new and comprehensive sequence-independent array (Universal Bio-Signature Detection Array) was designed with approximately 373,000 probes. The main feature of this array is that the probes are computationally derived and sequence independent. There is one probe for each possible 9-mer sequence, thus 49(262,144) probes. Each genome hybridized on this array has a unique pattern of signal intensities corresponding to each of these probes. These signal intensities were used to generate an un-biased cluster analysis of signal intensity hybridization patterns that can easily distinguish species into accepted and known phylogenomic relationships. Within limits, the array is highly sensitive and is able to detect synthetically mixed pathogens. Examples of unique hybridization signal intensity patterns are presented for differentBrucellaspecies as well as relevant host species and other pathogens. These results demonstrate the utility of the UBDA array as a diagnostic tool in pathogen forensics.ConclusionsThis pathogen detection system is fast, accurate and can be applied to any species. Hybridization patterns are unique to a specific genome and these can be used to decipher the identity of a mixed pathogen sample and can separate hosts and pathogens into their respective phylogenomic relationships. This technology can also differentiate between different species and classify genomes into their known clades. The development of this technology will result in the creation of an integrated biomarker-specific bio-signature, multiple select agent specific detection system.
Magnetic resonance imaging for lung cancer detection: Experience in a population of more than 10,000 healthy individuals
Authors: Wu Nai-Yuan , Cheng Hui-Cheng , Ko James S , Cheng Yu-Chen , Lin Po-Wei , Lin Wei-Chan , Chang Cheng-Yen , Liou Der-Ming 
Published: June 2011

Abstract

Background
Recent refinements of lung MRI techniques have reduced the examination time and improved diagnostic sensitivity and specificity. We conducted a study to assess the feasibility of MRI for the detection of primary lung cancer in asymptomatic individuals.

Methods
A retrospective chart review was performed on images of lung parenchyma, which were extracted from whole-body MRI examinations between October 2000 and December 2007. 11,766 consecutive healthy individuals (mean age, 50.4 years; 56.8% male) were scanned using one of two 1.5-T scanners (Sonata and Sonata Maestro, Siemens Medical Solutions, Erlangen, Germany). The standard protocol included a quick whole-lung survey with T2-weighted 2-dimensional half Fourier acquisition single shot turbo spin echo (HASTE) and 3-dimensional volumetric interpolated breath-hold examination (VIBE). Total examination time was less than 10 minutes, and scanning time was only 5 minutes. Prompt referrals and follow-ups were arranged in cases of suspicious lung nodules.

Results
A total of 559 individuals (4.8%) had suspicious lung nodules. A total of 49 primary lung cancers were diagnosed in 46 individuals: 41 prevalence cancers and 8 incidence cancers. The overall detection rate of primary lung cancers was 0.4%. For smokers aged 51 to 70 years, the detection rate was 1.4%. TNM stage I disease accounted for 37 (75.5%). The mean size of detected lung cancers was 1.98 cm (median, 1.5 cm; range, 0.5-8.2 cm). The most histological types were adenocarcinoma in 38 (77.6%).

Conclusion
Rapid zero-dose MRI can be used for lung cancer detection in a healthy population.
Limited importance of the dominant-negative effect of TP53missense mutations
Authors: Stoczynska-Fidelus Ewelina , Szybka Malgorzata , Piaskowski Sylwester , Bienkowski Michal , Hulas-Bigoszewska Krystyna , Banaszczyk Mateusz , Zawlik Izabela , Jesionek-Kupnicka Dorota , Kordek Radzislaw , Liberski Pawel P , Rieske Piotr 
Published: June 2011

Abstract

Background
Heterozygosity of TP53 missense mutations is related to the phenomenon of the dominant-negative effect (DNE). To estimate the importance of the DNE of TP53 mutations, we analysed the percentage of cancer cases showing a single heterozygous mutation of TP53 and searched for a cell line with a single heterozygous mutation of this gene. This approach was based on the knowledge that genes with evident DNE, such as EGFR and IDH1, represent nearly 100% of single heterozygous mutations in tumour specimens and cell lines.

Methods
Genetic analyses (LOH and sequencing) performed for early and late passages of several cell lines originally described as showing single heterozygous TP53 mutations (H-318, G-16, PF-382, MOLT-13, ST-486 and LS-123). Statistical analysis of IARC TP53 and SANGER databases. Genetic analyses of N-RAS, FBXW7, PTEN and STR markers to test cross-contamination and cell line identity. Cell cloning, fluorescence-activated cell sorting and SSCP performed for the PF-382 cell line.

Results
A database study revealed TP53 single heterozygous mutations in 35% of in vivo (surgical and biopsy) samples and only 10% of cultured cells (in vitro), although those numbers appeared to be overestimated. We deem that published in vivo TP53 mutation analyses are not as rigorous as studies in vitro, and we did not find any cell line showing a stable, single heterozygous mutation. G16, PF-382 and MOLT-13 cells harboured single heterozygous mutations temporarily. ST-486, H-318 and LS-123 cell lines were misclassified. Specific mutations, such as R175H, R273H, R273L or R273P, which are reported in the literature to exert a DNE, showed the lowest percentage of single heterozygous mutations in vitro (about 5%).

Conclusion
We suggest that the currently reported percentage of TP53 single heterozygous mutations in tumour samples and cancer cell lines is overestimated. Thus, the magnitude of the DNE of TP53 mutations is questionable. This scepticism is supported by database investigations showing that retention of the wild-type allele occurs with the same frequency as either nonsense or missense TP53 mutations.
c-Myc activates BRCA1 gene expression through distal promoter elements in breast cancer cells
Authors: Chen Yinghua , Xu Jinhua , Borowicz Stanley , Collins Cindy , Huo Dezheng , Olopade Olufunmilayo I 
Published: June 2011

Abstract

Background
The BRCA1 gene plays an important role in the maintenance of genomic stability. BRCA1 inactivation contributes to breast cancer tumorigenesis. An increasing number of transcription factors have been shown to regulate BRCA1 expression. c-Myc can act as a transcriptional activator, regulating up to 15% of all genes in the human genome and results from a high throughput screen suggest that BRCA1 is one of its targets. In this report, we used cultured breast cancer cells to examine the mechanisms of transcriptional activation of BRCA1 by c-Myc.

Methods
c-Myc was depleted using c-Myc-specific siRNAs in cultured breast cancer cells. BRCA1 mRNA expression and BRCA1 protein expression were determined by quantitative RT-PCR and western blot, respectively and BRCA1 promoter activities were examined under these conditions. DNA sequence analysis was conducted to search for high similarity to E boxes in the BRCA1 promoter region. The association of c-Myc with the BRCA1 promoter in vivo was tested by a chromatin immunoprecipitation assay. We investigated the function of the c-Myc binding site in the BRCA1 promoter region by a promoter assay with nucleotide substitutions in the putative E boxes. BRCA1-dependent DNA repair activities were measured by a GFP-reporter assay.

Results
Depletion of c-Myc was found to be correlated with reduced expression levels of BRCA1 mRNA and BRCA1 protein. Depletion of c-Myc decreased BRCA1 promoter activity, while ectopically expressed c-Myc increased BRCA1 promoter activity. In the distal BRCA1 promoter, DNA sequence analysis revealed two tandem clusters with high similarity, and each cluster contained a possible c-Myc binding site. c-Myc bound to these regions in vivo. Nucleotide substitutions in the c-Myc binding sites in these regions abrogated c-Myc-dependent promoter activation. Furthermore, breast cancer cells with reduced BRCA1 expression due to depletion of c-Myc exhibited impaired DNA repair activity.

Conclusions
The distal BRCA1 promoter region is associated with c-Myc and contributes to BRCA1 gene activation.
Biological Monitoring of Blood Naphthalene Levels as a Marker of Occupational Exposure to PAHs among Auto-Mechanics and Spray Painters in Rawalpindi
Authors: Kamal Atif , Qayyum Mazhar , Cheema Iqbal U , Rashid Audil 
Published: June 2011

Abstract

Background
Routine exposure to chemical contaminants in workplace is a cause for concern over potential health risks to workers. In Pakistan, reports on occupational exposure and related health risks are almost non-existent, which reflects the scarce availability of survey data and criteria for determining whether an unsafe exposure has occurred. The current study was designed to evaluate blood naphthalene (NAPH) levels as an indicator of exposure to polycyclic aromatic hydrocarbons (PAHs) among automobile workshop mechanics (MCs) and car-spray painters (PNs). We further determined the relationship between blood NAPH levels and personal behavioural, job related parameters and various environmental factors that may further be associated with elevated risks of occupational exposures to PAHs.

Methods
Sixty blood samples (n = 20 for each group i.e. MC, PN and control group) were collected to compare their blood NAPH levels among exposed (MCs and PNs) and un-exposed (control) groups. Samples were analyzed using high pressure liquid chromatography (HPLC). Data regarding demographic aspects of the subjects and their socioeconomic features were collected using a questionnaire. Subjects were also asked to report environmental hygiene conditions of their occupational environment.

Results
We identified automobile work areas as potential sites for PAHs exposure, which was reflected by higher blood NAPH levels among MCs. Blood NAPH levels ranged from 53.7 to 1980.6 μgL-1 and 54.1 to 892.9 μgL-1 among MCs and PNs respectively. Comparison within each group showed that smoking enhanced exposure risks several fold and both active and passive smoking were among personal parameters that were significantly correlated with log-transformed blood NAPH levels. For exposed groups, work hours and work experience were job related parameters that showed strong associations with the increase in blood NAPH levels. Poor workplace hygiene and ventilation were recognized as most significant predictors related to differences among workplaces that may enhance the extent of exposure to chemical contaminants.

Conclusions
It appeared that chemical exposure at the workplace may be influenced by multiple environmental factors, but poor workplace hygiene and duration of exposure (long work hours) were the most important factors. Smoking and negligence of workers regarding self protection were among some of the important personal behaviours than can be addressed with better training. There is also a need to improve workplaces hygiene and to rationalize work hours to minimize health risks. Since smoking was an important confounding factor that supplemented most of the actual occupational exposure, a study based on non-smoker subjects is needed to separate out the effects of smoking and other confounding factors that may obscure measurements of actual extent of occupational exposure.
Patient safety education for undergraduate medical students: a systematic review
Authors: Nie Yanli , Li Lin , Duan Yurong , Chen Peixian , Barraclough Bruce H , Zhang Mingming , Li Jing 
Published: June 2011

Abstract

Background
To reduce harm caused by health care is a global priority. Medical students should be able to recognize unsafe conditions, systematically report errors and near misses, investigate and improve such systems with a thorough understanding of human fallibility, and disclose errors to patients. Incorporating the knowledge of how to do this into the medical student curriculum is an urgent necessity. This paper aims to systematically review the literature about patient safety education for undergraduate medical students in terms of its content, teaching strategies, faculty availability and resources provided so as to identify evidence on how to promote patient safety in the curriculum for medical schools. This paper includes a perspective from the faculty of a medical school, a major hospital and an Evidence Based Medicine Centre in Sichuan Province, China.

Methods
We searched MEDLINE, ERIC, Academic Source Premier(ASP), EMBASE and three Chinese Databases (Chinese Biomedical Literature Database, CBM; China National Knowledge Infrastructure, CNKI; Wangfang Data) from 1980 to Dec. 2009. The pre-specified form of inclusion and exclusion criteria were developed for literature screening. The quality of included studies was assessed using Darcy Reed and Gemma Flores-Mateo criteria. Two reviewers selected the studies, undertook quality assessment, and data extraction independently. Differing opinions were resolved by consensus or with help from the third person.

Results
This was a descriptive study of a total of seven studies that met the selection criteria. There were no relevant Chinese studies to be included. Only one study included patient safety education in the medical curriculum and the remaining studies integrated patient safety into clinical rotations or medical clerkships. Seven studies were of a pre and post study design, of which there was only one controlled study. There was considerable variation in relation to contents, teaching strategies, faculty knowledge and background in patient safety, other resources and outcome evaluation in these reports. The outcomes from including patient safety in the curriculum as measured by medical students' knowledge, skills, and attitudes varied between the studies.

Conclusions
There are only a few relevant published studies on the inclusion of patient safety education into the undergraduate curriculum in medical schools either as a selective course, a lecture program, or by being integrated into the existing curriculum even in developed countries with advanced health and education systems. The integration of patient safety education into the existing curriculum in medical schools internationally, provides significant challenges.
Differential effects of dietary canola and soybean oil intake on oxidative stress in stroke-prone spontaneously hypertensive rats
Authors: Papazzo Annateresa , Conlan Xavier A , Lexis Louise , Lewandowski Paul A 
Published: June 2011

Abstract

Background
Canola oil shortens the life span of stroke-prone spontaneously hypertensive (SHRSP) rats compared with rats fed soybean oil when given as the sole dietary lipid source. One possible mechanism leading to the damage and deterioration of organs due to canola oil ingestion is oxidative stress. This study investigated the effect of canola oil intake on oxidative stress in this animal model.

Method
Male SHRSP rats, were fed a defatted control diet containing 10% wt/wt soybean oil or a defatted treatment diet containing 10% wt/wt canola oil, and given water containing 1% NaCl. Blood pressure was measured weekly. Blood was collected prior to beginning the diets and at the end of completion of the study for analysis of red blood cell (RBC) antioxidant enzymes, RBC and plasma malondialdehyde (MDA), plasma 8-isoprostane and plasma lipids.

Results
Canola oil ingestion significantly decreased the life span of SHRSP rats compared with soybean oil, 85.8 ± 1.1 and 98.3 ± 3.4 days, respectively. Systolic blood pressure increased over time with a significant difference between the diets at the 6th week of feeding. Canola oil ingestion significantly reduced RBC superoxide dismutase, glutathione peroxidase and catalase activities, total cholesterol and low-density lipoprotein cholesterol compared with soybean oil. There were no significant differences in RBC MDA concentration between canola oil fed and soybean oil fed rats. In contrast, plasma MDA and 8-isoprostane concentration was significantly lower in the canola oil group compared to the soybean oil group.

Conclusion
In conclusion, canola oil ingestion shortens the life span of SHRSP rats and leads to changes in oxidative status, despite an improvement in the plasma lipids.