1,156 research outputs found
Gene expression profiling in bladder cancer identifies potential therapeutic targets
Despite advances in management, bladder cancer remains a major cause of cancer related complications. Characterisation of gene expression patterns in bladder cancer allows the identification of pathways involved in its pathogenesis, and may stimulate the development of novel therapies targeting these pathways. Between 2004 and 2005, cystoscopic bladder biopsies were obtained from 19 patients and 11 controls. These were subjected to whole transcript-based microarray analysis. Unsupervised hierarchical clustering was used to identify samples with similar expression profiles. Hypergeometric analysis was used to identify canonical pathways and curated networks having statistically significant enrichment of differentially expressed genes. Osteopontin (OPN) expression was validated by immunohistochemistry. Hierarchical clustering defined signatures, which differentiated between cancer and healthy tissue, muscle-invasive or non-muscle invasive cancer and healthy tissue, grade 1 and grade 3. Pathways associated with cell cycle and proliferation were markedly upregulated in muscle-invasive and grade 3 cancers. Genes associated with the classical complement pathway were downregulated in non-muscle invasive cancer. Osteopontin was markedly overexpressed in invasive cancer compared to healthy tissue. The present study contributes to a growing body of work on gene expression signatures in bladder cancer. The data support an important role for osteopontin in bladder cancer, and identify several pathways worthy of further investigation
Mutation analysis for heterozygote detection and the prenatal diagnosis of cystic fibrosis
The cystic fibrosis gene was recently cloned, and a three-base deletion removing phenylalanine 508 from the coding region was identified as the mutation on the majority of cystic fibrosis chromosomes. We used the polymerase chain reaction and hybridization with allele-specific oligonucleotides to analyze the presence or absence of this mutation on 439 cystic fibrosis chromosomes and 433 normal chromosomes from non-Ashkenazic white families. This mutation was present on 75.8 percent of the cystic fibrosis chromosomes. Using the DNA markers XV-2c and KM-19, we found that 96 percent of cystic fibrosis chromosomes with the mutation had a single DNA haplotype that occurs frequently with cystic fibrosis chromosomes. This haplotype was also found on 54 percent of the cystic fibrosis chromosomes without the three-base deletion. The three-base deletion was found on only 30.3 percent of cystic fibrosis chromosomes from Ashkenazic families, although the common cystic fibrosis haplotype was present on 97 percent of cystic fibrosis chromosomes from Ashkenazic families. The ability to detect the common mutation causing cystic fibrosis represents a major improvement in prenatal diagnosis and heterozygote detection, particularly in families in which no DNA sample is available from the affected child, and provides an improved method of testing for spouses of carriers of cystic fibrosis. Mutation analysis introduces the possibility of population-based screening programs for carriers, which on the basis of the sample in this study, would currently identify about 57 percent of the non-Ashkenazic white couples at risk.published_or_final_versio
Cmr1/WDR76 defines a nuclear genotoxic stress body linking genome integrity and protein quality control
DNA replication stress is a source of genomic instability. Here we identify âchanged mutation rate 1 (âCmr1) as a factor involved in the response to DNA replication stress in Saccharomyces cerevisiae and show that âCmr1âtogether with âMrc1/âClaspin, âPph3, the chaperonin containing âTCP1 (CCT) and 25 other proteinsâdefine a novel intranuclear quality control compartment (INQ) that sequesters misfolded, ubiquitylated and sumoylated proteins in response to genotoxic stress. The diversity of proteins that localize to INQ indicates that other biological processes such as cell cycle progression, chromatin and mitotic spindle organization may also be regulated through INQ. Similar to âCmr1, its human orthologue âWDR76 responds to proteasome inhibition and DNA damage by relocalizing to nuclear foci and physically associating with CCT, suggesting an evolutionarily conserved biological function. We propose that âCmr1/âWDR76 plays a role in the recovery from genotoxic stress through regulation of the turnover of sumoylated and phosphorylated proteins
Infective endocarditis with Lactococcus garvieae in Japan: a case report
<p>Abstract</p> <p>Introduction</p> <p><it>Lactococcus garvieae </it>is a well-recognized fish pathogen, and it is considered a rare pathogen with low virulence in human infection. We describe the 11th case of <it>L. garvieae </it>infective endocarditis reported in the literature, and the first reported case in Japan.</p> <p>Case presentation</p> <p>We report a case of a 55-year-old Japanese woman who had native valve endocarditis with <it>L. garvieae</it>. The case was complicated by renal infarction, cerebral infarction, and mycotic aneurysms. After anti-microbial treatment, she was discharged from the hospital and is now well while being monitored in the out-patient clinic.</p> <p>Conclusion</p> <p>We encountered a case of <it>L. garvieae </it>endocarditis that occurred in a native valve of a healthy woman. The 16S ribosomal RNA gene sequencing was useful for the identification of this pathogen. Although infective endocarditis with <it>L. garvieae </it>is uncommon, it is possible to treat high virulence clinically.</p
photoproduction on the proton for photon energies from 0.725 to 2.875 GeV
Differential cross sections for the reaction have been
measured with the CEBAF Large Acceptance Spectrometer (CLAS) and a tagged
photon beam with energies from 0.725 to 2.875 GeV. Where available, the results
obtained here compare well with previously published results for the reaction.
Agreement with the SAID and MAID analyses is found below 1 GeV. The present set
of cross sections has been incorporated into the SAID database, and exploratory
fits have been made up to 2.7 GeV. Resonance couplings have been extracted and
compared to previous determinations. With the addition of these cross sections
to the world data set, significant changes have occurred in the high-energy
behavior of the SAID cross-section predictions and amplitudes.Comment: 18 pages, 10 figure
Differential cross sections and spin density matrix elements for the reaction gamma p -> p omega
High-statistics differential cross sections and spin density matrix elements
for the reaction gamma p -> p omega have been measured using the CLAS at
Jefferson Lab for center-of-mass (CM) energies from threshold up to 2.84 GeV.
Results are reported in 112 10-MeV wide CM energy bins, each subdivided into
cos(theta_CM) bins of width 0.1. These are the most precise and extensive omega
photoproduction measurements to date. A number of prominent structures are
clearly present in the data. Many of these have not previously been observed
due to limited statistics in earlier measurements
Effects of tutor-related behaviours on the process of problem-based learning
Tutors in a Problem-Based Learning (PBL) curriculum are thought to play active roles in guiding students to develop frameworks for use in the construction of knowledge. This implies that both subject-matter expertise and the ability of tutors to facilitate the learning process must be important in helping students learn. This study examines the behavioural effects of tutors in terms of subject-matter expertise, social congruence and cognitive congruence on studentsâ learning process and on their final achievement. The extent of studentsâ learning at each PBL phase was estimated by tracking the number of relevant concepts recalled at the end of each learning phase, while student achievement was based on studentsâ ability to describe and elaborate upon the relationship between relevant concepts learned. By using Analysis of Covariance, social congruence of the tutor was found to have a significant influence on learning in each PBL phase while all of the tutor-related behaviours had a significant impact on student achievement. The results suggest that the ability of tutors to communicate informally with students and hence create a less threatening learning environment that promotes a free flow exchange of ideas, has a greater impact on learning at each of the PBL phases as compared to tutorsâ subject-matter expertise and their ability to explain concepts in a way that is easily understood by students. The data presented indicates that these tutor-related behaviours are determinants of learning in a PBL curriculum, with social congruence having a greater influence on learning in the different PBL phases
Search for the pentaquark in the reaction
A search for the \thp in the reaction was completed
using the CLAS detector at Jefferson Lab. A study of the same reaction,
published earlier, reported the observation of a narrow \thp resonance. The
present experiment, with more than 30 times the integrated luminosity of our
earlier measurement, does not show any evidence for a narrow pentaquark
resonance. The angle-integrated upper limit on \thp production in the mass
range of 1.52 to 1.56 GeV/c for the reaction is
0.3 nb (95% CL). This upper limit depends on assumptions made for the mass and
angular distribution of \thp production. Using \lamstar production as an
empirical measure of rescattering in the deuteron, the cross section upper
limit for the elementary reaction is estimated to be
a factor of 10 higher, {\it i.e.}, nb (95% CL).Comment: 5 figures, submitted to PRL, revised for referee comment
Photodisintegration of He into p+t
The two-body photodisintegration of He into a proton and a triton has
been studied using the CEBAF Large-Acceptance Spectrometer (CLAS) at Jefferson
Laboratory. Real photons produced with the Hall-B bremsstrahlung-tagging system
in the energy range from 0.35 to 1.55 GeV were incident on a liquid He
target. This is the first measurement of the photodisintegration of He
above 0.4 GeV. The differential cross sections for the He
reaction have been measured as a function of photon-beam energy and
proton-scattering angle, and are compared with the latest model calculations by
J.-M. Laget. At 0.6-1.2 GeV, our data are in good agreement only with the
calculations that include three-body mechanisms, thus confirming their
importance. These results reinforce the conclusion of our previous study of the
three-body breakup of He that demonstrated the great importance of
three-body mechanisms in the energy region 0.5-0.8 GeV .Comment: 13 pages submitted in one tgz file containing 2 tex file and 22
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