Cytoplasmic polyadenylation and cytoplasmic polyadenylation element-dependent mRNA regulation are involved in Xenopus retinal axon development.

BACKGROUND: Translation in axons is required for growth cone chemotropic responses to many guidance cues. Although locally synthesized proteins are beginning to be identified, how specific mRNAs are selected for translation remains unclear. Control of poly(A) tail length by cytoplasmic polyadenylation element (CPE) binding protein 1 (CPEB1) is a conserved mechanism for mRNA-specific translational regulation that could be involved in regulating translation in axons. RESULTS: We show that cytoplasmic polyadenylation is required in Xenopus retinal ganglion cell (RGC) growth cones for translation-dependent, but not translation-independent, chemotropic responses in vitro, and that inhibition of CPE binding through dominant-negative interference severely reduces axon outgrowth in vivo. CPEB1 mRNA transcripts are present at low levels in RGCs but, surprisingly, CPEB1 protein was not detected in eye or brain tissue, and CPEB1 loss-of-function does not affect chemotropic responses or pathfinding in vivo. UV cross-linking experiments suggest that CPE-binding proteins other than CPEB1 in the retina regulate retinal axon development. CONCLUSION: These results indicate that cytoplasmic polyadenylation and CPE-mediated translational regulation are involved in retinal axon development, but that CPEB1 may not be the key regulator of polyadenylation in the developing retina.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

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An in vitro comparison between two methods of electrical resistance measurement for occlusal caries detection

Because of different measurement techniques and the easier design of the CRM prototype, this in vitro study aimed to compare the diagnostic performance and reproducibility of two electrical methods (Electronic Caries Monitor III, ECM and Cariometer 800, CRM) for occlusal caries detection, and to evaluate the effect of staining/ discoloration of fissures on diagnostic performance. Hundred and seventeen third molars with no apparent occlusal cavitation were selected. Six examiners inspected all specimens independently, using the CRM, and a subgroup of 4 using the ECM. Histological validation using a stereomicroscope was performed after hemisectioning. Intra- and interexaminer reproducibility was assessed by Lin's concordance correlation coefficient (CCC) and Bland and Altman analysis. Diagnostic performance parameters included sensitivity (SE), specificity (SP) and area under the ROC curve (A(z)). The CCC yielded an intra- and interexaminer reproducibility of 0.69/0.62 (ECM) and of 0.79/0.74 (CRM). The mean intra- and interexaminer 95% range of measurements (range between Bland and Altman limits of agreement) given in percentages of the instrument reading were 67%/65% for the ECM and 28%/33% for the CRM. A(z) at the D3-4 level was 0.74 (ECM) and 0.78 (CRM). The CRM showed at least equivalent diagnostic performance to the ECM. However, improvement is still desirable. Diagnostic performance appeared to be enhanced in discolored lesions; however, this may be related to sample lesion distribution characteristics. Copyright (C) 2006 S. Karger AG, Basel

Identification of a Blood-Based Protein Biomarker Panel for Lung Cancer Detection

Lung cancer is the deadliest cancer worldwide, mainly due to its advanced stage at the time of diagnosis. A non-invasive method for its early detection remains mandatory to improve patients’ survival. Plasma levels of 351 proteins were quantified by Liquid Chromatography-Parallel Reaction Monitoring (LC-PRM)-based mass spectrometry in 128 lung cancer patients and 93 healthy donors. Bootstrap sampling and least absolute shrinkage and selection operator (LASSO) penalization were used to find the best protein combination for outcome prediction. The PanelomiX platform was used to select the optimal biomarker thresholds. The panel was validated in 48 patients and 49 healthy volunteers. A 6-protein panel clearly distinguished lung cancer from healthy individuals. The panel displayed excellent performance: area under the receiver operating characteristic curve (AUC) = 0.999, positive predictive value (PPV) = 0.992, negative predictive value (NPV) = 0.989, specificity = 0.989 and sensitivity = 0.992. The panel detected lung cancer independently of the disease stage. The 6-protein panel and other sub-combinations displayed excellent results in the validation dataset. In conclusion, we identified a blood-based 6-protein panel as a diagnostic tool in lung cancer. Used as a routine test for high- and average-risk individuals, it may complement currently adopted techniques in lung cancer screening.publishedVersio

Quantification of myocardial blood flow with 82Rb positron emission tomography: clinical validation with 15O-water

PURPOSE: Quantification of myocardial blood flow (MBF) with generator-produced (82)Rb is an attractive alternative for centres without an on-site cyclotron. Our aim was to validate (82)Rb-measured MBF in relation to that measured using (15)O-water, as a tracer 100% of which can be extracted from the circulation even at high flow rates, in healthy control subject and patients with mild coronary artery disease (CAD). METHODS: MBF was measured at rest and during adenosine-induced hyperaemia with (82)Rb and (15)O-water PET in 33 participants (22 control subjects, aged 30 ± 13 years; 11 CAD patients without transmural infarction, aged 60 ± 13 years). A one-tissue compartment (82)Rb model with ventricular spillover correction was used. The (82)Rb flow-dependent extraction rate was derived from (15)O-water measurements in a subset of 11 control subjects. Myocardial flow reserve (MFR) was defined as the hyperaemic/rest MBF. Pearson's correlation r, Bland-Altman 95% limits of agreement (LoA), and Lin's concordance correlation ρ (c) (measuring both precision and accuracy) were used. RESULTS: Over the entire MBF range (0.66-4.7 ml/min/g), concordance was excellent for MBF (r = 0.90, [(82)Rb-(15)O-water] mean difference ± SD = 0.04 ± 0.66 ml/min/g, LoA = -1.26 to 1.33 ml/min/g, ρ(c) = 0.88) and MFR (range 1.79-5.81, r = 0.83, mean difference = 0.14 ± 0.58, LoA = -0.99 to 1.28, ρ(c) = 0.82). Hyperaemic MBF was reduced in CAD patients compared with the subset of 11 control subjects (2.53 ± 0.74 vs. 3.62 ± 0.68 ml/min/g, p = 0.002, for (15)O-water; 2.53 ± 1.01 vs. 3.82 ± 1.21 ml/min/g, p = 0.013, for (82)Rb) and this was paralleled by a lower MFR (2.65 ± 0.62 vs. 3.79 ± 0.98, p = 0.004, for (15)O-water; 2.85 ± 0.91 vs. 3.88 ± 0.91, p = 0.012, for (82)Rb). Myocardial perfusion was homogeneous in 1,114 of 1,122 segments (99.3%) and there were no differences in MBF among the coronary artery territories (p > 0.31). CONCLUSION: Quantification of MBF with (82)Rb with a newly derived correction for the nonlinear extraction function was validated against MBF measured using (15)O-water in control subjects and patients with mild CAD, where it was found to be accurate at high flow rates. (82)Rb-derived MBF estimates seem robust for clinical research, advancing a step further towards its implementation in clinical routine

relating conversational expressiveness to social presence and accpetance of an assistive social robot

Exploring the relationship between social presence, conversational expressiveness, and robot acceptance, we set up an experiment with a robot in an eldercare institution, comparing a more and less social condition. Participants showed more expressiveness with a more social agent and a higher score on expressiveness correlated with higher scores on social presence. Furthermore, scores on social presence correlated with the scores on the intention to use the system in the near future. However, we found no correlation between conversational expressiveness and robot acceptance

Empirical comparison of cross-platform normalization methods for gene expression data

<p>Abstract</p> <p>Background</p> <p>Simultaneous measurement of gene expression on a genomic scale can be accomplished using microarray technology or by sequencing based methods. Researchers who perform high throughput gene expression assays often deposit their data in public databases, but heterogeneity of measurement platforms leads to challenges for the combination and comparison of data sets. Researchers wishing to perform cross platform normalization face two major obstacles. First, a choice must be made about which method or methods to employ. Nine are currently available, and no rigorous comparison exists. Second, software for the selected method must be obtained and incorporated into a data analysis workflow.</p> <p>Results</p> <p>Using two publicly available cross-platform testing data sets, cross-platform normalization methods are compared based on inter-platform concordance and on the consistency of gene lists obtained with transformed data. Scatter and ROC-like plots are produced and new statistics based on those plots are introduced to measure the effectiveness of each method. Bootstrapping is employed to obtain distributions for those statistics. The consistency of platform effects across studies is explored theoretically and with respect to the testing data sets.</p> <p>Conclusions</p> <p>Our comparisons indicate that four methods, DWD, EB, GQ, and XPN, are generally effective, while the remaining methods do not adequately correct for platform effects. Of the four successful methods, XPN generally shows the highest inter-platform concordance when treatment groups are equally sized, while DWD is most robust to differently sized treatment groups and consistently shows the smallest loss in gene detection. We provide an R package, CONOR, capable of performing the nine cross-platform normalization methods considered. The package can be downloaded at <url>http://alborz.sdsu.edu/conor</url> and is available from CRAN.</p

Development and psychometric properties the Barriers to Access to Care Evaluation scale (BACE) related to people with mental ill health

Many people with mental illness do not seek or delay seeking care. This study aimed to develop, and provide an initial validation of, a comprehensive measure for assessing barriers to access to mental health care including a 'treatment stigma' subscale, and to present preliminary evidence about the prevalence of barriers experienced by adults currently or recently using secondary mental health services in the UK

Climate change impact modelling needs to include cross-sectoral interactions

Climate change impact assessments often apply models of individual sectors such as agriculture, forestry and water use without considering interactions between these sectors. This is likely to lead to misrepresentation of impacts, and consequently to poor decisions about climate adaptation. However, no published research assesses the differences between impacts simulated by single-sector and integrated models. Here we compare 14 indicators derived from a set of impact models run within single-sector and integrated frameworks across a range of climate and socio-economic scenarios in Europe. We show that single-sector studies misrepresent the spatial pattern, direction and magnitude of most impacts because they omit the complex interdependencies within human and environmental systems. The discrepancies are particularly pronounced for indicators such as food production and water exploitation, which are highly influenced by other sectors through changes in demand, land suitability and resource competition. Furthermore, the discrepancies are greater under different socio-economic scenarios than different climate scenarios, and at the sub-regional rather than Europe-wide scale