Notch mRNA Expression in Drosophila Embryos Is Negatively Regulated at the Level of mRNA 3′ Processing

Notch receptor regulates differentiation of almost all tissues and organs during animal development. Many mechanisms function at the protein level to finely regulate Notch activity. Here we provide evidence for Notch regulation at an earlier step - mRNA 3′ processing. Processing at the Notch consensus polyadenylation site appears by default to be suppressed in Drosophila embryos. Interference with this suppression, by a mutation, results in increased levels of polyadenylated Notch mRNA, excess Notch signaling, and severe developmental defects. We propose that Notch mRNA 3′ processing is negatively regulated to limit the production of Notch protein and render it a controlling factor in the generation of Notch signaling

Enhanced Auditory Neuron Survival Following Cell-Based BDNF Treatment in the Deaf Guinea Pig

Exogenous neurotrophin delivery to the deaf cochlea can prevent deafness-induced auditory neuron degeneration, however, we have previously reported that these survival effects are rapidly lost if the treatment stops. In addition, there are concerns that current experimental techniques are not safe enough to be used clinically. Therefore, for such treatments to be clinically transferable, methods of neurotrophin treatment that are safe, biocompatible and can support long-term auditory neuron survival are necessary. Cell transplantation and gene transfer, combined with encapsulation technologies, have the potential to address these issues. This study investigated the survival-promoting effects of encapsulated BDNF over-expressing Schwann cells on auditory neurons in the deaf guinea pig. In comparison to control (empty) capsules, there was significantly greater auditory neuron survival following the cell-based BDNF treatment. Concurrent use of a cochlear implant is expected to result in even greater auditory neuron survival, and provide a clinically relevant method to support auditory neuron survival that may lead to improved speech perception and language outcomes for cochlear implant patients

ECG measurement parameters of athletes are reliable when made with a smartphone based ECG device

Pre-participation cardiac screening including electrocardiogram (ECG) is a subject of controversy among sports medicine practitioners. Opponents of pre-participation ECG screen site concerns regarding the cost and accuracy of the testing. Recently, a single lead ECG accessory has become available for use with smartphones. The purpose of this study was to evaluate the between and within rater validity and reliability of the Kardia device in recording the ECG parameters rate, rhythm, and PR, QRS, and QT intervals. The ECG parameter made with the smartphone were also compared to same measures made using a 12 lead electrocardiograph. This investigation used a repeated measures cross-sectional design. The investigation was conducted in 2 separate phases using separate participant samples. Phase 1 (N=10) was used to determine the within rater reliability with the Kardia device. Phase 2 (N=12) was used to determine the reliability between the Kardia device and the 12 lead electrocardiograph. The between rater and between device reliability for the rate, QT interval and QRS duration parameters ranged good to very good (ICC = 0.667 – 0.981). The current investigation showed that the reliability of the ECG parameters measured using the smartphone technology ranged from good to very good. This paper serves as support for a technological advancement that will help advance the debate on the utility of ECG testing as part of the athletic pre-participation physical

Total elemental composition of soils in Sub-Saharan Africa and relationship with soil forming factors

AbstractA thorough understanding of the variation in total soil element concentrations is important especially in the Sub-Saharan Africa (SSA) soil contexts for agricultural and environmental management at large scale. Fingerprinting of soil elemental composition may form a useful basis for evaluating soils in a way that relates to soil-forming factors and inherent soil functional properties. The objectives of this paper are to quantify the proportion of variability in total elemental composition by total X-ray fluorescence (TXRF) method of 1074 soil samples from the Africa Soil Information Service (AfSIS) Project baseline and to determine the relationships with soil forming factors. The samples were from 34 sentinel sites measuring 10×10km, randomized within major climate zones in SSA. Within each sentinel site there were sixteen spatially stratified 1km2 clusters, within which there were ten 100m2 plots. The within and between site patterns of variation in total element composition of 17 elements; Al, P, K, Ca, Ti, V, Cr, Mn, Fe, Ni, Cu, Zn, Ga, Sr, Y, Ta, and Pb, were explored. Total element concentration values were within the range reported globally for soil Cr, Mn, Zn, Ni, V, Sr, and Y and higher than reported range for Al, Cu, Ta, Pb, and Ga. There were significant variations (P<0.05) in total element composition within and between the sites for all the elements analyzed with the greatest proportion of total variance and number of significant variance components occurring at the site (55–88%) followed by the cluster nested within site (10–40%) levels. The explorations of the relationships between element composition data and site factors using Random Forest regression demonstrated that soil-forming factors have important influence on total elemental composition in the soil. The fact that the soil-forming factors are related to the concentration of naturally occurring elements in the soil gives rise to the notion that they might be predicted from the soils' element composition. Results implied that >70% of variation in soil element composition patterns can be predicted using information in existing databases or readily observable features. Successful use of TXRF technique would open up possibilities for using total soil elemental composition fingerprints as a useful basis for characterizing soils in a way that relates to soil-forming factors and inherent soil functional properties

A realistic assessment of methods for extracting gene/protein interactions from free text

Background: The automated extraction of gene and/or protein interactions from the literature is one of the most important targets of biomedical text mining research. In this paper we present a realistic evaluation of gene/protein interaction mining relevant to potential non-specialist users. Hence we have specifically avoided methods that are complex to install or require reimplementation, and we coupled our chosen extraction methods with a state-of-the-art biomedical named entity tagger. Results: Our results show: that performance across different evaluation corpora is extremely variable; that the use of tagged (as opposed to gold standard) gene and protein names has a significant impact on performance, with a drop in F-score of over 20 percentage points being commonplace; and that a simple keyword-based benchmark algorithm when coupled with a named entity tagger outperforms two of the tools most widely used to extract gene/protein interactions. Conclusion: In terms of availability, ease of use and performance, the potential non-specialist user community interested in automatically extracting gene and/or protein interactions from free text is poorly served by current tools and systems. The public release of extraction tools that are easy to install and use, and that achieve state-of-art levels of performance should be treated as a high priority by the biomedical text mining community

Improved results of induction chemoradiation before surgical intervention for selected patients with stage IIIA-N2 non–small cell lung cancer

ObjectiveOptimal management of stage IIIA-N2 non–small cell lung cancer remains controversial. The surgical arm of the North American Intergroup 0139 trial was adopted as the standard treatment for patients with resectable N2 disease at the University Health Network. Results after 7 years of experience are reported.MethodsThis is a retrospective study of consecutive patients with biopsy-proved T1-3 N2 M0 lung cancer who underwent induction chemoradiation before surgical intervention from January 1997 through August 2004. Induction chemotherapy consisted of cisplatin, 50 mg/m2, on days 1 and 8; etoposide, 50 mg/m2, on days 1 to 5, weeks 1 and 5; and concurrent daily external beam radiotherapy to 45 Gy. Lung resection was performed within 6 weeks of completion of chemoradiation, followed by 2 further cycles of consolidation chemotherapy.ResultsBetween January 1997 and August 2004, 40 patients were treated according to this protocol (25% T1, 62.5% T2, 7.5% T3, and 5% T4). Overall and disease-free median survivals were 40 and 37.1 months, respectively, whereas overall and disease-free 3-year survivals were 51.7% and 52.3%, respectively. R0 resection was achieved in 92.5%. The overall operative mortality rate was 7.5% (0% for lobectomy and 27% for pneumonectomy). Notably, all mortalities occurred within the first 2 years of our experience with this regimen.ConclusionChemoradiation before pulmonary resection in carefully selected patients with surgically resectable stage IIIA (N2) non–small cell lung cancer can lead to improved overall and disease-free survival

The potential to narrow uncertainty in projections of stratospheric ozone over the 21st century

Future stratospheric ozone concentrations will be determined both by changes in the concentration of ozone depleting substances (ODSs) and by changes in stratospheric and tropospheric climate, including those caused by changes in anthropogenic greenhouse gases (GHGs). Since future economic development pathways and resultant emissions of GHGs are uncertain, anthropogenic climate change could be a significant source of uncertainty for future projections of stratospheric ozone. In this pilot study, using an "ensemble of opportunity" of chemistry-climate model (CCM) simulations, the contribution of scenario uncertainty from different plausible emissions pathways for ODSs and GHGs to future ozone projections is quantified relative to the contribution from model uncertainty and internal variability of the chemistry-climate system. For both the global, annual mean ozone concentration and for ozone in specific geographical regions, differences between CCMs are the dominant source of uncertainty for the first two-thirds of the 21st century, up-to and after the time when ozone concentrations return to 1980 values. In the last third of the 21st century, dependent upon the set of greenhouse gas scenarios used, scenario uncertainty can be the dominant contributor. This result suggests that investment in chemistry-climate modelling is likely to continue to refine projections of stratospheric ozone and estimates of the return of stratospheric ozone concentrations to pre-1980 levels

Coordination risk and cost impacts on economic development in poor rural areas

This paper addresses issues relevant to a critical problem in economic development: how to get rapid pro-poor economic growth in poor rural areas in Africa and South Asia where most of the world’s dollar a day poor live. It examines constraints to the development of coordinated exchange systems in poor rural areas, focusing on the core problem of thin markets and low density of economic activity in these areas. Transaction cost and risk analysis is integrated into a conventional neoclassical production economics framework to describe the existence of low level equilibrium traps in transactions and supply chains and to generate important insights for development policy

ECG measurement parameters of athletes are reliable when made with a smartphone based ECG device

Pre-participation cardiac screening including electrocardiogram (ECG) is a subject of controversy among sports medicine practitioners. Opponents of pre-participation ECG screen site concerns regarding the cost and accuracy of the testing. Recently, a single lead ECG accessory has become available for use with smartphones. The purpose of this study was to evaluate the between and within rater validity and reliability of the Kardia device in recording the ECG parameters rate, rhythm, and PR, QRS, and QT intervals. The ECG parameter made with the smartphone were also compared to same measures made using a 12 lead electrocardiograph. This investigation used a repeated measures cross-sectional design. The investigation was conducted in 2 separate phases using separate participant samples. Phase 1 (N=10) was used to determine the within rater reliability with the Kardia device. Phase 2 (N=12) was used to determine the reliability between the Kardia device and the 12 lead electrocardiograph. The between rater and between device reliability for the rate, QT interval and QRS duration parameters ranged good to very good (ICC = 0.667 – 0.981). The current investigation showed that the reliability of the ECG parameters measured using the smartphone technology ranged from good to very good. This paper serves as support for a technological advancement that will help advance the debate on the utility of ECG testing as part of the athletic pre-participation physical