SLocX: Predicting Subcellular Localization of Arabidopsis Proteins Leveraging Gene Expression Data

Despite the growing volume of experimentally validated knowledge about the subcellular localization of plant proteins, a well performing in silico prediction tool is still a necessity. Existing tools, which employ information derived from protein sequence alone, offer limited accuracy and/or rely on full sequence availability. We explored whether gene expression profiling data can be harnessed to enhance prediction performance. To achieve this, we trained several support vector machines to predict the subcellular localization of Arabidopsis thaliana proteins using sequence derived information, expression behavior, or a combination of these data and compared their predictive performance through a cross-validation test. We show that gene expression carries information about the subcellular localization not available in sequence information, yielding dramatic benefits for plastid localization prediction, and some notable improvements for other compartments such as the mitochondrion, the Golgi, and the plasma membrane. Based on these results, we constructed a novel subcellular localization prediction engine, SLocX, combining gene expression profiling data with protein sequence-based information. We then validated the results of this engine using an independent test set of annotated proteins and a transient expression of GFP fusion proteins. Here, we present the prediction framework and a website of predicted localizations for Arabidopsis. The relatively good accuracy of our prediction engine, even in cases where only partial protein sequence is available (e.g., in sequences lacking the N-terminal region), offers a promising opportunity for similar application to non-sequenced or poorly annotated plant species. Although the prediction scope of our method is currently limited by the availability of expression information on the ATH1 array, we believe that the advances in measuring gene expression technology will make our method applicable for all Arabidopsis proteins

Increasing student engagement through virtual interactions: how?

Our ongoing research is focusing on identifying and taxonomising the elements and the factors that affect learner engagement with virtual worlds when hybrid virtual learning models are used. Our main hypothesis links learner engagement with interactions, both in the virtual world and in the physical classroom. In order to examine this subject, there is an elaboration on and consideration of aspects such as the learners’ prior experiences in the use of virtual worlds, their preconceptions about using them as a learning tool and the impact that the instructional designers’ choices have on enhancing the opportunities for interactions. In this paper, we examine the impact that the orientation process has on university students who study computer science and have almost no experience in the use of virtual worlds. Our findings suggest that the orientation process contributed positively to students’ smooth induction and that resulted in having meaningful and engaging interactions. Furthermore, students’ simultaneous coexistence in both environments eliminated the drawbacks of each educational approach and broadened the network of interactions

Gaviscon® vs. omeprazole in symptomatic treatment of moderate gastroesophageal reflux. a direct comparative randomised trial

<p>Abstract</p> <p>Background</p> <p>Medical management of GERD mainly uses proton pump inhibitors. Alginates also have proven efficacy. The aim of this trial was to compare short-term efficacy of an alginate (Gaviscon^®, 4 × 10 mL/day) and omeprazole (20 mg/day) on GERD symptoms in general practice.</p> <p>Methods</p> <p>A 14-day multicentre randomised double-blind double-dummy non-inferiority trial compared Gaviscon^®(4 × 10 mL/day) and omeprazole (20 mg/day) in patients with 2-6 day heartburn episodes weekly without alarm signals. The primary outcome was the mean time to onset of the first 24-h heartburn-free period after initial dosing. Secondary outcomes were the proportion of patients without heartburn by D7, pain relief by D7, and reduction in pain intensity by D7 and D14.</p> <p>Results</p> <p>278 patients were recruited; 120 were included in the Gaviscon^®group and 121 in the omeprazole group for the per protocol non-inferiority analysis. The mean time to onset of the first 24-h heartburn-free period after initial dosing was 2.0 (± 2.2) days for Gaviscon^®and 2.0 (± 2.3) days for omeprazole (<it>p </it>= 0.93); mean intergroup difference was 0.01 ± 1.55 days (95% CI = -0.41 to 0.43): i.e., less than the lower limit of the 95% CI of -0.5 days predetermined to demonstrate non-inferiority. The mean number of heartburn-free days by D7 was significantly greater in the omeprazole group: 3.7 ± 2.3 days vs. 3.1 ± 2.1 (<it>p </it>= 0.02). On D7, overall quality of pain relief was slightly in favour of omeprazole (<it>p </it>= 0.049). There was no significant difference in the reduction in pain intensity between groups by D7 (<it>p = </it>0.11) or D14 (<it>p = </it>0.08). Tolerance and safety were good and comparable in both groups.</p> <p>Conclusion</p> <p>Gaviscon^®was non-inferior to omeprazole in achieving a 24-h heartburn-free period in moderate episodic heartburn, and is a relevant effective alternative treatment in moderate GERD in primary care.</p> <p>Trial registration</p> <p><a href="http://www.controlled-trials.com/ISRCTN62203233">ISRCTN62203233</a>.</p

嶺南通訊 Lingnan Newsletter (第63期)

https://commons.ln.edu.hk/lingnan_newsletter/1062/thumbnail.jp

Comprehensive prediction of novel microRNA targets in Arabidopsis thaliana

MicroRNAs (miRNAs) are 20–24 nt long endogenous non-coding RNAs that act as post-transcriptional regulators in metazoa and plants. Plant miRNA targets typically contain a single sequence motif with near-perfect complementarity to the miRNA. Here, we extended and applied the program RNAhybrid to identify novel miRNA targets in the complete annotated Arabidopsis thaliana transcriptome. RNAhybrid predicts the energetically most favorable miRNA:mRNA hybrids that are consistent with user-defined structural constraints. These were: (i) perfect base pairing of the duplex from nucleotide 8 to 12 counting from the 5′-end of the miRNA; (ii) loops with a maximum length of one nucleotide in either strand; (iii) bulges with no more than one nucleotide in size; and (iv) unpaired end overhangs not longer than two nucleotides. G:U base pairs are not treated as mismatches, but contribute less favorable to the overall free energy. The resulting hybrids were filtered according to their minimum free energy, resulting in an overall prediction of more than 600 novel miRNA targets. The specificity and signal-to-noise ratio of the prediction was assessed with either randomized miRNAs or randomized target sequences as negative controls. Our results are in line with recent observations that the majority of miRNA targets are not transcription factors

Temporal Dynamics of European Bat Lyssavirus Type 1 and Survival of Myotis myotis Bats in Natural Colonies

Many emerging RNA viruses of public health concern have recently been detected in bats. However, the dynamics of these viruses in natural bat colonies is presently unknown. Consequently, prediction of the spread of these viruses and the establishment of appropriate control measures are hindered by a lack of information. To this aim, we collected epidemiological, virological and ecological data during a twelve-year longitudinal study in two colonies of insectivorous bats (Myotis myotis) located in Spain and infected by the most common bat lyssavirus found in Europe, the European bat lyssavirus subtype 1 (EBLV-1). This active survey demonstrates that cyclic lyssavirus infections occurred with periodic oscillations in the number of susceptible, immune and infected bats. Persistence of immunity for more than one year was detected in some individuals. These data were further used to feed models to analyze the temporal dynamics of EBLV-1 and the survival rate of bats. According to these models, the infection is characterized by a predicted low basic reproductive rate (R0 = 1.706) and a short infectious period (D = 5.1 days). In contrast to observations in most non-flying animals infected with rabies, the survival model shows no variation in mortality after EBLV-1 infection of M. myotis. These findings have considerable public health implications in terms of management of colonies where lyssavirus-positive bats have been recorded and confirm the potential risk of rabies transmission to humans. A greater understanding of the dynamics of lyssavirus in bat colonies also provides a model to study how bats contribute to the maintenance and transmission of other viruses of public health concern

Larotrectinib versus Prior Therapies in Tropomyosin Receptor Kinase Fusion Cancer: An Intra-Patient Comparative Analysis.

Randomized controlled basket trials investigating drugs targeting a rare molecular alteration are challenging. Using patients as their own control overcomes some of these challenges. Growth modulation index (GMI) is the ratio of progression-free survival (PFS) on the current therapy to time to progression (TTP) on the last prior line of therapy; GMI ≥ 1.33 is considered a threshold of meaningful clinical activity. In a retrospective, exploratory analysis among patients with advanced tropomyosin receptor kinase (TRK) fusion cancer treated with the selective TRK inhibitor larotrectinib who received ≥1 prior line of therapy for locally advanced/metastatic disease, we determined the proportion of patients with GMI ≥ 1.33; patients who had not progressed by data cut-off were censored for PFS. Among 72 eligible patients, median GMI was 2.68 (range 0.01-48.75). Forty-seven patients (65%) had GMI ≥ 1.33; 13/25 patients (52%) with GMI < 1.33 had not yet progressed on larotrectinib. Kaplan-Meier estimates showed a median GMI of 6.46. The probability of attaining GMI ≥ 1.33 was 0.75 (95% confidence interval (CI), 0.65-0.85). Median TTP on previous treatment was 3.0 months (95% CI, 2.6-4.4). Median PFS on larotrectinib was not estimable ((NE); 95% CI, NE; hazard ratio, 0.220 (95% CI, 0.146-0.332)). This analysis suggests larotrectinib improves PFS for patients with TRK fusion cancer compared with prior therapy

New World Hantaviruses Activate IFNλ Production in Type I IFN-Deficient Vero E6 Cells

Hantaviruses indigenous to the New World are the etiologic agents of hantavirus cardiopulmonary syndrome (HCPS). These viruses induce a strong interferon-stimulated gene (ISG) response in human endothelial cells. African green monkey-derived Vero E6 cells are used to propagate hantaviruses as well as many other viruses. The utility of the Vero E6 cell line for virus production is thought to owe to their lack of genes encoding type I interferons (IFN), rendering them unable to mount an efficient innate immune response to virus infection. Interferon lambda, a more recently characterized type III IFN, is transcriptionally controlled much like the type I IFNs, and activates the innate immune system in a similar manner.We show that Vero E6 cells respond to hantavirus infection by secreting abundant IFNlambda. Three New World hantaviruses were similarly able to induce IFNlambda expression in this cell line. The IFNlambda contained within virus preparations generated with Vero E6 cells independently activates ISGs when used to infect several non-endothelial cell lines, whereas innate immune responses by endothelial cells are specifically due to viral infection. We show further that Sin Nombre virus replicates to high titer in human hepatoma cells (Huh7) without inducing ISGs.Herein we report that Vero E6 cells respond to viral infection with a highly active antiviral response, including secretion of abundant IFNlambda. This cytokine is biologically active, and when contained within viral preparations and presented to human epithelioid cell lines, results in the robust activation of innate immune responses. We also show that both Huh7 and A549 cell lines do not respond to hantavirus infection, confirming that the cytoplasmic RNA helicase pathways possessed by these cells are not involved in hantavirus recognition. We demonstrate that Vero E6 actively respond to virus infection and inhibiting IFNlambda production in these cells might increase their utility for virus propagation

Parsimonious Higher-Order Hidden Markov Models for Improved Array-CGH Analysis with Applications to Arabidopsis thaliana

Array-based comparative genomic hybridization (Array-CGH) is an important technology in molecular biology for the detection of DNA copy number polymorphisms between closely related genomes. Hidden Markov Models (HMMs) are popular tools for the analysis of Array-CGH data, but current methods are only based on first-order HMMs having constrained abilities to model spatial dependencies between measurements of closely adjacent chromosomal regions. Here, we develop parsimonious higher-order HMMs enabling the interpolation between a mixture model ignoring spatial dependencies and a higher-order HMM exhaustively modeling spatial dependencies. We apply parsimonious higher-order HMMs to the analysis of Array-CGH data of the accessions C24 and Col-0 of the model plant Arabidopsis thaliana. We compare these models against first-order HMMs and other existing methods using a reference of known deletions and sequence deviations. We find that parsimonious higher-order HMMs clearly improve the identification of these polymorphisms. Moreover, we perform a functional analysis of identified polymorphisms revealing novel details of genomic differences between C24 and Col-0. Additional model evaluations are done on widely considered Array-CGH data of human cell lines indicating that parsimonious HMMs are also well-suited for the analysis of non-plant specific data. All these results indicate that parsimonious higher-order HMMs are useful for Array-CGH analyses. An implementation of parsimonious higher-order HMMs is available as part of the open source Java library Jstacs (www.jstacs.de/index.php/PHHMM)

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure