Nanopore direct RNA sequencing maps the complexity of Arabidopsis mRNA processing and m6A modification

Understanding genome organization and gene regulation requires insight into RNA transcription, processing and modification. We adapted nanopore direct RNA sequencing to examine RNA from a wild-type accession of the model plant Arabidopsis thaliana and a mutant defective in mRNA methylation (m6A). Here we show that m6A can be mapped in full-length mRNAs transcriptome-wide and reveal the combinatorial diversity of cap-associated transcription start sites, splicing events, poly(A) site choice and poly(A) tail length. Loss of m6A from 3’ untranslated regions is associated with decreased relative transcript abundance and defective RNA 30 end formation. A functional consequence of disrupted m6A is a lengthening of the circadian period. We conclude that nanopore direct RNA sequencing can reveal the complexity of mRNA processing and modification in full-length single molecule reads. These findings can refine Arabidopsis genome annotation. Further, applying this approach to less well-studied species could transform our understanding of what their genomes encode

Melatonin for rapid eye movement sleep behavior disorder in Parkinson's disease : a randomised controlled trial

Background Melatonin may reduce REM-sleep behavior disorder (RBD) symptoms in Parkinson's disease (PD), though robust clinical trials are lacking. Objective To assess the efficacy of prolonged-release (PR) melatonin for RBD in PD. Methods Randomized, double-blind, placebo-controlled, parallel-group trial with an 8-week intervention and 4-week observation pre- and postintervention (ACTRN12613000648729). Thirty PD patients with rapid eye movement sleep behavior disorder were randomized to 4 mg of prolonged-release melatonin (Circadin) or matched placebo, ingested orally once-daily before bedtime. Primary outcome was the aggregate of rapid eye movement sleep behavior disorder incidents averaged over weeks 5 to 8 of treatment captured by a weekly diary. Data were included in a mixed-model analysis of variance (n = 15 per group). Results No differences between groups at the primary endpoint (3.4 events/week melatonin vs. 3.6 placebo; difference, 0.2; 95% confidence interval = -3.2 to 3.6; P = 0.92). Adverse events included mild headaches, fatigue, and morning sleepiness (n = 4 melatonin; n = 5 placebo). Conclusion Prolonged-release melatonin 4 mg did not reduce rapid eye movement sleep behavior disorder in PD. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society

Are benthic fluxes important for the availability of Si in the Gulf of Finland?

We estimated the efflux of dissolved silicon (DSi) from sediments in the Gulf of Finland and compared it to sedimentation fluxes, burial of Si and existing data on Si loading and stocks, reassessing the reliability of existing Si budgets. Benthic fluxes of DSi measured in situ and in vitro were several times higher than estimates from diffusion calculations. The spatial variability in the open Gulf of Finland was relatively small, while both very high and low fluxes were measured from coastal areas. Fluxes were highest in late summer and lowest in early spring. In our re-assessed budget we present a new lower estimate for Si burial in the sediments, ca. 6 Gmol a(-1) and show that more than half of the sedimentation flux of Si is released back into the water column. Changes in the efficiency of internal DSi recycling may thus affect the prevalence of siliceous phytoplankton within the ecosystem, and the diatom spring bloom may be regulated by the functioning of this internal recycling pump. We also show that the seasonal variation in benthic DSi fluxes and dissolved phosphate fluxes is similar, and that a tentative connection between hypoLxia and high DSi efflux exists. (C) 2017 Elsevier B.V. All rights reserved.Peer reviewe

The optimized Rayleigh-Ritz scheme for determining the quantum-mechanical spectrum

The convergence of the Rayleigh-Ritz method with nonlinear parameters optimized through minimization of the trace of the truncated matrix is demonstrated by a comparison with analytically known eigenstates of various quasi-solvable systems. We show that the basis of the harmonic oscillator eigenfunctions with optimized frequency ? enables determination of boundstate energies of one-dimensional oscillators to an arbitrary accuracy, even in the case of highly anharmonic multi-well potentials. The same is true in the spherically symmetric case of V (r) = {\omega}2r2 2 + {\lambda}rk, if k > 0. For spiked oscillators with k < -1, the basis of the pseudoharmonic oscillator eigenfunctions with two parameters ? and {\gamma} is more suitable, and optimization of the latter appears crucial for a precise determination of the spectrum.Comment: 22 pages,8 figure

Reactions to graphic and text health warnings for cigarettes, sugar-sweetened beverages, and alcohol:An online randomized experiment of US adults.

We aimed to examine reactions to graphic versus text-only warnings for cigarettes, SSBs, and alcohol. A convenience sample of US adults completed an online survey in 2018 (n=1,352 in the analytic sample). We randomly assigned participants to view a: 1) text-only warning without efficacy information (i.e., message intended to increase consumers’ confidence in their ability to stop using the product), 2) text-only warning with efficacy information, 3) graphic warning without efficacy information, or 4) graphic warning with efficacy information. Participants viewed their assigned warning on cigarettes, SSBs, and alcohol, in a random order. Across product types, graphic warnings were perceived as more effective than text-only warnings (p<.001) and led to lower believability, greater reactance (i.e., resistance), more thinking about harms, and lower product appeal (all p<.05); policy support did not differ. Compared to SSB and alcohol warnings, cigarette warnings led to higher perceived message effectiveness, believability, fear, thinking about harms, policy support, and greater reductions in product appeal (all p<.05). The efficacy information did not influence any outcomes. Graphic warnings out-performed text-only warnings on key predictors of behavior despite causing more reactance

Signing While Driving: An Investigation of Divided Attention Resources Among Deaf Drivers

Safely operating vehicles require significant visual attention. While attention can be divided, cognitive resources are not limitless. Deaf and hearing participants engaged in a simulated driving task while simultaneously engaging in a conversation in their preferred language. Results indicated that hearing drivers may have a performance advantage over deaf drivers, though it is so minor that it will not likely be seen outside of the laboratory setting. The results also indicated differing cognitive processing among hearing and deaf drivers. The results may inform policy, reduce stigma, and serve as the base for future research on deaf-specific cognitive factors of driving

The Movement Imagery Questionnaire-Revised, Second Edition (MIQ-RS) Is a Reliable and Valid Tool for Evaluating Motor Imagery in Stroke Populations

Mental imagery can improve motor performance in stroke populations when combined with physical therapy. Valid and reliable instruments to evaluate the imagery ability of stroke survivors are needed to maximize the benefits of mental imagery therapy. The purposes of this study were to: examine and compare the test-retest intra-rate reliability of the Movement Imagery Questionnaire-Revised, Second Edition (MIQ-RS) in stroke survivors and able-bodied controls, examine internal consistency of the visual and kinesthetic items of the MIQ-RS, determine if the MIQ-RS includes both the visual and kinesthetic dimensions of mental imagery, correlate impairment and motor imagery scores, and investigate the criterion validity of the MIQ-RS in stroke survivors by comparing the results to the KVIQ-10. Test-retest analysis indicated good levels of reliability (ICC range: .83–.99) and internal consistency (Cronbach α: .95–.98) of the visual and kinesthetic subscales in both groups. The two-factor structure of the MIQ-RS was supported by factor analysis, with the visual and kinesthetic components accounting for 88.6% and 83.4% of the total variance in the able-bodied and stroke groups, respectively. The MIQ-RS is a valid and reliable instrument in the stroke population examined and able-bodied populations and therefore useful as an outcome measure for motor imagery ability

DAP Kinase-Related Apoptosis-Inducing Protein Kinase 2 (DRAK2) Is a Key Regulator and Molecular Marker in Chronic Lymphocytic Leukemia

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in the Western World and it is characterized by a marked degree of clinical heterogeneity. An impaired balance between pro- and anti-apoptotic stimuli determines chemorefractoriness and outcome. The low proliferation rate of CLL cells indicates that one of the primary mechanisms involved in disease development may be an apoptotic failure. Here, we study the clinical and functional significance of DRAK2, a novel stress response kinase that plays a critical role in apoptosis, T-cell biology, and B-cell activation in CLL. We have analyzed CLL patient samples and showed that low expression levels of DRAK2 were significantly associated with unfavorable outcome in our CLL cohort. DRAK2 expression levels showed a positive correlation with the expression of DAPK1, and TGFBR1. Consistent with clinical data, the downregulation of DRAK2 in MEC-1 CLL cells strongly increased cell viability and proliferation. Further, our transcriptome data from MEC-1 cells highlighted MAPK, NF-&kappa;B, and Akt and as critical signaling hubs upon DRAK2 knockdown. Taken together, our results indicate DRAK2 as a novel marker of CLL survival that plays key regulatory roles in CLL prognosis

Update to the Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) protocol: statistical analysis plan for a prospective, multicenter, double-blind, adaptive sample size, randomized, placebo-controlled, clinical trial.

BACKGROUND: Observational research suggests that combined therapy with Vitamin C, thiamine and hydrocortisone may reduce mortality in patients with septic shock. METHODS AND DESIGN: The Vitamin C, Thiamine and Steroids in Sepsis (VICTAS) trial is a multicenter, double-blind, adaptive sample size, randomized, placebo-controlled trial designed to test the efficacy of combination therapy with vitamin C (1.5 g), thiamine (100 mg), and hydrocortisone (50 mg) given every 6 h for up to 16 doses in patients with respiratory or circulatory dysfunction (or both) resulting from sepsis. The primary outcome is ventilator- and vasopressor-free days with mortality as the key secondary outcome. Recruitment began in August 2018 and is ongoing; 501 participants have been enrolled to date, with a planned maximum sample size of 2000. The Data and Safety Monitoring Board reviewed interim results at N = 200, 300, 400 and 500, and has recommended continuing recruitment. The next interim analysis will occur when N = 1000. This update presents the statistical analysis plan. Specifically, we provide definitions for key treatment and outcome variables, and for intent-to-treat, per-protocol, and safety analysis datasets. We describe the planned descriptive analyses, the main analysis of the primary end point, our approach to secondary and exploratory analyses, and handling of missing data. Our goal is to provide enough detail that our approach could be replicated by an independent study group, thereby enhancing the transparency of the study. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03509350. Registered on 26 April 2018