Importance of adenosine-to-inosine editing adjacent to the anticodon in an Arabidopsis alanine tRNA under environmental stress

In all organisms, transfer RNAs (tRNAs) undergo extensive post-transcriptional modifications. Although base modifications in the anticodon are known to alter decoding specificity or improve decoding accuracy, much less is known about the functional relevance of modifications in other positions of tRNAs. Here, we report the identification of an A-to-I tRNA editing enzyme that modifies the tRNA-Ala(AGC) in the model plant Arabidopsis thaliana. The enzyme is homologous to Tad1p, a yeast tRNA-specific adenosine deaminase, and it selectively deaminates the adenosine in the position 3'-adjacent to the anticodon (A(37)) to inosine. We show that the AtTAD1 protein is exclusively localized in the nucleus. The tad1 loss-of-function mutants isolated in Arabidopsis show normal accumulation of the tRNA-Ala(AGC), suggesting that the loss of the I(37) modification does not affect tRNA stability. The tad1 knockout mutants display no discernible phenotype under standard growth conditions, but produce less biomass under environmental stress conditions. Our results provide the first evidence in support of a physiological relevance of the A(37)-to-I modification in eukaryotes

Curating for Accessibility

Accessibility of research data to disabled users has received scant attention in literature and practice. In this paper we briefly survey the current state of accessibility for research data and suggest some first steps that repositories should take to make their holdings more accessible. We then describe in depth how those steps were implemented at the Qualitative Data Repository (QDR), a domain repository for qualitative social-science data. The paper discusses accessibility testing and improvements on the repository and its underlying software, changes to the curation process to improve accessibility, as well as efforts to retroactively improve the accessibility of existing collections. We conclude by describing key lessons learned during this process as well as next steps

Generalized multifractality at metal-insulator transitions and in metallic phases of 2D disordered systems

We study generalized multifractality characterizing fluctuations and correlations of eigenstates in disordered systems of symmetry classes AII, D, and DIII. Both metallic phases and Andersonlocalization transitions are considered. By using the non-linear sigma-model approach, we construct pure-scaling eigenfunction observables. The construction is verified by numerical simulations of appropriate microscopic models, which also yield numerical values of the corresponding exponents. In the metallic phases, the numerically obtained exponents satisfy Weyl symmetry relations as well as generalized parabolicity (proportionality to eigenvalues of the quadratic Casimir operator). At the same time, the generalized parabolicity is strongly violated at critical points of metal-insulator transitions, signalling violation of local conformal invariance. Moreover, in classes D and DIII, even the Weyl symmetry breaks down at critical points of metal-insulator transitions. This last feature is related with a peculiarity of the sigma-model manifolds in these symmetry classes: they consist of two disjoint components. Domain walls associated with these additional degrees of freedom are crucial for ensuring Anderson localization and, at the same time, lead to the violation of the Weyl symmetry.Comment: 36 pages, 14 figure

Metal-insulator transition in a 2D system of chiral unitary class

We perform a numerical investigation of Anderson metal-insulator transition (MIT) in a twodimensional system of chiral symmetry class AIII by combining finite-size scaling, transport, density of states, and multifractality studies. The results are in agreement with the sigma-model renormalization-group theory, where MIT is driven by proliferation of vortices. We determine the phase diagram and find an apparent non-universality of several parameters on the critical line of MIT, which is consistent with the analytically predicted slow renormalization towards the ultimate fixed point of the MIT. The localization-length exponent $\nu$ is estimated as $\nu = 1.55 \pm 0.10$.Comment: 11 pages, 10 figure

Baseline characteristics and treatment-emergent risk factors associated with cerebrovascular event and death with risperidone in dementia patients

BACKGROUND: Use of antipsychotics to treat behavioural symptoms of dementia has been associated with increased risks of mortality and stroke. Little is known about individual patient characteristics that might be associated with bad or good outcomes. AIMS: We examined the risperidone clinical trial data to look for individual patient characteristics associated with these adverse outcomes. METHOD: Data from all double-blind randomised controlled trials of risperidone in dementia patients (risperidone n = 1009, placebo n = 712) were included. Associations between characteristics and outcome were analysed based on crude incidences and exposure-adjusted incidence rates, and by time-to-event analyses using Cox proportional hazards regression. Interactions between treatment (risperidone or placebo) and characteristic were analysed with a Cox proportional hazards regression model with main effects for treatment and characteristic in addition to the interaction term. RESULTS: Baseline complications of depression (treatment by risk factor interaction on cerebrovascular adverse event (CVAE) hazard ratio (HR): P = 0.025) and delusions (P = 0.043) were associated with a lower relative risk of CVAE in risperidone-treated patients (HR = 1.47 and 0.54, respectively) compared to not having the complication (HR = 5.88 and 4.16). For mortality, the only significant baseline predictor in patients treated with risperidone was depression, which was associated with a lower relative risk (P<0.001). The relative risk of mortality was increased in risperidone patients treated with anti-inflammatory medications (P = 0.021). CONCLUSIONS: Only anti-inflammatory medications increased mortality risk with risperidone. The reduced risks of CVAE in patients with comorbid depression and delusions, and of mortality with depression, may have clinical implications when weighing the benefits and risks of treatment with risperidone in patients with dementia