Potential pathogenic mechanisms underlying Fragile X Tremor Ataxia Syndrome: RAN translation and/or RNA gain-of-function?

Fragile X-associated tremor/ataxia syndrome (FXTAS) is an inherited neurodegenerative disease caused by an expansion of 55–200 CGG repeats located in the FMR1 gene. The main clinical and neuropathological features of FXTAS are progressive intention tremor and gait ataxia associated with brain atrophy, neuronal cell loss and presence of ubiquitin-positive intranuclear inclusions in both neurons and astrocytes. At the molecular level, FXTAS is characterized by increased expression of FMR1 sense and antisense RNA containing expanded CGG or GGC repeats, respectively. Here, we discuss the putative molecular mechanisms underlying FXTAS and notably recent reports that expanded CGG and GGC repeats may be pathogenic through RAN translation into toxic proteins.     

Translation and validation of the Canadian diabetes risk assessment questionnaire in China

Objectives

To adapt the Canadian Diabetes Risk Assessment Questionnaire for the Chinese population and to evaluate its psychometric properties.

Design and Sample

A cross‐sectional study was conducted with a convenience sample of 194 individuals aged 35–74 years from October 2014 to April 2015.

Methods

The Canadian Diabetes Risk Assessment Questionnaire was adapted and translated for the Chinese population. Test–retest reliability was conducted to measure stability. Criterion and convergent validity of the adapted questionnaire were assessed using 2‐hr 75 g oral glucose tolerance tests and the Finnish Diabetes Risk Scores, respectively. Sensitivity and specificity were evaluated to establish its predictive validity.

Results

The test–retest reliability was 0.988. Adequate validity of the adapted questionnaire was demonstrated by positive correlations found between the scores and 2‐hr 75 g oral glucose tolerance tests (r = .343, p < .001) and with the Finnish Diabetes Risk Scores (r = .738, p < .001). The area under receiver operating characteristic curve was 0.705 (95% CI .632, .778), demonstrating moderate diagnostic value at a cutoff score of 30. The sensitivity was 73%, with a positive predictive value of 57% and negative predictive value of 78%.

Conclusions

Our results provided evidence supporting the translation consistency, content validity, convergent validity, criterion validity, sensitivity, and specificity of the translated Canadian Diabetes Risk Assessment Questionnaire with minor modifications. This paper provides clinical, practical, and methodological information on how to adapt a diabetes risk calculator between cultures for public health nurses.     

The Queuine Micronutrient: Charting a Course from Microbe to Man

Micronutrients from the diet and gut microbiota are essential to human health and wellbeing. Arguably, among the most intriguing and enigmatic of these micronutrients is queuine, an elaborate 7-deazaguanine derivative made exclusively by eubacteria and salvaged by animal, plant and fungal species. In eubacteria and eukaryotes, queuine is found as the sugar nucleotide queuosine within the anticodon loop of transfer RNA isoacceptors for the amino acids tyrosine, asparagine, aspartic acid and histidine. The physiological requirement for the ancient queuine molecule and queuosine modified transfer RNA has been the subject of varied scientific interrogations for over four decades, establishing relationships to development, proliferation, metabolism, cancer, and tyrosine biosynthesis in eukaryotes and to invasion and proliferation in pathogenic bacteria, in addition to ribosomal frameshifting in viruses. These varied effects may be rationalized by an important, if ill-defined, contribution to protein translation or may manifest from other presently unidentified mechanisms. This article will examine the current understanding of queuine uptake, tRNA incorporation and salvage by eukaryotic organisms and consider some of the physiological consequence arising from deficiency in this elusive and lesser-recognized micronutrient.     

Complexities in the process of translating research documents in cross-cultural settings

ABSTRACT

In multilingual societies, where researchers and participants often do not speak the same language, research is a challenge as a mismatch of understanding between researchers, research instruments and participants often occurs. Reporting on the translation process is crucial because of the potential implications for the validity of the data that follow from it. We aimed to report on the complexities of such a translation process and many considerations that came to our attention. Methodologically, we used a detailed case study to demonstrate that the complexity of translation might be underestimated by researchers who may neglect to report on the challenges that they experience to benefit the wider research community. We emphasise that translating documents, particularly between languages that are not cognate, requires time and financial resources that researchers often do not anticipate or plan for. By discussing what happened to texts that were translated, and how we as researchers were challenged by considerations that were primarily linguistic but also straddled cultural and socio-political domains, we hope to encourage a deeper understanding of the translation task. We conclude that consideration of these complexities is necessary if the aim is the development of translated documents which complement the researchers’ goals.     

Translation and validation of the clinical learning environment,supervision and nurse teacher scale (CLES + T) in Croatian language

Clinical practice is essential to nursing education as it provides experience with patients and work environments that prepare students for future work as nurses. The aim of this study was to translate the “Clinical Learning Environment, Supervision and Nurse Teacher” questionnaire in Croatian language and test its validity and reliability in practice. The study was performed at the Faculty of medicine, Josip Juraj Strossmayer University of Osijek, Croatia in April 2014. The translated questionnaire was submitted to 136 nursing students: 20 males and 116 females. Our results reflected a slightly different factor structure, consisting of four factors. All translated items of the original constructs “Supervisory relationship”, “Role of nurse teacher” and “Leadership style of the ward manager” loaded on factor 1. Items of “Pedagogical atmosphere on the ward” are distributed on two factors (3 and 4). The items of “Premises of nursing on the ward” loaded on factor 2. Three items were identified as problematic and iteratively removed from the analysis. The translated version of the aforementioned questionnaire has properties suitable for the evaluation of clinical practice for nursing students within a Croatian context and reflects the specifics of the nursing clinical education in this country.     

Conserved residues in yeast initiator tRNA calibrate initiation accuracy by regulating preinitiation complex stability at the start codon

Eukaryotic initiator tRNA (tRNA_i) contains several highly conserved unique sequence features, but their importance in accurate start codon selection was unknown. Here we show that conserved bases throughout tRNA_i, from the anticodon stem to acceptor stem, play key roles in ensuring the fidelity of start codon recognition in yeast cells. Substituting the conserved G31:C39 base pair in the anticodon stem with different pairs reduces accuracy (the Sui⁻ [suppressor of initiation codon] phenotype), whereas eliminating base pairing increases accuracy (the Ssu⁻ [suppressor of Sui⁻] phenotype). The latter defect is fully suppressed by a Sui⁻ substitution of T-loop residue A54. These genetic data are paralleled by opposing effects of Sui⁻ and Ssu⁻ substitutions on the stability of methionylated tRNA_i (Met-tRNA_i) binding (in the ternary complex [TC] with eIF2-GTP) to reconstituted preinitiation complexes (PICs). Disrupting the C3:G70 base pair in the acceptor stem produces a Sui⁻ phenotype and also reduces the rate of TC binding to 40S subunits in vitro and in vivo. Both defects are suppressed by an Ssu⁻ substitution in eIF1A that stabilizes the open/P_OUT conformation of the PIC that exists prior to start codon recognition. Our data indicate that these signature sequences of tRNA_i regulate accuracy by distinct mechanisms, promoting the open/P_OUT conformation of the PIC (for C3:G70) or destabilizing the closed/P_IN state (for G31:C39 and A54) that is critical for start codon recognition.