Folate catabolites in spot urine as non-invasive biomarkers of folate status during habitual intake and folic acid supplementation.

Folate status, as reflected by red blood cell (RCF) and plasma folates (PF), is related to health and disease risk. Folate degradation products para-aminobenzoylglutamate (pABG) and para-acetamidobenzoylglutamate (apABG) in 24 hour urine have recently been shown to correlate with blood folate. Since blood sampling and collection of 24 hour urine are cumbersome, we investigated whether the determination of urinary folate catabolites in fasted spot urine is a suitable non-invasive biomarker for folate status in subjects before and during folic acid supplementation. Immediate effects of oral folic acid bolus intake on urinary folate catabolites were assessed in a short-term pre-study. In the main study we included 53 healthy men. Of these, 29 were selected for a 12 week folic acid supplementation (400 µg). Blood, 24 hour and spot urine were collected at baseline and after 6 and 12 weeks and PF, RCF, urinary apABG and pABG were determined. Intake of a 400 µg folic acid bolus resulted in immediate increase of urinary catabolites. In the main study pABG and apABG concentrations in spot urine correlated well with their excretion in 24 hour urine. In healthy men consuming habitual diet, pABG showed closer correlation with PF (rs = 0.676) and RCF (rs = 0.649) than apABG (rs = 0.264, ns and 0.543). Supplementation led to significantly increased folate in plasma and red cells as well as elevated urinary folate catabolites, while only pABG correlated significantly with PF (rs = 0.574) after 12 weeks. Quantification of folate catabolites in fasted spot urine seems suitable as a non-invasive alternative to blood or 24 hour urine analysis for evaluation of folate status in populations consuming habitual diet. In non-steady-state conditions (folic acid supplementation) correlations between folate marker (RCF, PF, urinary catabolites) decrease due to differing kinetics

Structure of Ctk3, a subunit of the RNA polymerase II CTD kinase complex, reveals a non-canonical CTD-interacting domain fold.

CTDK-I is a yeast kinase complex that phosphorylates the C-terminal repeat domain (CTD) of RNA polymerase II (Pol II) to promote transcription elongation. CTDK-I contains the cyclin-dependent kinase Ctk1 (homologous to human CDK9/CDK12), the cyclin Ctk2 (human cyclin K), and the yeast-specific subunit Ctk3, which is required for CTDK-I stability and activity. Here we predict that Ctk3 consists of a N-terminal CTD-interacting domain (CID) and a C-terminal three-helix bundle domain. We determine the X-ray crystal structure of the N-terminal domain of the Ctk3 homologue Lsg1 from the fission yeast Schizosaccharomyces pombe at 2.0 Å resolution. The structure reveals eight helices arranged into a right-handed superhelical fold that resembles the CID domain present in transcription termination factors Pcf11, Nrd1, and Rtt103. Ctk3 however shows different surface properties and no binding to CTD peptides. Together with the known structure of Ctk1 and Ctk2 homologues, our results lead to a molecular framework for analyzing the structure and function of the CTDK-I complex. This article is protected by copyright. All rights reserved

Sentido e experiência no âmbito da atividade cognitiva Meaning and experience in the scope of cognitive activity

O artigo objetiva pensar a posição do problema do sentido em sua relação com a atividade cognitiva no que concerne à questão do significado das metodologias de primeira, segunda e terceira pessoas. Essa relação do sentido com a atividade cognitiva é analisada com a ajuda do pensamento bergsoniano, através do exemplo da percepção da fala. O sentido aparece como um movimento de pensamento que é pressuposto pela atividade cognitiva e não se esgota nela, mas corresponde à multiplicidade mais vasta da experiência e que ultrapassa tanto o eu quanto a experiência que se torna consciente para ele. Propõe-se, então, ligar o problema do sentido àquele das espécies de relação que se entretecem na experiência.<br>The article proposes an examination of the problem of sense in its relation to cognitive activity as it concerns the question of the meaning of methodologies in first, second and third person. This relationship of sense with cognitive activity is analyzed within the perspective of Bergson's thought, through the example of speech perception. The sense appears as a movement of thought that is presupposed by cognitive activity and is not limited to it. In fact, it concerns the largest multiplicity of experience and surpasses both the self and the experience that becomes conscious to him. It is then proposed to connect the problem of sense to that referred to the sorts of relation that are interwoven in experience

Validating task analysis for error identification: reliability and validity of a human error prediction technique

This paper reports on the theoretical and empirical developments for an error prediction methodology called task analysis for error identification (TAFEI). Other researchers have noted the need for theoretically driven approaches that are able to provide practical utility in error prediction. Theoretical developments include the concept of 'rewritable routines', which describe the loop between cognitive processing, action and devices states. This has been proposed as a way of unifying ideas from systems theory and cognitive psychology. The empirical research shows that TAFEI is superior to heuristic methods, which supports the idea that structured methods assist in error prediction. The validation study shows that TAFEI reaches acceptable levels in terms of test - retest reliability and concurrent validity. It is believed that the method has reached a level of maturity after 10 years of development work. This is demonstrated by the many uses to which the method has been put, including that of a design tool

Daily variation and effect of dietary folate on urinary pteridines

Introduction: Urinary pteridines are putative molecular biomarkers for noninvasive cancer screening and prognostication. Central to their translational biomarker development is the need to understand the sources and extent of their non-epidemiological variation. Objectives: This study was designed to characterize the two primary sources of urinary pteridine variance: daily variation and the effect of dietary folate. Methods: Daily variation was studied by collecting urine specimens (n = 81) three times daily for 3 days. The effect of dietary folate was investigated in a treatment study in which urine specimens (n = 168) were collected daily during a control week and a treatment week during which participants received dietary folate supplements. Measurements of six urinary pteridines were made using high-performance liquid chromatography–tandem mass spectrometry. Coefficients of variation were calculated to characterize daily variance between and within subjects, while nearest neighbor non-parametric analyses were used to identify diurnal patterns and measure dietary folate effects. Results: Daily variance was approximately 35 % RSD for both within-day and between-day periods for most pteridines. Diurnal patterns in response to circadian rhythms were similarly observed for urinary pteridines. Folate supplementation was shown to alter urinary pteridine profiles in a pathway dependent manner, suggesting that dietary folate may regulate endogenous neopterin and biopterin biosynthesis. Conclusions: Urinary pteridine levels were found to be responsive to both daily variation and folate supplementation. These findings provide new insights into pteridine biosynthesis and regulation as well as useful information for the design of future clinical translational research