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

The deuteron: structure and form factors

A brief review of the history of the discovery of the deuteron in provided. The current status of both experiment and theory for the elastic electron scattering is then presented.Comment: 80 pages, 33 figures, submited to Advances in Nuclear Physic

Growth and energy and protein intake of preterm newborns in the first year of gestation-corrected age

CONTEXT: There are few longitudinal studies that analyze the growth and nutritional status parameters of children born prematurely. OBJECTIVE: To evaluate the growth and dietary intake of preterm newborns in the first year of gestation-corrected age. DESIGN: Prospective clinical study. SETTING: Tertiary care hospital. PATIENTS: 19 children (7 male) who were born prematurely, with birth weight between 1000g and 2000g, which was adequate for the gestational age. PROCEDURES: At 3, 6, 9 and 12 months of gestation-corrected age, children were evaluated in relation to weight, height and cephalic perimeter, using the National Center for Health Statistics as the standard reference, and the Rozalez-Lopez and Frisancho standards for brachial perimeter and triceps and subscapular skinfolds. The calculated dietary intake was compared to the Recommended Dietary Allowances. MAIN MEASUREMENTS: The Z score was calculated for the weight/age, height/age and weight/height relationships, and the percentiles of the perimeters and skinfolds were considered. Dietary intake records were made using the 24-hour Dietary Recall and the Food Frequency Intake Questionnaire methods. The Virtual Nutri software was used to calculate energy and protein intake. RESULTS: The weight/age, height/age and weight/height relationships and the brachial perimeter and triceps skinfold were statistically greater in the first semester in relation to the second. The cephalic perimeter remained above the 50th percentile for the ages studied and there was no difference in the subscapular skinfold between the first and second semesters, remaining below the 50th percentile. The calorie and protein intake, although statistically lower in the first than in the second semester, always remained above the recommended. CONCLUSIONS: The pace of growth is greater in the first semester than in the second, not reaching the standard expected for full-term newborns, with the exception of the cephalic perimeter, which remains adequate. Calorie/protein intake shows an inverse relationship with growth speed, remaining above the recommended for full-term newborns, although with difficulty in depositing subcutaneous fat, in spite of the high caloric intake.CONTEXTO: Atualmente há estudos longitudinais limitados que definem parâmetros de crescimento e estado nutricional de crianças nascidas prematuras. OBJETIVO: Avaliar o crescimento e a ingestão dietética em recém-nascidos pré-termo no primeiro ano de idade corrigida. TIPO DE ESTUDO: Estudo clínico prospectivo. LOCAL: Hospital de cuidados terciários. PACIENTES: 19 crianças (sete do sexo masculino) nascidas prematuras, adequadas para a idade gestacional, com peso de nascimento entre 1.000 g e 2.000 g, acompanhadas aos 3, 6, 9 e 12 meses de idade corrigida. PROCEDIMENTOS: Aos 3, 6, 9 e 12 meses de idade corrigida, as crianças foram avaliadas quanto ao peso, estatura e perímetros utilizando-se, como padrão de referência, o National Center of Health Statistics e quanto à circunferência braquial e às dobras cutâneas triciptal e subescapular, utilizando-se o padrão de Ronalez-Lopez e de Frisancho. A ingestão dietética calculada foi comparada às Recommended Dietary Allowances. RESULTADOS: As relações peso/idade, estatura/idade, peso/estatura, circunferência braquial e dobra cutânea do tríceps foram estatisticamente maiores no primeiro semestre em relação ao segundo. O perímetro cefálico manteve-se acima do percentil 50 nas idades estudadas e a dobra cutânea subescapular não mostrou diferença entre o primeiro e o segundo semestres, mantendo-se abaixo do percentil 50. A ingestão de calorias e proteínas, apesar de estatisticamente menor no primeiro do que no segundo semestre, permaneceu sempre maior do que o recomendado. CONCLUSÕES: O ritmo de crescimento mostra maior velocidade no primeiro semestre do que no segundo, não atingindo o padrão esperado para os recém-nascidos a termo, com exceção do perímetro cefálico, que se mantém adequado. A ingestão de calorias/proteínas mostra relação inversa com o ritmo de crescimento, permanecendo acima do recomendado para nascidos a termo, havendo, porém, dificuldade de deposição de gordura subcutânea, apesar da alta ingestão calórica.Universidade PaulistaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUNIFESP, EPMSciEL

The spatial structure of lithic landscapes : the late holocene record of east-central Argentina as a case study

Fil: Barrientos, Gustavo. División Antropología. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Catella, Luciana. División Arqueología. Facultad de Ciencias Naturales y Museo. Universidad Nacional de La Plata; ArgentinaFil: Oliva, Fernando. Centro Estudios Arqueológicos Regionales. Facultad de Humanidades y Artes. Universidad Nacional de Rosario; Argentin

The relationship between cadence, pedalling technique and gross efficiency in cycling

Technique and energy saving are two variables often considered as important for performance in cycling and related to each other. Theoretically, excellent pedalling technique should give high gross efficiency (GE). The purpose of the present study was to examine the relationship between pedalling technique and GE. 10 well-trained cyclists were measured for GE, force effectiveness (FE) and dead centre size (DC) at a work rate corresponding to ~75% of VO2max during level and inclined cycling, seat adjusted forward and backward, at three different cadences around their own freely chosen cadence (FCC) on an ergometer. Within subjects, FE, DC and GE decreased as cadence increased (p < 0.001). A strong relationship between FE and GE was found, which was to great extent explained by FCC. The relationship between cadence and both FE and GE, within and between subjects, was very similar, irrespective of FCC. There was no difference between level and inclined cycling position. The seat adjustments did not affect FE, DC and GE or the relationship between them. Energy expenditure is strongly coupled to cadence, but force effectiveness, as a measure for pedalling technique, is not likely the cause of this relationship. FE, DC and GE are not affected by body orientation or seat adjustments, indicating that these parameters and the relationship between them are robust to coordinative challenges within a range of cadence, body orientation and seat position that is used in regular cycling

Off-Target Effects of Psychoactive Drugs Revealed by Genome-Wide Assays in Yeast

To better understand off-target effects of widely prescribed psychoactive drugs, we performed a comprehensive series of chemogenomic screens using the budding yeast Saccharomyces cerevisiae as a model system. Because the known human targets of these drugs do not exist in yeast, we could employ the yeast gene deletion collections and parallel fitness profiling to explore potential off-target effects in a genome-wide manner. Among 214 tested, documented psychoactive drugs, we identified 81 compounds that inhibited wild-type yeast growth and were thus selected for genome-wide fitness profiling. Many of these drugs had a propensity to affect multiple cellular functions. The sensitivity profiles of half of the analyzed drugs were enriched for core cellular processes such as secretion, protein folding, RNA processing, and chromatin structure. Interestingly, fluoxetine (Prozac) interfered with establishment of cell polarity, cyproheptadine (Periactin) targeted essential genes with chromatin-remodeling roles, while paroxetine (Paxil) interfered with essential RNA metabolism genes, suggesting potential secondary drug targets. We also found that the more recently developed atypical antipsychotic clozapine (Clozaril) had no fewer off-target effects in yeast than the typical antipsychotics haloperidol (Haldol) and pimozide (Orap). Our results suggest that model organism pharmacogenetic studies provide a rational foundation for understanding the off-target effects of clinically important psychoactive agents and suggest a rational means both for devising compound derivatives with fewer side effects and for tailoring drug treatment to individual patient genotypes

Mining for genotype-phenotype relations in Saccharomyces using partial least squares

<p>Abstract</p> <p>Background</p> <p>Multivariate approaches are important due to their versatility and applications in many fields as it provides decisive advantages over univariate analysis in many ways. Genome wide association studies are rapidly emerging, but approaches in hand pay less attention to multivariate relation between genotype and phenotype. We introduce a methodology based on a BLAST approach for extracting information from genomic sequences and Soft- Thresholding Partial Least Squares (ST-PLS) for mapping genotype-phenotype relations.</p> <p>Results</p> <p>Applying this methodology to an extensive data set for the model yeast <it>Saccharomyces cerevisiae</it>, we found that the relationship between genotype-phenotype involves surprisingly few genes in the sense that an overwhelmingly large fraction of the phenotypic variation can be explained by variation in less than 1% of the full gene reference set containing 5791 genes. These phenotype influencing genes were evolving 20% faster than non-influential genes and were unevenly distributed over cellular functions, with strong enrichments in functions such as cellular respiration and transposition. These genes were also enriched with known paralogs, stop codon variations and copy number variations, suggesting that such molecular adjustments have had a disproportionate influence on <it>Saccharomyces </it>yeasts recent adaptation to environmental changes in its ecological niche.</p> <p>Conclusions</p> <p>BLAST and PLS based multivariate approach derived results that adhere to the known yeast phylogeny and gene ontology and thus verify that the methodology extracts a set of fast evolving genes that capture the phylogeny of the yeast strains. The approach is worth pursuing, and future investigations should be made to improve the computations of genotype signals as well as variable selection procedure within the PLS framework.</p

Homoplastic microinversions and the avian tree of life

Background: Microinversions are cytologically undetectable inversions of DNA sequences that accumulate slowly in genomes. Like many other rare genomic changes (RGCs), microinversions are thought to be virtually homoplasyfree evolutionary characters, suggesting that they may be very useful for difficult phylogenetic problems such as the avian tree of life. However, few detailed surveys of these genomic rearrangements have been conducted, making it difficult to assess this hypothesis or understand the impact of microinversions upon genome evolution. Results: We surveyed non-coding sequence data from a recent avian phylogenetic study and found substantially more microinversions than expected based upon prior information about vertebrate inversion rates, although this is likely due to underestimation of these rates in previous studies. Most microinversions were lineage-specific or united well-accepted groups. However, some homoplastic microinversions were evident among the informative characters. Hemiplasy, which reflects differences between gene trees and the species tree, did not explain the observed homoplasy. Two specific loci were microinversion hotspots, with high numbers of inversions that included both the homoplastic as well as some overlapping microinversions. Neither stem-loop structures nor detectable sequence motifs were associated with microinversions in the hotspots. Conclusions: Microinversions can provide valuable phylogenetic information, although power analysis indicate

Anatomical Specializations for Nocturnality in a Critically Endangered Parrot, the Kakapo (Strigops habroptilus)

The shift from a diurnal to nocturnal lifestyle in vertebrates is generally associated with either enhanced visual sensitivity or a decreased reliance on vision. Within birds, most studies have focused on differences in the visual system across all birds with respect to nocturnality-diurnality. The critically endangered Kakapo (Strigops habroptilus), a parrot endemic to New Zealand, is an example of a species that has evolved a nocturnal lifestyle in an otherwise diurnal lineage, but nothing is known about its' visual system. Here, we provide a detailed morphological analysis of the orbits, brain, eye, and retina of the Kakapo and comparisons with other birds. Morphometric analyses revealed that the Kakapo's orbits are significantly more convergent than other parrots, suggesting an increased binocular overlap in the visual field. The Kakapo exhibits an eye shape that is consistent with other nocturnal birds, including owls and nightjars, but is also within the range of the diurnal parrots. With respect to the brain, the Kakapo has a significantly smaller optic nerve and tectofugal visual pathway. Specifically, the optic tectum, nucleus rotundus and entopallium were significantly reduced in relative size compared to other parrots. There was no apparent reduction to the thalamofugal visual pathway. Finally, the retinal morphology of the Kakapo is similar to that of both diurnal and nocturnal birds, suggesting a retina that is specialised for a crepuscular niche. Overall, this suggests that the Kakapo has enhanced light sensitivity, poor visual acuity and a larger binocular field than other parrots. We conclude that the Kakapo possesses a visual system unlike that of either strictly nocturnal or diurnal birds and therefore does not adhere to the traditional view of the evolution of nocturnality in birds