257 research outputs found

    Sugars and circadian regulation make major contributions to the global regulation of diurnal gene expression in Arabidopsis

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    The diurnal cycle strongly influences many plant metabolic and physiological processes. Arabidopsis thaliana rosettes were harvested six times during 12-h-light/12-h-dark treatments to investigate changes in gene expression using ATH1 arrays. Diagnostic gene sets were identified from published or in-house expression profiles of the response to light, sugar, nitrogen, and water deficit in seedlings and 4 h of darkness or illumination at ambient or compensation point [CO2]. Many sugar-responsive genes showed large diurnal expression changes, whose timing matched that of the diurnal changes of sugars. A set of circadian-regulated genes also showed large diurnal changes in expression. Comparison of published results from a free-running cycle with the diurnal changes in Columbia-0 (Col-0) and the starchless phosphoglucomutase (pgm) mutant indicated that sugars modify the expression of up to half of the clock-regulated genes. Principle component analysis identified genes that make large contributions to diurnal changes and confirmed that sugar and circadian regulation are the major inputs in Col-0 but that sugars dominate the response in pgm. Most of the changes in pgm are triggered by low sugar levels during the night rather than high levels in the light, highlighting the importance of responses to low sugar in diurnal gene regulation. We identified a set of candidate regulatory genes that show robust responses to alterations in sugar levels and change markedly during the diurnal cycle

    Preoperative Assessment of Language Dominance through Combined Resting-State and Task-Based Functional Magnetic Resonance Imaging

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    Brain lesions in language-related cortical areas remain a challenge in the clinical routine. In recent years, the resting-state fMRI (RS-fMRI) was shown to be a feasible method for preoperative language assessment. The aim of this study was to examine whether language-related resting-state components, which have been obtained using a data-driven independent-component-based identification algorithm, can be supportive in determining language dominance in the left or right hemisphere. Twenty patients suffering from brain lesions close to supposed language-relevant cortical areas were included. RS-fMRI and task-based (TB-fMRI) were performed for the purpose of preoperative language assessment. TB-fMRI included a verb generation task with an appropriate control condition (a syllable switching task) to decompose language-critical and language-supportive processes. Subsequently, the best fitting ICA component for the resting-state language network (RSLN) referential to general linear models (GLMs) of the TB-fMRI (including models with and without linguistic control conditions) was identified using an algorithm based on the Dice index. Thereby, the RSLNs associated with GLMs using a linguistic control condition led to significantly higher laterality indices than GLM baseline contrasts. LIs derived from GLM contrasts with and without control conditions alone did not differ significantly. In general, the results suggest that determining language dominance in the human brain is feasible both with TB-fMRI and RS-fMRI, and in particular, the combination of both approaches yields a higher specificity in preoperative language assessment. Moreover, we can conclude that the choice of the language mapping paradigm is crucial for the mentioned benefits

    An Alternate Method of Classifying Allergic Bronchopulmonary Aspergillosis Based on High-Attenuation Mucus

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    Allergic bronchopulmonary aspergillosis (ABPA) is classified radiologically based on the findings of central bronchiectasis (CB) and other radiologic features (ORF). However, the long-term clinical significance of these classifications remains unknown. We hypothesized that the immunological activity and outcomes of ABPA could be predicted on HRCT chest finding of high-attenuation mucus (HAM), a marker of inflammatory activity. In this study, we evaluate the severity and clinical outcomes of ABPA with different radiological classifications. specific IgE levels, eosinophil count) severity of the disease and clinical outcomes in various classifications were analyzed.Of the 234 (123 males, 111 females; mean age, 34.1 years) patients, 55 (23.5%) had normal HRCT, 179 (76.5%) had CB, 49 (20.9%) had HAM, and 27 (11.5%) had ORF. All immunological markers were consistently higher in the HAM classification, while in other classifications these findings were inconsistent. On multivariate analysis, the factors predicting frequent relapses were presence of HAM (OR 7.38; 95% CI, 3.21–17.0) and CB (OR 3.93; 95% CI, 1.63–9.48) after adjusting for ORF.The classification scheme based on HAM most consistently predicts immunological severity in ABPA. Central bronchiectasis and HAM are independent predictors of recurrent relapses in ABPA. Hence, HAM should be employed in the radiological classification of ABPA

    Genome-wide association identifies ATOH7 as a major gene determining human optic disc size

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    Optic nerve assessment is important for many blinding diseases, with cup-to-disc ratio (CDR) assessments commonly used in both diagnosis and progression monitoring of glaucoma patients. Optic disc, cup, rim area and CDR measurements all show substantial variation between human populations and high heritability estimates within populations. To identify loci underlying these quantitative traits, we performed a genome-wide association study in two Australian twin cohorts and identified rs3858145, P = 6.2 × 10−10, near the ATOH7 gene as associated with the mean disc area. ATOH7 is known from studies in model organisms to play a key role in retinal ganglion cell formation. The association with rs3858145 was replicated in a cohort of UK twins, with a meta-analysis of the combined data yielding P = 3.4 × 10−10. Imputation further increased the evidence for association for several SNPs in and around ATOH7 (P = 1.3 × 10−10 to 4.3 × 10−11, top SNP rs1900004). The meta-analysis also provided suggestive evidence for association for the cup area at rs690037, P = 1.5 × 10−7, in the gene RFTN1. Direct sequencing of ATOH7 in 12 patients with optic nerve hypoplasia, one of the leading causes of blindness in children, revealed two novel non-synonymous mutations (Arg65Gly, Ala47Thr) which were not found in 90 unrelated controls (combined Fisher's exact P = 0.0136). Furthermore, the Arg65Gly variant was found to have very low frequency (0.00066) in an additional set of 672 controls
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