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To identify genetic variants associated with head circumference in infancy, we performed a meta-analysis of seven genome-wide association studies (GWAS) (N = 10,768 individuals of European ancestry enrolled in pregnancy and/or birth cohorts) and followed up three lead signals in six replication studies (combined N = 19,089). rs7980687 on chromosome 12q24 (P = 8.1 x 10(-9)) and rs1042725 on chromosome 12q15 (P = 2.8 x 10(-10)) were robustly associated with head circumference in infancy. Although these loci have previously been associated with adult height(1), their effects on infant head circumference were largely independent of height (P = 3.8 x 10(-7) for rs7980687 and P = 1.3 x 10(-7) for rs1042725 after adjustment for infant height). A third signal, rs11655470 on chromosome 17q21, showed suggestive evidence of association with head circumference (P = 3.9 x 10(-6)). SNPs correlated to the 17q21 signal have shown genome-wide association with adult intracranial volume(2), Parkinson's disease and other neurodegenerative diseases(3-5), indicating that a common genetic variant in this region might link early brain growth with neurological disease in later life.
A catalog of genetic loci associated with kidney function from analyses of a million individuals
(2019)
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through transancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these,147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
During aging, intracranial volume remains unchanged and represents maximally attained brain size, while various interacting biological phenomena lead to brain volume loss. Consequently, intracranial volume and brain volume in late life reflect different genetic influences. Our genome-wide association study (GWAS) in 8,175 community-dwelling elderly persons did not reveal any associations at genome-wide significance (P < 5 x 10(-8)) for brain volume. In contrast, intracranial volume was significantly associated with two loci: rs4273712 (P = 3.4 x 10(-11)), a known height-associated locus on chromosome 6q22, and rs9915547 (P = 1.5 x 10(-12)), localized to the inversion on chromosome 17q21. We replicated the associations of these loci with intracranial volume in a separate sample of 1,752 elderly persons (P = 1.1 x 10(-3) for 6q22 and 1.2 x 10(-3) for 17q21). Furthermore, we also found suggestive associations of the 17q21 locus with head circumference in 10,768 children (mean age of 14.5 months). Our data identify two loci associated with head size, with the inversion at 17q21 also likely to be involved in attaining maximal brain size.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function.
Humans typically read at incredibly fast rates, because they predict likely occurring words from a given context. Here, we used functional near-infrared spectroscopy (fNIRS) to track the ultra-rapid hemodynamic responses of words presented every 280 ms in a naturally paced sentence context. We found a lower occipital deoxygenation to unpredictable than to predictable words. The greater hemodynamic responses to unexpected words suggest that the visual features of expected words have been pre-activated previous to stimulus presentation. Second, we tested opposing theoretical proposals about the role of the medial orbitofrontal cortex (OFC): Either OFC may respond to the breach of expectation; or OFC is activated when the present stimulus matches the prediction. A significant interaction between word frequency and predictability indicated OFC responses to breaches of expectation for low- but not for high-frequency words: OFC is sensitive to both, bottom-up processing as mediated by word frequency, as well as top-down predictions. Particularly, when a rare word is unpredictable, OFC becomes active. Finally, we discuss how a high temporal resolution can help future studies to disentangle the hemodynamic responses of single trials in such an ultra-rapid event succession as naturally paced reading. (C) 2014 Elsevier Inc. All rights reserved.
In this paper, we investigate HNCO by resonant and nonresonant Auger electron spectroscopy at the K-edges of carbon, nitrogen, and oxygen, employing soft X-ray synchrotron radiation. In comparison with the isosteric but linear CO2 molecule, spectra of the bent HNCO molecule are similar but more complex due to its reduced symmetry, wherein the degeneracy of the π-orbitals is lifted. Resonant Auger electron spectra are presented at different photon energies over the first core-excited 1s → 10a′ resonance. All Auger electron spectra are assigned based on ab initio configuration interaction computations combined with the one-center approximation for Auger intensities and moment theory to consider vibrational motion. The calculated spectra were scaled by a newly introduced energy scaling factor, and generally, good agreement is found between experiment and theory for normal as well as resonant Auger electron spectra. A comparison of resonant Auger spectra with nonresonant Auger structures shows a slight broadening as well as a shift of the former spectra between −8 and −9 eV due to the spectating electron. Since HNCO is a small molecule and contains the four most abundant atoms of organic molecules, the reported Auger electron decay spectra will provide a benchmark for further theoretical approaches in the computation of core electron spectra.
Selenium (Se) is an essential micronutrient for human health. Se deficiency affects hundreds of millions of people worldwide, particularly in developing countries, and there is increasing awareness that suboptimal supply of Se can also negatively affect human health. Selenium enters the diet primarily through the ingestion of plant and animal products. Although, plants are not dependent on Se they take it up from the soil through the sulphur (S) uptake and assimilation pathways. Therefore, geographic differences in the availability of soil Se and agricultural practices have a profound influence on the Se content of many foods, and there are increasing efforts to biofortify crop plants with Se. Plants from the Brassicales are of particular interest as they accumulate and synthesize Se into forms with additional health benefits, such as methylselenocysteine (MeSeCys). The Brassicaceae are also well-known to produce the glucosinolates; S-containing compounds with demonstrated human health value. Furthermore, the recent discovery of the selenoglucosinolates in the Brassicaceae raises questions regarding their potential bioefficacy. In this review we focus on Se uptake and metabolism in the Brassicaceae in the context of human health, particularly cancer prevention and immunity. We investigate the close relationship between Se and S metabolism in this plant family, with particular emphasis on the selenoglucosinolates, and consider the methodologies available for identifying and quantifying further novel Se-containing compounds in plants. Finally, we summarize the research of multiple groups investigating biofortification of the Brassicaceae and discuss which approaches might be most successful for supplying Se deficient populations in the future.
The boundary paradigm (Rayner, 1975) with a novel preview manipulation was used to examine the extent of parafoveal processing of words to the right of fixation. Words n + 1 and n + 2 had either correct or incorrect previews prior to fixation (prior to crossing the boundary location). In addition, the manipulation utilized either a high or low frequency word in word n + 1 location on the assumption that it would be more likely that n + 2 preview effects could be obtained when word n + 1 was high frequency. The primary findings were that there was no evidence for a preview benefit for word n + 2 and no evidence for parafoveal-on-foveal effects when word n + 1 is at least four letters long. We discuss implications for models of eye-movement control in reading.
Just and Carpenter (1980) presented a theory of reading based on eye fixations wherein their "psycholinguistic" variables accounted for 72% of the variance in word gaze durations. This comment raises some statistical and theoretical problems with their use of simultaneous regression analysis of gaze duration measures and with the resulting theory of reading. A major problem was the confounding of perceptual with psycholinguistic factors. New eye fixation data are presented to support these criticisms. Analysis of fixations within words revealed that most gaze duration variance was contributed by number of fixations rather than by fixation duration.
The development of phonetic codes in memory of 141 pairs of normal and disabled readers from 7.8 to 16.8 years of age was tested with a task adapted from L. S. Mark, D. Shankweiler, I. Y. Liberman, and C. A. Fowler (Memory & Cognition, 1977, 5, 623–629) that measured false-positive errors in recognition memory for foil words which rhymed with words in the memory list versus foil words that did not rhyme. Our younger subjects replicated Mark et al., showing a larger difference between rhyming and nonrhyming false-positive errors for the normal readers. The older disabled readers' phonetic effect was comparable to that of the younger normal readers, suggesting a developmental lag in their use of phonetic coding in memory. Surprisingly, the normal readers' phonetic effect declined with age in the recognition task, but they maintained a significant advantage across age in the auditory WISC-R digit span recall test, and a test of phonological nonword decoding. The normals' decline with age in rhyming confusion may be due to an increase in the precision of their phonetic codes.
Dyslexic and normal readers' eye movements were compared while tracking a moving fixation point and in reading. Contrary to previous reports, the dyslexic and normal readers did not differ in their number of saccades, percentage of regressions, or stability of fixations in the tracking task. Thus, defective oculomotor control was not associated with or a causal factor in dyslexia, and the dyslexics' abnormal eye movements in reading must be related to differences in higher cognitive processes. However, individual differences in oculmotor efficiency, independent of reading ability, were found within both the dyslexic and normal groups, and these differences were correlated in reading and tracking tasks.
Protanopie, deuteranopic and tritanopic neutral points were computed by determining the wavelength of light that produced the same quantal-catch ratio in the photopigments as that produced by a broad-band light of specified color temperature (range: 2 800—6 600 K). The Vos-Walraven primaries were used as photopigment absorption spectra that were screened by varying densities of ocular (0.5—2.5 at 400 nm) and macular (0.0—1.0 at 460 nm) pigmentation. The computations were carried out in 1 nm steps for the wavelength range of 380 to 720 nm. Most of the empirically determined mean, neutral-point loci in the literature were predicted from these computations to within 1—2nm when average ocular and macular pigment densities were used. The neutral-point range associated with the extreme values of the prereceptoral screening pigments was up to 25 nm for protanopes and deuteranopes and up to 13 nm for tritanopes.
We examined individual differences in masked repetition priming by re-analyzing item-level response-time (RT) data from three experiments. Using a linear mixed model (LMM) with subjects and items specified as crossed random factors, the originally reported priming and word-frequency effects were recovered. In the same LMM, we estimated parameters describing the distributions of these effects across subjects. Subjects’ frequency and priming effects correlated positively with each other and negatively with mean RT. These correlation estimates, however, emerged only with a reciprocal transformation of RT (i.e., -1/RT), justified on the basis of distributional analyses. Different correlations, some with opposite sign, were obtained (1) for untransformed or logarithmic RTs or (2) when correlations were computed using within-subject analyses. We discuss the relevance of the new results for accounts of masked priming, implications of applying RT transformations, and the use of LMMs as a tool for the joint analysis of experimental effects and associated individual differences.
The boundary paradigm (Rayner, 1975) with a novel preview manipulation was used to examine the extent of parafoveal processing of words to the right of fixation. Words n+1 and n+2 had either correct or incorrect previews prior to fixation (prior to crossing the boundary location). In addition, the manipulation utilized either a high or low frequency word in word n+1 location on the assumption that it would be more likely that n+2 preview effects could be obtained when word n+1 was high frequency. The primary findings were that there was no evidence for a preview benefit for word n+2 and no evidence for parafoveal-on-foveal effects when word n+1 is at least four letters long. We discuss implications for models of eye-movement control in reading.
Experimental and quantitative research in the field of human language processing and production strongly depends on the quality of the underlying language material: beside its size, representativeness, variety and balance have been discussed as important factors which influence design, analysis and interpretation of experiments and their results. This volume brings together creators and users of both general purpose and specialized lexical resources which are used in psychology, psycholinguistics, neurolinguistics and cognitive research. It aims to be a forum to report experiences and results, review problems and discuss perspectives of any linguistic data used in the field.
The main goal of our target article was to provide concrete recommendations for improving the replicability of research findings. Most of the comments focus on this point. In addition, a few comments were concerned with the distinction between replicability and generalizability and the role of theory in replication. We address all comments within the conceptual structure of the target article and hope to convince readers that replication in psychological science amounts to much more than hitting the lottery twice.
People perceive sentences more favourably after hearing or reading them many times. A prominent approach in linguistic theory argues that these types of exposure effects (satiation effects) show direct evidence of a generative approach to linguistic knowledge: only some sentences improve under repeated exposure, and which sentences do improve can be predicted by a model of linguistic competence that yields natural syntactic classes. However, replications of the original findings have been inconsistent, and it remains unclear whether satiation effects can be reliably induced in an experimental setting at all. Here we report four findings regarding satiation effects in wh-questions across German and English. First, the effects pertain to zone of well-formedness rather than syntactic class: all intermediate ratings, including calibrated fillers, increase at the beginning of the experimental session regardless of syntactic construction. Second, though there is satiation, ratings asymptote below maximum acceptability. Third, these effects are consistent across judgments of superiority effects in English and German. Fourth, wh-questions appear to show similar profiles in English and German, despite these languages being traditionally considered to differ strongly in whether they show effects on movement: violations of the superiority condition can be modulated to a similar degree in both languages by manipulating subject-object initiality and animacy congruency of the wh-phrase. We improve on classic satiation methods by distinguishing between two crucial tests, namely whether exposure selectively targets certain grammatical constructions or whether there is a general repeated exposure effect. We conclude that exposure effects can be reliably induced in rating experiments but exposure does not appear to selectively target certain grammatical constructions. Instead, they appear to be a phenomenon of intermediate gradient judgments.
It is well established that fixation durations during reading vary with processing difficulty, but there are different views on how oculomotor control, visual perception, shifts of attention, and lexical (and higher cognitive) processing are coordinated. Evidence for a one-to-one translation of input delay into saccadic latency would provide a much needed constraint for current theoretical proposals. Here, we tested predictions of such a direct-control perspective using the stimulus-onset delay (SOD) paradigm. Words in sentences were initially masked and, on fixation, were individually unmasked with a delay (0-, 33-, 66-, 99-ms SODs). In Experiment 1, SODs were constant for all words in a sentence; in Experiment 2, SODs were manipulated on target words, while nontargets were unmasked without delay. In accordance with predictions of direct control, nonzero SODs entailed equivalent increases in fixation durations in both experiments. Yet, a population of short fixations pointed to rapid saccades as a consequence of low-level information at nonoptimal viewing positions rather than of lexical processing. Implications of these results for theoretical accounts of oculomotor control are discussed.
Additive and interactive effects of word frequency, stimulus quality, and semantic priming have been used to test theoretical claims about the cognitive architecture of word-reading processes. Additive effects among these factors have been taken as evidence for discrete-stage models of word reading. We present evidence from linear mixed-model analyses applied to 2 lexical decision experiments indicating that apparent additive effects can be the product of aggregating over- and underadditive interaction effects that are modulated by recent trial history, particularly the lexical status and stimulus quality of the previous trial's target. Even a simple practice effect expressed as improved response speed across trials was powerfully modulated by the nature of the previous target item. These results suggest that additivity and interaction between factors may reflect trial-to-trial variation in stimulus representations and decision processes rather than fundamental differences in processing architecture.
Replicability of findings is at the heart of any empirical science. The aim of this article is to move the current replicability debate in psychology towards concrete recommendations for improvement. We focus on research practices but also offer guidelines for reviewers, editors, journal management, teachers, granting institutions, and university promotion committees, highlighting some of the emerging and existing practical solutions that can facilitate implementation of these recommendations. The challenges for improving replicability in psychological science are systemic. Improvement can occur only if changes are made at many levels of practice, evaluation, and reward.
I. Introduction A. Theoretical Framework and Selection of Tests B. Related Studies of Reading Disability Subtypes C. Overview of Specific Questions and Article Outline II. Selection criteria nd performance on standardized measures III. Group differences between disabled and normal readers A. Phonetic Memory B. Picture-Naming Speed and Automatic Responses to Print C. Phonological and Orthographic Skill D. Easy Regular and Exception Word Reading E. Difficult Regular and Exception Words IV. Individual diferences in reading disability A. Phonological Skill, Orthographic Skill, and the Regularity Effect B. Phonological Skill, Orthographic Skill, and Spelling Errors V. Eye movement reading style A. The "Plodder-Explorer" Dimension of Eye Movement Reading Style B. Eye Movements, Coding Skills, and Spelling Ratings C. Verbal Intelligence and the Plodder-Explorer Dimension D. Eye Movements in a Nonreading Task and the "Visual-Spatial" Subtype VI. Distribution and etiology of reading disabilities A. Distribution Issues B. Etiology of Reading Disabilities VII. Summary and new directions in research
Contents: I. Introduction II. Word Coding Processes A. Word Recognition B. Orthographic Coding C. Phonological Coding III. Eye Monitor and Reading Task IV. Group Differences V. Dimensions of Individual Differences A. Regressive Fixation Index and Word Recognition B. Regressive Fixation Index and IQ C. Regressive Fixation Index and Saccade Length D. Regressive Fixation Index and Relative Phonological Skill VI. Multiple Regression Models of Individual Differences A. Disabled Readers in the Aloud Condition B. Disabled Readers in the Silent Condition C. Normal Readers in Silent and Aloud Conditions VII. Conclusions