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| 2. |
- Sampson, Joshua N., et al.
(author)
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Analysis of Heritability and Shared Heritability Based on Genome-Wide Association Studies for 13 Cancer Types
- 2015
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In: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 107:12
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Journal article (peer-reviewed)abstract
- Background: Studies of related individuals have consistently demonstrated notable familial aggregation of cancer. We aim to estimate the heritability and genetic correlation attributable to the additive effects of common single-nucleotide polymorphisms (SNPs) for cancer at 13 anatomical sites. Methods: Between 2007 and 2014, the US National Cancer Institute has generated data from genome-wide association studies (GWAS) for 49 492 cancer case patients and 34 131 control patients. We apply novel mixed model methodology (GCTA) to this GWAS data to estimate the heritability of individual cancers, as well as the proportion of heritability attributable to cigarette smoking in smoking-related cancers, and the genetic correlation between pairs of cancers. Results: GWAS heritability was statistically significant at nearly all sites, with the estimates of array-based heritability, h(l)(2), on the liability threshold (LT) scale ranging from 0.05 to 0.38. Estimating the combined heritability of multiple smoking characteristics, we calculate that at least 24% (95% confidence interval [CI] = 14% to 37%) and 7% (95% CI = 4% to 11%) of the heritability for lung and bladder cancer, respectively, can be attributed to genetic determinants of smoking. Most pairs of cancers studied did not show evidence of strong genetic correlation. We found only four pairs of cancers with marginally statistically significant correlations, specifically kidney and testes (rho = 0.73, SE = 0.28), diffuse large B-cell lymphoma (DLBCL) and pediatric osteosarcoma (rho = 0.53, SE = 0.21), DLBCL and chronic lymphocytic leukemia (CLL) (rho = 0.51, SE = 0.18), and bladder and lung (rho = 0.35, SE = 0.14). Correlation analysis also indicates that the genetic architecture of lung cancer differs between a smoking population of European ancestry and a nonsmoking Asian population, allowing for the possibility that the genetic etiology for the same disease can vary by population and environmental exposures. Conclusion: Our results provide important insights into the genetic architecture of cancers and suggest new avenues for investigation.
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| 3. |
- Tiegs, Scott D., et al.
(author)
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Global patterns and drivers of ecosystem functioning in rivers and riparian zones
- 2019
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In: Science Advances. - Washington : American Association of Advancement in Science. - 2375-2548. ; 5:1
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Journal article (peer-reviewed)abstract
- River ecosystems receive and process vast quantities of terrestrial organic carbon, the fate of which depends strongly on microbial activity. Variation in and controls of processing rates, however, are poorly characterized at the global scale. In response, we used a peer-sourced research network and a highly standardized carbon processing assay to conduct a global-scale field experiment in greater than 1000 river and riparian sites. We found that Earth's biomes have distinct carbon processing signatures. Slow processing is evident across latitudes, whereas rapid rates are restricted to lower latitudes. Both the mean rate and variability decline with latitude, suggesting temperature constraints toward the poles and greater roles for other environmental drivers (e.g., nutrient loading) toward the equator. These results and data set the stage for unprecedented "next-generation biomonitoring" by establishing baselines to help quantify environmental impacts to the functioning of ecosystems at a global scale.
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| 4. |
- Wang, Zhaoming, et al.
(author)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 6. |
- Pruszynski, J. Andrew, et al.
(author)
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A Rapid Tactile-Motor Reflex Automatically Guides Reaching toward Handheld Objects
- 2016
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In: Current Biology. - : Elsevier BV. - 0960-9822 .- 1879-0445. ; 26:6, s. 788-792
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Journal article (peer-reviewed)abstract
- The ability to respond quickly and effectively when objects in the world suddenly change position is essential for skilled action, and previous work has documented how unexpected changes in the location of a visually presented target during reaching can elicit rapid reflexive (i.e., automatic) corrections of the hand's trajectory [1-12]. In object manipulation and tool use, the sense of touch can also provide information about changes in the location of reach targets. Consider the many tasks where we reach with one hand to part of an object grasped by the other hand: reaching to a berry while holding a branch, reaching for a cap while grasping a bottle, and reaching toward a dog's collar while holding the dog's leash. In such cases, changes in the position of the reach target, due to wind, slip, or an active agent, can be detected, in principle, through touch. Here, we show that when people reach with their right hand to a target attached to the far end of a rod contacted, at the near end, by their left hand, an unexpected change in target location caused by rod rotation rapidly evokes an effective reach correction. That is, spatial information about a change in target location provided by tactile inputs to one hand elicits a rapid correction of the other hand's trajectory. In addition to uncovering a tactile-motor reflex that can support manipulatory actions, our results demonstrate that automatic reach corrections to moving targets are not unique to visually registered changes in target location.
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| 7. |
- Pruszynski, J. Andrew, et al.
(author)
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Fast and accurate edge orientation processing during object manipulation
- 2018
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In: eLIFE. - : ELIFE SCIENCES PUBLICATIONS LTD. - 2050-084X. ; 7
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Journal article (peer-reviewed)abstract
- Quickly and accurately extracting information about a touched object’s orientation is a critical aspect of dexterous object manipulation. However, the speed and acuity of tactile edge orientation processing with respect to the fingertips as reported in previous perceptual studies appear inadequate in these respects. Here we directly establish the tactile system’s capacity to process edge-orientation information during dexterous manipulation. Participants extracted tactile information about edge orientation very quickly, using it within 200 ms of first touching the object. Participants were also strikingly accurate. With edges spanning the entire fingertip, edge-orientation resolution was better than 3° in our object manipulation task, which is several times better than reported in previous perceptual studies. Performance remained impressive even with edges as short as 2 mm, consistent with our ability to precisely manipulate very small objects. Taken together, our results radically redefine the spatial processing capacity of the tactile system.
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| 8. |
- Armstrong, Irene T, et al.
(author)
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Waiting for a hand : saccadic reaction time increases in proportion to hand reaction time when reaching under a visuomotor reversal
- 2013
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In: Frontiers in Human Neuroscience. - : Frontiers Media SA. - 1662-5161. ; 7, s. 319-
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Journal article (peer-reviewed)abstract
- Although eye movement onset typically precedes hand movement onset when reaching to targets presented in peripheral vision, arm motor commands appear to be issued at around the same time, and possibly in advance, of eye motor commands. A fundamental question, therefore, is whether eye movement initiation is linked or yoked to hand movement. We addressed this issue by having participants reach to targets after adapting to a visuomotor reversal (or 180° rotation) between the position of the unseen hand and the position of a cursor controlled by the hand. We asked whether this reversal, which we expected to increase hand reaction time (HRT), would also increase saccadic reaction time (SRT). As predicted, when moving the cursor to targets under the reversal, HRT increased in all participants. SRT also increased in all but one participant, even though the task for the eyes-shifting gaze to the target-was unaltered by the reversal of hand position feedback. Moreover, the effects of the reversal on SRT and HRT were positively correlated across participants; those who exhibited the greatest increases in HRT also showed the greatest increases in SRT. These results indicate that the mechanisms underlying the initiation of eye and hand movements are linked. In particular, the results suggest that the initiation of an eye movement to a manual target depends, at least in part, on the specification of hand movement.
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| 9. |
- Baugh, Lee A., et al.
(author)
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Material evidence : interaction of well-learned priors and sensorimotor memory when lifting objects
- 2012
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In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 108:5, s. 1262-1269
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Journal article (peer-reviewed)abstract
- Skilled object lifting requires the prediction of object weight. When lifting new objects, such prediction is based on well-learned size-weight and material-density correlations, or priors. However, if the prediction is erroneous, people quickly learn the weight of the particular object and can use this knowledge, referred to as sensorimotor memory, when lifting the object again. In the present study, we explored how sensorimotor memory, gained when lifting a given object, interacts with well-learned material-density priors when predicting the weight of a larger but otherwise similar-looking object. Different groups of participants 1st lifted 1 of 4 small objects 10 times. These included a pair of wood-filled objects and a pair of brass-filled objects where 1 of each pair was covered in a wood veneer and the other was covered in a brass veneer. All groups then lifted a larger, brass-filled object with the same covering as the small object they had lifted. For each lift, we determined the initial peak rate of change of vertical load-force rate and the load-phase duration, which provide estimates of predicted object weight. Analysis of the 10th lift of the small cube revealed no effects of surface material, indicating participants learned the appropriate forces required to lift the small cube regardless of object appearance. However, both surface material and core material of the small cube affected the 1st lift of the large block. We conclude that sensorimotor memory related to object density can contribute to weight prediction when lifting novel objects but also that long-term priors related to material properties can influence the prediction.
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| 10. |
- Baugh, Lee A., et al.
(author)
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Representing multiple object weights : competing priors and sensorimotor memories
- 2016
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In: Journal of Neurophysiology. - : American Physiological Society. - 0022-3077 .- 1522-1598. ; 116:4, s. 1615-1625
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Journal article (peer-reviewed)abstract
- When lifting an object, individuals scale lifting forces based on long-term priors relating external object properties (such as material and size) to object weight. When experiencing objects that are poorly predicted by priors, people rapidly form and update sensorimotor memories that can be used to predict an object's atypical size-weight relation in support of predictively scaling lift forces. With extensive experience in lifting such objects, long-term priors, assessed with weight judgments, are gradually updated. The aim of the present study was to understand the formation and updating of these memory processes. Participants lifted, over multiple days, a set of black cubes with a normal size-weight mapping and green cubes with an inverse size-weight mapping. Sensorimotor memory was assessed with lifting forces, and priors associated with the black and green cubes were assessed with the size-weight illusion (SWI). Interference was observed in terms of adaptation of the SWI, indicating that priors were not independently adjusted. Half of the participants rapidly learned to scale lift forces appropriately, whereas reduced learning was observed in the others, suggesting that individual differences may be affecting sensorimotor memory abilities. A follow-up experiment showed that lifting forces are not accurately scaled to objects when concurrently performing a visuomotor association task, suggesting that sensorimotor memory formation involves cognitive resources to instantiate the mapping between object identity and weight, potentially explaining the results of experiment 1. These results provide novel insight into the formation and updating of sensorimotor memories and provide support for the independent adjustment of sensorimotor memory and priors.
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