| 1. |
- Margulies, Elliott H, et al.
(författare)
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Analyses of deep mammalian sequence alignments and constraint predictions for 1% of the human genome
- 2007
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Ingår i: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 17:6, s. 760-774
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Tidskriftsartikel (refereegranskat)abstract
- A key component of the ongoing ENCODE project involves rigorous comparative sequence analyses for the initially targeted 1% of the human genome. Here, we present orthologous sequence generation, alignment, and evolutionary constraint analyses of 23 mammalian species for all ENCODE targets. Alignments were generated using four different methods; comparisons of these methods reveal large-scale consistency but substantial differences in terms of small genomic rearrangements, sensitivity (sequence coverage), and specificity (alignment accuracy). We describe the quantitative and qualitative trade-offs concomitant with alignment method choice and the levels of technical error that need to be accounted for in applications that require multisequence alignments. Using the generated alignments, we identified constrained regions using three different methods. While the different constraint-detecting methods are in general agreement, there are important discrepancies relating to both the underlying alignments and the specific algorithms. However, by integrating the results across the alignments and constraint-detecting methods, we produced constraint annotations that were found to be robust based on multiple independent measures. Analyses of these annotations illustrate that most classes of experimentally annotated functional elements are enriched for constrained sequences; however, large portions of each class (with the exception of protein-coding sequences) do not overlap constrained regions. The latter elements might not be under primary sequence constraint, might not be constrained across all mammals, or might have expendable molecular functions. Conversely, 40% of the constrained sequences do not overlap any of the functional elements that have been experimentally identified. Together, these findings demonstrate and quantify how many genomic functional elements await basic molecular characterization.
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| 2. |
- Moore, Derek G., et al.
(författare)
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Infants perceive human point-light displays as solid forms
- 2007
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Ingår i: Cognition. - : Elsevier BV. - 0010-0277 .- 1873-7838. ; 104, s. 377-396
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Tidskriftsartikel (refereegranskat)abstract
- While five-month-old infants show orientation-specific sensitivity to changes in the motion and occlusion patterns of human point-light displays, it is not known whether infants are capable of binding a human representation to these displays. Furthermore, it has been suggested that infants do not encode the same physical properties for humans and material objects. To explore these issues we tested whether infants would selectively apply the principle of solidity to upright human displays. In the first experiment infants aged six and nine months were repeatedly shown a human point-light display walking across a computer screen up to 10 times or until habituated. Next, they were repeatedly shown the walking display passing behind an in-depth representation of a table, and finally they were shown the human display appearing to pass through the table top in violation of the solidity of the hidden human form. Both six- and nine-month-old infants showed significantly greater recovery of attention to this final phase. This suggests that infants are able to bind a solid vertical form to human motion. In two further control experiments we presented displays that contained similar patterns of motion but were not perceived by adults as human. Six- and nine-month-old infants did not show recovery of attention when a scrambled display or an inverted human display passed through the table. Thus, the binding of a solid human form to a display in only seems to occur for upright human motion. The paper considers the implications of these findings in relation to theories of infants’ developing conceptions of objects, humans and animals. ?? 2006 Elsevier B.V. All rights reserved.
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| 3. |
- Muheim, Rachel, et al.
(författare)
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Calibration of magnetic and celestial compass cues in migratory birds - a review of cue-conflict experiments
- 2006
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Ingår i: Journal of Experimental Biology. - : The Company of Biologists. - 1477-9145 .- 0022-0949. ; 209:1, s. 2-17
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Forskningsöversikt (övrigt vetenskapligt/konstnärligt)abstract
- Migratory birds use multiple sources of compass information for orientation, including the geomagnetic field, the sun, skylight polarization patterns and star patterns. In this paper we review the results of cue-conflict experiments designed to determine the relative importance of the different compass mechanisms, and how directional information from these compass mechanisms is integrated. We focus on cue-conflict experiments in which the magnetic field was shifted in alignment relative to natural celestial cues. Consistent with the conclusions of earlier authors, our analyses suggest that during the premigratory season, celestial information is given the greatest salience and used to recalibrate the magnetic compass by both juvenile and adult birds. Sunset polarized light patterns from the region of the sky near the horizon appear to provide the calibration reference for the magnetic compass. In contrast, during migration, a majority of experiments suggest that birds rely on the magnetic field as the primary source of compass information and use it to calibrate celestial compass cues, i.e. the relative saliency of magnetic and celestial cues is reversed. An alternative possibility, however, is suggested by several experiments in which birds exposed to a cue conflict during migration appear to have recalibrated the magnetic compass, i.e. their response is similar to that of birds exposed to cue conflicts during the premigratory season. The general pattern to emerge from these analyses is that birds exposed to the cue conflict with a view of the entire sunset sky tended to recalibrate the magnetic compass, regardless of whether the cue conflict occurred during the premigratory or migratory period. In contrast, birds exposed to the cue conflict in orientation funnels and registration cages that restricted their view of the region of sky near the horizon (as was generally the case in experiments carried out during the migratory season) did not recalibrate the magnetic compass but, instead, used the magnetic compass to calibrate the other celestial compass systems. If access to critical celestial cues, rather than the timing of exposure to the cue conflict (i.e. premigratory vs migratory), determines whether recalibration of the magnetic compass occurs, this suggests that under natural conditions there may be a single calibration reference for all of the compass systems of migratory birds that is derived from sunset (and possibly also sunrise) polarized light cues from the region of sky near the horizon. In cue-conflict experiments carried out during the migratory season, there was also an interesting asymmetry in the birds' response to magnetic fields shifted clockwise and counterclockwise relative to celestial cues. We discuss two possible explanations for these differences: (1) lateral asymmetry in the role of the right and left eye in mediating light-dependent magnetic compass orientation and (2) interference from the spectral and intensity distribution of skylight at sunset with the response of the light-dependent magnetic compass.
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| 4. |
- Pace, Rishika A., et al.
(författare)
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Collagen VI glycine mutations: Perturbed assembly and a spectrum of clinical severity
- 2008
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Ingår i: Annals of Neurology. - : Wiley. - 1531-8249 .- 0364-5134. ; 64:3, s. 294-303
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The collagen VI muscular dystrophies, Bethlem myopathy and Ullrich congenital muscular dystrophy, form a continuum of clinical phenotypes. Glycine mutations in the triple helix have been identified in both Bethlem and Ullrich congenital muscular dystrophy, but it is not known why they cause these different phenotypes. Methods: We studied eight new patients who presented with a spectrum of clinical severity, screened the three collagen VI messenger RNA for mutations, and examined collagen VI biosynthesis and the assembly pathway. Results: All eight patients had heterozygous glycine mutations toward the N-terminal end of the triple helix. The mutations produced two assembly phenotypes. In the first patient group, collagen VI dimers accumulated in the cell but not the medium, microfibril formation in the medium was moderately reduced, and the amount of collagen VI in the extracellular matrix was not significantly altered. The second group had more severe assembly defects: some secreted collagen VI tetramers were not disulfide bonded, microfibril formation in the medium was severely compromised, and collagen VI in the extracellular matrix was reduced. Interpretation: These data indicate that collagen VI glycine mutations impair the assembly pathway in different ways and disease severity correlates with the assembly abnormality. In mildly affected patients, normal amounts of collagen VI were deposited in the fibroblast matrix, whereas in patients with moderate-to-severe disability, assembly defects led to a reduced collagen VI fibroblast matrix. This study thus provides an explanation for how different glycine mutations produce a spectrum of clinical severity.
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