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To haplotype the X chromosome of two additional samples (MB59 and GBM103), we performed ChIP-seq for histone marks H3K36me3 and macroH2A1. Histone variant macroH2A1 is known to show an ?1.5-fold uniform [http://en.wikipedia.org/wiki/Ribonucleotide_reductase Ribonucleotide reductase] enrichment along the inactive X chromosome (Mietton et?al., 2009). In contrast, H3K36me3 is enriched in actively transcribed regions and therefore on Xa. Thus, by sequencing both histone marks to sufficiently high depth to infer allele frequencies of mutations, a mutation on Xi should have a high allele frequency in the macroH2A1 reads and a low allele frequency in H3K36me3, which we clearly observed for the germline mutations (data not shown). Integrating matching RNA-seq data with mutations showing particularly high/low macroH2A1/H3K36me3 allele frequencies (Extended Experimental Procedures), 31 SNVs were haplotyped in glioblastoma GBM103, with only 3 SNVs locating to Xa (p?[http://www.selleckchem.com/products/ch5424802.html CH5424802] female patients in which the inactive X?chromosome was present, and haplotyping of four individual samples clearly indicates that X hypermutation is confined to the inactive X chromosome. To assess whether X chromosome hypermutation is a general feature of multiple tumor types, we analyzed the somatic mutation rate of the X chromosome in an additional ?300 whole-cancer genomes, including our own published and unpublished data from five different cancer entities (pilocytic [http://www.selleckchem.com/products/VX-770.html VX-770] astrocytoma, glioblastoma, ependymoma, B cell lymphoma, and prostate carcinoma) complemented by published mutation call sets of six different cancer types: breast cancer (Nik-Zainal et?al., 2012), neuroblastoma (Molenaar et?al., 2012), chronic lymphocytic leukemia (Puente et?al., 2011), acute myeloid leukemia (Welch et?al., 2012), colorectal carcinoma (Bass et?al., 2011), and retinoblastoma (Zhang et?al., 2012). We observed X chromosome hypermutation in a significant fraction of cancer genomes from female samples (56/191, 29%) comprising nine different cancer entities across a diverse set of childhood tumors as well as adult solid and hematopoietic malignancies (Tables 1 and S1 and Figure?4).
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13, binomial test)1. Analyses of the mean looking time of all fixations on the first box (where the agent has seen the ball being transferred) and the window above and as well as the second box (where the agent has not seen the ball being transferred) and the window above during the anticipation phase of the test trial did not result in any statistically significant effect [Mfirstbox = 533 ms, SD = 479 ms, Msecond box = 913 ms, SD = 682 ms, t(21) = 1.77, p = 0.09]. The infants�� first anticipatory look to the side where the actor last saw the ball and proportion of looking the side where the actor last saw the ball correlated  (r = 0.77, p  variables such as mean looking time toward the videos before the anticipation phase, referential looks toward the actor��s head, and number of correct anticipatory looks during the familiarization trials did not reveal any statistically significant findings. A-not-B Task and BSID The mean number of incorrect searches at location A was 1.4 (SD = 1.7, range 0�C5). Nine infants did not perform an incorrect search at location A, six infants searched at location A one time, two infants each searched at location A two, four, and five times, and one infants searched at location A three times. Infants�� mean IQ score  in the BSID was 93.3 (SD = 10.3, range 79�C117). Four infants [http://www.selleckchem.com/products/CAL-101.html CAL-101 manufacturer] received a score below 85, 17 infants received a score within 85 and 115, and one infant received a score above 115. In order to assess whether infants who were excluded performed worse in the A-not-B  task than infants who were included in the study we compared their performance. We did not find a difference between both mean scores, M(excluded) = 1.4 (SD = 1.6), t  task and the A-not-B task for the toddlers�� first fixation in the false-belief task (r = -0.02, p = 0.92, Spearman rank correlation, see Figure ?Figure22 for group differences between infants who anticipated correctly and incorrectly in the false-belief task) or for the proportion of mean looking time of fixations on the first box �C where the agent has seen the ball being placed (r = 0.11, p = 0.63, Spearman rank correlation). This remained after controlling for cognitive development measured in the BSID (r = -0.06, p = 0.78; r = -0.15, p = 0.49, Spearman rank correlation). FIGURE 2 Number of incorrect searches at location A in the A-not-B task for infants whose first fixation in the false-belief task was directed to the location where the actor last saw the ball (correct) and whose first fixation was directed to the location where ...

Версія за 14:41, 30 червня 2017

13, binomial test)1. Analyses of the mean looking time of all fixations on the first box (where the agent has seen the ball being transferred) and the window above and as well as the second box (where the agent has not seen the ball being transferred) and the window above during the anticipation phase of the test trial did not result in any statistically significant effect [Mfirstbox = 533 ms, SD = 479 ms, Msecond box = 913 ms, SD = 682 ms, t(21) = 1.77, p = 0.09]. The infants�� first anticipatory look to the side where the actor last saw the ball and proportion of looking the side where the actor last saw the ball correlated (r = 0.77, p variables such as mean looking time toward the videos before the anticipation phase, referential looks toward the actor��s head, and number of correct anticipatory looks during the familiarization trials did not reveal any statistically significant findings. A-not-B Task and BSID The mean number of incorrect searches at location A was 1.4 (SD = 1.7, range 0�C5). Nine infants did not perform an incorrect search at location A, six infants searched at location A one time, two infants each searched at location A two, four, and five times, and one infants searched at location A three times. Infants�� mean IQ score in the BSID was 93.3 (SD = 10.3, range 79�C117). Four infants CAL-101 manufacturer received a score below 85, 17 infants received a score within 85 and 115, and one infant received a score above 115. In order to assess whether infants who were excluded performed worse in the A-not-B task than infants who were included in the study we compared their performance. We did not find a difference between both mean scores, M(excluded) = 1.4 (SD = 1.6), t task and the A-not-B task for the toddlers�� first fixation in the false-belief task (r = -0.02, p = 0.92, Spearman rank correlation, see Figure ?Figure22 for group differences between infants who anticipated correctly and incorrectly in the false-belief task) or for the proportion of mean looking time of fixations on the first box �C where the agent has seen the ball being placed (r = 0.11, p = 0.63, Spearman rank correlation). This remained after controlling for cognitive development measured in the BSID (r = -0.06, p = 0.78; r = -0.15, p = 0.49, Spearman rank correlation). FIGURE 2 Number of incorrect searches at location A in the A-not-B task for infants whose first fixation in the false-belief task was directed to the location where the actor last saw the ball (correct) and whose first fixation was directed to the location where ...