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Qin, S.

Publications and source records attributed to Qin, S..

6 recordsLinked to original sources

Hydroxymethylated-P16 Allele Is Transcription-Inactive

Background5-Methylcytosine can be oxidized into 5-hydroxymethylcytosine (5hmC) in the genome. Methylated-P16 (P16M) can be oxidized into completely hydroxymethylated-P16 (P16H) in human cancer and precancer cells. The aim of this study is to investigate the biological function of P16H.\n\nMethodsTrue P16M and P16H were analyzed using bisulfite/TAB-based assays. A ZFP-based P16-specific dioxygenase (P16-TET) was constructed and used to induce P16H. Cell proliferation and migration were determined with a series of biological analyses.\n\nResults(A) The 5hmCs were enriched in the antisense-strand of the P16 exon-1 in HCT116 and AGS cells containing methylated-P16 alleles (P16M). (B) P16-TET induced both P16H and P16 demethylation in H1299 and AGS cells and reactivated P16 expression. Notably, P16H was only detectable in the sorted P16-TET H1299 and AGS cells that did not show P16 expression. (C) P16-TET significantly inhibited the xenograft growth derived from H1299 cells in NOD-SCID mice, but did not inhibit the growth of P16-deleted A549 control cells. P16-siRNA knockdown could rescue P16-TET-inhibited cell migration.\n\nConclusionHydroxymethylated P16 alleles are transcriptionally inactive.\n\nAUTHOR SUMMARYIt is well known that 5-methylcytosine (5mC) in genomic DNA of mammalian cells can be oxidized into 5-hydroxymethylcytosine (5hmC) and other derivates by DNA dioxygenase TETs. While conversion of 5mC to 5hmC plays an important role in active DNA demethylation through further oxidations, a certain proportion of 5hmCs remain in the genome. Although it is supposed that occurrence of 5hmCs may contribute to the flexibility of chromatin and the protection of the bivalent promoters from hypermethylation, the direct effect of 5hmCs on gene transcription is unknown. In the present study, we engineered a zinc-finger protein-based P16-specific DNA dioxygenase and used it to induce P16 hydroxymethylation and demethylation in cancer cells. Our results demonstrate, for the first time, that the hydroxymethylated P16 alleles retain transcriptionally inactive. This is supported by our recent findings that mRNAs are always transcribed only from the unmethylated P16 strands, but not from the hydroxymethylated/methylated strands in HCT116 cells, and that the risks for malignant transformation are similar for patients with the P16 methylation-positive oral epithelial dysplasia with and without P16 hydroxymethylation in a prospective study.

molecular biology

Soil bacterial biomass and diversity are affected by different furrow-ridge mulched management systems during potato continuous cropping

The soil bacterial composition is vital for sustainable agriculture due to its importance in biogeochemical processes in the soil environment. Multiple management systems, such as different furrow-ridge mulched cropping systems, have been established to reduce the damage caused by continuous cropping of potato (Solanum tuberosum L.). However, little is known about the responses of soil bacterial biomass and diversity to these systems. In this study, six different ridge-furrow film planting patterns were tested in a 2-year continuous cropping potato field: flat plot without mulch (CK), flat plot with mulch (T1), on-ridge planting with full mulch (T2), on-furrow planting with full mulch (T3), on-ridge planting with half mulch (T4), and on-furrow planting with half mulch (T5). The soil physicochemical properties and bacterial composition were significantly affected by the planting pattern. Mulched soils, especially T2, maintained better soil physicochemical properties than controls. Fully mulched soil maintained higher bacterial biomass and diversity. Among the dominant genera, the abundances of Nitrosomonadaceae in T2 and T4 were higher than those in the other treatments. Consequently, compared with the other treatments, on-ridge with mulching patterns resulted in better soil physicochemical properties and high bacterial biomass and diversity, which could reduce the economic losses due to potato production by continuous cropping.

microbiology

Unbiased Age-Appropriate Structural Brain Atlases for Chinese Pediatrics

In magnetic resonance imaging (MRI) studies of children brain development, structural brain atlases usually serve as important references of pediatric population in which individual images are spatially normalized into a common or standard stereotactic space. However, the existing popular children brain atlases (e.g., National Institutes of Health pediatric atlases, NIH-PD atlases) are made mostly based on MR images from Western populations, and are thus insufficient to characterize the brains of Chinese children due to the neuroanatomical differences that are relevant to genetic and environmental factors. By collecting high-quality T1- and T2- weighted MR images from 328 typically developing Chinese children aged from 6 to 12 years old, we created a set of age-appropriate Chinese pediatric (CHN-PD) atlases using an unbiased template construction algorithm. The CHN-PD atlases included the head/brain templates, the symmetric brain template, the gender-specific brain templates and the corresponding tissue probability atlases. Moreover, the atlases contained multiple age-specific templates with a one-year interval. A direct comparison of the CHN-PD and the NIH-PD atlases revealed remarkable anatomical differences bilaterally in the lateral frontal and parietal regions and somatosensory cortex. While applying the CHN-PD atlases to two independent Chinese pediatric datasets (N = 114 and N = 71, respectively), machine-learning regression approaches revealed higher prediction accuracy on brain ages than the usage of NIH-PD atlases. These results suggest that the CHN-PD brain atlases are necessary and important for future typical and atypical developmental studies in Chinese pediatric population. Currently, the CHN-PD atlases have been released on the NITRC website (https://www.nitrc.org/projects/chn-pd).

neuroscience

Ultra-Rapid Serial Visual Presentation Reveals Dynamics of Feedforward and Feedback Processes in the Ventral Visual Pathway

Human visual recognition activates a dense network of overlapping feedforward and recurrent neuronal processes, making it hard to disentangle processing in the feedforward from the feedback direction. Here, we used ultra-rapid serial visual presentation to suppress sustained activity that blurs the boundaries of processing steps, enabling us to resolve two distinct stages of processing with MEG multivariate pattern classification. The first processing stage was the rapid activation cascade of the bottom-up sweep, which terminated early as visual stimuli were presented at progressively faster rates. The second stage was the emergence of categorical information with peak latency that shifted later in time with progressively faster stimulus presentations, indexing time-consuming recurrent processing. Using MEG-fMRI fusion with representational similarity, we localized recurrent signals in early visual cortex. Together, our findings segregated an initial bottom-up sweep from subsequent feedback processing, and revealed the neural signature of increased recurrent processing demands for challenging viewing conditions.

neuroscience

Functional connectivity mechanisms subserving automatic emotion regulation by implementation intention

Automatic emotion regulation (AER) has received increasing attention. However, the effortless hypothesis of AER has yet to be directly tested and the neural mechanisms supporting AER remain unclear. Here, we addressed these two issues, by simultaneous recording behavioral assessments and functional MRI (fMRI) signals when thirty-one participants were required to watch neutral and disgust pictures in three experimental conditions: Watching, Goal Intention (GI) and Reappraisal by Implementation Intention (RII). RII decreased negative feelings and bilateral amygdala activity without engendering cognitive efforts, evidenced by the reduced self-reported efforts and less prefrontal engagement during RII compared to Watching and GI. These regulation effects should not be explained by emotional habituation, as further experiment did not show significant emotional habituation for the repetition of the same stimuli. Moreover, RII and GI produced similar functional connectivity (FC) of vACC (ventral anterior cingulate cortex) to left insula and right precuneus, corresponding to the common goal pursuit component of both strategies. Furthermore, RII relative to GI exhibited weaker FC in distributed brain networks subserving effortful control (e.g. inferior-superior parietal lobe FC), memory retrieval (e.g. inferior-middle temporal lobes and lingual-putamen FCs), aversive anticipation and emotion-related motor planning (e.g. putamen-operculum and vACC-supramarginal gyrus FCs). These findings suggest that RII downregulates disgust effortlessly, most likely mediated by the reduced online mobilization of neural systems subserving emotion-related coping.

neuroscience

Decoding the orientation of contrast edges from MEG evoked and induced responses

1Visual gamma oscillations have been proposed to subserve perceptual binding, but their strong modulation by diverse stimulus features confounds interpretations of their precise functional role. Overcoming this challenge necessitates a comprehensive account of the relationship between gamma responses and stimulus features. Here we used multivariate pattern analyses on human MEG data to characterize the relationships between gamma responses and one basic stimulus feature, the orientation of contrast edges. Our findings confirmed we could decode orientation information from induced responses in two dominant frequency bands at 24-32 Hz and 50-58 Hz. Decoding was higher for cardinal than oblique orientations, with similar results also obtained for evoked MEG responses. In contrast to multivariate analyses, orientation information was mostly absent in univariate signals: evoked and induced responses in early visual cortex were similar in all orientations, with only exception an inverse oblique effect observed in induced responses, such that cardinal orientations produced weaker oscillatory signals than oblique orientations. Taken together, our results showed multivariate methods are well suited for the analysis of gamma oscillations, with multivariate patterns robustly encoding orientation information and predominantly discriminating cardinal from oblique stimuli.

neuroscience