Biology subjects

Tian, Q.

Publications and source records attributed to Tian, Q..

51 records · Page 3Linked to original sources

bioRxiv2021

Identification of upstream transcription factor binding sites in orthologous genes using mixed Student's t-test statistics

BackgroundTranscription factor (TF) regulates the transcription of DNA to messenger RNA by binding to upstream sequence motifs. Identifying the locations of known motifs in whole genomes is computationally intensive. Methodology/Principal FindingsThis study presents a computational tool, named "Grit", for screening TF-binding sites (TFBS) by coordinating transcription factors to their promoter sequences in orthologous genes. This tool employs a newly developed mixed Students t-test statistical method that detects high-scoring conserved and non-conserved binding sites among species. The program performs sequence scanning at a rate of 3.2 Mb/s on a quad-core Amazon server and has been benchmarked by the well-established ChIP-Seq datasets, putting Grit amongst the top-ranked TFBS predictors. It marginally outperforms the well-known transcription factor motif scanning tools, Pscan (4.8%) and FIMO (17.8%), in analyzing well-documented ChIP-Atlas human genome Chip-Seq datasets. SignificanceGrit is a good alternative to current available motif scanning tools and is publicly available at http://www.thua45.cn/grit under an academic free license. Author SummaryLocating transcription factor-binding (TF-binding) site in the genome and identification their function is fundamental in understanding various biological processes. Improve the performance of the prediction tools is important because accurate TF-binding site prediction can save cost and time for wet-lab experiments. Also, genome wide TF-binding site prediction can provide new insights for transcriptome regulation in system biology perspective. This study developed a new TF-binding site prediction tool based on mixed Students t-test statistical method. The tool is amongst the top-ranked TF-binding site predictors, as such, it can help the researchers in TF-binding site identification and transcriptional regulation mechanism interpretation of genes.

bioinformatics↗

bioRxiv2021

Role of YAP in early ectodermal specification anda Huntington's Disease model of human neurulation

The Hippo pathway, a highly conserved signaling cascade that functions as an integrator of molecular signals and biophysical states, ultimately impinges upon the transcription coactivator Yes-associated protein 1 (YAP). Hippo-YAP signaling has been shown to play key roles both at the early embryonic stages of implantation and gastrulation, and later during neurogenesis. To explore YAPs potential role in neurulation, we used self-organizing neuruloids grown from human embryonic stem cells on micropatterned substrates. We identified YAP activation as a key lineage determinant, first between neuronal ectoderm and non-neuronal ectoderm, and later between epidermis and neural crest, indicating that YAP activity can enhance the effect of BMP4 stimulation and therefore affect ectodermal specification at this developmental stage. Because aberrant Hippo-YAP signaling has been implicated in the pathology of Huntingtons Disease (HD), we used isogenic mutant neuruloids to explore the relationship between signaling and the disease. We found that HD neuruloids demonstrate ectopic activation of gene targets of YAP and that pharmacological reduction of YAPs transcriptional activity can partially rescue the HD phenotype.

developmental biology↗

bioRxiv2021

Shisa7 phosphorylation regulates GABAergic transmission and neurodevelopmental behaviors

GABA-A receptors (GABAARs) are crucial for development and regulation of the central nervous system. Altered GABAergic signaling is hypothesized to be involved in the pathophysiology of neurodevelopmental disorders. Nevertheless, how aberrant cellular and molecular mechanisms affect GABAARs in these diseases remain elusive. Recently, we identified Shisa7 as a GABAAR auxiliary subunit that modulates GABAAR trafficking, kinetics, and pharmacology, and discovered a phosphorylation site in Shisa7 (S405) critical for extrasynaptic 5-GABAAR trafficking and tonic inhibition. However, the role of S405 phosphorylation in the regulation of synaptic inhibition, plasticity, and behavior remains unknown. Here, we found that expression of a phospho-null mutant (Shisa7 S405A) in heterologous cells and neurons diminishes 2-GABAAR trafficking. Subsequently, we generate a Shisa7 S405A knock-in (KI) mouse line that displays reduced surface expression of GABAARs in hippocampal neurons. Importantly, both synaptic and tonic inhibition are decreased in KI mice. Moreover, chemically induced inhibitory long-term potentiation is impaired, highlighting a critical role of Shisa7 S405 in GABAergic plasticity. Lastly, KI mice exhibit enhanced locomotor activity and grooming associated with neurodevelopmental disorders. Collectively, our study reveals a phosphorylation site critical for Shisa7-dependent trafficking of synaptic and extrasynaptic GABAARs which contributes to behavioral endophenotypes displayed in neurodevelopmental disorders.

neuroscience↗

bioRxiv2021

High-fidelity, high-spatial-resolution diffusion MRI of the ex-vivo whole human brain on the 3T Connectom scanner using structured low-rank EPI ghost correction

Diffusion MRI (dMRI) of whole, intact, fixed postmortem human brain at high spatial resolution serves as key bridging technology for 3D mapping of structural connectivity and tissue microstructure at the mesoscopic scale. Ex vivo dMRI offers superior spatial resolution compared to in vivo dMRI but comes with its own technical challenges due to the significantly reduced T2 relaxation times and decreased diffusivity incurred by tissue fixation. The altered physical properties of fixed tissue necessitate the use of alternative acquisition strategies to preserve SNR and achieve sufficient diffusion weighting. Multi-shot or segmented 3D echo planar imaging (EPI) sequences have been used to shorten echo times (TEs) with reduced distortions from field inhomogeneity and eddy currents on small-bore MR scanners and have been adopted for high b-value dMRI of ex vivo whole human brain specimens. The advent of stronger gradients on human MRI scanners has led to improved image quality and a wider range of diffusion-encoding parameters for dMRI but at the cost of more severe eddy currents that result in spatial and temporal variations in the background magnetic field, which cannot be corrected for using standard vendor-provided ghost correction solutions. In this work, we show that conventional ghost correction techniques based on navigators and linear phase correction may be insufficient for EPI sequences using strong diffusion-sensitizing gradients in ex vivo dMRI experiments, resulting in orientationally biased dMRI estimates. This previously unreported problem is a critical roadblock in any effort to leverage scanners with ultra-high gradients for high-precision mapping of human neuroanatomy at the mesoscopic scale. We propose an advanced reconstruction method based on structured low-rank matrix modeling that reduces the ghosting substantially. We show that this method leads to more accurate and reliable dMRI metrics, as exemplified by diffusion tensor imaging and high angular diffusion imaging analyses in distributed neuroanatomical areas of fixed whole human brain specimens. Our findings advocate for the use of advanced reconstruction techniques for recovering unbiased metrics from ex vivo dMRI acquisitions and represent a crucial step toward making full use of strong diffusion-encoding gradients for neuroscientific studies seeking to study brain structure at multiple spatial scales.

neuroscience↗

bioRxiv2021

Distinct regulation of tonic GABAergic inhibition by NMDA receptor subtypes

Tonic inhibition mediated by extrasynaptic {gamma}-aminobutyric acid type A receptors (GABAARs) play important roles in the regulation of various brain functions. However, the regulatory mechanisms for tonic inhibition remain largely unknown. Here we report distinct actions of GluN2A- and GluN2B-containing subtypes of NMDA receptors (NMDARs) on tonic inhibition in hippocampal neurons. Mechanistically, GluN2A- and GluN2B-containing NMDARs play differential roles in 5-GABAAR internalization. Additionally, GluN2A-, but not GluN2B-, containing receptors are required for the homeostatic potentiation of tonic inhibition. In an acute seizure model induced by kainic acid, tonic inhibition is decreased during acute seizures, while it is increased 24 h later, and these alterations are dependent on the distinct GluN2-containing NMDARs. Collectively, these data reveal a critical link between NMDARs and extrasynaptic GABAARs in both physiological and pathological conditions.

neuroscience↗

bioRxiv2021

A 48-Channel Receive Array Coil for Mesoscopic Diffusion-Weighted MRI of Human ex vivo Brain Imaging on the 3T Connectome Scanner

In vivo diffusion-weighted magnetic resonance imaging is limited in signal-to-noise-ratio (SNR) and acquisition time, which constrains spatial resolution to the macroscale regime. Ex vivo imaging, which allows for arbitrarily long scan times, is critical for exploring human brain structure in the mesoscale regime without loss of SNR. Standard head array coils designed for patients are sub-optimal for imaging ex vivo whole brain specimens. The goal of this work was to design and construct a 48-channel ex vivo whole brain array coil for high-resolution and high b-value diffusion-weighted imaging on a 3T Connectome scanner. The coil was validated with bench measurements and characterized by imaging metrics on an agar brain phantom and an ex vivo human brain sample. The two-segment coil former was constructed for a close fit to a whole human brain, with small receive elements distributed over the entire brain. Imaging tests including SNR and G-factor maps were compared to a 64-channel head coil designed for in vivo use. There was a 2.9-fold increase in SNR in the peripheral cortex and a 1.3-fold gain in the center when compared to the 64-ch head coil. The 48-channel ex vivo whole brain coil also decreases noise amplification in highly parallel imaging, allowing acceleration factors of approximately one unit higher for a given noise amplification level. The acquired diffusion-weighted images in a whole ex vivo brain specimen demonstrate the applicability of the developed coil for high-resolution and high b-value diffusion-weighted ex vivo brain MRI studies.

bioengineering↗

bioRxiv2021

Thinopyrum intermedium TiAP1 interacts with a chitin deacetylase from Blumeria graminis f. sp. tritici and increases the resistance to Bgt in wheat

The biotrophic fungal pathogen Blumeria graminis f. sp. tritici (Bgt) is a crucial factor causing reduction of global wheat production. Wild wheat relatives, e.g. Thinopyrum intermedium, is one of the wild-used parents in wheat disease-resistant breeding. From T. intermedium line, we identified the aspartic acid protein gene, TiAP1, which involved in resistance against Bgt. TiAP1 is a secreted protein that accumulates in large amounts at the infection sites of powdery mildew and extends to the intercellular space. Yeast two-hybrid showed that it interacted with the chitin deacetylase (BgtCDA1) of Bgt. The yeast expression, purification, and invitro test confirmed the chitin deacetylase activity of BgtCDA1. The bombardment and VIGS mediated host-induced gene silencing showed BgtCDA1 promotes the invasion of Bgt. Transcriptome analysis showed the cell wall xylan metabolism, lignin biosynthesis-related, and defence genes involved in the signal transduction were upregulated in the transgenic TiAP1 wheat induced by Bgt. The TiAP1 in wheat may inactivate the deacetylation function of BgtCDA1, cause chitin oligomers expose to wheat chitin receptor, then trigger the wheat immune response to inhibit the growth and penetration of Bgt, and thereby enhance the tolerance of wheat to pathogens.

plant biology↗

bioRxiv2021

High-fidelity fast volumetric brain MRI using a hybrid denoising generative adversarial network (HDnGAN)

PurposeReducing scan times is important for wider adoption of high-resolution volumetric MRI in research and clinical practice. Emerging fast imaging and deep learning techniques provide promising strategies to accelerate volumetric MRI without compromising image quality. In this study, we aim to leverage an advanced fast imaging technique, wave-controlled aliasing in parallel imaging (Wave-CAIPI), and a novel denoising generative adversarial network (GAN) to achieve accelerated high-fidelity, high-signal-to-noise-ratio (SNR) volumetric MRI. Methods3D T2-weighted fluid-attenuated inversion recovery (FLAIR) image data were acquired on 33 multiple sclerosis (MS) patients using a prototype Wave-CAIPI sequence (acceleration factor R=3x2, 2.75 minutes) and a standard T2-SPACE FLAIR sequence (R=2, 7.25 minutes). A hybrid denoising GAN entitled "HDnGAN" composed of a 3D generator (i.e., a modified 3D U-Net entitled MU-Net) and a 2D discriminator was proposed to denoise Wave-CAIPI images with the standard FLAIR images as the target. HDnGAN was trained and validated on data from 25 MS patients by minimizing a combined content loss (i.e., mean squared error (MSE)) and adversarial loss with adjustable weight{lambda} , and evaluated on data from 8 patients unseen during training. The quality of HDnGAN-denoised images was compared to those from other denoising methods including AONLM, BM4D, MU-Net, and 3D GAN in terms of their similarity to standard FLAIR images, quantified using MSE and VGG perceptual loss. The images from different methods were assessed by two neuroradiologists using a five-point score regarding sharpness, SNR, lesion conspicuity, and overall quality. Finally, the performance of these denoising methods was compared at higher noise levels using simulated data with added Rician noise. ResultsHDnGAN effectively denoised noisy Wave-CAIPI images with sharpness and rich textural details, which could be adjusted by controlling{lambda} . Quantitatively, HDnGAN ({lambda}=10-3) achieved low MSE (7.43 x10-4{+/-}0.94x10-4) and the lowest VGG perceptual loss (1.09x10-2{+/-}0.18x10-2). The reader study showed that HDnGAN ({lambda}=10-3) significantly improved the SNR of Wave-CAIPI images (4.19{+/-}0.39 vs. 2.94{+/-}0.24, P<0.001), outperformed AONLM (4.25{+/-}0.56 vs. 3.75{+/-}0.90, P=0.015), BM4D (3.31{+/-}0.46, P<0.001), MU-Net (3.13{+/-}0.99, P<0.001) and 3D GAN ({lambda}=10-3) (3.31{+/-}0.46, P<0.001) regarding image sharpness, and outperformed MU-Net (4.21{+/-}0.67 vs. 3.29{+/-}1.28, P<0.001) and 3D GAN ({lambda}=10-3) (3.5{+/-}0.82, P=0.001) regarding lesion conspicuity. The overall quality score of HDnGAN ({lambda}=10-3) (4.25{+/-}0.43) was significantly higher than those from Wave-CAIPI (3.69{+/-}0.46, P=0.003), BM4D (3.50{+/-}0.71, P=0.001), MU-Net (3.25{+/-}0.75, P<0.001), and 3D GAN ({lambda}=10-3) (3.50{+/-}0.50, P<0.001), with no significant difference compared to standard FLAIR images (4.38{+/-}0.48, P=0.333). The advantages of HDnGAN over other methods were more obvious at higher noise levels. ConclusionHDnGAN provides robust and feasible denoising while preserving rich textural detail in empirical volumetric MRI data and is superior on both quantitative and qualitative evaluation compared to the original Wave-CAIPI images and images denoised using standard methods. HDnGAN concurrently benefits from the improved image synthesis performance of the 3D convolution and the increased number of samples for training the 2D discriminator from a limited number of subjects. Our study supports the use of HDnGAN in combination with modern fast imaging techniques such as Wave-CAIPI to achieve high-fidelity fast volumetric MRI.

neuroscience↗

bioRxiv2020

Robust vestibular self-motion signals in macaque posterior cingulate region

Self-motion signals, distributed ubiquitously across parietal-temporal lobes, propagate to limbic hippocampal system for vector-based navigation via hubs including posterior cingulate cortex (PCC) and retrosplenial cortex (RSC). Although numerous studies have indicated that posterior cingulate areas are involved in spatial tasks, it is unclear about how their neurons represent self-motion signals. By providing translation and rotation stimuli to macaques on a 6-degree-of-freedom motion platform, we discovered robust vestibular responses in PCC. A combined 3-dimensional spatiotemporal model captured data well and revealed multiple temporal components including velocity, acceleration, jerk, and position. The former three signals, but not position, conveyed consistent spatial information. Compared to PCC, RSC contained moderate vestibular temporal modulations and lacked significant spatial tuning. Visual self-motion signals were much weaker in both regions compared to the vestibular signals. We conclude that macaque posterior cingulate region carries vestibular-dominant self-motion signals with plentiful temporal components that could be useful for path integration.

neuroscience↗

bioRxiv2020

In vivo human whole-brain Connectom diffusion MRI dataset at 760 μm isotropic resolution

We present a whole-brain in vivo diffusion MRI (dMRI) dataset acquired at 760 m isotropic resolution and sampled at 1260 q-space points across 9 two-hour sessions on a single healthy subject. The creation of this benchmark dataset is possible through the synergistic use of advanced acquisition hardware and software including the high-gradient-strength Connectom scanner, a custom-built 64-channel phased-array coil, a personalized motion-robust head stabilizer, a recently developed SNR-efficient dMRI acquisition method, and parallel imaging reconstruction with advanced ghost reduction algorithm. With its unprecedented resolution, SNR and image quality, we envision that this dataset will have a broad range of investigational, educational, and clinical applications that will advance the understanding of human brain structures and connectivity. This comprehensive dataset can also be used as a test bed for new modeling, sub-sampling strategies, denoising and processing algorithms, potentially providing a common testing platform for further development of in vivo high resolution dMRI techniques. Whole brain anatomical T1-weighted and T2-weighted images at submillimeter scale along with field maps are also made available.

neuroscience↗

bioRxiv2020

Improved cortical surface reconstruction using sub-millimeter resolution MPRAGE by image denoising

Automatic cerebral cortical surface reconstruction is a useful tool for cortical anatomy quantification, analysis and visualization. Recently, the Human Connectome Project and several studies have shown the advantages of using T1-weighted magnetic resonance (MR) images with sub-millimeter isotropic spatial resolution instead of the standard 1-millimeter isotropic resolution for improved accuracy of cortical surface positioning and thickness estimation. Nonetheless, sub-millimeter resolution images are noisy by nature and require averaging multiple repetitions to increase the signal-to-noise ratio for precisely delineating the cortical boundary. The prolonged acquisition time and potential motion artifacts pose significant barriers to the wide adoption of cortical surface reconstruction at sub-millimeter resolution for a broad range of neuroscientific and clinical applications. We address this challenge by evaluating the cortical surface reconstruction resulting from denoised single-repetition sub-millimeter T1-weighted images. We systematically characterized the effects of image denoising on empirical data acquired at 0.6 mm isotropic resolution using three classical denoising methods, including denoising convolutional neural network (DnCNN), block-matching and 4-dimensional filtering (BM4D) and adaptive optimized non-local means (AONLM). The denoised single-repetition images were found to be highly similar to 6-repetition averaged images, with a low whole-brain averaged mean absolute difference of [~]0.016, high whole-brain averaged peak signal-to-noise ratio of [~]33.5 dB and structural similarity index of 0.92, and minimal gray matter-white matter contrast loss (2% to 9%). The whole-brain mean absolute discrepancies in gray-white surface placement, gray-CSF surface placement and cortical thickness estimation were lower than 165 m, 155 m and 145 m--sufficiently accurate for most applications. The denoising performance is equivalent to averaging [~]2.5 repetitions of the data in terms of image similarity, and 1.6-2.2 repetitions in terms of the cortical surface placement accuracy. The scan-rescan precision of the cortical surface positioning and thickness estimation was lower than 170 m. Our unique dataset and systematic characterization support the use of denoising methods for improved cortical surface reconstruction sub-millimeter resolution.

bioengineering↗

bioRxiv2020

Phylogenetic analysis by SNP and development of SSR marker in Passiflora

Information of the Passiflora genome is still very limited. Understand the evolutionary relationship between different species of Passiflora, and develop a large number of SSR markers to provide a basis for the genetic improvement of Passiflora. Applying restriction site associated DNA sequencing (RAD-Seq) technology, we studied the phylogeny, simple sequence repeat (SSR) and marker transferability of 10 accessions of 6 species of Passiflora. Taking the partial assembly sequence of accessions P4 as the reference genome, we constructed the phylogenetic tree using the detected 46,451 high-quality single nucleotide polymorphisms (SNPs), showing that P6, P7, P8 and P9 were a single one while P5 and P10 were clustered together, and P1, P2, P3 and P4 were closer in genetic relationship. Using P8 as the reference genome, a total of 12,452 high-quality SNPs were used to construct phylogenetic tree. P3, P4, P7, P8, P9 and P10 were all single branch while P1 and P2 were clustered together, and P5 and P6 were clustered into one branch. A principal component analysis (PCA) revealed a similar population structure, which four cultivated passion fruits forming a tight cluster. A total of 2,614 SSRs were identified in the genome of 10 Passiflora accessions. The core motifs were AT, GA, AAG etc., 2-6 bases, 4-16 repeats, and 2,515 pairs of SSR primer were successfully developed. Tthe SSR transferability in cultivated passion fruits is the best. These results will contribute to the study of genomics and molecular genetics in passion fruit.

molecular biology↗

bioRxiv2019

The genomic sequence and comparative genomic analysis of cultivated passion fruit(Passiflora edulis L.)

Cultivated passion fruit is a fruit tree widely cultivated in southern China, but little is known about its genomics, which seriously restricts the molecular genetics research of passion fruit. In this study, we analyzed the 165.7Mb representative genome sequences. The results showed that the passion fruit genome contained a large number of simple sequence repeats (SSR). Compared to the cassava and peach genomes, the passion fruit genome has 23,053 predicted genes. These genes can be aligned to 282 plant genomes. GO annotation indicated that these genes are involved in metabolic pathways of carbohydrates, organic acids, lipids and other molecules. KEGG pathway enrichment assigned these genes into five major categories and 19 secondary functions. Cluster analysis of gene families showed that 12,767 genes could be clustered into 9,868 gene families and 291 unique gene families. On the evolutionary relationship, the passion fruit is closely related to Populus trichocarpa and Ricinus communis, but the rate of evolution is slower. In summary, this genomic analysis result is informative, and will facilitate the future studies on gene functions of passion fruit.

genomics↗

bioRxiv2018

Vitamin A supplement after neonatal Streptococcus pneumoniae pneumonia alters CD4+T cell subset and inhibits allergic asthma in mice model

BackgroundPreviously, we showed that neonatal pneumonia caused by Streptococcus pneumoniae (S. pneumoniae) promoted adulthood ovalbumin (OVA) induced allergic asthma. Many studies have demonstrated that vitamin A deficiency induced the development of allergic asthma. Whether neonatal S. pneumoniae pneumonia promoted allergic asthma development was associated with vitamin A concentrations remains unclear.\n\nMethodsFemale BALB/c neonates were infected with S. pneumoniae strain D39 and subsequently treated with vitamin A. Vitamin A concentrations in lung, serum and liver were monitored on 2, 5, 7, 14, 21, 28 days post infection. Four weeks after infection, mice were sensitized and challenged with OVA to induce allergic airway disease (AAD) in early adulthood. Twenty-four hours after the final challenge, lung histo-pathology, cytokine concentrations in bronchoalveolar lavage fluid (BALF), airway hyperresponsiveness (AHR) and lung CD4+T cells were measured.\n\nResultsWe demonstrated that neonatal S. pneumoniae pneumonia induce lung vitamin A deficiency up to early adulthood. Moreover, neonatal S. pneumoniae pneumonia aggravated airway inflammatory cells accumulation and increased AHR during AAD, decreased Foxp3+Treg and Th1 productions remarkably, while Th2 cell expression was increased significantly. Further study indicated that vitamin A supplement after neonatal S. pneumoniae pneumonia can promote Foxp3+Treg and Th1 productions, decrease Th2 cell expressions, alleviate AHR and inflammatory cells infiltration during AAD.\n\nConclusionsUsing a mouse model, we demonstrate that Vitamin A supplement after neonatal Streptococcus pneumoniae pneumonia alters the CD4+T cell subset and inhibits the development of early adulthood allergic asthma.

immunology↗

bioRxiv2018

High-throughput identification and marker development of perfect SSR for cultivated genus of passion fruit (Passiflora edulis)

Simple sequence repeat (SSR) markers are characterized by high polymorphism, good reproducibility and co-dominance etc. They can be easily applied to develop efficient, simple and practical molecular markers. In the present study, bioinformatics methods were applied to identify high-throughput perfect SSRs of cultivar Passiflora genome. A total of 13104 perfect SSRs were obtained. SSR core sequence structure is mainly 2-4 bases, the maximum numbers are TA, AT, TC and AG. The maximum numbers of repetitions were up to 20 times. A total of 12934 pairs of SSR markers were developed by using bioinformatics software, and 20 pairs of markers were selected for amplification specificity assessment of MTX and WJ10, and the polymorphism rate was as high as 60%. The large-scale development of the SSR markers of Passiflora cultivar has paved a foundation for the efficient utilization of the germplasm resources of passion fruit, genetic improvement of the varieties and molecular breeding.

genomics↗