Biology subjects

Xiong, J.

Publications and source records attributed to Xiong, J..

11 recordsLinked to original sources

bioRxiv2018

Mapping Mouse Brain Slice Sequence to a Reference Brain Without 3D Reconstruction

Histological brain slices are widely used in neuroscience to study anatomical organization of neural circuits. Since data from many brains are collected, mapping the slices to a reference atlas is often the first step in interpreting results. Most existing methods rely on an initial reconstruction of the volume before registering it to a reference atlas. Because these slices are prone to distortion during sectioning process and often sectioned with nonstandard angles, reconstruction is challenging and often inaccurate. We propose a framework that maps each slice to its corresponding plane in the atlas to build a plane-wise mapping and then perform 2D nonrigid registration to build pixel-wise mapping. We use the L2 norm of the Histogram of Oriented Gradients (HOG) of two patches as the similarity metric for both steps, and a Markov Random Field formulation that incorporates tissue coherency to compute the nonrigid registration. To fix significantly distorted regions that are misshaped or much smaller than the control grids, we trained a context-aggregation network to segment and warp them to their corresponding regions with thin plate spline. We have shown that our method generates results comparable to an expert neuroscientist and is significantly better than reconstruction-first approaches.

bioinformatics↗

bioRxiv2018

Corilagin controls post-parasiticide schistosome egg-induced liver fibrosis by inhibiting Stat6 signalling pathway

This study aims to explore the effect of Corilagin (Cor) on post-parasiticide schistosome egg-induced hepatic fibrosis through the Stat6 signalling pathway in vitro and in vivo. Cellular and animal models were established and treated by Corilagin. The inhibitory effect of Corilagin was also confirmed in RAW264.7 cells in which Stat6 was overexpressed based on the GV367-Stat6-EGFP lentiviral vector system and in which Stat6 was knock-downed by gene specific siRNAs. As a result, Corilagin prevented increases in the protein level of Phospho-Stat6 (P-Stat6). Both the mRNA and protein levels of the downstream mediators SOCS1, KLF4, and PPAR{gamma}/{delta} were markedly suppressed after Corilagin treatment. Expression of ARG1 and FIZZ1/Retnla, Ym1, TGF-{beta} and PDGF in serum were also inhibited by Corilagin. The pathological changes, area of granulomas of liver sections, and degree of hepatic fibrosis were significantly alleviated in the Corilagin group. The areas of CD68- and CD206-positive cells stained by immunofluorescence were significantly decreased by Corilagin. In conclusion, Corilagin can suppress post-parasiticide schistosome egg-induced hepatic fibrosis by inhibiting the Stat6 signalling pathway and provide a new therapeutic strategy for schistosomiasis liver fibrosis.

pharmacology and toxicology↗

bioRxiv2018

The key lethal effect existed in the antibacterial behavior of short, medium, and long chain fatty acid monoglycerides on Escherichia coli

Monoglyceride is an amphiphilic molecule with promising antimicrobial activity for bacteria; however, the key lethal effect in its antibacterial behavior was still unknown. In the study, monobutyrate (MB), monolaurate (ML), monomyristate (MM) were selected to represent the short, medium, and long chain monoglycerides to compare their inhibitory effect against Escherichia coli, and a new dose-dependent inhibitory mechanism was proposed by the key lethal effect. The minimal inhibitory concentration and antibacterial curve showed a huge diversity existed in biology activity of MB, ML and MM. The results in scanning electron microscopy and flow cytometry assay indicated that the interference level of MB on cell membrane was obviously weaker than that of ML and MM, while the latter two had similar performance in increasing cell permeability at low doses. The results presented in UV-Vis spectroscopy, cell cycle and biomacromolecules synthesis inhibition assay showed that the cell cycle of Escherichia coli was obviously affected by three monoglycerides at doses near MIC, which was therefore regarded as the key lethal effect. The reason for the better biological activity of MM than ML was the stronger interference ability on bacterial cell cycle. In addition, an expanded antibacterial mode was raised that cell permeability increase at low doses was antimicrobial basis, cell cycle arrest at medium doses played the key lethal effect, and cell lysis at high doses was the result of combined action.

microbiology↗

bioRxiv2018

The identification of critical lethal action in antimicrobial mechanism of glycerol monomyristate against foodborne pathogens

Glycerol monomyristate (GMM) is a promising antimicrobial substance due to its broad antibacterial spectrum: however, the critical lethal action in its antimicrobial mechanism for foodborne pathogens remains unclear. In the present study, the inhibitory activities of GMM on Escherichia coli (E. coli), Staphylococcus aureus (S. aureus) and Candida albicans (C. albicans) were compared, and its membrane and intracellular action mechanism was investigated. The results showed that the susceptibility of E. coli to GMM was the highest, followed by S. aureus, and C. albicans being the poorest. Using flow cytometry, the GMM dose causing above 50% permeability ratio on E. coli was lower than that on S. aureus. The images from scanning electron microscope revealed no doses difference existed between the two strains when the obvious cell damage occurred. Furthermore, cell cycle and multiple fluorescent staining assays showed only the cell division of E. coli and S. aureus, excluding that of C. albicans, was obviously affected at 1/4 MIC and 1/2 MIC, indicating that the DNA interfere and subsequent cell division inhibition was likely to be the critical lethal action with doses near MIC, which can also explain the poor sensitivity of C. albicans.\n\nImportanceFoodborne pathogens, as a common source of biological pollution in the food industry, can cause millions of food poisoning incidents each year, which poses great risks to consumers health and safety. The use of monoglyceride as an edible surfactant to inhibit the growth of food-borne microorganisms has been a long time, but the relevant antibacterial mechanism is too broad to accurately grasp its key lethal effect and its action doses, which not only affects the antibacterial efficiency, but also may result in the abnormalities of food flavor when adding at overdoses. The significance of the study is to identify the key lethal effect and its action doses, which will greatly enhance the understanding of the response mechanism of different types of foodborne pathogens to monoglycerides, and provide a more reasonable reference for differential control and treatment of different gastrointestinal infections when combined with antibiotics in clinical.

microbiology↗

bioRxiv2018

Dynamics of the sex ratio in Tetrahymena thermophila

Sex is often hailed as one of the major successes in evolution, and in sexual organisms the maintenance of proper sex ratio is crucial. As a large unicellular eukaryotic lineage, ciliates exhibit tremendous variation in mating systems, especially the number of sexes and the mechanism of sex determination (SD), and yet how the populations maintain proper sex ratio is poorly understood. Here Tetrahymena thermophila, a ciliate with seven mating types (sexes) and probabilistic SD mechanism, is analyzed from the standpoint of population genetics. It is found based on a newly developed population genetics model that there are plenty of opportunities for both the co-existence of all seven sexes and the fixation of a single sex, pending on several factors, including the strength of natural selection. To test the validity of predictions, five experimental populations of T. thermophila were maintained in the laboratory so that the factors that can influence the dynamics of sex ratio could be controlled and measured. Furthermore, whole-genome sequencing was employed to examine the impact of newly arisen mutations. Overall, it is found that the experimental observations highly support theoretical predictions. It is expected that the newly established theoretical framework is applicable in principle to other multi-sex organisms to bring more insight into the understanding of the maintenance of multiple sexes in a natural population.

evolutionary biology↗

bioRxiv2018

Anatomical, Physiological, and Functional Heterogeneity of the Dorsal Raphe Serotonin System

The dorsal raphe (DR) constitutes a major serotonergic input to the forebrain, and modulates diverse functions and brain states including mood, anxiety, and sensory and motor functions. Most functional studies to date have treated DR serotonin neurons as a single, homogeneous population. Using viral-genetic methods, we found that subcortical-vs. cortical-projecting serotonin neurons have distinct cell body distributions within the DR and different degrees of coexpressing a vesicular glutamate transporter. Further, the amygdala-and frontal cortex-projecting DR serotonin neurons have largely complementary whole-brain collateralization patterns, receive biased inputs from presynaptic partners, and exhibit opposite responses to aversive stimuli. Gain-and loss-of-function experiments suggest that amygdala-projecting DR serotonin neurons promote anxiety-like behavior, whereas frontal cortex-projecting neurons promote active coping in face of challenge. These results provide compelling evidence that the DR serotonin system contains parallel sub-systems that differ in input and output connectivity, physiological response properties, and behavioral functions.

neuroscience↗

bioRxiv2017

Predominant Patterns of Splicing Evolution on Human, Chimpanzee, and Macaque Evolutionary Lineages

Although splicing is widespread and evolves rapidly among species, the mechanisms driving this evolution, as well as its functional implications, are not yet fully understood. We analyzed the evolution of splicing patterns based on transcriptome data from five tissues of humans, chimpanzees, rhesus macaques, and mice. In total, 1,526 exons and exon sets from 1,236 genes showed significant splicing differences among primates. More than 60% of these differences represent constitutive-to-alternative exon transitions while an additional 25% represent changes in exon inclusion frequency. These two dominant evolutionary patterns have contrasting conservation, regulation, and functional features. The sum of these features indicates that, despite their prevalence, constitutive-to-alternative exon transitions do not substantially contribute to long-term functional transcriptome changes. Conversely, changes in exon inclusion frequency appear to be functionally relevant, especially for changes taking place in the brain on the human evolutionary lineage.

evolutionary biology↗

bioRxiv2017

SPIN1 promotes tumorigenesis by blocking the uL18-MDM2-p53 pathway

Ribosomal proteins (RPs) play important roles in modulating the MDM2-p53 pathway. However, less is known about the upstream regulators of the RPs. Here we identify SPIN1 (Spindlin 1) as a novel binding partner of human RPL5/uL18 that is important for this pathway. SPIN1 ablation activates p53, suppresses cell growth, reduces clonogenic ability, and induces apoptosis of cancer cells by sequestering uL18 in the nucleolus, preventing it from interacting with MDM2, and thereby alleviating uL18-mediated inhibition of MDM2 ubiquitin ligase activity towards p53. SPIN1 deficiency increases ribosome-free uL18 and uL5 (human RPL11), which are required for SPIN1 depletion-induced p53 activation. Analysis of cancer genomic databases suggests that SPIN1 is highly expressed in several human cancers, and its overexpression is positively correlated with poor prognosis in cancer patients. Altogether, our findings reveal that the oncogenic property of SPIN1 is highly attributed to its negative regulation of uL18, leading to p53 inactivation.

cancer biology↗

bioRxiv2017

5-Hydroxymethylcytosine signatures in cell-free DNA provide information about tumor types and stages

5-Hydroxymethylcytosine (5hmC) is an important mammalian DNA epigenetic modification that has been linked to gene regulation and cancer pathogenesis. Here we explored the diagnostic potential of 5hmC in circulating cell-free DNA (cfDNA) using a sensitive chemical labeling-based low-input shotgun sequencing approach. We sequenced cell-free 5hmC from 49 patients of seven different cancer types and found distinct features that could be used to predict cancer types and stages with high accuracy. Specifically, we discovered that lung cancer leads to a progressive global loss of 5hmC in cfDNA, whereas hepatocellular carcinoma and pancreatic cancer lead to disease-specific changes in the cell-free hydroxymethylome. Our proof of principle results suggest that cell-free 5hmC signatures may potentially be used not only to identify cancer types but also to track tumor stage in some cancers.\n\nOne Sentence SummaryAnalyzing the epigenetic modification 5-hydroxymethylcysoine in circulating cell-free DNA reveals tumor tissue of origin and stages for cancer diagnostics.

genomics↗

bioRxiv2017

Toxicity Of Chlordane At Early Developmental Stage Of Zebrafish

Chlordane is highly toxic organochlorine pesticides that have been widely used throughout the world for decades and posing adverse effects on the environment. Contents detected in tissue and blood samples have resulted in a raising concern for their potential effects on wildlife and humans. In this study, we investigate the potential effect of chlordane on the development of zebrafish embryos. Zebrafish larvae were treated with different concentrations (0, 25, 50, 100, 200 ng/L) of chlordane from 12 hours postfertilization (hpf). Different early stage parameters were observed at 1, 2, 3 and 4 day post-fertilization (dpf). Chlordane-exposed zebrafish larvae appeared significant lower survival rate, developmental and hatching time delay and decreased embryo productivity. The heartbeat rate and blood flow were decreased in a dose dependent manner. These results suggested that exposure to real life of chlordane led to direct morphological and phenotypic changes and effects systems related to development and reproduction even in short-term manner.

pharmacology and toxicology↗

bioRxiv2016

Combining transcription factor binding affinities with open-chromatin data for accurate gene expression prediction

The binding and contribution of transcription factors (TF) to cell specific gene expression is often deduced from open-chromatin measurements to avoid costly TF ChIP-seq assays. Thus, it is important to develop computational methods for accurate TF binding prediction in open-chromatin regions (OCRs). Here, we report a novel segmentation-based method, TEPIC, to predict TF binding by combining sets of OCRs with position weight matrices. TEPIC can be applied to various open-chromatin data, e.g. DNaseI-seq and NOMe-seq. Additionally, Histone-Marks (HMs) can be used to identify candidate TF binding sites. TEPIC computes TF affinities and uses open-chromatin/HM signal intensity as quantitative measures of TF binding strength. Using machine learning, we find low affinity binding sites to improve our ability to explain gene expression variability compared to the standard presence/absence classification of binding sites. Further, we show that both footprints and peaks capture essential TF binding events and lead to a good prediction performance. In our application, gene-based scores computed by TEPIC with one open-chromatin assay nearly reach the quality of several TF ChIP-seq datasets. Finally, these scores correctly predict known transcriptional regulators as illustrated by the application to novel DNaseI-seq and NOMe-seq data for primary human hepatocytes and CD4+ T-cells, respectively.

bioinformatics↗