Biology subjects

Han, Z.

Publications and source records attributed to Han, Z..

139 records · Page 8Linked to original sources

bioRxiv2019

TSUNAMI: Translational Bioinformatics Tool Suite For Network Analysis And Mining

Gene co-expression network (GCN) mining identifies gene modules with highly correlated expression profiles across samples/conditions. It helps to discover latent gene/molecular interactions, identify novel gene functions, and extract molecular features from certain disease/condition groups, thus help to identify disease biomarkers. However, there lacks an easy-to-use tool package for users to mine GCN modules that are relatively small in size with tightly connected genes that can be convenient for downstream Gene Ontology (GO) enrichment analysis, as well as modules that may share common members. To address this need, we develop a GCN mining tool package TSUNAMI (Tools SUite for Network Analysis and MIning) which incorporates our state-of-the-art lmQCM algorithm to mine GCN modules in public and user-input data (microarray, RNA-seq, or any other numerical omics data), then performs downstream GO and enrichment analysis based on the modules identified. It has several features and advantages: (i) user friendly interface and the real-time co-expression network mining through web server; (ii) direct access and search of GEO and TCGA databases as well as user-input expression matrix (microarray, RNA-seq, etc.) for GCN module mining; (iii) multiple co-expression analysis tools to choose with highly flexible of parameter selection options; (iv) identified GCN modules are summarized to eigengenes, which are convenient for user to check their correlation with other clinical traits; (v) integrated downstream Enrichr enrichment analysis and links to other GO tools; (vi) visualization of gene loci by Circos plot in any step. The web service is freely accessible through URL: http://spore.ph.iu.edu:3838/zhihuan/TSUNAMI/. Source code is available at https://github.com/huangzhii/TSUNAMI/.

bioinformatics↗

bioRxiv2019

Principles of 3D Nucleus Organization and Epigenetic Regulation in Diploid Genome Revealed by Multi-omic Data from Hybrid Mouse

Most mammalian genomes are diploid and previous studies have extensively investigated the average epigenetic profiles of homologous chromosomes. Here we use hybrid mice to distinguish the epigenetic status and three-dimensional organization of homologous chromosomes. We generated Hi-C, ChIP-seq and RNA-seq datasets from CD4 T cells of B6, Cast and hybrid mice, respectively, and systematically analyzed the 3D nucleus organization and epigenetic regulation. Our data indicate that the inter-chromosomal interaction patterns between homologous chromosomes are similar and the similarity is highly correlated with their allelic co-expression levels. Construction of 3D nucleus based on allele-specific interaction frequency revealed symmetric positioning of homologous chromosomes in the 3D nuclear space. The inter-chromosomal interactions at centromeres are significantly weaker than those at telomeres, indicating positioning of centromeres toward the inside of chromosome territories and telomeres toward the surface of chromosome territories. The majority A|B compartments or topologically associated domains (TADs) are consistent between B6 and Cast. We found 58% of the haploids in hybrids maintain their parental compartment status at B6/Cast divergent compartments due to cis-effect. About 95% of the trans-effected B6/Cast divergent compartments converge to same compartment status potentially due to a shared cellular environment. We found the differentially expressed genes between the two haploids in hybrid were associated with either genetic associated cis-effects or epigenetic associated trans-effects. The widespread epigenetic differences between B6 and Cast suggest that epigenetic changes may be major contributors to differences between B6 and Cast. Our data revealed symmetrical positioning of homologous chromosomes in 3D nucleus and enhanced our understanding of allele-specific epigenetic regulation.

genomics↗

bioRxiv2019

Molecular characterization of carbapenem-resistant Klebsiella pneumoniae isolates with focus on antimicrobial resistance

The enhancing incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP)-mediated infections in Mengchao Hepatobiliary Hospital of Fujian Medical University in 2017 is the motivation behind this investigation to study gene phenotypes and resistance-associated genes of emergence regarding the CRKP strains. In current study, seven inpatients are enrolled in the hospital with complete treatments. The carbapenem-resistant K. pneumoniae whole genome is sequenced using MiSeq short-read and Oxford Nanopore long-read sequencing technology. Prophages are identified to assess genetic diversity within CRKP genomes. The investigation encompassed eight CRKP strains that collected from the patients enrolled as well as the environment, which illustrate that blaKPC-2 is responsible for phenotypic resistance in six CRKP strains that K. pneumoniae sequence type (ST11) is informed. The plasmid with IncR, ColRNAI and pMLST type with IncF[F33:A-:B-] co-exist in all ST11 with KPC-2-producing CRKP strains. Along with carbapenemases, all K. pneumoniae strains harbor two or three extended spectrum {beta}-lactamase (ESBL)-producing genes. fosA gene is detected amongst all the CRKP strains. The single nucleotide polymorphisms (SNP) markers are indicated and validated among all CRKP strains, providing valuable clues for distinguishing carbapenem-resistant strains from conventional K. pneumoniae. In conclusion, ST11 is the main CRKP type, and blaKPC-2 is the dominant carbapenemase gene harbored by clinical CRKP isolates from current investigations.

bioengineering↗

bioRxiv2019

A unified neurocognitive model of the anterior temporal lobe contributions to semantics, language, social behaviour & face recognition

AbstractThe anterior temporal lobes (ATL) have become a key brain region of interest in cognitive and clinical neuroscience. Contemporary explorations are founded upon neuropsychological investigations of semantic dementia (SD) that describe the patients selective semantic impairment and the variations in their language, behavioural and face recognition abilities. The purpose of this investigation was to generate a single unified model which captures the known cognitive-behavioural variations in SD, and integrates with the considerable database on healthy semantic function and other patient groups. A new analytical approach was able to capture the graded neuropsychological differences and map these to the patients distribution of frontotemporal atrophy. Multiple regression and principal component analyses confirmed that the degree of generalised semantic impairment was related to the patients total, bilateral ATL atrophy. Verbal production and word-finding abilities were related to total ATL atrophy as well as to the balance of left>right ATL atrophy. Behavioural apathy was found to relate positively to the degree of orbitofrontal atrophy and negatively to total temporal volumes. Disinhibited behaviour was related to right ATL and orbitofrontal atrophy and face recognition to right ATL volumes. Rather than positing mutually-exclusive sub-categories, the data-driven model repositions semantics, language, social behaviour and face recognition into a continuous frontotemporal neurocognitive space.

neuroscience↗

bioRxiv2019

Performance of bitumen coating sheet using biomass pyrolysis oil

The \"green\" production of bitumen has raised increasing interest in recent years to reduce the environmental, energy and petro-based concerns. Bio-oil, prepared by biomass pyrolysis, can be used as substitute for petro-based bitumen in bitumen or bitumen-based coatings, for its similar properties of good adhesion and anti-corrosion characteristics. Although biomass is a renewable and widespread chemicals resource, its value-added utilization is still difficult. Several studies have qualitatively demonstrated the use of bio-bitumen in practical applications. The present study investigates the effects and properties and the incorporation of bio-bitumen shown to improve the performance of traditional petro-bitumen to some extent. Bio-bitumen was prepared from biomass pyrolysis oil and applied to self-adhesive and doped hot-melt sheets. Resulting physical properties demonstrate that bio-bitumen is a potential substitute in bitumen coating sheet.\n\nIMPLICATIONSThis paper is intended to verify the effect of pyrolyzed bio-oil from wheat straw on the performance of bitumen, as well as the feasibility of application in the coating sheet. Up to now, the research on bio-bitumen is mainly in pavement bitumen. In the present research, bio-bitumen was applied to the coating sheet in different proportions. Interestingly, the prepared coating sheet exhibited higher adhesion. Other performances, such as temperature stability, mechanical strength and temperature flexibility of coating sheet showed improvement in the presence of bio- oil, which indicated the suitability of bio-oil in coating sheet bitumen.

bioengineering↗

bioRxiv2019

Cell Fate Determining Molecular Switches and Signaling Pathway in Pax7-expressing Somitic Mesoderm

Pax7-expressing progenitor cells in the somitic mesoderm differentiate into multiple lineages, such as brown adipose tissue, dorsal dermis, as well as muscle in the dorsal trunk and the diaphragm; however, the key molecular switches that determine and control the process of lineage commitment and cell fate are unknown. To probe the mechanisms behind mesoderm development, Pax7creER/R26-stop-EYFP embryos were tamoxifen-induced at E9.5 to label Pax7+ cells for lineage tracing and collected at later time points for analysis. The YFP-labelled cells which belonged to the Pax7 lineage were enriched by fluorescence-activated cell sorting (FACS) and subject to single-cell RNA profiling. We observed that a subpopulation of cells differentiated into the myogenic lineage, showing Myf5 expression as early as E12.5, whereas the rest of the population was fibroblast-like and appeared to be the early stage of the adipogenic and dermal lineages. Cells at E14.5 had distinct myogenic populations that expressed Myod1 and Myog; we also identified other populations with Ebf2 or Twist2 expression, which could belong to adipogenic or dermal lineages, respectively. Cell surface markers were also found for each specific lineage, providing insights in sorting strategy for lineage-of-interest for further functional evaluation. Adipogenic lineage was successfully sorted with a combination of Pdgfra and Thy1 antibodies. In addition, we found that upregulation of Wnt signaling pathway activity is dynamically regulated in dermal lineage. Finally, transcription factors that could potentially drive, or reprogram cell fate, were identified at different developmental time points.\n\nSummary statementInvestigation of Pax7 lineage transcriptomic profile at single-cell level identified multiple cell types, fate commitment time point, surface markers, transcription factors and signaling pathways that determine cell fate.

developmental biology↗

bioRxiv2018

Quantum energy levels of glutamate modulate neural biophotonic signals

Glutamate is the most abundant excitatory neurotransmitter in the brain, and it plays an essential and important role in neural functions. Hypofunction of the glutamatergic pathway and the changes in the glutamate-glutamine cycle function are important neuropathological mechanisms of severe mental disorders including schizophrenia and depression. Current studies have shown that glutamate can induce neural biophotonic activity and transmission, which may involve the mechanism of photon quantum brain; however, it is unclear whether such a mechanism follows the principle of quantum mechanics. Here we show that the action of glutamate on its receptors leads to a decrease in its quantum energy levels, and glutamate then partially or completely loses its function to further induce the biophotonic activity in mouse brain slices. The reduced quantum energy levels of glutamate can be restored by direct-current electrical discharges and the use of energy transfer of chloroplast photosynthesis; hence, the quantum energy recovered glutamate can again induce significant biophotonic activity. Furthermore, the changes in quantum energy levels of glutamate are related to the exchange and transfer of electron energy on its active hydrogen atom. These findings suggest that the glutamate-induced neural biophotonic signals may be involved in the transfer of the quantum energy levels of glutamate, which implies a quantum mechanism of neurotransmitter action. The process of glutamate recycling that is related to the synergism of neurons and glial cells and certain key enzymes may be necessary for the recovery of quantum energy levels of glutamate after completion of the neural signal transmission. These findings may also provide a new idea to develop \"quantum drugs\".

neuroscience↗

bioRxiv2018

Genetic interactions among Ghd7, Ghd7.1, Ghd8 and Hd1 contribute to large variation in heading date in rice

Several major heading date genes are sensitive to photoperiod and jointly regulate heading date in rice. However, it is not clear how these genes coordinate rice heading. In this study, a near-isogenic F2 population with Ghd7, Ghd7.1, Ghd8 and Hd1 segregating in the Zhenshan 97 (ZS97) background was used to evaluate the genetic interactions among these four genes under natural long-day (NLD) and natural short-day (NSD) conditions, and a series of Ghd7.1-segregating populations in different backgrounds were developed to estimate the genetic effects of Ghd7.1 on heading date under both conditions. Tetragenic, trigenic and digenic interactions among these four genes were observed under both conditions. In the functional Hd1 backgrounds, the strongest digenic interaction was Ghd7 by Ghd8 under NLD conditions but was Ghd7 by Ghd7.1 under NSD conditions. Interestingly, Ghd7.1 acted as a flowering suppressor under NLD conditions, while it functioned alternatively as an activator or a suppressor under NSD conditions depending on the status of the other three genes. Based on the performances of 16 homozygous four-gene combinations, a positive correlation between heading date and yield was found under NSD conditions, but changed to a negative correlation when heading date was over 90 days under NLD conditions. These results demonstrate the importance of genetic interactions in the rice flowering regulatory network and will help breeders to select favorable combinations to maximize rice yield potential for different ecological areas.

genetics↗

bioRxiv2018

Termination of non-coding transcription in yeast relies on both a CTD-interaction domain and a CTD-mimic in Sen1

Pervasive transcription is a widespread phenomenon leading to the production of a plethora of non-coding RNAs (ncRNAs) without apparent function. Pervasive transcription poses a risk that needs to be controlled to prevent the perturbation of gene expression. In yeast, the highly conserved helicase Sen1 restricts pervasive transcription by inducing termination of non-coding transcription. However, the mechanisms underlying the specific function of Sen1 at ncRNAs are poorly understood. Here we identify a motif in an intrinsically disordered region of Sen1 that mimics the phosphorylated carboxy terminal domain (CTD) of RNA polymerase II and characterize structurally its recognition by the CTD-interacting domain of Nrd1, an RNA-binding protein that binds specific sequences in ncRNAs. In addition, we show that Sen1-dependent termination strictly requires the recognition of the CTD by the N-terminal domain of Sen1. We provide evidence that the Sen1-CTD interaction does not promote Sen1 initial recruitment but rather the capacity of Sen1 to induce the release of paused RNAPII from the DNA. Our results shed light onto the network of protein-protein interactions that control termination of non-coding transcription by Sen1.

genetics↗

bioRxiv2018

Functional connectivity alterations of the temporal lobe and hippocampus in semantic dementia and Alzheimer’s disease

The severe semantic memory impairments in semantic dementia have been attributed to a pronounced atrophy and functional disruption of the anterior temporal lobes. In contrast, the medial and posterior temporal lobe damage predominantly found in patients with Alzheimers disease has been associated with episodic memory disturbance. However, the two dementia subtypes share hippocampal deterioration, despite a relatively spared episodic memory in semantic dementia. To gain more insight into the mutual and divergent functional alterations seen in Alzheimers disease and semantic dementia, we assessed the differences in intrinsic functional connectivity between temporal lobe regions in patients with Alzheimers disease (n = 16), semantic dementia patients from two international sites (n = 23), and healthy controls (n = 17). In an exploratory study, we used a functional parcellation of the temporal cortex to extract time series. The Alzheimers disease group showed a single connection with reduced functional connectivity as compared to the controls. This connection was located between the right orbitofrontal cortex and the right anterior temporal lobe. In contrast, functional connectivity was decreased in the semantic dementia group in six connections, mainly involving the hippocampus, lingual gyrus, temporal pole, and orbitofrontal cortex. We identified a common pathway with semantic dementia, since the functional connectivity between the right anterior temporal lobe and the right orbitofrontal cortex was reduced in both types of dementia. This might be related to social knowledge deficits as part of semantic memory decline. However, such interpretations are preferably made in the context of all disease-specific semantic impairments and functional connectivity changes. Despite some limitations owed to the two database sites, this study provides a first preliminary picture of the brains functional dysconnectivity in Alzheimers disease and semantic dementia. Future studies are needed to replicate findings of such a common pathway with matched diagnosis, neuropsychological, and data MRI acquisition procedures.

neuroscience↗

bioRxiv2018

High-throughput automatic training system for odor-based learned behaviors in head-fixed mice

Understanding neuronal mechanisms of cognitive behaviors requires efficient behavioral assays. We designed a high-throughput automatic training system (HATS) for olfactory behaviors in head-fixed mice. The hardware and software were constructed to enable automatic training with minimal human intervention. The integrated system was composed of customized 3D-printing supporting components, an odor-delivery unit with fast response, Arduino based hardware-controlling and data-acquisition unit. Furthermore, the customized software was designed to enable automatic training in all training phases, including lick-teaching, shaping, and learning. Using HATS, we trained mice to perform delayed non-match to sample (DNMS), delayed paired association (DPA), Go/No-go (GNG), and GNG reversal tasks. These tasks probed cognitive functions including sensory discrimination, working memory, decision making, and cognitive flexibility. Mice reached stable levels of performance within several days in the tasks. HATS enabled an experimenter to train eight mice simultaneously, therefore greatly enhanced the experimental efficiency. Combined with causal perturbation and activity recording techniques, HATS can greatly facilitate our understanding of the neural-circuitry mechanisms underlying cognitive behaviors.

neuroscience↗

bioRxiv2018

Targeted epigenomic changes to the maize methylome resulting from tissue culture

DNA methylation can contribute to the maintenance of genome integrity and regulation of gene expression. In most situations, DNA methylation patterns are inherited quite stably. However, changes in DNA methylation can occur at some loci as a result of tissue culture resulting in somaclonal variation. A sequence-capture bisulfite sequencing approach was implemented to monitor context-specific DNA methylation patterns in ~15Mb of the maize genome for a population of plants that had been regenerated from tissue culture. Plants that have been regenerated from tissue culture exhibit gains and losses of DNA methylation at a subset of genomic regions. There was evidence for a high rate of homozygous changes to DNA methylation levels that occur consistently in multiple independent tissue culture lines suggesting the existence of a targeted process for altering epigenetic state during tissue culture. The consistent changes induced by tissue culture include both gains and losses of DNA methylation and can affect CG, CHG or both contexts within a region. The majority of changes in DNA methylation exhibit stable inheritance although there is some evidence for stochastic reacquisition of the initial epigenetic state in some individuals. This study provides insights into the susceptibility of some loci and potential mechanisms that could contribute to altered DNA methylation and epigenetic state that occur during tissue culture in plant species.

plant biology↗

bioRxiv2017

Subtle perturbations of the maize methylome reveal genes and transposons silenced by DNA methylation

DNA methylation is a chromatin modification that can provide epigenetic regulation of gene and transposon expression. Plants utilize several pathways to establish and maintain DNA methylation in specific sequence contexts. The chromomethylase (CMT) genes maintain CHG (where H = A, C or T) methylation. The RNA-directed DNA methylation (RdDM) pathway is important for CHH methylation. Transcriptome analysis was performed in a collection of Zea mays lines carrying mutant alleles for CMT or RdDM-associated genes. While the majority of the transcriptome was not affected, we identified sets of genes and transposon families sensitive to context-specific decreases in DNA methylation in mutant lines. Many of the genes that are up-regulated in CMT mutant lines have high levels of CHG methylation, while genes that are differentially expressed in RdDM mutants are enriched for having nearby mCHH islands, providing evidence that context-specific DNA methylation directly regulates expression of a small number of genes. The analysis of a diverse set of inbred lines revealed that many genes regulated by CMTs exhibit natural variation for DNA methylation and gene expression. Transposon families with differential expression in the mutant genotypes show few defining features, though several families up-regulated in RdDM mutants show enriched expression in endosperm, highlighting the importance for this pathway during reproduction. Taken together, our findings suggest that while the number of genes and transposon families whose expression is reproducibly affected by mild perturbations in context-specific methylation is small, there are distinct patterns for loci impacted by RdDM and CMT mutants.

plant biology↗