Biology subjects

Bi, Y.

Publications and source records attributed to Bi, Y..

90 records · Page 5Linked to original sources

bioRxiv2020

Idiosyncratic Tower of Babel: Individual differences in word meaning representation increase along abstractness

Humans primarily rely on language to communicate, based on a shared understanding of the basic building blocks of communication: words. However, words also have idiosyncratic aspects of meaning. Do we mean the same things when we use the same words? Classical philosophers disagreed on this point, speculating that words have more similar meanings across individuals if they are either more experiential (John Locke) or more abstract (Bertrand Russell). Here, we empirically characterize the individual variation pattern of 90 words using both behavioral and neuroimaging measures. We show that the magnitude of individual meaning disagreement is a function of how much language or sensory experience a word associates with, and this variation increases with abstractness of a word. Uncovering the cognitive and neural origins of word meaning disagreements across individuals has implications for potential mechanisms to modulate such disagreements.

neuroscience↗

bioRxiv2020

Preference for animate domain sounds in the fusiform gyrus of blind individuals is modulated by shape-action mapping transparency

In high-level visual shape areas in the human brain, preference for inanimate objects is observed regardless of stimulation modality (visual/auditory/tactile) and subjects visual experience (sighted/blind individuals), whereas preference for animate entities seems robust only in the visual modality. Here, we test a hypothesis explaining this effect: visual shape representations can be reliably activated through different sensory modalities when they are systematically related to action system representations. We studied fMRI activations in congenitally blind and sighted subjects listening to animal, object, and human sounds. We found that, in blind individuals, the typical anatomical location of the fusiform face area responds to human facial expression sounds, with a clear mapping between the facial motor action and the resulting face shape, but not to speech or animal sounds. Using face areas activation in the blind subjects we could distinguish between specific facial expressions used in the study, but not between specific speech sounds. We conclude that auditory stimulation can reliably activate visual representations of those stimuli - inanimate or animate - for which shape and action computations are transparently related. Our study suggests that visual experience is not necessary for the development of functional preference for face-related information in the fusiform gyrus.

neuroscience↗

bioRxiv2020

Tumor-on-a-chip platform to interrogate the role of macrophages in tumor progression

Tumor-infiltrating leukocytes, in particular macrophages, play an important role in tumor behavior and clinical outcome. The spectrum of macrophage subtypes ranges from antitumor "M1"-type to protumor "M2"-type macrophages. Tumor-associated macrophages (TAMs) typically display phenotypic features of both M1 and M2, and the population distribution is thought to be dynamic and evolve as the tumor progresses. However, our understanding of how TAMs impact the tumor microenvironment remains limited by the lack of appropriate 3D in vitro models that can capture cell to cell dynamics at high spatial and temporal resolution. Using our recently developed micro-physiological "tumor-on-a-chip" (TOC) device, we present here our findings on the impact of defined macrophage subsets on tumor behavior. The TOC device design contains three adjacent and connected chambers in which both the upper and lower chambers are loaded with tumor cells while the central chamber contains a dynamic, perfused, living microvascular network. Introduction of human pancreatic or colorectal cancer cells together with M1-polorized macrophages significantly inhibited tumor growth and tumor-induced angiogenesis. Protein analysis and antibody-based neutralization studies confirmed that these effects were mediated through production of chemokines CXCL9, CXCL10, and CXCL11. By contrast, M2-macrophages mediated increased tumor cell migration into the vascularized chamber and did not inhibit tumor growth or angiogenesis. In fact, single-cell RNA-sequencing showed that M2 macrophages further segregated endothelial cells into two distinct subsets, corresponding to static cells in vessels versus active cells involved in angiogenesis. The impact of M2 macrophages was mediated mostly by production of MMP7 and ANGPT2. In summary, our data demonstrate the utility of the TOC device to mechanistically probe biological questions in a 3D in vitro microenvironment. Insight BoxMacrophages in the tumor microenvironment are key determinants of tumor behavior and clinical outcome. The macrophage subset composition and its functional impact change as tumors progress or during treatment, but adequate models to study this are lacking. We developed a tumor-on-a-chip model of perfused 3D tumor growth to probe the impact of defined macrophage subsets. Our data is consistent with previously described macrophage activity in the tumor microenvironment, and provides potential new molecular targets. Herein, we demonstrate feasibility of probing immuno-oncology questions in a 3D in vitro microenvironment and at a spatiotemporal resolution.

cancer biology↗

bioRxiv2020

Visual featural topography in the human ventral visual pathway

Visual object recognition in humans and nonhuman primates is achieved by the ventral visual pathway (ventral occipital-temporal cortex, VOTC), which shows a well-documented object domain structure. An on-going question has been what type of information is processed in higher-order VOTC that underlies such observations, with recent evidence suggesting effects of certain visual features. Combining computational vision models, fMRI experiment using a parametric-modulation approach, and natural image statistics of common objects, we depicted the neural distribution of a comprehensive set of visual features in VOTC, identifying voxel sensitivities to specific feature sets across geometry/shape, Fourier power, and color. The visual feature combination pattern in VOTC is significantly explained by their relationships to different types of response-action computation (Fight-or-Flight, Navigation, and Manipulation), as derived from behavioral ratings and natural image statistics. These results offer the first comprehensive visual featural map in VOTC and a plausible theoretical explanation as a mapping onto different types of downstream response-action systems.

neuroscience↗

bioRxiv2020

A Comprehensive Multi-Center Cross-platform Benchmarking Study of Single-cell RNA Sequencing Using Reference Samples

Single-cell RNA sequencing (scRNA-seq) has become a very powerful technology for biomedical research and is becoming much more affordable as methods continue to evolve, but it is unknown how reproducible different platforms are using different bioinformatics pipelines, particularly the recently developed scRNA-seq batch correction algorithms. We carried out a comprehensive multi-center cross-platform comparison on different scRNA-seq platforms using standard reference samples. We compared six pre-processing pipelines, seven bioinformatics normalization procedures, and seven batch effect correction methods including CCA, MNN, Scanorama, BBKNN, Harmony, limma and ComBat to evaluate the performance and reproducibility of 20 scRNA-seq data sets derived from four different platforms and centers. We benchmarked scRNA-seq performance across different platforms and testing sites using global gene expression profiles as well as some cell-type specific marker genes. We showed that there were large batch effects; and the reproducibility of scRNA-seq across platforms was dictated both by the expression level of genes selected and the batch correction methods used. We found that CCA, MNN, and BBKNN all corrected the batch variations fairly well for the scRNA-seq data derived from biologically similar samples across platforms/sites. However, for the scRNA-seq data derived from or consisting of biologically distinct samples, limma and ComBat failed to correct batch effects, whereas CCA over-corrected the batch effect and misclassified the cell types and samples. In contrast, MNN, Harmony and BBKNN separated biologically different samples/cell types into correspondingly distinct dimensional subspaces; however, consistent with this algorithms logic, MNN required that the samples evaluated each contain a shared portion of highly similar cells. In summary, we found a great cross-platform consistency in separating two distinct samples when an appropriate batch correction method was used. We hope this large cross-platform/site scRNA-seq data set will provide a valuable resource, and that our findings will offer useful advice for the single-cell sequencing community.

genomics↗

bioRxiv2020

A novel bat coronavirus reveals natural insertions at the S1/S2 cleavage site of the Spike protein and a possible recombinant origin of HCoV-19

The unprecedented epidemic of pneumonia caused by a novel coronavirus, HCoV-19, in China and beyond has caused public health concern at a global scale. Although bats are regarded as the most likely natural hosts for HCoV-191,2, the origins of the virus remain unclear. Here, we report a novel bat-derived coronavirus, denoted RmYN02, identified from a metagenomics analysis of samples from 227 bats collected from Yunnan Province in China between May and October, 2019. RmYN02 shared 93.3% nucleotide identity with HCoV-19 at the scale of the complete virus genome and 97.2% identity in the 1ab gene in which it was the closest relative of HCoV-19. In contrast, RmYN02 showed low sequence identity (61.3%) to HCoV-19 in the receptor binding domain (RBD) and might not bind to angiotensin-converting enzyme 2 (ACE2). Critically, however, and in a similar manner to HCoV-19, RmYN02 was characterized by the insertion of multiple amino acids at the junction site of the S1 and S2 subunits of the Spike (S) protein. This provides strong evidence that such insertion events can occur in nature. Together, these data suggest that HCoV-19 originated from multiple naturally occurring recombination events among those viruses present in bats and other wildlife species.

microbiology↗

bioRxiv2019

Molecular mechanisms behind global distribution of earthworm revealed by the genome

Earthworms (Annelida: Crassiclitellata), are widely distributed around the world due to their great adaptability. However, lack of a high-quality genome sequence prevents gaining the many insights into physiology, phylogeny, and genome evolution that could come from a good earthworm genome. Herein, we report a complete genome assembly of the earthworm Amynthas corticis of about 1.2 Gb, based on a strategy combining third-generation long-read sequencing and Hi-C mapping. A total of 29,256 protein-coding genes are annotated in this genome. Analysis of resequencing data indicates that this earthworm is a triploid species. Furthermore, gene family evolution analysis shows that comprehensive expansion of gene families in the earthworm genome has produced more defensive functions compared with other species in Annelida. Quantitative proteomic iTRAQ analysis shows 97 immune related proteins and 16S rDNA sequences shows 88 microbes with significantly response to pathogenic Escherichia coli O157:H7. Our genome assembly provides abundant and valuable resources for the earthworm research community, serving as a first step toward uncovering the mysteries of this species, may explain its powerful defensive functions adapt to complex environment and invasion from molecular level.

genomics↗

bioRxiv2019

A novel xenograft model of human HCC in immunocompetent mouse

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors that threaten human health; thus, the establishment of an animal model with clinical features similar to human liver cancer is of important practical significance. Taking advantage of the novel microcarrier-6, human HCC cells was injected into immunocompetent mice to establish a novel human HCC patient-derived xenograft (PDX) model. Primary HCC cells were isolated from fresh liver cancer tissues, which were subsequently co-cultured with microcarrier-6 to construct a three-dimensional tumor cell culture model in vitro. The HCC-microcarrier complex was implanted into mice by subcutaneous inoculation, and the tumor formation time, tumor formation rate, and pathological manifestation were recorded. Changes of immune parameters in mice were detected by flow cytometry. The success rate was 60% (6/10) in the establishment of liver cancer PDX mouse model, and the total tumor formation rate of the tumor-forming model is 80-100%. H&E staining and immunohistochemical experiments indicate that the model well retained the characteristics of the primary tumor. Interestingly, M2 macrophages in tumor-bearing mice increased significantly, and the levels of CD4+ T cells were significantly reduced. Through the application of the microcarrier-6 in immunocompetent mice, we successfully established a novel human HCC PDX model, which can be used to better study and further elucidate the occurrence and pathogenic mechanism of HCC.

cancer biology↗

bioRxiv2019

Highly efficient transgenesis with miniMos in Caenorhabditis briggsae

C. briggsae as a companion species for C. elegans has played an increasingly important role in study of evolution of development, gene regulation and genome. Aided by the isolation of its sister spices, it has recently been established as a model for speciation study. To take full advantage of the species for comparative study, an effective transgenesis method especially those with single copy insertion is important for functional comparison. Here we modified a transposon-based transgenesis methodology that had been originally developed in C. elegans but worked marginally in C. briggsae. By incorporation of a heat shock step, the transgenesis efficiency in C. briggsae with single copy insertion is comparable to that in C. elegans. We used the method to generate 54 independent insertions mostly consisting of a mCherry tag over the C. briggsae genome. We demonstrated the use of the tags in identifying interacting loci responsible for hybrid male sterility between C. briggsae and C. nigoni when combined with the GFP tags we generated previously. Finally, we demonstrated that C. briggsae has developed native immunity against the C. elegans toxin, PEEL-1, but not SUP-35, making the latter a potential negative selection marker against extrachromosomal array.\n\nSummaryNematode C. briggsae has been used for comparative study against C. elegans over decades. Importantly, a sister species has recently been identified, with which C. briggsae is able to mate and produce viable hybrid progeny. This opens the possibility of using nematode species as a model for speciation study for the first time. To take full advantage of C. briggsae for comparative study, an effective transgenesis method to generate single copy insertion is important especially for functional comparison. An attempt was made previously to generate single copy insertion with transposon-based transgenesis methodology, which had been originally developed in C. elegans but with limited success in C. briggsae. Here we modified the transposon-based methodology by incorporation of a heat shock step, which allows us to achieve a much higher transgenesis efficiency in C. briggsae with single copy insertion. We used the method to generate 54 independent insertions mostly consisting of a mCherry tag over the C. briggsae genome. We demonstrated the use of the tags in identifying interacting loci responsible for hybrid male sterility between C. briggsae and C. nigoni when combined with the GFP tags we generated previously. Finally, we demonstrated that C. briggsae has developed native immunity against the C. elegans toxin, PEEL-1, but not SUP-35, making the latter a potential negative selection marker against extrachromosomal array. Taken together, the modified transgenesis methodology and the transgenic strains generated in this study are expected to further facilitate C. briggsae as a model for comparative study or speciation study.

genetics↗

bioRxiv2019

Two Forms of Knowledge Representations in the Human Brain

Sensory experience shapes what and how knowledge is stored in the brain -- our knowledge about the color of roses depends in part on the activity of color-responsive neurons based on experiences of seeing roses. We study the brain basis of color knowledge in congenitally blind individuals whose color knowledge can only be obtained through language descriptions. We found that some regions support color knowledge only in the sighted. More importantly, a region in the left dorsal anterior temporal lobe supports object color knowledge in both the blind and sighted groups, indicating the existence of a sensory-independent knowledge coding system in both groups. Thus, there are (at least) two forms of object knowledge representations in the human brain: sensory-derived and cognitively-derived knowledge, supported by different brain systems.

neuroscience↗

bioRxiv2019

BSU1 family phosphatases mediate Flagellin-FLS2 signaling through a specific phosphocode.

Hundreds of leucine-rich repeat receptor kinases (LRR-RKs) have evolved to control diverse processes of growth, development, and immunity in plants; the mechanisms that link LRR-RKs to distinct cellular responses are not understood. Here we show that two LRR-RKs, the brassinosteroid hormone receptor BRI1 (BRASSINOSTEROID INSENSITIVE 1) and the flagellin receptor FLS2 (FLAGELLIN SENSING 2), regulate downstream glycogen synthase kinase 3 (GSK3) and mitogen-activated protein (MAP) kinases, respectively, through phosphocoding of the BRI1-SUPPRESSOR1 (BSU1) phosphatase. BSU1 was previously identified as a component that inactivates GSK3s in the BRI1 pathway. We found surprisingly that loss of the BSU1 family phosphatases activates effector-triggered immunity (ETI) and impairs flagellin-triggered MAP kinase activation and immunity. The flagellin-activated BOTRYTIS-INDUCED KINASE 1 (BIK1) phosphorylates BSU1 at serine-251. Mutation of serine-251 reduces the ability of BSU1 to mediate flagellin-induced MAP kinase activation and immunity, but not its abilities to suppress ETI and interact with GSK3, which is enhanced through the phosphorylation of BSU1 at serine-764 upon brassinosteroid signaling. These results demonstrate that BSU1 plays an essential role in immunity and transduces brassinosteroid-BRI1 and flagellin-FLS2 signals using different phosphorylation sites. Our study illustrates that phosphocoding in shared downstream components provides signaling specificities for diverse plant receptor kinases.

plant biology↗

bioRxiv2018

Novel haplotypes and networks of AVR-Pik alleles in Magnaporthe oryzae

Li J, Wang Q, Li C, Bi Y, Fu X, Wang R. 2018. Novel haplotypes and networks of AVR-Pik alleles in Magnaporthe oryzae. PLoS Pathog _______.\n\nRice blast disease is one of the most destructive fungal diseases of rice world-wide. The avirulence (AVR) genes of Magnaporthe oryzae are recognized by the cognate resistance (R) genes of rice, and trigger race specific resistance. Here, we studied the possible evolutionary pathways in the evolution of AVR-Pik alleles by analyzing the DNA sequence variation and assayed for their avirulence function to the cognate Pik alleles resistance genes under field conditions in China. Results of PCR products showed that 278 isolates of M. oryzae carry AVR-Pik alleles among genomic DNA of 366 isolates of M. oryzae collected from Yunnan Province, China. Among of them, 66.7-90.3% of M. oryzae carry AVR-Pik alleles from six regions of Yunnan. Moreover, 10 AVR-Pik haplotypes encoding five novel AVR-Pik variants were identified among 201 isolates. The AVR-Pik alleles stepwise evolved to virulence from avirulent forms via base substitution. These findings demonstrate that AVR-Pik alleles are under positive selection and mutations are responsible for defeating race-specific resistance Pik alleles in nature.\n\nAuthor summaryThe interaction of resistance gene (R) of rice and avirulence (AVR) gene of rice blast fungi are belong to the gene-for-gene theory, the variation of AVR is one of the major reasons for generation new race. To detect the variation of AVR gene in isolates population of Magnaporthe oryzae collected from rice production fields, will helpful for evaluated the effectiveness of R gens in rice production areas. The Pik allele contained five R genes of Pik, Pikh, Pikp, Pikm and Piks, and the corresponding to the AVR genes of AVR-Pik/kh/kp/km/ks of M. oryzae. The Pik gene specifically recognizes and prevents infections by isolates of M. oryzae that contain AVR-Pik. The molecular variation of AVR-Pik alleles of M. oryzae and Pik alleles of rice remains unclear. Here we demonstrated that polymorphism and distribution of AVR-Pik alleles in Yunnan Province, China. By pathogenicity assays to detect function of the different haplotypes of AVR-Pik, for the first time we show detour and stepwise evolution of AVR-Pik alleles in rice production areas of Yunnan. The functional AVR-Pik possesses diversified sequence structures, and is under positive selection pressure in nature.

evolutionary biology↗

bioRxiv2018

Genome wide screen reveals a specific interaction between autosome and X that is essential for hybrid male sterility

Hybrid male progeny from interspecies cross are more prone to sterility or inviability than hybrid female progeny, and the male sterility and inviability often demonstrate a parent-of-origin asymmetry. However, the underlying mechanism of asymmetric sterility or inviability remains elusive. We previously established a genome-wide hybrid incompatibility (HI) landscape between Caenorhabditis briggsae and C. nigoni by phenotyping a large collection of C. nigoni strains each carrying a C. briggsae introgression. In this study, we investigate the genetic mechanism of asymmetric sterility and inviability in both hybrid male and female progeny between the two species. Specifically, we performed reciprocal crosses between C. briggsae and different C. nigoni strains that each carries a GFP-labeled C. briggsae genomic fragment referred to as introgression, and scored the HI phenotypes in the F1 progeny. The aggregated introgressions cover 94.6% of the C. briggsae genome, including 100% of the X chromosome. Surprisingly, we observed that two C. briggsae X fragments that produce C. nigoni male sterility as an introgression rescued hybrid F1 sterility in males fathered by C. briggsae, indicating that at least two separate X-autosome interactions are involved in the hybrid male sterility. In addition, we identified another two C. briggsae genomic intervals on the Chromosome II or IV, respectively, which can rescue the inviability, but not the sterility, of hybrid F1 males fathered by C. nigoni, suggesting the involvement of differential epistatic interactions in the asymmetric hybrid male fertility and inviability. Importantly, backcrossing of the rescued sterile males with C. nigoni led to isolation of a 1.1-Mb genomic interval that specifically interacts with an X-linked introgression, which is essential for hybrid male fertility. We further identified three C. briggsae genomic intervals on the Chromosome I, II and III, respectively that produce inviability in all F1 progeny dependent or independent of the parent-of-origin. Taken together, we identified multiple independent interacting loci that are responsible for asymmetric hybrid male and female sterility and inviability, which provides important insights into the asymmetric HI and lays a foundation for their molecular characterization.\n\nAuthor summaryIt is common that closely related species can mate with each other, but their hybrid progeny are often sterile or inviable, especially in the male progeny. The mechanism underlying the asymmetric sterility or inviability remains poorly understood. We previously addressed this question between two nematodes, Caenorhabditis briggsae and C. nigoni, by systematic substitution of various parts of the C. nigoni genome with its C. briggsaes equivalent followed by phenotypic examination. Here we investigate the genetic mechanism of the asymmetric sterility and inviability in the hybrid F1 male and female progeny between the two species. We achieved this through crossing a cohort of C. nigoni strains each carrying a substitution with C. briggsae, which led to differential homozygosity of the C. briggsae substitution in the hybrid progeny. The aggregated substitutions cover 94.6% of the C. briggsae genome, including 100% of the X chromosome. Surprisingly, we identified two C. briggsae X fragments that produced C. nigoni male sterility as a substitution but rescued hybrid F1 sterility in males fathered by C. briggsae, indicating that at least two separate X-autosome interactions are involved in the hybrid male sterility. In addition, we identified multiple genomic intervals on C. briggsae autosomes that can rescue the inviability, but not the sterility, of hybrid F1 males fathered by C. nigoni. Importantly, we isolated a 1.1-Mb genomic interval that specifically interacts with an X-linked introgression, which is essential for hybrid male fertility. We further identified three C. briggsae genomic intervals on the Chromosome I, II and III, respectively that produce inviability in all F1 progeny dependent or independent of the parent-of-origin. The identified interacting loci lays a foundation for their molecular characterization.

evolutionary biology↗

bioRxiv2018

Systematic Allelic Analysis Defines the Interplay of Key Pathways in X Chromosome Inactivation

Xist RNA, the master regulator of X chromosome inactivation, acts in cis to induce chromosome silencing through the stepwise recruitment of factors that modify underlying chromatin structure. Whilst considerable progress has been made towards defining key silencing factors and the elements to which they bind, their relative contribution to silencing different genes, and their relationship with one another is poorly understood. Here we describe a systematic analysis of Xist-mediated allelic silencing in ES cell-based models. We show that Spen, recruited through the Xist A-repeat, plays a central role, being critical for silencing of all except a subset of weakly expressed genes. Polycomb, recruited through the Xist B/C-repeat, also plays a key role, favouring silencing of genes with pre-existing H3K27me3 chromatin. LBR and the Rbm15/ m6A-methyltransferase complex, previously proposed to have a central role, make at most a minor contribution to gene silencing. We integrate our findings in a comprehensive model for Xist-mediated chromosome silencing.

genetics↗

bioRxiv2018

Structural insight into the mechanism of neuraminidase inhibitor-resistant mutations in human-infecting H10N8 Influenza A virus

The emergence of drug resistance in avian influenza virus (AIV) is a serious concern for public health. Neuraminidase (NA) isolated from a fatal case of avian-origin H10N8 influenza virus infection was found to carry a drug-resistant mutation, NA-Arg292Lys (291 in N8 numbering). In order to understand the full potential of H10N8 drug resistance, the virus was first passaged in the presence of the most commonly used neuraminidase inhibitors (NAIs), oseltamivir and zanamivir. As expected, the Arg292Lys substitution was detected after oseltamivir treatment, however a novel Val116Asp substitution (114 in N8 numbering) was selected by zanamivir treatment. Next generation sequencing (NGS) confirmed that the mutations arose early (after passages 1-3) and became dominant in the presence of the NAI inhibitors. Extensive crystallographic studies revealed that N8-Arg292Lys resistance results mainly from loss of interactions with the inhibitor carboxylate, while rotation of Glu276 was not impaired as observed in the N9-Arg292Lys, a group 2 NA structure. In the case of Val116Asp, the binding mode between oseltamivir and zanamivir is different. Asp151 forms stabilized hydrogen bond to guanidine group of zanamivir, which may compensate the resistance caused by Val116Asp. By contrast, the amino group of oseltamivir is too short to maintain this hydrogen bond, which result in resistant. Moreover, the oseltamivir-zanamivir hybrid inhibitor MS-257 displays higher effectiveness to Val116Asp than oseltamivir, which support this notion.\n\nAuthor SummaryAside from vaccination, NAIs are currently the only alternative for the clinical treatment and prophylaxis of influenza. Understanding the mechanisms of resistance is critical to guide in drug development. In this study, two drug-resistant NA substitutions, Val116Asp and Arg292Lys, were discovered from oseltamivir and zanamivir treatment of H10N8 virus. Crystal structural analyses revealed two distinct mechanisms of these two resistant mutations and provide the explanation for the difference in susceptibility of different NAIs. Zanamivir and laninamivir were more effective against the resistant variants than oseltamivir, and Arg292Lys results in more serious oseltamivir resistance in N9 than N8 subtype. This study is well-correlated to influenza pandemic/epidemic pre-warning, as the discovery of inhibitor resistant viruses will help for new drug preparedness.

microbiology↗

bioRxiv2018

Recovered and dead outcome patients caused by influenza A (H7N9) virus infection show different pro-inflammatory cytokine dynamics during disease progress and its application in real-time prognosis

The persistent circulation of influenza A(H7N9) virus within poultry markets and human society leads to sporadic epidemics of influenza infections. Severe pneumonia and acute respiratory distress syndrome (ARDS) caused by the virus lead to high morbidity and mortality rates in patients. Hyper induction of pro-inflammatory cytokines, which is known as \"cytokine storm\", is closely related to the process of viral infection. However, systemic analyses of H7N9 induced cytokine storm and its relationship with disease progress need further illuminated. In our study we collected 75 samples from 24 clinically confirmed H7N9-infected patients at different time points after hospitalization. Those samples were divided into three groups, which were mild, severe and fatal groups, according to disease severity and final outcome. Human cytokine antibody array was performed to demonstrate the dynamic profile of 80 cytokines and chemokines. By comparison among different prognosis groups and time series, we provide a more comprehensive insight into the hypercytokinemia caused by H7N9 influenza virus infection. Different dynamic changes of cytokines/chemokines were observed in H7N9 infected patients with different severity. Further, 33 cytokines or chemokines were found to be correlated with disease development and 11 of them were identified as potential therapeutic targets. Immuno-modulate the cytokine levels of IL-8, IL-10, BLC, MIP-3a, MCP-1, HGF, OPG, OPN, ENA-78, MDC and TGF-{beta} 3 are supposed to be beneficial in curing H7N9 infected patients. Apart from the identification of 35 independent predictors for H7N9 prognosis, we further established a real-time prediction model with multi-cytokine factors for the first time based on maximal relevance minimal redundancy method, and this model was proved to be powerful in predicting whether the H7N9 infection was severe or fatal. It exhibited promising application in prognosing the outcome of a H7N9 infected patients and thus help doctors take effective treatment strategies accordingly.

immunology↗

bioRxiv2018

Bisulfite-free, Base-resolution, and Quantitative Sequencing of Cytosine Modifications

The deamination of unmodified cytosine to uracil by treatment with bisulfite has for decades been the gold standard for sequencing epigenetic DNA modifications including 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). However, this harsh chemical reaction degrades the majority of the DNA and generates sequencing libraries with low complexity. Here, we present a novel bisulfite-free and base-resolution sequencing method, TET Assisted Pic-borane Sequencing (TAPS), for detection of 5mC and 5hmC. TAPS relies on mild reactions, detects modifications directly without affecting unmodified cytosines and can be adopted to detect other cytosine modifications. Compared with bisulfite sequencing, TAPS results in higher mapping rates, more even coverage and lower sequencing costs, enabling higher quality, more comprehensive and cheaper methylome analyses.\n\nOne Sentence SummaryA bisulfite-free and base-resolution method to directly sequence epigenetically modified cytosine.

genomics↗

bioRxiv2018

How do blind people represent rainbows? Disentangling components of conceptual representations.

How do we represent information that has no sensory features? How are abstract concepts like \"freedom\", devoid of external perceptible referents, represented in the brain? To address the role of sensory information in the neural representation of concepts, we investigated how people born blind process concepts whose referents are imperceptible to them because of their visual nature (e.g. \"rainbow\", or \"red\"). We find that the left dorsal anterior temporal lobe (ATL) shows preference both to typical abstract concepts (\"freedom\") and to concepts whose referents are not sensorially-available to the blind (\"rainbow\"), as compared to partially sensorially-perceptible referents (e.g. \"rain\"). Activation pattern similarity in dorsal ATL is related to the sensorial-accessibility ratings of the concepts in the blind. Parts of inferior-lateral aspects of ATL and the temporal pole responded preferentially to abstract concepts devoid of any external referents (\"freedom\") relative to imperceptible objects, in effect distinguishing between object and non-object concepts. The medial ATL showed a preference for concrete concepts (\"cup\"), along with a preference for partly perceptible items to the blind (\"rain\", as compared with \"rainbow\"), indicating this regions role in representing concepts with sensory referents beyond vision. The findings point to a new division of labor among medial, dorsal and lateral aspects of ATL in representing different properties of object and non-object concepts.

neuroscience↗