Biology subjects

Li, F.

Publications and source records attributed to Li, F..

At least 19 recordsLinked to original sources

bioRxiv2018

Cytologic, Genetic, and Proteomic Analysis of a Yellow Leaf Mutant of Sesame (Sesamum indicum L.), Siyl-1

Leaf color mutation in sesame always affects the growth and development of plantlets, and their yield. To clarify the mechanisms underlying leaf color regulation in sesame, we analyzed a yellow-green leaf mutant. Genetic analysis of the mutant selfing revealed 3 phenotypes--YY, light-yellow (lethal); Yy, yellow-green; and yy, normal green--controlled by an incompletely dominant nuclear gene, Siyl-1. In YY and Yy, the number and morphological structure of the chloroplast changed evidently, with disordered inner matter, and significantly decreased chlorophyll content. To explore the regulation mechanism of leaf color mutation, the proteins expressed among YY, Yy, and yy were analyzed. All 98 differentially expressed proteins (DEPs) were classified into 5 functional groups, in which photosynthesis and energy metabolism (82.7%) occupied a dominant position. Our findings provide the basis for further molecular mechanism and biochemical effect analysis of yellow leaf mutants in plants.

genetics↗

bioRxiv2018

Rapid CD4 cell loss is caused by specific CRF01_AE cluster with V3 signatures favoring CXCR4 usage

HIV-1 evolved into various genetic subtypes and circulating recombinant forms (CRFs) in the global epidemic, with the same subtype or CRF usually having similar phenotype. Being one of the worlds major CRFs, CRF01_AE infection was reported to associate with higher prevalence of CXCR4 (X4) viruses and faster CD4 decline. However, the underlying mechanisms remain unclear. We identified eight phylogenetic clusters of CRF01_AE in China and hypothesized that they may have different phenotypes. In the national HIV molecular epidemiology survey, we discovered that people infected by CRF01_AE cluster 4 had significantly lower CD4 count (391 vs. 470, p < 0.0001) and higher prevalence of predicted X4-using viruses (17.1% vs. 4.4%, p < 0.0001) compared to those infected by cluster 5. In a MSM cohort, X4-using viruses were only isolated from sero-convertors infected by cluster 4, which associated with rapid CD4 loss within the first year of infection (141 vs. 440, p = 0.01). Using co-receptor binding model, we identified unique V3 signatures in cluster 4 that favor CXCR4 usage. We demonstrate for the first time that HIV-1 phenotype and pathogenicity can be determined at the phylogenetic cluster level in a single subtype. Since its initial spread to human from chimpanzee in 1930s, HIV-1 remains undergoing rapid evolution in larger and more diverse population. The divergent phenotype evolution of two major CRF01_AE clusters highlights the importance in monitoring the genetic evolution and phenotypic shift of HIV-1 to provide early warning for the appearance of more pathogenic strains such as CRF01_AE cluster 4.\n\nSignificance StatementPast studies on HIV-1 evolution were mainly at the genetic level. This study provides well-matched genotype and phenotype data and demonstrates disparate pathogenicity of two major CRF01_AE clusters. While both CRF01_AE cluster 4 and cluster 5 are mainly spread through the MSM route, cluster 4 but not cluster 5 causes fast CD4 loss, which is associated with the higher prevalence CXCR4 viruses in cluster 4. The higher CXCR4 use tendency in cluster 4 is derived from its unique V3 loop favoring CXCR4 binding. This study for the first time demonstrates disparate HIV-1 phenotype between different phylogenetic clusters. It is important to monitor HIV-1 evolution at both the genotype and phenotype level to identify and control more pathogenic HIV-1 strains.

microbiology↗

bioRxiv2018

Neurogenetic dissection of the Drosophila innate olfactory processing center

Animals exhibit innate behaviours in response to a variety of sensory stimuli such as olfactory cues. In Drosophila, a higher olfactory centre called the lateral horn (LH) is implicated in innate behaviour. However, our knowledge of the structure and function of the LH is scant, due to the lack of sparse neurogenetic tools for this brain region. Here we generate a collection of split-GAL4 driver lines providing genetic access to 82 LH cell-types. We identify the neurotransmitter and axo-dendritic polarity for each cell-type. Using these lines were create an anatomical map of the LH. We found that [~]30% of LH projections converge with outputs from the mushroom body, the site of olfactory learning and memory. Finally, using optogenetic activation of small groups of LH neurons. We identify cell-types that drive changes in either valence or specific motor programs, such as turning and locomotion. In summary we have generated a resource for manipulating and mapping LH neurons in both light and electron microscopy and generated insights into the anatomy and function of the LH.

neuroscience↗

bioRxiv2018

A cell atlas of the adult Drosophila midgut

Studies of the adult Drosophila midgut have provided a number of insights on cell type diversity, stem cell regeneration, tissue homeostasis and cell fate decision. Advances in single-cell RNA sequencing (scRNA-seq) provide opportunities to identify new cell types and molecular features. We used inDrop to characterize the transcriptome of midgut epithelial cells and identified 12 distinct clusters representing intestinal stem cells (ISCs), enteroblasts (EBs), enteroendocrine cells (EEs), enterocytes (ECs) from different regions, and cardia. This unbiased approach recovered 90% of the known ISCs/EBs markers, highlighting the high quality of the dataset. Gene set enrichment analysis in conjunction with electron micrographs revealed that ISCs are enriched in free ribosomes and possess mitochondria with fewer cristae. We demonstrate that a subset of EEs in the middle region of the midgut expresses the progenitor marker esg and that individual EEs are capable of expressing up to 4 different gut hormone peptides. We also show that the transcription factor klumpfuss (klu) is expressed in EBs and functions to suppress EE formation. Lastly, we provide a web-based resource for visualization of gene expression in single cells. Altogether, our study provides a comprehensive resource for addressing novel functions of genes in the midgut epithelium.

genetics↗

bioRxiv2018

The effect of varied exercise intensity on antioxidant function, and aortic endothelial cell function and serum lipids in a non-alcoholic fatty liver disease rats.

Exercise and diet may improve cardio-metabolic health in non-alcoholic fatty liver disease, but the optimal exercise prescription remains unclear. We aimed to compare the effects of diet and exercise at different intensities on antioxidant function, and aortic endothelial cell function and serum lipids in a non-alcoholic fatty liver disease rats. Fifty Sprague Dawley rats (180-220g) were randomly divided into two experimental groups and fed either standard rodent chow diet or a high-fat diet. After16 weeks, these animals that received the HFD were randomly separated into a high fat control group or three exercise training groups: HF and low intensity exercise, HF and moderate intensity exercise, HF and incremental intensity exercise, these experimental rats keep sedentary or training for the next 6 weeks. Markers of Aortic Oxidative stress were detected using assay kit. Immunohistochemical analysis was performed to determine the expression level of eNOS and ET-1. Lipid metabolism parameters were detected with an automatic analyzer. Exercise at different intensities improved lipid metabolism, enhanced anti-oxidation function, reduced MDA, increased NO, and improved the expression of eNOS and ET-1 protein levels. Decreased blood lipids were exhibited in all exercise groups. Notably, moderate intensity exercise demonstrated more effect on increasing GSH contents, and decreased the expression of ET-1 protein levels.

physiology↗

bioRxiv2018

Specific activation of HIV-1 from monocytic reservoir cells by bromodomain inhibitor in humanized mice in vivo

The combination antiretroviral therapy (cART) effectively suppresses HIV-1 infection and enables HIV-infected individuals to live long productive lives. However, the persistence of HIV-1 reservoir cells with latent or low-replicating HIV-1 in patients under cART make HIV-1 infection an incurable disease. Recent studies have focused on the development of strategies such as epigenetic modulators to activate and purge these reservoirs. Bromodomain inhibitors (BETi) are epigenetic modulating compounds able to activate viral transcription in HIV-1 latency cell lines in a positive transcription elongation factor b (P-TEFb)-dependent manner. Little is known about the efficacy of activating HIV-1 reservoir cells under cART by BETi in vivo. In this study, we seek to test the potential of a BETi (I-BET151) in activating HIV-1 reservoir cells under effective cART in humanized mice in vivo. We discover that I-BET151 efficiently activates HIV-1 transcription in monocytic cells, but not in CD4+ T cells, during suppressive cART in vivo. We further reveal that HIV-1 proviruses in monocytic cells are more sensitive to I-BET151 treatment than in T cells in vitro. Finally, we demonstrate that I-BET151-activated viral transcription in monocytic cells is dependent on both CDK2 and CDK9, whereas only CDK9 is involved in activation of HIV-1 by I-BET151 in T cells. Our findings indicate a role of myeloid cells in HIV-1 persistence, and highlights the limitation of measuring or targeting T cell reservoirs alone in terms of HIV-1 cure, as well as provides a potential strategy to reactivate monocytic reservoirs during cART.\n\nIMPORTANCEIt has been reported the low level of active P-TEFb critically contributes to the maintenance of HIV-1 latency or low-replication in HIV-1 reservoir cells under cART. Bromodomain inhibitors are used to activate HIV-1 replication in vitro but their effect on activation of the HIV-1 resevoirs with cART in vivo is not clear. We found that BETi (I-BET151) treatment reactivated HIV-1 gene expression in humanized mice during suppressive cART. Interestingly, I-BET151 preferentially reactivated HIV-1 gene expression in monocytic cells, but not in CD4 T cells. Furthermore, I-BET151 significantly increased HIV-1 transcription in monocytic cells, but not in latently infected CD4 T cells, via CDK2-dependent mechanisms. Our findings suggest that BETi can preferentially activate monocytic HIV-1 reservoir cells, and a combination of latency reversal agents targeting different cell types and pathways is needed to achieve reactivation of different HIV-1 reservoir cells during cART.

immunology↗

bioRxiv2018

The Feeding Connectome: Convergence of Monosynaptic and Polysynaptic Sensory Paths onto Common Motor Outputs

Little is known about the organization of central circuits by which external and internal sensory inputs act on motor outputs to regulate fundamental behaviors such as feeding. We reconstructed, from a whole CNS EM volume, the synaptic map of input and output neurons that underlie food intake behavior of Drosophila larvae. The input neurons originate from enteric, pharyngeal and external sensory organs and converge onto seven distinct sensory synaptic compartments within the CNS, as defined by distribution patterns of their presynaptic sites. The output neurons consist of pharyngeal motor neurons, serotonergic modulatory neurons, and neuroendocrine neurons that target the ring gland, a key endocrine organ. Monosynaptic connections from a set of sensory synaptic compartments cover the motor and endocrine targets in overlapping domains. Polysynaptic routes can be superimposed on top of the monosynaptic connections, resulting in divergent sensory paths that converge on common motor outputs. A completely different set of sensory compartments is connected to the mushroom body calyx of the memory circuits. Our results illustrate a circuit architecture in which monosynaptic and multisynaptic connections from sensory inputs traverse onto output neurons via a series of converging paths.

neuroscience↗

bioRxiv2018

A macrophage-pericyte axis directs tissue restoration via Amphiregulin-induced TGFβ activation

The Epidermal Growth Factor Receptor ligand Amphiregulin has a well-documented role in the restoration of tissue homeostasis following injury; however, the mechanism by which Amphiregulin contributes to wound repair remains unknown. Here we show that Amphiregulin functions by releasing bio-active TGFb from latent complexes via integrin-v activation. Using acute injury models in two different tissues, we found that by inducing TGFb activation on mesenchymal stromal cells (aka pericytes), Amphiregulin induced their differentiation into myo-fibroblasts, thereby selectively contributing to the restoration of vascular barrier function within injured tissue. Furthermore, we identified macrophages as a critical source of Amphiregulin, revealing a direct effector mechanism by which these cells contribute to tissue restoration following acute injury. Combined, these observations expose a so far under-appreciated mechanism of how cells of the immune system selectively control the differentiation of tissue progenitor cells during tissue repair and inflammation.

immunology↗

bioRxiv2018

A genetically-encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice

Dopamine (DA) is a central monoamine neurotransmitter involved in many physiological and pathological processes. A longstanding yet largely unmet goal is to measure DA changes reliably and specifically with high spatiotemporal precision, particularly in animals executing complex behaviors. Here we report the development of novel genetically-encoded GPCR-Activation-Based-DA (GRABDA) sensors that enable these measurements. In response to extracellular DA rises, GRABDA sensors exhibit large fluorescence increases ({Delta}F/F0[~]90%) with sub-second kinetics, nanomolar to sub-micromolar affinities, and excellent molecular specificity. Importantly, GRABDA sensors can resolve a single-electrical-stimulus evoked DA release in mouse brain slices, and detect endogenous DA release in the intact brains of flies, fish, and mice. In freely-behaving mice, GRABDA sensors readily report optogenetically-elicited nigrostriatal DA release and depict dynamic mesoaccumbens DA changes during Pavlovian conditioning or during sexual behaviors. Thus, GRABDA sensors enable spatiotemporal precise measurements of DA dynamics in a variety of model organisms while exhibiting complex behaviors.

neuroscience↗

bioRxiv2018

Inductive reasoning differs between taxonomic and thematic contexts: Electrophysiological evidence

Inductive reasoning can be performed in different contexts, but it is unclear whether the neural mechanism of inductive reasoning performed in a thematic context (e.g., panda has x, so bamboo has x) is the same as that performed in a taxonomic context (e.g., panda has x, so bear has x). In the present study, participants were required to judge whether a conclusion was acceptable or not based on its premise, for which the taxonomic or thematic distances between premise and conclusion objects were either far or near. The ERP results indicated that the effect of reasoning context (taxonomic vs. thematic) was initially observed in the P2 component; while the distance effect (far vs. near) was observed in N400 and late components. Moreover, the distance effect on thematic-based inductive reasoning was found in the frontal and frontal-central brain regions, while the distance effect in taxonomic-based inductive reasoning conditions was found in the central-parietal and parietal regions. These results support the view that inductive reasoning is performed differently under different semantic contexts.

neuroscience↗

bioRxiv2018

SLIMEr: probing flexibility of lipid metabolism in yeast with an improved constraint-based modeling framework

A recurrent problem in genome-scale metabolic models (GEMs) is to correctly represent lipids as biomass requirements, due to the numerous of possible combinations of individual lipid species and the corresponding lack of fully detailed data. In this study we present SLIMEr, a formalism for correctly representing lipid requirements in GEMs using commonly available experimental data. SLIMEr enhances a GEM with mathematical constructs where we Split Lipids Into Measurable Entities (SLIME reactions), in addition to constraints on both the lipid classes and the acyl chain distribution. By implementing SLIMEr on the consensus GEM of Saccharomyces cerevisiae, we can predict accurate amounts of lipid species, analyze the flexibility of the resulting distribution, and compute the energy costs of moving from one metabolic state to another. The approach shows potential for better understanding lipid metabolism in yeast under different conditions. SLIMEr is freely available at https://github.com/SysBioChalmers/SLIMEr.

systems biology↗

bioRxiv2018

Reduced but not Enhanced Default Mode Network Functional Connectivity in Major Depressive Disorder: Evidence from 25 Cohorts in the REST-meta-MDD Project

Major Depressive Disorder (MDD) is common and disabling, but its neural pathophysiology remains unclear. Functional brain network studies in MDD have largely had limited statistical power and data analysis approaches have varied widely. The REST-meta-MDD Project of resting-state fMRI (R-fMRI) addresses these issues. The 25 research groups in China composing the REST-meta-MDD Project contributed R-fMRI data of 1,300 patients with MDD and 1,128 normal controls (NCs). The data were preprocessed locally with a standardized protocol prior to aggregated group analyses. We focused on functional connectivity (FC) within the default mode network (DMN), frequently reported to show increased FC in MDD. We found decreased instead of increased DMN FC when comparing 848 MDDs with 794 NCs from 17 sites after data exclusion. We found FC reduction only in recurrent MDD, not in first-episode drug-naive MDD. Decreased DMN FC was associated with medication usage but not with MDD duration. DMN FC was also positively related to symptom severity but only in recurrent MDDs. Exploratory analyses also revealed alterations of local intrinsic activity in MDD. We confirmed the key role of DMN in MDD but found reduced rather than increased FC within the DMN. Future studies should test whether decreased DMN FC mediates treatment response. This manuscript announces the publicly available resting-state fMRI indices of the REST-meta-MDD consortium shared via the R-fMRI Maps Project.\n\nSIGNIFICANCE STATEMENTFunctional connectivity within the default mode network in major depressive disorder patients has been frequently reported abnormal but with contradicting directions in previous small sample size studies. By creating the REST-meta-MDD consortium containing neuroimaging data of 1,300 depressed patients and 1,128 normal controls from 25 research groups in China, we found decreased default mode network functional connectivity in depressed patients, driven by patients with recurrent depression, and associated with current medication treatment but not with disease duration. These findings suggest that default mode network functional connectivity remains a prime target for understanding the pathophysiology of depression, with particular relevance to revealing mechanisms of effective treatments.

neuroscience↗

bioRxiv2018

Lysyl oxidase inhibition drives the transdifferentiation from lung adenocarcinoma to squamous cell carcinoma in mice

LKB1 is frequently mutated in human non-small cell lung cancer (NSCLC) and Lkb1 deletion in mice triggered the lung adenocarcinoma (ADC) to squamous cell carcinoma (SCC) transdifferentiation (AST) through lysyl oxidase (LOX)-dependent extracellular matrix remodeling. Here we show that pharmacological inhibition of lysyl oxidase in KrasG12D/Trp53L/L mouse model, which is known to produce lung ADC only, triggers the ADC-to-SCC transdifferentiation independent of LKB1 status. Treatments of two different inhibitors of lysyl oxidase decrease collagen deposition and promote redox accumulation, and eventually trigger the AST. Importantly, these transited SCC show strong resistance to lysyl oxidase inhibition in stark contrast to ADC. Collectively, these findings establish a new AST mouse model independent of LKB1 inactivation status.

cancer biology↗

bioRxiv2018

metamicrobiomeR: an R package for analysis of microbiome relative abundance data using zero-inflated beta GAMLSS and meta-analysis across studies using random effect models

BackgroundThe rapid growth of high-throughput sequencing-based microbiome profiling has yielded tremendous insights into human health and physiology. Data generated from high-throughput sequencing of 16S rRNA gene amplicons are often preprocessed into composition or relative abundance. However, reproducibility has been lacking due to the myriad of different experimental and computational approaches taken in these studies. Microbiome studies may report varying results on the same topic, therefore, meta-analyses examining different microbiome studies to provide robust results are important. So far, there is still a lack of implemented methods to properly examine differential relative abundances of microbial taxonomies and to perform meta-analysis examining the heterogeneity and overall effects across microbiome studies.\n\nResultsWe developed an R package metamicrobiomeR that applies Generalized Additive Models for Location, Scale and Shape (GAMLSS) with a zero-inflated beta (BEZI) family (GAMLSS-BEZI) for analysis of microbiome relative abundance datasets. Both simulation studies and application to real microbiome data demonstrate that GAMLSS-BEZI well performs in testing differential relative abundances of microbial taxonomies. Importantly, the estimates from GAMLSS-BEZI are log(odds ratio) of relative abundances between groups and thus are comparable between microbiome studies. As such, we also apply random effects meta-analysis models to pool estimates and their standard errors across microbiome studies. We demonstrate the meta-analysis workflow and highlight the utility of our package on four studies comparing gut microbiomes between male and female infants in the first six months of life.\n\nConclusionsGAMLSS-BEZI allows proper examination of microbiome relative abundance data. Random effects meta-analysis models can be directly applied to pool comparable estimates and their standard errors to evaluate the heterogeneity and overall effects across microbiome studies. The examples and workflow using our metamicrobiomeR package are reproducible and applicable for the analyses and meta-analyses of other microbiome studies.

bioinformatics↗

bioRxiv2018

Effects of exclusive breastfeeding on infant gut microbiota: a meta-analysis across studies and populations

Literature regarding the differences in gut microbiota between exclusively breastfed (EBF) and non-EBF infants is meager with large variation in methods and results. We performed a meta-analysis of seven studies (a total of 1825 stool samples from 684 infants) to investigate effects of EBF compared to non-EBF on infant gut microbiota across different populations. In the first 6 months of life, overall bacterial diversity, gut microbiota age, relative abundances of Bacteroidetes and Firmicutes and microbial-predicted pathways related to carbohydrate metabolism were consistently increased; while relative abundances of pathways related to lipid, vitamin metabolism and detoxification were decreased in non-EBF vs. EBF infants. The perturbation in microbial-predicted pathways associated with non-EBF was larger in infants delivered by C-section than delivered vaginally. Longer duration of EBF mitigated diarrhea-associated gut microbiota dysbiosis and the effects of EBF persisted after 6 months of age. These consistent findings across vastly different populations suggest that one of the mechanisms of short and long-term benefits of EBF may be alteration in gut microbes.

microbiology↗

bioRxiv2018

Detection of race-specific resistance against Puccinia coronata f. sp. avenae in Brachypodium species

Oat crown rust caused by Puccinia coronata f. sp. avenae is the most destructive foliar disease of cultivated oat. Characterization of genetic factors controlling resistance responses to Puccinia coronata f. sp. avenae in non-host species could provide new resources for developing disease protection strategies in oat. We examined symptom development and fungal colonization levels of a collection of Brachypodium distachyon and B. hybridum accessions infected with three North American P. coronata f. sp. avenae isolates. Our results demonstrated that colonization phenotypes are dependent on both host and pathogen genotypes, indicating a role for race-specific responses in these interactions. These responses were independent of the accumulation of reactive oxygen species. Expression analysis of several defense-related genes suggested that salicylic acid and ethylene-mediated signaling, but not jasmonic acid are components of resistance reaction to P. coronata f. sp. avenae. Our findings provide the basis to conduct a genetic inheritance study to examine if effector-triggered immunity contributes to non-host resistance to P. coronata f. sp. avenae in Brachypodium species.

pathology↗

bioRxiv2018

Dectin-3 recognizes cryptococcal glucuronoxylomannan to initiate host defense against cryptococcosis

Cryptococcus neoformans and Cryptococcus gattii cause life-threatening meningoencephalitis and pneumonia in immunosuppressed and immunocompetent individuals. Given the structural differences of major polysaccharide glucuronoxylomannan (GXM) between C. neoformans and C. gattii, it remains unclear that how innate immune system recognizes GXM. Here, we report that C-type lectin receptor Dectin-3 (MCL encoded by Clec4d) is a direct receptor for GXMs from C. neoformans serotype AD (C.n-AD) and C. gattii serotype B (C.g-B). GXMs from C.n-AD and C.g-B activated both NF-{kappa}B and ERK pathways to induce the pro-inflammatory cytokine production, whereas it was completely abolished due to deficiency of Dectin-3 or its downstream adaptor protein CARD9. Upon pulmonary C.n-AD and C.g-B infection, Dectin-3- and CARD9-deficient mice were highly susceptible and showed augmented lung injury due to impairment of alveolar macrophage accumulation and killing activities. These results demonstrate that Dectin-3 contributes to host immunity against Cryptococcus infection through selectively recognizingGXM.

immunology↗

bioRxiv2018

A catalog of microbial genes from the bovine rumen reveals the determinants of herbivory

BackgroundThe rumen microbiota provides essential services to its host and, through its role in ruminant production, contributes to human nutrition and food security. A thorough knowledge of the genetic potential of rumen microbes will provide opportunities for improving the sustainability of ruminant production systems. The availability of gene reference catalogs from gut microbiomes has advanced the understanding of the role of the microbiota in health and disease in humans and other mammals. In this work, we established a catalog of reference prokaryote genes from the bovine rumen.\n\nResultsUsing deep metagenome sequencing we identified 13,825,880 non-redundant prokaryote genes from the bovine rumen. Compared to human, pig and mouse gut metagenome catalogs, the rumen is larger and richer in functions and microbial species associated with the degradation of plant cell wall material and production of methane. Genes encoding enzymes catalyzing the breakdown of plant polysaccharides showed a particularly high richness that is otherwise impossible to infer from available genomes or shallow metagenomics sequencing. The catalog expands by several folds the dataset of carbohydrate-degrading enzymes described in the rumen. Using an independent dataset from a group of 77 cattle fed 4 common dietary regimes, we found that only <0.1% of genes were shared by all animals, which contrast with a large overlap for functions, i.e. 63% for KEGG functions. Different diets induced differences in the relative abundance rather than the presence or absence of genes explaining the great adaptability of cattle to rapidly adjust to dietary changes.\n\nConclusionsThese data bring new insights into functions, carbohydrate-degrading enzymes and microbes of the rumen that is complementing the available information on microbial genomes. The catalog is a significant biological resource enabling deeper understanding of phenotypes and biological processes and will be expanded as new data is made available.

microbiology↗