Biology subjects

Tang, M.

Publications and source records attributed to Tang, M..

At least 127 records · Page 7Linked to original sources

bioRxiv2020

Mechanism of negative regulation of NF-κB by N4BP1

Many immune responses depend upon activation of NF-{kappa}B, a key transcription factor in the elicitation of a cytokine response. Here we demonstrate that N4BP1 inhibited TLR-dependent activation of NF-{kappa}B by interacting with the NF-{kappa}B signaling essential modulator (NEMO, also known as I{kappa}B kinase {gamma}) to attenuate NEMO-NEMO dimerization or oligomerization. The UBA-like (ubiquitin associated-like) and CUE-like (ubiquitin conjugation to ER degradation) domains in N4BP1 mediated the interaction with the NEMO COZI domain. Both in vitro and in mice, N4bp1 deficiency specifically enhanced TRIF-independent (TLR2, TLR7, or TLR9-mediated), but not TRIF-dependent (TLR3 or TLR4-mediated), NF-{kappa}B activation leading to increased production of proinflammatory cytokines. In response to TLR4 or TLR3 activation, TRIF caused activation of caspase 8, which cleaved N4BP1 distal to residues D424 and D490 and abolished its inhibitory effect. N4bp1-/- mice also exhibited diminished numbers of T cells in the peripheral blood. Our work identifies N4BP1 as an inhibitory checkpoint protein that must be overcome to activate NF-{kappa}B, and a TRIF-initiated caspase 8-dependent mechanism by which this is accomplished.

immunology↗

bioRxiv2020

Proteomics study of colorectal cancer and adenomatous polyps identifies TFR1, SAHH, and HV307 as potential biomarkers for screening

Colorectal cancer (CRC) is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions will promote early medical intervention and treatment, thus reducing morbidity and mortality. Proteins are generally considered key biomarkers of cancer. Herein, we performed a quantitative, tissue-original proteomics study in a cohort of ninety patients from pre-cancerous to cancerous conditions by liquid chromatography-tandem mass spectrometry. A total of 134,812 peptides, 8,697 proteins, 2,355 (27.08%) union differentially expressed proteins (DEPs), and 409 shared DEPs (compared with adjacent tissues) were identified. The number of DEPs showed a positive correlation with increasing severity of illness. The union and shared DEPs were both enriched in the KEGG pathway of focal adhesion, metabolism of xenobiotics by cytochrome P450, and drug metabolism - cytochrome P450. Among the 2,355 union DEPs, 32 were selected for identification and validation by multiple reaction monitoring from twenty plasma specimens. Of these, three proteins, transferrin receptor protein 1 (TFR1), adenosylhomocysteinase (SAHH), and immunoglobulin heavy variable 3-7 (HV307), were significantly differentially expressed and displayed the same expression pattern in plasma as observed in the tissue data. In conclusion, TFR1, SAHH, and HV307 may be considered as potential biomarkers for screening of CRC. SignificanceCRC is a malignant tumour with high morbidity and mortality worldwide. Efficient screening strategies for CRC and pre-cancerous lesions can play an important role in addressing the issue of high morbidity and mortality. Screening of molecular biomarkers provide a non-invasive, cost-effective and effective approach. Proteins are generally considered key molecular biomarkers of cancer. Our study reports a quantitative proteomics analysis of protein biomarkers for colorectal cancer (CRC) and adenomatous polyps and identifies TFR1, SAHH, and HV307 as potential biomarkers for screening. The research makes a significant contribution to the literature because whereas mass spectrometry-based proteomics research has been widely used for clinical research, its application to clinical translation is lacking as parallel specimens ranging from pre-cancerous to cancerous tissues, according to the degree of disease progression, have not been readily assessed.

biochemistry↗

bioRxiv2020

Co-infection of influenza A virus enhances SARS-CoV-2 infectivity

The upcoming flu season in the northern hemisphere merging with the current COVID-19 pandemic raises a potentially severe threat to public health. Through experimental co-infection of IAV with either pseudotyped or SARS-CoV-2 live virus, we found that IAV pre-infection significantly promoted the infectivity of SARS-CoV-2 in a broad range of cell types. Remarkably, increased SARS-CoV-2 viral load and more severe lung damage were observed in mice co-infected with IAV in vivo. Moreover, such enhancement of SARS-CoV-2 infectivity was not seen with several other viruses probably due to a unique IAV segment as an inducer to elevate ACE2 expression. This study illustrates that IAV has a special nature to aggravate SARS-CoV-2 infection, and prevention of IAV is of great significance during the COVID-19 pandemic.

microbiology↗

bioRxiv2020

Genomic features underlying the evolutionary transitions of Apibacter to honey bee gut symbionts

The symbiotic bacteria associated with honey bee gut have likely transformed from a free-living or parasitic lifestyle, through a close evolutionary association with the insect host. However, little is known about the genomic mechanism underlying bacterial transition to exclusive adaptation to the bee gut. Here we compared the genomes of bee gut symbionts Apibacter with their close relatives living in different lifestyles. We found that despite of general reduction in the Apibacter genome, genes involved in amino acid synthesis and monosaccharide detoxification were retained, which were likely beneficial to the host. Interestingly, the microaerobic Apibacter species have specifically acquired genes encoding for the nitrate respiration (NAR). The NAR system is also conserved in the cohabiting bee microbe Snodgrassella, although with a differed structure. This convergence implies a crucial role of respiratory nitrate reduction for microaerophilic microbiomes to colonize bee gut epithelium. Genes involved in lipid, histidine degradation are substantially lost in Apibacter, indicating a transition of the energy source utilization. Particularly, genes involved in the phenylacetate degradation to generate host toxic compounds, as well as other virulence factors were lost, suggesting the loss of pathogenicity. Antibiotic resistance genes were only sporadically distributed among Apibacter species, but condensed in their pathogenic relatives, which may be related to the remotely living feature and less exposure to antibiotics of their bee hosts. Collectively, this study advances our understanding of genomic transition underlying specialization in bee gut symbionts. ImportanceInvestigations aiming to uncover the genetic determinants underlying the transition to a gut symbiotic lifestyle were scarce. The vertical transmitted honey bee gut symbionts of genus Apibacter provided an rare opportunity to tackle this, as evolving from family Flavobacteriaceae, they had phylogenetic close relatives living various lifestyles. Here, we documented that Apibacter have both preserved and horizontally acquired host beneficial genes including monosaccharides detoxification that may have seeded a mutualistic relationship with the host. In contrast, multiple virulence factors and antibiotic resistance genes have been lost. Importantly, an highly efficient and genomic well organized respiratory nitrate reduction pathway is conserved across all Apibacter spp., as well as in majority of Snodgrassella, which colonize the same habitat as Apibacter, suggesting an crucial role it played in living inside the gut. These findings highlight genomic changes paving ways to the transition to a honey bee gut symbiotic lifestyle.

genetics↗

bioRxiv2020

HieRFIT: Hierarchical Random Forest for Information Transfer

The emergence of single-cell RNA sequencing (scRNA-seq) has led to an explosion in novel methods to study biological variation among individual cells, and to classify cells into functional and biologically meaningful categories. Here, we present a new cell type projection tool, HieRFIT (Hierarchical Random Forest for Information Transfer), based on hierarchical random forests. HieRFIT uses a priori information about cell type relationships to improve classification accuracy, taking as input a hierarchical tree structure representing the class relationships, along with the reference data. We use an ensemble approach combining multiple random forest models, organized in a hierarchical decision tree structure. We show that our hierarchical classification approach improves accuracy and reduces incorrect predictions especially for inter-dataset tasks which reflect real life applications. We use a scoring scheme that adjusts probability distributions for candidate class labels and resolves uncertainties while avoiding the assignment of cells to incorrect types by labeling cells at internal nodes of the hierarchy when necessary. Using HieRFIT, we re-analyzed publicly available scRNA-seq datasets showing its effectiveness in cell type cross-projections with inter/intra-species examples. HieRFIT is implemented as an R package and it is available at (https://github.com/yasinkaymaz/HieRFIT/releases/tag/v1.0.0)

bioinformatics↗

bioRxiv2020

Chromatin State Dynamics Confers Specific Therapeutic Strategies in Enhancer Subtypes of Colorectal Cancer

The extent and function of chromatin state aberrations during colorectal cancer (CRC) progression is not completely understood. Here, by comprehensive epigenomic characterization of 56 tumors, adenomas, and their matched normal tissues, we define the dynamics of chromatin states during the progression of colorectal cancer. H3K27ac-marked active enhancer state could distinguish between different stages of CRC progression. By epigenomic editing, we present evidence that gains of tumor-specific enhancers for crucial oncogenes, such as ASCL2 and FZD10, was crucial for excessive proliferation. Consistently, combination of MEK plus bromodomain (BET) inhibition was found to have synergistic effects in CRC patient-derived xenograft (PDX) models. Probing inter-tumor heterogeneity, we identified four distinct enhancer subtypes (EpiC), three of which correlate well with previously defined transcriptomic subtypes (CMSs). Importantly, CMS2 can be divided into two EpiC subgroups with significant survival differences. Leveraging such correlation, we devised a combinatorial therapeutic strategy of enhancer-blocking bromodomain inhibitors with pathway-specific inhibitors (PARPi, EGFRi, and TGF{beta}i) for three EPIC groups. Our data suggest that the dynamics of active enhancer underlies colorectal cancer progression and the patient-specific active enhancer patterns govern their unique gene expression patterns which can be leveraged for precision combination therapy.

cancer biology↗

bioRxiv2020

Genetically Determined Strength of Natural Killer Cells is Enhanced by Adaptive HLA class I Admixture in East Asians

Human natural killer (NK) cells are essential for controlling infection, cancer and fetal development. NK cell functions are modulated by interactions between polymorphic inhibitory killer cell immunoglobulin-like receptors (KIR) and polymorphic HLA-A, -B and -C ligands expressed on tissue cells. All HLA-C alleles encode a KIR ligand and contribute to reproduction and immunity. In contrast, only some HLA-A and -B alleles encode KIR ligands and they focus on immunity. By high-resolution analysis of KIR and HLA-A, -B and -C genes, we show that the Chinese Southern Han are significantly enriched for interactions between inhibitory KIR and HLA-A and -B. This enrichment has had substantial input through population admixture with neighboring populations, who contributed HLA class I haplotypes expressing the KIR ligands B*46:01 and B*58:01, which subsequently rose to high frequency by natural selection. Consequently, over 80% of Southern Han HLA haplotypes encode more than one KIR ligand. Complementing the high number of KIR ligands, the Chinese Southern Han KIR locus combines a high frequency of genes expressing potent inhibitory KIR, with a low frequency of those expressing activating KIR. The Southern Han centromeric KIR region encodes strong, conserved, inhibitory HLA-C specific receptors, and the telomeric region provides a high number and diversity of inhibitory HLA-A and -B specific receptors. In all these characteristics, the Southern Han represent other East Asians, whose NK cell repertoires are thus enhanced in quantity, diversity and effector strength, likely through natural selection for resistance to endemic viral infections.

immunology↗

bioRxiv2020

Single-cell multimodal glioma analyses reveal epigenetic regulators of cellular plasticity and environmental stress response

Glioma intratumoral heterogeneity enables adaptation to challenging microenvironments and contributes to universal therapeutic resistance. Here, we integrated 914 single-cell DNA methylomes, 55,284 single-cell transcriptomes, and bulk multi-omic profiles across 11 adult IDH-mutant or IDH-wild-type gliomas to delineate sources of intratumoral heterogeneity. We found that local DNA methylation instability, or epimutation burden, was elevated in more aggressive tumors, reflected intratumoral variability, linked with transcriptional disruption, and associated with environmental stress response. We show that the activation of cell-state specific transcription factors is impacted by epimutations and that loosened epigenetic control may facilitate cellular plasticity. Our analyses support that somatic copy number alterations (SCNAs) promote epigenetic instability and that SCNAs largely precede epigenetic and transcriptomic diversification during glioma evolution. We confirmed the link between genetic and epigenetic instability by analyzing larger cohorts of bulk longitudinally collected and spatially separated DNA methylation data. Increased DNA methylation instability was associated with accelerated disease progression, and recurrently selected DNA methylation changes were enriched for environmental stress response pathways. Our work provides an integrative framework to better understand glioma evolution and highlights the importance of epigenetic heterogeneity in shaping therapeutic response.

cancer biology↗

bioRxiv2020

High-Accuracy Multiplexed SARS-CoV-2 Antibody Assay with Avidity and Saliva Capability on a Nano-Plasmonic Platform

The outbreak and rapid spread of SARS-CoV-2 virus has led to a dire global pandemic with millions of people infected and ~ 400,000 deaths thus far. Highly accurate detection of antibodies for COVID-19 is an indispensable part of the effort to combat the pandemic1,2. Here we developed two-plex antibody detection against SARS-CoV-2 spike proteins3 (the S1 subunit and receptor binding domain RBD) in human serum and saliva on a near-infrared nano-plasmonic gold (pGOLD) platform4-8. By testing nearly 600 serum samples, pGOLD COVID-19 assay achieved ~ 99.78 % specificity for detecting both IgG and IgM with 100 % sensitivity in sera collected > 14 days post disease symptom onset, with zero cross-reactivity to other diseases. Two-plex correlation analysis revealed higher binding of serum IgM to RBD than to S1. IgG antibody avidity toward multiple antigens were measured, shedding light on antibody maturation in COVID-19 patients and affording a powerful tool for differentiating recent from remote infections and identifying re-infection by SARS-CoV-2. Just as important, due to high analytical sensitivity, the pGOLD COVID-19 assay detected minute amounts of antibodies in human saliva, offering the first non-invasive detection of SARS-CoV-2 antibodies.

biochemistry↗

bioRxiv2020

Evaluating single-cell cluster stability using the Jaccard similarity index

MotivationOne major goal of single-cell RNA sequencing (scRNAseq) experiments is to identify novel cell types. With increasingly large scRNAseq datasets, unsupervised clustering methods can now produce detailed catalogues of transcriptionally distinct groups of cells in a sample. However, the interpretation of these clusters is challenging for both technical and biological reasons. Popular clustering algorithms are sensitive to parameter choices, and can produce different clustering solutions with even small changes in the number of principal components used, the k nearest neighbor, and the resolution parameters, among others. ResultsHere, we present a set of tools to evaluate cluster stability by subsampling, which can guide parameter choice and aid in biological interpretation. The R package scclusteval and the accompanying Snakemake workflow implement all steps of the pipeline: subsampling the cells, repeating the clustering with Seurat, and estimation of cluster stability using the Jaccard similarity index. The Snakemake workflow takes advantage of high-performance computing clusters and dispatches jobs in parallel to available CPUs to speed up the analysis. The scclusteval package provides functions to facilitate the analysis of the output, including a series of rich visualizations. AvailabilityR package scclusteval: https://github.com/crazyhottommy/scclusteval Snakemake workflow: https://github.com/crazyhottommy/pyflow_seuratv3_parameter Contacttsackton@g.harvard.edu, tangming2005@gmail.com Supplementary informationSupplementary data are available at Bioinformatics online.

bioinformatics↗

bioRxiv2020

Single-cell RNA-sequencing of peripheral neuroblastic tumors reveals an aggressive transitional cell state at the junction of an adrenergic-mesenchymal transdifferentiation trajectory

Peripheral neuroblastic tumors (PNTs) are the most common extracranial solid tumors in early childhood. They represent a spectrum of neural crest derived tumors including neuroblastoma, ganglioneuroblastoma and ganglioneuroma. PNTs exhibit heterogeneity due to interconverting malignant cell states described as adrenergic/nor-adrenergic or mesenchymal/neural crest cell in origin. The factors determining individual patient levels of tumor heterogeneity, their impact on the malignant phenotype, and the presence of other cell states are unknown. Here, single-cell RNA-sequencing analysis of 4267 cells from 7 PNTs demonstrated extensive transcriptomic heterogeneity. Trajectory modelling showed that malignant neuroblasts move between adrenergic and mesenchymal cell states via a novel state that we termed a "transitional" phenotype. Transitional cells are characterized by gene expression programs linked to a sympathoadrenal development, and aggressive tumor phenotypes such as rapid proliferation and tumor dissemination. Among primary bulk tumor patient cohorts, high expression of the transitional gene signature was highly predictive of poor prognosis when compared to adrenergic and mesenchymal expression patterns. High transitional gene expression in neuroblastoma cell lines identified a similar transitional H3K27-acetylation super-enhancer landscape, supporting the concept that PNTs have phenotypic plasticity and transdifferentiation capacity. Additionally, examination of PNT microenvironments, found that neuroblastomas contained low immune cell infiltration, high levels of non-inflammatory macrophages, and low cytotoxic T lymphocyte levels compared with more benign PNT subtypes. Modeling of cell-cell signaling in the tumor microenvironment predicted specific paracrine effects toward the various subtypes of malignant cells, suggesting further cell-extrinsic influences on malignant cell phenotype. Collectively, our study reveals the presence of a previously unrecognized transitional cell state with high malignant potential and an immune cell architecture which serve both as potential biomarkers and therapeutic targets.

cancer biology↗

bioRxiv2020

Anethole dithiolethione improves liver fatty acid metabolism in hamster fed high-fat diets

"Lipotoxicity" induced by excessive accumulation of free fatty acids (FFAs) in the liver, especially saturated FAs and their toxic metabolites, is closely related to metabolic diseases such as nonalcoholic fatty liver disease (NAFLD). Hydrogen sulfide (H2S), a novel gaseous signaling molecule, has been reported to have lipid-lowering effects, but its effect on FAs metabolism remains unclear. The purpose of this study was to investigate the effect and mechanisms of anethole dithiolethione (ADT, a sustained-release H2S donor) on hepatic FAs metabolism. ADT was administered daily for 4 weeks in male Syrian golden hamsters fed a high fat diet (HFD), and FAs profiles of liver tissues were analyzed using GC-MS. The results showed that in HFD-fed hamsters, ADT treatment significantly reduced the accumulation of saturated and monounsaturated fatty acids (C16:0, C18:0, C16:1, and C18:1n9), while increased the content of n-6 and n-3 series polyunsaturated fatty acids (C20:3n6, C20:4n6, and C22:6n3). Mechanistically, ADT obviously inhibited the overexpression of ACC1, FAS and SCD1, and up-regulated the levels of FATPs, L-FABP, CPT1, FADS1 and FADS2. Notably, ADT evidently induced Mitofusin1 to facilitate mitochondrial fusion and optimize {beta}-oxidation. These findings suggest that ADT plays a beneficial role by regulating the synthesis, desaturation, {beta}-oxidation, uptake, binding/isolation, and transport of FAs. In conclusion, ADT is effective in improving liver FAs metabolic disorders and liver injuries caused by HFD.

pharmacology and toxicology↗

bioRxiv2019

Out of the Qinghai-Tibetan Plateau and get flourishing - the evolution of Neodon voles (Rodentia: Cricetidae) revealed by systematic sampling and low coverage whole genome sequencing

Neodon, genus of a short time evolutionary history, was reported to be diverged from its relatives in early stage of Pleistocene. Only 4 species were well documented in Neodon for a long period of time until last years when a systematic work described and added three new species, adjusted three species used to belong to Lasiopodomys, Phaiomys, Microtus to Neodon and removed one species (Neodon juldaschi) to genus Blanfordimys, leading to a total of eight species recorded in Neodon. To gain a better insight into the phylogeny and ecology of Neodon, we have systematically sampled Neodon species along the whole Hengduan and Himalayan Mountains in the last 20 years. In addition to morphological identification, we generated 1x - 15x whole genome sequencing (WGS) data and achieved the mitochondrial genomes and an average of 5,382 nuclear genes for each morpho-species. Both morphology and phylogeny results supported an extra six new species in Neodon (nominated Neodon shergylaensis sp. nov., N. namchabarwaensis sp. nov., N. liaoruii sp. nov., N. chayuensis sp. nov., N. bomiensis sp. nov., and N. bershulaensis sp. nov.). This is the first study that included Neodon samples covering its entire distribution area in China and this systematic sampling also revealed a long-time underestimation of Neodons diversity, and suggested its speciation events linked highly to founder event via dispersal (from Plateau to surrounding mountains). The results also revealed that the Qinghai-Tibetan Plateau is the center of origin of Neodon, and the impetus of speciation include climate change, isolation of rivers and mountains.

zoology↗

bioRxiv2019

C17orf53 defines a novel pathway involved in inter-strand crosslink repair

ATR kinase is a master regulator of genome maintenance and participates in DNA replication and various DNA repair pathways. In a genome-wide screening for ATR-dependent fitness genes, we identified a previously uncharacterized gene, C17orf53, whose loss led to hypersensitivity to ATR inhibition. C17orf53 is conserved in vertebrate and is required for efficient cell proliferation. Loss of C17orf53 slowed down DNA replication and led to pronounced ICL repair defect. Further genetic analyses revealed that C17orf53 functions downstream in ICL repair pathway, probably by affecting the loading of repair factors such as RAD54. In addition, we showed that C17orf53 is a ssDNA- and RPA-binding protein, both of which are important for its functions in the cell. Taken together, C17orf53 is a novel component involved in ICL repair pathway.

biochemistry↗

bioRxiv2019

Bivalent and Broad Chromatin Domains Regulate Pro-metastatic Drivers in Melanoma

Chromatin deregulation is an emerging hallmark of cancer. However, the extent of epigenetic aberrations during tumorigenesis and their relationship with genetic aberrations are poorly understood. Using ChIP-sequencing for enhancers (H3K27ac and H3K4me1), promoters (H3K4me3), active transcription (H3K79me2) and polycomb (H3K27me3) or heterochromatin (H3K9me3) repression we generated chromatin state profiles in metastatic melanoma using 46 tumor samples and cell lines. We identified a strong association of NRAS, but not BRAF mutations, with bivalent states harboring H3K4me3 and H3K27me3 marks. Importantly, the loss and gain of bivalent states occurred on important pro-metastasis regulators including master transcription factor drivers of mesenchymal phenotype including ZEB1, TWIST1, SNAI1 and CDH1. Unexpectedly, a subset of these and additional pro-metastatic drivers (e.g. POU3F2, SOX9 and PDGFRA) as well as melanocyte-specific master regulators (e.g. MITF, ZEB2, and TFAP2A) were regulated by exceptionally wide H3K4me3 domains that can span tens of thousands of kilobases suggesting roles of this new epigenetic element in melanoma metastasis. Overall, we find that BRAF, NRAS and WT melanomas may use bivalent states and broad H3K4me3 domains in a specific manner to regulate pro-metastatic drivers. We propose that specific epigenetic traits - such as bivalent and broad domains - get assimilated in the epigenome of pro-metastatic clones to drive evolution of cancer cells to metastasis.

cancer biology↗

bioRxiv2019

Epistatic Transcription Factor Networks Differentially Modulate Arabidopsis Growth and Defense

Plants integrate internal and external signals to finely coordinate growth and defense allowing for maximal fitness within a complex environment. One common model for the relationship between growth and defense is a trade-off model in which there is a simple negative interaction between growth and defense theoretically driven by energy costs. However, there is a developing consensus that the coordination of growth and defense likely involves a more conditional and intricate connection. To explore how a transcription factor network may coordinate growth and defense, we used high-throughput phenotyping to measure growth and flowering in a set of single and pairwise mutants previously linked to the aliphatic glucosinolate defense pathway. Showing the link between growth and aliphatic glucosinolate defense, 17 of the 20 tested TFs significantly influence plant growth and/or flowering time. These effects were conditional upon the environment, age of the plant and more critically varied amongst the phenotypes when using the same genotype. The phenotypic effects of the TF mutants on SC GLS accumulation and on growth did not display a simple correlation, supporting the coordination model. We propose that large transcription factor networks create a system to integrate internal and external signals and separately modulate growth and the accumulation of the defensive aliphatic GLS.

plant biology↗

bioRxiv2019

Auxin-sensitive Aux/IAA proteins mediate drought tolerance in Arabidopsis by regulating glucosinolate levels

A detailed understanding of abiotic stress tolerance in plants is essential to provide food security in the face of increasingly harsh climatic conditions. Glucosinolates (GLSs) are secondary metabolites found in the Brassicaceae that protect plants from herbivory and pathogen attack. Here we report that in Arabidopsis, aliphatic GLS levels are regulated by the auxin-sensitive Aux/IAA repressors IAA5, IAA6, and IAA19. These proteins act in a transcriptional cascade that maintains expression of GLS levels when plants are exposed to drought conditions. Loss of IAA5/6/19 results in reduced GLS levels and decreased drought tolerance. Further, we show that this phenotype is associated with a defect in stomatal regulation. Application of GLS to the iaa5,6,19 mutants restores stomatal regulation and normal drought tolerance. GLS action is dependent on the receptor kinase GHR1, suggesting that GLS may signal via reactive oxygen species. These results provide a novel connection between auxin signaling, GLS levels and drought response.\n\nOne Sentence SummaryAux/IAA proteins promote drought tolerance by regulating glucosinolate levels.

plant biology↗

bioRxiv2019

The differential distribution of bacteria between cancerous and noncancerous ovarian tissues in situ

The female upper reproductive tract, including the uterus, fallopian tubes and ovaries, is believed to be a sterile environment. With the improvement of bacterial detection, the theory of the sterile female upper reproductive tract has been frequently challenged in recent years. However, thus far, no researchers have used ovaries as study targets. Six women who were diagnosed with ovarian cancer were included in the cancer group, and ten women who were diagnosed with a noncancerous ovarian condition (including three patients with uterine myoma and seven patients with uterine adenomyosis) were included in the control group. Immunohistochemistry staining using an antibacterial lipopolysaccharide (LPS) antibody was used to confirm the presence of bacteria in the ovarian tissues. In addition, 16S rRNA sequencing was used to compare the differences in the bacteria between ovarian cancer tissues and noncancerous ovarian tissues. BugBase and Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) were used to predict the functional composition of the bacteria. Bacterial LPS was present in ovarian cancer tissue and noncancerous ovarian tissue, which implied the presence of bacteria in ovarian tissue. When compared to the noncancerous ovarian bacteria at the phylum level, the cancerous ovarian bacteria were composed of increased Aquificae and Planctomycetes and decreased Crenarchaeota. When predicting metagenomes, gene functions associated with the potentially pathogenic and the oxidative stress-tolerant phenotype were enriched in the ovaries of the cancer group. Forty-six significantly different KEGG pathways existed in the ovarian bacteria of the cancer group compared to that of the control group. Different bacteria compositions were present in cancerous and noncancerous ovarian tissues. Author summaryAbdominal solid viscera have always been believed to be absolutely sterile. With the improvement of bacterial detection, this concept is being challenged. Researchers found some bacteria existed in endometrial diseases, the question of whether the ovaries are sterile is still unclear. Therefore, we assume that the bacteria in ovarian tissue are associated with ovarian cancer. When compared to the noncancerous ovarian bacteria at the phylum level, the cancerous ovarian bacteria were composed of increased Aquificae and Planctomycetes and decreased Crenarchaeota. When predicting metagenomes, gene functions associated with the potentially pathogenic and the oxidative stress-tolerant phenotype were enriched in the ovaries of the cancer group. Forty-six significantly different KEGG pathways existed in the ovarian bacteria of the cancer group compared to that of the control group. Different bacteria compositions were present in cancerous and noncancerous ovarian tissues.

microbiology↗