Biology subjects

Xu, G.

Publications and source records attributed to Xu, G..

At least 127 records · Page 7Linked to original sources

bioRxiv2020

Seneca Valley virus intercellular transmission mediated by exosomes

Exosomes are cup-shaped vesicles that are secreted by cells and are involved in the intercellular transport of a variety of substances, including proteins, RNA, and liposomes. Studies have shown that pathogenic microorganisms are contained in exosomes extracted from pathogenic micro-infected cells. The Seneca Valley virus (SVV) is a non-encapsulated single-stranded positive-strand RNA virus that causes ulceration in the pigs nose, the appearance of blisters, and other clinical symptoms similar to foot-and-mouth disease (FMD). Whether exosomes from SVV-infected cells can mediate SVV intercellular transmission is of great significance. There have been no studies showing whether exosomes can carry SVV in susceptible and non-susceptible cells. Here, we first extracted and identified exosomes from SVV-infected IBRS-2 cells. It was confirmed that replication of SVV can be inhibited when IBRS-2 cells treated with exosomes inbihitor GW4869. Furthermore, laser confocal microscopy and qRT-PCR experiments were performed to investigate whether exosomes can carry SVV and enable the virus to proliferate in susceptible and non-susceptible cells. Finally, exosome-mediated intercellular transmission can not be completely blocked by SVV-specific neutralizing antibodies. Taken together, this study showed that exosomes extracted from the SVV-infected IBRS-2 cells can carry SVV and transmit productive SVV infection between SVV susceptible and non-susceptible cells, this transmit infection is resistant to SVV specific neutralization antibody. IMPORTANCEExosomes participate in intercellular communnication between cells. Exosomes derived from virus-infected cells can mediate virus transmission or/and regulate immune response. However, the function of exosomes that from SVV-infected host cells during SVV transmission is unclear. Here, we demonstrate SVV can utilize host exosomes to establish productive infection in intercellular transmission. Furthermore, exosome-mediated SVV transmission is resistant to SVVV-specific neutralizing antibodies. This discovery sheds light on neutralizing antibodies resistant to SVVV transmission by exosomes as a potential immune evasion mechanism.

immunology↗

bioRxiv2020

Clinically applicable histopathological diagnosis system for gastric cancer detection using deep learning

Gastric cancer is among the most malignant tumours with the highest incidence and mortality rates. The early detection and accurate histopathological diagnosis of gastric cancer are essential factors that can help increase the chances of successful treatment. While the worldwide shortage of pathologists has imposed burdens on current histopathology services, it also offers a unique opportunity for the use of artificial intelligence assistance systems to alleviate the workload and increase diagnostic accuracy. To the best of our knowledge, there has not been a clinically applicable histopathological assistance system with high accuracy that can generalize to whole slide images created with diverse digital scanner models from different hospitals. Here, we report a clinically applicable artificial intelligence assistance system developed at the Chinese PLA General Hospital, China, using a deep convolutional neural network trained with 2,123 pixel-level annotated H&E-stained whole slide images. The model achieved a sensitivity near 100% and an average specificity of 80.6% on a real-world test dataset, which included 3,212 whole slide images digitalized with three scanner models. We showed that the system could aid pathologists in improving diagnostic accuracy and preventing misdiagnoses. Moreover, we demonstrated that our system could perform robustly with 1,582 whole slide images from two other medical centres. Our study suggests the feasibility and benefits of using histopathological artificial intelligence assistance systems in routine practice scenarios.Competing Interest StatementXiaoqing Zhang is the founder of Thorough Images. Shuhao Wang is the co-founder and chief technology officer (CTO) of Thorough Images. Calvin Ku, Cancheng Liu, Zhuo Sun, Gang Xu, Yuefeng Wang are algorithm researchers of Thorough Images. All remaining authors have declared no conflicts of interest.View Full Text

pathology↗

bioRxiv2020

Alteration of fecal microbial compositions and bacterial taxa in female osteoporotic patients

BackgroundGut microbiota, mainly characterized by fecal bacterial compositions, affects human immune system and pathophysiological development. Our aim was to measure the quantitative differences of fecal bacterial compositions between osteoporotic patients and healthy subjects, and to identify novel bacterial taxa that speculate the incidence of osteoporosis in female. MethodWe recruited 104 female subjects, including 45 osteoporotic individuals and 59 healthy control. Fecal samples were collected for further analysis by 16S rRNA quantitative arrays and bioinformatics analysis. ResultsAnalyses of - and {beta}-diversity demonstrated that the diversity and composition of fecal bacterial compositions were both significant different in osteoporosis group, as compared with healthy group. Multiple bacterial genera were significantly increased (e.g., Roseburia and Bacteroides) or decreased (e.g., Streptococcus and Dorea) in the osteoporotic cases. Furthermore, the osteoporosiscould be efficiently determined by the random forest model based on differential taxa (area under ROC curve = 0.93). ConclusionThere were obvious different fecal microbial characteristics between female osteoporosis and healthy subjects. These findings provided evidence for understanding the host-gut microbiota interplay in female osteoporosis, and supported clinical applications of gut microbiota analysis for female osteoporosis diagnosis

microbiology↗

bioRxiv2019

α-ketoglutaric acid stimulates muscle hypertrophy and fat loss through OXGR1-dependent adrenal activation

Beneficial effects of resistance exercise on metabolic health and particularly muscle hypertrophy and fat loss are well established, but the underlying chemical and physiological mechanisms are not fully understood. Here we identified a myometabolite-mediated metabolic pathway that is essential for the beneficial metabolic effects of resistance exercise in vivo. We showed that substantial accumulation of the tricarboxylic acid cycle intermediate -ketoglutaric acid (AKG) is a metabolic signature of resistance exercise performance. Interestingly, human plasma AKG level is also negatively correlated with BMI. Pharmacological elevation of circulating AKG induces muscle hypertrophy, brown adipose tissue (BAT) thermogenesis, and white adipose tissue (WAT) lipolysis in vivo. We further found that AKG stimulates the adrenal release of adrenaline through 2-oxoglutarate receptor 1 (OXGR1) expressed in adrenal glands. Finally, by using both loss-of-function and gain-of-function mouse models, we showed that OXGR1 is essential for AKG-mediated exercise-induced beneficial metabolic effects. These findings reveal an unappreciated mechanism for the salutary effects of resistance exercise, using AKG as a systemically-derived molecule for adrenal stimulation of muscle hypertrophy and fat loss.

molecular biology↗

bioRxiv2019

Role of Chemokine and TNF signaling pathway in oral squamous cell carcinoma: A RNA deep sequencing analysis of oral buccal mucosa squamous carcinoma model of Chinese hamster

Oral cancer is one of the most common cancers in the world, meanwhile, differentially expressed genes are thought to regulate the development and progression of oral squamous cell carcinomas (OSCC). In this study we screened RNA transcripts from the oral buccal mucosa of healthy male Chinese hamster, divided into 3 groups: a control group with no disposal, a solvent control group coated with acetone solvent, and an experimental group coated with 0.5% DMBA acetone solution by high-throughput RNA sequencing. Tophat and Bowtie were used to align the high-quality reads into transcripts, DEseq was used to analysis the expression of differential gene. Then, the Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted. The chemokine and TNF signaling pathway were differentially expression and the mRNA expression of CXCL1, CXCL2, CXCL3, CCL7, MMP9, monitored by qRT-PCR, increased remarkably in the cancer group and coincided with the result of RNA-Sequencing. Meanwhile, the CXCL1, CXCL2, CXCL3, and CCL7 are significantly enriched in the chemokine signaling pathway, and CXCL1, CXCL2, CXCL3, and MMP9 are significantly enriched in the tumor necrosis factor (TNF) signaling pathway. The differentially expression of the chemokine and TNF signaling pathway was a response to the invasion of the organism immune system due to oral buccal mucosa squamous carcinoma. All the findings provided novel insights for further molecular researches of oral cancer.

molecular biology↗

bioRxiv2019

Hormone Levels Are Related to Altered Functional Connectivity in Prolactinomas

Background and ObjectiveProlactinomas may cause drastic hormone fluctuations throughout the body. It is not fully understood how endogenous hormone disorders such as prolactinomas reshape the patients brain. By employing the resting-state functional magnetic resonance imaging technique, we aimed to investigate the whole-brain functional connectivity (FC) and its relationship with hormone levels in patients with prolactinomas.\n\nMethodsUsing whole-brain and seed-based functional connectivity analyses, we compared FC metrics between 33 prolactinoma patients and 31 healthy controls matched with age, sex, and handedness. Then we performed partial correlation analysis to examine the relationship between FC metrics and hormone levels.\n\nResultsCompared to healthy controls, we found that prolactinoma patients showed significantly increased thalamocortical (visual cortex) and cerebellar-cerebral connectivity. In addition, endogenous hormone levels were positively correlated with the increased FC, and the hormone-FC relationships showed sex difference in prolactinoma patients.\n\nConclusionsOur findings are the first to reveal the altered FC patterns and sex-dependent hormone-FC relationships in prolactinoma patients, indicating the important role of hormone levels in the neural mechanism of brain reorganization and hyperactive intrinsic connections in prolactinomas.

neuroscience↗

bioRxiv2019

Comparative investigation into formycin A and pyrazofurin A biosynthesis reveals branch pathways for the construction of C-nucleoside scaffolds

Formycin A (FOR-A) and pyrazofurin A (PRF-A) are purine-related C-nucleoside antibiotics, in which ribose and a pyrazole-derived base are linked by a C-glycosidic bond, however, the logic underlying the biosynthesis of these molecules has remained largely unexplored. Here, we report the discovery of the pathways for FOR-A and PRF-A biosynthesis from diverse actinobacteria, and demonstrate that their biosynthesis is initiated by a lysine N6-monooxygenase. Moreover, we show that the forT and prfE (individually related to FOR-A and PRF-A biosynthesis) mutants are correspondingly capable of accumulating the unexpected pyrazole-related intermediates, compound 11 and 9a. We also decipher the enzymatic basis of ForT/PrfE for the C-glycosidic bond formation in FOR-A/PRF-A biosynthesis. To our knowledge, ForT/PrfE represents the first example of {beta}-RFA-P ({beta}-ribofuranosyl-aminobenzene 5-phosphate) synthase-like enzymes governing C-nucleoside scaffold construction in natural product biosynthesis. These data establish a foundation for combinatorial biosynthesis of related purine nucleoside antibiotics, and also open the way for target-directed genome mining of PRF-A/FOR-A related antibiotics.\n\nIMPORTANCEFormycin A (FOR-A) and pyrazofurin A (PRF-A) are well known for their unusual chemical structures and remarkable biological activities. Actually, deciphering FOR-A/PRF-A biosynthesis will not only expand biochemical repertoire for novel enzymatic reactions, but also permit the target-oriented genome mining of FOR-A/PRF-A related C-nucleoside antibiotics.

biochemistry↗

bioRxiv2019

uORFlight: a vehicle towards uORF-mediated translational regulation mechanisms in eukaryotes

Upstream open reading frames (uORFs) are prevalent in eukaryotic mRNAs. They act as a translational control element for precisely tuning the expression of the downstream major open reading frame (mORF) with essential cellular functionalities. uORF variation has been clearly associated with several human diseases. In contrast, natural uORF variants in plants have not ever been identified or linked with any phenotypic changes. The paucity of such evidence encouraged us to generate this database-uORFlight (http://uorflight.whu.edu.cn). It facilitates the exploration of uORF variation among different splicing models of Arabidopsis and rice genes. Most importantly, users can evaluate uORF frequency among different accessions at the population scale and find out the causal single nucleotide polymorphism (SNP) or insertion/deletion (INDEL) which can be associated with phenotypic variation through database mining or simple experiments. Such information will help to make hypotheses of uORF function in plant development or adaption to changing environments on the basis of the cognate mORF function. This database also curates plant uORF relevant literature into distinct groups. To be broadly interesting, our database expands uORF annotation into more species of fungi (Botrytis cinerea), plant (Brassica napus, Glycine max, Gossypium raimondii, Medicago truncatula, Solanum lycopersicum, Solanum tuberosum, Triticum aestivum and Zea mays), metazoan (Caenorhabditis elegans and Drosophila melanogaster) and vertebrate (Homo sapiens, Mus musculus and Danio rerio). Therefore, uORFlight will light up the runway toward how uORF genetic variation determines phenotypic diversity and advance our understanding of translational control mechanisms.

genomics↗

bioRxiv2019

The C. elegans RIG-I homolog drh-1 mediates the Intracellular Pathogen Response upon viral infection

Mammalian RIG-I-like receptors detect viral dsRNA and 5 triphosphorylated RNA to activate transcription of interferon genes and promote antiviral defense. The C. elegans RIG-I-like receptor DRH-1 promotes defense through antiviral RNA interference, but less is known about its role in regulating transcription. Here we describe a role for drh-1 in directing a transcriptional response in C. elegans called the Intracellular Pathogen Response (IPR), which is associated with increased pathogen resistance. The IPR includes a set of genes induced by diverse stimuli including intracellular infection and proteotoxic stress. Previous work suggested that the proteotoxic stress caused by intracellular infections might be the common trigger of the IPR, but here we demonstrate that different stimuli act through distinct pathways. Specifically, we demonstrate that DRH-1/RIG-I is required for inducing the IPR in response to Orsay virus infection, but not in response to other triggers like microsporidian infection or proteotoxic stress. Furthermore, drh-1 appears to be acting independently of its known role in RNAi. Interestingly, expression of the replication competent Orsay virus RNA1 segment alone is sufficient to induce most of the IPR genes in a manner dependent on RNA dependent RNA polymerase activity and on drh-1. Altogether, these results suggest that DRH-1 is a pattern-recognition receptor that detects viral replication products to activate the IPR stress/immune program in C. elegans.\n\nImportanceC. elegans lacks homologs of most mammalian pattern recognition receptors, and how nematodes detect pathogens is poorly understood. We show that the C. elegans RIG-I homolog drh-1 mediates induction of the Intracellular Pathogen Response (IPR), a novel transcriptional defense program, in response to infection by the natural C. elegans viral pathogen Orsay virus. drh-1 appears to act as a pattern-recognition receptor to induce the IPR transcriptional defense program by sensing the products of viral RNA-dependent RNA polymerase activity. Interestingly, this signaling role of drh-1 is separable from its previously known role in antiviral RNAi. In addition, we show that there are multiple host pathways for inducing the IPR, shedding light on the regulation of this novel transcriptional immune response.

microbiology↗

bioRxiv2019

A Novel L-Serine Exporter and Its Positive Regulator in Corynebacterium glutamicum

Exporters play an essential role in the fermentative production of amino acids. In Corynebacterium glutamicum, ThrE, which can export O_SCPCAPLC_SCPCAP-threonine and O_SCPCAPLC_SCPCAP-serine, is the only identified O_SCPCAPLC_SCPCAP-serine exporter so far. In this study, a novel O_SCPCAPLC_SCPCAP-serine exporter NCgl0580 was identified and characterized in C. glutamicum {Delta}SSAAI (SSAAI), and named as SerE (encoded by serE). Deletion of serE in SSAAI led to a 56.5% decrease in O_SCPCAPLC_SCPCAP-serine titer, whereas overexpression of serE compensated for the lack of serE with respect to O_SCPCAPLC_SCPCAP-serine titer. A fusion protein with SerE and enhanced green fluorescent protein (EGFP) was constructed to confirm that SerE localized at the plasma membrane. The function of SerE was studied by peptide feeding approaches, and the results showed that SerE is a novel exporter for O_SCPCAPLC_SCPCAP-serine and O_SCPCAPLC_SCPCAP-threonine in C. glutamicum. Subsequently, the interaction of a known O_SCPCAPLC_SCPCAP-serine exporter ThrE and SerE was studied, and the results suggested that SerE is more important than ThrE in O_SCPCAPLC_SCPCAP-serine export in SSAAI. Probe plasmid and electrophoretic mobility shift assays (EMSA) revealed NCgl0581 as the transcriptional regulator of SerE. Comparative transcriptomics between SSAAI and the NCgl0581 deletion strain showed that NCgl0581 regulated the transcription of 115 genes in C. glutamicum, among which the transcriptional level of NCgl0580 decreased 280-fold in a NCgl0581 deletion strain, indicating that NCgl0581 is a positive regulator of SerE. Thus, this study provides a novel target for O_SCPCAPLC_SCPCAP-serine and O_SCPCAPLC_SCPCAP-threonine export engineering as well as a novel global transcriptional regulator NCgl0581 in C. glutamicum.\n\nImportanceExporters are gaining increasing attention for improving industrial production of amino acids. This study identified a novel exporter NCgl0580 for O_SCPCAPLC_SCPCAP-serine and O_SCPCAPLC_SCPCAP-threonine in C. glutamicum, and its positive regulator (NCgl0581), which was shown to be a novel global transcriptional regulator in C. glutamicum. This study provides a new target for engineering efflux of O_SCPCAPLC_SCPCAP-serine and O_SCPCAPLC_SCPCAP-threonine, expands the exporter and transcriptional regulator family, and enriches our understanding of amino acid transport system in C. glutamicum.

bioengineering↗

bioRxiv2019

Fecal microbiota as a non-invasive biomarker to predict the tissue iron accumulation in intestine epithelial cells and liver

Iron is an essential trace mineral for the growth, systemic metabolism, and immune response. Imbalance of tissue iron absorption and storage leads to various diseases. The excessive iron accumulation is associated with inflammation and cancer while iron deficiency leads to growth retardation. Studies investigated in Kenyan infants and school children suggests that both low and high iron intake result in dysbiosis of gut microbiota. This would lead to the disruption of microbial diversity, an increase of pathogen abundance and the induction of intestinal inflammation. Despite this progress, in-depth studies investigating the relationship between iron availability and gut microbiota is not completely explored. In the current study, we established a murine model to study the connection between iron and microbiota by feeding mice with either iron-deprived or -fortified diet. To identify key microbiota related to iron levels, we combined the 16S rRNA amplicon sequencing with the innovated bioinformatic algorithms, such as RDA, co-occurrence, and machine learning to identify key microbiota. Manipulation of iron levels in the diet leads to systemic iron dysregulation and dysbiosis of gut microbiota. The bioinformatic algorithms used here detect five key bacteria that correlate with systemic iron levels. Leveraging on these key microbiotas, we also established a prediction model which could precisely distinguish the individual under either iron-deprived or iron-fortified physiological condition to further prove the link between microbiota and systemic iron homeostasis. This innovated and non-invasive approach could be potentially used for the early diagnosis and therapy of iron-dysregulation related diseases, e.g. anemia, inflammatory disease, fibrosis, and cancers.

microbiology↗

bioRxiv2019

FAK activity sustains intrinsic and acquired ovarian cancer resistance to platinum chemotherapy

Gene copy number changes, cancer stem cell (CSC) increases, and platinum chemotherapy resistance contribute to poor prognosis in patients with recurrent high grade serous ovarian cancer (HGSOC). CSC phenotypes involving Wnt-{beta}-catenin and aldehyde dehydrogenase activities, platinum resistance, and tumor initiating frequency are here associated with spontaneous genetic gains, including genes encoding KRAS, MYC and FAK, in a new murine model of ovarian cancer (KMF). Noncanonical FAK signaling was sufficient to sustain human and KMF tumorsphere proliferation, CSC survival, and platinum resistance. Increased FAK tyrosine phosphorylation occurred in HGSOC patient tumors surviving neo-adjuvant platinum and paclitaxel chemotherapy and platinum resistant tumorspheres acquired FAK dependence for growth. Importantly, combining a pharmacologic FAK inhibitor with platinum overcame chemoresistance and triggered apoptosis in vitro and in vivo. Knockout, rescue, genomic and transcriptomic analyses collectively identified more than 400 genes regulated along a FAK/{beta}-catenin/Myc axis impacting stemness and DNA repair in HGSOC, with 66 genes gained in a majority of Cancer Genome Atlas samples. Together, these results support combinatorial testing of FAK inhibitors for the treatment of recurrent ovarian cancer.\n\nGraphical Summary\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=125 SRC=\"FIGDIR/small/594184_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (52K):\norg.highwire.dtl.DTLVardef@20c737org.highwire.dtl.DTLVardef@1f714faorg.highwire.dtl.DTLVardef@823560org.highwire.dtl.DTLVardef@7e6219_HPS_FORMAT_FIGEXP M_FIG C_FIG Key PointsO_LIHigh grade serous ovarian carcinoma tumors contain PTK2 (FAK) 8q24.3 gains associated with prognostic differences.\nC_LIO_LIKMF, a new murine ovarian cancer model with K-Ras, Myc, and FAK gene gains and intrinsic platinum resistance.\nC_LIO_LIFAK activation in tumors surviving platinum chemotherapy promotes cancer stem cell survival.\nC_LIO_LIFAK facilitates a {beta}-catenin-Myc signaling axis controlling gene expression supporting platinum resistance.\nC_LIO_LIFAK activity is essential for KMF tumor growth and is a targetable cellular adaptation of platinum resistance.\nC_LI

cancer biology↗

bioRxiv2018

Infection-generated electric field in gut epithelium drives bidirectional migration of macrophages

Many bacterial pathogens hijack macrophages to egress from the port of entry to the lymphatic/blood-stream, causing dissemination of life-threatening infections. However, the underlying mechanisms are not well understood. Here, we report that Salmonella infection generates directional electric fields (EF) in the follicle-associated epithelium of mouse cecum. In vitro application of an EF, mimicking the infection-generated electric field (IGEF), induces directional migration of primary mouse macrophages to the anode, which is reversed to the cathode upon Salmonella infection. This infection-dependent directional switch is independent of the Salmonella pathogenicity island 1 (SPI-1) type III secretion system. The switch is accompanied by a reduction of sialic acids on glycosylated surface components during phagocytosis of bacteria, which is absent in macrophages challenged by microspheres. Moreover, enzymatic cleavage of terminally exposed sialic acids reduces macrophage surface negativity and severely impairs directional migration of macrophages in response to EF. Based on these findings, we propose that macrophages are attracted to the site of infection by a combination of chemotaxis and galvanotaxis; after phagocytosis of bacteria, surface electrical properties of the macrophage change, and galvanotaxis directs the cells away from the site of infection.\n\nAbbreviationsCFU, colony-forming unit; Con A, Concanavalin A; EF, electric field; FAE, follicle-associated epithelium; GNL, Galanthus Nivalis lectin; IGEF, infection-generated electric field; Ji, electric current density; MAL-2, Maackia Amurensis lectin II; MLN, mesenteric lymph node; MOI, multiplicity of infection; nMFI, normalized mean fluorescence intensity; RCA-1, Ricinus Communis Agglutinin I; SNA, Sambucus Nigra lectin; S. Typhimurium, Salmonella enterica serotype Typhimurium; SPI-1, Salmonella pathogenicity island 1; PDMS, polydimethylsiloxane; TEP, trans-epithelial potential difference; TLR, Toll-like receptors; WGEF, wound-generated electric field

cell biology↗

bioRxiv2018

Surge of Corticocardiac Coupling in SHRSP Rats Exposed to Forebrain Cerebral Ischemia

Sudden death is an important but under-recognized consequence of stroke. Acute stroke can disturb central control of autonomic function, and result in cardiac dysfunction and sudden death. Previous study showed that bilateral common carotid artery ligation (BCCAL) in spontaneously hypertensive stroke-prone rats (SHRSP) is a well-established model for forebrain ischemic sudden death. This study aims to investigate the temporal dynamic changes in electrical activities of the brain and heart and functional interactions between the two vital organs following forebrain ischemia. EEG and ECG signals were simultaneously collected from 9 SHRSP and 8 Wistar-Kyoto (WKY) rats. RR interval and cardiac arrhythmias were analyzed to investigate the cardiac response to brain ischemia. EEG power and coherence (CCoh) analysis were conducted to study the cortical response. Corticocardiac coherence (CCCoh) and directional connectivity (CCCon) were analyzed to determine brain-heart connection. Heart rate variability (HRV) was analyzed to evaluate autonomic functionality. BCCAL resulted in 100% mortality in SHRSP within 14 hours, whereas no mortality was observed in WKY. The functionality of both the brain and the heart were significantly altered in SHRSP compared to WKY after BCCAL. SHRSP rats, but not WKY rats, exhibited intermittent surge of CCCoh, which paralleled the elevated CCCon and reduced HRV, following the onset of ischemia until sudden death. Elevated brain-heart coupling invariably associated with the disruption of the autonomic nervous system and the risk of sudden death. This study may improve our understanding of the mechanism of ischemic stroke-induced sudden death.

physiology↗

bioRxiv2018

Root Colonization and Growth Promotion of Soybean, Wheat and Chinese Cabbage by Bacillus cereus YL6

Phosphate-solubilizing bacteria (PSB) have been isolated and used in agricultural production. However, comprehensive research on PSB colonizing the rhizosphere of different plants and promoting plant growth is lacking. This study was conducted to study the growth-promoting effects and colonizing capacity of the PSB strain YL6. The YL6 strain not only increased the biomass of pot-planted soybean and wheat but also increased the yield and growth of Chinese cabbage under field conditions. The promotion of growth in these crops by strain YL6 was related to its capacities to dissolve inorganic and organic phosphorus and to produce a certain amount of indole-3-acetic (IAA) and gibberellin (GA). After YL6 was applied to soybean, wheat and Chinese cabbage, the rhizosphere soil available phosphorus (available P) content increased by 120.16%, 62.47% and 7.21%, respectively, and the plant total phosphorus increased by 198.60%, 6.20% and 78.89%, respectively, compared with those of plants without the addition of YL6. To determine whether the phosphate solubilizing bacteria colonized these plants, YL6 labeled with green fluorescent protein (YL6-GFP) was inoculated into plant rhizospheres. YL6-GFP first colonized the root surface and hairs and then penetrated into intercellular spaces and vessels. Collectively, these results demonstrate that YL6 promoted the growth of three different crops and colonized them in a similar way and therefore provide a solid foundation for probing into mechanisms by which phosphate-solubilizing bacteria affect plant growth.

microbiology↗

bioRxiv2018

The landscape and diagnostic potential of T and B cell repertoire in Immunoglobulin A Nephropathy

Immunoglobulin A Nephropathy (IgAN) is the most common glomerulonephritis worldwide. In IgAN, immune complex deposite in glomerular mesangium, which induce inflammation and affect the kidneys normal functions. However, the exact pathogenesis of IgAN is still incompletely understood. Further, in current practice the clinical diagnosis relies on needle biopsy on renal tissue. Therefore, a non-invasive method for clinical diagnosis and prognosis surveillance of the disease is in high demand. In this paper, we investigated both the T cell receptor bata chain (TCRB) and immunoglobulin heavy chain (IGH) repertoire of kidney infiltrating and circulating lymphocytes of IgAN patients by immune repertoire high throughput sequencing. We found that the features of TCRB and IGH in the renal tissues were remarkably different from that in blood, including a decreased repertoire diversity and increased IgA and IgG frequency, and more activated B cells. The CDR3 length of PBMC TCRB and IGH in patients is significantly shorter than that in healthy controls, which is the result of both VDJ rearrangement and clone selection. We also found that the IgA1 frequency in the PBMC of IgAN is significant higher than that in other Nephropathy (NIgAN) and healthy control, which is consistent with the previous reports on the level of IgA1 producing B cells and serum IgA1. Significantly, we identified a set of IgAN disease related TCRB and IGH CDR3s, which can be used to distinguish IgAN from NIgAN and healthy controls from the blood with high accuracy. These results indicated that TCRB and IGH repertoire can potentially serve as non-invasive biomarkers for IgAN diagnosis. The characteristics of kidney infiltrating and circulating lymphocytes repertoire shed light on IgAN detection, treatment and surveillance.

immunology↗

bioRxiv2018

Endothelial cells secreted ET-1 augments DN via inducing EM accumulation of MCs in ETBR-/- mice

ETBR deficiency may contribute to the progression of DN in a STZ model, but the underlying mechanism is not fully revealed. In this study, STZ-diabetic ETBR-/- mice was characterized by increased serum creatinine, urinary albumin and ET-1 expression, and enhanced glomerulosclerosis compared with STZ-diabetic WT mice. HG conditioned media of ETBR-/- endothelial cells promoted MC proliferation and upregulated ECM-related proteins, and ET-1 knockout in endothelial cells or inhibition of ET-1/ETAR in MC suppressed MC proliferation. ET-1 was over-expressed in ETBR-/- endothelial cells and was regulated by NF-kapapB pathway. And ET-1/ETBR suppressed NF-kappaB via eNOS to modulate ET-1 in endothelial cells. Furthermore, ET-1/ETAR promoted RhoA/ROCK pathway in MC, and accelerated MC proliferation and ECM accumulation. In vivo experiments proved ETBR-/- mice inhibited NF-kappaB pathway to ameliorate DN and eNOS mice had similar results. Hence, in HG-exposed ETBR-/- endothelial cells, suppression of ET-1/ETBR activated NF-kappaB pathway via inhibiting eNOS to secrete large amount of ET-1. Due to the communication between endothelial cells and MCs, ET-1/ETAR in MC promoted RhoA/ROCK pathway to accelerate MC proliferation and ECM accumulation.

biochemistry↗

bioRxiv2018

The plasma miR-122 basal levels respond to circulating catecholamine in rats

miR-122 in circulation is a promising non-invasive biomarker as a replacement or supplement of current serum biomarkers for liver injuries. But the concept was questioned by recent studies, mainly due to its release from hepatocytes in absence of overt cellular injuries. In this study, we reported that the hepatic metabolism of circulating catecholamines resulted in the release of hepatocyte-specific miR-122. Acute stress-induced hepatocellular deformation was histopathologically different from drug-induced liver injury with significant increases of plasma miR-122 levels. The basal levels of human plasma miR-122 could be significantly altered by emotional responses. Interday variances of plasma miR-122 measurements were reduced effectively by stress-relief measures. The metabolism of basal circulating norepinephrine and epinephrine in liver might contribute to the basal levels of plasma miRNAs expressed in hepatocytes.

molecular biology↗