Biology subjects

Ji, C.

Publications and source records attributed to Ji, C..

44 records · Page 3Linked to original sources

bioRxiv2020

Mutations, Recombination and Insertion in the Evolution of 2019-nCoV

BackgroundThe 2019 novel coronavirus (2019-nCoV or SARS-CoV-2) has spread more rapidly than any other betacoronavirus including SARS-CoV and MERS-CoV. However, the mechanisms responsible for infection and molecular evolution of this virus remained unclear. MethodsWe collected and analyzed 120 genomic sequences of 2019-nCoV including 11 novel genomes from patients in China. Through comprehensive analysis of the available genome sequences of 2019-nCoV strains, we have tracked multiple inheritable SNPs and determined the evolution of 2019-nCoV relative to other coronaviruses. ResultsSystematic analysis of 120 genomic sequences of 2019-nCoV revealed co-circulation of two genetic subgroups with distinct SNPs markers, which can be used to trace the 2019-nCoV spreading pathways to different regions and countries. Although 2019-nCoV, human and bat SARS-CoV share high homologous in overall genome structures, they evolved into two distinct groups with different receptor entry specificities through potential recombination in the receptor binding regions. In addition, 2019-nCoV has a unique four amino acid insertion between S1 and S2 domains of the spike protein, which created a potential furin or TMPRSS2 cleavage site. ConclusionsOur studies provided comprehensive insights into the evolution and spread of the 2019-nCoV. Our results provided evidence suggesting that 2019-nCoV may increase its infectivity through the receptor binding domain recombination and a cleavage site insertion. One Sentence SummaryNovel 2019-nCoV sequences revealed the evolution and specificity of betacoronavirus with possible mechanisms of enhanced infectivity.

microbiology↗

bioRxiv2019

Golden pompano genome and embryo transcriptome shed light on regulation of minor ZGA gene on heart and vascular development

BACKGROUNDAngiogenesis is closely associated with angiogenesis-dependent diseases including cancers and ocular diseases. Anti-angiogenic therapeutics have been focusing on the (VEGF)/VEGFR signaling axis. However, the clinical resistance, high cost and frequent administration of anti-VEGF drugs make it urgent to discover novel angiogenic pathways.VE-PTP (ptprb) is a novel target with great anti-angiogenic potential. However, it is unclear whether upstream signaling pathways targeting VE-PTP exist in angiogenesis. METHODSWhole genome and embryo transcriptome sequencing were applied to discover the new gene nxhl. Transgenic zebrafish model, morpholino knockdown and small interfering RNA were used to explore the role of nxhl in angiogenesis both in vitro and in vivo. RNA pulldown, RIP and ChIRP-MS were used to identify interactions between RNA and protein. RESULTSWe discovered a novel zebrafish gene nxhl which is a homologue of the conserved gene nxh that co-expressed with some key genes essential for embryo development in vertebrate. Nxhl deletion causes angiogenesis defects in embryo. Moreover, nxhl is essential to mediate effects of angiogenesis in vivo and in vitro, and ptprb depletion duplicates the phenotypes of nxhl deficiency. Importantly, nxhl acts upstream of ptprb and regulates many extreme important ptprb-linked angiogenic genes by targeting VE-PTP (ptprb) through interactions with NCL. Notably, nxhl deletion decreases the phosphorylation of NCL T76 and increases the acetylation of NCL K88, suggesting nxhl may regulate downstream VE-PTP signaling pathways by mediation of NCL posttranslational modification. This is the first description of the interaction between nxhl and NCL, NCL and VE-PTP (ptprb), uncovering a novel nxhl-NCL-VE-PTP signaling pathway on angiogenesis regulation. CONCLUSIONSOur study identifies nxhl controlling angiogenesis by targeting VE-PTP through interactions with NCL, uncovering novel upstream controllers of VE-PTP. This nxhl-NCL-VE-PTP pathway may be a therapeutic target in the treatment of angiogenesis-dependent diseases. Clinical PerspectiveO_ST_ABSWhat Is New?C_ST_ABSO_LIWe report a novel nxhl-NCL-VE-PTP signaling pathway that controls angiogenesis. C_LIO_LIWe for the first time demonstrate that nxhl interacts with NCL which simultaneously binds to VE-PTP that plays key roles on EC adherens junction, integrity and vascular homeostasis. C_LIO_LINxhl also controls some other crucial VE-PTP-linked downstream angiogenic genes (such as Tie2, VEGFaa, VEGFR2, Erbb2, S1pr1 and Hey2) which explain the phenotypes induced by the nxhl deficiency. C_LIO_LIOur study indicates the key role of nxhl on controlling angiogenesis as an upstream regulator of VE-PTP. C_LI What Are the Clinical Implications?O_LIThere are several ongoing researches investigating the utility of VE-PTP or NCL inhibitors on treatment of angiogenesis-dependent diseases including a range of cancers and nonneoplastic diseases, such as AMD, DME, RA and atherosclerosis. C_LIO_LITargeting the nxhl-NCL-VE-PTP pathway may facilitate therapeutic angiogenesis in patients with cancers or ocular diseases such as DME. C_LIO_LIOur study highlights the great potential of nxhl on anti-angiogenic therapeutics by targeting VE-PTP. C_LI

genomics↗

bioRxiv2019

AKT2 deficiency causes sarcopenia and metabolic disorder of skeletal muscle

Skeletal muscle is responsible for the majority of glucose disposal in the body. Insulin resistance in the skeletal muscle accounts for 85-90% of the impairment of total body glucose disposal in patients with tye 2 diabetes (T2D). However, the mechanism remains controversial. AKT2 is a protein kinase performing important functions in the regulation of glucose metabolism. We observed that mice deficient for AKT2 (AKT2 KO) exhibited decreased body weight and lean mass and showed impaired glucose tolerance, compared to their age- and gender-matched wild type mice (WT). Therefore, to test whether AKT2 deficiency causes deficits in skeletal muscle development and metabolism, we analyzed the expression of molecules related to skeletal muscle development, glucose uptake and metabolism in young (3 months) and old (8 months) mice. We found that AMPK phosphorylation and MEF2A expression were downregulated in young AKT2 KO mice, and this downregulation was inverted by AMPK activation. We also observed reduced mtDNA abundance and reduced expression of genes involved in mitochondrial biogenesis in the skeletal muscle of adult AKT2 KO mice, which was prevented by AMPK activation. However, GLUT4 expression was regulated by AKT2 in an AMPK-independent manner in skeletal muscle. During high-fat-diet (HFD)-induced obesity, AKT2 KO mice exhibited increased insulin resistance compared to WT mice. Our study establishes a new and important function of AKT2 in regulating glucose uptake and AMPK-dependent development and mitochondrial biogenesis in skeletal muscle.

molecular biology↗

bioRxiv2019

Hsa_circ_0001947 suppresses acute myeloid leukemia progression by sponging hsa-miR-329-5p and regulating CREBRF expression

Acute myeloid leukemia (AML) is a heterogeneous group of diseases resulting from clonal transformation of hematopoietic precursors through the acquisition of chromosomal rearrangements and multiple gene mutations. Accumulating evidence has indicated that aberrantly expressed circular RNAs (circRNAs) are involved in cancer development and progression. However, their clinical values and biological roles in AML remain unclear. In this study, we identified the aberrantly down-regulated profile of hsa_circ_0001947 in AML through microarray analysis and validated it with quantitative reverse transcription polymerase chain reaction (qRT-PCR). Then, we explored the clinical significance, biological functions and regulatory mechanisms of hsa_circ_0001947 in AML patients. The results showed that lower hsa_circ_0001947 expression was positively correlated with higher leukemia cells in bone marrow or peripheral blood, indicating poor prognosis. Further, bioinformatics analysis demonstrated hsa_circ_0001947-hsa-miR-329-5p-CREBRF network. Down-regulation of hsa_circ_0001947 by siRNA promoted cell proliferation, inhibited apoptosis, reduced drug resistance of AML cells, and also decreased the expression of its targeted gene, CREBRF. The mimics of hsa-miR-329-5p reduced drug resistance and decreased the expression of CREBRF, while its inhibitor manifested anti-leukemia effects and increased CREBRF expression. In vivo studies revealed that silencing hsa_circ_0001947 promoted the tumor growth in BALB/c nude mice. Collectively, our findings suggest that hsa_circ_0001947 functions as a tumor inhibitor to suppress AML cell proliferation through hsa-miR-329-5p/CREBRF axis, which would be a novel target for AML therapy.

cancer biology↗

bioRxiv2019

An efficient method to clone TAL effector genes from Xanthomonas oryzae using Gibson assembly

TALes (Transcription Activator-Like effectors) represent the largest family of type III effectors among pathogenic bacteria and play a critical role in the process of infection. Strains of Xanthomonas oryzae pv. oryzae (Xoo) and some strains of other Xanthomonas pathogens contain large numbers of TALe genes. Previous techniques to clone individual or a complement of TALe genes through conventional strategies are inefficient and time-consuming due to multiple genes (up to 29 copies) in a given genome and technically challenging due to the repetitive sequences (up to 33 nearly identical 102-nucleotide repeats) of individual TALe genes. Thus, only a limited number of TALe genes have been molecularly cloned and characterized, and the functions of most TALe genes remain unknown. Here, we present an easy and efficient cloning technique to clone TALe genes selectively through in vitro homologous recombination and single strand annealing and demonstrate the feasibility of this approach with four different Xoo strains. Based on the Gibson assembly strategy, two complementary vectors with scaffolds that can preferentially capture all TALe genes from a pool of genomic fragments were designed. Both vector systems enabled cloning of a full complement of TALe genes from each of four Xoo strains and functional analysis of individual TALes in rice in approximately one month compared to three months by previously used methods. The results demonstrate a robust tool to advance TALe biology and a potential for broad usage of this approach to clone multiple copies of highly competitive DNA elements in any genome of interest.

microbiology↗

bioRxiv2019

BAG3 and SYNPO (synaptopodin) facilitate phospho-MAPT/Tau degradation via autophagy in neuronal processes

A major cellular catabolic pathway in neurons is macroautophagy/autophagy, through which misfolded or aggregation-prone proteins are sequestered into autophagosomes that fuse with lysosomes, and are subsequently degraded. MAPT (microtubule associated protein tau) is one of the protein clients of autophagy. Given that accumulation of hyperphosphorylated MAPT contributes to the pathogenesis of Alzheimer disease and other tauopathies, decreasing endogenous MAPT levels has been shown to be beneficial to neuronal health in models of these diseases. A previous study demonstrated that the HSPA/HSP70 co-chaperone BAG3 (BCL2 associated athanogene 3) facilitates endogenous MAPT clearance through autophagy. These findings prompted us to further investigate the mechanisms underlying BAG3-mediated autophagy in the degradation of endogenous MAPT. Here we demonstrate for the first time that BAG3 plays an important role in autophagic flux in the neuritic processes of mature neurons (20-24 days in vitro [DIV]) through interaction with the post-synaptic cytoskeleton protein SYNPO (synaptopodin). Loss of either BAG3 or SYNPO impeded the fusion of autophagosomes and lysosomes predominantly in the post-synaptic compartment. A block of autophagy leads to accumulation of the autophagic receptor protein SQSTM1/p62 (sequestosome 1) as well as MAPT phosphorylated at Ser262 (p-Ser262). Furthermore, p-Ser262 appears to accumulate in autophagosomes at post-synaptic densities. Overall these data provide evidence of a novel role for the co-chaperone BAG3 in synapses. In cooperation with SYNPO, it functions as part of a surveillance complex that facilitates the autophagic clearance of MAPT p-Ser262, and possibly other MAPT species at the post-synapse. This appears to be crucial for the maintenance of a healthy, functional synapse.

neuroscience↗

bioRxiv2018

Isolation and characterization of antagonistic bacteria with the potential for biocontrol of soil-borne wheat diseases

Bacillus amyloliquefaciens subsp. plantarum XH-9 is a plant-beneficial rhizobacterium that shows good antagonistic potential against phytopathogens by releasing diffusible and volatile antibiotics, and secreting hydrolytic enzymes. Furthermore, the XH-9 strain possesses important plant growth-promoting characteristics, including nitrogen fixation (7.92 {+/-} 1.05 mg/g), phosphate solubilization (58.67 {+/-} 4.20 g/L), potassium solubilization (10.07 {+/-} 1.26 g/mL), and the presence of siderophores (4.92 {+/-} 0.46 g/mL), indole-3-acetic acid (IAA) (7.76 {+/-} 0.51 g/mL) and 1-aminocyclopropane-1-carboxylic acid deaminase (ACC-deaminase) (4.67 {+/-} 1.21 nmol/[mg*h]). Moreover, the XH-9 strain showed good capacities for wheat, corn, and chili root colonization, which are critical prerequisites for controlling soil-borne diseases as a bio-control agent. Real-time quantitative polymerase chain reaction experiments showed that the amount of Fusarium oxysporum DNA associated with the XH-9 strain after treatment significantly decreased compared with control group. Accordingly, wheat plants inoculated with the XH-9 strain showed significant increases in the plant shoot heights (14.20%), root lengths (32.25%), dry biomass levels (11.93%), and fresh biomass levels (16.28%) relative to the un-inoculated plants. The results obtained in this study suggest that the XH-9 strain has potential as plant-growth promoter and biocontrol agent when applied in local arable land to prevent damage caused by F. oxysporum and other phytopathogens.\n\nImportancePlant diseases, particularly soilborne pathogens, play a significant role in the destruction of agricultural resources. Although these diseases can be controlled to some extent with crop and fungicides, while these measures increase the cost of production, promote resistance, and lead to environmental contamination, so they are being phased out. Plant growth-promoting rhizobacteria are an alternative to chemical pesticides that can play a key role in crop production by means of siderophore and indole-3-acetic acid production, antagonism to soilborne root pathogens, phosphate and potassium solubilization, and nitrogen fixation. These rhizobacteria can also promote a beneficial change in the microorganism community by significantly reducing its pathogenic fungi component. Their use is fully in accord with the principles of sustainability.

microbiology↗

bioRxiv2018

Efficacy of fecal sampling as a gut proxy in the study of chicken gut microbiota

BackgroundDespite the convenience and noninvasiveness of fecal sampling, the fecal microbiota does not fully represent that of the gastrointestinal (GI) tract, and the efficacy of fecal sampling to accurately represent the gut microbiota in birds is poorly understood. In this study, we aim to identify the efficacy of feces as a gut proxy in birds using chickens as a model. We collected 1,026 samples from 206 chickens, including duodenum, jejunum, ileum, cecum and feces samples, for 16S rRNA amplicon sequencing analyses.\n\nResultsIn this study, the efficacy of feces as a gut proxy was partitioned to microbial community membership and community structure. Most taxa in the small intestine (84.11 - 87.28%) and ceca (99.39%) could be identified in feces. Microbial community membership was reflected with a gut anatomic feature, but community structure was not. Excluding shared microbes, the small intestine and ceca contributed 34.12 and 5.83% of the total fecal members, respectively. The composition of Firmicutes members in the small intestine and that of Actinobacteria, Bacteroidetes, Firmicutes and Proteobacteria members in the ceca could be well mirrored by the observations in fecal samples ({rho} = 0.54 - 0.71 and 0.71 - 0.78, respectively, P < 0.001). However, there were few significant correlations for each genus between feces and each of the 4 gut segments, and these correlations were not high ({rho} = -0.2 - 0.4, P < 0.05) for most genera.\n\nConclusionsOur results provide evidence that the good potential of feces to identify most taxa in chicken guts, but it should be interpreted with caution by using feces as a proxy for gut in microbial structure analyses. This work provides insights and future directions regarding the usage of fecal samples in studies of the gut microbiome.

microbiology↗