Biology subjects

Qiao, H.

Publications and source records attributed to Qiao, H..

45 records · Page 3Linked to original sources

bioRxiv2019

Unsupervised content-preserving transformation for optical microscopy

The development of deep learning and the open access to a substantial collection of imaging data provide a potential solution to computational image transformation, which is gradually changing the landscape of optical imaging and biomedical research. However, current implementations of deep learning usually operate in a supervised manner and the reliance on a laborious and error-prone data annotation procedure remains a barrier towards more general applicability. Here, we propose an unsupervised image transformation to facilitate the utilization of deep learning for optical microscopy, even in some cases where supervised models cannot apply. By introducing a saliency constraint, the unsupervised model, dubbed as Unsupervised content-preserving Transformation for Optical Microscopy (UTOM), can learn the mapping between two image domains without requiring paired training data and avoid the distortion of the image content. UTOM shows promising performances in a wide range of biomedical image transformation tasks, including in silico histological staining, fluorescence image restoration, and virtual fluorescence labeling. Quantitative evaluations elucidate that UTOM achieves stable and high-fidelity image transformations across different imaging conditions and modalities. We anticipate that our framework will encourage a paradigm shift in training neural networks and enable more applications of artificial intelligence in biomedical imaging.

bioinformatics↗

bioRxiv2019

3D observation of large-scale subcellular dynamics in vivo at the millisecond scale

Observing large-scale three-dimensional (3D) subcellular dynamics in vivo at high spatiotemporal resolution has long been a pursuit for biology. However, both the signal-to-noise ratio and resolution degradation in multicellular organisms pose great challenges. Here, we propose a method, termed Digital Adaptive Optics Scanning Lightfield Mutual Iterative Tomography (DAOSLIMIT), featuring both 3D incoherent synthetic aperture and tiled wavefront correction in post-processing. We achieve aberration-free fluorescence imaging in vivo over a 150 x 150 x 16 m3 field-of-view with the spatiotemporal resolution up to 250 nm laterally and 320 nm axially at 100 Hz, corresponding to a huge data throughput of over 15 Giga-voxels per second. Various fast subcellular processes are observed, including mitochondrial dynamics in cultured neurons, membrane dynamics in zebrafish embryos, and calcium propagation in cardiac cells, human cerebral organoids, and Drosophila larval neurons, enabling simultaneous in vivo studies of morphological and functional dynamics in 3D.

cell biology↗

bioRxiv2019

Phenological matching drives wheat pest range shift under climate change

Shifting geographical ranges of crop pests and pathogens in response to climate change pose a threat to food security (1, 2). The orange wheat blossom midge (Sitodiplosis mosellana Gehin) is responsible for significant yield losses in China (3), the worlds largest wheat producer. Here we report that rising temperatures in the North China Plain have resulted in a mean northward range shift of 3.3{degrees} (58.8 km per decade) from the 1950s to 2010s, which accelerated to 91.3 km per decade after 1985 when the highly toxic pesticide hexachlorocyclohexane (HCH) was banned (4). Phenological matching between wheat midge adult emergence and wheat heading in this new expanded range has resulted in greater damage to wheat production. Around $286.5 million worth of insecticides were applied to around 19 million hectares in an attempt to minimize wheat midge damage to crops between 1985 and 2016. Despite use of these pesticides, wheat midge caused losses of greater than 0.95 million metric tons of grain during this period. Our results demonstrate the potential for indirect negative impacts of climate change on crop production and food security, and constitute the first large scale example of plant pest range shift due to global warming.

ecology↗

bioRxiv2018

miR-425 suppresses EMT and inhibits the development of TNBC (triple-negative breast cancer) by targeting TGF-β 1/SMAD 3 signaling pathway

BackgroundEMT has the crucial effect on the progression and metastasis of tumor. This work will elucidate the role of miR-425 in EMT and development of TNBC.\n\nMethodsThe differential miRNA expression among non-tumor, para-tumor (adjacent tissue of tumor) and tumor tissues was analyzed. The luciferase activities of TGF-{beta}1 3 UTR treated with miR-425 were determined. Then human breast cancer cell lines were dealt with mimics or inhibitors of miR-425, and then the cell proliferation and migration, invasion ability were assessed. The expression of TGF-{beta}1 and markers of epithelial cell and mesenchymal cell were analyzed. The influences of miR-425 on development of TNBC through inducing EMT by targeting TGF-{beta} 1 and TGF-{beta}1/SMAD3 signaling pathway in TNBC cell lines were investigated. Furthermore, Xenograft mice were used to explore the potential roles of miR-425 on EMT and development of TNBC in vivo.\n\nResultsCompared with non-tumor tissues, 9 miRNAs were upregulated and 3 miRNAs were down-regulated in tumor tissues. The relative expression of miR-425 in tumor tissues was obviously much lower than that in para-tumor and non-tumor tissues. MiR-425 suppressed TGF-{beta}1 expression, additionally inhibited expression of mesenchymal cell markers, while exerted effects on cell proliferation and migration of TNBC cell lines. Moreover, the agomir of miR-425 could protect against development process in murine TNBC xenogarft model.\n\nConclusionsOur results demonstrated that miR-425 targets to TGF-{beta}1, and was a crucial suppressor on EMT and development of TNBC through inhibiting TGF-{beta}1/SMAD3 signaling pathway. It suggested that aim at TGF-{beta}1/SMAD3 signaling pathway by enhancing relative miR-425 expression, was a feasible therapy strategy for TNBC.

cancer biology↗

bioRxiv2018

Investigation of novel functions of three genes in oriental river prawn, Macrobrachium nipponense: Molecular Cloning, Expression, and In situ Hybridization Analysis

Three genes were predicted to be potentially involved in the male sexual development in M. nipponense, including the Gem-associated protein 2-like isoform X1 (GEM), Ferritin peptide, and DNA polymerase zeta catalytic subunit (Rev3). In this study, we aimed to investigate their novel functions in depth. The full-length cDNA sequence of Mn-GEM was 1,018 bp, encoding 258 amino acids. The partial Mn-Rev3 cDNA sequence was 6,832 bp, encoding 1,203 amino acids. Tissue distribution indicated that all of these three genes have higher expression level in testis and androgenic gland, implying their novel functions in male sexual development. In situ hybridization analysis further confirmed the novel roles of these three genes. Rev3 promote the testis development during the whole reproductive cycle, while GEM and ferritin only promote the activation of testis development. Besides, these three genes play essential roles in funicular structure development surrounding the androgenic gland cells, which promote and support the formation of androgenic gland cells. The expression in hepatopancreas cells also suggested their role in immune system in M. nipponense. This study advances our understanding of male sexual development in M. nipponense, as well as providing the basis for further studies of male sexual differentiation and development in crustaceans.

zoology↗

bioRxiv2018

TP53I11 Suppresses Extracellular Matrix-independent Survival and Mesenchymal Transition in Mammary Epithelial Cells

Extracellular matrix (ECM)-independent survival is an essential prerequisite for tumor metastasis and a hallmark of epithelial cancer stem cells and epithelial-mesenchymal transition (EMT). We found that, in MCF10A and MDA-MB-231 cells, loss of TP53I11 (Tumor Protein P53 Inducible Protein 11) enhanced the ECM-independent survival and suppressed glucose starvation induced cell death by increasing the activation of AMPK that confer cells metabolic flexibility to survive under stress conditions. We show here that, TP53I11 enhanced glycolysis and promoted proliferation of MCF10A and MDA-MB-231 cells in normal culture, but exerted negative effect on EMT, cell migration and invasion, and its overexpression suppressed tumor progression and metastasis of MDA-MB-231 cells in vivo. Considering cancer cells also are confronted with the hostile environment such as nutrient scarcity during tumorigenesis and metastasis, our findings suggested that the disruption of metabolic flexibility by TP53I11 through inhibiting AMPK activation resulted in the suppression of tumorigenesis and metastasis of breast cancer.

molecular biology↗

bioRxiv2018

YES1 amplification: a mechanism of acquired resistance to EGFR inhibitors identified by transposon mutagenesis and clinical genomics

In approximately 30% of patients with EGFR-mutant lung adenocarcinomas whose disease progresses on EGFR inhibitors, the basis for acquired resistance remains unclear. We have integrated transposon mutagenesis screening in an EGFR-mutant cell line and clinical genomic sequencing in cases of acquired resistance to identify novel mechanisms of resistance to EGFR inhibitors. The most prominent candidate genes identified by insertions in or near the genes during the screen were MET, a gene whose amplification is known to mediate resistance to EGFR inhibitors, and the gene encoding the Src family kinase YES1. Cell clones with transposon insertions that activated expression of YES1 exhibited resistance to all three generations of EGFR inhibitors and sensitivity to pharmacologic and siRNA-mediated inhibition of YES1. Analysis of clinical genomic sequencing data from cases of acquired resistance to EGFR inhibitors revealed amplification of YES1 in 5 cases, 4 of which lacked any other known mechanisms of resistance. Pre-inhibitor samples, available for 2 of the 5 patients, lacked YES1 amplification. None of 136 post-inhibitor samples had detectable amplification of other Src family kinases (SRC, FYN). YES1 amplification was also found in 2 of 17 samples from ALK fusion-positive lung cancer patients who had progressed on ALK TKIs. Taken together, our findings identify acquired amplification of YES1 as a novel, recurrent, and targetable mechanism of resistance to EGFR inhibition in EGFR-mutant lung cancers, and demonstrate the utility of transposon mutagenesis in discovering clinically relevant mechanisms of drug resistance.\n\nSIGNIFICANCEDespite high response rates to treatment with small molecule inhibitors of EGFR tyrosine kinase activity, patients with EGFR-mutant lung adenocarcinomas eventually develop resistance to these drugs. In many cases, the basis of acquired resistance remains unclear. We have used a transposon mutagenesis screen in an EGFR-mutant cell line and clinical genomic sequencing in cases of acquired resistance to identify amplification of YES1 as a novel and targetable mechanism of resistance to EGFR inhibitors in EGFR-mutant lung cancers.

cancer biology↗

bioRxiv2018

Impeding DNA Break Repair Enables Oocyte Quality Control

Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death is triggered by defects in chromosome synapsis and recombination, which involve repair of programmed DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocytes elimination in meiotic mutants require RNF212. RNF212 sensitizes cells to DSB-induced apoptosis within a narrow window when chromosomes desynapse during the transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a \"memory\" of meiotic defects that enables quality control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.

genetics↗

bioRxiv2016

A SUMO-Ubiquitin Relay Recruits Proteasomes to Chromosome Axes to Regulate Meiotic Recombination

Meiosis produces haploid gametes through a succession of chromosomal events including pairing, synapsis and recombination. Mechanisms that orchestrate these events remain poorly understood. We found that the SUMO-modification and ubiquitin-proteasomes systems regulate the major events of meiotic prophase in mouse. Interdependent localization of SUMO, ubiquitin and proteasomes along chromosome axes was mediated largely by RNF212 and HEI10, two E3 ligases that are also essential for crossover recombination. RNF212-dependent SUMO conjugation effected a checkpoint-like process that stalls recombination by rendering the turnover of a subset of recombination factors dependent on HEI10-mediated ubiquitylation. We propose that SUMO conjugation establishes a precondition for designating crossover sites via selective protein stabilization. Thus, meiotic chromosome axes are hubs for regulated proteolysis via SUMO-dependent control of the ubiquitin-proteasome system.\n\nOne Sentence SummaryChromosomal events of meiotic prophase in mouse are regulated by proteasome-dependent protein degradation.

genetics↗