Biology subjects

Qian, C.

Publications and source records attributed to Qian, C..

65 records · Page 4Linked to original sources

bioRxiv2020

RIPK2 Stabilizes c-Myc and is an Actionable Target for Inhibiting Prostate Cancer Metastasis

Despite advances in diagnosis and treatment, metastatic prostate cancer remains incurable and is associated with high mortality rates. Thus, novel actionable drug targets are urgently needed for therapeutic interventions in advanced prostate cancer. Here we report receptor-interacting protein kinase 2 (RIPK2) as an actionable drug target for suppressing prostate cancer metastasis. RIPK2 is frequently amplified in lethal prostate cancers and its overexpression is associated with disease progression and aggressiveness. Genetic and pharmacological inhibition of RIPK2 significantly suppressed prostate cancer progression in vitro and metastasis in vivo. Multi-level proteomic analysis revealed that RIPK2 strongly regulates c-Myc protein stability and activity, largely by activating the MKK7/JNK/c-Myc phosphorylation pathway--a novel, non-canonical RIPK2 signaling pathway. Targeting RIPK2 inhibits this phosphorylation pathway, and thus promotes the degradation of c-Myc--a potent oncoprotein for which no drugs have been approved for clinical use yet. These results support targeting RIPK2 for personalized therapy in prostate cancer patients towards improving survival.

cancer biology↗

bioRxiv2020

Clinical Characteristics and Risk of Second Primary Lung Cancer After Cervix Cancer: A Population-Based Study

BackgroundLung cancer as a second primary malignancy is increasingly common, but the clinical characteristics of second primary non-small cell lung cancer after cervix cancer (CC-NSCLC) in comparison with first primary non-small cell lung cancer (NSCLC1) is unknown. MethodsThe Surveillance, Epidemiology and EndResults (SEER) cancer registry between 1998 and 2010 was used to conduct a large population-based cohort analysis. Demographic and clinical characteristics as well as prognostic data were systematically analyzed. We further compared overall survival (OS) in the two cohorts. Risk factors of secondary primary lung cancer in cervical cancer patients were also analyzed. Results557 (3.52%) had developed second primary lung cancer after cervix cancer and 451 were eligible for inclusion in the final analyses. In comparison to NSCLC1, patients with CC-NSCLC had a higher rate of squamous cell carcinoma (SCC) (36.59% vs. 19.07%, p<0.01). Median OS was longer for CC-NSCLC than for NSCLC1 before propensity score matching (PSM) (16 vs. 13months) but there was no significant difference after PSM. High-risk factors in cervical cancer to developing CC-NSCLC include: 50-79years old, black race (OR 1.417; 95%CI 1.095-1.834; p<0.05)and history of radiotherapy (OR 1.392; 95%CI 1.053-1.841; p<0.05). Conclusion50-79years old, black race and history of radiotherapy were independent risk factors of second primary lung cancer in cervical cancer patient. CC-NSCLC patients had distinctive clinical characteristics and a better prognosis compared with NSCLC1 patients.

cancer biology↗

bioRxiv2020

New and improved GRAB fluorescent sensors for monitoring dopaminergic activity in vivo

The monoamine neuromodulator dopamine (DA) plays a critical role in the brain, and the ability to directly measure dopaminergic activity is essential for understanding its physiological functions. We therefore developed the first red fluorescent GPCR-activation-based DA (GRABDA) sensors and optimized versions of green fluorescent GRABDA sensors following our previous studies. In response to extracellular DA, both the red and green GRABDA sensors have a large increase in fluorescence ({Delta}F/F0 values of 150% and 340%, respectively), with subcellular resolution, subsecond kinetics, and nanomolar to submicromolar affinity. Moreover, both the red and green GRABDA sensors readily resolve evoked DA release in mouse brain slices, detect compartmental DA release in live flies with single-cell resolution, and report optogenetically elicited nigrostriatal DA release as well as mesoaccumbens dopaminergic activity during sexual behavior in freely behaving mice. Importantly, co-expressing red GRABDA with either green GRABDA or the calcium indicator GCaMP6s provides a robust tool for simultaneously tracking neuronal activity and dopaminergic signaling in distinct circuits in vivo.

neuroscience↗

bioRxiv2020

Meta-analysis of the effects of sleep deprivation on depression in patients and animals

ObjectiveResearch on the antidepressant effects of sleep deprivation (SD) is lagging and has not produced completely uniform results in humans and animals. The present study aimed to reassess the effect of SD on patients and animals by meta-analysis based on updated research. MethodsWe searched PubMed, Embase and Cochrane Library for articles since the first relevant literature published up to June 10th, 2019. Data on sample characteristics, features of SD, and tests for depression were extracted. ResultsFourteen articles were included, eight on humans and six on animals. We found that when the duration of SD in patients was 7-14 days, it reflected antidepression [-1.52 (-2.07, -0.97); I2=19.6%]. In animals, the results of sucrose consumption experiments showed that SD has depressogenic effects [-1.06 (-1.63, -0.49); I2=81.1%], while the results of forced swimming experiments showed that SD treated depression [-1.17 (-2.19, -0.16); I2=80.1%], regardless of the duration of sleep deprivation. ConclusionSD can be an effective antidepressant measure when the duration is 7-14 days in patients. In animal studies, SD has shown more antidepressant effects when measured by forced swimming experiments, whereas using sucrose consumption tests had the effect of worsening depression.

neuroscience↗

bioRxiv2020

Layer-dependent multiplicative effects of spatial attention on contrast responses in human early visual cortex

Attention mechanisms at different cortical layers of human visual cortex remain poorly understood. Using submillimeter-resolution fMRI at 7T, we investigated the effects of top-down spatial attention on the contrast responses across different cortical depths in human early visual cortex. Gradient echo (GE) T2* weighted BOLD signal showed an additive effect of attention on contrast responses across cortical depths. Compared to the middle cortical depth, attention modulation was stronger in the superficial and deep depths of V1, and also stronger in the superficial depth of V2 and V3. Using ultra-high resolution (0.3mm in-plane) balanced steady-state free precession (bSSFP) fMRI, a multiplicative scaling effect of attention was found in the superficial and deep layers, but not in the middle layer of V1. Attention modulation of low contrast response was strongest in the middle cortical depths, indicating baseline enhancement or contrast gain of attention modulation on feedforward input. Finally, the additive effect of attention on T2* BOLD can be explained by strong nonlinearity of BOLD signals from large blood vessels, suggesting multiplicative effect of attention on neural activity. These findings support that top-down spatial attention mainly operates through feedback connections from higher order cortical areas, and a distinct mechanism of attention may also be associated with feedforward input through subcortical pathway. HighlightsO_LIResponse or activity gain of spatial attention in superficial and deep layers C_LIO_LIContrast gain or baseline shift of attention in V1 middle layer C_LIO_LINonlinearity of large blood vessel causes additive effect of attention on T2* BOLD C_LI

neuroscience↗

bioRxiv2020

Fully Automated Peptide Mapping Protocol for Multi-Attribute Method by Liquid Chromatography-Tandem Mass Spectroscopy with a High-Throughput Robotic Liquid Handling System

The multi-attribute method (MAM) based on liquid chromatography-tandem mass spectroscopy is emerging as a powerful tool to directly monitor multiple product quality attributes simultaneously. Preparation of samples for MAM, however, is labor intensive, involving protein denaturation, disulfide bond reduction, free cysteine alkylation, and enzymatic digestion steps, which require significant analyst hands-on time while limiting result turnaround. Such complexity can also render nontrivial variations across analysts and laboratories. We describe the development of a fully automated peptide mapping procedure with a high-throughput robotic liquid handling system to improve sample handling capability and outcome reproducibility while saving analyst hands-on time. The automated procedure is completely hands-free, and setup requires the analyst only to prenormalize the sample concentrations and load buffers and reagents at their designated positions on the robotic deck. The robotic liquid handler performs all the subsequent preparation steps and stores the digested samples on a chiller unit to await retrieval. The convenience and flexibility provided by this automated peptide mapping method provides substantial benefits over manual sample preparation protocols. The optimized, automated procedure showed good reproducibility and results that were comparable to those of the manual procedure with respect to sequence coverage, digestion completeness, and quantification of posttranslational modifications. With this increased throughput, coupled with fast MAM analysis, more comprehensive characterization can be achieved.

biochemistry↗

bioRxiv2019

Light-induced polyp retraction and tissue rupture in the photosensitive, reef-building coral Acropora muricata

Coral reefs are in alarming decline due to climate emergency, pollution and other man-made disturbances. The numerous ecosystem services derived from coral reefs are underpinned by the growth and physical complexity of reef-forming corals. Our knowledge of their fundamental biology is limited by available technology. We need a better understanding of larval settlement and development, skeletogenesis, interactions with pathogens and symbionts, and how this biology interacts with environmental factors such as light exposure, temperature, and ocean acidification. We here focus on a fast-growing key coloniser, Acropora muricata. To enable dynamic imaging of the photosensitive organism at different scales, we developed light-sheet illumination for fluorescence microscopy of small coral colonies. Our approach reveals live polyps in previously unseen detail. An imaging range for Acropora muricata with no measurable photodamage is defined based upon polyp expansion, coral tissue reaction, and photobleaching. We quantify polyp retraction as a photosensitive behavioural response and show sparse zooxanthellar expulsion and coral tissue rupture at higher intensities of blue light. The simple and flexible technique enables non-invasive continuous dynamic imaging of highly photosensitive organisms with sizes between 1 mm3 and 5 cm3, for eight hours, at high temporal resolution, on a scale from multiple polyps down to cellular resolution. This live imaging tool opens a new window into the dynamics of reef-building corals.

developmental biology↗

bioRxiv2019

Non-invasive neuromodulation using rTMS and the Electromagnetic-Preceptive Gene (EPG) facilitates plasticity after nerve injury

Peripheral nerve injury leads to altered cortical excitation-inhibition balance which is associated with sensory dysfunctions. We tested if non-invasive repetitive transcranial magnetic stimulation (rTMS) which has shown to induce neuronal excitability, and cell-specific magnetic activation via the Electromagnetic-perceptive gene (EPG) which is a novel gene that was identified and cloned from Kryptopterrus bicirrhis and demonstrated to evoke neural responses when magnetically stimulated, can restore cortical excitability. A battery of behavioral tests, fMRI and immunochemistry were performed in the weeks following limb denervation in rats. The results demonstrate that neuromodulation significantly improved long-term mobility, decreased anxiety and enhanced neuroplasticity. The study also identifies the acute post-injury phase as a critical time for intervention. Moreover, the results implicate EPG as an effective cell-specific neuromodulation approach. Together, these results reinforce the growing amount of evidence from human and animal studies that are establishing neuromodulation as an effective strategy to promote plasticity and rehabilitation.

neuroscience↗

bioRxiv2019

Neuronal histone methyltransferase EZH2 regulates neuronal morphogenesis, synaptic plasticity, and cognitive behavior of mice

Recent studies showed that in the nervous system histone methyltransferase EZH2-mediated trimethylation of histone H3 lysine 27 (H3K27me3) acts to regulate neural stem cell proliferation and fate specificity through silencing different gene sets. Here we explored the function of EZH2 in early post-mitotic excitatory neurons by generating a neuronal specific Ezh2 conditional knockout mouse line. The results showed that lack of neuronal EZH2 led to delayed neuronal migration, more complex dendritic arborization, and significantly increased dendritic spine density. RNA-sequencing (RNA-seq) experiments comparing control and Ezh2 knockout neurons revealed that neuronal EZH2 regulated genes related to neuronal morphogenesis. In particular, Pak3 was identified as a target gene suppressed by EZH2 and H3K27me3, and expression of dominant negative PAK3 reversed Ezh2 knockout-induced higher dendritic spine density. Lastly, lack of neuronal EZH2 resulted in impaired memory behaviors in adult mice. Our results demonstrated that neuronal EZH2 played important roles in controlling multiple steps of neuronal morphogenesis during development, which had long-lasting effects on cognitive function in adult mice.

neuroscience↗

bioRxiv2019

Neural circuits mediating visual stabilization during active motion in zebrafish

Visual stabilization is an inevitable requirement for animals during active motion interaction with the environment. Visual motion cues of the surroundings or induced by self-generated behaviors are perceived then trigger proper motor responses mediated by neural representations conceptualized as the internal model: one part of it predicts the consequences of sensory dynamics as a forward model, another part generates proper motor control as a reverse model. However, the neural circuits between the two models remain mostly unknown. Here, we demonstrate that an internal component, the efference copy, coordinated the two models in a push-pull manner by generating extra reset saccades during active motion processing in larval zebrafish. Calcium imaging indicated that the saccade preparation circuit is enhanced while the velocity integration circuit is inhibited during the interaction, balancing the internal representations from both directions. This is the first model of efference copy on visual stabilization beyond the sensorimotor stage.

neuroscience↗

bioRxiv2018

SeqOthello: Query over RNA-seq experiments at scale

We present SeqOthello, an ultra-fast and memory-efficient indexing structure to support arbitrary sequence query against large collections of RNA-seq experiments. SeqOthello requires only five minutes to conduct a global survey of 11,658 fusion events against 10,113 TCGA Pan-Cancer RNA-seq datasets on a standard computer with 19.1 GB memory space. The query recovers 92.7% of tier-1 fusions curated by TCGA Fusion Gene Database and further reveals 270 novel fusion occurrences, all of which present as tumor-specific. The entire index is only 76 GB, achieving a 700:1 compression ratio relative to the original sequencing data and making it extremely portable. This is the first sequence search index constructed on the scale of TCGA data. By providing a reference-free, alignment-free, and parameter-free sequence search system, SeqOthello will enable large-scale integrative studies using sequence-level data, an undertaking not previously practicable for many individual labs. SeqOthello is currently available at https://github.com/LiuBioinfo/SeqOthello.

bioinformatics↗