Biology subjects

Qiao, Z.

Publications and source records attributed to Qiao, Z..

26 records · Page 2Linked to original sources

bioRxiv2021

Calcium-independent but voltage-dependent secretion (CiVDS) mediates synaptic transmission in a mammalian central synapse

A central principle of synaptic transmission is that action potential-induced presynaptic neurotransmitter release occurs exclusively via Ca2+-dependent secretion (CDS). The discovery and mechanistic investigations of Ca2+-independent but voltage-dependent secretion (CiVDS) have demonstrated that the action potential per se is sufficient to trigger neurotransmission in the somata of primary sensory and sympathetic neurons in mammals. One key question remains, however, whether CiVDS contributes to central synaptic transmission. Here we report, in the central transmission from presynaptic (dorsal root ganglion) to postsynaptic (spinal dorsal horn) neurons, (1) excitatory postsynaptic currents (EPSCs) are mediated by glutamate transmission through both CiVDS (up to 87%) and CDS; (2) CiVDS-EPSCs are independent of extracellular and intracellular Ca2+; (3) CiVDS is >100 times faster than CDS in vesicle recycling with much less short-term depression; (4) the fusion machinery of CiVDS includes Cav2.2 (voltage sensor) and SNARE (fusion pore). Together, an essential component of activity-induced EPSCs is mediated by CiVDS in a central synapse.

neuroscience↗

bioRxiv2021

Single Cell Biological Microlasers Powered by Deep Learning

Cellular lasers are cutting-edge technologies for biomedical applications. Due to the enhanced interactions between light and cells in microcavities, cellular properties and subtle changes of cells can be significantly reflected by the laser emission characteristics. In particular, transverse laser modes from single-cell lasers which utilize Fabry-Perot cavities are highly correlated to the spatial biophysical properties of cells. However, the high chaotic and complex variation of laser modes limits their practical applications for cell detections. Deep learning technique has demonstrated its powerful capability in solving complex imaging problems, which is expected to be applied for cell detections based on laser mode imaging. In this study, deep learning technique was applied to analyze laser modes generated from single-cell lasers, in which a correlation between laser modes and physical properties of cells was built. As a proof-of-concept, we demonstrated the predictions of cell sizes using deep learning based on laser mode imaging. In the first part, bioinspired cell models were fabricated to systematically study how cell sizes affect the characteristics of laser modes. By training a convolutional neuron network (CNN) model with laser mode images, predictions of cell model diameters with a sub-wavelength accuracy were achieved. In the second part, deep learning was employed to study laser modes generated from biological cells. By training a CNN model with laser mode images acquired from astrocyte cells, predictions of cell sizes with a sub-wavelength accuracy were also achieved. The results show the great potential of laser mode imaging integrated with deep learning for cell analysis and biophysical studies.

biophysics↗

bioRxiv2020

Chemical composition, antimicrobial and antioxidant activities of essential oils from the receptacle of sunflower (Helianthus annuus L.)

Sunflower (Helianthus annuus L.) contains active ingredients, such as flavonoids, alkaloids and tannins. However, few studies have focused on essential oils from the receptacle of sunflower (SEOs). The chemical composition, antimicrobial and antioxidant activities of SEOs were assessed whether SEOs could be used as nature preservatives and medicines. The extraction rate of SEOs was 0.4% by using hydro-distillation and solvent with petroleum ether, which is much higher than that by only using hydro-distillation (0.2%) in the previous study. A total of 81 volatile constituents of SEOs were identified by gas chromatography-mass spectrometry (GC-MS). The main constituents of SEOs were -pinene (31.17%), calamenene (5.66%), -terpineol (4.71%), verbenone (3.15%), kaur-16-ene (2.52%) and terpinolene (1.47%). The antimicrobial activities of SEOs were assessed against three bacteria (E. coli, P. aeruginosa, and S. aureus) and two fungi (S. cerevisiae and Candida albicans). The MIC of SEOs against P. aeruginosa and S. aureus was 0.2 mg/mL. The MIC of SEOs against S. cerevisiae was 3.2 mg/mL. The MIC of SEOs against E. coli and Candida albicans was 6.4 mg/mL. The results showed that SEOs had high antibacterial and antifungal actions. The antioxidant activity was determined with three different analytical assays (DPPH, ABTS and iron reducing ability). The results of antioxidant activities showed that SEOs had high antioxidant activities. The results proved that SEOs could be used as natural preservatives and medicines, due to its excellent antimicrobial and antioxidant activities.

microbiology↗

bioRxiv2020

Performance characterization of PCR-free whole genome sequencing for clinical diagnosis

PurposeTo evaluate the performance of PCR-free whole genome sequencing (WGS) for clinical diagnosis, and thereby revealing how experimental parameters affect variant detection. MethodsAll the 5 NA12878 samples were sequenced using MGISEQ-2000. NA12878 samples underwent WGS with differing DNA input and library preparation protocol (PCR-based versus PCR-free protocols for library preparation). The DP (depth of coverage) and GQ (genotype quality) of each sample were compared. We developed a systematic WGS pipeline for the analysis of down-sampling samples of the 5 NA12878 samples. The performance of each sample was measured for sensitivity, coverage of depth and breadth of coverage of disease-related genes and CNVs. ResultsIn general, NA12878-2 (PCR-free WGS) showed better DP and GQ distribution than NA12878-1 (PCR-based WGS). With a mean depth of ~40X, the sensitivity of homozyous and heterozygous SNPs of NA12878-2 showed higher sensitivity (>99.77% and > 99.82%) than NA12878-1, and positive predictive value (PPV) exceeded 99.98% and 99.07%. The sensitivity and PPV of homozygous and heterozygous indels for NA12878-2 (PCR-free WGS) showed great improvement than NA128878-1. The breadths of coverage for disease-related genes and CNVs are slightly better for samples with PCR-free library preparation protocol than the sample with PCR-based library preparation protocol. DNA input also influences the performance of variant detection in samples with PCR-free WGS. ConclusionDifferent experimental parameters may affect variant detection for clinical WGS. Clinical scientists should know the range of sensitivity of variants for different methods of WGS, which would be useful when interpreting and delivering clinical reports.

genetics↗

bioRxiv2019

Genome-wide association study identifies 143 loci associated with 25 hydroxyvitamin D concentration.

Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes. In a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration in 417,580 Europeans we identified 143 independent loci in 112 1-Mb regions providing new insights into the physiology of vitamin D and implicating genes involved in (a) lipid and lipoprotein metabolism, (b) dermal tissue properties, and (c) the sulphonation and glucuronidation of 25OHD. Mendelian randomization models found no robust evidence that 25OHD concentration had causal effects on candidate phenotypes (e.g. BMI, psychiatric disorders), but many phenotypes had (direct or indirect) causal effects on 25OHD concentration, clarifying the relationship between 25OHD status and health.

genetics↗

bioRxiv2018

The effect of plasma lipids and lipid lowering interventions on bone mineral density: a Mendelian randomization study

Statin treatment increases bone mineral density (BMD) and reduces fracture risk, but the underlying mechanism is unclear. We used Mendelian randomization (MR) to assess whether this relation is explained by a specific effect in response to statin use, or by a general effect of lipid-lowering. We utilized 400 single nucleotide polymorphisms (SNPs) robustly associated with plasma lipid levels and results from a heel BMD GWAS (derived from quantitative ultrasound) in 426,824 individuals from the UK Biobank. We performed univariate and multivariable MR analyses of low-density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C) and triglyceride levels on BMD. To test whether the effect of statins on BMD was mediated by lowering lipid levels, MR was repeated with and without SNPs in the HMGCR region, the gene targeted by statins. Univariate MR analyses provided evidence for a causal effect of LDL-C on BMD ({beta} = -0.060; -0.084 to -0.036; P = 4x10-6; standard deviation change in BMD per standard deviation change in LDL-C, with 95% CI), but not HDL or triglycerides. Multivariable MR analysis suggested that the effect of LDL-C on BMD was independent of HDL-C and triglycerides, and sensitivity analyses involving MR Egger and weighted median MR approaches suggested that the LDL-C results were robust to pleiotropy. MR analyses of LDL-C restricted to SNPs in the HMGCR region showed similar effects on BMD({beta} = -0.083; -0.132 to -0.034; P = 0.001) to those excluding these SNPs ({beta} = -0.063; -0.090 to -0.036; P = 8x10-6). Bidirectional MR analyses provided some evidence for a causal effect of BMD on plasma LDL-C levels. Our results suggest that effects of statins on BMD are at least partly due to their LDL-C lowering effect. Further studies are required to examine the potential role of modifying plasma lipid levels in treating osteoporosis.

epidemiology↗

bioRxiv2018

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors

Birth weight (BW) variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. These associations have been proposed to reflect the lifelong consequences of an adverse intrauterine environment. In earlier work, we demonstrated that much of the negative correlation between BW and adult cardio-metabolic traits could instead be attributable to shared genetic effects. However, that work and other previous studies did not systematically distinguish the direct effects of an individuals own genotype on BW and subsequent disease risk from indirect effects of their mothers correlated genotype, mediated by the intrauterine environment. Here, we describe expanded genome-wide association analyses of own BW (n=321,223) and offspring BW (n=230,069 mothers), which identified 278 independent association signals influencing BW (214 novel). We used structural equation modelling to decompose the contributions of direct fetal and indirect maternal genetic influences on BW, implicating fetal- and maternal-specific mechanisms. We used Mendelian randomization to explore the causal relationships between factors influencing BW through fetal or maternal routes, for example, glycemic traits and blood pressure. Direct fetal genotype effects dominate the shared genetic contribution to the association between lower BW and higher type 2 diabetes risk, whereas the relationship between lower BW and higher later blood pressure (BP) is driven by a combination of indirect maternal and direct fetal genetic effects: indirect effects of maternal BP-raising genotypes act to reduce offspring BW, but only direct fetal genotype effects (once inherited) increase the offsprings later BP. Instrumental variable analysis using maternal BW-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring BP. In successfully separating fetal from maternal genetic effects, this work represents an important advance in genetic studies of perinatal outcomes, and shows that the association between lower BW and higher adult BP is attributable to genetic effects, and not to intrauterine programming.

genetics↗

bioRxiv2016

p53 dynamically directs TFIID assembly on target gene promoters

The p53 tumor suppressor protein is a central regulator that turns on vast gene networks to maintain cellular integrity upon various stimuli. p53 activates transcription initiation in part by aiding recruitment of TFIID to the promoter. However, the precise means by which p53 dynamically interacts with TFIID to facilitate assembly on target gene promoters remains elusive. To address this key question, we have undertaken an integrated approach involving single molecule fluorescence microscopy, single particle cryo-electron microscopy, and biochemistry. Our real-time single molecule imaging demonstrates that TFIID alone binds poorly to native p53 target promoters. p53 unlocks TFIIDs ability to bind DNA by increasing TFIID contacts with both the core promoter and a region surrounding p53s response element (RE). Analysis of single molecule dissociation kinetics reveals that TFIID interacts with promoters via transient and prolonged DNA binding modes that are each regulated by p53. Importantly, our structural work reveals that TFIIDs conversion from a canonical form to a rearranged DNA-binding conformation is enhanced in the presence of DNA and p53. Notably, TFIIDs interaction with DNA induces p53 to rapidly dissociate, effectively liberating the RE on the promoter. Collectively, these findings indicate that p53 dynamically escorts and loads the basal transcription machinery onto its target promoters.

biochemistry↗