Biology subjects

Chen, Z.

Publications and source records attributed to Chen, Z..

At least 937 records · Page 52Linked to original sources

bioRxiv2018

Noninvasive prenatal detection of fetal trisomy and single gene disease by shotgun sequencing of placenta originated exosome DNA: a proof-of-concept validation

BackgroundDuring human pregnancy, Placental trophectoderm cells can release exosomes into maternal circulation. Trophoblast cells also give rise to cell-free DNA (cfDNA) and has been used for noninvasive prenatal screening for chromosomal aneuploidy. We intended to prove the existence of exosomal DNA (exoDNA) in the exosomes of maternal blood and compared exoDNA with plasma cfDNA in terms of genome distribution, fragment length, and the possibility of detecting genetic diseases.\n\nMethodsMaternal blood from 20 euploid pregnancies, 9 T21 pregnancies, 3 T18 pregnancies, 1 T13 pregnancy and 2 pregnancies with FGFR3 mutations were obtained. Exosomes enriched from maternal plasma were confirmed by transmission electronic microscopy (TEM), western blotting and flow cytometry. ExoDNA was extracted and its fetal origin was confirmed by realtime fluorescence quantitative PCR(Q-PCR). Besides, exoDNA content was uncovered by Q-PCR. To characterize exoDNA and compare with cfDNA, pair-end whole genome sequencing was performed. Lastly, the fetal risk of genetic diseases was analyzed using the exoDNA sequencing data.\n\nResultsExoDNA span on all 23 pairs of chromosomes and mitochondria, sharing a similar distribution pattern and higher GC content comparing with cfDNA. ExoDNA showed shorter fragments yet lower fetal fraction than cfDNA. ExoDNA could be used to determine fetal gender correctly, and all trisomies as well as de novo FGFR3 mutations.\n\nConclusionsWe proved that fetal exoDNA could be identified in the exosomes extracted from maternal plasma. ExoDNA shared some similar features to cfDNA and could potentially be used to detect genetic diseases in fetus.

genetics↗

bioRxiv2018

MR-PET head motion correction based on co-registration of multi-contrast MR images

Head motion is a major source of image artefacts in neuroimaging studies and can lead to degradation of the quantitative accuracy of reconstructed PET images. Simultaneous Magnetic Resonance-Positron Emission Tomography (MR-PET) makes it possible to estimate head motion information from high-resolution MR images and then correct motion artefacts in PET images. In this paper, we introduce a fully automated PET motion correction method, MR-guided MAF, based on the co-registration of multi-contrast MR images. The performance of the MR-guided MAF method was evaluated using MR-PET data acquired from a cohort of ten healthy participants who received a slow infusion of fluorodeoxyglucose ([18-F]FDG). Compared with conventional methods, MR guided PET image reconstruction can reduce head motion introduced artefacts and improve the image sharpness and quantitative accuracy of PET images acquired using simultaneous MR-PET scanners. The fully automated motion estimation method has been implemented as a publicly available web-service.

bioinformatics↗

bioRxiv2018

Simultaneous task-based BOLD-fMRI and FDG functional PET for measurement of neuronal metabolism in the human visual cortex

Studies of task-evoked brain activity are the cornerstone of cognitive neuroscience, and unravel the spatial and temporal brain dynamics of cognition in health and disease. Blood oxygenation level dependent functional magnetic resonance imaging (BOLD-fMRI) is one of the most common methods of studying brain function in humans. BOLD-fMRI indirectly infers neuronal activity from regional changes in blood oxygenation and is not a quantitative metric of brain function. Regional variation in glucose metabolism, measured using [18-F] fluorodeoxyglucose positron emission tomography (FDG-PET), provides a more direct and interpretable measure of neuronal activity. However, while the temporal resolution of BOLD-fMRI is in the order of seconds, standard FDG-PET protocols provide a static snapshot of glucose metabolism. Here, we develop a novel experimental design for measurement of task-evoked changes in regional blood oxygenation and glucose metabolism with high temporal resolution. Over a 90-min simultaneous BOLD-fMRI/FDG-PET scan, [18F] FDG was constantly infused to 10 healthy volunteers, who viewed a flickering checkerboard presented in a hierarchical block design. Dynamic task-related changes in blood oxygenation and glucose metabolism were examined with temporal resolution of 2.5sec and 1-min, respectively. Task-related, temporally coherent brain networks of haemodynamic and metabolic connectivity were maximally related in the visual cortex, as expected. Results demonstrate that the hierarchical block design, together with the infusion FDG-PET technique, enabled both modalities to track task-related neural responses with high temporal resolution. The simultaneous MR-PET approach has the potential to provide unique insights into the dynamic haemodynamic and metabolic interactions that underlie cognition in health and disease.

neuroscience↗

bioRxiv2018

A comprehensive framework to capture the arcana of neuroimaging analysis

Mastering the \"arcana of neuroimaging analysis\", the obscure knowledge required to apply an appropriate combination of software tools and parameters to analyse a given neuroimaging dataset, is a time consuming process. Therefore, it is not typically feasible to invest the additional effort required generalise workflow implementations to accommodate for the various acquisition parameters, data storage conventions and computing environments in use at different research sites, limiting the reusability of published workflows.\n\nWe present a novel software framework, Abstraction of Repository-Centric ANAlysis (Arcana), which enables the development of complex, \"end-to-end\" workflows that are adaptable to new analyses and portable to a wide range of computing infrastructures. Analysis templates for specific image types (e.g. MRI contrast) are implemented as Python classes, which define a range of potential derivatives and analysis methods. Arcana retrieves data from imaging repositories, which can be BIDS datasets, XNAT instances or plain directories, and stores selected derivatives and associated provenance back into a repository for reuse by subsequent analyses. Workflows are constructed using Nipype and can be executed on local workstations or in high performance computing environments. Generic analysis methods can be consolidated within common base classes to facilitate code-reuse and collaborative development, which can be specialised for study-specific requirements via class inheritance. Arcana provides a framework in which to develop unified neuroimaging workflows that can be reused across a wide range of research studies and sites.

bioinformatics↗

bioRxiv2018

Using pan RNA-seq analysis to reveal the ubiquitous existence of 5′ end and 3′ end small RNAs

In this study, we used pan RNA-seq analysis to reveal the ubiquitous existence of 5 end and 3 end small RNAs. 5 and 3 sRNAs alone can be used to annotate mitochondrial with 1-bp resolution and nuclear non-coding genes and identify new steady-state RNAs, which are usually from functional genes. Using 5, 3 and intronic sRNAs, we revealed that the enzymatic dsRNA cleavage and RNAi could involve in the RNA degradation and gene expression regulation of U1 snRNA in human. The further study of 5, 3 and intronic sRNAs help rediscover double-stranded RNA (dsRNA) cleavage, RNA interference (RNAi) and the regulation of gene expression, which challenges the classical theories. In this study, we provided a simple and cost effective way for the annotation of mitochondrial and nuclear non-coding genes and the identification of new steady-state RNAs, particularly long non-coding RNAs (lncRNAs). We also provided a different point of view for cancer and virus, based on the new discoveries of dsRNA cleavage, RNAi and the regulation of gene expression.

bioinformatics↗

bioRxiv2018

Bacteroides fragilis defense against Cronobacter sakazakii -induced pathogenicity by regulating the intestinal epithelial barrier function and attenuating both apoptotic and pyroptotic cell death

Cronobacter sakazakii (CS), an important pathogen, is associated with the development of necrotizing enterocolitis (NEC), infant sepsis, and meningitis. Several randomized prospective clinical trials demonstrated that oral probiotics could decrease the incidence of NEC. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. However, it remains unclear how ZY-312 protects the host from the effects of CS infection. To understand the underlying mechanisms triggering the probiotic effects, we tested the hypothesis that there was a cross-talk between probiotics/probiotics-modulated microbiota and the local immune system, governed by the permeability of the intestinal mucosa using in vitro and in vivo models for the intestinal permeability. The probiotic effects of ZY-312 on intestinal epithelial cells were first examined, which revealed that ZY-312 inhibited CS invasion, CS-induced dual cell death (pyroptosis and apoptosis), and epithelial barrier dysfunction in vitro and in vivo. ZY-312 also decreased the expression of an inflammasome (NOD-like receptor family member pyrin domain-containing protein 3 (NLRP3), caspase-3, and serine protease caspase-1 in a neonatal rat model. Furthermore, ZY-312 significantly modulated the compositions of the intestinal bacterial communities, and decreased the relative abundances of Proteobacteria, Gamma proteobacteria, but increased the relative abundance of Bacteroides and Bacillus in neonatal rats. In conclusion, our findings have shown for the first time that the probiotic, B. fragilis ZY-312, suppresses CS-induced NEC by modulating the pro-inflammatory response and dual cell death (apoptosis and pyroptosis).\n\nAuthor summaryCronobacter sakazakii, a major necrotizing enterocolitis pathogen, is used as a model microorganism for the study of opportunistic bacteria in the pathogenesis of necrotizing enterocolitis. Here, we have now unequivocally demonstrated that both apoptotic and pyroptotic stimuli contribute to the pathogenesis of Cronobacter sakazakii -induced necrotizing enterocolitis. Previously, we isolated and characterized a novel probiotic, B. fragilis strain ZY-312. We found that the ZY-312 defense against Cronobacter sakazakii-induced necrotizing enterocolitis by inhibiting Cronobacter sakazakii invasion, epithelial barrier dysfunction, the expression of inflammatory cytokines and dual cell death (pyroptosis and apoptosis). This study demonstrates the utility of ZY-312 as a promising probiotic agent for the prevention and treatment of various intestinal diseases, including NEC.

microbiology↗

bioRxiv2018

Single-cell microRNA/mRNA co-sequencing reveals non-genetic heterogeneity and novel regulatory mechanisms

Co-measurement of multiple omic profiles from the same single cells opens up the opportunity to decode molecular regulation that underlie intercellular heterogeneity in development and disease. Here, we present co-sequencing of microRNAs and mRNAs in the same single cells using a half-cell genomics approach. This method demonstrates good robustness (~95% success rate) and reproducibility (R2=0.93 for both miRNAs and mRNAs), and yields paired half-cell miRNA and mRNA profiles that could be independently validated. Linking the level of miRNAs to the expression of predicted target mRNAs across 19 single cells that are phenotypically identical, we observe that the predicted targets are significantly anti-correlated with the variation of abundantly expressed miRNAs, suggesting that miRNA expression variability alone may lead to non-genetic cell-to-cell heterogeneity. Genome-scale analysis of paired miRNA-mRNA co-profiles further allows us to derive and validate new regulatory relationships of cellular pathways controlling miRNA expression and variability.

systems biology↗

bioRxiv2018

Downregulation of insulin-like growth factor binding protein 5 is involved in intervertebral disc degeneration via the ERK signaling pathway

Introduction Introduction Results Discussion Material and methods Conflict of interest References Intervertebral disc degeneration (IDD) is a disease of discs connecting adjoining vertebrae in which structural damage causes the degeneration of the disc and the surrounding area. This disease represents a common cause of back pain, and its treatment is costly and relatively ineffective (Kepler et al., 2013), with patients who do not achieve improvement with conservative management possibly requiring surgery (Lurie et al., 2014; Postacchini, 1996). It has been reported that the central features of IDD are the reduction in the nucleus pulposus (NP) cell population and the loss of extracellular matrix molecules (ECM), which eventually leads to major changes in the ...

molecular biology↗

bioRxiv2018

Distribution of duck-origin parvovirus in Cherry Valley ducks in vivo over time and histopathological investigation

In 2015, we successfully isolated a strain of duck-origin parvovirus from Cherry Valley ducks, which we named QH-L01. In this study, duck-origin parvovirus in Cherry Valley ducks was quantified and localized by quantitative real-time PCR (qPCR) and immunohistochemistry (IHC), and pathological damage to the tissues and organs was observed by hematoxylin-eosin staining (HE staining). qPCR showed that the viral load was higher in the spleen, brain, lung, cecum, ileum, and duodenum over time. The results from IHC experiments showed positive reactions in hepatocytes, epithelium of the lung atrium, myocardial cells, goblet cells of the intestine, and brain cells. Primary histological examination revealed pulmonary lobule depletion and dilation in the lung as well as necrosis and erosion of the villus tips in the duodenum, ileum and cecum. This study is the first demonstration that duck-origin parvovirus can be transmitted from the spleen to the brain and lung, resulting in proliferation and dissemination of the virus to the cecum, ileum, duodenum and other tissues through the blood. The lung, duodenum, ileum and cecum may thus represent the main target tissues and organs for duck-origin parvovirus.

zoology↗

bioRxiv2018

Inoculation with Pisolithus tinctorius may ameliorate acid rain impacts on soil microbial communities associated with Pinus massoniana seedlings

Human activities accelerate acidification, particularly as acid rain, which may have lasting impacts on soil abiotic and biotic parameters. However, the effects of acidification on aboveground vegetation, belowground communities, and carbon cycling remains unresolved. We examined the effects of long-term acidic treatments and Pisolithus inoculation on plants, soils, and microbial communities in pine plantations and found that exposure to severely-acidic treatments diminished plant performance, altered microbial communities, and decreased organic matter, nitrate, and available phosphorus. Although we did not detect any benefits of Pisolithus inoculation for Pinus seedlings impacted by severely-acidic treatments, when these severe treatments were inoculated with Pisolithus, both soil properties and microbial community composition shifted. We posit that inoculation with Pisolithus may alleviate stressful environmental conditions, and change the structure of mycorrhizal fungal communities. Although acidification may alter biogeochemical cycles and constrain aboveground and belowground communities, Pisolithus inoculation may provide benefits to some components of forested ecosystems.

ecology↗

bioRxiv2018

Structural basis for recruitment of DAPK1 to the KLHL20 E3 ligase

BTB-Kelch proteins form the largest subfamily of Cullin-RING E3 ligases, yet their substrate complexes are mapped and structurally characterized only for KEAP1 and KLHL3. KLHL20 is a related CUL3-dependent ubiquitin ligase linked to autophagy, cancer and Alzheimers disease that promotes the ubiquitination and degradation of substrates including DAPK1, PML and ULK1. We identified a LPDLV-containing recruitment site in the DAPK1 death domain and determined the 1.1 [A] crystal structure of a KLHL20-DAPK1 complex. DAPK1 binds to KLHL20 as a loose helical turn that inserts deeply into the central pocket of the Kelch domain to contact all six blades of the {beta}-propeller. Here, KLHL20 forms a salt bridge as well as hydrophobic interactions that include a tryptophan and cysteine residue ideally positioned for covalent inhibitor development. The structure highlights the diverse binding modes of circular substrate pockets versus linear grooves and suggests a novel E3 ligase for protac-based drug design.

molecular biology↗

bioRxiv2018

Population based hospitalization burden of laboratory-confirmed hand, foot and mouth disease caused by multiple enterovirus serotypes in southern China

BackgroundHand, foot and mouth disease (HFMD) is spread widely across Asia, and the hospitalization burden is as yet not well understood. Here, we estimated serotype-specific and age-specific hospitalization rates of HFMD in Southern China.\n\nMethodsWe enrolled pediatric patients admitted to 3/3 county-level hospitals and 3/23 township level hospitals in Anhua county, Hunan (CN) with HFMD, and collected samples to identify enterovirus serotypes by RT-PCRs between October 2013 and September 2016. The information of other eligible but un-enrolled patients were retrospectively collected from the same six hospitals. Monthly number of hospitalizations for all causes was collected from each of 23 township level hospitals to extrapolate hospitalizations associated with HFMD among these.\n\nResultsDuring the three years, an estimated 3,236 pediatric patients were hospitalized with lab-confirmed HFMD, and among these only one patient was severe. The mean hospitalization rates were 660 (95% CI: 638-684) per 100,000 person-years for lab-confirmed HFMD, with higher rates among CV-A16 and CV-A6 associated HFMD (213 vs 209 per 100,000 person-years), and lower among EV-A71, CV-A10 and other enteroviruses associated HFMD (134, 39 and 66 per 100,000 person-years, p<0.001). Children aged 12-23 months had the highest hospitalization rates (3,594/100,000 person-years), followed by those aged 24-35 months (1,828/100,000 person-years) and 6-11 months (1,572/100,000 person-years). Compared with other serotypes, CV-A6-associated hospitalizations were evident at younger ages.\n\nConclusionsOur study indicates a substantial hospitalization burden associated with non-severe HFMD in a rural county in southern China. Future mitigation policies should take into account the disease burden identified, and optimize interventions for HFMD.

epidemiology↗

bioRxiv2018

A novel function of Galactomyces candidum in highly efficient ammonia nitrogen removal from low C:N wastewater

A strain of bacteria that demonstrated efficient nitrogen removal potential under low C:N conditions was screened from landfill leachate. The strain was identified as Galactomyces candidum by ITS sequencing, and growth density and removal of ammonia nitrogen were assessed after 24 h of incubation. The results showed that the optimum ammonia nitrogen reduction conditions for G. candidum was at pH 8.0 and 30 {degrees}C, with a C:N ratio of 1.5:1; the highest rate of ammonia nitrogen removal was 93.1%. This novel function of G. candidum offers great potential in the removal of ammonia nitrogen from sewage, especially in low C:N wastewater. Our study provides a new theoretical basis for the industrial application of bacteria in the biochemical treatment of wastewater and reduces environmental pollution.\n\nA novel function and potential of Galamyces candidum in the removal of ammonia nitrogen from wastewater treatment was found, which provides a theoretical basis for the treatment of ammonia in wastewater.

microbiology↗

bioRxiv2018

Active information maintenance in working memory by a sensory cortex

Working memory is a critical function of the brain to maintain and manipulate information over delay periods of seconds. Sensory areas have been implicated in working memory; however, it is debated whether the delay-period activity of sensory regions is actively maintaining information or passively reflecting top-down inputs. We hereby examined the anterior piriform cortex, an olfactory cortex, in head-fixed mice performing a series of olfactory working memory tasks. Information maintenance is necessary in these tasks, especially in a dual-task paradigm in which mice are required to perform another distracting task while actively maintaining information during the delay period. Optogenetic suppression of the piriform cortex activity during the delay period impaired performance in all the tasks.Furthermore, electrophysiological recordings revealed that the delay-period activity of the anterior piriform cortex encoded odor information with or without the distracting task.Thus, this sensory cortex is critical for active information maintenance in working memory.

neuroscience↗

bioRxiv2018

Opposing effects of impulsivity and mindset on sources of science self-efficacy and STEM interest in adolescents

Impulsivity has been linked to academic performance in the context of Attention Deficit Hyperactivity Disorder, though its influence on a wider spectrum of students remains largely unexplored, particularly in the context of STEM learning (i.e. science, technology, engineering, and math). STEM learning was hypothesized to be more challenging for impulsive students, since it requires the practice and repetition of tasks as well as concerted attention to task performance. Impulsivity was assessed in a cross-sectional sample of 2,476 students in grades 6-12. Results show impulsivity affects a larger population of students, not limited to students with learning disabilities. Impulsivity was associated with lower sources of science self-efficacy (SSSE) scores, interest in all STEM domains (particularly math), and self-reported STEM skills. The large negative effect observed for impulsivity was opposed by \"growth\" mindset, which describes a students belief in the importance of effort when learning is difficult. Mindset had a large positive effect, which was associated with greater SSSE, STEM interest, and STEM skills. When modeled together, results suggest that mindset interventions may benefit impulsive students who struggle with STEM. Together, these data suggest important interconnected roles for impulsivity and mindset that can influence secondary students STEM trajectories.

scientific communication and education↗

bioRxiv2018

De Novo assembly of the goldfish (Carassius auratus) genome and the evolution of genes after whole genome duplication

For over a thousand years throughout Asia, the common goldfish (Carassius auratus) was raised for both food and as an ornamental pet. Selective breeding over more than 500 years has created a wide array of body and pigmentation variation particularly valued by ornamental fish enthusiasts. As a very close relative of the common carp (Cyprinus carpio), goldfish shares the recent genome duplication that occurred approximately 14-16 million years ago (mya) in their common ancestor. The combination of centuries of breeding and a wide array of interesting body morphologies is an exciting opportunity to link genotype to phenotype as well as understanding the dynamics of genome evolution and speciation. Here we generated a high-quality draft sequence of a \"Wakin\" goldfish using 71X PacBio long-reads. We identified 70,324 coding genes and more than 11,000 non-coding transcripts. We found that the two sub-genomes in goldfish retained extensive synteny and collinearity between goldfish and zebrafish. However, \"ohnologous\" genes were lost quickly after the carp whole-genome duplication, and the expression of 30% of the retained duplicated gene diverged significantly across seven tissues sampled. Loss of sequence identity and/or exons determined the divergence of the expression across all tissues, while loss of conserved, non-coding elements determined expression variance between different tissues. This draft assembly also provides an important resource for comparative genomics with the very commonly used zebrafish model (Danio rerio), and for understanding the underlying genetic causes of goldfish variants.

genomics↗

bioRxiv2018

Two essential replicative DNA polymerases exchange dynamically during DNA replication and after replication fork arrest

The replisome is the multi-protein complex responsible for faithful replication of chromosomal DNA. Using single-molecule super-resolution imaging, we characterized the dynamics of three replisomal proteins in live Bacillus subtilis cells: the two replicative DNA polymerases, PolC and DnaE, and a processivity clamp loader subunit, DnaX. We quantified the protein mobility and dwell times during normal replication and following both damage-independent and damage-dependent replication fork stress. With these results, we report the dynamic and cooperative process of DNA replication based on changes in the measured diffusion coefficients and dwell times. These experiments show that the replisomal proteins are all highly dynamic and that the exchange rate depends on whether DNA synthesis is active or arrested. Our results also suggest coupling between PolC and DnaX in the DNA replication process, and indicate that DnaX provides an important role in synthesis during repair. Furthermore, our results show that DnaE provides a limited contribution to chromosomal replication and repair.

biophysics↗

bioRxiv2018

Selective inhibition of CA IX over CA XII using benzene sulfonamides: Disconnect between CA activity and growth inhibition in breast cancer cells

Carbonic anhydrases (CAs) have been linked to tumor progression, particularly membrane-bound CA isoform IX (CA IX). The role of CA IX in the context of breast cancer is to regulate the pH of the tumor microenvironment. In contrast to CA IX, expression of CA XII, specifically in breast cancer, is associated with better outcome despite performing the same catalytic function. In this study, we have structurally modeled the orientation of bound ureido-substituted benzene sulfonamides (USBs) within the active site of CA XII, in comparison to CA IX and cytosolic off-target CA II, to understand isoform specific inhibition. This has identified specific residues within the CA active site, which differ between isoforms that are important for inhibitor binding and isoform specificity. The ability of these sulfonamides to block CA IX activity in breast cancer cells is less effective than their ability to block activity of the recombinant protein (by one to two orders of magnitude depending on the inhibitor). The same is true for CA XII activity but now they are two to three orders of magnitude less effective. Thus, there is significantly greater specificity for CA IX activity over CA XII. While the inhibitors block cell growth, without inducing cell death, this again occurs at two orders of magnitude above the Ki values for inhibition of CA IX and CA XII activity in their respective cell types. Surprisingly, the USBs inhibited cell growth even in cells where CA IX and CA XII expression was ablated. Despite the potential for these sulfonamides as chemotherapeutic agents, these data suggest that we reconsider the role of CA activity on growth potentiation.

cancer biology↗