Biology subjects

Chen, Q.

Publications and source records attributed to Chen, Q..

At least 433 records · Page 24Linked to original sources

bioRxiv2019

Placental Editome Profiling Reveals Widespread RNA-Editing Dysregulation in Preeclampsia

Dysregulated RNA editing is well documented in several diseases such as cancer. The extent to which RNA editing might be involved in diseases originated in the placenta remains unknown, because RNA editing has rarely been studied in the placenta. Here, we have systematically profiled RNA editome on the placentae from 9 patients with early-onset severe preeclampsia (EOSPE) and 32 normal subjects, and a widespread RNA editing dysregulation in EOSPE has been identified. The mis-edited gene set is enriched with known preeclampsia-associated genes and differentially expressed genes in EOSPE. The \"RNA editing events\" at two microRNA binding sites in 3-UTR of the LEP mRNA were generated, which could lead to increased expression level of LEP in trophoblast cells. Upregulation of LEP were also observed in the placentae of PE patients. These results suggest that widespread placental RNA editing may be involved in placental development and dysregulation of RNA editing in the placenta may contribute to the pathogenesis of preeclampsia.

genomics↗

bioRxiv2019

Quality Matters: Biocuration Experts on the Impact of Duplication and Other Data Quality Issues in Biological Databases

The volume of biological database records is growing rapidly, populated by complex records drawn from heterogeneous sources. A specific challenge is duplication, that is, the presence of redundancy (records with high similarity) or inconsistency (dissimilar records that correspond to the same entity). The characteristics (which records are duplicates), impact (why duplicates are significant), and solutions (how to address duplication), are not well understood. Studies on the topic are neither recent nor comprehensive. In addition, other data quality issues, such as inconsistencies and inaccuracies, are also of concern in the context of biological databases. A primary focus of this paper is to present and consolidate the opinions of over 20 experts and practitioners on the topic of duplication in biological sequence databases. The results reveal that survey participants believe that duplicate records are diverse; that the negative impacts of duplicates are severe, while positive impacts depend on correct identification of duplicates; and that duplicate detection methods need to be more precise, scalable, and robust. A secondary focus is to consider other quality issues. We observe that biocuration is the key mechanism used to ensure the quality of this data, and explore the issues through a case study of curation in UniProtKB/Swiss-Prot as well as an interview with an experienced biocurator. While biocuration is a vital solution for handling of data quality issues, a broader community effort is needed to provide adequate support for thorough biocuration in the face of widespread quality concerns.

scientific communication and education↗

bioRxiv2019

N-Acetyl Cysteine Abrogates Silver-Induced Reactive Oxygen Species in Human Cells Without Altering Silver-Based Antimicrobial Activity

Silver-based antimicrobials are widely used topically to treat infections associated with multi-drug resistant (MDR) pathogens. Expanding this topical use to aerosols to treat lung infections requires understanding and preventing silver toxicity in the respiratory tract. A key mechanism resulting in silver-induced toxicity is the production of reactive oxygen species (ROS). In this study, we have verified ROS generation in silver-treated bronchial epithelial (16HBE) cells prompting evaluation of three antioxidants, N-acetyl cysteine (NAC), ascorbic acid, and melatonin, to identify potential prophylactic agents. Among them, NAC was the only candidate that abrogated the ROS generation in response to silver exposure resulting in the rescue of these cells from silver-associated toxicity. Further, this protective effect directly translated to restoration of metabolic activity, as demonstrated by the normal levels of citric acid cycle metabolites in NAC-pretreated silver-exposed cells. As a result of the normalized citric acid cycle, cells pre-incubated with NAC demonstrated significantly higher levels of adenosine triphosphate (ATP) levels compared with NAC-free controls. Moreover, we found that this prodigious capacity of NAC to rescue silver-exposed cells was due not only to its antioxidant activity, but also to its ability to directly bind silver. Despite binding to silver, NAC did not alter the antimicrobial activity of silver.\n\nImportanceAlthough silver is a potent, broad-spectrum antibiotic, silver-induced toxicity, primarily due to generation of ROS, remains a concern limiting its use beyond treatment of wounds. NAC has been widely used as an antioxidant to rescue eukaryotic cells from metal-associated toxicity. Thus, we have evaluated the capacity of NAC to abrogate silver toxicity in a human bronchial epithelial cell line (16HBE) as a step towards expanding the use of silver-based antimicrobials to treat lung infections. We found that NAC pre-incubation resurrects a healthy metabolic state in bronchial epithelial cells exposed to silver ions via a combination of its antioxidant and metal-binding properties. Finally, this ability of NAC to rescue silver-exposed eukaryotic cells does not alter the antimicrobial activity of silver. Thus, a silver-NAC combination holds tremendous potential as a future, non-toxic antimicrobial agent.

pharmacology and toxicology↗

bioRxiv2019

Distinct molecular processes in placentae involved in two major subtypes of preeclampsia

Patients with preeclampsia display a spectrum of onset time and severity of clinical presentation, yet the underlying molecular bases for the early-onset and late-onset clinical subtypes are not known. Since the root cause of PE is thought to be located in the placentae, we carried out RNA-seq on 65 high-quality placenta samples, including 33 from 30 patients and 32 from 30 control subjects, to search for molecular features. We identified two functionally distinct sets of dysregulated genes in two major subtypes: metabolism-related genes, notably transporter genes, in early-onset severe preeclampsia and immune-related genes in late-onset severe preeclampsia, while the late-onset mild preeclampsia could not be distinguished from normal controls. A small number of dysregulated transcription factors may drive the widespread gene dysregulation in both early-onset and late-onset patients. These results suggest that early-onset and late-onset severe preeclampsia have different molecular mechanisms, whereas the late-onset mild preeclampsia may have no placenta-specific causal factors.

genomics↗

bioRxiv2019

Computational redesign of PETase for plastic biodegradation by GRAPE strategy

The excessive use of plastics has been accompanied by severe ecologically damaging effects. The recent discovery of a PETase from Ideonella sakaiensis that decomposes poly(ethylene terephthalate) (PET) under mild conditions provides an attractive avenue for the biodegradation of plastics. However, the inherent instability of the enzyme limits its practical utilization. Here, we devised a novel computational strategy (greedy accumulated strategy for protein engineering, GRAPE). A systematic clustering analysis combined with greedy accumulation of beneficial mutations in a computationally derived library enabled the design of a variant, DuraPETase, which exhibits an apparent melting temperature that is drastically elevated by 31 {degrees}C and strikingly enhanced degradation performance toward semicrystalline PET films (23%) at mild temperatures (over two orders of magnitude improvement). The mechanism underlying the robust promotion of enzyme performance has been demonstrated via a crystal structure and molecular dynamics simulations. This work shows the capabilities of computational enzyme design to circumvent antagonistic epistatic effects and provides a valuable tool for further understanding and advancing polyester hydrolysis in the natural environment.

synthetic biology↗

bioRxiv2019

CRISPR/Cas13a signal amplification linked immunosorbent assay (CLISA)

The enzyme-linked immunosorbent assay (ELISA) is a basic technique used in analytical and clinical investigations. However, conventional ELISA is still not sensitive enough to detect ultra-low concentrations of biomarkers for the early diagnosis of cancer, cardiovascular risk, neurological disorders, and infectious diseases. Herein we show a mechanism utilizing the CRISPR/Cas13a-based signal export amplification strategy, which double-amplifies the output signal by T7 RNA polymerase transcription and CRISPR/Cas13a collateral cleavage activity. This process is termed the CRISPR/Cas13a signal amplification linked immunosorbent assay (CLISA). The proposed method was validated by detecting an inflammatory factor, human interleukin-6 (human IL-6), and a tumor marker, human vascular endothelial growth factor (human VEGF), which achieved limit of detection (LOD) values of 45.81 fg/mL (2.29 fM) and 32.27 fg/m (0.81 fM), respectively, demonstrating that CLISA is at least 102-fold more sensitive than conventional ELISA.

molecular biology↗

bioRxiv2019

Reconstructing species evolutionary trees using the numerical features of microRNA

Research has revealed that some microRNAs show obvious lineage or species specificity, but others show highly conserved properties among species. Based on these properties, we aimed to reconstruct a species evolution tree using a new technique that refers to the numerical features of microRNA. First, we selected 132 microRNA numerical features that included base content, secondary structure matching state frequency, free energy features and information entropy features, and 32 species that included 22 animals, 9 plants and a representative virus group. Second, we found several significantly different numerical features among lineages or species by statistical analysis and confirmed that differences in each numerical feature were not identical. Third, we designed a comprehensive feature and confirmed that it showed obvious lineage and species specificity. Last, species trees were built using the comprehensive feature. The results showed that the reconstructed species tree was almost in keeping with the actual chronological order of species evolution. This indicated that our analysis was effective. Our research strategy offers a new route for investigating species evolution.

bioinformatics↗

bioRxiv2019

Discovery Function Labels Based On Numerical Features Of MicroRNA Found In Plant

MicroRNAs(miRNAs),are a class of small endogenous non-coding RNAs that play Important post-transcriptional regulation role by degrading targeted mRNAs or repressing mRNA translation. We screened 84 miRNAs belonging to 21 conserved family from 4014 miRNAs in miRBase database which distributed in 47 plant species. Of the predicted 274 target genes,42 GO terms were found in the Gene Ontology. With the 135 numerical features which extracted by perl program, the difference significantly result of ANOVA (P<0.001) and multiple comparison show that the function labels G...,GC content and Helix in biological process, cellular component and biological function, respectively. Our result have suggested a potential connection between numerical features of miRNAs and the function of target genes of miRNAs.

bioinformatics↗

bioRxiv2019

A new strategy for selection of crop cultivated varieties based on yield factors driving and meteorological prediction

Meteorological conditions, as an uncontrollable factor, have a direct impact on the growth and yield of crops in the field. Its particularly important to choose the cultivated varieties suitable for environmental change. As for this problem, a new strategy for selection of crop cultivated varieties is proposed in this paper. The experiment selected Harbin pilot (Heilongjiang, China) and Changchun pilot (Jilin, China). In the experiment, the cultivated varieties suitable for forecasting meteorological conditions in 2015 could be provided according to the meteorological data of 2005-2014 years and the yield data of different soybean varieties in Harbin pilot. The same method was also taken in Changchun pilot. The results showed that the recommended varieties of Harbin pilot and Changchun pilot had 70% and 50% probability respectively for selection of soybean cultivated varieties when the yield evaluation trait was 100-seed-weight. As for seed weight per plant, the possibility of more than 60% of the recommended varieties in two pilots is to provide prejudgment. Therefore, this method can help to improve the current situation of the impact of uncontrollable meteorological conditions on crop yield and also can be applied to the selection of any other crops cultivated varieties under a certain environment.

plant biology↗

bioRxiv2019

Discovering Differences and Similarities among Species Based on Numeric Features of microRNAs

Numeric features of microRNA (miRNA) are different from the other RNAs and play a key role in the course of miRNA recognition. Are there significant differences about such numeric features between different species? Are there some species specific about it? In order to answer questions, we implemented the Kolmogorov-Smirnov test for 32 species based on 132 numeric features of miRNAs. Results demonstrate that almost all kinds of miRNA secondary structures matching frequencies show highly similar, and this means that such secondary structure tend to be specific to miRNAs. Length of pre-miRNA, minimal free energy (MFE), and number of stacks show bigger difference between different species, and this means that such features tend to be species-specific. In order to discover differences and similarities among species based on numeric features of miRNAs, we design two tools-species difference map and feature difference map. By species difference map, we find that numeric features of miRNAs can represent class attribute of species and the map basically describe relationship between different species. By feature difference map, we find that there are huge difference about difference of every numeric feature between different species, and this means that strength of such difference is not uniform. Meantime, it means that numeric feature of miRNAs can represent different attributes of corresponding species. Our study present relationship between different species by brand new style-numeric features of miRNAs.

bioinformatics↗

bioRxiv2019

Single-cell molecular and cellular architecture of neurohypophyseal cell types in the adult mouse

The neurohypophysis (NH), located at the posterior lobe of the pituitary, is a major neuroendocrine tissue, which mediates osmotic balance, blood pressure, reproduction, and lactation by means of releasing the neurohormones oxytocin and arginine-vasopressin from the brain into the peripheral blood circulation. The major cellular components of the NH are hypothalamic axonal termini, fenestrated endothelia and pituicytes, the resident astroglia. However, despite the physiological importance of the NH, the exact molecular signature defining neurohypophyseal cell types and in particular the pituicytes, remains unclear. Using single cell RNA sequencing, we captured seven distinct cell types in the NH and intermediate lobe (IL) of adult male mouse. We revealed novel pituicyte markers showing higher specificity than previously reported. Single molecule in situ hybridization revealed spatial organization of the major cell types implying intercellular communications. We present a comprehensive molecular and cellular characterization of neurohypophyseal cell-types serving as a valuable resource for further functional research.\n\nSignificance StatementThe neurohypophysis (NH) is a major neuroendocrine interface, which allows the brain to regulate the function of peripheral organs in response to specific physiological demands. Despite its importance, a comprehensive molecular description of cell identities in the NH is still lacking. Utilizing single cell RNA sequencing technology, we identified the transcriptomes of five major neurohypophyseal cell types in the adult male mice and mapped the spatial distribution of selected cell types in situ. We revealed an unexpected cellular heterogeneity of the neurohypophysis and provide novel molecular markers for neurohypophyseal cell types with higher specificity than previously reported.

neuroscience↗

bioRxiv2019

Comparative transcriptomics reveal that adaptive evolution in immune genes drives the local adaptation and speciation of schizothoracine fish

Transcriptomic information can increase our understanding of the molecular processes underlying speciation. The schizothoracine fish, the largest and most diverse taxon within the Qinghai-Tibetan Plateau (QTP) ichthyofauna, are widespread in drainages throughout the QTP. These fish thus serve as an ideal model group with which to investigate how molecular evolution drives local adaptation during speciation. Here, we performed an interspecific comparative analysis of the transcriptomes of 13 schizothoracine fish species, and identified the key positively selected genes (PSGs) associated with significantly enriched functions and metabolite pathway acting on the specific lineages (or species) in the schizothoracine fish. We generated 64,637,602-83,968,472 sequence reads per schizothoracine fish species using Illumina sequencing, yielding 95,251-145,805 unigenes per species. We identified 52 out of 2,064 orthologous genes as candidate genes, which have probably been subject to positive selection along the whole schizothoracine fish lineage. Nine of these candidate genes were significantly enriched in key GO functions and metabolite pathways, all of which were associated with the immune system. The lineage-specific evolution test showed species-specific differences among the nine candidate PSGs, probably due to ecological differences among drainages, as well as among micro-habitats in the same drainage (e.g., benthic and pelagic). Here, we provide evidence that the adaptive evolution of immune genes, along with the uplift of the QTP, allowed new schizothoracine species to colonize ecologically novel environments or to exploit vacant ecological niches during speciation.\n\nSupplemental material available at FigShare: https://doi.org/10.25387/.

evolutionary biology↗

bioRxiv2019

Mutations beget more mutations - The baseline mutation rate and runaway accumulation

There is a sizable literature on mutation rate evolution (Drake 1991; Makova and Li 2002; Lynch 2011; Scally and Durbin 2012; Sung, et al. 2012) but few studies incorporate the recent genomic data from somatic tissues that suggest the operation of mutators. These data show that the mutation burden among cancer samples may vary by several orders of magnitude (Kandoth, et al. 2013; Lawrence, et al. 2013). We now propose a runaway model, applicable to both the germline and the soma, whereby the accumulation of mutator mutations forms a positive-feedback loop. In this loop, any mutator mutation would increase the probability of acquiring the next mutator, thus triggering a runaway escalation in mutation rate. The process can be initiated more readily if there are many weak, rather than a few strong, mutators. Interestingly, even a small increase in the mutation rate at birth could trigger the runaway process, resulting in unfit progeny in slowly reproducing species. In such species, the need to minimize the risk of this uncontrolled accumulation would entail a mutation rate that may seem unnecessarily low. In comparison, species that starts and ends reproduction much sooner do not face the risk and may set the baseline mutation rate higher. The mutation rate would evolve as the generation time changes, therefore explaining many puzzling evolutionary phenomena (Elango, et al. 2006; Thomas, et al. 2010; Langergraber, et al. 2012; Thomas, et al. 2018; Besenbacher, et al. 2019).

evolutionary biology↗

bioRxiv2019

The relative transmissibility of shigellosis among male and female individuals in Hubei Province, China: a modelling study

ObjectiveShigellosis has been a heavy burden in China. However, its relative transmissibility in male and female individuals remains unclear.\n\nMethodA sex-based Susceptible-Exposed-Infectious/Asymptomatic-Recovered (SEIAR) model was applied to explore the dataset of reported shigellosis cases built by Hubei Province from 2005 to 2017. Two indicators, secondary attack rate (SAR) and relative ratio of SAR between males and females, were developed to assess the relative transmissibility in males and females.\n\nResultsThe number of cases and reported incidences in males and females demonstrated a significant decreasing trend (Male trend:{chi} 2 = 11.268, P = 0.001, Female trend:{chi} 2 = 11.144, P = 0.001). SEIAR model had a great fitting effect with the data of shigellosis (P < 0.001). Our simulation revealed that, when parameter {beta}fm = 0, the greatest decrease in cases were obtained for different genders. The median value for SARmm was 2.3225 x 10-8 (Range: 1.7574 x 10-8 - 3.8565 x 10-8), SARmf was 2.5729 x 10-8 (Range: 1.3772 x 10-8 - 3.2773 x 10-8), SARfm was 2.7630 x 10-8 (Range: 1.8387 x 10-8 - 4.2638 x 10-8) and SARff was 2.1061 x 10-8 (Range: 1.0201 x 10-8 - 3.2140 x 10-8). The median value of relative ratio calculated by SAR in mm versus (vs) mf was 0.93 (Range: 0.75 - 1.47), mm vs fm was 0.90 (Range: 0.41 - 1.81), mm vs ff was 1.07 (Range: 0.55 - 2.93), mf vs fm was 0.99 (Range: 0.32 - 1.25), mf vs ff was 1.17 (Range: 0.43 - 3.21) and ff vs fm was 0.75 (Range: 0.35 - 1.06).\n\nConclusionTransmissibility of shigellosis is different among male and female individuals. Shigellosis seems to be more transmissible in males than in females.\n\nAuthor summaryShigellosis, also known as bacillary dysentery, is an infectious disease caused by the genus Shigella spp. Developing countries have high disease burden of shigellosis. However, its relative transmissibility in male and female individuals remains unclear. In this study, we employed a mathematical model to explore the dataset of reported shigellosis cases built by Hubei Province, China from 2005 to 2017. Two indicators, secondary attack rate (SAR) and relative ratio of SAR between males and females, were developed to assess the relative transmissibility in males and females. We found that shigellosis has medium transmissibility among male and female individuals. The disease seems to be more transmissible in males than in females.

epidemiology↗

bioRxiv2019

Novel syngeneic animal model of tobacco-associated oral cancer reveals the activity of in situ anti-CTLA-4

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Tobacco use is the main risk factor for HNSCC, and tobacco-associated HNSCCs have poor prognosis and response to available treatments. Recently approved anti-PD-1 immune checkpoint inhibitors showed limited activity ([≤]20%) in HNSCC, highlighting the need to identify new therapeutic options. For this, mouse models that accurately reflect the complexity of the HNSCC mutational landscape and tumor immune environment are urgently needed. Here, we report the first mouse HNSCC model system that recapitulates the human tobacco-related HNSCC mutanome, in which tumors grow when implanted in the tongue of immunocompetent mice. These HNSCC lesions have similar immune infiltration and response rates to anti-PD-1 ([≤]20%) immunotherapy as human HNSCCs. Remarkably, we found that >70% of HNSCC lesions respond to intratumoral anti-CTLA-4. This syngeneic HNSCC mouse model provides a platform for the development of novel immunotherapeutic options for HNSCC.

cancer biology↗

bioRxiv2019

Machine-Learning Prediction of Comorbid Substance Use Disorders in ADHD Youth Using Swedish Registry Data

BackgroundChildren with attention-deficit/hyperactivity disorder (ADHD) have a high risk for substance use disorders (SUDs). Early identification of at-risk youth would help allocate scarce resources for prevention programs.\n\nMethodsPsychiatric and somatic diagnoses, family history of these disorders, measures of socioeconomic distress and information about birth complications were obtained from the national registers in Sweden for 19,787 children with ADHD born between 1989-1993. We trained 1) cross-sectional machine learning models using data available by age 17 to predict SUD diagnosis between ages 18-19; and 2) a longitudinal model to predict new diagnoses at each age.\n\nResultsThe area under the receiver operating characteristic curve (AUC) was 0.73 and 0.71 for the random forest and multilayer perceptron cross-sectional models. A prior diagnosis of SUD was the most important predictor, accounting for 25% of correct predictions. However, after excluding this predictor, our model still significantly predicted the first-time diagnosis of SUD during age 18-19 with an AUC of 0.67. The average of the AUCs from longitudinal models predicting new diagnoses one, two, five and ten years in the future was 0.63.\n\nConclusionsSignificant predictions of at-risk co-morbid SUDs in individuals with ADHD can be achieved using population registry data, even many years prior to the first diagnosis. Longitudinal models can potentially monitor their risks over time. More work is needed to create prediction models based on electronic health records or linked population-registers that are sufficiently accurate for use in the clinic.

neuroscience↗

bioRxiv2019

TeoNAM: a nested association mapping population for domestication and agronomic trait analysis in maize

Recombinant inbred lines (RILs) are an important resource for mapping genes controlling complex traits in many species. While RIL populations have been developed for maize, a maize RIL population with multiple teosinte inbred lines as parents has been lacking. Here, we report a teosinte nested association mapping population (TeoNAM), derived from crossing five teosinte inbreds to the maize inbred line W22. The resulting 1257 BC1S4 RILs were genotyped with 51,544 SNPs, providing a high-density genetic map with a length of 1540 cM. On average, each RIL is 15% homozygous teosinte and 8% heterozygous. We performed joint linkage mapping (JLM) and genome-wide association study (GWAS) for 22 domestication and agronomic traits. A total of 255 QTLs from JLM were identified with many of these mapping to known genes or novel candidate genes. TeoNAM is a useful resource for QTL mapping for the discovery of novel allelic variation from teosinte. TeoNAM provides the first report that PROSTRATE GROWTH1, a rice domestication gene, is also a QTL associated with tillering in teosinte and maize. We detected multiple QTLs for flowering time and other traits for which the teosinte allele contributes to a more maize-like phenotype. Such QTL could be valuable in maize improvement.

genetics↗

bioRxiv2019

Emergence and Genetic Analysis of Avian Gyrovirus 2 Variants-Related Gyrovirus in Farmed King-ratsnakes (Elaphe carinata): the First Report in China

Avian gyrovirus 2 (AGV2), which is similar to chicken infectious anemia virus, is a new member of the Circovirus genus. AGV2 has been detected not only in chicken but also in human tissues and feces. In this study, a total of 91 samples (8 liver tissues and 83 faecal samples) collected from king-ratsnakes (Elaphe carinata) at 7 separate farms in Hubei and Henan, China, were analyzed to detect AGV2 DNA via specific PCR. The results indicated a low positive rate of AGV2 (6.59%, 6/91) in the studied animals, and all of the positive samples were from the same farm. The AGV2 strain HB2018S1 was sequenced, and the genome with a total length of 2376 nt contained three partially overlapping open reading frames: VP1, VP2, and VP3. Phylogenetic tree analysis revealed that the HB2018S1, NX1506-1 strain from chickens in China belong to the same clade, with nucleotide homology as high as 99.5%. In total, 10 amino acid mutation sites, including 44R/K, 74T/A, 256 C/R, 279L/Q, and 373V/A in AGV2 VP1; 60I/T, 125T/I, 213D/N, and 215L/S in AGV2 VP2; and 83H/Y in AGV2 VP3, were found in the genome of HB2018S1 that were different from those observed in most reference strains, suggesting that the differences are related to an transboundary movement among hosts which needs to be further elucidated.\n\nIMPORTANCERecently, AGV2 has been detected in live poultry markets and human blood in mainland China. Previous findings indicated future studies should investigate the large geographic distribution of AGV2 and monitor the variants, the host range, and the associated diseases. To the best of our knowledge, this study is the first report on AGV2 infected poikilotherm, suggested that cross-host transmission of viruses with circular single-stranded DNA genomes would be a public health concern.

epidemiology↗